bluuebunny/crossref_metadata_2025 huggingface dataset:
Tendencias de Remunicipalización de la Gestión Publica de Agua
Authors: Heilmann Maria de Jesus R. A.
Published: November 2018

Este articulo hace una reflexión entorno de las nuevas tendencias de remunicipalización de la gestión pública directa de los servicios de suministro de agua. Se pone de manifiesto el concepto de ‘remunicipalización’, donde son destacados los elementos de la “ineficiência” e de fallas de funcionamento de los operadores privados, en la ejecución del servicio público municipal. También, se hace referência al concepto de ‘reinternalización’, establecendo un comparativo entre los dos fenómenos, desde el enclave con el Derecho Administrativo. En otro matiz, se aborda los puntos clave del proceso de remunicipalización del servicio público de agua, se destacando los riesgos externos suportados por los usuarios y la administración pública al cambio del nuevo sistema operativo. En ese contexto, hace hincapié con la teoría económica de “elección pública” aportada al derecho administrativo, y de su relevancia al tema de la ‘gestión contractual’ de concesiones indirectas en colaboración con empresas privadas (contratistas). Por último, volviese analizar un caso en concreto, la remunicipalización del servicio de abastecimiento de agua en la comunidad de Paris, considerado uno de los retos más significativos a fomentar el debate en otros sistemas jurídicos.
A Lei Antiterrorismo Brasileira à Luz da Teoria do Direito Penal do Inimigo
Authors: Lacerda Nathália Polyana C. , Lacerda Murilo Couto , Guimarães Rejaine Silva
Published: November 2018

O presente trabalho visa uma análise da teoria do direito penal do inimigo, denominado pela doutrina de terceira velocidade do Direito Penal, bem como as consequências da Lei Antiterrorismo 13.260/2016 em vigor no ordenamento jurídico brasileiro que trouxe grandes repercussões nos meios social e político. A grande novidade da lei é a autorização para que o Estado possa realizar ações inovadoras, punindo pessoas por previsões de crimes que nem sequer se iniciaram, uma espécie de aplicabilidade do direito penal do inimigo de tal forma que não ofenda os direitos e garantias fundamentais dos cidadãos, demonstrando evidente aplicação do direito penal do autor. A modalidade de pesquisa é de caráter essencialmente exploratório, sondagem bibliográfica e documental, amparando-se no modelo descritivo. Conclui-se que o direito penal do inimigo deve ser aplicado a todos aqueles considerados inimigos que visam infringir a norma, o direito penal do inimigo deve antecipar a tutela penal, para punir atos preparatórios, o que ocorreu em julho do corrente ano no Brasil, para evitar futuros danos a milhares de pessoas. Criminosos que atentam contra a própria estrutura do Estado, contra a coletividade, devem ser punidos com a rigorosidade de suas condutas.
Desenvolvimento Econômico, Sociedade e Meio Ambiente: uma Análise Crítica Sobre a Zona Franca de Manaus
Authors: Campos Hélio Silvio Ourém , Erminio Maria Ivanúcia Mariz
Published: November 2018

A Zona Franca de Manaus, sancionada, para o modelo atual, pelo Decreto-Lei 288 de 1967 assinado pelo então Presidente Castelo Branco, instituiu incentivos fiscais para implementação de uma Zona Franca, cujo objetivo principal consistia no desenvolvimento social e econômico como também promover a habitação de uma área estratégica com o intuito de promover a segurança nacional da região conhecida hoje como Amazônia Ocidental. Este trabalho se propôs a analisar, através do método de pesquisa exploratório, descritivo e explicativo sob as ferramentas de pesquisa bibliográfica, documental, estudo de caso e análise de dados, os fundamentos econômicos que norteiam os polos de desenvolvimento e, por fim, a forma com a qual a Suframa, autarquia responsável pela Zona Franca de Manaus, vem gerindo o Polo Industrial de Manaus e se vem obtendo sucesso na concretização dos seus objetivos.
Open Implantation of Autologous Chondrocytes Cultured on Porcine Collagen Membrane for the Treatment of a Full-Thickness Patellar Cartilage Lesion
Authors: Schmiesing Andrew M. , Ridley T.J. , Macalena Jeffrey A.
Published: November 2018

Large cartilage defects in the knee are debilitating for patients and challenging for surgeons to treat. Autologous chondrocyte implantation (ACI) has gained popularity over the past 20 years and has become the treatment of choice for large cartilage defects for some surgeons. Termed matrix-applied ACI (MACI), use of autologous chondrocytes cultured on porcine collagen membrane has recently been approved by the U.S. Food and Drug Administration for the treatment of symptomatic full-thickness cartilage defects in the knee. This new technique for cartilage repair is the third generation of chondrocyte implantation technology and the first to involve the use of a scaffolding to grow chondrocytes
1
. MACI is a simpler technique than previous generations and has more reliable chondrocyte seeding. Research has shown that patients do well postoperatively, with improvements in patient-reported outcome out to 5 years postoperatively
3
. These improvements are statistically greater for patients who underwent MACI when compared to those who underwent microfracture
2
. (1) Preoperative evaluation: patients are indicated for a cartilage procedure after magnetic resonance imaging (MRI) and clinical examination. (2) Stage 1: a diagnostic arthroscopy is performed, and chondrocytes are harvested and cultured. (3) Approach: a short vertical incision is made, followed by a medial parapatellar arthrotomy. (4) Debridement: the lesion is identified and debrided back to stable cartilage. (5): Hemostasis: hemostasis is obtained with an epinephrine-soaked sponge. (6) Template creation: foil is used to create a template of the lesion. (7) Cells cutting: with use of the foil, the membrane of cells is cut to the appropriate size and shape. (8) Implantation: the cut membrane is placed on the lesion and secured with fibrin glue. (9) Testing: the knee is taken through a range of motion and the stability of the membrane is confirmed. (10) Closure: standard closure in layers is performed.
Clinical Evaluation of Compound Salvia Droplet Pills in the Treatment of Stable Angina Pectoris:Study Protocol for a Randomized Double-blind Control Trial
Authors: Liu Zhi , Wang Zhen , Gao Rui , Wang Hui , Zheng Wenke , Liu Chunxiang , Chen Jing
Published: November 2018

Background
SAP (Stable Angina Pectoris, SAP) is a clinical syndrome characterized by acute and temporary myocardial ischemia and hypoxia due to an increase in the myocardial load resulting from a fixed severe stenosis of the coronary artery. Its’ characteristics include paroxysmal pressure pain or tightness in the prothorax, primarily retrosternal pain, which can radiate to the precordium and upper left ulna. It often occurs during physical exertion and lasts for several minutes. Traditional Chinese Medicine (TCM) has unique advantages in treating this disease due to holistic, dynamic and dialectical system of thought regarding life and diseases. Clinical efficacy is the basis for the survival and development of Traditional Chinese Medicine. Scientifically evaluating the clinical efficacy of such TCM treatments is of great importance for promoting its’ modernization and internationalization. In this study, we aimed to observe the therapeutic effects of Compound Salvia Droplet Pills on patients with SAP (Qi deficiency and blood stasis), as shown by a standardized clinical study on the treatment of SAP by means of supplementing qi and activating blood circulation by taking TCM treatments for CHD, thereby providing a practical and valuable clinical treatment approach.

Methods
A randomized, controlled trial was designed to evaluate the efficacy and safety of Compound Salvia Droplet Pills for the treatment of SAP.
A proposed total of 60 patients with SAP (Qi deficiency and blood stasis type) are to be entered into the study.
The patients shall be randomly assigned to treatment groups (compound Salvia Droplet Pills, 10 pills/time, 3 times a day, + aspirin enteric - coated tablets 100mg/time, once a day) or the control group (compound Salvia Droplet Pills mimetics, 10 pills/time, 3 times a day, + aspirin enteric - coated tablets 100mg/time, once a day), duration of 28 ±1, and follow-up for 14 ± 3 days.
Primary outcome measures: angina pectoris symptom scores and TCM syndrome scores.
Secondary outcome measures: ECG, incidence and mortality of cardiovascular events, etc.

Discussion
This is a randomized controlled trial for Compound Salvia Droplet Pills to treat SAP on the basis of conventional therapy, to preliminarily evaluate the efficacy in the treatment of patients with SAP (angina symptoms, signs and reducing the use of vasodilator drugs, etc.), and follows up on the short -term prognosis of patients to provide clinical evidence for the use of compound Salvia Droplet Pills in patients with SAP.
Dosage and routes of administration of prostaglandin: Practical implications for the reproduction of cows, mares and pigs
Authors: NALASKOWSKA MARCELINA , JAŚKOWSKI JĘDRZEJ M. , HERUDZIŃSKA MAGDALENA , HENKLEWSKI RADOMIR , BIAZIK ANNA , GEHRKE MAREK
Published: November 2018

Prostaglandin F2α and its synthetic analogues, because of their luteolytic properties, have found wide application in the reproduction of domestic animals, including cattle, swine and horses. They are used to induce and synchronize heat, ovulation and parturition, as well as to improve the results of insemination and early-stage pregnancy termination. The ongoing discussions regarding animal welfare include the question of the lowest effective dose of hormones in individual species and how it could be reduced by selecting the optimal route of hormone administration. Intramuscular injection is the recommended method of administering prostaglandins to cows, pigs and mares. Due to the different sensitivities of these species to prostaglandins, the recommended therapeutic dose varies significantly from one species to another. The luteolytic effect also depends on the route of administration. Studies on alternative routes of injection report good therapeutic effects after administration of the hormone subcutaneously (SC), into intravaginal submucosa (IVSM), at the BAI-HUI acupuncture point or at the ischiorectal fossa (IRF). The injection site, the dose and the type of prostaglandin used may intensify negative effects, such as an increase in the heart or breathing rate and increased sweating.
The influence of inflammaging on oncogenesis
Authors: MADEJ JANUSZ A.
Published: November 2018

There is a specific antagonism between an aging organism and neoplasia, in which the tumor is considered to influence the local tissue. It returns to some atavistic features, including the thermodynamic approach (2nd law of thermodynamics, Fig. 1), causing the rejuvenation of the surrounding tissue. The existence of various theories of oncogenesis entitles their supplementation with the theory of inflammaging: an entropic inflammation that can potentially have an indirect influence on the oncogenesis. This theory covers the effects of various causes of aging, including genetically programmed changes, telomere dependent processes and damage of genome, epigenome and proteome particles. The paper describes the patomechanism of inflammaging, including the role of mitochondria (point mutations and deletions especially in mtDNA), oxidative stress with overproduction and accumulation of free radicals and NFkB factor (nuclear factor kappa-light chain-enhancer of activated B cells) and the possibility of the influence of inflammaging on oncogenesis (Fig. 2). The inflamma-ging is programmed by hypothalamus using the immune-neuro-endocrine system, including gonadotropin releasing hormone (GnRH) that inhibits the NFkB factor with the inactivation of kinase IKK-beta. Regardless of that, the chronic inflammation, exceeding its defensive competence, lasts for years and can also be the beginning of neoplastic cells proliferation.
Sexual activity of different gilt genotype groups of the Pulawska breed during oestrus
Authors: BABICZ MAREK , PASTWA MARCIN , SKRZYPCZAK EWA , ŁUSZCZEWSKA-SIERAKOWSKA IWONA , WAWRZYNIAK AGATA
Published: November 2018

The aim of the study was to analyze sexual activities of gilts representing various genotype groups in the RBP4 and MC4R locus. Observations of gilt behaviour during the first and the second oestrus (before initiation of the reproduction phase) were carried out in the Pulawska breed from conservation breeding. The evaluation process comprised the duration of the heat as well as the intensity of heat behaviours. Polymorphism identification in RBP4 (SNP: rs55618789) and MC4R (SNP: rs81219178) genes was performed, which resulted in the identification of three (MC4R: AA, AG and GG) and two (RBP4: CC and CT) gilt genotype groups. Significantly varying sexual activities were observed: the most intensive heat symptoms were demonstrated by CT gilts in the course of the first (P ≤ 0.05) and second (P ≤ 0.01) oestrus (locus RBP4) reaching, on average, 2.15 ± 0.13 and 2.52 ± 0.13 pt. It was further determined that the heats of CT gilts lasted longer and this difference, in the second heat, was significant (P ≤ 0.01). In the case of the MC4R locus, significant differences in gilt sexual activities were observed only in the course of the second oestrus (P ≤ 0.05). In addition, a strong association was also demonstrated of AA (locus MC4R) and CC (locus RBP4) genotypes with the thickness of the subcutaneous fat tissue (P ≤ 0.05) amounting in these gilts to 11.57 ± 0.21 mm and 11.50 ± 0.19 mm, respectively.
MIGRANTI E RICHIEDENTI ASILO: SOGGETTI DI DIRITTO O NON-PERSONE? DIRITTO ALLA SALUTE E MECCANISMI DI INCLUSIONE ED ESCLUSIONE NEL CONTESTO DEI PROCESSI MIGRATORI CONTEMPORANEI
Authors: Finco Matteo
Published: November 2018

Os chamados direitos humanos são caracterizados por uma reivindicação de universalidade: eles deveria ser desconectados dos atributos de cidadania e deveria assim ser reconhecidos a todos, em virtude da pertença de cada indivíduo à espécie humana. Ao mesmo tempo, os migrantes – especialmente os requerentes de asilo – na verdade parecem incorporar e reproduzir claramente a distinção entre pessoa física e pessoa jurídica, com consequências muitas vezes dramáticas. Objetivo deste artigo é analizar a categoria dos chamados migrantes económicos e os sinais do fenômeno da criminalização da imigração, para verificar se é possível afirmar que os migrantes são – de fato – considerados não-pessoas, que não se beneficiam dos direitos humanos. O trabalho é realizado por meio de análises bibliográficas e reflexões teóricas. As conclusões sugerem que o dispositivo da cidadania parece representar o requisito essencial para beneficiar dos direitos humanos.
Towards a water quality database for raw and validated data with emphasis on structured metadata
Authors: Plana Queralt , Alferes Janelcy , Fuks Kevin , Kraft Tobias , Maruéjouls Thibaud , Torfs Elena , Vanrolleghem Peter A.
Published: November 2018

On-line continuous monitoring of water bodies produces large quantities of high frequency data. Long-term quality control and applicability of these data require rigorous storage and documentation. To carry out these activities successfully, a database has to be built. Such a database should provide the simplicity to store and document all relevant data and should be easy to use for further data evaluation and interpretation. In this paper, a comprehensive database structure for water quality data is proposed. Its goal is to centralize the data, standardize their format, provide easy access, and, especially, document all relevant information (metadata) associated with the measurements in an efficient way. The emphasis on data documentation enables the provision of detailed information not only on the history of the measurements (e.g., where, how, when and by whom was the value measured) but also on the history of the equipment (e.g., sensor maintenance, calibration/validation history), personnel (e.g., experience), projects, sampling sites, etc. As such, the proposed database structure provides a robust and efficient tool for functional data storage and access, allowing future use of data collected at great expense.
Comparative Activity of Adenosine Deaminase Acting on RNA (ADARs) Isoforms for Correction of Genetic Code in Gene Therapy
Authors: Azad Md. Thoufic A. , Qulsum Umme , Tsukahara Toshifumi
Published: November 2018

Introduction:

Members of the adenosine deaminase acting on RNA (ADAR) family of enzymes
consist of double-stranded RNA-binding domains (dsRBDs) and a deaminase domain (DD)
that converts adenosine (A) into inosine (I), which acts as guanosine (G) during translation. Using the
MS2 system, we engineered the DD of ADAR1 to direct it to a specific target. The aim of this work
was to compare the deaminase activities of ADAR1-DD and various isoforms of ADAR2-DD.

Materials and Methods:

We measured the binding affinity of the artificial enzyme system on a Biacore
™ X100. ADARs usually target dsRNA, so we designed a guide RNA complementary to the target
RNA, and then fused the guide sequence to the MS2 stem-loop. A mutated amber (TAG) stop
codon at 58 amino acid (TGG) of EGFP was targeted. After transfection of these three factors into
HEK 293 cells, we observed fluorescence signals of various intensities.

Results:

ADAR2-long without the Alu-cassette yielded a much higher fluorescence signal than
ADAR2-long with the Alu-cassette. With another isoform, ADAR2-short, which is 81 bp shorter at
the C-terminus, the fluorescence signal was undetectable. A single amino acid substitution of
ADAR2-long-DD (E488Q) rendered the enzyme more active than the wild type. The results of fluorescence
microscopy suggested that ADAR1-DD is more active than ADAR2-long-DD. Western blots
and sequencing confirmed that ADAR1-DD was more active than any other DD.

Conclusion:

This study provides information that should facilitate the rational use of ADAR variants
for genetic restoration and treatment of genetic diseases.
Preparation, Characterization, and In Vitro pH-sensitivity Evaluation of Superparamagnetic Iron Oxide Nanoparticle- Misonidazole pH-sensitive Liposomes
Authors: Li Bibo , Li Biqiang , He Daiying , Feng Changyan , Luo Zhibin , He Mei
Published: November 2018

Background:

The use of Misonidazole (MISO), the first and a potential hypoxic tumor cell
radiosensitizer, has been limited by peripheral neurotoxicity, thus discouraging phase III clinical trials.

Objective:

To develop a targeted drug delivery and tracing System with pH-sensitive liposomes
(SpHLs) and Superparamagnetic Iron Oxide Nanoparticles (SPIONs) to counter MISO-related adverse
effects and to enable tracing under magnetic resonance.

Methods:

SPION-MISO-SpHLs were prepared by a reverse evaporation and freeze-thawing method.
HPLC and phenanthroline spectrophotometry were established for MISO and Fe determination. The
characterization and in vitro pH-sensitivity of SPION-MISO-SpHLs were evaluated.

Results:

The maximal entrapment efficiencies of MISO and SPIONs in SPION-MISO-SpHLs were
30.2% and 23.7%, respectively. The cumulative release rates of MISO and SPIONs were respectively
2.49 and 2.47 times higher in pH 5.5 than in pH 7.4 buffer. The mean particle size of SPION-MISOSpHLs
was 950 nm. The zeta potential was -58.9 mV in pH 7.4 buffer and 36.3 mV in pH 5.5 buffer.
SEM imaging showed that SPION-MISO-SpHLs had similar spherical morphologies. SPIONs were
packed in the center of liposomes and were well dispersed in a TEM graph. Magnetization curve
showed that SPION-MISO-SpHLs retained superparamagnetic properties. SPION-MISO-SpHLs were
compared with MISO+SPION+blank liposome in hypoxia and control groups of A549 cells. MISO and
SPION concentrations in culture medium showed significant differences between the same concentration
groups (P < 0.0001) and at different times (P < 0.0001).

Conclusion:

SPION-MISO-SpHLs possess pH-dependent release ability and superparamagnetism, and
thus provides a system for targeted delivery and tracing under magnetic resonance.
Insulin Therapy in Pregnancy Hypertensive Diseases and its Effect on the Offspring and Mother Later in Life
Authors: Mate Alfonso , Blanca Antonio J. , Salsoso Rocío , Toledo Fernando , Stiefel Pablo , Sobrevia Luis , Vázquez Carmen M.
Published: November 2018

Pregnancy hypertensive disorders such as Preeclampsia (PE) are strongly correlated with insulin resistance, a condition in which the metabolic handling of D-glucose is deficient. In addition, the impact of preeclampsia is enhanced by other insulin-resistant disorders, including polycystic ovary syndrome and obesity. For this reason, there is a clear association between maternal insulin resistance, polycystic ovary syndrome, obesity and the development of PE. However, whether PE is a consequence or the cause of these disorders is still unclear. Insulin therapy is usually recommended to pregnant women with diabetes mellitus when dietary and lifestyle measures have failed. The advantage of insulin therapy for Gestational Diabetes Mellitus (GDM) patients with hypertension is still controversial; surprisingly, there are no studies in which insulin therapy has been used in patients with hypertension in pregnancy without or with an established GDM. This review is focused on the use of insulin therapy in hypertensive disorders in the pregnancy and its effect on offspring and mother later in life. PubMed and relevant medical databases have been screened for literature covering research in the field especially in the last 5-10 years.
Synthesis of Dihydropyrimidinones (DHPMs) and Hexahydro Xanthene Catalyzed by 1,4-Diazabicyclo [2.2.2] Octane Triflate Under Solvent-Free Condition
Authors: Deepa  , Yadav Geeta D. , Aalam Mohd J. , Chaudhary Pooja , Singh Surendra
Published: November 2018

Objective:

DABCO salts were evaluated as catalysts for the Biginelli reaction between 4- methoxybenzaldehyde, urea and ethyl acetoacetate under solvent-free conditions. 1,4-Diazabicyclo [2.2.2] octane triflate was found to be a simple, inexpensive, highly efficient catalyst for Biginelli reaction for a variety aromatic aldehyde with urea and ethyl acetoacetate at 80°C afforded corresponding 3,4-dihydropyrimidinones in 50-99% yields after 30-120 minutes. 1,3-Cyclohexadione was used in place of ethyl acetoacetate in the absence of urea this methodology is giving hexahydro xanthene derivatives in good to excellent yields after 3-4 hours.

Methods:

DABCO salt 4 (5 mol%), 4-methoxybenzaldehyde (0.73 mmol) and urea (0.73 mmol) were stirred for 10 minutes at 80°C, then ethyl acetoacetate (1.5 equiv.) was added and reaction mixture was stirred at 80°C for specified time. The resulting solution was stirred continuously and progress of the reaction was followed by TLC. The crude reaction mixture was purified by flash column chromatography on silica gel (hexane/ethyl acetate (1:2)) to give pure desired product.

Results:

Reaction conditions of the Biginelli reaction were optimized using 4-methoxybenzaldehyde (0.73 mmol), urea (0.73 mmol), and ethyl acetoacetate (5 equiv.) as model substrates catalyzed by 1,4-Diazabicyclo [2.2.2] octane triflate (5 mol%) in a different solvents, screening of different catalysts and different temperatures. Neat condition was found to be the best for the Biginelli condensation and corresponding 3,4- dihydropyrimidinones was obtained in good to excellent yields. When the reaction was carried out with benzaldehyde derivatives and cyclohexane-1,3-dione in place of ethyl acetoacetate in the absence of urea, solely corresponding hexahydro xanthene derivatives were obtained in 61-91% yields.

Conclusion:

In conclusion, we have applied salts of 1,4-Diaza-bicyclo [2.2.2] octane as catalysts in the Biginelli condensation and corresponding 3,4-dihydropyrimidinones were obtained in 50- 99% yields under solvent free conditions. This methodology is having advantages like simple work-up; low loading of catalyst and reaction was performed at moderate temperature under solvent-free conditions.
Synthesis of Limonin Derivatives with Improved Anti-inflammatory and Analgesic Properties
Authors: Jia Chengshu , Hu Bin , Ji Yingying , Su Yourui , Gong Guoqing , Zhu Qihua , Xu Yungen
Published: November 2018

Background:

Limonoids represent an important class of natural products which possess a
broad range of biological activities. Albeit their enormous potentials as therapeutic candidates, they
usually suffer from low bioavailability, poor aqueous solubility and relatively weak biological
activities which result in significant challenges in the clinic applications. Therefore, the exploration
and development of novel limonin derivatives with improved drug-like properties through the
structural modifications recently have attracted great attention in the biological and medicinal
chemistry field.

Methods:

Based on the structural modifications of C17-furan ring in limonin, a series of limonin
derivatives was designed, synthesized and screened for their anti-inflammatory and analgesic
activities in vivo.

Results and Conclusion:

Preliminary pharmacological studies revealed that most tested compounds
exhibited more potent anti-inflammatory and analgesic efficacies than lead molecule limonin.
Especially, for compound 3f, it exhibited a stronger anti-inflammatory effect than that of naproxen
and comparable analgesic potency with aspirin. In the formalin test, 3f showed an obviously
attenuated phase-II pain response which indicated that it may produce an anti-inflammatory effect in
the periphery. Furthermore, the significantly low hERG inhibition (IC50 >100 μM) and high LD50
value of target molecule 3f further demonstrated it as a promising analgesic/anti-inflammatory
candidate with excellent drug-like profiles.
Synthesis, Antiproliferative, and Antioxidant Activities of Substituted N-[(1,3,4-Oxadiazol-2-yl) Methyl] Benzamines
Authors: Ahsan Mohamed Jawed , Bhandari Lakshya , Makkar Shally , Singh Rajan , Hassan Mohd. Zaheen , Geesi Mohammed H. , Bakht Mohamed Afroz , Jadav Surender Singh , Balaraju Tuniki , Riadi Yassine , Rani Sandhya , Khalilullah Habibullah , Gorantla Vasubabu , Hussain Afzal
Published: November 2018

Background:

Oxadiazole emerged as an important class of heterocyclic compound with diverse biological activities like anticancer, antitubercular, anticonvulsant, anti-tubulin, antimicrobial, anti-inflammatory, antioxidant etc.

Objective:

The objective of this study is to synthesis series of twelve substituted N-[(1,3,4-oxadiazol-2- yl)methyl]benzamines (6a-l) and their evaluation as antiproliferative and antioxidant agents.

Methods:

The substituted N-[(1,3,4-oxadiazol-2-yl)methyl]benzamines (6a-l) analogues were synthesized as per the reported procedure. The antiproliferative activity was tested against nine different panels cancer cell lines (leukemia, colon, renal, non-small cell lung, breast, CNS, melanoma, prostate, and ovarian cancer) at 10 µM drug concentrations as per the NCI US Protocol.

Results:

2-(5-((3-Chloro-4-fluorophenylamino)methyl)-1,3,4-oxadiazol-2-yl)phenol (6e) revealed the significant antiproliferative activity among the series of title compounds (6a-l). The compound, 6e showed maximum sensitivity towards CCRF-CEM, MCF-7, MOLT-4, T-47D, and SR cell lines with percent growth inhibitions (%GIs) of 79.92, 56.67, 39.62, 34.71 and 33.35, respectively. Furthermore, the compounds, 6e and 6c showed promising antioxidant activity with an IC50 value of 15.09 and 19.02 µM, respectively in DPPH free radicals (FR) scavenging activity.R

Conclusion:

The present study may support a significant value in cancer drug discovery programme.
Synthesis of Novel 2,3-Dihydro-5,6-dimethoxy-2-((piperidin-4-yl)methyl) inden-1-one Derivatives as Acetyl Cholinesterase Inhibitors
Authors: Prasad Salekoppal B.B. , Mysore Sachin , Raj C.S. Ashok , Rangappa Kanchugarakoppalu S. , Mahadevaiah K. , Kumar Channapillekoppal S.A.
Published: November 2018

Background:

Novel carboxamides and thioureas of 2,3-dihydro-5,6-dimethoxy-2-((piperidin-
4-yl)methyl) inden-1-one were synthesized and their potential anticholinesterase activities were evaluated.
The inhibition potency of the compounds 17a-j and 19a-j against AChE was measured and evaluated
using Ellman’s spectrophotometric method. Among carboxamides series, compound 17f, 17i, 17j
and among thiourea series, compound 19a, 19b were found to be the most active.

Methods:

The scaffold 2,3-dihydro-5,6-dimethoxy-2-((piperidin-4-yl)methyl) inden-1-one 16, key intermediate
of drug donepezil has been synthesised in three steps and derivatised as carboxamides and
thioureas for SAR studies. Compounds 17a-j and 19a-j were characterised by 1H NMR and LCMS. The
inhibitory activity and antiamnesic effect were studied using different sources such as electric eel
AChE, human serum AChE and rat brain homogenate AChE.

Results:

The results of bioassays indicated that among all the synthesized compounds tested, five compounds
17f, 17i, 17j, 19a and 19b shows IC50 at a dose of 67, 42, 64, 52 and 63 nM respectively against
electric eel, human serum and rat brain homogenate, which lead to the suggestion that compound 17i
might be considered to be a potent AChE inhibitor.

Conclusion:

Derivatives of 2,3-dihydro-5,6-dimethoxy-2-((piperidin-4-yl)methyl)inden-1-one with
different substitutions were synthesised and tested for their AChE activity. The order of potency is
17i>17j>17f and 19a>19b. The other compounds screened failed to elicit any inhibition of acetyl cholinesterase
from rat brain homogenate. It may be concluded from this study that, for effective binding
and blocking the AChE activity, molecule needs to bind with peripheral site and active site of the enzyme.
Therefore, it can be summarized that by changing the functional group and substitution in the
scaffold 2,3-dihydro-5,6-dimethoxy-2-((piperidin-4-yl)methyl)inden-1-one needs to be studied for better
AChE inhibitory activity in future research.
Effect of Chemical Oxidation Routes on the Properties of Chitosan- MWCNT Nanocomposites
Authors: Sánchez Alejandro Gomez , Prokhorov Evgen , Luna-Barcenas Gabriel , Kovalenko Yuriy , Rivera-Muñoz Eric M. , Raucci Maria G. , Buonocore Giovanna
Published: November 2018

Background:

Chitosan-multiwall carbon nanotubes (CS-MWCNTs) nanocomposites are
an attractive material due to their biocompatibility and possibility to produce nanocomposites with
high conductivities and high mechanical properties. Both electrical and mechanical properties depend
upon the method of MWCNT chemical oxidation; this oxidation affects the interaction of CS
side groups with MWCNT’s surface groups. However, in the literature, there are no reports on how
different methods of MWCNT oxidation will affect the electrical and mechanical properties of related
nanocomposites.

Objective:

The objective of this work is to probe CS-MWCNT nanocomposite’s electrical and mechanical
properties by taking advantage of the presence of interfacial layer and its dependence on the
methods of MWCNTs chemical oxidation routes.

Methods:

Nanocomposites are prepared with non-functionalized MWCNT and functionalized
MWCNTs obtained by chemical oxidation treatments in HNO3 in H2SO4/NHO3 mixtures and commercially
carboxyl-terminated MWCNTs, respectively. Properties of MWCNTs and nanocomposites
were evaluated using SEM, FTIR, Raman, TGA, XRD, impedance and mechanical measurements.

Results:

It was shown that different chemical oxidation routes produce MWCNTs with a different
number of carboxylic groups and defects which influence the interaction between MWCNTs with CS
matrix and thickness of the interfacial layer between MWCNTs and CS matrix. Additionally, it was
shown that the formation of the interfacial layer dominates on the dispersion of MWCNTs and
affects on the electrical and mechanical percolation effects.

Conclusion:

It was shown that contrary to many studies previously reported, good dispersion of
MWCNT does not guarantee obtained nanocomposites with the best electrical and mechanical properties.
Sonic Hedgehog Signaling Activation Promotes Cardioprotective Strategies
Authors: Khera Himanshi , Awasthi Anupam , Mehan Sidharth
Published: November 2018

Background:

Hedgehog pathway plays a crucial role in the neovascularisation and angiogenesis during the embryonic stage in humans. Three genes of hedgehog protein isolated from humans are Sonic hedgehog, Desert hedgehog and Indian hedgehog gene. Two G-protein coupled receptors identified in the sonic hedgehog pathway served as patched receptor and smoothened receptor.

Materials and Methods:

Particularly, sonic hedgehog gene plays a versatile role in cellular homeostasis and can be a novel therapeutic target in the prevention of cardiovascular disorders. Further various sonic hedgehog modulators have been reported working as futuristic drug molecules in the modulation of cardiovascular dysfunctions.

Results:

However, there was limited literature availability that has summarized the possible mechanism of targeting Sonic hedgehog signaling pathway.

Conclusion:

Thus, the present review is aimed at exploring the role of targeting sonic hedgehog protein signaling and modulators as well as to enlighten that how targeting sonic hedgehog protein involves in the amelioration of atherosclerosis, ischemic heart diseases, vascular endothelial dysfunction, heart failure and congenital heart diseases.
Design, Synthesis and Evaluation of Novel 3/4-((Substituted benzamidophenoxy) methyl)-N-hydroxybenzamides/propenamides as Histone Deacetylase Inhibitors and Antitumor Agents
Authors: Anh Duong T. , Thuan Nguyen T. , Hai Pham-The , Huong Le-Thi-Thu , Yen Nguyen T.K. , Han Byung W. , Park Eun J. , Choi Yeo J. , Kang Jong S. , Hue Van T.M. , Han Sang-Bae , Nam Nguyen-Hai
Published: November 2018

Background:

Histone Deacetylase (HDAC) inhibitors represent an extensive class of targeted anticancer agents. Among the most explored structure moieties, hydroxybenzamides and hydroxypropenamides have been demonstrated to have potential HDAC inhibitory effects. Several compounds of these structural classes have been approved for clinical uses to treat different types of cancer, such as givinostat (ITF2357) and belinostat (PXD-101).

Aims:

This study aims at developing novel HDAC inhibitors bearing N-hydroxybenzamides and Nhydroxypropenamides scaffolds with potential cytotoxicity against different cancer cell lines.

Methods:

Two new series of N-hydroxybenzamides and N-hydroxypropenamides analogues (4a-j, 6a-j) designed based on the structural features of nexturastat A, AR-42, and PXD-101, were synthesized and evaluated for HDAC inhibitory potency as well as cytotoxicity against three human cancer cell lines (SW620 (colorectal adenocarcinoma), PC3 (prostate adenocarcinoma), and NCI-H23 (adenocarcinoma, non-small cell lung cancer). Molecular simulations were finally carried out to gain more insight into the structure-activity relationships.

Results:

It was found that the N-hydroxypropenamides (6a-e) displayed very good HDAC inhibitory potency and cytotoxicity. Various compounds, e.g. 6a-e, especially compound 6e, were up to 5-fold more potent than suberanilohydroxamic acid (SAHA) in terms of cytotoxicity. These compounds also comparably inhibited HDACs with IC50 values in the sub-micromolar range. Docking experiments showed that these compounds bound to HDAC2 at the enzyme active binding site with the same binding mode of SAHA, but with higher binding affinities.

Conclusions:

The two series of N-hydroxybenzamides and N-hydroxypropenamides designed and synthesized were potential HDAC inhibitors and antitumor agents. Further development of these compounds should be warranted.
Generation and Characterization of a Functional Nanobody Against Inflammatory Chemokine CXCL10, as a Novel Strategy for the Treatment of Multiple Sclerosis
Authors: Sadeghian-Rizi Tahereh , Behdani Mahdi , Khanahmad Hossein , Sadeghi Hamid Mirmohammad , Jahanian-Najafabadi Ali
Published: November 2018

Background & Objective: Chemokines and their receptors play a pivotal role in the pathogenesis
of various autoimmune diseases such as multiple sclerosis, infectious diseases, and also in
cancer metastasis via attraction of the pathogenic immune cells into the inflammation sites.

Methods:

Inflammatory chemokine CXCL10 as a T helper (Th)1-chemokine directs chemotaxis of
many cell subsets especially Th1 into the central nervous system (CNS) via its receptor CXCR3 and it
has been put forward as a potential therapeutic target in the treatment of multiple sclerosis. Nanobodies
are the smallest intact antigen binding fragments derived from heavy chain-only antibodies occurring
in camelids with unique biochemical and biophysical features which render them superior to conventional
antibodies or antibody fragments. Here, we describe the generation, selection, and characterization
of CXCL10-specific Nanobodies from camel immunized with CXCL10. The obtained
Nanobodies displayed high affinity towards CXCL10 about 10-11-10-8 M.

Results:

Then a Nanobody with the highest affinity named 3Nb12 was selected and investigated as a
migration inhibitor of CXCR3+ cells. Chemotaxis assay results showed that 3Nb12 blocked CXCL10-
CXCR3 binding and potently inhibited chemotaxis of CXCR3-transfected HEK293T cells.

Conclusion:

The nanobody 3Nb12 might be a promising specific and powerful blocking agent of
CXCL10 function, which can be used for diagnostic, therapeutic and research purposes in MS.
Xuesaitong May Protect Against Ischemic Stroke by Modulating Microglial Phenotypes and Inhibiting Neuronal Cell Apoptosis via the STAT3 Signaling Pathway
Authors: Li Fangfang , Zhao Haiping , Han Ziping , Wang Rongliang , Tao Zhen , Fan Zhibin , Zhang Sijia , Li Guangwen , Chen Zhigang , Luo Yumin
Published: November 2018

Background:

Xuesaitong mainly comprises Panax notoginseng saponins and has shown a
promising feature in an acute ischemic stroke model; however, its effect on long-term recovery following
stroke, and the related mechanisms, are unknown.

Methods:

The objective of this study was to investigate the long-term protective effects of xuesaitong
against ischemic stroke and its effect on microglial polarization. Experimental cerebral ischemia was induced
by middle cerebral artery occlusion (MCAO) for 45 min, and C57BL/6 mice were immediately injected
with xuesaitong or vehicle through the caudal vein at the onset of cerebral reperfusion consecutively
for 14 days. The animals were randomly divided into three groups: a sham-operated group, vehicle-treated
group and xuesaitong-treated group at a dose of 15μg/g. Subsequently, 2,3,5-triphenyltetrazolium chloride
staining was used to assess infarct volume, and adhesive removal tests and balance beam tests were used
to evaluate neurological deficits at days 1, 3, 7 and 14 following ischemia. Reverse-transcriptase polymerase
chain reaction and immunofluorescence staining for M1 markers (CD16, iNOS) and M2 markers
(CD206, arginase-1) were performed to characterize phenotypic changes in microglia. Elisa was used to
determine the release of pro-inflammatory and anti-inflammatory cytokines. TUNEL staining was conducted
to detect neuronal cell apoptosis, and western blots were used to determine the activation of signal
transducer and activator of transcription 3 (STAT3).

Results:

Our results revealed that xuesaitong treatment, compared with vehicle treatment, significantly
reduced cerebral infarct volume 1 and 3 days after MCAO and resulted in significant improvements in
long-term neurological outcomes. Furthermore, xuesaitong treatment, compared with vehicle treatment,
significantly reduced M1 markers and elevated M2 markers 7 and 14 days after MCAO at both
the mRNA and protein level in ipsilateral brain tissue. This finding was also accompanied by a reduction
in neuronal cell apoptosis and p-STAT3 transcription factor levels in the xuesaitong-treated group
compared with the vehicle-treated group.

Conclusion:

We demonstrated that xuesaitong has long-term neuroprotective effects against ischemic
stroke, possibly by promoting the polarization of microglia to an M2 phenotype and by inhibiting neuronal
cell death via down-regulation of the STAT3 signaling pathway, providing new evidence that
xuesaitong might be a promising therapeutic strategy for ischemic stroke.
Navigating Career Decisions in Dental Service Organizations: Practical Advice for Students, Residents, and Educators
Authors: Dunning David G. , Davis Kenneth J. , Lange Brian M.
Published: November 2018

The dental practice market continues to experience unprecedented changes, including the increasing presence and influence of dental service organizations (DSOs)—corporate entities that provide support and practice management for group practices in such areas as financial operations, human resources, marketing, and legal services. At the same time, increasing percentages of new dental graduates are choosing to pursue an initial career path in corporate dental practices. As a result, new graduates and others making a transition into private practice are likely to encounter complicated, multifaceted variables related to associateship opportunities. Experts in dental education are articulating a need for more instruction in practice management, particularly related to DSOs. Accordingly, this Perspectives article discusses issues in five broad categories focused on vetting career decisions in DSOs: business systems; the dental team and patients; clinical dentistry; compensation and professional development; and ownership positions. In addition to explaining the importance of these areas, the authors provide specific questions prospective associates should ask in considering these career options. These considerations should be useful for students and specialists who are preparing for their dental careers and for the educators who help to guide them.
Research Productivity of Directors of U.S. Advanced Education in Prosthodontics Programs
Authors: Sukotjo Cortino , Khan Anam , Yuan Judy Chia-Chun , Afshari Fatemeh , Weatherspoon Darien , Wee Alvin G.
Published: November 2018

The aims of this study were to measure the research productivity of directors of U.S. advanced education in prosthodontics programs (AEPP) and to identify associations between the directors’ publication metrics and professional characteristics. A list of AEPP directors was obtained from the American College of Prosthodontists website in December 2015. Information on gender, academic rank, and highest degree was collected from the institutional website for each individual. Citation databases (Scopus and Google Scholar) were searched for each director's h‐index and i10‐index (both indexes are based on numbers of citations of the author's articles) and total numbers of publications and citations. The search identified 50 AEPP directors. The majority were male and had a primary appointment at a university. Most held the rank of associate professor or professor and held both DDS and MS degrees. The mean h‐index and i10‐index of all directors were 6.32±6.97 and 6.84±10.77, respectively. Their mean numbers of publications and citations were 24.60±31.21 and 288.40±625.97, respectively. The analysis showed that the program directors affiliated with a university had significantly higher mean values for all indexes than those of non‐university‐affiliated program directors. Professors had productivity metrics significantly higher than those of other ranks in all measures of research productivity.
Teaching Silver Diamine Fluoride in U.S. Dental Schools’ Predoctoral Curricula
Authors: Ngoc Caroline Nguyen , Mehta Ritu , Donovan Terry E. , Ferreira Zandona Andrea G.
Published: November 2018

Silver diamine fluoride (SDF), a low‐cost topical agent used in many countries to arrest dental caries, was cleared as a desensitizing agent by the Food & Drug Administration for the U.S. market in 2014. The aim of this study was to survey U.S. dental schools regarding their teaching of SDF. Email invitations were sent to all accredited U.S. predoctoral dental education programs (n=66) in September 2016. Deans, chairs, and selected faculty members were asked to respond or forward the survey‐link provided to the appropriate person in their school. Under the assumption that some respondents from the same school were unaware of SDF implementation across departments, multiple responses from the same school were collapsed for analysis. A total of 62 schools (94% response rate) responded to the survey, and 67.7% of them reported that SDF was part of their curricula. There was a wide variation across dental schools’ teaching about SDF indications and protocols of application. All but one school consistently agreed on using SDF for arresting caries on primary teeth. Only 18 respondents were able to confirm if there was an existing protocol at their school for the use of SDF. When re‐application after initially arresting caries with SDF was taught, 50% of respondents advocated 2×/year re‐application. Schools not teaching SDF (n=20) planned on including it in their curricula in the future. These findings suggest that, with the use of SDF increasing rapidly in the U.S. and its adoption in most dental schools, there is a need for the development of standardized evidence‐based protocols.
Developing of guided inquiry-based biochemistry practicum guidebook
Authors: Widyaningrum Diyah Ayu , Wijayanti Titik
Published: November 2018

There were no practicum guidebook in Biochemistry hands-on activity at IKIP Budi Utomo, Malang city, East Java-Indonesia. The purposeof this study was to develop a guided inquiry-based biochemistry practicum guidebook for students of IKIP Budi Utomo. The development of guidebook followed the 4D-Thiagajaran model which has 4 stages, namely define, design, develop, and disseminate. The types of the data in this study were qualitative and quantitative. The qualitative data was obtained from the validator suggestions. The quantitative data was obtained through validator assessment scores and legibility tests. The instruments used to collect data included validation sheets and questionnaires. The results showed that the practicum guidebook validation percentages were 93.48% (material experts), 100% (learning media expert), and 81.5% (teacher) which were categorized as very feasible. It can be concluded that the biochemistry practicum guidebook is highly suitable to be implemented.
Muito além de fractais, caleidoscópios ou conjuntos de Mandelbrot as teorias da informação e da comunicação
Authors: Pereira Rosane Da Conceição
Published: November 2018

Este artigo constitui uma abordagem crítica sobre algumas contribuições epistemológicas de saberes diversos, em relação às teorias da informação e comunicação contemporâneas. Pretende abrir discussões e ressaltar o problema da constituição do complexo objeto informação e comunicação, além de oferecer inteligibilidade mais ampla quanto ao seu alcance e limites. É a tentativa de desviar os estudos nessa área para a afirmação de um conjunto de saberes em processo, a partir dos conceitos transdisciplinaridade e historicidade. Contudo, sem incorrer em um aglomerado de doxoi nem na utopia de uma ciência plenamente acabada, que apreenda o mundo como uma totalidade intricada, apenas de modo otimista ou pessimista. O trabalho é de continuar o processo com prudência, antes que apoiar visões caleidoscópicas ou mandelbrotianas sobre as ciências da informação e comunicação, afastadas da realidade latino-americana, sobretudo brasileira.
O crítico no fulgor da maturidade
Authors: Moraes Dênis De
Published: November 2018

Resenha do livro:Moacy Cirne. Quadrinhos, sedução e paixão. Petrópolis : Vozes, 2001. 220p. ISBN: 85-326.2486-3