bluuebunny/crossref_metadata_2025 huggingface dataset:
Job-Related Stressors of Classical Instrumental Musicians: A Systematic Qualitative Review
Authors: Vervainioti A , Alexopoulos EC
Published: October 2018

Epidemiological studies among performing artists have found elevated stress levels and health effects, but scarcely the full range of stressors has been reported. We review here the existing literature on job-related stressors of classical instrumental musicians (orchestra musicians).
PubMed, Google Scholar and JSTOR databases were screened for relevant papers indexed up to August 2012. A total of 122 papers was initially identified which, after exclusion of duplicates and those not meeting eligibility criteria, yielded 67 articles for final analysis. We identified seven
categories of stressors affecting musicians in their everyday working lives: public exposure, personal hazards, repertoire, competition, job context, injury/illness, and criticism, but with interrelated assigned factors. The proposed categories provide a framework for future comprehensive
research on the impact and management of musician stressors.
Application of Infrared Thermal Imaging in a Violinist with Temporomandibular Disorder
Authors: Clemente M , Coimbra D , Silva A , Aguiar Branco C , Pinho JC
Published: October 2018

Temporomandibular disorders (TMD) consist of a group of pathologies that affect the masticatory muscles, temporomandibular joints (TMJ), and/or related structures. String instrumentalists, like many orchestra musicians, can spend hours with head postures that may influence the biomechanical
behavior of the TMJ and the muscles of the craniocervicomandibular complex (CCMC). The adoption of abnormal postures acquired during performance by musicians can lead to muscular hyperactivity of the head and cervical muscles, with the possible appearance of TMD. Medical infrared thermography
is a non-invasive procedure that can monitor the changes in the superficial tissue related to blood circulation and may serve as a complement to the clinical examination. The objective of this study was to use infrared thermography to evaluate, in one subject, the cutaneous thermal changes
adjacent to the CCMC that occur before, during, and after playing a string instrument.
Mapping Stress Profile and Rock Quality Variation in Tight Gas Sandstone Across a Geological Setting
Authors: Molenaar Mathieu , Lai Sonia , Kumar Rajeev Ranjan , Subbaih Surej Kumar , Al Ghafri Ali Maayouf , Talreja Rahul , Al Lawatia Redha Hasan , Al Busaidi Salim
Published: October 2018

In an unconventional reservoir exploration process, the horizontal stress profile across different rock types plays a critical role for drilling and frac design optimization. Present study provides insight about the challenge of estimating stress profile and breakdown pressure in tight sandstone gas reservoirs at 4900m-5500m TVD with varying petrophysical parameters across a complex geological setting. A geomechanical model is prepared prior to a hydraulic fracturing job based on open hole geophysical logs and history match borehole images features like breakouts and drilling induced fractures. Advanced sonic shear fast & slow radial profiles are inverted to directly estimate horizontal stress profile in applicable formations to constrain strain at different well locations. This helps to map changes in stress magnitude, contrast and direction in reservoir across different exploration areas. Algorithm has been successfully implemented earlier worldwide in deep water and has been tested successfully in tight shallow sandstone where dispersion data shows crossover of fast & slow shear near wellbore due to hoop stress. 3D anisotropic data from advanced sonic measurement has been utilized to predict true rock fabric based rock mechanical, elastic and stress profile in silty layers. It helps to understand containment of frac across different reservoirs and optimize stages. Rock types based on petrophysical results, image features and estimated breakdown pressure were used as reference for choosing frac stages. Post-frac closure and breakdown pressure values came close to estimated values using geomechanical results and provided confidence in strain values at different fields. Breakdown pressure seems to vary in range of 12500 psi to 19000 psi depending on stress and rock quality for same reservoir. Stress barrier at top of one reservoir vary at various locations as confirmed with tracer and pressure history match which was predicted using geomechanical model. This integrated petrophysical-geomechanics workflow has been utilized in two vertical wells for two reservoirs successfully to understand field level variation in closure and breakdown pressure and map degree of anisotropy with geological variation. Cost effective optimization of Frac design have been achieved through proper integrated approach saving rig time in decision making and avoiding extra stage as confirmed through Tracer logs.
Rock Fabric Analysis Based on Borehole Image Logs: Applications to Modeling Fracture Height Growth
Authors: Diaz H. Gamero , Desroches J.. , Williams R.. , Defeu C.. , Martin J.. , Cannon D..
Published: October 2018

Completion and production stimulation engineers use isotropic or transversely isotropicwith a vertical axis of symmetry (TIV) mechanical earth models (MEM) as an input to predict hydraulic fracture (HF) height growth. Occasionally the MEM results in models that predict fracture heights at odds with the observed fracture height in the field (e.g., fracture hits, microseismic monitoring). A potential solution to this discrepancyis to add rock fabric into the HF modeling process to better match the containment boundaries observed in the field. Laboratory large-block experiments have shown the importance of rock fabric for HF height growth and containment. Rock fabric in organic-rich mudstones (e.g., Barnett) andhybrid sequences (e.g., Wolfcamp, Eagle Ford), results from the depositional and diagenetic history of the basin andcomprises different elements relevant to HF modeling. Key rock fabric elements include: a) thin, hard layers (named stringers); b) weak beds (e.g., ash beds); and c) weak interfaces (e.g., mineralized fractures, lithology contacts).

The firstchallenge in usingrock fabric elements is identifying them with wireline logs (e.g., sonic logs). Because these features are thin, often only a few inches thick or less, they are less than the vertical resolution of most sonic logs. For thatreason, they are generally not considered in the creation of a MEM, which is the key input for modeling HF height growth. A novel rock fabric analysis workflow specifically targeted to HF height growth has been developed. It is based on high-resolution borehole images and the interpretation of the interaction of tensile drilling induced fractures with rock fabric. Qualitative flags (thickness and density of occurrence) are generated for all rock fabric elements found relevant to HF height containment, for subsequent integration into HF modeling. This offers a data-driven workflow to solve discrepancies between the hydraulic fracture heights predicted by models and those observed in the field. For weak interfaces, these flags are integrated into hydraulic fracture models as boundaries where the rock will undergo shear displacement and the fluid flow will experience complexity in its vertical path that will lead to effective containment. It is important to note that a single boundary might not stop fracture propagation, but rather a succession of boundaries is typically required to sufficiently contain a hydraulic fracture.
Formation Breakdown Pressure Prediction with Artificial Neural Networks
Authors: Kiss Akos , Fruhwirth Rudolf K. , Pongratz Reinhard , Maier Robert , Hofstätter Herbert
Published: October 2018

An innovative and more accurate method for formation breakdown pressure (FBP) prediction based on self-learning artificial neural networks (ANNs) is presented. Results are compared to industry wide accepted deterministic FBP prediction models. ANN model validity is proven to meet FBP prediction within a 10% error range demonstrating that ANN models are outperforming the eleven deterministic prediction models investigated.

Using field data from four different countries neural network models were trained including automatic prevention of over fitting and over training as well as avoiding to a great extent trapping in local error minima. Since field data are very heterogeneous, statistics about the model performance was controlled and validated for quality assurance via multifold cross validation.

The study is based on125 plus 14 (for verification purposes) data sets from fracture work executed with FBPs ranging from 4,333 to 16,707 psi. In a first step the data were applied to deterministic models used in the industry to investigate, evaluate and prove their validity. The results were compared and analysed according to an error analysis framework identifying their accuracy and precision. Six error analysis parameters were determined and the individual models ranked accordingly. Although some of the deterministic models perform well in specific areas, it was not possible to individuate a model which is valid for all investigated data sets meeting the error criteria of ± 10%. In the second step the same data were used to train neural network models. The results were evaluated, refined and QA/QCed for their robustness. The error analysis based on multifold cross validation proved that the proposed ANN models and methods provide consistent and robust results in nearly all cases within a ±10% error range from the actual measured value in all types of reservoir rock.

The novelty of the proposed method is its high accuracy and robustness in heterogeneous conditions. It was successfully applied to large FBP ranges, different locations and all types of reservoir formations. Because of matured QC tools to prove accuracy and validity of the proposed model, it can be easily retrained to handle new conditions providing results according to the set error criteria when additional real FBP data are available. For specific fields this can lead to a more restrict predicition criteria range. At the same time, the model can be used in case of incomplete data.
Vertical Well Fracture Height Growth Prediction in Thick, Condensate-Rich, Stacked Tight Gas Sandstones and Implications for Horizontal Wells
Authors: Dawson W.. , Ishteiwy O. A. , Al Busafi M.. , Masood N.. , Spain D. R.
Published: October 2018

Khazzan is a tight to low-end conventional gas field in the Sultanate of Oman. The target reservoir is a series of stacked sandstones with highly stressed, intercalated mudstones, which may provide baffles and barriers to vertical stimulation growth.

Calibrated petrophysical and geomechanical models are integrated within stimulation models to provide high confidence in stimulation geometry. Radioactive (RA) Tracer logs have been used on key wells throughout the development to determine stimulation height growth beyond and within the perforated interval.

Multi-stage stimulations deviating from the standard completion design may be required as the development covers an increasingly larger area. The calibrated stimulation models guide the completion design to ensure the resources are adequately stimulated.

Sensitivities on gross thickness, reservoir quality and fluids are performed, along with the timing of the subsequent stimulations, to determine the optimum stimulation strategy. This enables the long-term stimulation strategy to incorporate the right design at the right point in the well lift to maximise the value. Additional insights into horizontal well completions strategies are gained.

The completions petrophysicist provides a key integration point for the multiple disciplines involved in "geo-engineered completions".
Unlocking Tight Gas Volume with Integrated Multidisciplinary Diagnostic Approach
Authors: Lukmanov Rinat , Ibrahim Ehab
Published: October 2018

Miqrat is a complex clastic deep tight gas reservoir in the North of the Sultanate of Oman. The Lower unit of the Miqrat formation is feldspatic sand characterized by low permeability not exceeding 0.1 mD and porosity up to 12 %. Based on results of the appraisal campaign of Field X, it contains significant volume of gas. However the production test data after fraccing showed mixed results. The objective of this study to explain the production behavior in relation to the frac geometry.

Understanding the reason of possible overestimation of log derived Hydrocarbon saturation is important. Thus the interpretation of conventional and special logs was revisited. In parallel, all the available core data including SCAL and thin sections were dissected. Besides, the analysis of hydraulic fracture propagation, well tests, cement quality, PLT including Spectral Noise Log was performed.

The wells were subdivided into categories according to their production. –wells producing no water–wells with water channeling from the water leg of Middle Miqrat–wells with transition zone intervals with two-phase inflow of water and gas.

There are three main challenges that needed to be overcome. First challenge is to identify the high uncertainty in hydrocarbon saturation from the resistivity logs. Petrophysical evaluation shows that porosity profile derived from logs looks very similar in all wells with insignificant lateral variations. Hydrocarbon saturation estimated from logs looks also similar regardless of how deep or shallow the well is. However, production tests show different results, e.g. different flow rates and high water-cut are observed in some wells.

The second challenge to keep the frac height below the boundary between Lower Miqrat and Middle Miqrat, which consist of around 3 to 7 meters of shale and in most of the field it is bound with water. The third one is to cover the upper part of the zone below the shale since it is the best part of Lower Miqrat without breaking to the water leg of Middle Miqrat. A geomechanical model was created and several frac model iterations were run since in the early appraisal well that boundary was broken.

Investigation through multidisciplinary integrated team led to unlock the tight gas reserves in Lower Miqrat. Based on open hole log interpretation to create a geomechanical model. That model is being calibrated with DFIT, 3 different case hole logs and confirmed with production.
Experimental Investigation on Tool-Free Multi-Stage Acid Fracturing of Open-Hole Horizontal Wells by Using Diversion Agents
Authors: Mou Jianye , Hui Xuezhi , Wang Lei , Zhang Shicheng , Ma Xinfang
Published: October 2018

Multi-stage acid fracturing of horizontal wells is a necessary and effective technology in developing tight carbonates. In open-hole horizontal wells in high-temperature, naturally fractured deep formations, segmentation with tools is of high risk and costly, even ineffective sometimes, so segmentation with diversion agents is alternative to tools and was pilot tested in some fields. The stimulation results were satisfactory, and pressure response feature was in accord with expectation. However, this technique has not been studied experimentally or numerically extensively yet.

In this study, we investigated tool-free multi-stage fracturing experimentally in open-hole horizontal wells with diversion agents. Firstly, we designed a multi-stage tri-axial fracturing system and experimental procedures to satisfy the requirements of diverted fracturing in horizontal wells. Next we conducted a series of experiments to investigate feasibility of multi-stage fracturing with diversion agents using natural carbonate outcrop cubic blocks with the size of 300*300*300mm. CT scanning was used to obtained detailed fracture geometry after experiment. Finally we analyzed the effect of diversion agent type, concentration, and injection procedure on diversion.

The experimental results show that multi-stage fractures perpendicular to the open-hole horizontal wells was created, which verifies the validity of the tool-free multi-stage fracturing of open-hole horizontal wells with diversion agents. Proper agents or combinations can effectively plug the fracture generated previously and generate pressure high enough to initiate another fracture. The breaking pressure or propagation pressure of second fracture was monitored higher than the one of the first fracture. Under experiment conditions, 1-3mm fiber or combination of fiber and particle (0.8-1.2mm) can effectively plug fractures and realize segmentation. Concentration of diversion agents tested ranges 0.4-1.6wt%. Injection procedure for two-stage fracturing was fracturing fluid + diversion fluid + fracturing fluid. The amount of diverter and open-hole length are the vital factor for the success of experiments.

This study newly designed a multi-stage tri-axial fracturing system and experimental procedures for the diverted fracturing. The finding verified the validity of the tool-free multi-stage fracturing of open-hole horizontal wells with diversion agents and provides fundamental for field treatment design.
Drilling Through Depletion in the Bakken; Using Drill Bit Geomechanics to Inform Fracture Stimulation
Authors: Weddle P.. , McChesney J.. , Grande R.. , Marshall E.. , Scott E. L.
Published: October 2018

Seven years ago, some operators in the United States began geo-engineering completions to more efficiently stimulate unconventional horizontal wells. Typically, engineers and geoscientists rely on expensive open-hole logs or the over-simplified use of gamma ray to infer mechanical rock properties along the lateral. Engineers then select treatment stage intervals and place perforation clusters in similarly-stressed, "like rock" to minimize the geomechanical variability. Instead of traditional open-hole logging, this paper discusses geo-engineering applications of drill bit geomechanics.

Drill bit geomechanics is an innovative method for formation evaluation and reservoir characterization. It uses direct, continuous, high-resolution measurements of drilling vibrations recorded downhole. Using earthquake seismology models, one can infer rock properties from the measured drilling vibrations. These rock properties include Poisson's Ratio, Young's Modulus of Elasticity, and the presence of fractures perpendicular to the horizontal well. In this study, the Operator collected drill bit geomechanics data while drilling a new well ~8-34 ft below three existing horizontal wellbores, with over seven years of continuous production. The study well was a 9,500-ft lateral in the Bakken Formation in North Dakota. Using drill-bit-geomechanics-derived rock properties, the operator could confidently geo-engineer a completion, accounting for reservoir depletion from the older wells.

The drill bit geomechanics data showed dramatic changes in mechanical properties and fracturing where the study well intersected the older wells’ stimulated reservoir volumes (SRVs). The operator had a general idea of the wells’ SRVs from microseismic data acquired during two wells’ stimulations. Using the drill bit geomechanics data from the study well, the operator could more effectively constrain the drainage ellipses from the sparse microseismic data. The operator geo-engineered a 27-stage completion by combining "like rock" of the same reservoir pressure. Measured Instantaneous Shut-In Pressures (ISIPs) during the completion showed significantly lower ISIPs for the partially-depleted stages closest to the older wells. Thus, combining similarly-pressured stages was critical to the completion's success. Well performance has proven to be excellent for the area, even when compared to wells without depletion from older producing wellbores.

As shown in this case study, drill bit geomechanics is an economic, useful tool to identify depletion and accurately measure rock properties and fractures at a very high resolution.
3-D Interactions of Hydraulic Fractures with Natural Fractures
Authors: Shrivastava Kaustubh , Agrawal Shivam , Kumar Ashish , Sharma Mukul M.
Published: October 2018

During hydraulic fracturing, the interaction of hydraulic fractures with natural fractures can result in the formation of complex fracture networks. In the past these interactions have been captured in hydraulic fracturing models using crossing criteria developed based on two-dimensional geometries. In this work, we investigate the interaction of hydraulic fractures and natural fractures in three-dimensions and demonstrate that there can be significant differences in the observed interactions.

A hydraulic fracturing simulator is presented that solves the coupled fluid flow and geomechanics problem for three-dimensional fractures. The simulator captures the physics of fracture growth and the intersection of hydraulic fracture with pre-existing discrete fracture network. The model employs a robust algorithm to account for the stress relaxation due to the slippage of natural fractures. The displacement of failed natural fracture elements is calculated rigorously. The model allows the partial failure of three-dimensional natural fractures and accurately calculates the stresses acting on the plane of the natural fracture.

It is shown that a natural fracture inclined at an angle to an approaching hydraulic fracture experiences compression in one region (due to the stress shadow of the growing hydraulic fracture) and tension in other regions (in front of the approaching hydraulic fracture tip). The generated stresses can fail the natural fracture partially. The failure of the natural fracture relaxes the stresses around it, which can modify the direction of propagation of the approaching hydraulic fracture. In addition, if the elliptical front of the hydraulic fracture crosses an intact planar natural fracture, the three-dimensional geometry results in a line of intersection (between natural fracture and hydraulic fracture). This can lead to failure of the natural fracture even after the elliptical front has partially crossed the natural fracture. Such an interaction can allow the hydraulic fracture to both cross the natural fracture and activate (or dilate) it. These effects cannot be captured by two-dimensional simulations. This work improves our understanding of the interaction between hydraulic fractures and natural fractures. The novel results provide new insights into the mechanisms responsible for the complexity that is often observed in hydraulic fractures.
Twelve Years and Twelve Thousand Multi-Stage Horizontal Wells in the Bakken - How is Industry Continuing to Increase the Cumulative Production Per Well?
Authors: Pearson C. Mark , Griffin Larry G. , Strickland Stacy L. , Weddle Paul M.
Published: October 2018

Multi-stage horizontal well designs have been used since 2007 in the Bakken oil-field of North Dakota. Since then over 12,000 wells have been completed in either the Middle Bakken or Three Forks zones. Early-time production rates as measured by 180-day state-reported cumulative production have increased 4-fold over this period as industry has pursued a program of innovation and continuous improvement in completions technology with production per well increasing in ten of the twelve years.

Through a "Big-Data" analytical study comparing geological data, completions parameters, and state-reported production results the authors have evaluated the fundamental changes that have guided industry to produce these results over the past twelve years. While geological changes in different areas drove both the drilling "mania" during times of $100 oil and consequent contraction of the industry when wellhead prices dropped below $40 per BO; it is the advances in completion design and hydraulic fracturing that have driven macro performance over the twelve years - and resulted in this significant increase in production per well. These completion advances have allowed the region to compete on a global scale with production that while dipping to ~1.0 Million bopd in 2016 has now rebounded to over 1.2 Million bopd.

Large datasets of geological, completions and production data take years to assemble and analyze. Through the authors use of multivariate analysis techniques this paper presents the deterministic factors affecting well performance in the Bakken and provides guidance and best practices towards applying these techniques in emerging international plays.
An Integrated Analytics Platform for Completion Optimization and Reservoir Characterization
Authors: Yang Junjie , Stolyarov Sergey , Cazeneuve Eduardo , Simmons Jason , Kotov Sergey , Gadzhimizaev David
Published: October 2018

As laterals become longer with more stages, large datasets make evaluation of the information complicated and time consuming. Variations in the obtained data adds more uncertainty to the main industry challenges and questions, such as optimal well spacing, optimal completion (e.g., type of completion, stage and cluster spacing), optimal stimulation treatment (e.g., proppant type, mass and concentration, fluid type, volume and composition).

This paper describes a novel automated framework for completion optimization and post-fracture analysis. For pre-fracture analysis, this framework utilizes an integrated dataset from drilling and wireline logs, and automatically places clusters based on heterogeneity along the lateral. This information is then coupled with post-fracture data to examine fracture treating information (breakdown pressure, instantaneous shut in pressure, etc.) and correlate it to rock properties from each fracture stage. The newly identified correlation is looped back into the framework as a guideline for future frac design.

The strong correlation between subsurface rock properties and hydraulic fracture treatment parameters suggests that the previous captured heterogeneity reveals the fracture design efficiency, and the multivariable evaluation process can be accelerated by the machine learning platform. A statistical model was built on geomechanical and petrophysical properties used to design fracture treatments. Meanwhile, the platform automatically evaluates fracture treating signatures (surface treating pressure, pumping rate, ISIP, etc.) and links them with subsurface information for each stage. When the model is trained with a sufficient amount of data, it can be used as a real-time advisor that suggests a fracture treatment schedule (pump rate, sand concentration, fluid volume). The fracture geometry as well as the treatment efficiency can be optimized with the enhanced design. The model can eliminate or reduce the need for expensive subsurface characterization logging tools and provide quick recommendations for changes to the treatment.

This paper introduces an integrated solution to optimize fracture treatment design assisted by data analytics that can be further improved to solve other multivariable problems in the oil and gas industry.
A Quick Look Approach for Determining Instantaneous Shut-in Pressure ISIP and Friction Losses from Hydraulic Fracture Treatment Falloff Data
Authors: Menouar Nadia , Liu Guoqing , Ehlig-Economides Christine
Published: October 2018

The instantaneous shut-in pressure (ISIP) picked from the pressure falloff following each hydraulic fracturing treatment stage has been used to evaluate stress shadowing effects and required for modeling injection treatment behavior. However, the traditional methods for estimating ISIP as the pressure extrapolated back to the pumping time from a straight line through an arbitrary series of points on a plot of Cartesian falloff pressure versus time or the log of time have no theoretical justification. Further, the ISIP picked by either of these approaches is highly dependent on the selected points. In this paper, we show a more rigorous approach to quantify the ISIP and that also enables estimation of parameters governing wellbore, perforations and near-wellbore tortuosity friction losses.

The wellbore storage (WBS) effect complicates straightforward picking of the ISIP from the pressure curve at shut-in. The existing diagnostic fracture injection test (DFIT) analysis model coupling WBS with friction dissipation that enables estimation of friction losses and the ISIP for the DFIT analysis also enables estimation of these same parameters from falloff data following the hydraulic fracturing treatment.

The pressure difference and its derivative in the log-log diagnostic plot generated from the falloff at the end of the fracture pumping treatment is an effective diagnostic plot to identify portions of the data dominated by WBS and friction losses. Coupled WBS and friction loss dominate the immediate pressure falloff after the end of pumping, and frequently the treatment data include sufficient time to quantify friction losses. The wellbore and perforation friction loss and the total friction loss are picked using the log-log diagnostic plot. Changes in the correctly quantified ISIP estimated for successive treatment stages along the horizontal well may be related to a stress shadowing effect. Field examples demonstrate how the ISIP profile along a well compares between this approach and common field practices.

The paper provides a quick approach to evaluate friction losses and the ISIP from hydraulic fracturing treatment falloff data. The approach provides much more accurate and less uncertain ISIP estimates than current field practices.
Stimuli-responsive Drug Delivery Nanocarriers in the Treatment of Breast Cancer
Authors: Oshiro-Júnior João A. , Rodero Camila , Hanck-Silva Gilmar , Sato Mariana R. , Alves Renata Carolina , Eloy Josimar O. , Chorilli Marlus
Published: October 2018

Stimuli-responsive drug-delivery nanocarriers (DDNs) have been increasingly reported
in the literature as an alternative for breast cancer therapy. Stimuli-responsive DDNs
are developed with materials that present a drastic change in response to intrinsic/chemical
stimuli (pH, redox and enzyme) and extrinsic/physical stimuli (ultrasound, Near-infrared
(NIR) light, magnetic field and electric current). In addition, they can be developed using different
strategies, such as functionalization with signaling molecules, leading to several advantages,
such as (a) improved pharmaceutical properties of liposoluble drugs, (b) selectivity
with the tumor tissue decreasing systemic toxic effects, (c) controlled release upon different
stimuli, which are all fundamental to improving the therapeutic effectiveness of breast cancer
treatment. Therefore, this review summarizes the use of stimuli-responsive DDNs in the treatment
of breast cancer. We have divided the discussions into intrinsic and extrinsic stimuli and
have separately detailed them regarding their definitions and applications. Finally, we aim to
address the ability of these stimuli-responsive DDNs to control the drug release in vitro and
the influence on breast cancer therapy, evaluated in vivo in breast cancer models.
Design, Synthesis and Biological Potential of 5-(2-Amino-6-(3/4-bromophenyl)pyrimidin-4-yl)benzene-1,3-diol Scaffolds as Promising Antimicrobial and Anticancer Agents
Authors: Kumar Sanjiv , Narasimhan Balasubramanian , Lim Siong Meng , Ramasamy Kalavathy , Mani Vasudevan , Shah Syed Adnan Ali
Published: October 2018

Background:

A series of 5-(2-amino-6-(3/4-bromophenyl)pyrimidin-4-yl)benzene-1,3-diol
scaffolds was synthesized by Claisen-Schmidt condensation and characterized by NMR, IR, Mass and
elemental analyses.

Methods:

The synthesized pyrimidine scaffolds were screened for their antimicrobial activity by tube
dilution method as well for antiproliferative activity (human colorectal (HCT116) cancer cell line) by
SRB assay.

Results:

The antimicrobial screening results demonstrated that compounds, k6, k12, k14 and k20 were
found to be the most potent ones against selected microbial species. The anticancer screening results indicated
that compounds, k8 and k14 displayed potent anticancer activity against cancer cell line (HCT116).

Conclusion:

Further, the molecular docking study carried to find out the interaction between active
pyrimidine compounds with CDK-8 protein indicated that compound k14 showed best dock score with
better potency within the ATP binding pocket and may be used as a lead for rational drug designing of
the anticancer molecule.
2-Mercaptobenzimidazole Schiff Bases: Design, Synthesis, Antimicrobial Studies and Anticancer Activity on HCT-116 Cell Line
Authors: Tahlan Sumit , Narasimhan Balasubramanian , Lim Siong Meng , Ramasamy Kalavathy , Mani Vasudevan , Shah Syed A.A.
Published: October 2018

Background:

Increased rate of mortality due to the development of resistance to currently
available antimicrobial and anticancer agents initiated the need to develop new chemical entities for
the treatment of microbial infections and cancer.

Objective:

The present study was aimed to synthesize and evaluate antimicrobial and anticancer activities
of Schiff bases of 2-mercaptobenzimidazole.

Methods:

The Schiff bases of 2-mercaptobenzimidazole were synthesized from 4-(2-(1H-benzo[d]-
imidazol-2-ylthio)acetamido)benzohydrazide. The synthesized compounds were evaluated for antimicrobial
and anticancer activities by tube dilution method and Sulforhodamine-B (SRB) assay, respectively.

Results:

Compounds 8 (MICpa, an = 2.41, 1.20 µM/ml), 10 (MICse, sa = 2.50 µM/ml), 20 (MICec = 2.34
µM/ml) and 25 (MICca = 1.46 µM/ml) showed significant antimicrobial activity against tested bacterial
and fungal strains and compounds 20 (IC50 = 8 µg/ml) and 23 (IC50 = 7 µg/ml) exhibited significant
anticancer activity.

Conclusion:

In general, the synthesized derivatives exhibited moderate antimicrobial and anticancer
activities. Compounds 8 and 25 having high antifungal potential among the synthesized compounds
may be taken as lead molecules for the development of novel antifungal agents.
Ionic Liquid Assisted Synthesis of Some 2-Aminobenzenethiols
Authors: Jangid Dinesh K. , Ameta Keshav L. , Dhadda Surbhi , Guleria Anjali , Goswami Prakash G. , Khandelwal Chandra L.
Published: October 2018

Ionic Liquid assisted efficient synthesis of some 2-aminobenzenethiols has been reported
using three different Ionic Liquids (ILs) namely methylimidazolium tetrafluoroborate [MIM]+[BF4]−,
methylimidazolium chloride [MIM]+[Cl]− and methylimidazolium nitrate [MIM]+[NO3]−. A comparative
study has been carried out for the synthesis of target molecules in the presence and absence of IL,
leading to conclusion that maximum yield has been observed with [MIM]+[BF4]−.
NSCLC Structure-activity Relationship (SAR) Study of Diisothiocyanates for Antiproliferative Activity on A549 Human Non-small Cell Lung Carcinoma (NSCLC)
Authors: Chatwichien Jaruwan , Prachavna Buntarika , Suntivich Rinrada , Kumphune Sarawut
Published: October 2018

Isothiocyanate functional group (-N=C=S) is widely accepted as an important moiety for anti- cancer effects of naturally occurring isothiocyanate compounds (ITCs). Herein, a series of diisothiocyanate (diITCs) derivatives were synthesized and evaluated in antiproliferative assays on A549 human non-small cell lung cancer and IMR90 human foetal lung cell lines for structure-activity relationship (SAR) and cancer cell selectivity studies. Results showed that aliphatic and benzylic diITCs were more cytotoxic to A549 cells than natural ITCs; benzyl isothiocyanate (BITC) and phenyl isothiocyanate (PITC), and a currently available anticancer drug; etoposide. Aromatic diITCs were not as active. Notably, most of the diITCs reported in this work were significantly more selective than etoposide to inhibit proliferation of the cancer cells (A549) over the normal cells (IMR90). This study demonstrated a guideline to modify chemical structures of diITCs for anti-NSCLC agents.
Metabolic Effects of Metformin in Humans
Authors: Adeva-Andany María M. , Rañal-Muíño Eva , Fernández-Fernández Carlos , Pazos-García Cristina , Vila-Altesor Matilde
Published: October 2018

Background:

Both insulin deficiency and insulin resistance due to glucagon secretion cause
fasting and postprandial hyperglycemia in patients with diabetes.

Introduction:

Metformin enhances insulin sensitivity, being used to prevent and treat diabetes, although
its mechanism of action remains elusive.

Results:

Patients with diabetes fail to store glucose as hepatic glycogen via the direct pathway (glycogen
synthesis from dietary glucose during the post-prandial period) and via the indirect pathway (glycogen
synthesis from “de novo” synthesized glucose) owing to insulin deficiency and glucagoninduced
insulin resistance. Depletion of the hepatic glycogen deposit activates gluconeogenesis to replenish
the storage via the indirect pathway. Unlike healthy subjects, patients with diabetes experience
glycogen cycling due to enhanced gluconeogenesis and failure to store glucose as glycogen. These defects
raise hepatic glucose output causing both fasting and post-prandial hyperglycemia. Metformin reduces
post-prandial plasma glucose, suggesting that the drug facilitates glucose storage as hepatic glycogen
after meals. Replenishment of glycogen store attenuates the accelerated rate of gluconeogenesis
and reduces both glycogen cycling and hepatic glucose output. Metformin also reduces fasting hyperglycemia
due to declining hepatic glucose production. In addition, metformin reduces plasma insulin
concentration in subjects with impaired glucose tolerance and diabetes and decreases the amount of insulin
required for metabolic control in patients with diabetes, reflecting improvement of insulin activity.
Accordingly, metformin preserves β-cell function in patients with type 2 diabetes.

Conclusion:

Several mechanisms have been proposed to explain the metabolic effects of metformin,
but evidence is not conclusive and the molecular basis of metformin action remains unknown.
Regulation for Prescribing and Dispensing System of Cannabis: the Italian Case
Authors: Minghetti Paola , Marini Valentina , Zaccara Viviana , Casiraghi Antonella
Published: October 2018

Background:

The medicinal properties of cannabis are now recognized. Indeed, in many
countries, lawmakers have introduced specific laws and programmes to allow patients to use cannabis
preparations in various forms; nevertheless, controversial situations can still be found. In Europe, medicinal-
grade cannabis is mainly available as standardized dried flower tops of the cannabis plant used
in magistral formulas. These are pharmaceutical preparations compounded in a pharmacy – following
Good Compounding Practices - in accordance with a physician’s prescription for an individual patient.
Aim of this work is to discuss the available Cannabis based preparations and regulation for prescription
and distribution, with reference to Italy.

Methods:

We undertook a structured search of Italian laws, ministerial decree and circulars related to
therapeutic use of Cannabis, interpreted in light of Italian Society of Compounding Pharmacists’ (SIFAP)
position.

Results:

Seven documents were analysed. Cannabis can be orally administered to patients - as a dried
drug dosed in filter or capsules for infusion or as an extract in olive oil prepared in a pharmacy - or inhaled
with a specific vaporizer. Considering the costs and limited availability of Dutch medicinal-grade
cannabis, the Italian Government, with the latest Decree of November 9th, 2015, has authorized the
production of cannabis in the Military Pharmaceutical Chemical Institute on Florence, describing also
the therapeutic use of cannabis and the requirements to be adhered to by physicians and pharmacists.

Conclusion:

A well-established national regulation guarantees the proper therapeutic use of Cannabis.
Description of preparation method in monograph Pharmacopoeia will be the way to assure quality and
therefore the efficacy of these products.
Simultaneous Bioanalysis of Prodrug Oseltamivir and its Metabolite Oseltamivir Carboxylic Acid in Human Plasma by LC/MS/MS Method and its Application to Disposition Kinetics
Authors: Sireesha Dodda , Ajitha Makula , Narayana Kandhagatta Raj
Published: October 2018

Introduction:

A selective, sensitive, precise and rapid analytical method using liquid chromatography-
tandem mass spectrometry (LC/MS/MS) for simultaneous determination of oseltamivir and
oseltamivir carboxylic acid in plasma has been developed and validated, using oseltamivir-D5 and oseltamivir
acid-D3 as internal standards.

Methods:

The analytes were extracted from 300μL of human plasma using solid phase extraction technique.
A mixture of methanol and 0.1% formic acid (60:40, v/v) was used as mobile phase at a flow rate
of 0.7mL/min, to separate the analytes on Zorbax SB-C18 (50x4.6mm, 3.5μm) analytical column.

Results:

The calibration curves obtained were linear over the concentration ranges of 0.5-200ng/mL and
2.0-800ng/mL for oseltamivir and oseltamivir carboxylic acid respectively. A run time of 2.5min makes
it possible to analyze more than 350 plasma samples in a day, thereby increasing the productivity.

Conclusion:

The present method was applied successfully to a clinical pharmacokinetic study in South
Indian male subjects with 75mg oseltamivir phosphate capsule under fasting conditions and the results
were authenticated by incurred sample reanalysis.
COMPARISON OF THREE OPTIONS FOR TREATMENT OF CALCANEAL FRACTURE
Authors: Kalensky V. O. , Ivanov P. A. , Sharifullin F. A. - K. , Zabavskaya O. A.
Published: October 2018

Until now the problem of selecting a conservative or operative treatment option for calcaneal fractures and moreover the choice of the most optimal surgical procedure for such lesions have not been solved. Thus, comparative studies in this area is one of the most important tasks of the modern traumatology. Purpose of the study — to compare treatment outcomes, pattern and complications rate following the use of three treatment options for calcaneal fractures. Material and Methods. The authors analyzed treatment outcomes of 95 patients from 2013 till 2016. Mean age of patients was 39.04±12.51 years. Patients were divided into three groups: group 1 consisted of 41 patients with 54 fractures who underwent functional conservative treatment; group 2 consisted of 18 patients with 22 fractures treated by open reduction and plate fixation; group 3 consisted of 36 patients with 40 fractures treated by minimally invasive reduction and intramedullary fixation. Groups did not differ in respect of risk factors rate and rate of surgical risks under ABCDEF scale. Outcomes were evaluated basing on roentgenological criteria of reduction, complications rate and the functional scales FFI (Foot Function Index) and LEFS (Lower Extremity Functional Score). Results. Mean follow up was 20.8±9.0 months. Catamnesis was controlled in 68 out of 95 patients (71.6%). Variances were observed for all criteria of reduction quality between group 1 (no reduction) and groups 2 and 3. Groups 2 and 3 demonstrated similar criteria in respect of reduction quality of posterior articular surface, restoration of height and axis of calcaneus (р0.05). FFI and LEFS scores in group 1 were inferior to results in groups 2 and 3 (р0.05) at 6 and 12 months follow up. At 24 months follow up the variances persisted for mean values but were not statistically significant (р0.05). No differences between groups 2 and 3 were observed during all follow up terms (р0.05). Sum rate of complications in wound healing in group 2 was significantly higher than in groups 1 and 3 (р = 0.033). Conclusion. Any of the described options of surgical treatment resulted in an earlier functional restoration after calcaneal fractures as compared to conservative treatment. Reduction quality and late functional outcomes did not vary between the study groups, however, the rate of complications for wound healing in the group with open internal fixation was higher.
HOW MANY REVISION ARTHROPLASTIES DO WE UNDERTAKE PRIOR TO ARTHRODESIS? (CASE REPORT OF A PATIENT WITH RHEUMATOID KNEE ARTHRITIS)
Authors: Kulyaba T. A. , Kornilov N. N. , Croitoru I. I. , Solomin L. N. , Bovkis G. Yu. , Korchagin K. L. , Ivanov P. P.
Published: October 2018

The authors present a clinical case of a female patient with seropositive rheumatoid polyarthritis mainly affecting the knee joints. The patient underwent a primary total bilateral knee replacement. Surgical site infection required multiple revisions including replacement of extensive bone defects of AORI type 3 by structural femur and tibia allografts as well as allografting of extensor mechanism. Repeated attempts to eliminate infection, to gain support ability of extremities and joints motion were not successful. Long-term staged surgical treatment resulted in removal of prostheses and bilateral knee arthrodesis to restore support function of the extremities.
STAGED SURGICAL RECONSTRUCTION OF MASSIVE PELVIC DEFECT
Authors: Pavlov V. V. , Pronskikh A. A. , Mamyladze T. Z. , Bazlov V. A. , Efimenko M. V. , Zhilenko V. Yu. , Tsegelnikov M. M.
Published: October 2018

Purpose of the study — to illustrate on a particular clinical case an option of treatment for patients with severe pelvic defects by a staged surgery: vascularized bone grafting and revision arthroplasty using custom made implant produced by laser sintering based on layered 3D-visualisation. Material and Methods. Female, 61 years old, was admitted to clinic in 2016 with aseptic loosening of acetabular component and polyethylene insert wear following arthroplasty with total cementless prosthesis. Revision arthroplasty was made with hemispherical augment and anti-protrusion ring. On day 7th after the surgery a dislocation of prosthesis head, pubic bone fracture, migration of acetabular component and bone defect with pelvic discontinuity occurred due to trauma. To restore continuity of the pelvic ring and supportability of the lower limb the authors performed a staged multisession procedure: removal of prosthesis, free vascularized bone grafting by costal vascular pedicle graft and plating fixation of the pelvis. 6 months after the first stage a custom made prosthesis was implanted. Such prosthesis was produced based on a 3D pelvis reconstruction model by layered visualization and with evaluation of bone density on the Hounsfield scale and was printed on 3D-printer by laser sintering from LPW-TI64-GD23-TYPE5 titanium. Results. The authors did not observe any septic complications, dislocations and components migration in the early postoperative period. Function was assessed by Harris Hip Score. Scores prior to arthroplasty by a custom made implant was 12 points, one month postoperatively — 30 points, three months postoperatively — 51 points, six months postoperatively — 74 points. Life quality scores by SF-36 were reported as follows: prior to surgery РН — 21.32; МН — 40.92; one month postoperatively РН — 40.66; МН — 55.80; three months postoperatively РН — 52.14; МН — 57.81; six months postoperatively РН — 62.46; МН — 72.08. Conclusion. Vascularized bone autoplasty allows to restore pelvic continuity, and the use of custom made implants — to restore supportability of the lower limb and hip function in case of an extensive pelvic defect.
SURGICAL TREATMENT OF TRAPEZIOMETACARPAL OSTEOARTHRITIS (REVIEW)
Authors: Rodomanova L. A. , Orlova I. V.
Published: October 2018

The sellar joint plays a key role in wrist function ensuring thumb contraposition when gripping. Lesions of sellar joint are accompanied by pain syndrome and deformity of the first metacarpal which substantially affects life quality of the patients. The authors carried the analysis of literature dedicated to surgical treatment of degenerative lesions of trapeziometacarpal joint. The present review describes features of joint anatomy and biomechanics, reports the key factors contributing to disease progression, covers various approaches and criteria for selection of surgical options for reconstruction of sellar joint.