bluuebunny/crossref_metadata_2025 huggingface dataset:
A Method for Estimation of Minimum Effective Pore Throat Radius from Routine Core Analysis Data in Chalk and its Applications
Authors: Nourani Meysam , Schovsbo Niels Hemmingsen , Meyer Aurelien G. , Taheriotaghsara Mirhossein , Sigalas Lykourgos , Olsen Dan , Stemmerik Lars
Published: May 2019

A method for estimating minimum effective pore throat radius from Routine Core Analysis porosity and absolute permeability data is introduced for chalk samples. This method can reduce the need for conducting mercury capillary pressure measurement in the lab to obtain minimum effective throat radius of chalk samples and allow sample screening prior to time consuming core flood.

The investigation was based on four sets of chalk porosity and permeability data from Rørdal, Stevns Klint and two North Sea wells from Dan and Tyra SE fields. For each porosity and absolute permeability data point, three new parameters are calculated from the entire data set of porosity and absolute permeability values. Using these parameters, the model estimates capillary pressures at very low mercury saturations. First, the capillary entry pressure is calculated from Røgen and Fabricius’ empirical correlation. Hereafter a line is fitted between capillary pressures and mercury saturations at very low mercury saturations including the mercury entry point. The extrapolated line crosses the capillary pressure curve at a high mercury saturation between 0.91 and 0.99, which represents a minimum affective pore throat radius. The validity of the method is verified using a set of mercury capillary pressure measurements of chalk core samples. In the following, a correlation between ultimate laboratory oil recovery achieved from a water flooding process, and an expression consists of minimum effective pore throat radius and specific surface area is presented. Our analysis shows that higher oil recovery by water flooding is related to lower minimum effective pore throat radiuses and higher average pore throat radiuses. Using this simple relationship, one can screen samples and evaluate ultimate oil recovery performance by water flooding before conducting core-flooding experiments. In addition, an empirical index is developed to estimate wettability of chalk samples from calculated Rmin, Rave and Rmax of chalk samples.
Multi-String Isolation Logging - A Cost Effective Solution for P&A
Authors: Zhang Jun , Mahbod Pouya , Shafer Randall , Mueller Dan , Anderson Callum
Published: May 2019

During offshore oil and gas well decommissioning, well casing cement bond verification is frequently a critical initial step of well plug and abandonment (P&A) operations. This is done to determine the isolation between geological intervals. To acquire the essential data, conventional cement bond logs (CBLs) and ultrasonic imaging logs require unimpeded access to the casing annulus. Consequently, the production tubing needs to be removed from the wells. These operations are costly as they require securing the well and removing the tubing with an offshore rig, in some cases a mobile offshore drilling unit. If cement integrity or isolation could be determined without removing the production tubing, operational time and costs would be significantly reduced. Hence, multi-string cement bond evaluation for isolation verification without pulling the tubing has been desired by the oil and gas industry for many years.

The innovation described in this paper, consisting of a novel methodology and an associated logging apparatus, leads to a new technique that can evaluate cement bond or isolation around the casing through the production tubing. The acoustic energy emitted and received by a logging tool inside the production tubing travels through tubing and the surrounding annulus to determine the attenuation caused by the material behind the outer casing. The smaller bonding signal, challenged by the dominating signal from the tubing wall, is then successfully identified through unique frequency domain signal processing.

The accuracy of a multi-string logging technology has been verified by extensive offshore field tests in Southern North Sea. Side-by-side comparisons with conventional CBL and ultrasonic logs after the tubing is pulled out have been conducted. The field tests also demonstrate the multi-string logging technology is applicable to all typical casing and tubing weight or size combinations and provides quantitative assessments on isolation conditions of wells through the production tubing.
OpenLab: Design and Applications of a Modern Drilling Digitalization Infrastructure
Authors: Saadallah Nejm , Gravdal Jan Einar , Ewald Robert , Moi Sonja , Ambrus Adrian , Daireaux Benoit , Sivertsen Stian , Hellang Kristian , Shor Roman , Sui Dan , Sandor Stefan Ioan , Chojnacki Marek , Odgaard Jacob
Published: May 2019

The transition towards drilling automation in the oil and gas industry has increased the need for digital infrastructures for development and testing of new technology. This includes infrastructures to facilitate changes in work processes and technical competences. This paper describes the design and use of OpenLab Drilling, a digital infrastructure with applications in education, technology development and testing.

OpenLab Drilling offers access to a high fidelity drilling process simulator capable of simulating transient hydraulics, temperature, torque and drag, and cuttings transport. Since 2018, the infrastructure has been publicly available for students, researchers and engineers who need realistic drilling data for technology development, demonstration and education. The simulated drilling data can be accessed by several means. First, through a user-friendly web application used as a tool for teaching the physics involved in drilling operations. Secondly, drilling data can be accessed programmatically through a web API or via programming language APIs written in MATLAB, Python and .NET. Thirdly, OpenLab offers a fast communication interface that can be used for applications that are closer to hardware, and which require a realistic Hardware in The Loop (HIL) infrastructure.

This paper describes the objectives of OpenLab as a project, its system architecture, its simulation capabilities, the design of its web application, and its various communication interfaces. The paper also presents projects that uses OpenLab in education, research on machine learning, semantical representation of drilling data, and other industrial relevant activities. The paper is naturally divided in two parts: The design of the infrastructure, and its applications.
Data on Work – An Untapped Asset for Operational Improvements
Authors: Clark Alex , Larsen Henrik W. , Nordtvedt Jan-Erik , Stafford Bart T. , Unneland Trond
Published: May 2019

The push within the oil and gas industry towards digitalization hold great promises for optimizing operations and improving efficiency. Therefore, most oil and gas companies have large initiatives within digitalization – huge efforts on data acquisition, Industrial Internet of Things, Artificial Intelligence (AI), Machine Learning (ML) etc. – all digital opportunities introduced to the industry in recent years. We look at data and models as oil and gas "assets" – much like physical assets used in operations (wells, platforms, compressors etc.). Thus, there is a perceived inherent value in data for operations.

For effective operations, the interesting part of data, models and digital capabilities, is the feedback loop it allows to the physical asset itself. One wants to close/open a valve for optimal production, ensure maintenance on machinery and ensure safe scaffolding operations without sending people offshore during planning. There are two types of feedback opportunities to the physical asset – either through automation or by humans. Both humans and automation algorithms can get advice from some "co-bot" based on AI, ML or other digital opportunities. When the feedback is given automatically, we have full control over the work performed by the algorithm or cobot, while the same is not the case when humans are involved.

At certain level engineers and operators know how to do the work – this is embedded into known "work processes." However, the actual interpretation of a work processes into concrete activities may lead to different tasks for team members – even for the same work. This gives lack of repeatability, inconsistency in operations, and makes effective collaborations challenging. In many ways, we lack (real time) data on the work itself, when it's done by humans.

This paper addresses this issue – we explain why data on the work and how effectively it is performed should be regarded as an asset in a similar way to real-time data and reservoir models. We show technologies and examples allowing organization to assess data on the work itself. We discuss how teams can work differently, and how technology can be used to drive consistency and KPIs toward more effective operations.
Reservoir Stress-Path Measured During Depletion and Re-Pressurization in the Valhall Field
Authors: Kristiansen Tron G. , Bauer Andreas , Flatebø Roar , Guida Assia , Nes Olav-Magnar , Skomedal Øyvind
Published: May 2019

Reservoir stress path is most often used to couple the pore pressure change in a reservoir to the resulting change in the minimum horizontal stress in the reservoir. This stress path can directly be measured in a reservoir. The pore pressure is typically measured using standard equipment for doing so during drilling of wells. These pressure measurement devices are either run on wireline or in logging while drilling (LWD) tools. The minimum horizontal stress is typically measured in a hydraulic fracturing operation designed for this purpose. This operation can be performed under a casing shoe (often referred to as an extended leak-off test), through perforations (often referred to as a mini-frac test) or between two packer elements (referred to as a micro-frac test). The stress path will impact many geomechanical aspects in a field development, like wellbore stability, lost circulation (fracture gradient change) and solids production to name three. In the literature there are limited datasets on stress-paths during depletion, and even less on re-pressurization resulting from injection. The Valhall dataset is unique in the industry since it contains hundreds of tests from three different chalk formations. The data has been gathered from mini-frac tests as part of hydraulic propped fracturing stimulation jobs over a 36-year period, and is from an oil and gas industry perspective of very high quality. Water injection has been ongoing in the Tor reservoir the last 13 years and large amounts of data can be used to measure the stress path during re-pressurization. The Valhall data indicate one stress path for depletion and a slightly different stress path during re-pressurization. We compare the measured stress paths with predictions based on core measurements and numerical models and discuss the impact of pore collapse, fault reactivation, arching, and processes during re-pressurization
Corneal wavefront guided versus aberration free transepithelial photorefractive keratectomy in myopic patients with high pre-existing corneal higher order aberrations
Authors: Ellakwa Amin Faisal , Zaki Marwa Ali , Ashour Rana Mohammed
Published: May 2019

Objectives

to compare the efficacy, safety and predictability of corneal wavefront guided (WFG) and aberration free ablation in single-step transepithelial photorefractive keratectomy (TransPRK) in myopic patients with high pre-existing corneal higher order aberrations (HOAs).

Background

Corneal WFG and aberration free treatments have been proposed as methods to achieve better visual, refractive, and optical outcomes.

Methods

Non-randomized controlled trailwas conducted in El-HekmaEye-LASIK center, Menoufia governorate, Egypt during the period from January 2017 to December 2017. TransPRK was performed to eligible myopic patients with or without astigmatism with corneal HOAs ≥ 0.35 µ utilizing either aberration free or corneal WFG patterns provided by ORKCAM software (SCHWIND eye-tech-solutions, Kleinostheim, Germany). Uncorrected distance visual acuity (UDVA), manifest and cycloplegic refractions, best spectacle corrected distance visual acuity (CDVA), thorough slit lamp examination and corneal topography were assessed and repeated six months postoperatively.

Results

Six months postoperatively, 97.6% and 100% of patients achieved MRSE within ± 1D with 76.2% and 66.67% of patients achieved UDVA of ≥20/20 in aberration free and corneal WFG groups respectively. Both groups showed increase in spherical and total corneal HOAs, with no significant difference in corneal WFG (p=0.08, p=0.28 respectively) while significantly higher postoperatively in aberration free group (p<0.001, p=0.001 respectively). Coma and trefoil aberrations declined after corneal WFG technique, yet increased after aberration free one.

Conclusions

both aberration free and corneal WFG TransPRK were safe, effective and predictable in treatment of myopia in patients with high pre-existing corneal HOAs with better aberrometric outcomes in corneal WFG group.
Drug resistance of pathogens causing nosocomial infection in orthopedics from 2012 to 2017: a 6-year retrospective study
Authors: Zhang Bin , Yang Xiaowei , Guo Runsheng , Xie Banglin , Lai Qi , Xu Jiaxiang , Hu Niya , Wan Lijun , Dai Min
Published: May 2019

Abstract

Background

Hospital-acquired infections (HAIs) are an emerging global problem that increases in-hospital mortality, length of stay, and cost. Orthopedics departments experience a particularly high infection rate, partially due to their heavy reliance on invasive medical devices. We performed a 6-year retrospective study to provide valuable insight into appropriate antibiotic use in HAI cases. We also aimed to understand how hospitals could reduce pathogen drug resistance in a population that overuses antibiotics.

Methods

All data (2012–2017) were obtained from the Hospital Information Warehouse and Clinical Microbiology Laboratory.

Results

We isolated 1392 pathogen strains from patients admitted to the orthopedics department during 2012–2017. Escherichia coli (14.7%, 204/1392), Enterobacter cloacae (13.9%, 193/1392), and Staphylococcus aureus (11.3%, 157/1392) were the most common pathogens causing nosocomial infections. The dominant gram-negative bacterium was E. coli, with high resistance to ampicillin, levofloxacin, cotrimoxazole, gentamicin, and ciprofloxacin, in that order. E. coli was least resistant to amikacin, cefoperazone-sulbactam, meropenem, imipenem, and piperacillin-tazobactam. The most dominant gram-positive bacterium was S. aureus, highly resistant to penicillin and ampicillin, but not resistant to fluoroquinolones and cotrimoxazole. We also did not observe isolate resistance to nitrofurantoin, linezolid, and vancomycin. Analysis of risk factors related to multidrug-resistant bacteria showed that patients with open fractures were significantly more susceptible to methicillin-resistant S. aureus infections (p < 0.05). Additionally, extended-spectrum β-lactamase-producing E. coli infections occurred significantly more often in patients with degenerative diseases (p < 0.05). Elderly patients tended to be more susceptible to multidrug-resistant bacterial infections, but this outcome was not statistically significant.

Conclusions

Antimicrobial resistance is a serious problem in orthopedics. To effectively control antimicrobial resistance among pathogens, we advocate extensive and dynamic monitoring of MDR bacteria, coupled with careful use of antibiotics.

Key words: hospital acquired infections; orthopedics; drug resistance; multidrug resistance
Incidence of Post Dural Puncture Headache and Associated Factors Following Spinal Anaesthesia for Caesarean Delivery in Mulago National Referral Hospital
Authors: Nambooze Philo , Samuel Kizito , Kiggundu John Baptist , Kintu Andrew , Nabukenya Mary T.
Published: May 2019

Background

Spinal anaesthesia is a cost effective anaesthesia technique commonly used for abdominal procedures like caesarean sections. The incidence of post dural puncture headaches (PDPH) which is one of the most reported complications) remains unknown in Uganda. We set out to study the incidence of PDPH and associated factors following spinal anaesthesia in mothers delivering by caesarean section in Mulago National Referral Hospital.

Methods

Prospective cohort study among 1294 women that received spinal anaesthesia for emergency caesarean section delivery from July 2015 to February 2016. Consecutive sampling was applied to recruit participants. Pre-tested interviewer administered questionnaires were used to collect information on demographics and associated factors. Both bivariate and multivariate logistic regressions were used with a P value of 0.05 and confidence interval of 95% being considered statistically significant.

Results

The incidence of PDPH was found to be 48.8% (n=239/1294) (95%CI: 46.0-51.6). Significant factors associated with PDPH were history of spinal anaesthesia OR 1.3 95% CI (1.0-1.6) p=0.04 and loss more than 500mls of blood during surgery OR 2.2, 95% CI (1.1-4.2) P=0.02.

Conclusion

Results from our study indicate high incidence of PDPH women undergoing spinal anesthesia for Caesarean section. Prior exposure to spinal anesthesia and blood loss of more than 500mls are the major associated factors. There is need to objectively screen women at risk for PDPH prior to caesarean section and institute appropriate interventions.
miR-21 promotes bevacizumab induced epithelial-mesenchymal transition in retinal pigment epithelial cells by regulating Snail expression via TGFβ1/smad2/3 signaling pathway
Authors: Yang Lingling , Hua Yingbin , Zhou Li , Song Shan , Xu Haifeng
Published: May 2019

Background

The purpose of this study was to investigate the role of microRNA-21 (miR-21) on bevacizumab (BEV)-induced Epithelial-mesenchymal transition (EMT) in retinal pigment epithelial (RPE) cells in vitro.

Methods

Human retinal pigment epithelial cells line (ARPE-19) were exposed to clinical dosage of BEV and miR-21 expression was measured by qRT-PCR assay. The effects of miR-21 on BEV-induced EMT were examined through gain- or loss- expression of miR-21 using miR-21 mimic or inhibitor. The expression of α-smooth muscle actin (α-SMA), E-cadherin, Snail, TGFβ1 and smad2/3 were detected by western blot. TGFβ1/smad2/3 signaling was inhibited by using SB431542 and SIS3.

Results

Clinical dosage of BEV caused EMT and enhanced miR-21 expression in ARPE-19 cells. The inhibition of miR-21 attenuated the EMT effect of BEV, while over-expression of miR-21 promoted this activity. Snail was up-regulated by BEV and the promotion was partially suppressed by miR-21 inhibitor and aggravated by miR-21 mimic. miR-21 regulated BEV-induced TGFβ1 increasing and smad2/3 phosphorylation. The EMT and Snail expression promoted by BEV and miR-21 mimic in ARPE-19 cells was impaired by inhibition of TGFβ1/smad2/3 signaling.

Conclusions

miR-21 promoted BEV-induced EMT in ARPE cells through up-regulating of Snail expression via regulation of TGFβ1/smad2/3 signaling pathway. miR-21 might be a potential miRNA-based therapeutic target in reducing BEV-induced subretinal fibrosis.
Effect of Nitric Oxide on Seed Germination and Dormancy in Empress Trees
Authors: Liu Jia , Xue Tingting , Shen Yongbao
Published: May 2019

Freshly harvested empress tree (Paulownia elongata) seeds have physiologic dormancy. The aim of this study was to investigate the effects of exogenous and endogenous nitric oxide (NO) on the dormancy and germination of empress tree seeds. After treatment with different concentrations of sodium nitroprusside (an NO-releasing compound) solution, the germination percentage of seeds under 12 h of continuous light was significantly greater. Seed germination percentage was promoted significantly by 10–4 M sodium nitroprusside plus cold stratification compared with seeds treated with cold stratification only. At different hours during imbibition, empress tree seeds treated with 2-(4-carboxyphenyl)-4, 4, 5, 5- tetramethylimidazoline -1-oxyl-3-oxide potassium salt (c-PTIO), NG-nitro-L-arginine methyl ester (L-NAME), and sodium tungstate showed reduced seed germination percentages. During the early hours of imbibition, c-PTIO or sodium tungstate treatment inhibited seed germination significantly. The results showed that both exogenous and endogenous NO can release empress tree seed dormancy. Endogenous NO oxide was involved in dormancy release and germination of seeds during the early stages of imbibition. Wider application of NO may be used for breaking seed dormancy in other species.
Water reuse in the production of non-reinforced concrete elements: An alternative for decentralized wastewater management
Authors: Duarte Natalia Cangussu , Amaral Ana Elitha dos Santos , Gomes Bianca Graziella Lento Araujo , Siqueira Gustavo Henrique , Tonetti Adriano Luiz
Published: May 2019

Replacement of water by treated wastewater in concrete production, totally or in part, could lead to great water economy. Therefore, this experiment evaluated compressive strength from non-reinforced concrete samples produced with a combination of potable water (PW) and treated domestic wastewater (TW) at four different proportions: 0, 50, 75, and 100% of TW in the mixture. Ten samples were prepared for each proportion and the samples were tested for axial compression on the 28th day after concrete preparation. The data were statistically evaluated to analyze the influence of TW in concrete quality. It was possible to note that there was no significant difference between concretes produced using only PW and those produced with 50 and 75% TW, but when only TW was used, the concrete compressive strength increased on average 17.7%, which indicates the good potential of water reuse in the production of non-reinforced concrete elements.
Electrodialysis-based zero liquid discharge in industrial wastewater treatment
Authors: Havelka Jan , Fárová Hana , Jiříček Tomáš , Kotala Tomáš , Kroupa Jan
Published: May 2019

Over the past few decades, reverse osmosis (RO) has been the dominant technology employed in zero liquid discharge (ZLD) systems for industrial wastewater treatment (WWT). However, RO is limited to a maximum operating salinity of about 75 g kg−1. Electrodialysis (ED) is a potentially attractive option as it can achieve much higher concentrations, thereby reducing the capacity and energy demand of the subsequent evaporation step. Feed-and-bleed experiments were undertaken on a laboratory-scale ED stack using a series of model solutions based on the most common inorganic salts with the aim of determining maximum achievable concentrations. The maximum salt concentration achievable via ED ranged between 104.2 and 267.6 g kg−1, with levels predominantly limited by water transport. In addition, a straightforward review of how ED incorporation can affect ZLD process economics is presented. The operational cost of an ED-based ZLD system for processing RO retentate was almost 20% lower than comparable processes employing high-efficiency RO and disc tubular RO. As the ED-based ZLD system appears economically preferable, and as maximum achievable concentrations greatly exceeded RO operating limits, it would appear to be a promising approach for bridging the gap between RO and evaporation, and may even eliminate the evaporation step altogether.
Perioperative use of levosimendan in cardiac surgery
Authors: Lomivorotov V. V. , Yeremenko A. A. , Boboshko V. A. , Abubakirov M. N.
Published: May 2019

It is known that low cardiac output in patients undergoing cardiac surgery is associated with organ dysfunction and mortality in the postoperative period. Catecholamines have been the standard therapy for many years, although they carry substantial risks for adverse cardiac and systemic effects, and have been reported to be associated with increased mortality. On the other hand, the calcium sensitiser and potassium channel opener levosimendan has been shown to improve the cardiac function with

no imbalance in oxygen consumption, and to have protective effects in other organs. Several clinical trials have found beneficial effects of cardiogenic and non-cardiogenic perioperative use of levosimendan. The aim of this article was to describe the mechanism of levosimendan action, as well as to overview the current data regarding its clinical application.

Received 22 April 2015. Accepted 18 June 2015.

 

 
Endothelin Receptor Antagonism: A New Era in the Treatment of Pulmonary Arterial Hypertension
Authors: Channick Richard N. , Rubin Lewis J.
Published: May 2019

The endothelin system has been extensively studied over the last several years. It is clear that endothelin-1 (ET-1) is a key mediator in pulmonary vascular biology and physiology. Abnormal increases in ET-1 production and decreased pulmonary clearance appear to play a major pathogenetic and perpetuating role in the pulmonary hypertensive process, through their vasconstrictive, smooth muscle cell proliferative and profibrotic effects. The degree of overexpression of ET-1 may correlate with the severity of pulmonary hypertension (PH). Advances in understanding the role of ET-1 in pulmonary hypertension have driven the development of endothelin receptor antagonists. One such agent, bosentan (Tracleer), is FDA approved for pulmonary arterial hypertension. Bosentan was approved following two randomized, placebo-controlled, double-blind studies that both showed marked improvement in exercise capacity after treatment with bosentan. The beneficial effects of bosentan appear to be sustained in most patients followed for as long as 22 months. Other uses for endothelin receptor antagonists are being examined, such as in combination with epoprostenol (Flolan) or in pediatric PH patients.
The Nuts and Bolts of Interpreting Hemodynamics in Pulmonary Hypertension Associated With Diastolic Heart Failure
Authors: Mathier Michael A.
Published: May 2019

With the widespread application of transthoracic echocardiography as a screening tool for pulmonary hypertension (PH), we have come to appreciate the prevalence of PH associated with diastolic heart failure. Diastolic heart failure (DHF, sometimes called heart failure with preserved, or normal, left ventricular ejection fraction [HFpEF]) is quite common, and PH appears to be a fairly frequent component of DHF.1–3 The epidemiology of these conditions is described in the article by Dr Soto in this issue of Advances. There is a complex relationship between DHF and PH: the 2 may exist independent of each other or in combination; and when they exist in combination, the PH may be in proportion or out of proportion to the DHF. Cardiac catheterization is critical in differentiating among these patterns, and this distinction may lead to important modifications in treatment strategy. This requires, however, a full understanding of the proper performance and interpretation of cardiac catheterization, as well as the potential pitfalls that can limit the utility of the procedure. This article will discuss these aspects of cardiac catheterization as they pertain to patients with pulmonary arterial hypertension (PAH) and PH associated with DHF. A number of important aspects of cardiac catheterization are not covered here due to space limitations but can be obtained in a more detailed text.4
Potential Interventions Against BMPR2-Related Pulmonary Hypertension
Authors: West James , Loyd James E. , Hamid Rizwan
Published: May 2019

For more than 60 years, researchers have sought to understand the molecular basis of idiopathic pulmonary arterial hypertension (PAH). Recognition of the heritable form of the disease led to the creation of patient registries in the 1980s and 1990s, and discovery of BMPR2 as the cause of roughly 80% of heritable PAH in 2000. With discovery of the disease gene came opportunity for intervention, with focus on 2 alternative approaches. First, it may be possible to correct the effects of BMPR2 mutation directly through interventions targeted at correction of trafficking defects, increasing expression of the unmutated allele, and correction of splicing defects. Second, therapeutic interventions are being targeted at the signaling consequences of BMPR2 mutation. In particular, therapies targeting cytoskeletal and metabolic defects caused by BMPR2 mutation are currently in trials, or will be ready for human trials in the near future. Translation of these findings into therapies is the culmination of decades of research, and holds great promise for treatment of the underlying molecular bases of disease.
Anatomy of Congenital Heart Disease Lesions Associated With Pulmonary Arterial Hypertension
Authors: Kiefer Todd L. , Bashore Thomas
Published: May 2019

Adult congenital heart disease represents a growing population of patients. Many patients survive to adulthood and lead functional, productive lives. In fact, there are more adults living with congenital heart disease than pediatric patients. Many adult patients will have had prior surgical repair as children. However, some patients present in adulthood with a new diagnosis of congenital heart disease. Furthermore, there are a variety of complications associated with each individual congenital lesion and specific surgical repair procedure.
Medical Treatment Options/Advances in Portopulmonary Hypertension: How the Spectrum Is Expanding
Authors: Benza Raymond L.
Published: May 2019

[Editor's Note: This article is Part 2 of coverage that began in the last issue on pulmonary hypertension in the setting of liver disease. Whereas the first articles discussed pathophysiology and liver transplantation, this article reviews medical treatment and related options.]
Pulmonary Arterial Hypertension In Adults With Congenital Heart Disease: General Overview of Disease Mechanisms
Authors: Schulze-Neick Ingram , Deanfield John E.
Published: May 2019

Adults with congenital heart disease (CHD) have become a rapidly expanding group of complex patients requiring multidisciplinary care in specialty centers by those trained in CHD. They represent one of the most challenging subgroups of patients with pulmonary arterial hypertension (PAH) due to the presence of structural heart disease with or without coexisting cyanosis and its complications. The primary focus of attention for these patients is the lungs, whose vascular system is affected by shunt flow, or is also congenitally malformed, or has been altered by surgical procedures. When PAH develops, it affects physical exercise tolerance, travel to high altitudes, pregnancy, operability, and anesthesia (myocardial failure due to pulmonary hypertensive crisis), and thus general morbidity and mortality in this special patient group.
Expanded Use of PAH Medications
Authors: Fagan Karen A. , Mubarak Kamal K. , Safdar Zeenat , Waxman Aaron , Zamanian Roham T.
Published: May 2019

This discussion was moderated by Karen A. Fagan, MD, Professor and Director, Division of Pulmonary Medicine, University of South Alabama College of Medicine, Mobile, Alabama. Panel members included Kamal K. Mubarak, MD, Assistant Professor of Medicine, Director, Pulmonary Hypertension Clinic, Wayne State University, Detroit, Michigan; Zeenat Safdar, MD, Assistant Professor of Medicine, Department of Medicine, Section of Pulmonary, Critical Care, and Sleep Medicine, Baylor College of Medicine, Houston, Texas; Aaron Waxman, MD, PhD, Associate Professor of Medicine, Harvard Medical School, Director, Pulmonary Vascular Disease Program and Pulmonary Critical Care Unit, Massachusetts General Hospital, Boston, Massachusetts; and Roham T. Zamanian, MD, Assistant Professor of Medicine, Director, Adult Pulmonary Hypertension Clinical Service, Vera Moulton Wall Center for Pulmonary Vascular Disease, Stanford University School of Medicine, Stanford, California.
Ethical Considerations for RCTs in PAH
Authors: Halpern Scott , Badesch David B. , McGoon Michael D. , Park Myung
Published: May 2019

A roundtable discussion on ethical issues relating to the conduct of randomized clinical trials (RCTs) with pulmonary arterial hypertension (PAH) patients was held during the May 2009 American Thoracic Society meeting in San Diego. Scott Halpern, MD, PhD, MBE, Assistant Professor of Medicine and Epidemiology, Pulmonary, Allergy, and Critical Care Division, and Senior Fellow in the Center for Bioethics at the University of Pennsylvania, Philadelphia, facilitated the discussion among participants Myung H. Park, MD, Director, Pulmonary Vascular Diseases Program, University of Maryland School of Medicine, Baltimore, Maryland; David B. Badesch, MD, Professor of Medicine, Divisions of Pulmonary Sciences and Critical Care Medicine, and Cardiology, and Clinical Director of the Pulmonary Hypertension Center, University of Colorado at Denver Health Sciences Center; and Michael D. McGoon, MD, Professor of Medicine, Department of Cardiology, Pulmonary Hypertension Clinic, Mayo Clinic, Rochester, Minnesota.
Pulmonary Hypertension and Lung Transplantation, 2010
Authors: Frost Adaani E.
Published: May 2019

Pulmonary arterial hypertension is a disease characterized by progressive resistance to flow across the pulmonary vascular bed, resulting in death from progressive right heart failure. The evolution of the currently approved therapies for certain pulmonary arterial hypertension functional classes has resulted in a considerable improvement in 1-year survival. However, substantial risk remains. For those patients judged to be deteriorating on therapy, bilateral sequential lung transplant or, occasionally, heart-lung transplant is the preferred option. Review of the literature suggests many relatively simple, routinely acquired clinical and hemodynamic indices that appear to predict risk of mortality and hence need for transplant. The current LAS, in sharp contrast, substantially disenfranchises patients with pulmonary arterial hypertension. It is hoped that validation of some or all of these risk factors, as is being undertaken in the REVEAL database, may permit development of a reliable, simple, and widely applicable tool for assessing mortality risk and hence need for transplant referral in our PAH patients.
Surgical Treatment of Pulmonary Arterial Hypertension
Authors: Cantu Edward , Davis R. Duane
Published: May 2019

Significant advances in the treatment of pulmonary arterial hypertension have occurred in the last several years. The decision to refer a patient for transplantation requires a dynamic approach. Candidate selection and timing of referral to transplant centers is critical for success, particularly with current allocation protocols that do not take into account the severity of illness. Though long-term success is tempered by chronic allograft dysfunction and infection, considerable improvements in outcomes have established lung transplantation for pulmonary arterial hypertension as an efficacious and life-prolonging treatment. However, transplantation should be reserved for patients who have failed the best available medical therapy. Ideally, transplantation occurs when the clinically deteriorating patient has enough reserve to survive long enough to be transplanted but is not debilitated enough to jeopardize the graft. There is significant uncertainty with regard to this ideal.
A World of Research Subjects: Informed Consent and Benefit Sharing*
Authors: Annas George J. , Grodin Michael A.
Published: May 2019

The most important question for any research project is whether the research should be done at all. Only after this is answered do issues of how and where to do the research become relevant. When doing research in another country, however, the whether and where questions become intertwined. This is because the recent globalization of clinical trials is itself suspect. What is the motivation for the sudden upsurge in clinical trials in other countries? Who benefits from the globalization of research, and who is put at risk? Some advantages have been suggested, including reduced regulation, less oversight, decreased costs, and more rapid results, but none of these alone (or together) is sufficient to justify the expansion of medical research to an underserved, disenfranchised, and exploitable population. The only justification is that the proposed research addresses a question that can only be answered by this unique population and the results must bring short- and long-term benefit. The research remains suspect until ethical norms are met. The subjects must never be worse off from participating in the trials than if they had never participated.
Insight into Mechanistic Action of Thymoquinone Induced Melanogenesis in Cultured Melanocytes
Authors: Zaidi Kamal U. , Khan Firoz N. , Ali Sharique A. , Khan Kausar P.
Published: May 2019

Background:

Melanin plays a crucial role in camouflage, social communication and
protection against harmful ultraviolet radiations. Melanin is synthesized by melanocytes through
melanogenesis and several intrinsic and extrinsic factors are involved during the process. Any
change occuring in the normal melanogenesis process can cause severe pigmentation problems of
hypopigmentation or hyperpigmentation.

Objective:

The present study is based on the evaluation of the effect of thymoquinone on
melanogenesis and their possible mechanism of action using the B16F10 melanoma cell line for the
production via blocking signaling pathways.

Methods:

Phase contrast microscopy, cell viability, tyrosinase activity, melanin content and
western blot analysis were used in the present study.

Results:

In the present investigation, cultured melanocytes exhibit that the stimulation of melanin
synthesis when treated with thymoquinone. Tyrosinase activity and melanin production in B16F10
melanoma cell line was increased in doze-dependent manner. In western blot, we investigated the
involvement of the cAMP/PKA pathway in thymoquinone induced melanogenesis. It was observed
protein kinase inhibitors PKA, PKC, PKB and MEK1 decreased the stimulatory effects of
thymoquinone from 11.45- fold value to 8.312, 6.631, 4.51, and 7.211-fold value, respectively.
However, the results also prove that thymoquinone may partially induce tyrosinase expression via
PKA, PKB, PKC and MEK1 signaling pathways.

Conclusion:

The present finding proposed that thymoquinone is a protective challenger for
melanogenesis and it might be useful for the treatment of hypopigmentary disorders.
Brain Cancer-Activated Microglia: A Potential Role for Sphingolipids
Authors: Bottai Daniele , Adami Raffaella , Paroni Rita , Ghidoni Riccardo
Published: May 2019

:

Almost no neurological disease exists without microglial activation. Microglia has exert a pivotal role in the maintenance of the central nervous system and its response to external and internal insults. Microglia have traditionally been classified as, in the healthy central nervous system, “resting”, with branched morphology system and, as a response to disease, “activated”, with amoeboid morphology; as a response to diseases but this distinction is now outmoded. The most devastating disease that hits the brain is cancer, in particular glioblastoma. Glioblastoma multiforme is the most aggressive glioma with high invasiveness and little chance of being surgically removed. During tumor onset, many brain alterations are present and microglia have a major role because the tumor itself changes microglia from the pro-inflammatory state to the anti-inflammatory and protects the tumor from an immune intervention.

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What are the determinants of these changes in the behavior of the microglia? In this review, we survey and discuss the role of sphingolipids in microglia activation in the progression of brain tumors, with a particular focus on glioblastoma.
Gold Nanoparticles as Targeted Delivery Systems and Theranostic Agents in Cancer Therapy
Authors: Mioc Alexandra , Mioc Marius , Ghiulai Roxana , Voicu Mirela , Racoviceanu Roxana , Trandafirescu Cristina , Dehelean Cristina , Coricovac Dorina , Soica Codruta
Published: May 2019

Cancer is still a leading cause of death worldwide, while most chemotherapies induce nonselective toxicity and severe systemic side effects. To address these problems, targeted nanoscience is an emerging field that promises to benefit cancer patients. Gold nanoparticles are nowadays in the spotlight due to their many well-established advantages. Gold nanoparticles are easily synthesizable in various shapes and sizes by a continuously developing set of means, including chemical, physical or eco-friendly biological methods. This review presents gold nanoparticles as versatile therapeutic agents playing many roles, such as targeted delivery systems (anticancer agents, nucleic acids, biological proteins, vaccines), theranostics and agents in photothermal therapy. They have also been outlined to bring great contributions in the bioimaging field such as radiotherapy, magnetic resonance angiography and photoacoustic imaging. Nevertheless, gold nanoparticles are therapeutic agents demonstrating its in vitro anti-angiogenic, anti-proliferative and pro-apoptotic effects on various cell lines, such as human cervix, human breast, human lung, human prostate and murine melanoma cancer cells. In vivo studies have pointed out data regarding the bioaccumulation and cytotoxicity of gold nanoparticles, but it has been emphasized that size, dose, surface charge, sex and especially administration routes are very important variables.
Molecular and Clinical Investigations on Portuguese Patients with Multiple acyl-CoA Dehydrogenase Deficiency
Authors: Henriques Bárbara J. , Lucas Tânia G. , Martins Esmeralda , Gaspar Ana , Bandeira Anabela , Nogueira Célia , Brandão Otilia , Rocha Hugo , Vilarinho Laura , Gomes Cláudio M.
Published: May 2019

Background:

Multiple Acyl-CoA Dehydrogenase Deficiency (MADD) is a congenital rare
metabolic disease with broad clinical phenotypes and variable evolution. This inborn error of
metabolism is caused by mutations in the ETFA, ETFB or ETFDH genes, which encode for the
mitochondrial ETF and ETF:QO proteins. A considerable group of patients has been described to
respond positively to riboflavin oral supplementation, which constitutes the prototypic treatment for
the pathology.

Objectives:

To report mutations in ETFA, ETFB and ETFDH genes identified in Portuguese
patients, correlating, whenever possible, biochemical and clinical outcomes with the effects of
mutations on the structure and stability of the affected proteins, to better understand MADD
pathogenesis at the molecular level.

Methods:

MADD patients were identified based on the characteristic urinary profile of organic acids
and/or acylcarnitine profiles in blood spots during newborn screening. Genotypic, clinical and
biochemical data were collected for all patients. In silico structural analysis was employed using
bioinformatic tools carried out in an ETF:QO molecular model for the identified missense mutations.

Results:

A survey describing clinical and biochemical features of eight Portuguese MADD patients
was made. Genotype analysis identified five ETFDH mutations, including one extension
(p.X618QextX*14), two splice mutations (c.34+5G>C and c.405+3A>T) and two missense
mutations (ETF:QO-p.Arg155Gly and ETF:QO-p.Pro534Leu), and one ETFB mutation (ETFβ-
p.Arg191Cys). Homozygous patients containing the ETFDH mutations p.X618QextX*14,
c.34+5G>C and ETF:QO-p.Arg155Gly, all presented severe (lethal) MADD phenotypes. However,
when any of these mutations are in heterozygosity with the known ETF:QO-p.Pro534Leu mild
variant, the severe clinical effects are partly and temporarily attenuated. Indeed, the latter
destabilizes an ETF-interacting loop, with no major functional consequences. However, the position
155 in ETF:QO is localized at the ubiquinone binding and membrane interacting domain, and is
thus expected to perturb protein structure and membrane insertion, with severe functional effects.
Structural analysis of molecular models is therefore demonstrated to be a valuable tool to
rationalize the effects of mutations in the context of the clinical phenotype severity.

Conclusion:

Advanced molecular diagnosis, structural analysis and clinical correlations reveal that
MADD patients harboring a severe prognosis mutation in one allele can actually revert to a milder
phenotype by complementation with a milder mutation in the other allele. However, such patients
are nevertheless in a precarious metabolic balance which can revert to severe fatal outcomes
during catabolic stress or secondary pathology, thus requiring strict clinical follow-up.
Postprandial Hypertriglyceridaemia Revisited in the Era of Non-Fasting Lipid Profile Testing: A 2019 Expert Panel Statement, Main Text
Authors: Kolovou Genovefa D. , Watts Gerald F. , Mikhailidis Dimitri P. , Pérez-Martínez Pablo , Mora Samia , Bilianou Helen , Panotopoulos George , Katsiki Niki , Ooi Teik C. , Lopez-Miranda José , Tybjærg-Hansen Anne , Tentolouris Nicholas , Nordestgaard Børge G.
Published: May 2019

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Residual vascular risk exists despite the aggressive lowering of Low-Density Lipoprotein Cholesterol (LDL-C). A contributor to this residual risk may be elevated fasting, or non-fasting, levels of Triglyceride (TG)-rich lipoproteins. Therefore, there is a need to establish whethe a standardised Oral Fat Tolerance Test (OFTT) can improve atherosclerotic Cardiovascular (CV) Disease (ASCVD) risk prediction in addition to a fasting or non-fasting lipid profile.

:

An expert panel considered the role of postprandial hypertriglyceridaemia (as represented by an OFTT) in predicting ASCVD. The panel updated its 2011 statement by considering new studies and various patient categories. The recommendations are based on expert opinion since no strict endpoint trials have been performed.

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Individuals with fasting TG concentration <1 mmol/L (89 mg/dL) commonly do not have an abnormal response to an OFTT. In contrast, those with fasting TG concentration ≥2 mmol/L (175 mg/dL) or nonfasting ≥2.3 mmol/L (200 mg/dL) will usually have an abnormal response. We recommend considering postprandial hypertriglyceridaemia testing when fasting TG concentrations and non-fasting TG concentrations are 1-2 mmol/L (89-175 mg/dL) and 1.3-2.3 mmol/L (115-200 mg/dL), respectively as an additional investigation for metabolic risk prediction along with other risk factors (obesity, current tobacco abuse, metabolic syndrome, hypertension, and diabetes mellitus). The panel proposes that an abnormal TG response to an OFTT (consisting of 75 g fat, 25 g carbohydrate and 10 g proteins) is >2.5 mmol/L (220 mg/dL).

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Postprandial hypertriglyceridaemia is an emerging factor that may contribute to residual CV risk. This possibility requires further research. A standardised OFTT will allow comparisons between investigational studies. We acknowledge that the OFTT will be mainly used for research to further clarify the role of TG in relation to CV risk. For routine practice, there is a considerable support for the use of a single non-fasting sample.