bluuebunny/crossref_metadata_2025 huggingface dataset:
Prototype Development of a Tradespace Analysis Tool for Spaceflight Medical Resources
Authors: Antonsen Erik L. , Mulcahy Robert A. , Rubin David , Blue Rebecca S. , Canga Michael A. , Shah Ronak
Published: February 2018

INTRODUCTION: The provision of medical care in exploration-class spaceflight is limited by mass, volume, and power constraints, as well as limitations of available skillsets of crewmembers. A quantitative means of exploring the risks and benefits of inclusion or exclusion of
onboard medical capabilities may help to inform the development of an appropriate medical system. A pilot project was designed to demonstrate the utility of an early tradespace analysis tool for identifying high-priority resources geared toward properly equipping an exploration mission medical
system.METHODS: Physician subject matter experts identified resources, tools, and skillsets required, as well as associated criticality scores of the same, to meet terrestrial, U.S.-specific ideal medical solutions for conditions concerning for exploration-class spaceflight. A database
of diagnostic and treatment actions and resources was created based on this input and weighed against the probabilities of mission-specific medical events to help identify common and critical elements needed in a future exploration medical capability.RESULTS: Analysis of repository
data demonstrates the utility of a quantitative method of comparing various medical resources and skillsets for future missions. Directed database queries can provide detailed comparative estimates concerning likelihood of resource utilization within a given mission and the weighted utility
of tangible and intangible resources.DISCUSSION: This prototype tool demonstrates one quantitative approach to the complex needs and limitations of an exploration medical system. While this early version identified areas for refinement in future version development, more robust
analysis tools may help to inform the development of a comprehensive medical system for future exploration missions.Antonsen EL, Mulcahy RA, Rubin D, Blue RS, Canga MA, Shah R. Prototype development of a tradespace analysis tool for spaceflight medical resources. Aerosp Med Hum Perform. 2018; 89(2):108–114.
Evaluation of Low-Temperature Cracking Performance of Asphalt Pavements Using Acoustic Emission: A Review
Authors: Behnia Behzad , Buttlar William , Reis Henrique
Published: February 2018

Low-temperature cracking is a major form of distress that can compromise the structural integrity of asphalt pavements located in cold regions. A review of an Acoustic Emission (AE)-based approach is presented that is capable of assessing the low-temperature cracking performance of asphalt binders and asphalt pavement materials through determining their embrittlement temperatures. A review of the background and fundamental aspects of the AE-based approach with a brief overview of its application to estimate low-temperature performance of unaged, short-term, and long-term aged binders, as well as asphalt materials, is presented. The application of asphalt pavements containing recycled asphalt pavement (RAP) and recycled asphalt shingles (RAS) materials to thermal cracking assessment is also presented and discussed. Using the Felicity effect, the approach is capable of evaluating the self-healing characteristics of asphalt pavements and the effect of cooling cycles upon their fracture behavior. Using an iterative AE source location technique, the approach is also used to evaluate the efficiency of rejuvenators, which can restore aged asphalt pavements to their original crack-resistant state. Results indicate that AE allows for relatively rapid and inexpensive characterization of pavement materials and can be used towards enhancing pavement sustainability and resiliency to thermal loading.
Recent Advances in Atmospheric Chemistry of Mercury
Authors: Si Lin , Ariya Parisa
Published: February 2018

Mercury is one of the most toxic metals and has global importance due to the biomagnification and bioaccumulation of organomercury via the aquatic food web. The physical and chemical transformations of various mercury species in the atmosphere strongly influence their composition, phase, transport characteristics and deposition rate to the ground. Modeling efforts to evaluate the mercury cycling in the environment require an accurate understanding of atmospheric mercury chemistry. We focus this article on recent studies (since 2015) on improving our understanding of the atmospheric chemistry of mercury. We discuss recent advances in (i) determining the dominant atmospheric oxidant of elemental mercury (Hg0); (ii) understanding the oxidation reactions of Hg0 by halogen atoms and by nitrate radical (NO3); (iii) the aqueous reduction of oxidized mercury compounds (HgII); and (iv) the heterogeneous reactions of Hg on atmospherically-relevant surfaces. The need for future research to improve understanding of the fate and transformation of mercury in the atmosphere is also discussed.
Freshwater Diatoms as Indicators of Combined Long-Term Mining and Urban Stressors in Junction Creek (Ontario, Canada)
Authors: Lavoie Isabelle , Morin Soizic , Laderriere Vincent , Fortin Claude
Published: February 2018

Sudbury (Ontario, Canada) has a long mining history that has left the region with a distinctive legacy of environmental impacts. Several actions have been undertaken since the 1970s to rehabilitate this deteriorated environment, in both terrestrial and aquatic ecosystems. Despite a marked increase in environmental health, we show that the Junction Creek system remains under multiple stressors from present and past mining operations, and from urban-related pressures such as municipal wastewater treatment plants, golf courses and stormwater runoff. Water samples have elevated metal concentrations, with values reaching up to 1 mg·L−1 Ni, 40 μg·L−1 Zn, and 0.5 μg·L−1 Cd. The responses of diatoms to stressors were observed at the assemblage level (metal tolerant species, nutrient-loving species), and at the individual level through the presence of teratologies (abnormal diatom frustules). The cumulative criterion unit (CCU) approach was used as a proxy for metal toxicity to aquatic life and suggested elevated potential for toxicity at certain sites. Diatom teratologies were significantly less frequent at sites with CCU values <1, suggesting “background” metal concentrations as compared to sites with higher CCU values. The highest percentages of teratologies were observed at sites presenting multiple types of environmental pressures.
Skin-on-a-Chip: Transepithelial Electrical Resistance and Extracellular Acidification Measurements through an Automated Air-Liquid Interface
Authors: Alexander Frank A. , Eggert Sebastian , Wiest Joachim
Published: February 2018

Skin is a critical organ that plays a crucial role in defending the internal organs of the body. For this reason, extensive work has gone into creating artificial models of the epidermis for in vitro skin toxicity tests. These tissue models, called reconstructed human epidermis (RhE), are used by researchers in the pharmaceutical, cosmetic, and environmental arenas to evaluate skin toxicity upon exposure to xenobiotics. Here, we present a label-free solution that leverages the use of the intelligent mobile lab for in vitro diagnostics (IMOLA-IVD), a noninvasive, sensor-based platform, to monitor the transepithelial electrical resistance (TEER) of RhE models and adherent cells cultured on porous membrane inserts. Murine fibroblasts cultured on polycarbonate membranes were first used as a test model to optimize procedures using a custom BioChip encapsulation design, as well as dual fluidic configurations, for continuous and automated perfusion of membrane-bound cultures. Extracellular acidification rate (EAR) and TEER of membrane-bound L929 cells were monitored. The developed protocol was then used to monitor the TEER of MatTek EpiDermTM RhE models over a period of 48 h. TEER and EAR measurements demonstrated that the designed system is capable of maintaining stable cultures on the chip, monitoring metabolic parameters, and revealing tissue breakdown over time.
Dynamin-Related Protein 1 at the Crossroads of Cancer
Authors: Lima Ana Rita , Santos Liliana , Correia Marcelo , Soares Paula , Sobrinho-Simões Manuel , Melo Miguel , Máximo Valdemar
Published: February 2018

Mitochondrial dynamics are known to have an important role in so-called age-related diseases, including cancer. Mitochondria is an organelle involved in many key cellular functions and responds to physiologic or stress stimuli by adapting its structure and function. Perhaps the most important structural changes involve mitochondrial dynamics (fission and fusion), which occur in normal cells as well as in cells under dysregulation, such as cancer cells. Dynamin-related protein 1 (DRP1), a member of the dynamin family of guanosine triphosphatases (GTPases), is the key component of mitochondrial fission machinery. Dynamin-related protein 1 is associated with different cell processes such as apoptosis, mitochondrial biogenesis, mitophagy, metabolism, and cell proliferation, differentiation, and transformation. The role of DRP1 in tumorigenesis may seem to be paradoxical, since mitochondrial fission is a key mediator of two very different processes, cellular apoptosis and cell mitosis. Dynamin-related protein 1 has been associated with the development of distinct human cancers, including changes in mitochondrial energetics and cellular metabolism, cell proliferation, and stem cell maintenance, invasion, and promotion of metastases. However, the underlying mechanism for this association is still being explored. Herein, we review the published knowledge on the role of DRP1 in cancer, exploring its interaction with different biological processes in the tumorigenesis context.
Different Risk Factors for Very Low Birth Weight, Term-Small-for-Gestational-Age, or Preterm Birth in Japan
Authors: Tamura Naomi , Hanaoka Tomoyuki , Ito Kumiko , Araki Atsuko , Miyashita Chihiro , Ito Sachiko , Minakami Hisanori , Cho Kazutoshi , Endo Toshiaki , Sengoku Kazuo , Ogasawara Katsuhiko , Kishi Reiko
Published: February 2018

From 1985 to 2013, the mean birth weight of infants in Japan decreased from 3120 g to 3000 g, and the low-birth-weight rate among live births increased from 6.3% to 9.6%. No prospective study has elucidated the risk factors for poor fetal growth and preterm birth in recent Japanese parents, such as increased parental age, maternal body figure, assisted reproductive technology (ART), and socioeconomic status. Participants were mother–infant pairs (n = 18,059) enrolled in a prospective birth cohort in Hokkaido, Japan from 2002 to 2013. Parental characteristics were obtained via self-reported questionnaires during pregnancy. Medical records helped identify very-low-birth-weight (VLBW; <1500g), term-small-for-gestational-age (term-SGA), and preterm-birth (PTB; <37 weeks) infants. We calculated relative risks (RRs) for PTB, VLBW, and term-SGA birth based on parental characteristics. The prevalence of PTB, VLBW, and term-SGA was 4.5%, 0.4%, and 6.5%, respectively. Aged parents and ART were risk factors for PTB and VLBW. Maternal alcohol drinking during pregnancy increased the risk; a parental educational level of ≥16 years reduced risk of term-SGA. Maternal pre-pregnancy BMI of <18.5 kg/m2 increased the risk of PTB and term-SGA. The RR for low BMI was highest among mothers who have low educational level. Among various factors, appropriate nutritional education to maintain normal BMI is important to prevent PTB and term-SGA in Japan.
Sarcoma Spheroids and Organoids—Promising Tools in the Era of Personalized Medicine
Authors: Colella Gianluca , Fazioli Flavio , Gallo Michele , De Chiara Annarosaria , Apice Gaetano , Ruosi Carlo , Cimmino Amelia , De Nigris Filomena
Published: February 2018

Cancer treatment is rapidly evolving toward personalized medicine, which takes into account the individual molecular and genetic variability of tumors. Sophisticated new in vitro disease models, such as three-dimensional cell cultures, may provide a tool for genetic, epigenetic, biomedical, and pharmacological research, and help determine the most promising individual treatment. Sarcomas, malignant neoplasms originating from mesenchymal cells, may have a multitude of genomic aberrations that give rise to more than 70 different histopathological subtypes. Their low incidence and high level of histopathological heterogeneity have greatly limited progress in their treatment, and trials of clinical sarcoma are less frequent than trials of other carcinomas. The main advantage of 3D cultures from tumor cells or biopsy is that they provide patient-specific models of solid tumors, and they overcome some limitations of traditional 2D monolayer cultures by reflecting cell heterogeneity, native histologic architectures, and cell–extracellular matrix interactions. Recent advances promise that these models can help bridge the gap between preclinical and clinical research by providing a relevant in vitro model of human cancer useful for drug testing and studying metastatic and dormancy mechanisms. However, additional improvements of 3D models are expected in the future, specifically the inclusion of tumor vasculature and the immune system, to enhance their full ability to capture the biological features of native tumors in high-throughput screening. Here, we summarize recent advances and future perspectives of spheroid and organoid in vitro models of rare sarcomas that can be used to investigate individual molecular biology and predict clinical responses. We also highlight how spheroid and organoid culture models could facilitate the personalization of sarcoma treatment, provide specific clinical scenarios, and discuss the relative strengths and limitations of these models.
Comparison of SF6 and CF4 Plasma Treatment for Surface Hydrophobization of PET Polymer
Authors: Resnik Matic , Zaplotnik Rok , Mozetic Miran , Vesel Alenka
Published: February 2018

The fluorination of the polymer polyethylene terephthalate in plasma created from SF6 or CF4 gas at various pressures was investigated. The surface was analysed by X-ray photoelectron spectroscopy and water contact angle measurements, whereas the plasma was characterized by optical emission spectroscopy. The extent of the polymer surface fluorination was dependent on the pressure. Up to a threshold pressure, the amount of fluorine on the polymer surface and the surface hydrophobicity were similar, which was explained by the full dissociation of the SF6 and CF4 gases, leading to high concentrations of fluorine radicals in the plasma and thus causing the saturation of the polymer surface with fluorine functional groups. Above the threshold pressure, the amount of fluorine on the polymer surface significantly decreased, whereas the oxygen concentration increased, leading to the formation of the hydrophilic surface. This effect, which was more pronounced for the SF6 plasma, was explained by the electronegativity of both gases.
Visualization of MMP-2 Activity Using Dual-Probe Nanoparticles to Detect Potential Metastatic Cancer Cells
Authors: Lee Aeju , Kim Sung Hoon , Lee Hyun , Kim Bohee , Kim Yoon Suk , Key Jaehong
Published: February 2018

Matrix metalloproteinases (MMPs) are a family of zinc-dependent enzymes capable of degrading extracellular matrix components. Previous studies have shown that the upregulation of MMP-2 is closely related to metastatic cancers. While Western blotting, zymography, and Enzyme-Linked Immunosorbent Assays (ELISA) can be used to measure the amount of MMP-2 activity, it is not possible to visualize the dynamic MMP-2 activities of cancer cells using these techniques. In this study, MMP-2-activated poly(lactic-co-glycolic acid) with polyethylenimine (MMP-2-PLGA-PEI) nanoparticles were developed to visualize time-dependent MMP-2 activities. The MMP-2-PLGA-PEI nanoparticles contain MMP-2-activated probes that were detectable via fluorescence microscopy only in the presence of MMP-2 activity, while the Rhodamine-based probes in the nanoparticles were used to continuously visualize the location of the nanoparticles. This approach allowed us to visualize MMP-2 activities in cancer cells and their microenvironment. Our results showed that the MMP-2-PLGA-PEI nanoparticles were able to distinguish between MMP-2-positive (HaCat) and MMP-2-negative (MCF-7) cells. While the MMP-2-PLGA-PEI nanoparticles gave fluorescent signals recovered by active recombinant MMP-2, there was no signal recovery in the presence of an MMP-2 inhibitor. In conclusion, MMP-2-PLGA-PEI nanoparticles are an effective tool to visualize dynamic MMP-2 activities of potential metastatic cancer cells.
The Relationship between Maternal Nutrition during Pregnancy and Offspring Kidney Structure and Function in Humans: A Systematic Review
Authors: Lee Yu Qi , Collins Clare E. , Gordon Adrienne , Rae Kym M. , Pringle Kirsty G.
Published: February 2018

The intrauterine environment is critical for fetal growth and organ development. Evidence from animal models indicates that the developing kidney is vulnerable to suboptimal maternal nutrition and changes in health status. However, evidence from human studies are yet to be synthesised. Therefore, the aim of the current study was to systematically review current research on the relationship between maternal nutrition during pregnancy and offspring kidney structure and function in humans. A search of five databases identified 9501 articles, of which three experimental and seven observational studies met the inclusion criteria. Nutrients reviewed to date included vitamin A (n = 3), folate and vitamin B12 (n = 2), iron (n = 1), vitamin D (n = 1), total energy (n = 2) and protein (n = 1). Seven studies were assessed as being of “positive” and three of “neutral” quality. A variety of populations were studied, with limited studies investigating maternal nutrition during pregnancy, while measurements of offspring kidney outcomes were diverse across studies. There was a lack of consistency in the timing of follow-up for offspring kidney structure and/or function assessments, thus limiting comparability between studies. Deficiencies in maternal folate, vitamin A, and total energy during pregnancy were associated with detrimental impacts on kidney structure and function, measured by kidney volume, proteinuria, eGFRcystC and mean creatinine clearance in the offspring. Additional experimental and longitudinal prospective studies are warranted to confirm this relationship, especially in Indigenous populations where the risk of renal disease is greater.
Joint Sparse and Low-Rank Multitask Learning with Laplacian-Like Regularization for Hyperspectral Classification
Authors: He Zhi , Wang Yiwen , Hu Jie
Published: February 2018

Multitask learning (MTL) has recently provided significant performance improvements in supervised classification of hyperspectral images (HSIs) by incorporating shared information across multiple tasks. However, the original MTL cannot effectively exploit both local and global structures of the HSI and the class label information is not fully used. Moreover, although the mathematical morphology (MM) has attracted considerable interest in feature extraction of HSI, it remains a challenging issue to sufficiently utilize multiple morphological profiles obtained by various structuring elements (SEs). In this paper, we propose a joint sparse and low-rank MTL method with Laplacian-like regularization (termed as sllMTL) for hyperspectral classification by utilizing the three-dimensional morphological profiles (3D-MPs) features. The main steps of the proposed method are twofold. First, the 3D-MPs are extracted by the 3D-opening and 3D-closing operators. Different SEs are adopted to result in multiple 3D-MPs. Second, sllMTL is proposed for hyperspectral classification by taking the 3D-MPs as features of different tasks. In the sllMTL, joint sparse and low-rank structures are exploited to capture the task specificity and relatedness, respectively. Laplacian-like regularization is also added to make full use of the label information of training samples. Experiments on three datasets demonstrate the OA of the proposed method is at least about 2% higher than other state-of-the-art methods with very limited training samples.
An Optimal Image-Based Method for Identification of Acoustic Emission (AE) Sources in Plate-Like Structures Using a Lead Zirconium Titanate (PZT) Sensor Array
Authors: Yan Gang , Zhou Li
Published: February 2018

This paper proposes an innovative method for identifying the locations of multiple simultaneous acoustic emission (AE) events in plate-like structures from the view of image processing. By using a linear lead zirconium titanate (PZT) sensor array to record the AE wave signals, a reverse-time frequency-wavenumber (f-k) migration is employed to produce images displaying the locations of AE sources by back-propagating the AE waves. Lamb wave theory is included in the f-k migration to consider the dispersive property of the AE waves. Since the exact occurrence time of the AE events is usually unknown when recording the AE wave signals, a heuristic artificial bee colony (ABC) algorithm combined with an optimal criterion using minimum Shannon entropy is used to find the image with the identified AE source locations and occurrence time that mostly approximate the actual ones. Experimental studies on an aluminum plate with AE events simulated by PZT actuators are performed to validate the applicability and effectiveness of the proposed optimal image-based AE source identification method.
Split-Ring Resonator Sensor Penetration Depth Assessment Using In Vivo Microwave Reflectivity and Ultrasound Measurements for Lower Extremity Trauma Rehabilitation
Authors: Mohd Shah Syaiful Redzwan , Velander Jacob , Mathur Parul , Perez Mauricio D. , Asan Noor Badariah , Kurup Dhanesh G. , Blokhuis Taco J. , Augustine Robin
Published: February 2018

In recent research, microwave sensors have been used to follow up the recovery of lower extremity trauma patients. This is done mainly by monitoring the changes of dielectric properties of lower limb tissues such as skin, fat, muscle, and bone. As part of the characterization of the microwave sensor, it is crucial to assess the signal penetration in in vivo tissues. This work presents a new approach for investigating the penetration depth of planar microwave sensors based on the Split-Ring Resonator in the in vivo context of the femoral area. This approach is based on the optimization of a 3D simulation model using the platform of CST Microwave Studio and consisting of a sensor of the considered type and a multilayered material representing the femoral area. The geometry of the layered material is built based on information from ultrasound images and includes mainly the thicknesses of skin, fat, and muscle tissues. The optimization target is the measured S11 parameters at the sensor connector and the fitting parameters are the permittivity of each layer of the material. Four positions in the femoral area (two at distal and two at thigh) in four volunteers are considered for the in vivo study. The penetration depths are finally calculated with the help of the electric field distribution in simulations of the optimized model for each one of the 16 considered positions. The numerical results show that positions at the thigh contribute the highest penetration values of up to 17.5 mm. This finding has a high significance in planning in vitro penetration depth measurements and other tests that are going to be performed in the future.
Uncertainly Analysis of Two Types of Humidity Sensors by a Humidity Generator with a Divided-Flow System
Authors: Chen Ling-Hsi , Chen Chiachung
Published: February 2018

Humidity measurement is an important technique for the agricultural, foods, pharmaceuticals, and chemical industries. For the sake of convenience, electrical relative humidity (RH) sensors have been widely used. These sensors need to be calibrated to ensure their accuracy and the uncertainty measurement of these sensors has become a major concern. In this study, a self-made divided-flow generator was established to calibrate two types of electrical humidity sensors. The standard reference humidity was calculated from dew-point temperature and air dry-bulb temperature measured by a chilled mirror monitor. This divided-flow generator could produce consistent result of RH measurement results. The uncertainty of the reference standard increased with the increase of RH values. The combined uncertainty with the adequate calibration equations were ranged from 0.82% to 1.45% RH for resistive humidity sensors and 0.63% to 1.4% for capacitive humidity sensors, respectively. This self-made, divided-flow generator, and calibration method are cheap, time-saving, and easy to be used. Thus, the proposed approach can easily be applied in research laboratories.
The Responses of Plant Leaf CO2/H2O Exchange and Water Use Efficiency to Drought: A Meta-Analysis
Authors: Zhang Jinmeng , Jiang Hong , Song Xinzhang , Jin Jiaxin , Zhang Xiuying
Published: February 2018

Persistent drought severely inhibits plant growth and productivity, which negatively affects terrestrial primary productivity worldwide. Therefore, it is important to investigate the impacts of drought on plant leaf CO2/H2O exchange and water use efficiency. This study assessed the responses of net photosynthesis (Pn), stomatal conductance (Gs), transpiration (Tr), and instantaneous water use efficiency (WUE) to drought based on a worldwide meta-analysis of 112 published studies. The results demonstrated that drought decreased Pn, Tr, and Gs significantly and differently among different moderators. C4 plants had smaller Pn reduction than C3 plants, which gives C4 plants an advantage in Pn. But their WUE decreased under drought conditions, indicating a great flexibility in C4 WUE. Annual herbs sacrificed WUE (−6.2%) to maintain efficient Pn. Perennial herbs took a different strategy in response to drought with an increased WUE (25.1%). Deciduous tree species displayed a greater increase in WUE than conifers and evergreen species. Additionally, Gs had a significant correlation with Pn and Tr, but an insignificant correlation with WUE, which could be because WUE is affected by other factors (e.g., air flow, CO2 concentration, and relative humidity). These findings have significant implications for understanding the worldwide effects of drought on plant leaf CO2/H2O exchange and water use efficiency.
Future career intentions of recent GP graduates in Ireland: a trend analysis study
Authors: Pericin Ivana , Mansfield Gerard , Larkin James , Collins Claire
Published: February 2018

Background

A lack of manpower and negative health statistics have increased the workload for Irish GPs. Consequently, recent GP graduates are considering emigration or part-time employment.

Aim

To report on trends of the current status and future work intentions of recent GP graduates in Ireland.

Design & setting

Quantitative study based on online surveys in the Irish setting.

Method

A ‘career intentions’ survey was emailed to all recent GP graduates in Ireland, in 2014, 2015, and 2017. The data presented includes GPs who graduated in the previous 4 years at each survey time point. The average response rate across the three surveys was 38.2%.

Results

The number of graduates who had already emigrated increased over the survey years, accounted for 16.9% in 2014, 17.4% in 2015, and 19.2% in 2017 survey. The majority of doctors who emigrated did so in the first 2 years after graduation (74.7%). ‘Quality of life’ became the most frequent reason for emigration over the survey years, accounting for 32.0% in the 2017 survey. In the 2014 survey, 47.3% of graduates stated that they intend to work part-time in 5 years; this rose to 51.2% in 2015, reaching 60.0% in 2017. Female participants were more than twice as likely to plan to work part time in 5 years compared to their male colleagues, across all three surveys.

Conclusion

The first and second years after graduation were the most critical for emigration. Interventions in this period may reduce the 'brain drain' of Irish GPs. Part-time working is becoming more attractive and should be considered in future workforce planning.
Combined pulsed laser deposition and non-contact atomic force microscopy system for studies of insulator metal oxide thin films
Authors: Katsube Daiki , Yamashita Hayato , Abo Satoshi , Abe Masayuki
Published: February 2018

We have designed and developed a combined system of pulsed laser deposition (PLD) and non-contact atomic force microscopy (NC-AFM) for observations of insulator metal oxide surfaces. With this system, the long-period iterations of sputtering and annealing used in conventional methods for preparing a metal oxide film surface are not required. The performance of the combined system is demonstrated for the preparation and high-resolution NC-AFM imaging of atomically flat thin films of anatase TiO2(001) and LaAlO3(100).
Antibacterial activity of Ilex paraguariensis (Yerba Mate) against Gram-positive and Gram-negative bacteria
Authors: Noureddine Tania , Al Husseini Ziad , Nehme Ali , Abdel Massih Roula
Published: February 2018

Introduction: Limited research was performed on the antibacterial activity of the aqueous extract of Yerba Mate. The purpose of this study is to evaluate the anti-bacterial activity of Yerba Mate against Gram-positive and Gram-negative bacterial strains and its action against some resistant bacteria with genotypic molecular testing of resistance profiles.

Methodology: Commercial Ilex paraguariensis stems and leaves were purchased and extracts were prepared by adding water at 70oC for 2 hrs. ATCC bacterial strains and clinical strains from Centre Hospitalier Du Nord (CHN) were used for testing. Macro dilution method was used to determine the minimal inhibitory. Minimal bactericidal concentration (MBC) was determined by sub-culturing the tubes with clear broth. For phenotypic and genotypic detection of β-lactamases, Double Disk Synergy method, E-test, phenylboronic acid disc method and multiplex PCR were performed for the identification of the mechanisms of resistance.

Results: Antibacterial activity was observed against all tested strains, with a greater activity against Gram-positive bacteria. This study showed mostly a greater antibacterial activity of aqueous extract of Yerba Mate in comparison to different extraction methods published. In general, the MIC and MBC values ranged between 0.468 mg/mL and 15 mg/mL. No correlation was found between the different molecular resistance profiles and the antibacterial activity.

Conclusion: More studies are needed to determine the molecule or molecules responsible for this activity. Moreover, testing a wider range of bacterial isolates is important for a better understanding of the potential role of Yerba Mate.
Candida glabrata spondylodiscitis: A case report
Authors: El Khoury Christina , Younes Philippe , Hallit Rabih , Okais Nabil , Matta Matta Antoun
Published: February 2018

Introduction: Spondylodiscitis is an infection in the intervertebral disc space and adjacent end plates. It can be attributed to bacteria, mycobacteria or fungi. As the number of immunosuppressed patients continues to grow, the incidence of developing fungal infections has become more frequent.

Methodology: We report the case of a 53-year-old immunocompetent female patient with a fungal spondylodiscitis infection caused by Candida glabrata diagnosed by open surgical biopsy, one-month posturosepsis.

Results: Our patient with Candida glabrata was disease free in 6 months after being treated through surgical fusion at the level of C4-C5 and the use of intravenous micafungin followed by oral voriconazole for a total of 6 months.

Discussion: Fungal spondylodiscitis, especially due to Candida glabrata, remains a rare condition, usually suspected in immunocompromised and elderly patients. Without appropriate diagnosis and tailored surgical and medical treatment, the infection can be progressive and yield to deleterious complications such as vertebral destruction. Surgical debridement of the disc alongside fusion and antifungal therapy for a minimum of 3 months are highly recommended.
Molecular epidemiology and clonality of Acinetobacter spp in a Lebanese hospital over a period of one year
Authors: Soudeiha Micheline , Sokhn Elie Salem , Daoud Ziad , Sarkis Dolla
Published: February 2018

Introduction: The worldwide emergence of antimicrobial resistance in Acinetobacter spp and their clonal dissemination call for the investigation into Acinetobacter spp epidemiology.

Methodology: 100 nonrepetitive Acinetobacter spp isolates were recovered from patients admitted at Saint- George-Hospital-University-Medical-Center-Beirut, in a one-year period. Identification of the isolates was determined by the API20NE and confirmed by PCR amplification of blaOXA-51-like. Susceptibility to carbapenems and colistin were determined by the microdilution method and interpreted according to the CLSI, 2015.The β lactamase inhibitors: PBA, EDTA, and Cloxacillin were used for the detection of KPC, MBL and AmpC, respectively. ESBL producers were detected whenever a keyhole effect was observed between 3rd generation cephalosporin and Augmentin®. Simplex PCR was conducted for the genotypic detection of β lactamases. ERIC and 3LST-PCR were performed to determine the clonality of the isolates.

Results: Our findings showed that 84% were carbapenem resistant. Only one isolate was resistant to colistin. Phenotypically, 23 were ESBL, 15 KPC, 5 AmpC, and 4 MBL producers. PCR analysis showed that 99%, 93%, 77% and 3 % of the isolates harbored blaOXA-51-like, blaADC, blaOXA-23-like, and blaOXA-40-like, respectively. ERIC-PCR analysis showed that A.baumannii isolates were clustered in 19 possibly related and 30 closely related subtypes. The 3-LST-PCR showed that 86.2% of the A.baumannii isolates pertained to the ICII (international clone II).

Conclusion: Our study showed a predominance of OXA-23-like producers and dissemination of ICII. Inhibitor based method was shown not to be accurate for the prediction of carbapenemases in Acinetobacter spp. Infection control measures are needed for management of Acinetobacter spp infections.
Search for hits and early leads from soil bacteria to combat infectious diseases
Authors: Herrmann Jennifer
Published: February 2018

Introduction: Natural products are the source of a large fraction of the current pharmaceutics available against human disease. However, the discovery of novel compounds with new mechanisms of action is becoming increasingly challenging. We focused our work on soil-dwelling Myxobacteria from highly diverse samples, which are more and more recognized as an important natural product source.

Methodology: Our discovery pipeline combines traditional whole cell-based activity screens with state-of-the-art analytical techniques and a comprehensive dereplication process. Having identified an antimicrobial compound we aim at elucidating its target, MOA and MOR in diverse microbiological screens and by applying ‘omic’ technologies.

Results: Two case studies of currently investigated compound classes will be highlighted. Cystobactamids are novel topoisomerase inhibitors that display very pronounced activity on Gram-positive and Gram-negative bacteria. Telomycins from Streptomyces canus bind to cardiolipin and our studies revealed other putative cellular targets.

Conclusion: We were able to isolate several new natural products with potent and selective activity against clinically relevant pathogens. Interestingly, underlying MOAs often differ from those of already described antimicrobial agents.
Prevalence of carbapenem resistance genes and corresponding MIC90 in Enterobacteriaceae at a tertiary care center in Lebanon
Authors: Kissoyan Kohar Annie , Araj George F , Matar Ghassan M
Published: February 2018

Introduction: The aim of this study was to correlate genes involved in carbapenem resistance to MIC levels among clinical ESBL and non-ESBL producing carbapenem resistant Enterobacteriaceae (CRE) isolates of Escherichia coli and Klebsiella pneumoniae.

Methodology: E. coli (n = 76) and K. pneumoniae (n = 54), collected between July 2008 and July 2014, were analyzed. The MICs were determined against ertapenem (ERT), imipenem (IMP) and meropenem (MER). PCR was performed on all 130 isolates to amplify

the resistance and outer membrane proteins (OMPs) encoding genes: blaOXA-48, blaNDM-1, blaTEM-1, blaCTX-M-15, ompC and ompF. Sequencing was performed on selected isolates.

Results: The prevalence of blaOXA-48, blaNDM-1, blaTEM-1, and/or blaCTX-M-15 among E. coli isolates were 36%, 12%, 20% and 80%, respectively, while among K. pneumoniae they were 37%, 28%, 28% and 72%, respectively. K. pneumoniae isolates positive for any of these genes had an MIC90 > 32μg/mL against ERT, IMP and MER, while in E. coli isolates there was a variation in the MIC90 values. Porin impermeabilities were due to mutations in ompC and ompF genes in E. coli, and loss of ompC and ompF genes in K. pneumoniae, and increased MIC90 values.

Conclusion: The presence of more than one carbapenem resistance encoding gene and/or ESBL encoding gene did not have an effect on the MIC90 value in K. pneumoniae isolates, while in E. coli it showed higher MIC90 values.
Combating antimicrobial resistance using antimicrobial combination therapy and β–lactamase inhibitors
Authors: El-Hafi Bassam , Rasheed Sari Shawki , Salloum Noor A , Abou Fayad Antoine , Araj George F , Matar Ghassan M
Published: February 2018

Introduction: The range of antimicrobial agents used to treat bacterial infections is becoming limited with the constant increase in antimicrobial resistance (AMR). Several genetic factors underlie AMR, including β-lactamase-encoding genes such as blaCTXM-15 that confers resistance to third-generation cephalosporins, and blaOXA-48, blaNDM-1, and blaKPC-2 that confer resistance to carbapenems. Remaining treatment approaches for such resistant infections include antimicrobial combination therapy and the use of β-lactamase inhibitors. This study assesses the molecular effects of such treatment approaches on antimicrobial resistant Enterobacteriaceae clinical isolates in vitro and in vivo.
Methodology: Nine clinical Enterobacteriaceae isolates were included in the study. One harboring blaCTXM-15, one harboring blaOXA-48, one harboring blaKPC-2, two harboring blaNDM-1 and blaCTXM-15, and four harboring blaOXA-48 and blaCTXM-15. Minimal inhibitory concentrations were determined for carbapenems with β-lactamase inhibitors: avibactam, Ca-EDTA, and relebactam. Synergism between antibiotic combinations was determined by double disc diffusion when using colistin with several antibiotics. In vitro and in vivo gene expression levels were done on these combinations with and without inhibitors.
Results: The use of meropenem, imipenem, and ertapenem with the selected β-lactamase inhibitors restored isolate susceptibility in 100%, 87.5%, and 25% of the cases, respectively. Antimicrobial synergism was mostly detected between colistin and meropenem, fosfomycin, or tigecycline. Survival studies revealed the survival of most mice receiving antimicrobial combination therapy with inhibitors as compared to the controls. Overall gene expression levels of resistance genes were variable depending on treatment.
Conclusions: The threat of antibiotic resistant bacterial infections remains viable; however, different approaches to therapy are available.
Epidemiology of bacteremia after autologous hematopoietic stem cell transplantation in the absence of antibiotic prophylaxis
Authors: Moghnieh Rima , Mugharbil Anas , Youssef Ali , Jisr Tamima , Tamim Hani , Zahran Kamal , Khaldieh Samer , Abdallah Dania , Awad Lyn , Massri Oula , Rachini Najat , Hamdan Youssef , Ibrahim Ahmad
Published: February 2018

Introduction: Bacterial infections are frequent complications occurring after autologous hematopoietic stem-cell transplantation (AHSCT). Herein, we identified the bacterial ecology and its antibiogram in AHSCT patients. We assessed the incidence, contributing factors and outcome of prolonged neutropenia and bacteremia post-AHSCT in the absence of antibacterial prophylaxis.

Methodology: This is a retrospective chart review of 190 adult patients who underwent AHSCT for lymphoma and multiple myeloma, between 2005 and 2015 at a Lebanese hospital.

Results: Most of the isolated bacteria originated from urine (49%) followed by blood (30%) and were mainly Gram-negative (70%). Fluoroquinolone susceptibility was 57% among Gram-negative and Gram-positive isolates. Bacteremia was documented in 12.6% of the patients, with a predominant gram-negative etiology having 95% susceptibility to fluoroquinolones. The duration of neutropenia, < or > 7 days, did not affect the incidence of bacteremia (11% vs. 14% respectively, p = 0.17). Patients with lymphoma were more likely to have prolonged neutropenia compared to those with myeloma (p < 0.0001). The use of a central line and the development of central-line infections were significantly higher in Gram-positive bacteremia (p = 0.03, p = 0.008 respectively). Mucositis occurred more in Gram-negative bacteremia (p = 0.02). Total mortality rate was 3.7% in the whole population and that attributed to bacteremia was 12.5% in the bacteremia subgroup. Bacteremia was a predictor for mechanical ventilation (p = 0.003), septic shock and mortality (p = 0.025).

Conclusion: Since organisms causing bacteremia were still highly susceptible to fluoroquinolones and that the duration of neutropenia post-AHSCT didn't affect bacteremia, we concluded that fluoroquinolone prophylaxis is still valid yet, with close monitoring of resistance.
From bugs to drugs: Combating antimicrobial resistance by discovering novel antibiotics
Authors: Abou Fayad Antoine , Itani Dana , Miari Mariam , Tanelian Arax , Iweir Sereen , Matar Ghassan M
Published: February 2018

Introduction: Antimicrobial resistance (AMR) is emerging at an alarming rate as mortality due to resistant pathogens could rise to 10 million per year by 2050. Since AMR is against all clinically utilized antibiotics, finding novel antimicrobials with unexploited targets remains the main goal worldwide.  Soil microorganisms produce natural products as a significant number of drugs in clinical use are derived from these metabolites. Actinomycetes and Myxobacteria are soil dwelling microorganisms that produce secondary metabolites to be screened for antibacterial activity. More than 80% of clinically utilized antibiotics are either natural products or natural product-derived molecules such as vancomycin, teicoplanin, daptomycin, and tetracycline. This study aims to isolate and identify novel antimicrobials from Actinomycetes and Myxobacteria.

Methodology: Soil samples were collected from several areas in Lebanon. Samples were serially diluted for Actinomycetes isolation and boiled for Myxobacteria extraction, then plated on suitable media. Colonies obtained were purified and subjected to genomic DNA extraction then 16s rRNA analysis. Novel isolates were tested for their antimicrobial activity against Gram-positive Bacillus subtilis (ATCC 6051), Staphylococcus aureus (ATCC 29213, Newman, N315), Enterococcus faecalis (ATCC 19433), and Enterococcus faecium (DSMZ 17050), and Gram-negative Escherichia coli (ATCC 9637), Klebsiella pneumoniae (DSMZ), Pseudomonas aeruginosa (ATCC 27853, MEXAB), and Acinetobacter baumannii (ATCC 15308).

Results: Strain isolation and cultivation yielded a number of novel isolates whose extracts demonstrated strong antibacterial activity against pathogens including MRSA, VRE, and Escherichia coli (ATCC 9637).

Conclusion: Our efforts now focus on purifying these compounds, elucidate their structures and study their mode of action.
Comparison of virulence determinants among Acinetobacter baumannii Clinical isolates obtained from Spain and Lebanon
Authors: Dahdouh Elias Abdo , Suarez Rodriguez Monica , Daoud Ziad
Published: February 2018

Introduction. Acinetobacter baumannii is a pathogen that is causing concern due to its high genetic elasticity, allowing it to show high rates of antibiotic resistance and to express a wide range of virulence determinants. Several studies are aimed towards targeting the virulence of A. baumannii as an adjunct to antibiotic therapy. In this study, we investigate the difference in virulence determinants between A. baumannii isolates obtained from Spain and Lebanon

Methodology. Fifty-nine A. baumannii isolates were collected from La Paz Hospital, Spain, and 90 from St. George Hospital, Lebanon. The isolates were identified using VITEK-2. Biofilm formation was detected by crystal violet staining, hemolysis by blood agars, motility by surface motility assays, siderophore production by CAS assays, and proteolytic activity by azoalbumin assays.

Results. The expression of virulence determinants was highly variable among the isolates. Among the Spanish isolates, 84.4% produced biofilms, 54.2% showed hemolysis, and 69.5% produced siderophores. Among the Lebanese isolates, 85.6% produced strong biofilms, 47.8% showed hemolysis, and 57.8% produced siderophores. Proteolytic activity for the Spanish isolates (26.6 ± 8.4 U/L) was slightly higher than that of the Lebanese isolates (17.7 ± 9.5 U/L). Very few Spanish isolates (3) showed surface motility, as opposed to the majority of the Lebanese isolates (80) that showed surface motility.

Conclusion. The genomic plasticity of A. baumannii is demonstrated by its ability to differentially express virulence determinants. This highlights the need to treat each isolate as a unique case when attempting to use anti-virulence agents to treat A. baumannii infections.
Carriage trends and fitness cost of MDROs in Lebanese nursing homes
Authors: Challita Caren , Hafza Nourhane , Dahdouh Elias , Attieh Michel , Dandachi Iman , Daoud Ziad
Published: February 2018

Introduction: Nowadays, medical treatments efficiency is challenged by multi drug resistant organisms (MDROs). Lebanese nursing homes’ residents revealed high fecal carriage rates of MDR Enterobacteriacea. Previous studies claim that bacteria with resistant genes experience fitness cost. This study assesses the competitive growth of MDR Escherichia coli and Klebsiella pneumoniae.

Methodology: Fecal swabs were collected, during six consecutive months, from ten elderly residing in a Lebanese nursing home. All isolates were subject to API 20E (bioMerieux, Marcy L’ Etoile, France) and antimicrobial susceptibility (Kirby–Bauer method) testing. Phenotypically, ESBL (extended spectrum β-lactamase), MBL (metallo β-lactamase), AmpC and KPC (Klebsiella pneumoniae carbapenemase) were detected using EDTA, PBA, cloxacillin, and DDSTs (Biorad, Hercules, USA). Selected ESBL producing E. coli and K. pneumoniae underwent multiplex PCR analysis. Intra and inter-species in-vitro competition assays were conducted in multiple combinations.

Results: Among 117 collected isolates, E. coli was predominant (71.8%); 7.7% were ESBL and 5.1% AmpC producers. With E. coli intra-species assays, sensitive isolates out-competed all others, followed by ESBL, AmpC, and OXA-48 (oxacillin) producers. Inter-species assays, demonstrated a decreased fitness of ESBL producing K. pneumoniae in presence of sensitive E. coli. While out-competing ESBL producing E. coli required 2 sensitive K. pneumoniae isolates.

Conclusion: This study highlights resistant E. coli and K. pneumoniae frequency decrease in presence of sensitive isolates, endorsing the fitness cost hypothesis.  Hence, competing supplementary species reproducing gut flora, would ensure further steps in the fight against MDROs.