Identification of Topping Responsive Proteins in Tobacco Roots.

Abstract: The process of topping elicits many responses in the tobacco plant, including an increase in nicotine biosynthesis, and the secondary growth of roots. Some topping responsive miRNAs and genes have been identified in our previous study, but the mechanism of the tobacco response to topping has not yet been fully elucidated. In this study, topping responsive proteins isolated from tobacco roots were screened using two-dimensional electrophoresis. Of the proteins identified, calreticulin and auxin-responsive protein indole acetic acid (IAA9) were involved in the secondary growth of roots; leucine-rich repeat disease resistance, heat shock protein 70, and farnesyl pyrophosphate synthase 1 were involved in the wounding stress response; and F-box protein played an important role in promoting the ability of nicotine synthesis after topping. In addition, we identified five tobacco bHLH proteins (NtbHLH, NtMYC1a, NtMYC1b, NtMYC2a, and NtMYC2b) related to nicotine biosynthesis. NtMYC2 was suggested to be the main positive transcription factor, with NtbHLH protein being a negative regulator in the jasmonic acid (JA)-mediated activation of nicotine biosynthesis after topping. Tobacco topping activates a comprehensive range of biological processes involving the IAA and JA signaling pathways, and the identification of proteins involved in these processes will improve our understanding of the topping response.

Li|Fei|F| Zhang|Huizhen|H| Wang|Shaoxin|S| Xiao|Wanfu|W| Ding|Chao|C| Liu|Weiqun|W| Guo|Hongxiang|H|

topping
tobacco
secondary growth
nicotine synthesis
physiology response
roots proteome


Preventing transitions into injection drug use: A call for gender-responsive upstream prevention.

Abstract: In 2017, there were large increases (260-500%) in overdose deaths among women in the United States across age groups (30-64 years and 55-64 years). In addition, U.S. women who inject drugs (WWID) are at increased risk for substance use-related disease transmission, bacterial infections, as well as sexual and physical violence compared to men who inject drugs. Relatedly, women face unique access barriers to substance use-related services, such as stigma and low coverage of gender-specific drug use-related services. Despite these heightened risks experienced by WWID, interventions specifically tailored to preventing women from transitioning into injection drug use have not been developed to date. As such, we advocate for the development of gender-responsive programs to prevent injection drug use initiation. This is critical to ensuring a comprehensive approach to preventing injection drug use initiation among those populations at highest risk of injection-related morbidity and mortality.

Meyers|Stephanie A|SA|
Smith|Laramie R|LR|
Werb|Dan|D|

Prevention
Injection drug use
Gender
People who use drugs
Women who use drugs


Impaired Contextual Fear Extinction Learning is Associated with Aberrant Regulation of CHD-Type Chromatin Remodeling Factors.

Abstract: Successful attenuation of fearful memories is a cognitive process requiring initiation of highly coordinated transcription programs. Chromatin-modulating mechanisms such as DNA methylation and histone modifications, including acetylation, are key regulators of these processes. However, knowledge concerning the role of ATP-dependent chromatin remodeling factors (ChRFs) being required for successful fear extinction is lacking. Underscoring the potential importance of these factors that alter histone-DNA contacts within nucleosomes are recent genome-wide association studies linking several ChRFs to various human cognitive and psychiatric disorders. To better understand the role of ChRFs in the brain, and since to date little is known about ChRF expression in the brain, we performed a comprehensive survey of expression levels of 24 ATP-dependent remodelers across different brain areas, and we identified several distinct high molecular weight complexes by chromatographic methods. We next aimed to gain novel insight into the potential regulation of ChRFs in different brain regions in association with normal and impaired fear extinction learning. To this end, we established the 129S1/SvImJ (S1) laboratory mouse strain as a model for compromised contextual fear extinction learning that can be rescued by dietary zinc restriction (ZnR). Using this model along with genetically related but fear extinction-competent 129S6/SvEv (S6) mice as controls, we found that impaired fear extinction in S1 was associated with enhanced ventral hippocampal expression of CHD1 and reduced expression of CHD5 that was normalized following successful rescue of impaired fear extinction. Moreover, a select reduction in CHD3 expression was observed in the ventral hippocampus (vHC) following successful rescue of fear extinction in S1 mice. Taken together, these data provide novel insight into the regulation of specific ChRFs following an impaired cognitive process and its rescue, and they suggest that imbalance of CHD-type remodeler levels, which consequently may lead to changes of transcriptional programs, may be an underlying mechanism involved in impaired fear extinction learning and its therapeutic rescue.

Wille|Alexandra|A| Maurer|Verena|V| Piatti|Paolo|P| Whittle|Nigel|N| Rieder|Dietmar|D| Singewald|Nicolas|N| Lusser|Alexandra|A|

amygdala
anxiety behavior
epigenetics
gene regulation
nucleosome remodeling


Larvicidal, Repellent, and Irritant Potential of the Seed-Derived Essential oil of Apium graveolens Against Dengue Vector, Aedes aegypti L. (Diptera: Culicidae).

Abstract: Aedes aegypti L. is one of the primary disease vectors spreading various dreadful diseases throughout the world, specifically over tropics and subtropics. Keeping in view the adverse effects of chemical insecticides-based intervention measures, the eco-friendly and bio-degradable essential oil extracted from the seeds of celery, Apium graveolens were investigated for its efficacy against Ae. aegypti. Larvicidal bioassay carried out with the seed oil against early fourth instars of Ae. aegypti caused an LC50 and LC90 values of 16.10 and 29.08 ppm, respectively, after an exposure to 24 h. The cidal effect of the celery seed oil augmented by 1.2-fold; after an exposure to 48 h; revealing an LC50 value of 13.22 ppm. Interestingly, the seed oil did not cause immediate larval mortality, suggesting a delayed toxicity against the larval stage. Present investigations also revealed remarkable effective repellency of the oil leading to 100% protection till 165 min as compared to control that did not result in any repellency against adult Ae. aegypti. Interestingly, only one bite was recorded in the 165th-min after which only two bites were scored until 180 min of exposure of the adult mosquitoes to the oil. An exciting observation was that the knocked-down effect in adults exposed to 10% oil-impregnated papers. The contact irritancy assays with paper impregnated with 1% celery seed oil caused first flight only after 4 s resulting in an average of 63.66 flights during 15 min of exposure revealing the relative irritability of 26.97. The qualitative phytochemical analysis of the seed oil showed the presence of flavonoids, lactones, and terpenoids as the major constituents suggesting their probable role in the toxicity. Our results confirmed that celery seed essential oil can be used as an efficient larvicide and repellent against Ae. aegypti. The identification of the bioactive components, their mode of action, and studying effects on non-target organisms and the environment would help in devising mosquito-management strategies.

Kumar|Sarita|S| Mishra|Monika|M| Wahab|Naim|N| Warikoo|Radhika|R|

larvicide
repellent
irritancy
essential oil
% protection


Heuristic estimation of the α/β ratio for a cohort of Mexican patients with prostate cancer treated with external radiotherapy techniques.

Abstract:
Background
The aim of the study was to Estimate and compare the radiobiological ratio α/β with the heuristic method for a cohort of Mexican patients with prostate cancer (PCa) who were treated with external radiotherapy (RT) techniques at three Hospital Institutions in Mexico City. With the Kaplan-Meier technique and the Cox proportional hazards model, the biochemical relapse-free survival (bRFS) is determined and characterized for cohorts of Mexican patients with PCa who received treatment with external RT. Using these clinical outcomes, the radiobiological parameter α/β is determined using the heuristic methodology of Pedicini et. al.

Materials and methods
The α/β is calculated from the survival curves for different treatment schemes implemented at three distinct hospitals. The Pedicini's techniques allow to determine the parameters α/β, k and N  when treatments are not radiobiologically equivalent, therefore, are built up of a set of curved pairs for the biologically effective dose (BED) versus the ratio α/β, where the ratio is given by the intersection for each pair of curves.

Results
Six different values of α/β were found: the first α/β = 2.46 Gy, the second α/β = 3.30 Gy, the third for α/β = 3.25 Gy, the fourth α/β = 3.24 Gy, the fifth α/β = 3.38 Gy and the last α/β = 4.08 Gy. These values can be explained as follows: a) The bRFS of the schemes presents a statistical variation; b) The absorbed doses given to the patient present uncertainties on the physical dosimetry that are not on the modeling; c) Finally, in the model for the bRFS of Eq. (3), there are parameters that have to be considered, such as: the number of clonogenic tumor cells N  , the overall treatment time (OTT), the kick-off time for tumor repopulation T  and the repopulation doubling time. Therefore, the mean value to α/β for all schemes has an average value of 3.29 (± 0.52) Gy.

Conclusions
The value of   is determined from cohorts of Mexican patients with PC a treated with external radiotherapy using the time-dependent LQ model, which is a higher value with respect to the "dogma" value of α/β 1.5 Gy obtained with the LQ model without temporal dependence. Therefore, there is a possibility of optimizing treatments radiobiologically and improving the results of bRFS in Mexican patients with PCa treated with external radiotherapy.

α/β ratio
prostate cancer
PCa
biochemical relapse-free survival
bRFS
biologically effective dose
BED
time-dependent LQ model


β-Strand mimetic foldamers rigidified through dipolar repulsion.

Abstract: Many therapeutically relevant protein-protein interactions contain hot-spot regions on secondary structural elements, which contribute disproportionately to binding enthalpy. Mimicry of such α-helical regions has met with considerable success, however the analogous approach for the β-strand has received less attention. Presented herein is a foldamer for strand mimicry in which dipolar repulsion is a central determinant of conformation. Computation as well as solution- and solid-phase data are consistent with an ensemble weighted almost exclusively in favor of the desired conformation.

German|Elizabeth A|EA|
Ross|Jonathan E|JE|
Knipe|Peter C|PC|
Don|Michaela F|MF|
Thompson|Sam|S|
Hamilton|Andrew D|AD|

D018360:Crystallography, X-Ray
D008958:Models, Molecular
D015394:Molecular Structure
D010455:Peptides
D017433:Protein Structure, Secondary
D013816:Thermodynamics

protein-protein interactions
peptidomimetics
protein structures
solid-state structures
synthetic methods


Growing Canopy on a College Campus: Understanding Urban Forest Change through Archival Records and Aerial Photography.

Abstract: Many municipalities are setting ambitious tree canopy cover goals to increase the extent of their urban forests. A historical perspective on urban forest development can help cities strategize how to establish and achieve appropriate tree cover targets. To understand how long-term urban forest change occurs, we examined the history of trees on an urban college campus: the University of Pennsylvania in Philadelphia, PA. Using a mixed methods approach, including qualitative assessments of archival records (1870-2017), complemented by quantitative analysis of tree cover from aerial imagery (1970-2012), our analysis revealed drastic canopy cover increase in the late 20th and early 21st centuries along with the principle mechanisms of that change. We organized the historical narrative into periods reflecting campus planting actions and management approaches; these periods are also connected to broader urban greening and city planning movements, such as City Beautiful and urban sustainability. University faculty in botany, landscape architecture, and urban design contributed to the design of campus green spaces, developed comprehensive landscape plans, and advocated for campus trees. A 1977 Landscape Development Plan was particularly influential, setting forth design principles and planting recommendations that enabled the dramatic canopy cover gains we observed, and continue to guide landscape management today. Our results indicate that increasing urban tree cover requires generational time scales and systematic management coupled with a clear urban design vision and long-term commitments. With the campus as a microcosm of broader trends in urban forest development, we conclude with a discussion of implications for municipal tree cover planning.

Roman|Lara A|LA|
Fristensky|Jason P|JP|
Eisenman|Theodore S|TS|
Greenfield|Eric J|EJ|
Lundgren|Robert E|RE|
Cerwinka|Chloe E|CE|
Hewitt|David A|DA|
Welsh|Caitlin C|CC|

City planning history
Landscape design
Sustainable campus
Urban ecology
Urban environmental history
Urban tree canopy


Hypergraph Clustering Based on Game-Theory for Mining Microbial High-Order Interaction Module.

Abstract: Microbial community is ubiquitous in nature, which has a great impact on the living environment and human health. All these effects of microbial communities on the environment and their hosts are often referred to as the functions of these communities, which depend largely on the composition of the communities. The study of microbial higher-order module can help us understand the dynamic development and evolution process of microbial community and explore community function. Considering that traditional clustering methods depend on the number of clusters or the influence of data that does not belong to any cluster, this paper proposes a hypergraph clustering algorithm based on game theory to mine the microbial high-order interaction module (HCGI), and the hypergraph clustering problem naturally turns into a clustering game problem, the partition of network modules is transformed into finding the critical point of evolutionary stability strategy (ESS). The experimental results show HCGI does not depend on the number of classes, and can get more conservative and better quality microbial clustering module, which provides reference for researchers and saves time and cost. The source code of HCGI in this paper can be downloaded from https://github.com/ylm0505/HCGI.

hypergraph clustering
game-theory
Microbial higher-order module
evolutionary stability strategy


Magnetic Field-Controlled Lithium Polysulfide Semiliquid Battery with Ferrofluidic Properties.

Abstract: Large-scale energy storage systems are of critical importance for electric grids, especially with the rapid increasing deployment of intermittent renewable energy sources such as wind and solar. New cost-effective systems that can deliver high energy density and efficiency for such storage often involve the flow of redox molecules and particles. Enhancing the mass and electron transport is critical for efficient battery operation in these systems. Herein, we report the design and characterization of a novel proof-of-concept magnetic field-controlled flow battery using lithium metal-polysulfide semiliquid battery as an example. A biphasic magnetic solution containing lithium polysulfide and magnetic nanoparticles is used as catholyte, and lithium metal is used as anode. The catholyte is composed of two phases of polysulfide with different concentrations, in which most of the polysulfide molecules and the superparamagnetic iron oxide nanoparticles can be extracted together to form a high-concentration polysulfide phase, in close contact with the current collector under the influence of applied magnetic field. This unique feature can help to maximize the utilization of the polysulfide and minimize the polysulfide shuttle effect, contributing to enhanced energy density and Coulombic efficiency. Additionally, owing to the effect of the superparamagnetic nanoparticles, the concentrated polysulfide phase shows the behavior of a ferrofluid that is flowable with the control of magnetic field, which can be used for a hybrid flow battery without the employment of any pumps. Our innovative design provides new insight for a broad range of flow battery chemistries and systems.

Li|Weiyang|W| Liang|Zheng|Z| Lu|Zhenda|Z| Tao|Xinyong|X| Liu|Kai|K| Yao|Hongbin|H| Cui|Yi|Y|

ferrofluid
large-scale energy storage
flow battery
superparamagnetic nanoparticles
lithium polysulfide battery


Continuum in the X-Z---Y weak bonds: Z= main group elements.

Abstract: The Continuum in the variation of the X-Z bond length change from blue-shifting to red-shifting through zero- shifting in the X-Z---Y complex is inevitable. This has been analyzed by ab-initio molecular orbital calculations using Z= Hydrogen, Halogens, Chalcogens, and Pnicogens as prototypical examples. Our analysis revealed that, the competition between negative hyperconjugation within the donor (X-Z) molecule and Charge Transfer (CT) from the acceptor (Y) molecule is the primary reason for the X-Z bond length change. Here, we report that, the proper tuning of X- and Y-group for a particular Z- can change the blue-shifting nature of X-Z bond to zero-shifting and further to red-shifting. This observation led to the proposal of a continuum in the variation of the X-Z bond length during the formation of X-Z---Y complex. The varying number of orbitals and electrons available around the Z-atom differentiates various classes of weak interactions and leads to interactions dramatically different from the H-Bond. Our explanations based on the model of anti-bonding orbitals can be transferred from one class of weak interactions to another. We further take the idea of continuum to the nature of chemical bonding in general.

Joy|Jyothish|J|
Jose|Anex|A|
Jemmis|Eluvathingal D|ED|

continuum
negative hyperconjugation
charge transfer
weak interactions
red- and blue-shift


IL-27, IL-30, and IL-35: A Cytokine Triumvirate in Cancer.

Abstract: The role of the immune system in anti-tumor immunity cannot be overstated, as it holds the potential to promote tumor eradication or prevent tumor cell escape. Cytokines are critical to influencing the immune responses and interactions with non-immune cells. Recently, the IL-12 and IL-6 family of cytokines have accumulated newly defined members each with specific immune functions related to various cancers and tumorigenesis. There is a need to better understand how cytokines like IL-27, IL-30, and IL-35 interact with one another, and how a developing tumor can exploit these interactions to enhance immune suppression. Current cytokine-based immunotherapies are associated with cytotoxic side effects which limits the success of treatment. In addition to this toxicity, understanding the complex interactions between immune and cancer cells may be one of the greatest challenges to developing a successful immunotherapy. In this review, we bring forth IL-27, IL-30, and IL-35, "sister cytokines," along with more recent additions to the IL-12 family, which serve distinct purposes despite sharing structural similarities. We highlight how these cytokines function in the tumor microenvironment by examining their direct effects on cancer cells as well their indirect actions via regulatory functions of immune cells that act to either instigate or inhibit tumor progression. Understanding the context dependent immunomodulatory outcomes of these sister cytokines, as well as their regulation within the tumor microenvironment, may shed light onto novel cancer therapeutic treatments or targets.

Kourko|Olena|O| Seaver|Kyle|K| Odoardi|Natalya|N| Basta|Sameh|S| Gee|Katrina|K|

cytokines
cancer
immunotherapy
tumor microenvironment
signaling


Senescent B cells in aging and age-related diseases: Their role in the regulation of antibody responses.

Abstract: Immune cells with a senescence-associated secretory phenotype increase in the blood of elderly individuals or individuals with age-associated diseases or with infections. Although senescent immune cells do not proliferate, they are transcriptionally and metabolically active and affect the microenvironment through the secretion of pro-inflammatory mediators. An age-driven increase in senescent B, T and NK cells has been reported and the function of these cells has been characterized. Results published by different groups have demonstrated that cell senescence induces the accumulation of terminally-differentiated cells characterized by the arrest of cell proliferation but with an active secretory profile which regulates their function through the activation of pathways integrating senescence and energy-sensing signals. This review will focus on senescent B cells, their increase in aging, age-associated conditions and infections. Similarities with other senescent immune cells will be presented and discussed.

B cells
Antibody responses
Cell senescence
Inflammation


Muscle Glycogen Phosphorylase and Its Functional Partners in Health and Disease.

Abstract: Glycogen phosphorylase (PG) is a key enzyme taking part in the first step of glycogenolysis. Muscle glycogen phosphorylase (PYGM) differs from other PG isoforms in expression pattern and biochemical properties. The main role of PYGM is providing sufficient energy for muscle contraction. However, it is expressed in tissues other than muscle, such as the brain, lymphoid tissues, and blood. PYGM is important not only in glycogen metabolism, but also in such diverse processes as the insulin and glucagon signaling pathway, insulin resistance, necroptosis, immune response, and phototransduction. PYGM is implicated in several pathological states, such as muscle glycogen phosphorylase deficiency (McArdle disease), schizophrenia, and cancer. Here we attempt to analyze the available data regarding the protein partners of PYGM to shed light on its possible interactions and functions. We also underline the potential for zebrafish to become a convenient and applicable model to study PYGM functions, especially because of its unique features that can complement data obtained from other approaches.

muscle glycogen phosphorylase
glycogenolysis
PYGM
McArdle disease
schizophrenia
cancer
functional protein partners


Combined OX40 ligation plus CTLA-4 blockade: More than the sum of its parts.

Abstract: It is becoming clear that combination strategies will be necessary to augment cancer immunotherapy. We report that combination anti-OX40/anti-CTLA-4 mAb immunotherapy improves survival by enhancing effector T cell expansion and function, even while inducing Th2 cytokine production. Furthermore, IL-4 blockade in addition to combination therapy significantly improved anti-tumor efficacy.

Linch|Stefanie N|SN|
Redmond|William L|WL|


The regulation of Akt and FoxO transcription factors during dehydration in the African clawed frog (Xenopus laevis).

Abstract: The African clawed frog (Xenopus laevis) naturally tolerates severe dehydration using biochemical adaptation, one of which is the elevation of antioxidant defenses during whole-body dehydration. The present study investigated the role and regulation of a pathway known to regulate oxidative stress response, the Akt-FoxO signaling pathway, in clawed frog skeletal muscle, responding to medium (15%) and high (30%) dehydration. Protein levels of total and phosphorylated Akt, FoxO1, and FoxO3 were assessed via immunoblotting, in addition to the levels of the E3 ubiquitin ligase known to be associated with muscle atrophy, MAFbx. Akt activity/phosphorylation in addition to its total protein levels were decreased in the skeletal muscle during dehydration, and this corresponded with decreases in the relative phosphorylation of FoxO1 and FoxO3 as well on several residues. Akt is an inhibitor of FoxO1 and FoxO3 activity via phosphorylation, suggesting that FoxO activities were increased during dehydration stress. Furthermore, MAFbx showed decreased protein expression during high dehydration as well, suggesting that the clawed frog may exhibit some natural resistance to skeletal muscle atrophy during severe dehydration conditions. In addition to identifying that the suppression of Akt could lead to an activation of FoxO transcription factors in X. laevis during dehydration, these investigations suggest that X. laevis dehydration may implicate FoxO1 and FoxO3 in controlling skeletal muscle atrophy in X. laevis exposed to dehydration. This study implicates the Akt signaling pathway, its regulation of FoxO transcription factors, and FoxO-controlled targets, in stress adaptation against dehydration.

Akt
FoxO
Dehydration
Xenopus laevis
Immunoblot


A novel four- and pseudo-five-component reaction: unexpected efficient one-pot synthesis of 4H-thiopyran derivatives.

Abstract: A facile and convenient novel method is reported for the synthesis of substituted 4H-thiopyrans by reacting aldehydes, malononitrile, carbon disulfide, and primary amines at room temperature in the presence of triethylamine as a catalyst. This reaction affords the desired products in high purity and has advantages of excellent yields, simple work-up procedure, and short reaction time.

Mobinikhaledi|Akbar|A|
Bodaghifard|Mohammad Ali|MA|
Asadbegi|Sajad|S|

Isothiocyanate
MCR
Michael addition
Multicomponent reaction
One-pot reaction
Thiopyrans


First survey of hard ticks (Acari: Ixodidae) on cattle, sheep and goats in Boeen Zahra and Takistan counties, Iran.

Abstract:
OBJECTIVE
To carry out the distribution survey of hard ticks of livestock in Boeen Zahra and Takistan counties of Qazvin province from April 2010 to September 2010.

METHODS
Nearly about 2 638 sheep, 461 goats and 318 cattle of 38 herds in different geographical areas were searched for tick infestation.

RESULTS
The species compositions collected from the livestock of Boeen Zahra and Takistan were Haemaphysalis concinna (0.63%), Haemaphysalis sulcata (12.66%), Hyalomma anatolicum (3.80%), Hyalomma asiaticum (3.16%), Hyalomma detritum (5.70%), Hyalomma dromedarii (28.48%), Hyalomma marginatum (13.29%), Hyalomma schulzei (1.89%), Rhipicephalus bursa (3.16%) and Rhipicephalus sanguineus (3.16%), and for Takistan's livestock were Hyalomma dromedarii (9.86%), Hyalomma marginatum (13.29%), Hyalomma schulzei (1.89%) and Rhipicephalus sanguineus (3.16%), respectively. Hard ticks compositions in different topographic areas were different. Hyalomma species had the most prevalence in the areas.

CONCLUSIONS
The veterinary and public health investigation of the above species should be taken.

Shemshad|Masoomeh|M|
Shemshad|Khadijeh|K|
Sedaghat|Mohammad Mehdi|MM|
Shokri|Majid|M|
Barmaki|Alireza|A|
Baniardalani|Mojgan|M|
Rafinejad|Javad|J|

Hard ticks
Ixodidae
Cattle
Sheep
Goats
Boeen Zahra
Takistan
Iran


Zebrafish Models of Cancer-New Insights on Modeling Human Cancer in a Non-Mammalian Vertebrate.

Abstract: Zebrafish (Danio rerio) is a valuable non-mammalian vertebrate model widely used to study development and disease, including more recently cancer. The evolutionary conservation of cancer-related programs between human and zebrafish is striking and allows extrapolation of research outcomes obtained in fish back to humans. Zebrafish has gained attention as a robust model for cancer research mainly because of its high fecundity, cost-effective maintenance, dynamic visualization of tumor growth in vivo, and the possibility of chemical screening in large numbers of animals at reasonable costs. Novel approaches in modeling tumor growth, such as using transgene electroporation in adult zebrafish, could improve our knowledge about the spatial and temporal control of cancer formation and progression in vivo. Looking at genetic as well as epigenetic alterations could be important to explain the pathogenesis of a disease as complex as cancer. In this review, we highlight classic genetic and transplantation models of cancer in zebrafish as well as provide new insights on advances in cancer modeling. Recent progress in zebrafish xenotransplantation studies and drug screening has shown that zebrafish is a reliable model to study human cancer and could be suitable for evaluating patient-derived xenograft cell invasiveness. Rapid, large-scale evaluation of in vivo drug responses and kinetics in zebrafish could undoubtedly lead to new applications in personalized medicine and combination therapy. For all of the above-mentioned reasons, zebrafish is approaching a future of being a pre-clinical cancer model, alongside the mouse. However, the mouse will continue to be valuable in the last steps of pre-clinical drug screening, mostly because of the highly conserved mammalian genome and biological processes.

D015972:Gene Expression Regulation, Neoplastic

D023041:Xenograft Model Antitumor Assays

zebrafish, epigenetics, xenotransplantation, drug screen, pre-clinical cancer model


Assessing the influences of ecological restoration on perceptions of cultural ecosystem services by residents of agricultural landscapes of western China.

Abstract: Landscape change caused by ecological restoration projects has both positive and negative influences on human livelihoods, yet surprisingly little research on the cultural consequences of ecological restoration in agricultural landscapes has taken place. Cultural consequences can be captured in the ecosystem services framework as cultural ecosystem services (CES). However, assessment and valuation of these services to support decision-making for this essential ecosystem is lacking. To help fill this gap, we assessed the opinions of Chinese rural communities about CES and the changes in their perception under the Grain for Green program (GFG), a nationwide program to relieve the pressure on ecosystems (soil erosion and land degradation) by converting cultivated land or barren land on steep slopes into grassland and forests. We used Guyuan City in China's Ningxia Hui Autonomous Region as a case study, using a workshop to identify the CES provided by the agricultural landscape, followed by semi-structured household interviews to quantify perceptions of these CES. We found that all eight CES types identified by the workshop were perceived by the rural communities. Reforestation changed their perceptions of CES directly due to land cover change and indirectly due to the resulting economic changes and migration of mostly young workers in search of better jobs. Cultivated land was perceived as more important than forest for CES provision. In addition, residential areas were perceived as providing significant CES because of local traditions that produce close and highly social neighborhood bonds in agricultural landscapes.

Dou|Yuehan|Y| Zhen|Lin|L| Yu|Xiubo|X| Bakker|Martha|M| Carsjens|Gerrit-Jan|GJ| Xue|Zhichao|Z|

D003247:Conservation of Natural Resources

D052918:Environmental Restoration and Remediation

Ecological restoration
Cultural ecosystem services
Agricultural landscapes
Household survey
Human perception


RNA-seq analyses of Arabidopsis thaliana seedlings after exposure to blue-light phototropic stimuli in microgravity.

Abstract:
PREMISE
Plants synthesize information from multiple environmental stimuli when determining their direction of growth. Gravity, being ubiquitous on Earth, plays a major role in determining the direction of growth and overall architecture of the plant. Here, we utilized the microgravity environment on board the International Space Station (ISS) to identify genes involved influencing growth and development of phototropically stimulated seedlings of Arabidopsis thaliana.

METHODS
Seedlings were grown on the ISS, and RNA was extracted from 7 samples (pools of 10-15 plants) grown in microgravity (μg) or Earth gravity conditions (1-g). Transcriptomic analyses via RNA sequencing (RNA-seq) of differential gene expression was performed using the HISAT2-Stringtie-DESeq2 RNASeq pipeline. Differentially expressed genes were further characterized by using Pathway Analysis and enrichment for Gene Ontology classifications.

RESULTS
For 296 genes that were found significantly differentially expressed between plants in microgravity compared to 1-g controls, Pathway Analysis identified eight molecular pathways that were significantly affected by reduced gravity conditions. Specifically, light-associated pathways (e.g., photosynthesis-antenna proteins, photosynthesis, porphyrin, and chlorophyll metabolism) were significantly downregulated in microgravity.

CONCLUSIONS
Gene expression in A. thaliana seedlings grown in microgravity was significantly altered compared to that of the 1-g control. Understanding how plants grow in conditions of microgravity not only aids in our understanding of how plants grow and respond to the environment but will also help to efficiently grow plants during long-range space missions.

phototropism
transcriptomics
European Modular Cultivation System
spaceflight
tropisms


Updates on Management of Gastric Cancer.

Abstract:
PURPOSE OF REVIEW
Gastric adenocarcinoma is the fifth most common and the third most lethal cancer worldwide. Surgery is the only chance of cure, but recurrence is common, even with complete resection.

RECENT FINDINGS
Advances in diagnosis and staging, genomic classification, surgical resection and treatment of peritoneal disease, systemic chemotherapy and chemoradiation, and targeted and immune therapies have led to the current multidisciplinary approach to gastric adenocarcinoma. Treatment of gastric cancer is rapidly evolving in an effort to combat this challenging disease.

D000971:Antineoplastic Combined Chemotherapy Protocols

Gastric cancer
Gastric adenocarcinoma
CYTO-CHIP
FLOT
HIPEC
Siewert type III


Long-term in vivo degradation behaviour and biocompatibility of the magnesium alloy ZEK100 for use as a biodegradable bone implant.

Abstract: Magnesium alloys are the focus of research as resorbable materials for osteosynthesis, as they provide sufficient stability and would make surgery to remove implants unnecessary. The new degradable magnesium alloy ZEK100 was developed to improve the stability and corrosion resistance by alloying with zinc, rare earth metals and zirconium. As the implants were degraded to only a limited extent after 6 months implantation in a previous in vivo study the present study was conducted to evaluate the long-term degradation behaviour and biocompatibility in the same animal model over 9 and 12 months. Five rabbits each with intramedullary tibia implants were examined over 9 and 12 months. Three legs were left without an implant to serve as negative controls. Numerous examinations were performed in the follow-up (clinical examinations, serum analysis, and radiographic and in vivo micro-CT investigations) and after death (ex vivo micro-CT, histology, and implant analysis) to assess the in vivo degradation and biocompatibility. It could be shown that favourable in vivo degradation behaviour is not necessarily associated with good biocompatibility. Although ZEK100 provided a very high initial stability and positive biodegradation, it must be excluded from further biomedical testing as it showed pathological effects on the host tissue following complete degradation.

Dziuba|Dina|D|
Meyer-Lindenberg|Andrea|A|
Seitz|Jan Marten|JM|
Waizy|Hazibullah|H|
Angrisani|Nina|N|
Reifenrath|Janin|J|

In vivo
Degradation
Biocompatibility
Magnesium alloy
Long-term study


Ambient air pollution exposures and risk of drug-resistant tuberculosis.

Abstract:
BACKGROUND
Few epidemiological studies have explored the effects of air pollution on the risk of drug-resistant tuberculosis (DR-TB).

OBJECTIVE
To investigate the short and long term residential concentrations of ambient air pollutants (particulate matter <10 μm in diameter (PM10) and particulate matter≤2.5 μm in diameter (PM2.5), nitrogen dioxide (NO2), sulfur dioxide (SO2), ozone (O3), and carbon monoxide (CO)) in relation to the risk of DR-TB in a typical air pollution city, Jinan city, China.

METHODS
A total of 752 new culture-confirmed TB cases reported in TB prevention and control institutions of Jinan from January 1, 2014 to December 31, 2015 were included. Average individual-level concentrations of air pollution for 5 different exposure windows, vary from 90 days to 720 days to diagnosis were estimated using measurements from monitor closest to the patient home addresses. Logistic regression model adjusted for potential confounders was employed to evaluate correlation between air pollution and DR-TB risk at different five exposure windows individually.

RESULTS
There were substantially increased mono-drug resistance and poly-drug resistance risks for ambient PM2.5, PM10, O3, and CO exposures. High exposure to PM2.5, PM10, and CO was also significantly associated with increased incidence of multi-drug resistance (MDR) both in the single- and multi-pollutants regression models. The dominant positive associations for PM2.5was observed at 540 days exposure, for O3 was observed at 180 days exposure, and for PM10 and CO was observed from 90 days to 540 days exposures.

CONCLUSIONS
Our finding suggest that exposure to ambient air pollution (PM2.5, PM10, O3, and CO) are associated with increased risk of DR-TB. We provided epidemiological evidence of association between pollution exposure and mono-, poly- and multi-drug resistance.

Yao|Liu|L| LiangLiang|Cui|C| JinYue|Liu|L| WanMei|Song|S| Lili|Su|S| YiFan|Li|L| HuaiChen|Li|L|

Air pollution
Drug-resistant
China
Tuberculosis (TB)


Red Blood Cell Distribution Width Is Increased in Patients with Pemphigus: A Case-Control Study.

Abstract:
BACKGROUND
Red blood cell distribution width (RDW) has recently emerged as an inflammatory marker in several inflammatory diseases but has not been investigated in patients with pemphigus.

OBJECTIVE
We aimed to examine RDW percentage in patients with pemphigus relative to control subjects and to assess the association between this biomarker and the morphological characteristics of the disease.

METHODS
This case-control study included 183 pemphigus patients and 915 age- and sex-matched control subjects. RDW, hemoglobin, and mean corpuscular volume (MCV) were measured for all study participants.

RESULTS
The RDW was significantly higher in patients with pemphigus than in controls (13.7±1.3 vs. 13.4±1.1%, respectively; P=0.001). A significant association between RDW and pemphigus was demonstrated in multivariate analysis (odds ratio, 1.22; 95% confidence interval, 1.01-1.46; P=0.036). The RDW was higher in patients with pemphigus vulgaris (PV) than in pemphigus foliaceus (PF; P=0.043), and in those with mucocutaneous PV relative to those with mucosal only and cutaneous only PV. The RDW increased significantly following treatment (P<0.001).

CONCLUSION
Pemphigus patients demonstrated elevated RDW as compared with healthy controls. RDW may be a feasible biomarker in patients with pemphigus. Although it clearly does not replace any of the accepted diagnostic immunopathological criteria, increased RDW may be more suggestive of PV than PF, and of mucocutaneous rather than cutaneous PV. The remarkable increase following treatment may be ascribed to the corticosteroid-induced erythropoiesis.

Laufer Britva|Rimma|R|
Kridin|Mouhammad|M|
Kridin|Khalaf|K|

red blood cell distribution width
Pemphigus
RDW
inflammation
surrogate


Oxidative and cellular metabolic stress of Oreochromis mossambicus as biomarkers indicators of trace element contaminants.

Abstract: Antioxidative status, cellular metabolic stress and neurotransmitter enzyme assay as a pollution biomarker in Oreochromis mossambicus collected from Bhima river were investigated. O. mossambicus was collected from 18 different sites of Bhima river, which differ in their extent and type of contamination load. The antioxidative status were determined such as catalase (CAT), superoxide dismutase (SOD) and glutathione-s-transferase (GST) in the liver, gill, brain, gonad and kidney. All the studied parameters indicated potent signals for contamination of the aquatic water body. The antioxidative status was substantially high (p < 0.01) in the fish collected from Bhima river. The cellular stress enzymes such as lactate dehdrogenase (LDH), and malate dehydrogenase (MDH) in liver, gill, brain, gonad and muscle were remarkably (p < 0.01) elevated in O. mossambicus collected from Bhima river. The brain acetylcholine esterase (AChE) was noticeably inhibited (p < 0.01) whereas lipid peroxide (LPO) elevated in fish collected from a few sites. We also used morphological study as biomarkers indicators such as condition factor (CF), hepatosomatic index (HSI), gonadosomatic index (GSI). The results of condition factor and gonadosomatic index are significantly (p < 0.01) poor and hepatosomatic index was significantly (p < 0.01) elevated in O. mossambicus. The finding of the present investigation provides a rational application of oxidative stress, cellular stress, neurotransmitter, lipid peroxide and some morphological parameters to be used as biomarkers for biomonitoring the contamination of trace elements in polluted aquatic environment.

Kumar|Neeraj|N|
Krishnani|K K|KK|
Meena|K K|KK|
Gupta|Sanjay Kumar|SK|
Singh|N P|NP|

Antioxidative status
Cellular stress
Acetylcholine esterase
Lipid peroxide
Organosomatic index


Alcohol Consumption: Discussing Potential Risks for Informed Decisions in Breast Cancer Survivors.

Abstract:
BACKGROUND
Alcohol consumption is a known risk factor for breast cancer. Because breast cancer survivors are already at risk for recurrence, it is important to understand whether these survivors could benefit from survivor-specific recommendations for alcohol consumption.

OBJECTIVES
The purpose of this article was to review primary research specific to alcohol and breast cancer survivors to see whether those who consume alcohol experience more adverse effects.

METHODS
This literature review examined nine cohort studies specific to breast cancer survivors, alcohol consumption, and risks for breast cancer recurrence, breast cancer-specific mortality, and second primary breast cancers.

FINDINGS
Current guideline recommendations of a safe limit of one drink per day or less may not protect breast cancer survivors from cancer- related adverse events. The authors recommend that breast cancer survivors be educated about the associated risks of alcohol consumption so that they can make informed decisions about usage.

Terry|Katherine|K|
Mayer|Deborah K|DK|
Wehner|Kimberly|K|

alcohol consumption
breast cancer
recurrence
survivorship


MUAC as the sole discharge criterion from community-based management of severe acute malnutrition in Burkina Faso.

Abstract: The use of mid upper arm circumference (MUAC) measurement to screen and determine eligibility for admission to therapeutic feeding programs has been established, but evidence and programmatic experience to inform guidance on the use of MUAC as a discharge criterion is limited. We present results from a large-scale nutritional program using MUAC for admission and discharge and compare program outcomes and response to treatment when determining eligibility for discharge by proportional weight gain versus discharge by MUAC. The study population included all children admitted to the Ministry of Health therapeutic feeding program supported by Médecins Sans Frontières in northern Burkina Faso from September 2007 to December 2011 (n = 50,841). Recovery was high overall using both discharge criteria, with low risks of death, nonresponse, and transfer to inpatient care and high daily gains in weight, MUAC, weight-for-height Z score, and height. When discharge was made by MUAC only, recovery increased, while all adverse program outcomes and length of stay decreased, with increasing MUAC on admission. MUAC-based programming, where MUAC is integrated into program screening, admission, and discharge, is one of several new approaches that can be used to target resources to the most at-risk malnourished children and improve program efficiency and coherency. This analysis provides additional programmatic experience on the use of MUAC-based discharge criterion, but more work may be needed to inform optimal discharge thresholds across settings.

community-based management of acute malnutrition


Efficacy of a Newly Designed Cephalometric Analysis Software for McNamara Analysis in Comparison with Dolphin Software.

Abstract:
OBJECTIVES
Cephalometric norms of McNamara analysis have been studied in various populations due to their optimal efficiency. Dolphin cephalometric software greatly enhances the conduction of this analysis for orthodontic measurements. However, Dolphin is very expensive and cannot be afforded by many clinicians in developing countries. A suitable alternative software program in Farsi/English will greatly help Farsi speaking clinicians. The present study aimed to develop an affordable Iranian cephalometric analysis software program and compare it with Dolphin, the standard software available on the market for cephalometric analysis.

MATERIALS AND METHODS
In this diagnostic, descriptive study, 150 lateral cephalograms of normal occlusion individuals were selected in Mashhad and Qazvin, two major cities of Iran mainly populated with Fars ethnicity, the main Iranian ethnic group. After tracing the cephalograms, the McNamara analysis standards were measured both with Dolphin and the new software. The cephalometric software was designed using Microsoft Visual C++ program in Windows XP. Measurements made with the new software were compared with those of Dolphin software on both series of cephalograms. The validity and reliability were tested using intra-class correlation coefficient.

RESULTS
Calculations showed a very high correlation between the results of the Iranian cephalometric analysis software and Dolphin. This confirms the validity and optimal efficacy of the newly designed software (ICC 0.570-1.0).

CONCLUSION
According to our results, the newly designed software has acceptable validity and reliability and can be used for orthodontic diagnosis, treatment planning and assessment of treatment outcome.

Nouri|Mahtab|M|
Hamidiaval|Shadi|S|
Akbarzadeh Baghban|Alireza|A|
Basafa|Mohammad|M|
Fahim|Mohammad|M|

Analysis Software Orthodontics Cephalometry


Serum amyloid A in polycystic ovary syndrome.

Abstract: Polycystic ovary syndrome (PCOS), i.e., anovulation, hyperandrogenemia and polycystic ovary, is an endocrine-metabolic disease affecting reproductive aged women. Women with PCOS are likely to develop obesity, dyslipidemia, type 2 diabetes mellitus (T2DM) and cardiovascular diseases at a younger age. Despite high frequency and severe disease burden, the pathophysiological mechanisms of PCOS remain poorly defined and correspondingly have no therapeutic options. Emerging evidence has demonstrated that PCOS is accompanied with low-grade chronic inflammation and biomarkers thereof. Interestingly, serum amyloid A (SAA) has recently been identified as a potential marker of infection and inflammation and a number of studies have reported an association with PCOS. In this review, we explore the relationship between SAA and hyperandrogenemia, inflammation, obesity and insulin resistance, and provide convincing evidence for SAA as a potential inflammatory biomarker in PCOS.

Liu|Huiqing|H| Meng|Xingqi|X| Wang|Jinyuan|J| Wei|Yi|Y| Tang|Jinru|J| Lei|Xiaocan|X| He|Weiguo|W| Li|Suyun|S|

Serum amyloid A
Polycystic ovary syndrome
Hyperandrogenemia
Obesity
Inflammation
Insulin resistance


Precise control of maxillary multidirectional movement in Le Fort I osteotomy using a surgical guiding device.

Abstract: We introduced a surgical protocol to achieve accurate maxillary multidirectional movement in Le Fort I osteotomies. This comprised a way of controlling precision and a guiding device together with prebent titanium plates. We evaluated the protocol using a semiautomated 3-dimensional assessment in 22 patients with maxillary multidirectional movement (movement in three or more of six directions). Operations were all done between October 2015 and April 2017 by the same surgeon, who followed the protocol strictly. To evaluate the accuracy, we measured the deviation of the orientation of landmarks and of the upper dentition. All cases were followed up for at least a year. They all involved maxillary movement in at least three directions, and nine involved movement in six. The guiding device was used intraoperatively in all cases. Vertical deviation of the segments of bone was often detected during removal of bone, and sagittal deviation in three cases, but we found no transverse deviations. The assessment of accuracy showed that the mediolateral, anteroposterior, and superoinferior translations of landmarks were all less than 1mm, with mean values of 0.29, 0.43, and 0.39mm, respectively. The pitch, roll, and yaw of the upper dentition were also less than 1°, with mean values of 0.60°, 0.35°, 0.36°, respectively. The proposed protocol allowed accurate reposition of the maxilla with multidirectional movement during Le Fort I osteotomy.

Xue|C|C| Xu|H|H| Tian|Y|Y| Yang|X|X| Luo|E|E| Bai|D|D|

Le Fort I osteotomy
Titanium plate
CAD/CAM
Orthognathic surgery


Modern Diagnosis of Early Esophageal Cancer: From Blood Biomarkers to Advanced Endoscopy and Artificial Intelligence.

Abstract: Esophageal cancer (EC) is the seventh most common cancer and the sixth cause of cancer death worldwide. Histologically, esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) account for up to 90% and 20% of all ECs, respectively. Clinical symptoms such as dysphagia, odynophagia, and bolus impaction occur late in the natural history of the disease, and the diagnosis is often delayed. The prognosis of ESCC and EAC is poor in advanced stages, being survival rates less than 20% at five years. However, when the diagnosis is achieved early, curative treatment is possible, and survival exceeds 80%. For these reasons, mass screening strategies for EC are highly desirable, and several options are currently under investigation. Blood biomarkers offer an inexpensive, non-invasive screening strategy for cancers, and novel technologies have allowed the identification of candidate markers for EC. The esophagus is easily accessible via endoscopy, and endoscopic imaging represents the gold standard for cancer surveillance. However, lesion recognition during endoscopic procedures is hampered by interobserver variability. To fill this gap, artificial intelligence (AI) has recently been explored and provided encouraging results. In this review, we provide a summary of currently available options to achieve early diagnosis of EC, focusing on blood biomarkers, advanced endoscopy, and AI.

diagnosis
esophageal cancer
biomarkers
advanced endoscopy
artificial intelligence
early neoplasia


Comparative safety of high-dose versus standard-dose influenza vaccination in patients with end-stage renal disease.

Abstract:
BACKGROUND
High-dose influenza vaccine (HDV) is an alternative vaccination strategy in patients with end-stage renal disease (ESRD), though the safety of HDV has not been evaluated in this population. The objective of this study was to estimate the relative occurrence of adverse vaccine reactions in patients with ESRD following vaccination with HDV compared with standard-dose influenza vaccine (SDV).

METHODS
Using data from the United States Renal Data System, we identified patients with ESRD aged ≥ 65 years at influenza vaccination during yearly influenza seasons from 2010 through 2016. Patients were followed after vaccination to observe serious (anaphylaxis, angioedema, seizure, encephalopathy, Guillain-Barré syndrome [GBS], and short-term, all-cause mortality) and milder (urticaria/hives, rash, pain in limb, cellulitis, myalgia/myositis, fever, nausea and vomiting, diarrhea, and syncope) adverse events. Propensity score-weighted hazard ratios (HRs) and 95% confidence intervals (CIs) for HDV versus SDV were estimated with Cox proportional hazards models.

RESULTS
Of 520,876 vaccinations observed (mean age = 74.7 years at vaccination; 63% white race), 7.4% were HDV. For serious events, the weighted HRs were null for seizure, encephalopathy, and mortality and inestimable due to too few cases for anaphylaxis, angioedema, and GBS. For milder vaccine reactions, the weighted HRs demonstrated generally increased risks in the HDV group, including rash (HR = 1.86; 95% CI, 1.34-2.57), diarrhea (HR = 1.26; 95% CI, 1.07-1.50), pain in limb (HR = 1.23; 95% CI, 1.12-1.34), and myalgia/myositis (HR = 1.16; 95% CI, 1.04-1.30).

CONCLUSIONS
The risks of serious adverse events were low and similar between treatment groups; however, HDV recipients had increased risks of several milder adverse events compared with SDV recipients, consistent with clinical trial findings in the general population of older adults. These results add important information to inform the risk-benefit tradeoff of the use of HDV versus SDV in patients with ESRD.

Layton|J Bradley|JB|
McGrath|Leah J|LJ|
Sahrmann|John M|JM|
Ma|Yinjiao|Y|
Dharnidharka|Vikas R|VR|
O'Neil|Caroline|C|
Weber|David J|DJ|
Butler|Anne M|AM|

Safety
High-dose
Influenza vaccines
Adverse reactions
Hemodialysis


Mortality after Respiratory Isolation of Nontuberculous Mycobacteria. A Comparison of Patients Who Did and Did Not Meet Disease Criteria.

Abstract:
RATIONALE
The mortality of patients with respiratory tract isolates of nontuberculous mycobacteria (NTM) and their risk factors for death are not well described.

OBJECTIVES
To determine age-adjusted mortality rates for patients with respiratory NTM isolates and their causes of death and to examine whether American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) diagnostic criteria identify those at higher risk of death after NTM isolation.

METHODS
We linked vital records registries with a previously identified Oregon population-based cohort of patients with NTM respiratory isolation. We excluded patients with Mycobacterium gordonae (n = 33) and those who died (n = 21) at the time of first isolation. We calculated 5-year age-adjusted mortality rates. We used Kaplan-Meier and Cox proportional hazards analysis to examine the association of ATS/IDSA criteria and other risk factors with death.

RESULTS
Of 368 subjects with respiratory NTM isolates in 2005-2006, 316 were included in the survival analysis. Most (84%) of their cultures isolated Mycobacterium avium complex. 35.1% died in the 5 years following respiratory isolation. Five-year age-adjusted mortality rates were slightly higher for those meeting (28.7/1,000) versus not meeting (23.4/1,000) ATS/IDSA criteria. In multivariate analysis, older age (adjusted hazard ratio [aHR], 1.06; 95% confidence interval [CI], 1.04-1.07) and lung cancer (aHR, 2.77; 95% CI, 1.51-5.07) were associated with an increased risk of death. A trend was noted between meeting ATS/IDSA criteria and subsequent death (aHR, 1.37; 95% CI, 0.95-1.97). Among cases, male sex, older age, and immunosuppressive therapy use were independent risk factors for death.

CONCLUSIONS
In the State of Oregon, patients with NTM respiratory isolates have high mortality, regardless of whether they meet ATS/IDSA criteria for pulmonary NTM disease. Most patients die as a result of causes other than NTM infection.

Novosad|Shannon A|SA|
Henkle|Emily|E|
Schafer|Sean|S|
Hedberg|Katrina|K|
Ku|Jennifer|J|
Siegel|Sarah A R|SAR|
Choi|Dongseok|D|
Slatore|Christopher G|CG|
Winthrop|Kevin L|KL|

mortality
nontuberculous mycobacteria
natural history


Liquid-Phase Hot Deformation to Enhance Thermoelectric Performance of n-type Bismuth-Telluride-Based Solid Solutions.

Abstract: Bismuth-telluride-based solid solutions are the best commercial thermoelectric materials near room temperature. For their n-type polycrystalline compounds, the maximum figures of merit (zTs) are often less than 1.0 due to the degraded carrier mobility resulting from the loss of texture. Herein, a liquid-phase hot deformation procedure, during which the Bi2(Te,Se)3 ingots are directly hot deformed with the extrusion of liquid eutectic phase, is performed to enhance the thermoelectric performance of n-type Bi2(Te,Se)3 alloys. The deformation-induced dynamic recrystallization is remarkably suppressed due to the reduction of nucleation sites and the release of deformation stress by liquid phase, contributing to a weakened carrier scattering and enhanced carrier mobility. The liquid eutectic phase also facilitates the rotation of grains and enhanced (000l) texture, further improving carrier mobility. In addition, the dense dislocations and lattice distortion introduced into the matrix reduce the lattice thermal conductivity. As a result, a high zT value of 1.1 at 400 K is obtained, about 75% increment over the normal one-step hot deformed alloys. This work not only demonstrates a simple and efficient technique for achieving superior n-type Bi2Te3-based materials, but also elucidates the important role of liquid eutectic phase in hot deformation.

hot deformation
thermoelectric materials
bismuth tellurides
thermoelectric properties


Statistical models of critical phenomena in fuzzy biocognition.

Abstract: A recent line of study exploring statistical models of punctuated global broadcasts associated with attention states has focused on the evolutionary exaptation of the inevitable signal crosstalk between related sets of unconscious cognitive modules (UCM). This work invokes a groupoid treatment of the equivalence classes arising from information sources 'dual', in a formal sense, to the UCM, via a standard spontaneous symmetry breaking/lifting methodology abducted from statistical physics. A related approach involves an index theorem based on a stochastic empirical Onsager-like entropy-analog gradient model. Surprisingly, similar arguments may apply to 'fuzzy groupoid' generalizations likely to better fit biological complexities.

D016247:Information Storage and Retrieval

Crosstalk
Groupoid
Index theorem
Information theory
Phase transition


Protein surface charge effect on 3D domain swapping in cells for c-type cytochromes.

Abstract: Many c-type cytochromes (cyts) can form domain-swapped oligomers. The positively charged Hydrogenobacter thermophilus (HT) cytochrome (cyt) c552 forms domain-swapped oligomers during expression in the Escherichia coli (E. coli) expression system, but the factors influencing the oligomerization remain unrevealed. Here, we found that the dimer of the negatively charged Shewanella violacea (SV) cyt c5 exhibits a domain-swapped structure, in which the N-terminal helix is exchanged between protomers, similar to the structures of the HT cyt c552 and Pseudomonas aeruginosa (PA) cyt c551 domain-swapped dimers. Positively charged horse cyt c and HT cyt c552 domain swapped during expression in E. coli, whereas negatively charged PA cyt c551 and SV cyt c5 did not. Oligomers were formed during expression in E. coli for HT cyt c552 attached to either a co- or post-translational signal peptide for transportation through the cytoplasm membrane, but not for PA cyt c551 attached to either signal peptide. HT cyt c552 formed oligomers in E. coli in the presence and absence of rare codons. More oligomers were obtained from the in vitro folding of horse cyt c and HT cyt c552 by the addition of negatively charged liposomes during folding, whereas the amount of oligomers for the in vitro folding of PA cyt c551 and SV cyt c5 did not change significantly by the addition. These results indicate that the protein surface charge affects the oligomerization of c-type cyts in cells; positively charged c-type cyts assemble on a negatively charged membrane, inducing formation of domain-swapped oligomers during folding.

Yang|Hongxu|H| Yamanaka|Masaru|M| Nagao|Satoshi|S| Yasuhara|Kazuma|K| Shibata|Naoki|N| Higuchi|Yoshiki|Y| Hirota|Shun|S|

D001426:Bacterial Proteins
D003574:Cytochrome c Group
D004926:Escherichia coli
D000072417:Protein Domains
D055503:Protein Multimerization
D011550:Pseudomonas aeruginosa
D020592:Shewanella
D013499:Surface Properties

Protein surface charge
Domain swapping
c-type cytochrome
Oligomerization
Lipid-protein interaction


Ubiquitination regulates the neuroprotective function of the deubiquitinase ataxin-3 in vivo.

Abstract: Deubiquitinases (DUBs) are proteases that regulate various cellular processes by controlling protein ubiquitination. Cell-based studies indicate that the regulation of the activity of DUBs is important for homeostasis and is achieved by multiple mechanisms, including through their own ubiquitination. However, the physiological significance of the ubiquitination of DUBs to their functions in vivo is unclear. Here, we report that ubiquitination of the DUB ataxin-3 at lysine residue 117, which markedly enhances its protease activity in vitro, is critical for its ability to suppress toxic protein-dependent degeneration in Drosophila melanogaster. Compared with ataxin-3 with only Lys-117 present, ataxin-3 that does not become ubiquitinated performs significantly less efficiently in suppressing or delaying the onset of toxic protein-dependent degeneration in flies. According to further studies, the C terminus of Hsc70-interacting protein (CHIP), an E3 ubiquitin ligase that ubiquitinates ataxin-3 in vitro, is dispensable for its ubiquitination in vivo and is not required for the neuroprotective function of this DUB in Drosophila. Our work also suggests that ataxin-3 suppresses degeneration by regulating toxic protein aggregation rather than stability.

Tsou|Wei-Ling|WL|
Burr|Aaron A|AA|
Ouyang|Michelle|M|
Blount|Jessica R|JR|
Scaglione|K Matthew|KM|
Todi|Sokol V|SV|

D018507:Gene Expression Regulation, Developmental

Ubiquitin
Neuroprotection
Ataxin-3
Protease
Drosophila
Deubiquitination
Machado-Joseph Disease
Neurodegeneration
Polyglutamine Disease


Potential Use of Plastic Wastes for Low Thermal Conductivity Concrete.

Abstract: The use of plastics has increased over the years, thus resulting in a large volume of plastic waste being generated and accumulated in the environment. Due to its non-biodegradability and persistence, recycling processes have become one of the sustainable solutions for preventing environmental deterioration. Plastic wastes, including high density polyethylene (HDPE), low density polyethylene (LDPE), polypropylene (PP), and polyethylene terephthalate (PET), were collected from industrial sector and used as additional ingredients to improve concrete properties. Prior to concrete processing, an increase in wettability of plastic fibers using nonionic surfactant, Dehydol LS-12, was investigated. At the optimal concentration of 10 times of the critical micelle concentration (CMC), an interfacial tension and a contact angle were reduced to 31⁻32 mN/m and 65°⁻68°, respectively. Properties of concrete were determined and compared to those of the mortar samples. Porosity was found to increase with higher volume fraction of plastic fibers, whereas decreases in workability, bulk density, thermal conductivity, splitting tensile strength, and compressive strength were encountered. The lowest thermal conductivity was recorded for concrete samples prepared with 30% by volume of LDPE fibers, and the rest in descending order were HDPE, PP, and PET, respectively. Furthermore, the maximal inclusions of plastic fibers were 5% for HDPE and LDPE, 10% for PP, and 50% for PET so as to satisfy the precast concrete wall requirements.

low thermal conductivity concrete
building material
plastic waste utilization


Melody pulmonary valve bacterial endocarditis: experience in four pediatric patients and a review of the literature.

Abstract:
OBJECTIVES
The objectives of this manuscript are two-fold: (a) to describe the clinical characteristics and management of four pediatric patients with bacterial endocarditis (BE) after Melody pulmonary valve implantation (MPVI); and (b) to review the literature regarding Melody pulmonary valve endocarditis.

BACKGROUND
There are several reports of BE following MPVI. The clinical course, BE management and outcome remain poorly defined.

METHODS
This is a multi-center report of four pediatric patients with repaired tetralogy of Fallot (TOF) and BE after MPVI. Clinical presentation, echocardiogram findings, infecting organism, BE management, and follow-up assessment are described. We review available literature on Melody pulmonary valve endocarditis and discuss the prognosis and challenges in the management of these patients.

RESULTS
Of our four BE patients, two had documented vegetations and three showed worsening pulmonary stenosis. All patients remain asymptomatic after medical treatment (4) and surgical prosthesis replacement (3) at follow-up of 17 to 40 months. Analysis of published data shows that over half of patients undergo bioprosthesis explantation and that there is a 13% overall mortality. The most common BE pathogens are the Staphylococcus and Streptococcus species.

CONCLUSIONS
Our case series of four pediatric patients with repaired TOF confirms a risk for BE after MPVI. A high index of suspicion for BE should be observed after MPVI. All patients should be advised to follow lifelong BE prophylaxis after MPVI. In case of BE, surgery should be considered for valve dysfunction or no clinical improvement in spite of medical treatment.

Villafañe|Juan|J|
Baker|George Hamilton|GH|
Austin|Erle H|EH|
Miller|Stephen|S|
Peng|Lynn|L|
Beekman|Robert|R|

D019918:Heart Valve Prosthesis Implantation

transcatheter pulmonary valve implantation


Lessons learned with laparoscopic management of complicated grades of acute appendicitis.

Abstract:
BACKGROUND
Laparoscopy has not been consolidated as the approach of first choice in the management of complicated appendicitis. Methodological flaws and absence of disease stratification criteria have been implicated in that less evidence. The objective is to study the safe and effectiveness of laparoscopy in the management of complicated appendicitis according to laparoscopic grading system.

METHOD
From January 2008 to January 2011, 154 consecutive patients who underwent a laparoscopic appendectomy for complicated appendicitis were evaluated in the prospective way. The patient's age ranged from 12 to 75 years old (31.7 ± 13.3) and 58.3% were male. Complicated appendicitis refers to gangrenous and/or perforated appendix and were graded as 3A (segmental necrosis), 3B (base necrosis), 4A (abscess), 4B (regional peritonitis) and 5 (diffuse peritonitis). The outcomes including operative time, infection complication, operative complications and conversion rate were chosen to evaluate the procedure.

RESULTS
The grade 3A was the most frequent with 50 (32.4%) patients. The mean operative time was 69.4 ± 26.3 minutes. The grade 4A showed the highest mean operative time (80.1 ± 26.7 minutes). The wound and intra-abdominal infection rates were 2.6 and 4.6%, respectively. The base necrosis was the most important factor associated with the conversion (5.2%). The grades 4A and 5 were associated with greater possibility of intra-abdominal collection. There were no operative complications.

CONCLUSION
The laparoscopic management of all complicated grades of acute appendicitis is safe and effective and should be the procedure of first choice. The laparoscopic grading system allows us to assess patients in the same disease stage.

Gomes|Carlos Augusto|CA|
Junior|Cleber Soares|CS|
Costa|Evandro de Freitas Campos|Ede F|
Alves|Paula de Assis Pereira|Pde A|
de Faria|Carolina Vieira|CV|
Cangussu|Igor Vitoi|IV|
Costa|Luisa Pires|LP|
Gomes|Camila Couto|CC|
Gomes|Felipe Couto|FC|

Appendicitis Laparoscopy Appendectomy Treatment


Ginsenoside Rg1 ameliorates palmitic acid-induced insulin resistance in HepG2 cells in association with modulating Akt and JNK activity.

Abstract:
BACKGROUND
Hepatic insulin resistance can be induced by excess dietary intake of saturated fat. Ginsenoside Rg1 (GRg1), the major active ginsenoside enriched in tonic food ginseng, was reported to help alleviate liver diseases. In the present study, GRg1 was evaluated for its impact on palmitic acid (PA)-induced hepatic insulin resistance model in vitro.

METHODS
Insulin resistance in HepG2 cells was induced by 0.5 mM PA exposure for 24 h and then the effect of GRg1 on cellular glucose consumption was measured. Expression of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphate (G6Pase) were analyzed by Western blot and quantitative real-time polymerase chain reaction. Activation of protein kinases and transcript factor was analyzed by measuring protein phosphorylation. The influence of GRg1 on reactive oxygen species (ROS) production in HepG2 was also examined.

RESULTS
GRg1 reversed PA-induced decrease in glucose consumption of HepG2 cells by downregulating gluconeogenesis genes G6pase and PEPCK. GRg1 increased Akt activation but inhibited JNK activation in PA-challenged HepG2 cells. Cellular ROS level was elevated in insulin-resistant HepG2 cells but was reduced by GRg1.

CONCLUSIONS
Together these findings indicate that GRg1 protects against hepatic insulin resistance via preserving insulin signaling sensitivity and is a promising alternative medicine.

Mo|Jiao|J| Zhou|Yulin|Y| Yang|Renhua|R| Zhang|Pengli|P| He|Bo|B| Yang|Jianyu|J| Li|Shude|S| Shen|Zhiqiang|Z| Chen|Peng|P|

Ginsenoside Rg1
Insulin resistance
Gluconeogenesis
Free fatty acids


No correlation between sonographic and electrophysiological parameters in carpal tunnel syndrome.

Abstract: A prospective study was carried out to investigate any correlation between electrophysiological and sonographic findings in patients with a clinical diagnosis of carpal tunnel syndrome. A total of 113 patients (113 wrists) in 90 women and 23 men, with a mean age of 60 years, underwent sonographic and electrophysiological examination. Fifty-five patients (48%) had mild, 43 (38%) moderate and 12 (11%) had severe conduction disturbances and three patients had normal conduction. Sonographic measurements showed a cross-sectional area of the median nerve of 9.9 mm(2) at the forearm and 17.8 mm(2) at the tunnel inlet. The mean anteroposterior diameter (height) of the nerve at the tunnel inlet was 2.7 mm, and the lowest height inside the tunnel was 1.8 mm. No correlation was found between sonographic and electrophysiological parameters.

Carpal tunnel syndrome diagnosis
electrodiagnosis
ultrasonography


Associations among Employment Status, Health Behaviors, and Mental Health in a Representative Sample of South Koreans.

Abstract: The purpose of the present study was to compare the health behaviors, general health, and mental health of South Korean employees according to their employment status, and to examine how these associations vary across genders using the latest Korean National Examination Health and Nutrition Survey data. Logistic regression analyses were performed using employment status-permanent job, temporary job, and unemployed-as predictor variables and health-related variables as the outcome variables. Results indicated that temporary workers and the unemployed have higher odds of poor mental health regardless of gender. On the other hand, only male permanent workers were found to have a higher risk of problematic drinking compared to precarious workers and the unemployed. Meanwhile, only women showed a higher risk of current smoking in the temporary job and unemployed groups compared with permanent employees. Regarding general health, women, not men, in the temporary job group reported poorer general health (i.e., low health-related quality of life and higher self-perceived poor health) than those in other groups. These findings suggest that the development and implementation of intervention services, as well as organizational actions, need to consider differential impacts of unfavorable employment status on health issues according to gender.

Park|Se Jin|SJ|
Kim|Soo Yeon|SY|
Lee|Eun-Sun|ES|
Park|Subin|S|

employment status
health behavior
mental health
general health


Fermentation transforms the phenolic profiles and bioactivities of plant-based foods.

Abstract: Phenolics are a group of compounds derived from plants that have displayed potent biological activities and health-promoting effects. Fermentation is one of the most conventional but still prevalent bioprocessing methods in the food industry, with the potential to increase phenolic content and enhance its nutritive value. This review details the biotransformation of different classes of phenolics (hydroxycinnamic and hydroxybenzoic acids, flavonoids, tannins, stilbenoids, lignans, alkylresorcinols) by various microorganisms (lactic acid bacteria, yeast, filamentous fungi) throughout the fermentation process in plant-based foods. Several researchers have commenced the use of metabolic engineering, as in recombinant Saccharomyces cerevisiae yeast and Escherichia coli, to enhance the production of this transformation. The impact of phenolics on the metabolism of microorganisms and fermentation process, although complex, is reviewed for the first time. Moreover, this paper highlights the general effect of fermentation on the food's phenolic content, and its bioaccessibility, bioavailability and bioactivities including antioxidant capacity, anti-cancer, anti-diabetic, anti-inflammation, anti-obesity properties. Phenolics of different classes are converted into compounds that are often more bioactive than the parent compounds, and fermentation generally leads to a higher phenolic content and antioxidant activity in most studies. However, biotransformation of several phenolic classes is less studied due to its low concentration and apparent insignificance to the food system. Therefore, there is potential for application of metabolic engineering to further enhance the content of different phenolic classes and bioactivities in food.

Leonard|William|W| Zhang|Pangzhen|P| Ying|Danyang|D| Adhikari|Benu|B| Fang|Zhongxiang|Z|

Biotransformation
Metabolic engineering
Bioactive compounds
Microorganism metabolism
Nutritional properties
Phenolic compounds


A systematic review of the role of inflammatory biomarkers in acute, subacute and chronic non-specific low back pain.

Abstract:
BACKGROUND
Low back pain (LBP) is one of the greatest contributors to disability in the world and there is growing interest on the role of biomarkers in LBP. To purpose of this review was to analyze available evidence on the relationship between inflammatory biomarkers, clinical presentation, and outcomes in patients with acute, subacute and chronic non-specific low back pain (NSLBP).

METHODS
A search was performed in Medline, Embase, Cinahl and Amed databases. Studies which measured levels of inflammatory biomarkers in participants with NSLBP were included. Two reviewers independently screened titles and abstracts, full-texts, and extracted data from included studies. Methodological quality was assessed using the Newcastle Ottawa Quality Assessment Scale. Level of evidence was assessed using the modified GRADE approach for prognostic studies.

RESULTS
Seven primary studies were included in this review. All results assessed using the modified GRADE demonstrated low to very low quality evidence given the small number of studies and small sample. Three studies examined C-reactive protein (CRP), one of which found significantly higher CRP levels in an acute NSLBP group than in controls and an association between high pain intensity and elevated CRP. Three studies examined tumor necrosis factor alpha (TNF-α), two of which found elevated TNF-α in chronic NSLBP participants compared to controls. Two studies examined interleukin 6 (IL-6), none of which found a significant difference in IL-6 levels between NSLBP groups and controls. Two studies examined interleukin 1 beta (IL-β), none of which found a significant difference in IL-β levels between NSLBP groups and controls.

CONCLUSIONS
This review found evidence of elevated CRP in individuals with acute NSLBP and elevated TNF-Α in individuals with chronic NSLBP. There are a limited number of high-quality studies evaluating similar patient groups and similar biomarkers, which limits the conclusion of this review.

D059787:Acute Pain
D015415:Biomarkers
D059350:Chronic Pain
D006801:Humans
D018836:Inflammation Mediators
D017116:Low Back Pain

Systematic review
Inflammatory biomarkers
Non-specific low back pain
CRP
TNF-α
IL-6
Central sensitization
IL-1β


Hydrocephalus due to multiple ependymal malformations is caused by mutations in the MPDZ gene.

Abstract: Congenital hydrocephalus is considered as either acquired due to haemorrhage, infection or neoplasia or as of developmental nature and is divided into two subgroups, communicating and obstructive. Congenital hydrocephalus is either syndromic or non-syndromic, and in the latter no cause is found in more than half of the patients. In patients with isolated hydrocephalus, L1CAM mutations represent the most common aetiology. More recently, a founder mutation has also been reported in the MPDZ gene in foetuses presenting massive hydrocephalus, but the neuropathology remains unknown. We describe here three novel homozygous null mutations in the MPDZ gene in foetuses whose post-mortem examination has revealed a homogeneous phenotype characterized by multiple ependymal malformations along the aqueduct of Sylvius, the third and fourth ventricles as well as the central canal of the medulla, consisting in multifocal rosettes with immature cell accumulation in the vicinity of ependymal lining early detached from the ventricular zone. MPDZ also named MUPP1 is an essential component of tight junctions which are expressed from early brain development in the choroid plexuses and ependyma. Alterations in the formation of tight junctions within the ependyma very likely account for the lesions observed and highlight for the first time that primary multifocal ependymal malformations of the ventricular system is genetically determined in humans. Therefore, MPDZ sequencing should be performed when neuropathological examination reveals multifocal ependymal rosette formation within the aqueduct of Sylvius, of the third and fourth ventricles and of the central canal of the medulla.

Saugier-Veber|Pascale|P| Marguet|Florent|F| Lecoquierre|François|F| Adle-Biassette|Homa|H| Guimiot|Fabien|F| Cipriani|Sara|S| Patrier|Sophie|S| Brasseur-Daudruy|Marie|M| Goldenberg|Alice|A| Layet|Valérie|V| Capri|Yline|Y| Gérard|Marion|M| Frébourg|Thierry|T| Laquerrière|Annie|A|

Neuropathology
Autosomal recessive inheritance
Foetal hydrocephalus
MPDZ pathogenic variants
Multifocal malformation of the ependyma


Improving the retention and reusability of Alpha-amylase by immobilization in nanoporous polyacrylamide-graphene oxide nanocomposites.

Abstract: Alpha-amylase was immobilized inside three different polymeric matrices: polyacrylamide hydrogel (PAAm), polyacrylamide-graphene oxide nanocomposite (PAAm-GO) and alginate in order to study and compare the effect of the matrix on the catalytic performance. The morphology, swelling, mechanical properties, retention efficiency, and the catalytic behavior of these newly supported biocatalysts were studied. Nanocomposite made of PAAm-GO matrix incorporated 98% of the enzyme, likely through a cooperative effect, while alginate gels incorporated only 30%. Moreover, the enzyme retention using PAAm-GO reached a value of 97.5%. Starch hydrolysis catalyzed by the immobilized enzyme in PAAm-GO matrix showed similar kinetics profiles up to 5 cycles suggesting that the enzymatic activity is retained. These results compare very favorably with conventional immobilization in alginate where almost no activity was observed after 3 cycles. All results suggest that the PAAm matrices protect the biocatalyst allowing its reusability. Moreover, the improvements in enzyme catalytic properties via immobilization made this system as an excellent candidate in bio-industrial applications such as bioethanol production. Furthermore, the synthesized catalyst could produce a high yield of bioethanol by using enzymes and yeast immobilized in the same PAAm matrix. In this way, it is possible to produce sequential or simultaneous saccharification and fermentation.

Mulko|Lucinda|L|
Pereyra|Jesica Y|JY|
Rivarola|Claudia R|CR|
Barbero|Cesar A|CA|
Acevedo|Diego F|DF|

Alpha-amylase
Immobilization
Graphene oxide


Association of Vitamin D with Inflammatory Bowel Disease Activity in Pediatric Patients.

Abstract:
BACKGROUND
It has been known that vitamin D level (serum 25[OH]D) has correlation with inflammatory bowel disease (IBD). The purpose of this study is to investigate changes of serum 25[OH]D in pediatric IBD patients according to the disease activity.

METHODS
A total of 96 children and adolescent with IBD were enrolled in this retrospective study. Serologic inflammatory markers and clinical disease activity scores of the patients were collected, and their correlations with serum 25[OH]D were analyzed. Seasonal variations of serum 25[OH]D were also investigated both in active disease state and remission state.

RESULTS
Of the 96 patients, 41 (43%) were women and patients with a vitamin D deficiency (< 20 ng/mL) at diagnosis were 77 (80.2%). There was no significant difference between Crohn's disease and ulcerative colitis for serum 25[OH]D. Serum 25[OH]D was higher in remission group than in active disease group (12.4 [8.8-29] ng/mL vs. 17.9 [12.3-34.4] ng/mL; P < 0.001) and the difference was more significant than other micronutrients. There was no significant difference in serum 25[OH]D concentration between patients with ileal involvement and patients without ileal involvement. There were seasonal variations in the active phase, but there was no significant difference by season in the remission phase.

CONCLUSION
Serum 25[OH]D is inversely correlated with disease activity in IBD. Monitoring and supplementation is required especially for active disease status and in winter and spring season.

Vitamin D
Inflammatory Bowel Disease
Disease Activity
Pediatric
Crohn's Disease
Ulcerative Colitis


Current state of chikungunya fever laboratory diagnosis (review of literature).

Abstract: The article is about methods of chikungunya fever laboratory diagnosis. An algorithm for the study of biological material for the presence of antibodies against chikungunya virus and virus antigens is presented. The overview describes the information about commercial immunodiagnostic and genodiagnostic kits and their detailed specifications. The information presented in the review will be useful for doctors of clinical laboratory diagnostics to choose a method and an acceptable test system for laboratory confirmation of Chikungunya fever diagnosis, as well as differential diagnosis with other fevers, which have similar symptoms, common geographical distribution and carriers of infection.

D000956:Antigens, Viral
D065632:Chikungunya Fever
D002646:Chikungunya virus
D019411:Clinical Laboratory Techniques
D005334:Fever
D006801:Humans

laboratory diagnostics of arbovirus infections


Interferon alpha receptors and STAT1 as therapy predictors of a sustained virological response in hepatitis C/B co-infection.

Abstract:
OBJECTIVE
: To determine the expression of interferon alpha receptors 1 and 2 along with signal transducer and activator of transcription-1 in peripheral blood mononuclear cells of both hepatitis C mono-infected and hepatitis C and B co-infected patients, and to assess whether these targeted genes predict sustained virological response to interferon therapy.

METHODS
This cross-sectional study was carried out at the Army Medical College, Rawalpindi, Pakistan, from January 2012 to December 2015, and comprised hepatitis C mono-infected and hepatitis C and B co-infected patients. The patients were divided into groups 1 and 2. Group-1a and group-2a consisted of mono-infected and co-infected sustained responders, while group-1b and group-2b had mono-infected and co-infected non sustained responders. Peripheral blood mononuclear cells from healthy controls were also quantified for these subunits. Target gene expressions were studied by retro-transcription of respective messenger ribonuclieic acid extracted from the cells followed by polymerase chain reaction amplification.

RESULTS
Of the 191 subjects, there were 20(10.5%) in group-1a, 35(18.3%) in group-2a, 65(34%) in group-1b and 51(26.7%) in group-2b. The remaining 20(10.5%) were controls. Overall, 106 (55.5%) were males and 85 (44.5%) were females. Interferon alpha receptor 1 expression in groups 1a and 2a was significantly higher compared to groups 1b (p=0.018) and 2b (p 0.031). Signal transducer and activator of transcription-1 protein expression showed no significant difference (p=0.062 and p=0.519). No difference in expression was measured between the two sets of groups with regard to interferon alpha receptor 2 expression (p=0.278 and p=0.590).

CONCLUSIONS
Our results show that levels of IFNAR-1 mRNA expression may be a good predictor for IFN-related anti-viral activity in both HCV mono infected and HCV/HBV co-infected patients.

Hepatitis C virus, Hepatitis B virus, Interferon alpha receptor 1, Interferon alpha receptor 2 , In ter feron th erapy resp onse, Si gnal tran sd ucer and a c tiv ator of transcription 1


Pitch count adherence and injury assessment of youth baseball in South Carolina.

Abstract:
Introduction
Overuse injury in youth overhead athletes remains a concern. The introduction of pitch count guidelines was designed to limit the number of pitches per game. South Carolina is considered a warm weather climate which has been proven to expose overhead athletes to higher risk for injury. The purpose of this study was to detect baseline rates of arm pain and sequelae (injury, surgery, impact on participation) among southern youth baseball/softball players to better counsel players, parents, coaches and league administration on the prevention of arm injury.

Methods
A survey was distributed to 14 pediatric practices within the South Carolina Pediatric Practice Research Network. The 2-page survey included 28 closed-ended and descriptive questions that investigated physical and psychosocial responses during and after play. Additional questions were conducted on adherence and understanding of USA Baseball guidelines and pitch counting behavior.

Results
Two hundred and seventy three surveys were completed by parents of baseball/softball players. The players' average age was 11.6 years, who played on an average of 1.78 teams/leagues for 5.2 months each year. Only 26% of baseball players answered "Sometimes", "Often" or "Always" to their arm hurting. Arm fatigue, older age, parent/coach frustration with play, and months played were statistically significantly associated with arm pain. The survey revealed 58.9% of families were familiar with pitch count guidelines.

Discussion
Arm pain is relatively prevalent among the South Carolina youth baseball community and worse in older players and experience fatigue. This survey found lower percentage of youth overhead athletes experiencing arm discomfort when compared to prior studies. It is important for warm weather climate athletes to abide by guidelines, as they are more susceptible to arm injury. Increased recognition, education and compliance with pitch count guidelines will help protect these youth athletes from overuse injury.

Level of evidence
IV, Descriptive Epidemiology Study.

Eichinger|Josef K|JK|
Goodloe|J Brett|JB|
Lin|Jackie J|JJ|
Greenhouse|Alyssa|A|
Rao|Meghana V|MV|
Friedman|Richard J|RJ|
Roberts|James R|JR|

Pitch count
Pitching
Youth baseball
Arm pain
Survey study


CD8+T-bet+ cells as a predominant biomarker for inclusion body myositis.

Abstract:
BACKGROUND
Myositis is a heterogeneous group of muscular auto-immune diseases with clinical and pathological criteria that allow the classification of patients into different sub-groups. Inclusion body myositis is the most frequent myositis above fifty years of age. Diagnosing inclusion body myositis requires expertise and is challenging. Little is known concerning the pathogenic mechanisms of this disease in which conventional suppressive-immune therapies are inefficacious.

OBJECTIVES
Our aim was to deepen our understanding of the immune mechanisms involved in inclusion body myositis and identify specific biomarkers.

METHODS
Using a panel of thirty-six markers and mass cytometry, we performed deep immune profiling of peripheral blood cells from inclusion body myositis patients and healthy donors, divided into two cohorts: test and validation cohorts. Potential biomarkers were compared to myositis controls (anti-Jo1-, anti-3-hydroxyl-3-methylglutaryl CoA reductase-, and anti-signal recognition particle-positive patients).

RESULTS
Unsupervised analyses revealed substantial changes only within CD8+ cells. We observed an increase in the frequency of CD8+ cells that expressed high levels of T-bet, and containing mainly both effector and terminally differentiated memory cells. The senescent marker CD57 was overexpressed in CD8+T-bet+ cells of inclusion body myositis patients. As expected, senescent CD8+T-bet+ CD57+ cells of both patients and healthy donors were CD28nullCD27nullCD127null. Surprisingly, non-senescent CD8+T-bet+ CD57- cells in inclusion body myositis patients expressed lower levels of CD28, CD27, and CD127, and expressed higher levels of CD38 and HLA-DR compared to healthy donors. Using classification and regression trees alongside receiver operating characteristics curves, we identified and validated a frequency of CD8+T-bet+ cells >51.5% as a diagnostic biomarker specific to inclusion body myositis, compared to myositis control patients, with a sensitivity of 94.4%, a specificity of 88.5%, and an area under the curve of 0.97.

CONCLUSION
Using a panel of thirty-six markers by mass cytometry, we identify an activated cell population (CD8+T-bet+ CD57- CD28lowCD27lowCD127low CD38+ HLA-DR+) which could play a role in the physiopathology of inclusion body myositis, and identify CD8+T-bet+ cells as a predominant biomarker of this disease.

Dzangué-Tchoupou|Gaëlle|G| Mariampillai|Kuberaka|K| Bolko|Loïs|L| Amelin|Damien|D| Mauhin|Wladimir|W| Corneau|Aurélien|A| Blanc|Catherine|C| Allenbach|Yves|Y| Benveniste|Olivier|O|

D000368:Aged
D000369:Aged, 80 and over
D015415:Biomarkers
D018106:CD28 Antigens
D018414:CD8-Positive T-Lymphocytes
D006801:Humans
D008875:Middle Aged
D018979:Myositis, Inclusion Body
D020825:T-Box Domain Proteins

Biomarkers
Inclusion body myositis
Myositis
Deep immune profiling
Physiopathology
CD8+ T-bet+ cells


PERK mediates eIF2α phosphorylation responsible for BACE1 elevation, CREB dysfunction and neurodegeneration in a mouse model of Alzheimer's disease.

Abstract: Emerging evidence suggests that aberrant phosphorylation of eukaryotic initiation factor-2α (eIF2α) may induce synaptic failure and neurodegeneration through persistent translational inhibition of global protein synthesis. However, elevated phospho-eIF2α also paradoxically causes translational activation of a subset of messenger RNAs such as the β-secretase enzyme, β-site APP-cleaving enzyme 1 (BACE1) and cAMP response element binding protein (CREB) repressor, activating transcription factor 4 (ATF4). Therefore, we tested whether genetic reduction of the eIF2α kinase PERK may prevent these deleterious events and mitigate Alzheimer's disease (AD)-like neuropathology and cognitive impairments in the 5XFAD mouse model. PERK haploinsufficiency blocked overactivation of the PERK-eIF2α pathway, as evidenced by significant reductions in phosphorylation of PERK and eIF2α, in 5XFAD mice. PERK haploinsufficiency was sufficient to rescue memory deficits and cholinergic neurodegeneration in this AD model. Notably, PERK haploinsufficiency also prevented BACE1 elevations, resulting in reduced levels of amyloid-β peptides and plaque burden in 5XFAD mice. Moreover, CREB dysfunction was restored in PERK(+/-)·5XFAD mice concomitant with reversal of ATF4 upregulation. Together, these findings suggest that PERK may be a disease-modifying therapeutic target to prevent multiple memory-disrupting mechanisms associated with AD.

D053829:Amyloid Precursor Protein Secretases

D017362:Cyclic AMP Response Element-Binding Protein


Overcoming Obstacles in Designing and Sustaining a High-Quality Cardiovascular Procedure Environment.

Abstract: Accurate evaluation of the quality of invasive cardiology procedures requires appraisal of case selection, technical performance, and procedural and clinical outcomes. Regrettably, the medical care delivery system poses a number of obstacles to developing and sustaining a high-quality environment. The purposes of this viewpoint are to summarize the most common impediments, followed to summarize the most common impediments, followed by the optimal ways to design and sustain a quality assurance program to overcome these barriers. A 7-step program to create and implement an effective quality assurance program is outlined.

Klein|Lloyd W|LW|
Dehmer|Gregory J|GJ|
Anderson|H Vernon|HV|
Rao|Sunil V|SV|

quality assurance
invasive procedures
quality program


Indoor Air Quality Issues for Rocky Mountain West Tribes.

Abstract: Native American populations face considerable health disparities, especially among those who live on reservations, where access to healthcare, education, and safe housing can be limited. Previous research on tribal housing has raised concerns about housing construction, damage, and possible linkage to adverse health effects (e.g., asthma). This community-based participatory research (CBPR) project investigated indoor air quality issues on two Rocky Mountain west reservations. At the onset of the project, the research team formed a partnership with community advisory boards (CABs) consisting of representatives from tribal councils and community members. Research design, implementation, and dissemination all took place in full collaboration with the CABs following approval through official tribal resolutions. Residential homes were monitored for particulate matter with diameter <2.5 microns (PM2.5) and radon concentrations. Low-cost air quality sensors and activated charcoal radon test kits were placed in tribal households for 6-8 days. A large amount of data were below the sensor limit of quantification (LOQ), but several homes had daily averages that exceeded suggested PM2.5 guidelines, suggestive of the potential for high exposure. Additionally, nearly half of all homes sampled had radon levels above the EPA action level, with mitigation activities initiated for the most concerning homes. Findings from this study indicate the need for future community-wide assessments to determine the magnitude and patterns of indoor air quality issues.

Webb|Logan|L|
Sleeth|Darrah K|DK|
Handy|Rod|R|
Stenberg|Jared|J|
Schaefer|Camie|C|
Collingwood|Scott C|SC|

Native American
tribal housing
community-based participatory research
PM2.5
radon
environmental health


Ecotoxicity to Freshwater Organisms and Cytotoxicity of Nanomaterials: Are We Generating Sufficient Data for Their Risk Assessment?

Abstract: The aim of the present study was to investigate the eco-cytotoxicity of several forms of nanomaterials (NM), such as nano-CuO, nano-TiO2, nano-SiO2 and nano-ZnO, on different aquatic species (Raphidocelis subcapitata, Daphnia magna and Lemna minor) following standard protocols and on human cell lines (Caco-2, SV-80, HepG2 and HaCaT). Predicted no-effect concentrations (PNEC) or hazard concentrations for 5% of the species (HC5) were also estimated based on the compilation of data available in the literature. Most of the NM agglomerated strongly in the selected culture media. For the ecotoxicity assays, nano-CuO and nano-ZnO even in particle agglomeration state were the most toxic NM to the freshwater organisms compared to nano-TiO2 and nano-SiO2. Nano-ZnO was the most toxic NM to R. subcapitata and D. magna, while nano-CuO was found to be very toxic to L. minor. Nano-CuO was very toxic to Caco-2 and HepG2 cells, particularly at the highest tested concentrations, while the other NM showed no toxicity to the different cell lines. The HC5 and PNEC values are still highly protective, due to data limitations. However, the present study provides consistent evidence of the potential risks of both nano-CuO and nano-ZnO against aquatic organisms and also their effects on public health.

Andreani|Tatiana|T|
Nogueira|Verónica|V|
Gavina|Ana|A|
Fernandes|Saul|S|0000-0002-6207-9469
Rodrigues|José Luís|JL|
Pinto|Vera V|VV|
Ferreira|Maria José|MJ|
Silva|Amélia M|AM|0000-0002-7524-9914
Pereira|Carlos M|CM|0000-0002-8392-9581
Pereira|Ruth|R|0000-0001-6857-5968

risk assessment
Raphidocelis subcapitata
Daphnia magna
Lemna minor
human cell lines
PNEC
HC5
toxicity
metal oxide nanomaterials


Mitigating NO and N2O emissions from a pilot-scale oxidation ditch using bioaugmentation of immobilized aerobic denitrifying bacteria.

Abstract: Nitrous oxide (N2O) emission from wastewater treatment plants (WWTPs) requires urgent mitigation because of its significant contribution to the greenhouse effect. In this study, bioaugmentation was applied in a pilot-scale oxidation ditch with the aerobic denitrifying bacteria strain PCN-1 immobilized on polyurethane biocarriers, which demonstrated effective N2O mitigation. Microbial community analysis suggested that the bioaugmentation facilitated a symbiotic relationship of the bacterial populations between the activated sludge and the biocarriers. The denitrifying bacteria with well-known N2O reducing capabilities predominated on the biocarriers. Correspondingly, the increases of denitrifying genes and NO and N2O reductase provided evidence for the enhanced genetic potential for NO and N2O reduction. Besides, the enriched comammox Nitrospira on the biocarriers is proposed as another significant driver for N2O mitigation by avoiding nitrite accumulation. In addition, the bioaugmentation enhanced the stability and recovery capability of the system in the ammonia overload and aeration failure shock tests.

Tian|Zhichao|Z| Zhou|Nan|N| You|Wenbo|W| He|Da|D| Chang|Fang|F| Zheng|Maosheng|M|

Wastewater treatment
Greenhouse effect
Comammox
Pseudomonas stutzeri