Toxins, Vol. 8, Pages 196: Liquid Chromatography with a Fluorimetric Detection Method for Analysis of Paralytic Shellfish Toxins and Tetrodotoxin Based on a Porous Graphitic Carbon Column

Paralytic shellfish toxins (PST) traditionally have been analyzed by liquid chromatography with either pre- or post-column derivatization and always with a silica-based stationary phase. This technique resulted in different methods that need more than one run to analyze the toxins. Furthermore, tetrodotoxin (TTX) was recently found in bivalves of northward locations in Europe due to climate change, so it is important to analyze it along with PST because their signs of toxicity are similar in the bioassay. The methods described here detail a new approach to eliminate different runs, by using a new porous graphitic carbon stationary phase. Firstly we describe the separation of 13 PST that belong to different groups, taking into account the side-chains of substituents, in one single run of less than 30 min with good reproducibility. The method was assayed in four shellfish matrices: mussel (Mytillus galloprovincialis), clam (Pecten maximus), scallop (Ruditapes decussatus) and oyster (Ostrea edulis). The results for all of the parameters studied are provided, and the detection limits for the majority of toxins were improved with regard to previous liquid chromatography methods: the lowest values were those for decarbamoyl-gonyautoxin 2 (dcGTX2) and gonyautoxin 2 (GTX2) in mussel (0.0001 mg saxitoxin (STX)·diHCl kg−1 for each toxin), decarbamoyl-saxitoxin (dcSTX) in clam (0.0003 mg STX·diHCl kg−1), N-sulfocarbamoyl-gonyautoxins 2 and 3 (C1 and C2) in scallop (0.0001 mg STX·diHCl kg−1 for each toxin) and dcSTX (0.0003 mg STX·diHCl kg−1 ) in oyster; gonyautoxin 2 (GTX2) showed the highest limit of detection in oyster (0.0366 mg STX·diHCl kg−1). Secondly, we propose a modification of the method for the simultaneous analysis of PST and TTX, with some minor changes in the solvent gradient, although the detection limit for TTX does not allow its use nowadays for regulatory purposes.

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IJERPH, Vol. 13, Pages 639: Public Parks in Hong Kong: Characteristics of Physical Activity Areas and Their Users

Public parks, salient locations for engaging populations in health promoting physical activity, are especially important in high-density cities. We used the System for Observing Physical Activity in Communities (SOPARC) to conduct the first-ever surveillance study of nine public parks in Hong Kong (288 observation sessions during 36 weekdays and 36 weekend days) and observed 28,585 visitors in 262 diverse areas/facilities. Parks were widely used throughout the day on weekdays and weekend days and across summer and autumn; visitor rates were among the highest seen in 24 SOPARC studies. In contrast to other studies where teens and children dominated park use, most visitors (71%) were adults and seniors. More males (61%) than females used the parks, and they dominated areas designed for sports. Over 60% of visitors were observed engaging in moderate-to-vigorous physical activity, a rate higher than other SOPARC studies. Facilities with user fees were less accessible than non-fee areas, but they provided relatively more supervised and organized activities. Assessing parks by age, gender, and physical activity can provide useful information relative to population health. This study not only provides information useful to local administrators for planning and programming park facilities relative to physical activity, but it also provides a baseline for comparison by other high-density cities.

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Nanomaterials, Vol. 6, Pages 126: Quaternized Chitosan-Capped Mesoporous Silica Nanoparticles as Nanocarriers for Controlled Pesticide Release

Nanotechnology-based pesticide formulations would ensure effective utilization of agricultural inputs. In the present work, mesoporous silica nanoparticles (MSNs) with particle diameters of ~110 nm and pore sizes of ~3.7 nm were synthesized via a liquid crystal templating mechanism. A water-soluble chitosan (CS) derivative (N-(2-hydroxyl)propyl-3-trimethyl ammonium CS chloride, HTCC) was successfully capped on the surface of pyraclostrobin-loaded MSNs. The physicochemical and structural analyses showed that the electrostatic interactions and hydrogen bonding were the major forces responsible for the formation of HTCC-capped MSNs. HTCC coating greatly improved the loading efficiency (LC) (to 40.3%) compared to using bare MSNs as a single encapsulant (26.7%). The microstructure of the nanoparticles was revealed by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The pyraclostrobin-loaded nanoparticles showed an initial burst and subsequent sustained release behavior. HTCC-capped MSNs released faster than bare MSNs in the initial stage. Pyraclostrobin-loaded HTCC-capped MSNs with half doses of pyraclostrobin technical demonstrated almost the same fungicidal activity against Phomopsis asparagi (Sacc.), which obviously reduced the applied pesticide and enhanced the utilization efficiency. Therefore, HTCC-decorated MSNs demonstrated great potential as nanocarriers in agrochemical applications.

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Sensors, Vol. 16, Pages 990: A Three-Dimensional Shape-Based Force and Stiffness-Sensing Platform for Tendon-Driven Catheters

This paper presents an efficient shape-based three-axial force and stiffness estimator for active catheters commonly implemented in cardiac ablation. The force-sensing capability provides important feedback for catheterization procedures including real-time control and catheter steering in autonomous navigation systems. The proposed platform is based on the introduced accurate and computationally efficient Cosserat rod model for tendon-driven catheters. The proposed nonlinear Kalman filter formulation for contact force estimation along with the developed catheter model provides a real-time force observer robust to nonlinearities and noise covariance uncertainties. Furthermore, the proposed platform enables stiffness estimation in addition to tip contact force sensing in different operational circumstances. The approach incorporates pose measurements which can be achieved using currently developed pose-sensing systems or imaging techniques. The method makes the approach compatible with the range of forces applied in clinical applications. The simulation and experimental results verify the viability of the introduced force and stiffness-sensing technique.

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Entropy, Vol. 18, Pages 241: A Simulation-Based Study on Bayesian Estimators for the Skew Brownian Motion

In analyzing a temporal data set from a continuous variable, diffusion processes can be suitable under certain conditions, depending on the distribution of increments. We are interested in processes where a semi-permeable barrier splits the state space, producing a skewed diffusion that can have different rates on each side. In this work, the asymptotic behavior of some Bayesian inferences for this class of processes is discussed and validated through simulations. As an application, we model the location of South American sea lions (Otaria flavescens) on the coast of Calbuco, southern Chile, which can be used to understand how the foraging behavior of apex predators varies temporally and spatially.

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Religions, Vol. 7, Pages 84: Exploratory Psychometric Properties of the Farsi and English Versions of the Spiritual Needs Questionnaire (SpNQ)

The aim of this study was to translate and test the psychometric properties of a Farsi and an English version of the spiritual needs questionnaire (SpNQ) a measure originally developed in German. The World Health Organization guideline for translating and validating questionnaires was used. Participants were recruited from hospitals in Iran and New Zealand during an outpatient follow-up appointment after cancer treatment. People diagnosed with cancer in Iran (68) and New Zealand (54) completed and returned the SpNQ (at time 1) and within the two week time period (time 2). Cronbach's alpha ranged from 0.79 to 0.92, except for the existentialistic domain of the SpNQ (0.53–0.54). The coefficient of variation (CV) indicated minimal random variation between the assessments; the measures were generally stable, except for the item "existentialistic". The translated versions of the SpNQ have the potential to support a comprehensive assessment of cancer patients' spiritual needs.

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Water, Vol. 8, Pages 269: A Novel Approach for Estimating the Recurrence Intervals of Channel-Forming Discharges

Channel-forming discharges typically are associated with recurrence intervals less than five years and usually less than two years. However, the actual frequency of occurrence of these discharges is often several times more frequent than the statistical expectation. This result was confirmed by using the Log-Pearson Type 3 statistical method to analyze measured annual series of instantaneous peaks and peak daily means for 150 catchments in six states in the North Central Region of the United States. Discharge records ranged from 39 to 102 years and catchment sizes ranged from 29 to 6475 km2. For each state, mean values of the ratio of the calculated to the expected occurrences exceeded 1.0, for recurrence intervals from two years to 100 years with R-squared values varying from 0.64 to 0.97, respectively. However, catchment-by-catchment variability was too large for the relationships for each state to be useful. We propose a method, called Full Daily Distribution (FDD), which used all of the daily values for the available period of records. The approach provided ratios of calculated to expected occurrences that were approximately 1.0. For recurrence intervals less than five years, the FDD calculated discharges were much greater than those obtained by using the Log-Pearson Type 3 approach with annual series of instantaneous peaks or peak daily means. The method can also calculate discharges for recurrence intervals less than one year. The study indicates a need to enhance the Log-Pearson Type 3 method to provide better estimates of channel-forming discharges and that the proposed FDD could be a useful tool to this purpose.

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Catalysts, Vol. 6, Pages 95: The Performance of Electron-Mediator Modified Activated Carbon as Anode for Direct Glucose Alkaline Fuel Cell

Six different electron mediators were immobilized on the activated carbon (AC) anode and their effects on performance of a direct glucose alkaline fuel cell were explored. 2-hydroxy-1, 4-naphthoquinone (NQ), methyl viologen (MV), neutral red (NR), methylene blue (MB), 1, 5-dichloroanthraquinone (DA) and anthraquinone (AQ) were doped in activated carbon (AC), respectively, and pressed on nickel foam to fabricate the anodes. NQ shows comparable performance with MV, but with much lower cost and environmental impact. With NQ-AC anode, the fuel cell attained a peak power density of 16.10 Wm−2, peak current density of 48.09 Am−2, and open circuit voltage of 0.76 V under the condition of 1 M glucose, 3 M KOH, and ambient temperature. Polarization curve, EIS and Tafel measurements were also conducted to explore the mechanism of performance enhancement. The high performance is likely due to the enhanced charge transfer and more reactive sites provided on the anode.

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CX3CL1/CX3CR1 in Alzheimer’s Disease: A Target for Neuroprotection

CX3C chemokine ligand 1 (CX3CL1) is an intriguing chemokine belonging to the CX3C family. CX3CL1 is secreted by neurons and plays an important role in modulating glial activation in the central nervous system after binding to its sole receptor CX3CR1 which mainly is expressed on microglia. Emerging data highlights the beneficial potential of CX3CL1-CX3CR1 in the pathogenesis of Alzheimer's disease (AD), a common progressive neurodegenerative disease, and in the progression of which neuroinflammation plays a vital role. Even so, the importance of CX3CL1/CX3CR1 in AD is still controversial and needs further clarification. In this review, we make an attempt to present a concise map of CX3CL1-CX3CR1 associated with AD to find biomarkers for early diagnosis or therapeutic interventions.

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Feasibility and Safety of Absorbable Knotless Wound Closure Device in Laparoscopic Myomectomy

Purpose. Myomectomy has been performed through laparoscopy. Suturing is known as rate-limiting step in laparoscopic myomectomy. The present study was aimed at comparing the clinical outcomes of absorbable knotless wound closure device with the results of conventional suturing. Methods. This prospective study included 62 women who underwent laparoscopic myomectomy at Taipei City Hospital, Zhongxiao Branch, from January 2010 through to August 2012. The patients were randomized into two groups according to suturing materials, the knotless group and the 2-0 Vicryl suture group. Patient demographics, overall operative time, and intraoperative blood loss were compared between two groups. Results. Demographic characteristics and laboratory variables before surgery were comparable. Operative time was significantly shorter in knotless group compared with that in 2-0 Vicryl suture group ( versus minutes; ). The results revealed a significant difference in intraoperative blood loss between two groups (knotless versus 2-0 Vicryl: versus ). Use of absorbable knotless wound closure device was associated with greater hemostasis compared with that of 2-0 Vicryl. During a 2-year follow-up period, 12 patients (46.2%) from the group with absorbable knotless wound closure device and 14 patients (38.9%) from 2-0 Vicryl suture group became pregnant. Conclusion. Closure of myometrium using absorbable knotless wound closure device after laparoscopic myomectomy resulted in a shorter operative time and less blood loss.

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Carbon nanotubes functionalized by click chemistry as scaffolds for the preparation of electrochemical immunosensors. Application to the determination of TGF-beta 1 cytokine

Analyst, 2016, Accepted Manuscript
DOI: 10.1039/C6AN00941G, Paper

Esther Sanchez-Tirado, Araceli Gonzalez-Cortes, Paloma Yanez-Sedeno, Jose M Pingarron
An electrochemical immunosensor for the determination of the multifunctional Transforming Growth Factor [small beta]1 cytokine (TGF-[small beta]1) has been prepared using multi-walled carbon nanotubes (MWCNTs)-modified screen-printed carbon electrodes. MWCNTs were functionalized by...
The content of this RSS Feed (c) The Royal Society of Chemistry

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Naked-eye sensitive detection of alkaline phosphatase (ALP) and pyrophosphate(PPi) based on Horseradish Peroxidase Catalytic Colorimetric system with Cu(II)

Analyst, 2016, Accepted Manuscript
DOI: 10.1039/C6AN01124A, Paper

Dongmin Shi, Yue Sun, Lin Lin, Chunjun Shi, Xiaojun Zhang, Guangfeng Wang
In this paper, a novel colorimetric method for the detection of alkaline phosphatase (ALP) and pyrophosphate (PPi) was designed based on the Cu2+-horseradish peroxidase (HRP)-3,3[prime or minute],5,5[prime or minute]-tetra-methylbenzidine (TMB) -H2O2 system. In the...
The content of this RSS Feed (c) The Royal Society of Chemistry

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Impact of Treatment with Naloxegol for Opioid-Induced Constipation on Patients’ Health State Utility

Abstract

Introduction

Opioid-induced constipation (OIC) is the most common side effect of opioid treatment. Treatment for OIC typically involves a laxative. However, some patients have an inadequate response to these (laxative inadequate responders, or LIR). This has led to the development of treatments such as naloxegol. This analysis estimates the impact of naloxegol on the health state utility of LIR patients, examines if this utility impact is driven by the change in OIC status, and estimates the utility impact of relief of OIC.

Methods

The analysis was conducted using data from two 12-week randomized controlled trials, KODIAC 4 (ClinicalTrials.gov identifier, NCT01309841) and KODIAC 5 (ClinicalTrials.gov identifier, NCT01323790), plus KODIAC 7 (ClinicalTrials.gov identifier, NCT01395524), a 12-week extension to KODIAC 4. All were designed to assess the efficacy and safety of oral naloxegol (12.5 and 25 mg) compared to placebo. Health state utility data were collected through the EuroQol—five dimensions questionnaire (EQ-5D-3L). Descriptive analysis was undertaken to estimate how EQ-5D utility scores and EQ-5D domain responses varied with treatment, OIC status, and over time. A repeated measure mixed-effects model was used to predict the change from baseline in health state utility score over time.

Results

Compared with placebo, LIR patients treated with naloxegol 25 mg reported a 0.08 improvement in the EQ-5D overall score after 12 weeks of treatment. The analyses also suggest that change in OIC status is a key driver of the impact of OIC treatment on health state utility. When other factors are controlled, relieving OIC is associated with a 0.05 improvement in health state utility, although treatment with naloxegol is associated with an improvement in health state utility over and above the improvement in OIC status.

Conclusion

These analyses suggest that treatment with naloxegol improves patients' health state utility; driven predominantly by the relief of patients' constipation.

Funding

AstraZeneca.

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Cost-Effectiveness of Genotype 1 Chronic Hepatitis C Virus Treatments in Patients Coinfected with Human Immunodeficiency Virus in the United States

Abstract

Introduction

New treatments for chronic hepatitis C virus (HCV) are highly effective in patients coinfected with human immunodeficiency virus (HIV). This study estimated the cost-effectiveness of treatments for genotype 1 (GT1) HCV in HIV-coinfected patients.

Methods

A Markov model based on HCV natural history was used. The base-case analysis included both treatment-naïve and -experienced patients. Alternatives were ombitasvir/paritaprevir/ritonavir, dasabuvir with or without ribavirin (3D ± R) for 12 or 24 weeks, sofosbuvir plus peginterferon and R (SOF + PR) for 12 weeks, SOF + R for 24 weeks, and no treatment (NT). A subgroup analysis restricted to treatment-naïve, non-cirrhotic patients compared 3D ± R for 12 weeks to SOF plus ledipasvir (LDV) for 12 weeks and NT. Transition probabilities, utilities, and costs were obtained from the published literature. Outcomes were measured over a lifetime horizon and included rates of compensated cirrhosis, decompensated cirrhosis, hepatocellular carcinoma and liver-related death, total costs, life-years, quality-adjusted life-years (QALYs), and the incremental cost-effectiveness ratio (ICER).

Results

In the base-case, SOF + R was dominated by both SOF + PR and 3D ± R. Compared to SOF + PR, 3D ± R had an ICER of $45,581. The lifetime rates of liver morbidity and mortality were lower among those treated with 3D ± R compared to SOF + PR, SOF + R, or NT. In the subgroup analysis, 3D ± R was cost-effective compared to NT at a threshold of $50,000 per QALY (ICER $27,496). SOF/LDV had an ICER of $104,489 per QALY gained compared to 3D ± R.

Conclusion

In the GT1 HCV population coinfected with HIV, 3D ± R was cost-effective compared to NT, SOF + R, and SOF + PR. In the treatment-naïve sub-population, 3D ± R was cost-effective compared to NT and SOF/LDV.

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Factors and Regional Differences Associated with Endometriosis: A Multi-Country, Case–Control Study

Abstract

Introduction

The present study aimed to investigate clinical, lifestyle, and environmental factors associated with endometrioma (OMA) and/or deep infiltrating endometriosis (DIE) as determined by case–control comparison [women with superficial peritoneal endometriosis (SUP) or no endometriosis], and compare differences between factor associated with endometriosis at a national level.

Methods

This was three countries (China, Russia, and France), case–control study in 1008 patients. Patients were identified and enrolled during their first routine appointment with their physician post-surgery for a benign gynecologic indication, excluding pregnancy. Retrospective information on symptoms and previous medical history was collected via face-to-face interviews; patients also completed a questionnaire to provide information on current habits. For every DIE patient recruited (n = 143), two women without endometriosis (n = 288), two SUP patients (n = 288), and two OMA patients (n = 288) were recruited.

Results

For the overall population, factors significantly associated (P ≤ 0.05) with DIE or OMA [Odds ratio (OR) >1] were: previous use of hormonal treatment for endometriosis [OR 6.66; 95% confidence interval (CI) 4.05–10.93]; previous surgery for endometriosis (OR 1.95; 95% CI 1.11–3.43); and living or working in a city or by a busy area (OR 1.66; 95% CI 1.09–2.52). Differences between regions with regard to the diagnosis, symptomatology, and treatment of endometriosis exist.

Conclusion

The findings provide insight into potential risk factors for endometriosis and differences between regions in terms of endometriosis management and symptomatology. Further investigations are required to confirm the associations found in this study.

Trial registration

ClinicalTrials.gov identifier, NCT01351051.

Funding

Ipsen.

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Nitro-Oleic Acid Reduces J774A.1 Macrophage Oxidative Status and Triglyceride Mass: Involvement of Paraoxonase2 and Triglyceride Metabolizing Enzymes

Abstract

Nitro-fatty acids possess anti-atherogenic properties, but their effects on macrophage oxidative status and lipid metabolism that play important roles in atherosclerosis development are unclear. This study compared the effects of nitro-oleic acid (OLA-NO₂) with those of native oleic acid (OLA) on intracellular reactive oxygen species (ROS) generation, anti-oxidants and metabolism of triglycerides and cholesterol in J774A.1 macrophages. Upon incubating the cells with physiological concentrations of OLA-NO₂ (0–1 µM) or with equivalent levels of OLA, ROS levels measured by 2, 7-dichlorofluorescein diacetate, decreased dose-dependently, but the anti-oxidative effects of OLA-NO₂ were significantly augmented. Copper ion addition increased ROS generation in OLA treated macrophages without affecting OLA-NO₂ treated cells. These effects could be attributed to elevated glutathione levels and to increased activity and expression of paraoxonase2 that were observed in OLA-NO₂vs OLA treated cells. Beneficial effects on triglyceride metabolism were noted in OLA-NO₂vs OLA treated macrophages in which cellular triglycerides were reduced due to attenuated biosynthesis and accelerated hydrolysis of triglycerides. Accordingly, OLA-NO₂ treated cells demonstrated down-regulation of diacylglycerol acyltransferase1, the key enzyme in triglyceride biosynthesis, and increased expression of hormone-sensitive lipase and adipose triglyceride lipase that regulate triglyceride hydrolysis. Finally, OLA-NO₂vs OLA treatment resulted in modest but significant beneficial effects on macrophage cholesterol metabolism, reducing cholesterol biosynthesis rate and low density lipoprotein influx into the cells, while increasing high density lipoprotein-mediated cholesterol efflux from the macrophages. Collectively, compared with OLA, OLA-NO₂ modestly but significantly reduces macrophage oxidative status and cellular triglyceride content via modulation of cellular anti-oxidants and triglyceride metabolizing enzymes.

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Fermentation Quality and Additives: A Case of Rice Straw Silage

Rice cultivation generates large amount of crop residues of which only 20% are utilized for industrial and domestic purposes. In most developing countries especially southeast Asia, rice straw is used as part of feeding ingredients for the ruminants. However, due to its low protein content and high level of lignin and silica, there is limitation to its digestibility and nutritional value. To utilize this crop residue judiciously, there is a need for improvement of its nutritive value to promote its utilization through ensiling. Understanding the fundamental principle of ensiling is a prerequisite for successful silage product. Prominent factors influencing quality of silage product include water soluble carbohydrates, natural microbial population, and harvesting conditions of the forage. Additives are used to control the fermentation processes to enhance nutrient recovery and improve silage stability. This review emphasizes some practical aspects of silage processing and the use of additives for improvement of fermentation quality of rice straw.

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MicroRNAs as Salivary Markers for Periodontal Diseases: A New Diagnostic Approach?

The aim of this review is to discuss current findings regarding the roles of miRNAs in periodontal diseases and the potential use of saliva as a diagnostic medium for corresponding miRNA investigations. For periodontal disease, investigations have been restricted to tissue samples and five miRNAs, that is, miR-142-3p, miR-146a, miR-155, miR-203, and miR-223, were repeatedly validated in vivo and in vitro by different validation methods. Particularly noticeable are the small sample sizes, different internal controls, and different case definitions of periodontitis in in vivo studies. Beside of that, the validated miRNAs are associated with inflammation and therefore with various diseases. Furthermore, several studies successfully explored the use of salivary miRNA species for the diagnosis of oral cancer. Different cancer types were investigated and heterogeneous methodology was used; moreover, no overlap of results was found. In conclusion, five miRNAs have consistently been reported for periodontitis; however, their disease specificity, detectability, and expression in saliva and their importance as noninvasive markers are questionable. In principle, a salivary miRNA diagnostic method seems feasible. However, standardized criteria and protocols for preanalytics, measurements, and analysis should be established to obtain comparable results across different studies.

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Proteomics of Papillary Thyroid Carcinoma

Condition:   Papillary Thyroid Carcinoma
Intervention:  
Sponsor:   The Affiliated Hospital of Inner Mongolia Medical University
Recruiting - verified June 2016

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S-1 Concurrent With Radiotherapy Versus Radiotherapy for Elderly Patients With Esophageal Cancer

Conditions:   Esophageal Cancer;   Chemoradiation
Interventions:   Radiation: Radiotherapy 54 Gy;   Radiation: Radiotherapy 60 Gy;   Drug: S-1
Sponsor:   Zhejiang Cancer Hospital
Recruiting - verified June 2016

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Diagnostic Value of 18F-Choline PET/CT in Patients With a Thyroid Nodule With an Indeterminate Cytology: Pilot Study

Condition:   Thyroid Gland
Intervention:   Device: Radiation : PET-CT with F18-choline examination
Sponsors:   Centre Francois Baclesse;   Canceropôle Nord Ouest
Recruiting - verified May 2016

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Micromachines, Vol. 7, Pages 107: Farewell to Animal Testing: Innovations on Human Intestinal Microphysiological Systems

The human intestine is a dynamic organ where the complex host-microbe interactions that orchestrate intestinal homeostasis occur. Major contributing factors associated with intestinal health and diseases include metabolically-active gut microbiota, intestinal epithelium, immune components, and rhythmical bowel movement known as peristalsis. Human intestinal disease models have been developed; however, a considerable number of existing models often fail to reproducibly predict human intestinal pathophysiology in response to biological and chemical perturbations or clinical interventions. Intestinal organoid models have provided promising cytodifferentiation and regeneration, but the lack of luminal flow and physical bowel movements seriously hamper mimicking complex host-microbe crosstalk. Here, we discuss recent advances of human intestinal microphysiological systems, such as the biomimetic human "Gut-on-a-Chip" that can employ key intestinal components, such as villus epithelium, gut microbiota, and immune components under peristalsis-like motions and flow, to reconstitute the transmural 3D lumen-capillary tissue interface. By encompassing cutting-edge tools in microfluidics, tissue engineering, and clinical microbiology, gut-on-a-chip has been leveraged not only to recapitulate organ-level intestinal functions, but also emulate the pathophysiology of intestinal disorders, such as chronic inflammation. Finally, we provide potential perspectives of the next generation microphysiological systems as a personalized platform to validate the efficacy, safety, metabolism, and therapeutic responses of new drug compounds in the preclinical stage.

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Molecules, Vol. 21, Pages 838: Chemical Synthesis of Deoxynivalenol-3-β-d-[13C6]-glucoside and Application in Stable Isotope Dilution Assays

Modified mycotoxins have been gaining importance in recent years and present a certain challenge in LC-MS/MS analysis. Due to the previous lack of a labeled isotopologue of the modified mycotoxin deoxynivalenol-3-glucoside, in our study we synthesized the first 13C-labeled internal standard. Therefore, we used the Königs-Knorr method to synthesize deoxynivalenol-3-β-d-[13C6]-glucoside originated from unlabeled deoxynivalenol and [13C6]-labeled glucose. Using the synthesized isotopically-labeled standard deoxynivalenol-3-β-d-[13C6]-glucoside and the purchased labeled standard [13C15]-deoxynivalenol, a stable isotope dilution LC-MS/MS method was firstly developed for deoxynivalenol-3-glucoside and deoxynivalenol in beer. The preparation and purification of beer samples was based on a solid phase extraction. The validation data of the newly developed method gave satisfying results. Intra- and interday precision studies revealed relative standard deviations below 0.5% and 7%, respectively. The recoveries ranged for both analytes between 97% and 112%. The stable isotope dilution assay was applied to various beer samples from four different countries. In summary, deoxynivalenol-3-glucoside and deoxynivalenol mostly appeared together in varying molar ratios but were quantified in rather low contents in the investigated beers.

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Molecules, Vol. 21, Pages 840: Integrated Analysis of the Wood Oil from Xanthocyparis vietnamensis Farjon & Hiep. by Chromatographic and Spectroscopic Techniques

In order to get better knowledge about the volatiles produced by Xanthocyparis vietnamensis, a species recently discovered in Vietnam, its wood oil has been analyzed by a combination of chromatographic (GC, CC) and spectroscopic (GC-MS, 13C-NMR) techniques. Forty components that accounted for 87.9% of the oil composition have been identified. The composition is dominated by nootkatene (20.7%), 11,12,13-tri-nor-eremophil-1(10)-en-7-one (17.2%), γ-eudesmol (5.1%), nootkatone (4.7%), valencene (3.5%) and 13-nor-eremophil-1(10)-en-11-one (2.6%). The structure of two new compounds—10-epi-nor-γ-eudesmen-11-one and 12-hydroxy-isodihydroagarofuran—has been elucidated, while 11,12,13-tri-nor-eremophil-1(10)-en-7-ol is reported as a natural product for the first time. The composition of X. vietnamensis wood oil varied drastically from those of leaf oils, dominated by hedycaryol (34.4%), phyllocladene (37.8%) or by pimara-6(14)-15-diene (19.4%).

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IJMS, Vol. 17, Pages 1016: Screening of α-Tocopherol Transfer Protein Sensitive Genes in Human Hepatoma Cells (HepG2)

α-Tocopherol transfer protein (α-TTP) is a ~32 kDa protein expressed mainly in hepatocytes. The major function of the protein is to bind specifically to α-tocopherol and, together, the complex transfers from late lysosomes to the cell membrane. A previous study indicated that some factors might be required in the transferring process. However, there is little information available about the potential transferring factors. In addition, there remains much to learn about other physiological processes which α-TTP might participate in. Thus, in this study a human α-TTP eukaryotic expression vector was successfully constructed and expressed in human hepatoma cells (HepG2). The sensitive genes related to α-TTP were then screened by microarray technology. Results showed that expression of the vector in HepG2 cells led to the identification of 323 genes showing differential expression. The differentially expressed transcripts were divided into four main categories, including (1) cell inflammation; (2) cell cycle and cell apoptosis; (3) cell signaling and gene regulation; and (4) cellular movement. A few cellular movement related transcripts were selected and verified by quantitative real-time PCR. Expressions of some were significantly increased in α-TTP-expressed group, which indicated that these factors were likely to play a role in the transferring process.

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Atmosphere, Vol. 7, Pages 88: Semi-Physical Estimates of National-Scale PM10 Concentrations in China Using a Satellite-Based Geographically Weighted Regression Model

The estimation of ambient particulate matter with diameter less than 10 µm (PM10) at high spatial resolution is currently quite limited in China. In order to make the distribution of PM10 more accessible to relevant departments and scientific research institutions, a semi-physical geographically weighted regression (GWR) model was established in this study to estimate nationwide mass concentrations of PM10 using easily available MODIS AOD and NCEP Reanalysis meteorological parameters. The results demonstrated that applying physics-based corrections could remarkably improve the quality of the dataset for better model performance with the adjusted R2 between PM10 and AOD increasing from 0.08 to 0.43, and the fitted results explained approximately 81% of the variability in the corresponding PM10 mass concentrations. Annual average PM10 concentrations estimated by the semi-physical GWR model indicated that many residential regions suffer from severe particle pollution. Moreover, the deviation in estimation, which primarily results from the frequent changes in elevation, the spatially heterogeneous distribution of monitoring sites, and the limitations of AOD retrieval algorithm, was acceptable. Therefore, the semi-physical GWR model provides us with an effective and efficient method to estimate PM10 at large scale. The results could offer reasonable estimations of health impacts and provide guidance on emission control strategies in China.

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Molecules, Vol. 21, Pages 843: Resistance to DNA Damaging Agents Produced Invasive Phenotype of Rat Glioma Cells—Characterization of a New in Vivo Model

Chemoresistance and invasion properties are severe limitations to efficient glioma therapy. Therefore, development of glioma in vivo models that more accurately resemble the situation observed in patients emerges. Previously, we established RC6 rat glioma cell line resistant to DNA damaging agents including antiglioma approved therapies such as 3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and temozolomide (TMZ). Herein, we evaluated the invasiveness of RC6 cells in vitro and in a new orthotopic animal model. For comparison, we used C6 cells from which RC6 cells originated. Differences in cell growth properties were assessed by real-time cell analyzer. Cells' invasive potential in vitro was studied in fluorescently labeled gelatin and by formation of multicellular spheroids in hydrogel. For animal studies, fluorescently labeled cells were inoculated into adult male Wistar rat brains. Consecutive coronal and sagittal brain sections were analyzed 10 and 25 days post-inoculation, while rats' behavior was recorded during three days in the open field test starting from 25th day post-inoculation. We demonstrated that development of chemoresistance induced invasive phenotype of RC6 cells with significant behavioral impediments implying usefulness of orthotopic RC6 glioma allograft in preclinical studies for the examination of new approaches to counteract both chemoresistance and invasion of glioma cells.

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Gas-Diffusion Microfluidic Paper-Based Analytical Device ([small mu ]PAD) Coupled with Portable Surface-Enhanced Raman Scattering (SERS): Facile Determination of Sulphite in Wines

Analyst, 2016, Accepted Manuscript
DOI: 10.1039/C6AN00788K, Paper

Miao Chen, Hua Yang, Liya Rong, Xiaoqing Chen
A novel facile method for on-site determination of sulphite in wine using gas-diffusion microfluidic paper-based analytical device ([small mu ]PAD) combined with surface-enhanced Raman spectroscopy (SERS) was explored. The inexpensive and disposable...
The content of this RSS Feed (c) The Royal Society of Chemistry

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“Chemistry and Chemical Biology of Therapeutically Important Compounds”

Publication date: Available online 27 June 2016
Source:Bioorganic & Medicinal Chemistry
Author(s): Matthew David Disney




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Development of Hemolytic Anemia in a Nivolumab-Treated Patient with Refractory Metastatic Squamous Cell Skin Cancer and Chronic Lymphatic Leukemia

Management of patients with metastatic squamous cell skin cancer, refractory to initial therapy with standard chemotherapy and radiation protocols, remains difficult with poor overall prognosis and limited therapeutic options. Recently, promising response rates with nivolumab, a programmed death receptor-1-blocking antibody, in squamous cancer of the head and neck have been demonstrated. Considering the similar histological patterns of squamous cell cancer of the skin and squamous cell cancer of the head and neck, we assumed that nivolumab could also be effective in our patients with refractory metastatic squamous cell cancer of the skin. So far, there have been no clinical data on the therapeutic efficacy of nivolumab in squamous cell skin cancer. We here present a case of a patient with metastatic squamous cell skin cancer refractory to previous therapies, who showed a good response to nivolumab over a period of 5 months, but developed a serious hemolytic crisis under nivolumab treatment after eight applications.
Case Rep Oncol 2016;9:373–378

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A Giant Retroperitoneal Liposarcoma Encasing the Entire Left Kidney and Adherent to Adjacent Structures: A Case Report

Retroperitoneal liposarcoma is a rare tumor. The dimension and weight of liposarcoma are variable; those over 20 kg are called 'giant liposarcoma'. Herein, we report giant retroperitoneal liposarcoma measuring 45 cm in diameter and 25 kg in weight encasing the entire left kidney and adherent to adjacent structures. A 71-year-old woman presented for a regular checkup. Image study revealed a huge mass probably indicative of retroperitoneal liposarcoma encasing the entire left kidney and adherent to adjacent structures. We performed an organ-preserving surgical removal. The pathologic report was liposarcoma. At postoperative month 16, a follow-up CT revealed a locally recurrent tumor. The patient underwent surgical removal of the newly discovered mass. After the second surgery, the patient underwent regular follow-up CT for approximately 12 months, and to date, there has been no evidence of tumor recurrence. High-grade liposarcoma shows sensitivity to radiation therapy. However, the toxic effect of radiation therapy limits this option by treatment modality. The use of chemotherapy is also controversial. As a result, complete resection is the gold standard treatment. Here, we report a giant retroperitoneal liposarcoma encasing the entire left kidney and adherent to adjacent structures, describe successful organ-preserving surgical removal and discuss prognosis.
Case Rep Oncol 2016;9:368–372

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Pazopanib in Primary Cardiac Angiosarcoma of the Right Atrium: A Case Report

Primary heart tumors are an extremely rare oncological entity with primary cardiac sarcomas usually representing 20% of all primary cardiac tumorous lesions [Shanmugam: Eur J Cardiothorac Surg 2006;29: 925–932; Orlandi et al.: J Thorac Oncol 2010;5: 1483–1489]. Angiosarcoma is the most prevalent histology and despite a multidisciplinary approach tends to have a dismal prognosis [Shanmugam: Eur J Cardiothorac Surg 2006;29: 925–932; Fury et al.: Cancer J 2005;11: 241–247]. Based on the prevailing literature, we report a 48-year-old woman diagnosed with primary metastatic cardiac angiosarcoma who showed a severe hypersensitivity reaction to conventional chemotherapy with taxanes but an excellent response to treatment with the multitargeted receptor tyrosine kinase inhibitor pazopanib.
Case Rep Oncol 2016;9:363–367

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Postictal Magnetic Resonance Imaging Changes Masquerading as Brain Tumor Progression: A Case Series

Seizures are common among patients with brain tumors. Transient, postictal magnetic resonance imaging abnormalities are a long recognized phenomenon. However, these radiographic changes are not as well studied in the brain tumor population. Moreover, reversible neuroimaging abnormalities following seizure activity may be misinterpreted for tumor progression and could consequently result in unnecessary tumor-directed treatment. Here, we describe two cases of patients with brain tumors who developed peri-ictal pseudoprogression and review the relevant literature.
Case Rep Oncol 2016;9:358–362

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Arriving at the Right Diagnosis in an Era of Precision Medicine

In the era of precision medicine and targeted therapy, diagnostic inaccuracy can have tremendous ramifications. We present the case of a 61-year-old man initially diagnosed with small cell lung cancer by pathology. Prior to initiating chemotherapy, multidisciplinary discussions led to an amendment of the diagnosis to medullary thyroid cancer.
Case Rep Oncol 2016;9:351–357

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Exploration of the Dietary and Lifestyle Behaviors and Weight Status and Their Self-Perceptions among Health Sciences University Students in North Lebanon

University students may experience significant environmental changes that exert a negative influence on the quality of their diet and lifestyle. There is scarcity of data concerning the dietary and lifestyle behaviors and weight status of students in the health field in North Lebanon. To investigate these data, a cross-sectional survey was conducted including 369 health sciences students aged 18–25 chosen from four public and private universities in North Lebanon. Data were collected using a standardized interview questionnaire to determine sociodemographic, dietary, and lifestyle behaviors, appetite changes, stress related dietary behaviors, and food cravings, as well as self-perceptions of dietary adequacy, physical activity levels, and weight status. Body mass index was assessed. Results had revealed significant differences in some of the dietary consumption patterns and weight status among seniors compared to juniors. However, the overall prevalence of overweight and obesity recorded 32.2% and the dietary consumption patterns fall below recommended levels. Multivariate regression analysis showed that parental obesity, comfort eating, increased appetite, food cravings, and stressful eating were associated with increased risk of obesity while a healthy diet score was associated with decreased risk. The study's findings call for tailoring culture specific intervention programs which enable students to improve their dietary and lifestyle behaviors and control stress.

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Pharmaceuticals, Vol. 9, Pages 36: Site-Specific Labeling of Protein Kinase CK2: Combining Surface Display and Click Chemistry for Drug Discovery Applications

Human CK2 is a heterotetrameric constitutively active serine/threonine protein kinase and is an emerging target in current anti-cancer drug discovery. The kinase is composed of two catalytic CK2α subunits and two regulatory CK2β subunits. In order to establish an assay to identify protein-protein-interaction inhibitors (PPI) of the CK2α/CK2β interface, a bioorthogonal click reaction was used to modify the protein kinase α-subunit with a fluorophore. By expanding the genetic code, the unnatural amino acid para azidophenylalanine (pAzF) could be incorporated into CK2α. Performing the SPAAC click reaction (Strain-Promoted Azide-Alkyne Cycloaddition) by the use of a dibenzylcyclooctyne-fluorophore (DBCO-fluorophore) led to a specifically labeled human protein kinase CK2α. This site-specific labeling does not impair the phosphorylation activity of CK2, which was evaluated by capillary electrophoresis. Furthermore a dissociation constant (KD) of 631 ± 86.2 nM was determined for the substrate αS1-casein towards CK2α. This labeling strategy was also applied to CK2β subunit on Escherichia coli, indicating the site-specific modifications of proteins on the bacterial cell surface when displayed by Autodisplay.

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Materials, Vol. 9, Pages 520: Curcumin and Osteosarcoma: Can Invertible Polymeric Micelles Help?

Systematic review of experimental and clinical data on the use of curcumin in the treatment of osteosarcoma is presented. The current status of curcumin's therapeutic potential against bone cancer is analyzed in regard to using polymeric micelles (including recently developed invertible, responsive, micelles) as a platform for curcumin delivery to treat osteosarcoma. The potential of micellar assemblies from responsive macromolecules in a controlled delivery of curcumin to osteosarcoma cells, and the release using a new inversion mechanism is revealed.

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Sports, Vol. 4, Pages 36: Differences in Spatial Physical Activity Patterns between Weekdays and Weekends in Primary School Children: A Cross-Sectional Study Using Accelerometry and Global Positioning System

Targeting the weekend to promote physical activity (PA) in children seems to be promising given that they tend to be less physically active and, particularly, as the age-related decline in PA is more marked during weekends. Considering the ambiguity of why children are not able to maintain their PA level on weekends, the aim of the present study was to objectively investigate differences in children's spatial PA patterns between week and weekend days using the combination of Global Positioning System (GPS) and accelerometry. Seventy-four second graders (aged 7–9 years) and 98 sixth graders (aged 11–14 years) wore an accelerometer and GPS sensor for seven consecutive days to determine where children spend time and engage in PA. Time-matched accelerometer and GPS data was mapped with a geographic information system and multilevel analyses accounting for the hierarchical structure of the data were conducted. Differences between weekdays and weekends regarding the total time spent and the absolute and relative level of PA in various settings were found in both age groups. The findings support previous research pointing to the importance of targeting weekend PA, especially when children grow older. Future interventions should encourage children to use outdoor spaces more frequently on weekends, rather than stay at home, and to commute actively to destinations other than school.

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Sensors, Vol. 16, Pages 980: On Curating Multimodal Sensory Data for Health and Wellness Platforms

In recent years, the focus of healthcare and wellness technologies has shown a significant shift towards personal vital signs devices. The technology has evolved from smartphone-based wellness applications to fitness bands and smartwatches. The novelty of these devices is the accumulation of activity data as their users go about their daily life routine. However, these implementations are device specific and lack the ability to incorporate multimodal data sources. Data accumulated in their usage does not offer rich contextual information that is adequate for providing a holistic view of a user's lifelog. As a result, making decisions and generating recommendations based on this data are single dimensional. In this paper, we present our Data Curation Framework (DCF) which is device independent and accumulates a user's sensory data from multimodal data sources in real time. DCF curates the context of this accumulated data over the user's lifelog. DCF provides rule-based anomaly detection over this context-rich lifelog in real time. To provide computation and persistence over the large volume of sensory data, DCF utilizes the distributed and ubiquitous environment of the cloud platform. DCF has been evaluated for its performance, correctness, ability to detect complex anomalies, and management support for a large volume of sensory data.

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Cells, Vol. 5, Pages 29: Epithelial Intermediate Filaments: Guardians against Microbial Infection?

Intermediate filaments are abundant cytoskeletal components of epithelial tissues. They have been implicated in overall stress protection. A hitherto poorly investigated area of research is the function of intermediate filaments as a barrier to microbial infection. This review summarizes the accumulating knowledge about this interaction. It first emphasizes the unique spatial organization of the keratin intermediate filament cytoskeleton in different epithelial tissues to protect the organism against microbial insults. We then present examples of direct interaction between viral, bacterial, and parasitic proteins and the intermediate filament system and describe how this affects the microbe-host interaction by modulating the epithelial cytoskeleton, the progression of infection, and host response. These observations not only provide novel insights into the dynamics and function of intermediate filaments but also indicate future avenues to combat microbial infection.

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Photonics, Vol. 3, Pages 41: Engineering Multi-Section Quantum Cascade Lasers for Broadband Tuning

In an effort to overcome current limitations to electrical tuning of quantum cascade lasers, a strategy is proposed which combines heterogeneous quantum cascade laser gain engineering with sampled grating architectures. This approach seeks to not only widen the accessible spectral range for an individual emitter, but also compensate for functional non-uniformity of reflectivity and gain lineshapes. A trial laser with a dual wavelength core is presented which exhibits electroluminescence over a 750 cm−1 range and discrete single mode laser emission over a 700 cm−1 range. Electrical tuning over 180 cm−1 is demonstrated with a simple sampled grating design. A path forward to even wider tuning is also described using more sophisticated gain and grating design principles.

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Energies, Vol. 9, Pages 491: Frequency-Splitting-Free Synchronous Tuning of Close-Coupling Self-Oscillating Wireless Power Transfer

The synchronous tuning of the self-oscillating wireless power transfer (WPT) in a close-coupling condition is studied in this paper. The Hamel locus is applied to predict the self-oscillating points in the WPT system. In order to make the system operate stably at the most efficient point, which is the middle resonant point when there are middle resonant and split frequency points caused by frequency-splitting, the receiver (RX) rather than the transmitter (TX) current is chosen as the self-oscillating feedback variable. The automatic delay compensation is put forward to eliminate the influence of the intrinsic delay on frequency tuning for changeable parameters. In addition, the automatic circuit parameter tuning based on the phase difference is proposed to realize the synchronous tuning of frequency and circuit parameters. The experiments verified that the synchronous tuning proposed in this paper is effective, fully automatic, and more robust than the previous self-oscillating WPT system which use the TX current as the feedback variable.

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Land, Vol. 5, Pages 21: Agriculture on the Brink: Climate Change, Labor and Smallholder Farming in Botswana

Botswana is a semi-arid, middle-income African country that imports 90 percent of its food. Despite its relative prosperity, Botswana also suffers from one of the highest measures of income inequality in the world, persistent poverty, and relatively high levels of food insecurity. The objective of this paper is to explore how political economy, climate change and livelihood dynamics are synergistically impacting household food security. The major finding is that the marginalization of smallholder farming in Botswana has as much or more to do with domestic, regional and international political economy as it does with climate change. As such, international efforts to support climate change adaptation in Botswana will have a limited effect on smallholder farming livelihoods and rural food security unless such efforts take account of political economic constraints. Effective support must be based on a grounded understanding of the real drivers of marginalization and food insecurity. One initiative that merits further exploration is the government's backyard gardening initiative, which could be viewed as a pro-poor climate adaptation strategy. The findings of this paper are based on semi-structured interviews with policymakers and surveys with urban, peri-urban and rural households undertaken in 2012 and 2015.

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Horticulturae, Vol. 2, Pages 7: An Overview of Fertilization and Irrigation Management in the Conventional and Certified Organic Production of Vegetable Crops in Florida

The postharvest quality of vegetable crops from conventional and organic production systems depends on pre-harvest factors such as variety genetic potential, fertilization, and irrigation. The five principles of plant nutrition (plants absorb ions, not fertilizers; Leibeig's law of the minimum; nutrient application requires a source, a rate, a placement and a time of application; no correlation exists between total nutrient presence in the soil and availability; and plant nutrient concentration and yield are related) must be followed throughout the crop growth cycle. In certified organic production in the United States, cover crops, manure and composts may be used together with Organic Materials Review Institute–approved fertilizer products. A fertilization program usually includes (1) soil sampling and understanding the recommendation; (2) adjusting pH if necessary; (3) applying preplant fertilizer and developing a schedule for sidedressing or fertigation; (4) using foliar fertilization; (5) monitoring plant nutrient status; and (5) keeping fertilization records. The components of an irrigation schedule are (1) determining a target irrigation volume based on reference evapotranspiration and crop age; (2) adjusting this amount based on soil moisture content; (3) determining the contribution of rainfall; (4) developing a rule for splitting irrigation; and (5) keeping irrigation records. A poorly designed irrigation program can negate the benefits of a sound fertilization program. Challenges encountered in conventional and organic production include predicting nutrient release rates from organic materials, supplying enough N throughout the cropping season, identifying rescue strategies, keeping production costs low, and meeting the additional legal requirements of the food safety and best management practices programs.

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Horticulturae, Vol. 2, Pages 6: Estimating the Leaf Area of Cut Roses in Different Growth Stages Using Image Processing and Allometrics

Non-destructive, accurate, user-friendly and low-cost approaches to determining crop leaf area (LA) are a key tool in many agronomic and physiological studies, as well as in current agricultural management. Although there are models that estimate cut rose LA in the literature, they are generally designed for a specific stage of the crop cycle, usually harvest. This study aimed to estimate the LA of cut "Red Naomi" rose stems in several phenological phases using morphological descriptors and allometric measurements derived from image processing. A statistical model was developed based on the "multiple stepwise regression" technique and considered the stem height, the number of stem leaves, and the stage of the flower bud. The model, based on 26 stems (232 leaves) collected at different developmental stages, explained 95% of the LA variance (R2 = 0.95, n = 26, p < 0.0001). The mean relative difference between the observed and the estimated LA was 8.2%. The methodology had a high accuracy and precision in the estimation of LA during crop development. It can save time, effort, and resources in determining cut rose stem LA, enhancing its application in research and production contexts.

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Energies, Vol. 9, Pages 492: Hybrid Modulation of Bidirectional Three-Phase Dual-Active-Bridge DC Converters for Electric Vehicles

Bidirectional power converters for electric vehicles (EVs) have received much attention recently, due to either grid-supporting requirements or emergent power supplies. This paper proposes a hybrid modulation of the three-phase dual-active bridge (3ΦDAB) converter for EV charging systems. The designed hybrid modulation allows the converter to switch its modulation between phase-shifted and trapezoidal modes to increase the conversion efficiency, even under light-load conditions. The mode transition is realized in a real-time manner according to the charging or discharging current. The operation principle of the converter is analyzed in different modes and thus design considerations of the modulation are derived. A lab-scaled prototype circuit with a 48V/20Ah LiFePO4 battery is established to validate the feasibility and effectiveness.

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Peptide drugs accelerate BMP-2-induced calvarial bone regeneration and stimulate osteoblast differentiation through mTORC1 signaling

Both W9 and OP3-4 were known to bind the receptor activator of NF-κB ligand (RANKL), inhibiting osteoclastogenesis. Recently, both peptides were shown to stimulate osteoblast differentiation; however, the mechanism underlying the activity of these peptides remains to be clarified. A primary osteoblast culture showed that rapamycin, an mTORC1 inhibitor, which was recently demonstrated to be an important serine/threonine kinase for bone formation, inhibited the peptide-induced alkaline phosphatase activity. Furthermore, both peptides promoted the phosphorylation of Akt and S6K1, an upstream molecule of mTORC1 and the effector molecule of mTORC1, respectively. In the in vivo calvarial defect model, W9 and OP3-4 accelerated BMP-2-induced bone formation to a similar extent, which was confirmed by histomorphometric analyses using fluorescence images of undecalcified sections. Our data suggest that these RANKL-binding peptides could stimulate the mTORC1 activity, which might play a role in the acceleration of BMP-2-induced bone regeneration by the RANKL-binding peptides.

Micro CT and fluorescent images revealed that two RANKL-binding peptides, W9 and OP3-4, could equally accelerate BMP-2-induced local bone regeneration in a murine calvarial defect model. The yellow line shows the site of the reconstruction images in the middle panel. White lines show the size of the original defect.

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Effect of Aurantii Fructus Immaturus Flavonoid on the Contraction of Isolated Gastric Smooth Muscle Strips in Rats

This study was designed to investigate the effect of Aurantii fructus immaturus flavonoid (AFIF) on the contraction of isolated gastric smooth muscle in rats and explore its underlying mechanisms. Isolated antral longitudinal smooth muscle strip (ALSMS) and pyloric circular smooth muscle strip (PCSMS) of rats were suspended in tissue chambers. The responses of ALSMS and PCSMS to administration of AFIF were observed. Cyclic guanosine monophosphate (cGMP) and protein kinase G (PKG) levels of PCSMS were measured by ELISA kits. In this study, AFIF showed no significant effect on ALSMS contraction, but it dose-dependently reduced the mean contraction amplitude of PCSMS. When the concentration of AFIF reached 3000 g/mL, 6000 g/mL, and 10000 g/mL, its inhibitory effect on PCSMS contraction was significant. This effect of AFIF was weakened in Ca2+-rich environment. And N-nitro-L-arginine methyl (L-NAME), the inhibitor of nitric oxide synthase (NOS), significantly inhibited AFIF's action in comparison with control (). After incubation with AFIF for 30 min, levels of cGMP and PKG in PCSMS were significantly increased compared with control (). Our results suggest that AFIF has a dose-dependent diastolic effect on PCSMS in rats, which may be related to the regulatory pathway of NO/cGMP/PKG/Ca2+.

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Antibacterial and Antibiofilm Activity of Methanolic Plant Extracts against Nosocomial Microorganisms

Biofilm is a complex microbial community highly resistant to antimicrobials. The formation of biofilms in biotic and abiotic surfaces is associated with high rates of morbidity and mortality in hospitalized patients. New alternatives for controlling infections have been proposed focusing on the therapeutic properties of medicinal plants and their antimicrobial effects. In the present study the antimicrobial and antibiofilm activities of 8 methanolic plant extracts were evaluated against clinical isolated microorganisms. Preliminary screening by diffusion well assay showed the antimicrobial activity of Prosopis laevigata, Opuntia ficus-indica, and Gutierrezia microcephala. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined ranging from 0.7 to >15 mg/mL. The specific biofilm formation index (SBF) was evaluated before and after the addition of plant extracts (MBC × 0.75). Opuntia ficus-indica caused the major reduction on SBF in dose-dependent manner. Cytotoxic activity of plant extracts was determined using brine shrimp lethality test (Artemia salina L.). Lethal Dose concentration (LD50 values) of the plant extracts was calculated. LD50 values for P. laevigata and G. microcephala were 141.6 and 323.3 µg/mL, respectively, while O. ficus-indica showed a slight lethality with 939.2 µg/mL. Phytochemical analyses reveal the presence of flavonoids, tannins, and coumarines.

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Abnormal amygdala resting-state functional connectivity in irritable bowel syndrome

American Journal of Neuroradiology

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The effect of black tea (Camellia sinensis (L) Kuntze) on pediatrics with acute nonbacterial diarrhea: A randomized controlled trial

Journal of Evidence-Based Complementary & Alternative Medicine

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High frequency of KRAS mutation in early onset colorectal adenocarcinoma: Implications for pathogenesis

Human Pathology

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All-oral DAA regimens in HIV-HCV coinfected cirrhotic patients are efficient and safe. Real-life results from the prospective ANRS CO13 - HEPAVIH cohort

Clinical Infectious Diseases

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Retrospective study of laparoscopic versus open gastric resection for gastric gastrointestinal stromal tumors based on the propensity score matching method

Surgical Endoscopy

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