bluuebunny/crossref_metadata_2025 huggingface dataset:
Determination of Selenium in Meat Products by Hydride Generation Atomic Absorption Spectrophotometry
Authors: Tinggi Ujang
Published: February 2020

Wet digestion using a mixture of nitric, sulfuric, and perchloric acids and an aluminum block digester effectively and rapidly decomposed meat samples for selenium determination by hydride generation atomic absorption spectrophotometry. Digestion did not require constant attention by an operator. Selenium recoveries (range, 94-105%) from National Institute ofStandards and Technology standard reference materials and spiked samples were used to validate method accuracy. Coefficients of variation (CVs) of repeatability of in-house reference materials used forprecision study were 6.4 and 5.6%, respectively, for seafood mix and mutton liver. Selenium levels in meat products from Brisbane markets varied widely: 0.042-0.142,0.081- 0.42, and 0.050-0.198 μg/g (wet weight) respectively, for beef, chicken, and pork. Overall, selenium levels in manufactured meat ranged from0.041 to 0.189 fig/g. The levels of selenium foundinthis study were generally lower than those reported in Finland but comparable with those reported in some parts of the United States
Fusarium Mycotoxins in Corn and Corn Products in a High-Risk Area for Gastric Cancer in Shandong Province, China
Authors: Groves Frank D , Zhang Lian , Chang Yun-Sheng , Ross Frank P , Casper Howard , Norred William P , You Wei-Cheng , Fraumeni Joseph F
Published: February 2020

Consumption of fermented, but not unfermented, corn pancakes has been linked with elevated stomach cancer mortality rates in rural Linqu County in Shandong Province, China. Previous surveys of fungal contamination of corn in China have detected fumonisins, which are mycotoxins produced by Fusarium moniliforme. To determine whether mycotoxins might account for the increased risk of cancer among those consuming fermented pancakes, we obtained specimens of corn, cornmeal, unfermented and fermented pancake batter, and cooked fermented pancakes from each of 16 households in Linqu County for analysis by the U.S. Department of Agriculture. Fumonisins Bi, B2, and B3 were detected (≤0.5 μg/g) in 19,25, and 6% of the corn specimens, respectively, as well as in various corn products. No type A trichothecenes were detected; however, the type B trichothecenes deoxynivalenol and 15-acetyldeoxynivalenol were detected (≤0.5 μg/g) in 58 and 17% of the corn specimens, respectively, and zearalenone was detected (≤0.5 iig/g) in 15% of the cornmeal specimens. The mycotoxins were detected only at low levels (<10 μg/g), which did not increase with fermentation. These findings do not support the hypothesis that mycotoxin contamination increases the risk of gastric cancer among those who consume fermented Chinese pancakes.
An Immunoaffinity Column for the Determination of Peanut Protein in Chocolate
Authors: Newsome Harvey W , Abbott Michael
Published: February 2020

An immunoaffinity column was prepared from rabbit polyclonal antiserum for the determination of peanut protein from food matrixes. The anti-peanut immunoglobulin G was isolated from antiserum by affinity chromatography on a column coupled with peanut protein and then attached to an AminoLink gel. The column was applied to the determination of peanut protein in chocolate after extraction, immunoaffinity chromatography, and enzyme-linked immunosorbent assay (ELISA). Overall recoveries from chocolate spiked with 0.2–3.2 μg/g of peanut protein averaged 77% (range, 72–84%), and the minimum detection limit was 0.1 μg/g. Chromatography of extracts with the column improved detection limit and eliminated the matrix effect experienced with direct ELISA of chocolate extracts.
Determination of Iron in Raw Materials, During Fabric Processing, and in Wastewaters of the Textile Industry
Authors: Grabaric Zorana , Bokic Ljerka , Stefanovic Branka
Published: February 2020

The Schiff base 2-(2-pyridylmethyieneamino)phenol (PMAP) was investigated as a spectrophotometric reagent for determination of iron in caustic soda, cotton yarn and fabric, woolen fabric, and industrial water. The solution properties of Fe(III)-PMAP complexes were determined. At pH 4.4 and 5.6, Fe(III) forms stable complexes with PMAP, with molar absorption coefficients (ε) of 3.00 × 103 and 7.44 × 103/M.cm, respectively. Composition and cumulative stability constants were determined by the mole ratio method (MRM) and the mole fraction variation method (MFVM). At the lower pH (4.4), the predominant complex species in the solution obtained with both methods are ML2, with fairly good agreement of stability constants: log βML2 = 7.00 ± 0.04 with MRM and 7.31 ± 0.01 with MFVM. At the higher pH (5.6), the composition and stability constants of predominant complex species in the solution obtained with the 2 methods were not in good agreement, perhaps because of the coexistence of several species, such as Fe-PMAP, Fe-hydroxo, and Fe-acetate complexes. PMAP is a sensitive reagent for determination of Fe(III). The detection limit of 0.4 μg/mL is lower than those of other frequently used spectrophotometric reagents for Fe. The reagent is ecologically more acceptable, because extraction with organic solvents is avoided. All measurements were made at pH 5.6 because sensitivity was higher at this pH. The high Fe values obtained for industrial water (31.8 μg/mL) indicate that some modifications in the process have to be done. Concentration of Fe in wastewater was much lower (15.9 μg/mL). The results for cotton and woolen fabric indicate that accumulation of Fe in wool is much higher than in cotton (84.4 μg/mL and 29.3-53.1 μg/mL, respectively).
Bayesian Approach to Establishing Assay Limits
Authors: Varbanov Alexandre , Mowrey Daniel
Published: February 2020

A Bayesian method to establishing assay limits of detection and quantitation is proposed. It allows prior knowledge to be incorporated into the analysis of the limits. The posterior distributions of the limits in x (concentration) can be approximated well with the help of a simple simulation procedure. This allows good estimates of mean, variance, and other characteristics of those distributions to be computed. The approach is illustrated by an example with 2 made-up data sets.
Rapid and Simple Determination of Oxytetracycline in Chicken Products
Authors: Furusawa Naoto
Published: February 2020

A rapid and simple method for determining resid ual oxytetracycline (OTC) in chicken products(muscle, liver, and eggs) by high-performance liquid chromatography (HPLC) was developed. Samples were prepared by homogenization with acetonitrile-n-hexane (5 + 4, v/v) followed by centrifugation to minimize fat and protein contents. OTC in the acetonitrile layer was free from interfering compounds when examined by HPLC using a LiChrospher 100 RP-8 end-capped column, a mobile phase of acetonitrile–acetic acid–0.01 M disodium EDTA(28 + 2 + 70, v/v/v),and a photodiode array detector. Average recoveries from samples spiked with OTC (0.1, 0.2, and1.0 ppm) were >88%, with coefficients of variation between 2.3 and 5.1 %. The limit of detection was 0.05 ppm.
Application of Microbial Receptor Assay to Quantitation of Residues of Spectinomycin in Bovine Milk and Comparison with Liquid Chromatographic Analysis
Authors: Shaikh Badar , Schermerhorn Pat , Adam Laura A , Von Bredow Jurgen D
Published: February 2020

Spectinomycin-contaminated bovine milk samples were assayed by liquid chromatographic (LC) and microbial receptor methods. LC involved a newly developed analytical method to quantitate the concentration of spectinomycin in the contaminated milk samples. The receptor assay used reagents and the reaction system used for the Charm II spectinomycin assay. Three standard curves (selected range, full range, and second-order polynomial) were plotted for the receptor assay and used to quantitate spectinomycin in contaminated milk samples. The levels of spectinomycin obtained by the receptor assay, using only the standard curve in the selected range, were comparable to the results obtained by LC analysis.
Confirmation of Azaperone and Its Metabolically Reduced Form, Azaperol, in Swine Liver by Gas Chromatography/Mass Spectrometry
Authors: Adam Laura A
Published: February 2020

The method described confirms the use of the tranquilizer azaperone by detecting the parent compound and the metabolically reduced form, azaperol. Both are confirmed in swine liver at a target concentration of 10 ppb by gas chromatography/mass spectrometry (GC/MS) with electron ionization in the selected-ion-monitoring mode. Swine liver tissue is ground with dry ice. Acetonitrile is added to extract the drug from the tissue. Sodium chloride buffer is added to the extract in preparation for solid-phase extraction (SPE). The aqueous extract is loaded onto an SPE cartridge designed to extract acidic and neutral drug residues from biological matrixes. The cartridge is washed with methanol and conditioned with sodium phosphate buffer. Azaperone and azaperol residues are eluted with a 2% ammonium hydroxide in ethyl acetate. The extracts are evaporated to dryness under a stream of nitrogen and reconstituted in ethyl acetate for GC/MS analysis. A DB-1 analytical column is used to separate the compounds prior to electron ionization. The parent ion, the base peak ion, and one diagnostic fragment ion are monitored for both compounds. The method was validated with fortified tissue samples containing both azaperone and azaperol. Azaperone-incurred tissues also were analyzed, and the presence of the parent drug and the metabolically reduced form, azaperol, was confirmed.
Liquid Chromatographic Detection of Dowtherm A Contamination in Oleochemicals and Edible Oils
Authors: Moh Felix Mee Ho , Tang Thin Sue
Published: February 2020

A rapid and direct liquid chromatographic (LC) technique is described for the determination of a eutectic mixture of diphenyl oxide and biphenyl such as Dowtherm A thermal heating fluid (THF) in oleochemicals and palm olein. Analysis is performed with an RP-18 column with fluorescence detection (excitation at 247 nm and emission at 310 nm). The isocratic mobile phase (1.0 mL/min) consists of methanol and water (90 + 10, v/v). A linear calibration model (correlation coefficient = 0.9999) was developed directly from used Dowtherm A THF with the biphenyl peak (4.70 min) as a marker. Average recoveries from spiked glycerin, fatty alcohol mixture, methyl ester mixture, fatty acids, and palm olein were 90.9–108.7%, with a detection limit of 0.1 μg/mL. The technique requires no prior sample cleanup nor extraction steps and is good for quality assurance purposes.
Electrochemical Determination of Lacidipine
Authors: Squella Juan A , Iribarren Anny E , Sturm Juan C , Núñez-Vergara Luis J
Published: February 2020

Lacidipine is an antihypertensive drug that is oxidizable at the glassy carbon electrode. The voltammetric oxidation of lacidipine in aqueous-alcoholic solutions (70 + 30) produces a well-defined voltammetric peak when subjected to a differential pulse voltammetric experiment. This peak is due to oxidation of the dihydropyridine ring to a pyridine derivative. This voltammetric response result is irreversible, pH dependent, and diffusion controlled. The best resolution for the peak was obtained at pH 6 in Britton-Robinson buffer-ethanol (70 + 30). The peak potential at pH 6 was 800 mV against an Ag-AgCI reference electrode. A linear relationship between peak current and lacidipine concentration was obtained. For analytical purposes, a calibration curve for lacidipine that covered concentrations between 5 x 10-6 and 2 x 10-6 was used. Detection and quantitation limits were 3.52 x 10-6 and 3.78 x 10-6M, respectively. The repeatability of the measurement was 2%. On the basis of the voltammetric response, we also developed high-performance liquid chromatographic methods with electrochemical detection. For comparative purposes, we also developed a spectrophotometric method.
Determination of Residues of Azamethiphos in Salmon Tissue by Liquid Chromatography with Fluorescence Detection
Authors: Pfenning Allen P , Roybal José E , Turnipseed Sherri B , Gonzales Steve A , Hurlbut Jeffrey A
Published: February 2020

A liquid chromatographic (LC) method with fluorescence detection (FLD) is described for determining residues of the pesticide azamethiphos (AZA) in salmon tissue. The sample is extracted with ethyl acetate, centrifuged, dehydrated with anhydrous sodium sulfate, evaporated, reconstituted in water, and defatted with hexane. The aqueous phase is passed through a C18 solid-phase extraction (SPE) column. The SPE column is eluted with methanol, and the eluate is evaporated to dryness and then taken up in 10% acetonitrile (ACN) in water. The analyte is determined by LC using a C18 column, ACN-H2O (32 + 68) mobile phase, and FLD with excitation at 230 nm and emission at 345 nm. Composited salmon tissues were fortified with AZA at 5,10,21, 42, and 83 ng/g or ppb (target level, X = 10 ng/g). Overall recoveries were 86%, with between-day variability of 5.3%. The method detection limit was calculated as 1.2 ppb AZA based on a 5 g sample. The limit of quantitation as determined empirically by this method is the lower limit of the standard curve, approximately 5 ppb.
Determination of Fluoroquinolone Residues in Animal Tissues Using Escherichia coli as Indicator Organism
Authors: Choi Jason , Yee Arlene J , Thompson Dianne , Samoluk Jurek , Mitchell Mark , Black William D
Published: February 2020

Three strains of Escherichia coli(ATCC 128,10536, and 25922) and one strain of Bacillus subtilis (ATCC 3491) were compared as indicator microorganisms in microbial inhibition tests for their ability to detect fluoroquinolone residues. E. coli strains 128 and 10536 were most susceptible to fluoroquinolone residues, with detection limits of 35-50 μg/kg for enrofloxacin. Of the 2 strains, E. coli 10536 was slightly less susceptible. Ciprofloxacin was detected consistently by E. coli 128 at 30 μg/kg. Other fluoroquinolone drugs of veterinary interest detected by E. coli 128 were sarafloxacin and difloxacin at 100-250 μg/kg concentration. E. coli25922 yielded 100% sensitivity in detection of enrofloxacin only at the 250 μg/kg concentration, and ciprofloxacin and sarafloxacin at 200 μg/kg. B. subtilis detected only enrofloxacin 100% of the time at 250 μg/kg. The E. coli strains tested were insensitive to other antibacterials commonly used in animals, with the exception of ceftiofur which was detected by E. coli 128 and 10536 at 500 μg/kg. The B. subtilis strain was not effective in detecting the fluoroquinolone drugs, whereas the E. coli strains were selective for the fluoroquinolones. E. coli 128 was 100% effective in detecting enrofloxacin and ciprofloxacin in spiked diaphragm homogenate samples at 50 μg/kg. Of the microorganisms tested, E. coli strain ATCC 128 was highly suitable as an indicator microorganism in a microbial inhibition assay for selective detection of fluoroquinolone antibacterial residues in animal tissues.
Determination of Hexazinone in Groundwater by Direct-Injection High-Performance Liquid Chromatography
Authors: Perkins L Brian , Bushway Rodney J , Katz Lynn E
Published: February 2020

Hexazinone has been detected at levels ranging from 0.2 to 50 μg/L in many groundwater samples from eastern Maine over the past decade. A rapid and inexpensive direct-injection high-performance liquid chromatographic (HPLC) method has been developed to monitor contamination levels of the herbicide. The method is sensitive (limit of quantitation = 0.33 μg/L) and is linear to 33.0 μg/L (R2 = 0.9995). Direct injection results from 50 field samples compared well (R2 = 0.98) with an HPLC method using solid-phase extraction for concentration and cleanup. The technique is very reproducible (coefficients of variation of 0-8.4% within day and 3.0-13.2% between day) and eliminates loss of analyte because of fewer steps in the procedure.
Separation of Positional Isomers of Organic Acids and Dyestuff Food Additives by Nonaqueous Capillary Electrophoresis
Authors: Razee Saeid , Tamura Atsushi , Masujima Tsutomu
Published: February 2020

The merits of capillary electrophoresis in pure organic solvents were investigated for the separation of closely related positional isomers of dinitrobenzoic acid and isomeric pairs of dyestuff food additives, amaranth-new coccine and light green SF yellowish-brilliant blue. Instead of ordinary buffer salts, cetyltrimethylammonium bromide (CTAB), in methanol or methanol-acetonitrile, and sodium dodecyl sulfate (SDS), in methanol-ethanol, were the media used for the separation, in which a complete resolution of the tested compounds was achieved in a relatively short time. Both nonaquøous systems showed low levels of generated electric current, especially SDS in methanol-ethanol, which showed submicro ampere levels. As a result of low-joule heating and diminished adsorption of solutes on the capillary wall, a relative standard deviation of <0.4% was obtained for the migration times without use of temperature control and a washing step between runs. Addition of urea to the CTAB/methanol system was used for manipulation of electroosmotic flow, analysis time, and resolution. Although elution of the tested compounds in CTAB/acetonitrile was very fast, methanol-acetonitrile was found to be better for optimizing separation and analysis time. For the CTAB/methanol system, the separation pattern was independent of the sample matrix because of the opposite directions of the electroosmotic flow and the electrophoretic mobility of the anionic organic acid isomers. This caused removal of samples constituents including neutral and positively charged species from the capillary after the start of the electrophoretic run.
Separation of Arsenic and Selenium Species by Capillary Zone Electrophoresis in a Coated Capillary
Authors: Vanifatova Natalia G , Spivakov Boris Y , Mattusch Juergen , Wennrich Rainer
Published: February 2020

A capillary zone electrophoresis method was developed for the determination of 8 arsenic and selenium species in a polymer-coated capillary. Large-volume stacking with matrix removal was used for sensitivity enhancement. The entire analysis time was only a few minutes. The experimental sensitivity enhancement for 7 species was found to be near its theoretical value. Coating capillaries for long-term stability in alkaline buffer electrolytes was also investigated.
Formation of SMBH seeds in Population III star clusters through collisions: the importance of mass loss
Authors: Alister Seguel P J , Schleicher D R G , Boekholt T C N , Fellhauer M , Klessen R S
Published: February 2020

Runaway collisions in dense clusters may lead to the formation of supermassive black hole (SMBH) seeds, and this process can be further enhanced by accretion, as recent models of SMBH seed formation in Population III star clusters have shown. This may explain the presence of SMBHs already at high redshift, z > 6. However, in this context, mass loss during collisions was not considered and could play an important role for the formation of the SMBH seed. Here, we study the effect of mass loss, due to collisions of protostars, in the formation and evolution of a massive object in a dense primordial cluster. We consider both constant mass-loss fractions as well as analytic models based on the stellar structure of the collision components. Our calculations indicate that mass loss can significantly affect the final mass of the possible SMBH seed. Considering a constant mass loss of 5 per cent for every collision, we can lose between 60–80 per cent of the total mass that is obtained if mass loss were not considered. Using instead analytical prescriptions for mass loss, the mass of the final object is reduced by 15–40 per cent, depending on the accretion model for the cluster we study. Altogether, we obtain masses of the order of $10^4\, \mathrm{M}_{\odot }$, which are still massive enough to be SMBH seeds.
Changes in Cigarettes per Day and Biomarkers of Exposure Among US Adult Smokers in the Population Assessment of Tobacco and Health Study Waves 1 and 2 (2013–2015)
Authors: Rostron Brian L , Corey Catherine G , Chang Joanne T , van Bemmel Dana M , Miller Mollie E , Chang Cindy M
Published: February 2020

Introduction

Some studies have found some reduction in tobacco exposure and tobacco-related disease risk with decreased numbers of cigarettes smoked per day (CPD), but biomarker of exposure estimates by change in CPD are generally unavailable for the US population.

Methods

We analyzed biomarker of exposure data by smoking status from over 1100 adult exclusive daily cigarette smokers in Wave 1 of the Population Assessment of Tobacco and Health (PATH) Study who were either exclusive daily smokers or had quit tobacco use entirely at Wave 2. Wave 1 smoking categories consisted of “very light” (1–4 CPD), “light” (5–9 CPD), “moderate” (10–19 CPD), and “heavy” (20+ CPD), and Wave 2 categories were “quitters” (stopped smoking entirely), exclusive cigarette “reducers” (CPD decreased ≥ 50%), “maintainers” (CPD within 50%–150% of Wave 1 value), and “increasers” (CPD increased ≥ 50%).

Results

Complete quitters had significantly lower levels of TNE-2, NNAL, NNN, 2-Fluorene, HPMA, CYMA, and MHB3 at Wave 2 for all Wave 1 CPD categories, and decreases were often large. Moderate “reducers” had lower levels of NNAL and 1-Hydroxypyrene at Wave 2, and heavy “reducers” had lower levels of NNAL, 2-Fluorene, and MHB3. Light “increasers” had higher levels of TNE-2, NNAL, 2-Fluorene, CYMA, and cadmium at Wave 2, and heavy “increasers” had higher levels of NNAL and HPMA.

Conclusions

Smoking “reducers” and “increasers” had changes in some biomarker of tobacco exposure levels, but reductions were much greater and more consistent for complete quitters.

Implications

PATH longitudinal cohort study data show that some exclusive daily cigarette smokers increase or decrease CPD over time. These differences may result in moderate changes in the levels of some biomarkers such as NNAL. Even so, however, reductions in biomarker levels are much greater with complete smoking cessation.
Efficacy and safety of upadacitinib in Japanese patients with rheumatoid arthritis (SELECT-SUNRISE): a placebo-controlled phase IIb/III study
Authors: Kameda Hideto , Takeuchi Tsutomu , Yamaoka Kunihiro , Oribe Motohiro , Kawano Mitsuhiro , Zhou Yijie , Othman Ahmed A , Pangan Aileen L , Kitamura Susumu , Meerwein Sebastian , Tanaka Yoshiya
Published: February 2020

Objective

To evaluate upadacitinib efficacy and safety dose response in Japanese patients with active RA and an inadequate response to conventional synthetic DMARDs (csDMARDs).

Methods

This was a multicentre, phase IIb/III, dose-ranging study conducted in Japan, in which patients on previously stable csDMARDs were randomized to receive upadacitinib 7.5, 15 or 30 mg once daily or matching placebo for a 12-week double-blind period. The primary endpoint was a 20% improvement in ACR criteria (ACR20) response at week 12 using non-responder imputation. Key secondary endpoints included ACR50, ACR70 and 28-joint DAS with CRP (DAS28-CRP) remission and low disease activity. Adverse events were also assessed.

Results

Of 197 patients treated, 187 completed the double-blind period. At week 12, more patients receiving upadacitinib 7.5, 15 or 30 mg vs placebo met the ACR20 response (75.5%, 83.7%, 80.0% vs 42.9%; P < 0.001), with significant differences observed as early as week 1. Stringent responses, including ACR50, ACR70 and DAS28-CRP <2.6, were achieved by significantly higher proportions of patients on upadacitinib than placebo and by numerically higher proportions on upadacitinib 15 or 30 mg vs upadacitinib 7.5 mg. Adverse events and infections (serious infections, opportunistic infections and herpes zoster) were more common with upadacitinib vs placebo and numerically highest with upadacitinib 30 mg. There were no venous thromboembolic events reported.

Conclusion

Efficacy of upadacitinib was demonstrated in this population of Japanese patients with RA and an inadequate response to csDMARDs. Safety and tolerability were consistent with other upadacitinib RA studies. The 15 mg dose of upadacitinib showed the most favourable benefit–risk profile.

Trial registration

ClinicalTrials.gov, https://clinicaltrials.gov/ct2/show/NCT02720523.
Causes and possibilities to circumvent cyclophosphamide toxicity
Authors: Voelcker Georg
Published: February 2020

Cyclophosphamide is an inert prodrug converted into 4-hydroxycyclophosphamide (OHCP) by hepatic hydroxylation. OHCP is in equilibrium with its tautomeric aldophosphamide (ALDO). From ALDO, the cytotoxic active metabolites are formed enzymatically by phosphodiesterases; these are the alkylating metabolite phosphoramide mustard (PAM) and the proapoptotic aldehyde 3-hydroxypropanal (HPA). PAM damages the DNA by alkylation; HPA amplifies the thereby induced apoptosis. The generally accepted view that acrolein, which is believed to be formed in the formation of PAM by β-elimination from ALDO would be mainly responsible for the toxicity of cyclophosphamide, has to be revised because no acrolein is formed in the systemic circulation of patients after cyclophosphamide administration. It is shown that not acrolein, but OHCP itself is the true toxic metabolite of cyclophosphamide. Toxicity tests with OHCP and PAM were carried out, which demonstrated that OHCP unfolds its toxicity, not as a carrier of PAM but is toxic itself by reacting with nucleophilic groups of macromolecules, for example, thiol groups of membrane proteins. Further experiments demonstrate that the toxicity of oxazaphosphorine cytostatics may be drastically reduced if the formation of the pharmacologically active metabolite ALDO bypasses the formation of OHCP. Toxicity experiments in mice with S-ethanol-cyclophosphamide (SECP) that hydrolyzes to OHCP show that SECP is as toxic as OHCP, whereas the thiazolidine of ALDO, which hydrolyzes to ALDO bypassing OHCP is 7–9 times less toxic without loss of antitumor activity.
Albendazole suppresses cell proliferation and migration and induces apoptosis in human pancreatic cancer cells
Authors: Chen Haifeng , Weng Zhen , Xu Chunfang
Published: February 2020

This study aims to investigate the effects of albendazole on pancreatic cancer cells and to explore the possible mechanisms involved. MTT, colony formation, wound healing and Transwell assays and immunocytochemistry analyses of proliferation antigen Ki-67 were employed to evaluate the role of albendazole in pancreatic cancer cell line proliferation and migration. Moreover, flow cytometry cell apoptosis evaluation was used for mechanism analysis. Finally, the in-vivo effects of albendazole were examined in an in-vivo nude mouse xenograft model. Compared to the control treatment, albendazole significantly decreased the growth of the pancreatic cancer cell lines SW1990 and PANC-1 in a time- and dose-dependent manner, as evidenced by decreased MTT absorbance, colony number and Ki-67 levels. Furthermore, albendazole decreased cell migration in 2- and 3-dimensional models in a dose-dependent manner. In addition, albendazole increased the apoptotic cell ratio in a dose-dependent manner. Finally, the in-vivo results confirmed that albendazole could decrease tumor growth. We demonstrated the inhibitory effects of albendazole on pancreatic cell proliferation and migration in vitro and in vivo, which indicate that albendazole might serve as a novel treatment modality for pancreatic cancer.
Immune checkpoint inhibitors for the management of advanced non–small-cell lung carcinoma: a meta-analysis
Authors: Lai Li-ting , Zhan Zheng-yu , Feng Miao , Li Fan , Lai Lin-feng , Zhong Lu-xing
Published: February 2020

This study is a meta-analysis assessing the safety and efficacy of programmed cell death-1/cell death-ligand 1 (PD-1/PD-L1) inhibitors in order to improve their efficacy in advanced non–small-cell lung cancer. We retrieved studies of anti-PD-1/PD-L1 therapies for non–small-cell lung cancer from electronic databases; 17 clinical trials were analyzed. The pooled hazard ratios for overall and progression-free survival (PFS), and the odds ratios (ORs) for the objective response rate (ORR) and adverse effects were calculated using Review Manager 5.3. The pooled hazard ratios for overall and PFS were 0.69 and 0.74, respectively, and the pooled OR for the ORR was 1.78, implying a significant improvement in overall survival (OS), PFS, and ORR with administration of PD-1/PD-L1 inhibitors. In subgroup analysis, the ORs of the ORR were 2.48 in PD-L1 positive versus negative tumors, and 0.99 for a high dose of PD-1/PD-L1 inhibitors versus a low dose. The ORs for the occurrence of any treatment-related adverse effects and grades 3–5 treatment-related adverse effects were 0.33 and 0.30, respectively, suggesting a good safety profile. PD-1/PD-L1 immunotherapy has superior outcomes in terms of the ORR, OS, and PFS with tolerable adverse effects when compared with chemotherapy.
PERSISTENT REMNANTS OF DEXAMETHASONE INTRAVITREAL IMPLANT (OZURDEX)
Authors: Kim Jee Taek , Lee Seok Hyun , Choi Sang Uk
Published: February 2020

Purpose:

To describe persistent remnants of dexamethasone intravitreal implant (DEX implant) and evaluate the risk factors for remnant persistence in patients who received a DEX implant.

Methods:

This retrospective observational study involved a retrospective chart review of 133 eyes from 129 patients who received DEX implant injection.

Results:

Seventeen eyes of 17 patients (12.78%) exhibited remnant persistence >1 year after DEX implant injection; eight eyes (13.33%) were diagnosed with branching retinal vein occlusion, three eyes (14.28%) were diagnosed with central retinal vein occlusion, and six eyes (35.3%) were diagnosed with diabetic macular edema. The number of intravitreal DEX implant injections and triamcinolone acetonide injections administered to eyes with remnant persistence was significantly higher than that administered to the eyes without remnant persistence (P < 0.001 and P = 0.024, respectively). Remnants caused symptomatic floaters in 11.7% (2/17 eyes) of the patients with remnants and in 1.5% (2/133) of the entire patient cohort.

Conclusion:

DEX implant was not completely dissolved in the eyes that received multiple DEX implant or triamcinolone acetonide injections.
Could Soluble Cluster of Differentiation 163 Be Useful as Prognostic Biomarker in Patients With Complicated Intra-abdominal Infections?
Authors: Dimitrov Evgeni , Halacheva Krasimira , Enchev Emil , Minkov Georgi , Yovtchev Yovcho
Published: February 2020

Introduction

Early prognostic evaluation and timely treatment are crucial for the final outcome in patients with complicated intra-abdominal infections (cIAIs). Over the years, different biomarkers for early prognosis were explored, and yet none has shown ideal characteristics. This review aimed to assess the potential application of soluble cluster of differentiation 163 (sCD163) as outcome predictor in patients with cIAIs.

Methods

We have searched in PubMed database the literature relating the prognostic performance of sCD163 in patients with cIAIs and/or sepsis. Our search terms were soluble CD163, sCD163, intra-abdominal infections, complicated intra-abdominal infections, IAIs, cIAIs, sepsis, prognostic, outcome, and mortality.

Results

A total of 8 studies with 2308 patients met our inclusion criteria. Six studies showed significant prognostic value of sCD163 levels, and 2 showed no association between sCD163 and mortality.

Conclusions

This review found association between sCD163 levels and mortality. We concluded that sCD163 could be a reliable and meaningful mortality predictor in septic patients with cIAIs. Nevertheless, more large prospective studies with surgical patients only are needed before the final evaluation of this biomarker.
The Clinical Impact of 16S Ribosomal RNA Polymerase Chain Reaction Bacterial Sequencing in Infectious Endocarditis
Authors: El-Dalati Sami , Riddell James , Fagan Christopher , Owczarczyk Anna B. , Fukuhara Shinichi , Wasylyshyn Anastasia , Patel Twisha , Cinti Sandro
Published: February 2020

Introduction

Cases of possible and/or culture-negative endocarditis continue to be a diagnostic challenge. Performing bacterial 16S ribosomal RNA polymerase chain reaction (16S rRNA PCR) sequencing on cardiac valves allows providers to acquire microbiologic information that was previously unobtainable. However, few publications address how the polymerase chain reaction (PCR) results impact clinical management in endocarditis patients.

Methods

Between July 1, 2014, and December 31, 2018, we reviewed the results of all 16S rRNA PCR bacterial sequencing tests collected from cardiac valves at the University of Michigan. Each patient's chart was then evaluated by 2 independent infectious diseases physicians to determine whether the medical plans were impacted by the results.

Results

Forty-one patients were identified with associated 16S rRNA PCR testing from 165 explanted cardiac valves. Eighteen samples (43.9%) were positive, and 5 (12.2%) of 41 patients had their management plans changed based on the PCR findings. In 23 (56.1%) of 41 cases, the PCR result was never referenced by any medical provider in the electronic medical record. There were 7 cases (17.1%) where patients received 6 weeks of antibiotics despite presenting with possible culture-negative endocarditis, noninfectious operative findings, and negative valve PCRs, which were not reviewed.

Conclusions

16S rRNA PCR sequencing is a useful tool for obtaining a microbiologic diagnosis in cases of possible or culture-negative endocarditis. The test has potential to impact patient care and in a subset of cases could be used to deescalate antibiotic therapy. However, testing delays and cumbersome resulting methods impede bacterial sequencing from reaching its full potential as a diagnostic modality.
Exotic Pets as a Vector for Leptospirosis
Authors: Lacombe Valentin , Landais Mickaël , Urbanski Geoffrey , Callahan Jean-Christophe
Published: February 2020

Leptospira propagate via urine shedding by carrier animals with chronic renal infestation, particularly rodents. The growing trend of exotic pet ownership may increase the incidence of leptospirosis and lead to a new mode of transmission. We report a case of human leptospirosis whose highly suspected vector was a domestic ferret. Careful questioning did not reveal any recent usual context of leptospirosis transmission in our patient, and the only vector found was his pets, which had been in contact with rodents in previous years. Urinary sampling is technically difficult in ferrets, and the bacterial shedding is intermittent, so the evidence of chronic carriage in exotic pets is rarely reported. To be aware that exotic pets are a potential source of infection is important to suspect this polymorphic disease. The exposure to contaminated water or rodents by the pet, even several years prior, should lead to suspect leptospirosis.
Disseminated Streptococcus pneumoniae Infection Associated With an Intrauterine Device
Authors: Roberts Scott C. , Quinlan Maura P. , Galvin Shannon R.
Published: February 2020

Streptococcus pneumoniae is a common pathogen afflicting a wide variety of disease in both immunocompetent and immunocompromised individuals. Presentation can be variable in initial symptomatology, leading to difficulties in diagnosis and management. We present a case of septic shock due to S. pneumoniae associated with an intrauterine device in an immunocompromised patient.
Apneic Oxygenation for Emergency Intubations in the Pediatric Emergency Department—A Quality Improvement Initiative
Authors: Pek Jen Heng , Tan Hui Cheng , Shen Germac , Ong Yong-Kwang Gene
Published: February 2020

Introduction:

Emergency airway management of critically ill children in the Emergency Department (ED) is associated with the risk of intubation-related desaturation, which can be minimized by apneic oxygenation. We evaluated the use of apneic oxygenation in the pediatric ED and reported a quality improvement initiative to incorporate apneic oxygenation as a routine standard of care during rapid sequence intubations (RSIs).

Methods:

A baseline period from June 2016 to April 2017 highlighted the practice gaps. Quality improvement interventions were subsequently developed and implemented as a care bundle consisting of a pre-intubation checklist, placing reminders and additional oxygen source in resuscitation bays, incorporating into the responsibilities of the airway doctor and the airway nurse (copiloting), education during airway workshops and simulation training for doctors and nurses, as well as enhancing documentation of the intubation process. We monitored a post-intervention observation period from May 2017 to April 2018 for the effectiveness of the care bundle.

Results:

Apneic oxygenation was not performed in all 22 RSIs during the baseline period. Among 25 RSIs in the post-intervention observation period, providers performed apneic oxygenation in 17 (68%) cases. There was no significant difference in the utilization of apneic oxygenation among emergency physicians and pediatric anesthetists performing RSIs in the pediatric ED.

Conclusions:

We successfully implemented a care bundle targeted at incorporating apneic oxygenation as a routine standard of care during emergency intubations performed in ED. This method could be adopted by other pediatric EDs to improve airway management in critically ill children.
Event-related potential correlates of auditory feedback control of vocal production in experienced singers
Authors: Wu Xiuqin , Zhang Baofeng , Wei Lirao , Liu Hanjun , Liu Peng , Wang Wenda
Published: February 2020

Considerable evidence has shown that experienced singers are capable of voluntarily suppressing vocal compensations for consistent pitch perturbations in auditory feedback. Our recent behavioral study found that singers also compensated for brief pitch perturbations to a lesser degree than nonsingers in an involuntary manner. In the present event-related potential study, we investigated the neural correlates of involuntary vocal pitch regulation in experienced singers. All participants were instructed to vocalize the vowel sounds while their voice was unexpectedly shifted in pitch by –50 and –200 cents. The results revealed decreased cortical N1 and P2 responses to pitch perturbations and reduced involuntary vocal compensations for singers when compared to nonsingers. Moreover, larger vocal responses were significantly correlated with smaller cortical P2 responses for nonsingers, whereas this brain–behavior relationship did not exist for singers. These findings demonstrate that the cortical processing of involuntary auditory-motor integration for vocal pitch regulation can be shaped as a function of singing experience, suggesting that experienced singers may be less influenced by auditory feedback and rely more on somatosensory feedback or feedforward control as a consequence of singing training as compared to nonsingers.
Inhibitory CD200-receptor signaling is rewired by type I interferon
Authors: van der Vlist Michiel , Pascoal Ramos M. Inês , van den Hoogen Lucas L. , Hiddingh Sanne , Timmerman Laura , de Hond Titus A.P. , Kaan Ellen D. , van der Kroef Maarten , Lebbink Robert Jan , Peters Florence M.A. , Khoury-Hanold William , Fritsch-Stork Ruth , Radstake Timothy , Meyaard Linde
Published: February 2020

CD200 Receptor 1 (CD200R) is an established inhibitory immune receptor that inhibits TLR-induced cytokine production through Dok2 and RasGAP. RasGAP can be cleaved under certain conditions of mild cellular stress. We found that in the presence of cleaved RasGAP, CD200R loses its capacity to inhibit rpS6 phosphorylation. Furthermore, IFNα pre-stimulation of human mononuclear cells results in increased amounts of cleaved RasGAP. Coherently, upon pretreatment with increasing concentrations of IFNα, CD200R gradually shifts from an inhibitor to a potentiator of TLR7/8-inducedIFNGmRNA production. In peripheral blood mononuclear cells from Systemic Lupus Erythematosus (SLE) patients, a prototypic type I IFN disease, we found an increased proportion of cleaved RasGAP compared to healthy controls. In line with this, in subsets of SLE patients the inhibitory function of CD200R is lost or converted to a potentiating signal forIFNGmRNA production. Thus, our data show that type I IFN rewires CD200R signaling and suggest that this cell-extrinsic regulation of signaling could contribute to perpetuation of inflammation in SLE.
Model-based detection of putative synaptic connections from spike recordings with latency and type constraints
Authors: Ren Naixin , Ito Shinya , Hafizi Hadi , Beggs John M. , Stevenson Ian H.
Published: February 2020

Detecting synaptic connections using large-scale extracellular spike recordings presents a statistical challenge. While previous methods often treat the detection of each putative connection as a separate hypothesis test, here we develop a modeling approach that infers synaptic connections while incorporating circuit properties learned from the whole network. We use an extension of the Generalized Linear Model framework to describe the cross-correlograms between pairs of neurons and separate correlograms into two parts: a slowly varying effect due to background fluctuations and a fast, transient effect due to the synapse. We then use the observations from all putative connections in the recording to estimate two network properties: the presynaptic neuron type (excitatory or inhibitory) and the relationship between synaptic latency and distance between neurons. Constraining the presynaptic neuron’s type, synaptic latencies, and time constants improves synapse detection. In data from simulated networks, this model outperforms two previously developed synapse detection methods, especially on the weak connections. We also apply our model toin vitromultielectrode array recordings from mouse somatosensory cortex. Here our model automatically recovers plausible connections from hundreds of neurons, and the properties of the putative connections are largely consistent with previous research.

New & Noteworthy

Detecting synaptic connections using large-scale extracellular spike recordings is a difficult statistical problem. Here we develop an extension of a Generalized Linear Model that explicitly separates fast synaptic effects and slow background fluctuations in cross-correlograms between pairs of neurons while incorporating circuit properties learned from the whole network. This model outperforms two previously developed synapse detection methods in the simulated networks, and recovers plausible connections from hundreds of neurons inin vitromultielectrode array data.
Pantoea ananatisdefeatsAlliumchemical defenses with a plasmid-borne virulence gene cluster
Authors: Stice Shaun P. , Thao Kyle K. , Khang Chang Hyun , Baltrus David A. , Dutta Bhabesh , Kvitko Brian H.
Published: February 2020

Onion (Allium. cepaL), garlic (A. sativumL.), and other members of theAlliumgenus produce volatile antimicrobial thiosulfinates upon cellular damage. Allicin has been known since the 1950s as the primary antimicrobial thiosulfinate compound and odorant produced by garlic. However, the roles of endogenous thiosulfinate production in host-bacterial pathogen interactions have not been described. The bacterial onion pathogenPantoea ananatis, which lacks both the virulence Type III and Type II Secretion Systems, induces necrotic symptoms and extensive cell death in onion tissues dependent on a proposed secondary metabolite synthesis chromosomal gene cluster. We found strong correlation between the genetic requirements forP. ananatisto colonize necrotized onion tissue and its capacity for tolerance to the thiosulfinate allicin based on the presence of an eleven gene, plasmid-borne, virulence cluster of sulfur/redox genes. We have designated them ‘alt’ genes forallicin tolerance. We show that allicin and onion thiosulfinates restrict bacterial growth with similar kinetics. Thealtgene cluster is sufficient to confer allicin tolerance and protects the glutathione pool during allicin treatment. Independentaltgenes make partial phenotypic contributions indicating that they function as a collective cohort to manage thiol stress. Our work implicates endogenous onion thiosulfinates produced during cellular damage as mediators of interactions with bacteria. TheP. ananatis-onion pathosystem can be modeled as a chemical arms race of pathogen attack, host chemical counter-attack, and pathogen resistance.

Significance Statement

Alliums (e.g. onion and garlic), after sustaining cellular damage, produce potent antimicrobial thiosulfinates that react with cellular thiols. The bacterial onion pathogenPantoea ananatis, which lacks the virulence Type III and Type II Secretion Systems, induces cell death and necrotic symptoms on onions. We have identified a plasmid-borne cluster of sulfur/redox virulence genes that 1) are required forP. ananatisto colonize necrotized onion tissue, 2) are sufficient for tolerance to the thiosulfinates, and, 3) protect the glutathione pool during thiosulfinate treatment. We propose that the thiosulfinate production potential ofAlliumspp. governsAllium-bacterial interaction outcomes and that theP. ananatis-onion pathosystem can be modeled as a chemical arms race of attack and counterattack between the pathogen and host.
Phylogenetic background and habitat drive the genetic diversification ofEscherichia coli
Authors: Touchon Marie , Perrin Amandine , de Sousa Jorge André Moura , Vangchhia Belinda , Burn Samantha , O’Brien Claire L. , Denamur Erick , Gordon David , Rocha Eduardo PC
Published: February 2020

Escherichia coliis a commensal of birds and mammals, including humans. It can act as an opportunistic pathogen and is also found in water and sediments. Since most population studies have focused on clinical isolates, we studied the phylogeny, genetic diversification, and habitat-association of 1,294 isolates representative of the phylogenetic diversity of more than 5,000, mostly non-clinical, isolates originating from humans, poultry, wild animals and water sampled from the Australian continent. These strains represent the species diversity and show large variations in gene repertoires within sequence types. Recent gene transfer is driven by mobile elements and determined by habitat sharing and by phylogroup membership, suggesting that gene flow reinforces the association of certain genetic backgrounds with specific habitats. The phylogroups with smallest genomes had the highest rates of gene repertoire diversification and fewer but more diverse mobile genetic elements, suggesting that smaller genomes are associated with higher, not lower, turnover of genetic information. Many of these small genomes were in freshwater isolates suggesting that some lineages are specifically adapted to this environment. Altogether, these data contribute to explain why epidemiological clones tend to emerge from specific phylogenetic groups in the presence of pervasive horizontal gene transfer across the species.