bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of High-Performance Liquid Chromatographic and Thin-Layer Chromatographic Methods for Determination of Aloin in Herbal Products Containing Aloe vera
Authors: Durón Rosalba Ramírez , Almaguer Luca Ceniceros , Rocha Norma Cecilia Cavazos , Flores Perla Giovanna Silva , Torres Noem Waksman De
Published: July 2020

Aloe vera is a medicinal plant used worldwide to treat a variety of conditions and, as such, has important commercial value. Aloin is a principal component of aloe vera leaves and is used for quality control of products containing it. A semiquantitative thin-layer chromatographic (TLC) method for determining the concentration of aloin in aloe-based products was validated. The results were similar to those of a validated high-performance liquid chromatographic method; therefore, TLC, which is a simple, sensitive, specific, rapid, and cheap method, may be ideal for use in any laboratory for routine analysis of commercial products containing aloe vera.
Aflatoxin Testing in Peanuts: A Proficiency Assessment Scheme for Chinese Analytic Laboratories
Authors: Bao Lei , Bao Zhenmin , Zhang Yibing , Liang Chengzhu , Lu Ning , Liu Xintong , Jin Ying , Ze Pei Jun , Ge Manli , Tian Ling
Published: July 2020

This national assessment program was established by the China National Accreditation Service for Conformity Assessment (CNAS) to evaluate the aflatoxin-testing proficiency of a cross-section of Chinese laboratories. The Shan Dong Inspection and Quarantine Bureau of China conducted the assessment according to ISO 13528:2005 (E) and the International Harmonized Protocol for Proficiency Testing. The 77 laboratories that participated in the study had either been previously accredited by CNAS or were candidates for CNAS accreditation. The analytic samples for this testing scheme were prepared from naturally contaminated peanuts and diluted to approximately 10 g/kg for aflatoxin B1 and 18 g/kg for total aflatoxins. The Ss/p test (with a required result of Ss 0.3p) was used to evaluate the homogeneity of the test samples; sample stability was confirmed with a t-test. The performance of each laboratory was designated by a z-score that was calculated using robust statistics. The robust mean of the participants' results in this study was nearly coincident with the median. A modified Horwitz equation was used to determine the standard deviation. The study compared analytic results obtained by 5 different methods: high-performance liquid chromatography (LC), enzyme-linked immunosorbent assay, thin-layer chromatography, fluorometry, and LC with tandem mass spectrometry. A satisfactory performance rating required z-scores between 2 and 2 for the target analytes. Of the 73 laboratories that reported results for aflatoxin B1, 66 (90.4) performed satisfactorily. Of 32 laboratories that reported total aflatoxins (B1 B2 G1 G2), 30 (93.8) performed satisfactorily. Laboratories whose performance ratings were questionable or unsatisfactory were re-evaluated in a second interlaboratory comparison.
Single-Laboratory Validation of a High-Performance Liquid Chromatographic-Diode Array Detector-Fluorescence Detector/Mass Spectrometric Method for Simultaneous Determination of Water-Soluble Vitamins in Multivitamin Dietary Tablets
Authors: Chen Pei , Atkinson Renata , Wolf Wayne R
Published: July 2020

The purpose of this study was to develop a single-laboratory validated (SLV) method using high-performance liquid chromatography with different detectors diode array detector (DAD); fluorescence detector (FLD); and mass spectrometry (MS) for determination of 7 B-complex vitamins (B1-thiamin, B2-riboflavin, B3-nicotinamide, B6-pyridoxine, B9-folic acid, pantothenic acid, and biotin) and vitamin C in multivitamin/multimineral dietary supplements. The method involves the use of a reversed-phase octadecylsilyl column (4 m, 250 2.0 mm id) and a gradient mobile phase profile. Gradient elution was performed at a flow rate of 0.25 mL/min. After a 5 min isocratic elution at 100 A (0.1 formic acid in water), a linear gradient to 50 A and 50 B (0.1 formic acid in acetonitrile) at 15 min was employed. Detection was performed with a DAD as well as either an FLD or a triple-quadrupole MS detector in the multiple reaction monitoring mode. SLV was performed using Standard Reference Material (SRM) 3280 Multivitamin/Multimineral Tablets, being developed by the National Institute of Standards and Technology, with support by the Office of Dietary Supplements of the National Institutes of Health. Phosphate buffer (10 mM, pH 2.0) extracts of the NIST SRM 3280 were analyzed by the liquid chromatographic (LC)-DAD-FLD/MS method. Following extraction, the method does not require any sample cleanup/preconcentration steps except centrifugation and filtration.
Dipstick Format of an Improved ELISA for On-Site Atrazine Monitoring in Water in Pakistan
Authors: Maqbool Uzma , Anwar-ul-Haq  , Mahboob Sadia
Published: July 2020

A dipstick format was developed for on-site atrazine monitoring in water samples of different origins. It was derived from an in-house-developed ELISA based on polyclonal antibodies that also cross-react with hydroxyatrazine (30%) and terbuthylazine (17%). Test reagents were evaluated for temperature and pH stabilities and rapidity for field applications. Reagents performed well within a temperature range of 20-30°C and were tolerant to alkaline pH (up to 8.5) of the assay buffering system. Tracer incubation time could be reduced to 40 min. Bovine serum albumin addition (1%) in the assay buffer improved assay performance, giving 50% B/B0 (IC50) of 65 ng/L and the lowest LOD of 2 ng/L at 90 B/B0 (IC10). The dipstick ELISA format was standardized on a membrane support. Nylon membrane, positively charged, was superior to PVDF for qualitative or semiquantitative analysis regarding color intensity and stability. Tracer incubation time was further reduced to 30 min with a lowest LOD of 0.1 µg/L. For real sample screening with dipsticks, acceptable results were obtained for water. Significant correlation was found between dipstick and plate ELISA results. Validation using GC with a nitrogen-phosphorus detector and HPLC indicated that dipstick signals in aged water samples, which were mainly due to hydroxyatrazine, were significantly above European Commission regulations of 0.1 µg/L. However, dipsticks were superior, fast, and cost-effective.
Use of Alternative Carrier Materials in AOAC Official MethodSM 2008.05, Efficacy of Liquid Sporicides Against Spores of Bacillus subtilis on a Hard, Nonporous Surface, Quantitative Three-Step Method
Authors: Tomasino Stephen F , Rastogi Vipin K , Wallace Lalena , Smith Lisa S , Hamilton Martin A , Pines Rebecca M
Published: July 2020

The quantitative Three-Step Method (TSM) for testing the efficacy of liquid sporicides against spores of Bacillus subtilis on a hard, nonporous surface (glass) was adopted as AOAC Official MethodSM 2008.05 in May 2008. The TSM uses 5 5 1 mm coupons (carriers) upon which spores have been inoculated and which are introduced into liquid sporicidal agent contained in a microcentrifuge tube. Following exposure of inoculated carriers and neutralization, spores are removed from carriers in three fractions (gentle washing, fraction A; sonication, fraction B; and gentle agitation, fraction C). Liquid from each fraction is serially diluted and plated on a recovery medium for spore enumeration. The counts are summed over the three fractions to provide the density (viable spores per carrier), which is log10-transformed to arrive at the log density. The log reduction is calculated by subtracting the mean log density for treated carriers from the mean log density for control carriers. This paper presents a single-laboratory investigation conducted to evaluate the applicability of using two porous carrier materials (ceramic tile and untreated pine wood) and one alternative nonporous material (stainless steel). Glass carriers were included in the study as the reference material. Inoculated carriers were evaluated against three commercially available liquid sporicides (sodium hypochlorite, a combination of peracetic acid and hydrogen peroxide, and glutaraldehyde), each at two levels of presumed efficacy (medium and high) to provide data for assessing the responsiveness of the TSM. Three coupons of each material were evaluated across three replications at each level; three replications of a control were required. Even though all carriers were inoculated with approximately the same number of spores, the observed counts of recovered spores were consistently higher for the nonporous carriers. For control carriers, the mean log densities for the four materials ranged from 6.63 for wood to 7.14 for steel. The pairwise differences between mean log densities, except for glass minus steel, were statistically significant (P < 0.001). The repeatability standard deviations (Sr) for the mean control log density per test were similar for the four materials, ranging from 0.08 for wood to 0.13 for tile. Spore recovery from the carrier materials ranged from approximately 20 to 70: 20 (pine wood), 40 (ceramic tile), 55 (glass), and 70 (steel). Although the percent spore recovery from pine wood was significantly lower than that from other materials, the performance data indicate that the TSM provides a repeatable and responsive test for determining the efficacy of liquid sporicides on both porous and nonporous materials.
High-Performance Liquid Chromatographic and First Derivative of the Ratio Spectrophotometric Determination of Amlodipine and Valsartan in Their Binary Mixtures
Authors: Kul Dilek , Dogan-Topal Burcu , Kutucu Tugba , Uslu Bengi , Ozkan Sibel A
Published: July 2020

Amlodipine besylate (AML) is a long-acting calcium channel blocker used as an antihypertensive agent. Valsartan (VAL) is also used to treat hypertension, either alone or in combination with other agents. Two-component mixtures of AML and VAL were analyzed by HPLC and the ratio spectra of the first derivative spectrophotometric technique. The spectrophotometric method depends on the first derivative of the ratio-spectra by measurements of the amplitudes at 234.0 nm for VAL and 351.0 nm for AML. Calibration graphs were established for 0.520 g/mL AML and 132 g/mL VAL using the ratio spectra of the first derivative spectrophotometric method. In the HPLC method, an ACE 5 C18 (4.6 150 mm, 5 m) RP column at 30C with the mobile phase methanolacetonitrileNaH2PO4H2O buffer, including 5 mL/L triethylamine and adjusted to pH 3.0 (42 + 18 + 40, v/v/v) at 2.0 mL/min flow rate was used to separate both compounds with detection at 254.0 nm. Linearity was obtained in the concentration range of 0.5500 g/mL for AML and 5.0900 g/mL for VAL. The proposed methods have been extensively validated. These methods allow a number of cost- and time-saving benefits. They were successfully applied to the determination of AML and VAL in synthetic mixtures and in a pharmaceutical dosage form. There was no significant difference between the performance of the proposed methods regarding the mean and SD values. The proposed methods are simple, rapid, and suitable for QC applications.
Development and Validation of an HPTLC Method for Simultaneous Quantitation of Isoorientin, Isovitexin, Orientin, and Vitexin in Bamboo-Leaf Flavonoids
Authors: Wang Jin , Tang Feng , Yue Yongde , Guo Xuefeng , Yao Xi
Published: July 2020

A simple HPTLC method has been developed for the simultaneous determination of isoorientin, isovitexin, orientin, and vitexin, both pure and in commercial samples of bamboo-leaf flavonoids. The flavone C-glycosides, including isoorientin, isovitexin, orientin, and vitexin, were extracted from bamboo-leaf flavonoids with methanol and chromatographed on silica gel 60 plates in an automatic developing chamber with tetrahydrofurantolueneformic acidwater (16 8 2 1, v/v/v/v) mobile phase. Quantitation was obtained with UV detection at 350 nm. Polynomial calibration plots were constructed in the concentration range 2001200 ng/zone for isoorientin, 100600 ng/zone for isovitexin, 160960 ng/zone for orientin, and 30360 ng/zone for vitexin with good correlation coefficients (r ≥ 0.9995). The method was validated for precision (interday and intraday), repeatability, and accuracy. Accuracy of the method was evaluated by a recovery study conducted at three different levels, and the average recovery was found to be 93.95% for isoorientin, 95.30% for isovitexin, 99.79% for orientin, and 100.46% for vitexin. The proposed HPTLC method for estimation of isoorientin, isovitexin, orientin, and vitexin was found to be simple, precise, specific, and accurate and can be used for manufacturing QC of bamboo-leaf flavonoids or for governmental regulatory purposes.
Probability of Detection (POD) as a Statistical Model for the Validation of Qualitative Methods
Authors: Wehling Paul , LaBudde Robert A , Brunelle Sharon L , Nelson Maria T
Published: July 2020

A statistical model is presented for use in validation of qualitative methods. This model, termed Probability of Detection (POD), harmonizes the statistical concepts and parameters between quantitative and qualitative method validation. POD characterizes method response with respect to concentration as a continuous variable. The POD model provides a tool for graphical representation of response curves for qualitative methods. In addition, the model allows comparisons between candidate and reference methods, and provides calculations of repeatability, reproducibility, and laboratory effects from collaborative study data. Single laboratory study and collaborative study examples are given.
Solid-Phase Extraction and Atomic Absorption Spectrometric Determination of Cobalt Using an Octadecyl Bonded Silica Membrane Disk Modified with Cyanex 272
Authors: Karve Manjusha , Gholave Jayram V
Published: July 2020

A simple SPE method for determination of cobalt(II) using a C18 bonded silica membrane disk impregnated with Cyanex 272 has been developed. Cobalt(II) was quantitatively sorbed at pH 6.0 from a sample solution and eluted using 10.0 mL 1.0 M HNO3 prior to its flame atomic absorption spectrometric determination. The influence of eluting agents, the minimum volume and maximum flow rate of the eluent, and interfering ions on cobalt(II) was studied. The method developed for cobalt(II) had an LOD of 1.4 g/L, and a preconcentration factor >200 with an RSD of 0.6. The reusability of the modified disk was for 40 cycles. The method was applied for the determination of cobalt in certified samples, urine, and industrial sludge samples.
PSV-14 Effects of Cordyceps mushroom powder on nursery pig performance
Authors: Richert Jacob A , Palencia Jorge Y P , Chastain Clayton S , Thayer Morgan T , Richert Brian T , Nelssen Jim L
Published: July 2020

The objective of this study was to determine the optimal level of Cordyceps mushroom powder inclusion in diets for nursery pigs. One-hundred sixty crossbred pigs [(Duroc × (York × Landrace)] weaned at 18.8 d of age and weighing an average of 5.94 kg were used in a 35 day, 4 phase growth trial to evaluate Cordyceps mushroom powder as potential alternative to carbadox in nursery pig diets. Pigs were allotted by weight, sex, litter, and assigned to body weight (BW) blocks. Within BW blocks, sex ratios were constant in each pen. Each pen within a BW block was randomly assigned a dietary treatment. Growth performance was analyzed as a RCB design using BW, ADG, ADFI, G:F using GLM procedure of SAS 9.4. There were 5 or 6 pigs/pen and 6 pens/treatment. Five diets were used in the study: a negative diet or a positive control (Carbadox, 55 ppm); 300 or 600 ppm mushroom powder, and a step down treatment (900, 900, 450, 300, 150 ppm mushroom powder during weeks 1 through 5, respectively). At various points of the study, pigs fed the 300 ppm and the step-down mushroom powder treatments tended to have improved (P < 0.10) growth performance compared with those fed the negative control diet. During Phase 4 of the study, pigs fed Carbadox had greater ADG (P < 0.02) and improved feed efficiency (P < 0.09) compared to pigs fed the negative control diet. However, overall data showed that there were no statistical differences among treatments (P > 0.05). In summary, pigs fed 300 ppm mushroom powder or the step-down treatment showed comparable growth performance to pigs fed Carbadox. However, future research is needed under a greater disease challenge to examine mushroom powder’s full potential as an alternative to antibiotics.
Long non-coding RNA PHACTR2-AS1 promotes tongue squamous cell carcinoma metastasis by regulating Snail
Authors: Yuan Fenqian , Miao Zhiguo , Chen Wen , Wu Fanggeng , Wei Chao , Yong Jingkang , Xiao Can
Published: July 2020

Long non-coding RNA is an endogenous non-coding RNA that has currently been proved to be an important player in cancer cell biology. In the present study, we investigated the biological role of PHACTR2-AS1 in tongue squamous cell carcinoma (TSCC). PHACTR2-AS1 was preferentially localized in the cytoplasm, and was notably upregulated in TSCC tissues. High PHACTR2-AS1 was correlated with tumour differentiation, metastatic clinical features, relapse and shortened survival time. Depletion of PHACTR2-AS1 did not affect TSCC cell viability and colony formation ability, whereas substantially inhibited cell migration and invasion in vitro and lung metastasis in vivo. Mechanistically, PHACTR2-AS1 could sponge miR-137 to increase Snail expression, resulting in triggering epithelial–mesenchymal transition process, thereby promoting TSCC cell metastasis. Taken together, our data for the first time elucidate the metastasis-promoting role of PHACTR2-AS1 in TSCC, hinting a new therapeutic target for metastatic TSCC patients.
Risk Assessment of Deep Venous Thrombosis and Its Influencing Factors in Burn Patients
Authors: Peng Huan , Yue Liqing , Gao Hongmei , Zheng Ruolan , Liang Penghui , Wang Ang , He Ailan
Published: July 2020

The objective of this study is to explore the relevant risk factors of deep venous thrombosis (DVT) in burn patients. A retrospective analysis was conducted for the medical records of 845 hospitalized burn patients from September 2012 to August 2017. Caprini thrombosis risk assessment scale (CTRAS) was employed for evaluating the risks of DVT. Based upon whether or not DVT occurred, they were divided into non-DVT group (n = 830) and DVT group (n = 15). Among 360 (42.7%) patients with high-risk Caprini scores, only 30 patients received color Doppler examination of lower limb veins, and 15 patients were diagnosed as DVT with a diagnostic rate of 1.8%. Caprini scores of non-DVT and DVT groups were 4.30 ± 2.71 and 9.87 ± 1.46 points, respectively. There was statistically significant difference (P < .05). As revealed by stepwise Logistic regression analysis, age, lower limb burn, wound infection, femoral vein catheterization, and long bedriddening time (>40 days) were independent risk factors for DVT. Burn patients are particularly prone to develop DVT. Age, wound infection, femoral vein catheterization, and long bedriddening time (>40 days) are risk factors. Aggressive preventive measures of DVT should be implemented.
Structure of accretion flows in the nova-like cataclysmic variable RW Tri
Authors: Subebekova G , Zharikov S , Tovmassian G , Neustroev V , Wolf M , Hernandez M-S , Kučáková H , Khokhlov S
Published: July 2020

We obtained photometric observations of the nova-like (NL) cataclysmic variable RW Tri and gathered all available AAVSO and other data from the literature. We determined the system parameters and found their uncertainties using the code developed by us to model the light curves of binary systems. New time-resolved optical spectroscopic observations of RW Tri were also obtained to study the properties of emission features produced by the system. The usual interpretation of the single-peaked emission lines in NL systems is related to the bi-conical wind from the accretion disc’s inner part. However, we found that the Hα emission profile is comprised of two components with different widths. We argue that the narrow component originates from the irradiated surface of the secondary, while the broader component’s source is an extended, low-velocity region in the outskirts of the accretion disc, located opposite to the collision point of the accretion stream and the disc. It appears to be a common feature for long-period NL systems – a point we discuss.
Measuring the eccentricity of GW170817 and GW190425
Authors: Lenon Amber K , Nitz Alexander H , Brown Duncan A
Published: July 2020

Two binary neutron star mergers, GW170817 and GW190425, have been detected by Advanced LIGO and Virgo. These signals were detected by matched-filter searches that assume that the star’s orbit has circularized by the time their gravitational-wave emission is observable. This suggests that their eccentricity is low, but full parameter estimation of their eccentricity has not yet been performed. We use gravitational-wave observations to measure the eccentricity of GW170817 and GW190425. We find that the eccentricity at a gravitational-wave frequency of 10 Hz is e ≤ 0.024 and e ≤ 0.048 for GW170817 and GW190425, respectively (90 per cent confidence). This is consistent with the binaries being formed in the field, as such systems are expected to have circularized to e ≤ 10−4 by the time they reach the LIGO–Virgo band. Our constraint is a factor of 2 smaller that an estimate based on GW170817 being detected by searches that neglect eccentricity. However, we caution that we find significant prior dependence in our limits, suggesting that there is limited information in the signals. We note that other techniques used to constrain binary neutron star eccentricity without full parameter estimation may miss degeneracies in the waveform, and that for future signals, it will be important to perform full parameter estimation with accurate waveform templates.
Disequilibrium of Plasma Protease/Anti-Protease Due to Severe Periodontal Disease Contributes to Human Subarachnoid Hemorrhage
Authors: Yoshioka Shotaro , Miyamoto Takeshi , Satomi Junichiro , Tada Yoshiteru , Yagi Kenji , Shimada Kenji , Naruishi Koji , Shikata Eiji , Yamaguchi Izumi , Yamaguchi Tadashi , Korai Masaaki , Okayama Yoshihiro , Harada Masafumi , Kitazato Keiko T , Kanematsu Yasuhisa , Nagahiro Shinji , Takagi Yasushi
Published: July 2020

BACKGROUND

The pathophysiology of subarachnoid hemorrhages (SAHs) due to ruptured intracranial aneurysms (IAs) remains unclear. Although a relationship between SAHs and periodontal disease (PD) has been suggested, the mechanism requires clarification.

OBJECTIVE

To evaluate the relationship between PD and SAHs and to identify periodontal pathogens associated with SAHs.

METHODS

This prospective study included consecutive patients with ruptured (n = 11) and unruptured (n = 14) IAs and healthy controls (n = 8). The plasma and plaque subgingival bacterial deoxyribonucleic acid (DNA) levels in PD were evaluated by a dentist using the Community Periodontal Index of Treatment Needs (CPITN). Plasma levels of matrix metalloproteinase (MMP-9), tissue inhibitors of matrix metalloproteinase (TIMP2), and procollagen I were analyzed.

RESULTS

Patients with ruptured IAs, had significantly higher CPITN scores than the controls, suggesting that ruptured IAs were associated with severe PD. Although no rupture-specific bacteria were identified, the positive rate of plaque subgingival bacterial DNA was significantly higher in patients with severe PD than in those without severe PD. Multivariate logistic regression analysis indicated that bleeding on probing (BOP) was associated with ruptured IAs (odds ratio, 1.10; 95% confidence interval 1.04–1.20; P = .0001). BOP was positively associated with plasma MMP-9 levels and a disequilibrium in the MMP-9/TIMP2 ratio. BOP was negatively correlated with plasma procollagen I levels (P < .05, for each). This suggested that local inflammation with severe PD might have systemic effects and lead to ruptured IAs.

CONCLUSION

Disequilibrium of plasma protease/anti-protease associated with a high BOP rate in severe PD may be attributable to IA rupture.
Positive Impact of a Point-of-Care Molecular Influenza Test in the Emergency Department During the 2017–2018 Seasonal Influenza Epidemic
Authors: Martinot Martin , Greigert Valentin , Gravier Simon , Klein Stephane , Eyriey Magali , Pachart Anne , Kaiser Jean-Daniel , Zadeh Mahsa Mohseni , De Briel Dominique , Gottwalles Yannick , Thibaud Eric
Published: July 2020

During the 2017–2018 flu epidemic, the point-of-care Alere-i (n = 72) and reverse transcription polymerase chain reaction (n = 106) tests were compared. Patients in the point-of-care group were administered oseltamivir significantly more rapidly (9 hours vs 23 hours), they spent less time in the emergency department, and they had lower rates of antibiotic administration and hospitalization.
1413. Surveillance of Variant Creutzfeldt Jakob Disease, Based on the Non-confirmatory Diagnostic Criteria of the EU Case Definition, Greece, 2014–2018
Authors: Dougas Georgios , Mellou Kassiani , Mitrou Konstantinos , Kontopidou Flora , Georgakopoulou Theano , Tsiodras Sotirios
Published: July 2020

Background

Variant Creutzfeldt–Jakob disease (vCJD), is a form of CJD associated with consumption of tissues from cattle infected with bovine spongiform encephalopathy. Confirmation requires cerebral histopathologic examination, ascertaining spongiform change and extensive prion protein deposition with florid plaques. In Greece, the disease has been included in the Mandatory Notification System since 2004 however no reference laboratory has been available since 2009 due to low global occurrence. In 2014, the surveillance system was strengthened to also include possible and probable cases based on the non-confirmatory diagnostic criteria of the EU case definition. Hereby we present the results of the surveillance for 2014–2018.

Methods

A new reporting form for CJD was introduced at the national level, including fields aligned with EU case definition criteria for vCJD (preconditions, clinical, diagnostic, and epidemiological). The non-confirmatory diagnostic criteria for the classification of probable and possible vCJD cases were based on examinations routinely available at hospitals, namely EEG and cerebral MRI. Reported CJD cases were assessed according to the fulfillment of required combinations of EU criteria for possible, probable, and confirmed vCJD cases.

Results

From 2014 to 2018, 37 CJD cases were reported, with a median age of 67 years (IQR: 58–73) concerning mostly females (71.3%, 95% CI: 56.7–85.9%). Among the reported cases, 6 (16.2%) fulfilled only the preconditions, 8 (21.6%) fulfilled the preconditions and the clinical criteria, 21 (56.8%) had a compatible EEG, and 7 (18.9%) had a compatible MRI brain scan. Confirmatory examination was not performed to any of the CJD cases; however, no case was classified as possible or probable vCJD based on the EU case definition.

Conclusion

Notification of CJD patients from 2014 to 2018 in Greece, yielded no vCJD cases. The possible re-emergence of vCJD renders continuous surveillance of the disease imperative. Current EU case definition can support the surveillance of vCJD, by screening CJD patients for possible and probable vCJD cases with the utilization of conventional diagnostic examinations, available in most hospitals.

Disclosures

All authors: No reported disclosures.
1760. Outcomes of Acyclovir-Resistant Herpes Simplex Virus Infections in Hematologic Malignancies and Hematopoietic Cell Transplant
Authors: Ross Justine Abella , Dickter Jana , Tegtmeier Bernard , Dadwal Sanjeet
Published: July 2020

Background

Acyclovir-resistant (ACVr) herpes simplex virus (HSV) infection management is a challenge in patients with hematologic malignancies (HM) and hematopoietic cell transplant (HCT) recipients.

Methods

Retrospective review of patients aged ≥ 18 years with underlying HM and/or HCT and culture-positive ACVr HSV between 1/1/2009 and December 1/2017 at a tertiary cancer center. Clinical, laboratory, microbiological, and treatment data collected.

Results

33 patients identified; 25 (76%) acute leukemias, 3 (9%) chronic myeloid leukemia/chronic lymphocytic leukemia (CML/CLL), 3 (9%) lymphoma, 2 (6%) other HM, and 32 (97%) had HCT. Median age of patients was 59 years (25–73) and 64% of them are females. HCT type: 22 (67%) matched unrelated donor, 3 (9%) cord blood, and 7 (21%) matched related donor. All patients were on acyclovir prophylaxis prior to diagnosis. The median time to onset of ACVr HSV infection was 147 days after transplant. Infection site: 16 (49%) oral, 10 (30%), ano-genital, 5 (15%) oral and esophagus/lung, 2 (6%) esophagus/lung. Pertinent laboratory data on day of viral culture (median/range): white blood cell (WBC) 4.6 cells/µL (0.1–85.9), absolute neutrophil count (ANC) 2,316 cells/µL (0–17,000), absolute lymphocyte count (ALC) 574.5 cells/µL (0–84,182). Serum creatinine at start and end of treatment are 0.8 mg/dL (0.32–1.98) and 0.92 mg/dL (0.36–2.7), respectively. The median duration of treatment was 30 days (4–116). Treatment: 20 (61%) foscarnet, 2 (6%) cidofovir, 4 (12%) foscarnet and cidofovir, 1 (3%) valacyclovir, 5 (15%) high-dose acyclovir, 1 (3%) unknown. 8 (24%) received adjunctive topical therapy: 5 imiquimod, 3 cidofovir. 31 included in outcome analysis (data missing in 2). Infection resolved in 15/31 (48%) while 5/31 (16%) had persistent infection. Median ANC and ALC in those with resolved vs. persistent infection (respectively): 3,082 cells/µL and 642 cells/µL vs. 1,895 cells/µL and 380 cells/µL with a trend toward lower ANC and ALC in patients with persistent infection. Overall mortality was 35% (9/31) while ACVr HSV attributable mortality was 6.4% (2/31).

Conclusion

ACVr HSV is predominantly encountered in allogeneic HCT, particularly the unrelated donor recipients, and lower ANC/ALC may predispose to persistent infection.

Disclosures

All authors: No reported disclosures.
2258. Correlation of Electroencephalogram Findings and Dose Relative to Renal Function among Patients with Possible Cefepime-Induced Encephalopathy
Authors: Pettit Natasha N , Pisano Jennifer , Alshaikh Jumana T , Rangarajan Aditi , Issa Naoum
Published: July 2020

Background

Cefepime-induced encephalopathy (CIE) is thought to be a rare toxicity, with an overall incidence of <1%. However, the low incidence may be a result of under-recognition and difficulty in identifying the exact etiology of encephalopathy in hospitalized patients. Among patients with suspected CIE, electroencephalograms (EEGs) sometimes show abnormal activity like triphasic waveforms (TPWs). We asked whether the incidence of EEG findings consistent with CIE varies with cefepime (CFP) dose relative to eGFR (dose/eGFR). We also compared the incidence of these EEG findings in patients receiving CFP to the incidence in patients receiving piperacillin–tazobactam (PT).

Methods

In a retrospective analysis, data between 8/1/2016 and 5/24/2018 were extracted from the University of Chicago Clinical Data Warehouse. Patients 20–79 years old who received PT or CFP were included; those requiring renal replacement therapy or who had eGFR <10 mL/minute/BSA at baseline were excluded. The average daily dose of PT or CFP was calculated to determine dose/eGFR. Linear or logistic regressions were performed in STATA.

Results

EEGs were obtained in 66 (4.3%) of 1525 patients receiving CFP and in 28 (3.3%) of 842 receiving PT. TPWs were present in 19 (28%) of EEGs from the CFP group, and in none of the EEGs from the PT group. Figure 1 shows the correlation between CFP dose/eGFR ratio and occurrence/severity of TPWs. Ordered logistic regression analysis identified a coefficient of 20.9 (95% CI; 3.7–38.2). Figure 2 shows only a weak association between CFP dose/eGFR and background frequency (BFS; R2 = 0.05). In the PT group, BFS was not correlated with PT dose/eGFR (R2 = 0.01).

Conclusion

TPWs were more likely to be found in patients receiving CFP than PT, suggesting that in the absence of other metabolic abnormalities, TPWs might be specific for CFP. Higher CFP dose-to-eGFR ratios predispose to and potentially worsen the severity of TPWs. Unlike TPWs, BFS was only weakly associated with CFP dose/eGFR and even less associated with PT dose/eGFR ratio.

Disclosures

All authors: No reported disclosures.
648. Baloxavir Resistance: qPCR Detection of Antiviral Resistance Markers in Influenza A Virus
Authors: Tyler Aaron J , Grantham James , Diaz Manisha , Miralles Mauricio , Bartlett Katelyn , Foland Derek , Berg Amy , Howard Karen , Nelsen Donald J , Westergaard Jordyn , Wissel Mark , Kleiboeker Steve , Altrich Michelle
Published: July 2020

Background

Influenza (flu) infections affect a large subset of the population every year and have significant impacts on the health of patients, especially those with weak or compromised immune systems such as the elderly, children, cancer patients, and transplant recipients. Baloxavir marboxil was approved in October 2018 as a novel antiviral therapeutic for treating flu. During clinical trials, mutations were identified at the I28 codon of the polymerase acidic (PA) protein that greatly increased the resistance of a flu strain to this novel drug. In this study, a qPCR was developed and validated to identify these resistance mutations, allowing for guided therapy based on the resistance profile of the strain.

Methods

Flu A sequences (6,175) of the PA gene from the NCBI Influenza Virus Database collected over the last 5 years were compiled and aligned. Primers and probes were designed to target the I38 codon of the PA gene, and specific probes for each codon yielding a resistant amino acid mutation (I38T, -M, and -F) were designed. Locked nucleic acid (LNA) bases were used to increase the specificity of the probes. A combination of clinical flu specimens, laboratory strains, and synthetic constructs of each potential resistance mutation were used to validate the precision, sensitivity, and accuracy of the assay in nasopharyngeal swabs.

Results

Precision of the cycle threshold (Ct) values for each detector was determined to have a standard deviation of less than 3 for inter-assay and less than 2 for intra-assay replicates. Sensitivity was determined to be 800 copies/mL in nasopharyngeal swabs. Accuracy was found to be 92.3%. A single laboratory strain from the H1N1 2009 epidemic showed cross-reactivity with both wild-type and resistant probes, but no circulating clinical H1N1 samples tested showed this response.

Conclusion

The precision, sensitivity, and accuracy of a qPCR for resistance mutations to baloxavir marboxil support this assay’s utility as an aid in the treatment of flu in at-risk patient groups. This assay allows for rapid detection (<24 hours) of resistance markers to aid clinicians in improving flu case outcomes.

Disclosures

All authors: No reported disclosures.
665. In vitro Activity of Omadacycline Against Recent (2018) Bacterial Pathogens from the United States and Europe Obtained from Skin and Skin Structure, Respiratory, and Urinary Tract Infections
Authors: Huband Michael D , Pfaller Michael A , Streit Jennifer M , Sader Helio S , Flamm Robert K
Published: July 2020

Background

Omadacycline (OMC) was FDA approved to treat acute bacterial skin and skin structure infection (ABSSSI) and community-acquired bacterial pneumonia (CABP) for indicated organisms in 2018. Phase 2 OMC clinical trials for uncomplicated urinary tract infection (uUTI; NCT03425396) and acute pyelonephritis (NCT03757234) are ongoing. OMC is active against bacterial isolates expressing common tetracycline, penicillin, fluoroquinolone, and macrolide resistance mechanisms.

Methods

Isolates (14,000) were collected in 2018 from 31 medical centers located in the United States and 38 medical centers in Europe, including 3,458 staphylococci, 1,551 streptococci, 746 enterococci, 574 Haemophilus spp., and 5,690 Enterobacterales isolates. One isolate per patient infection episode was tested. Identifications were confirmed by MALDI-TOF MS and susceptibility testing was performed using CLSI broth microdilution methods.

Results

OMC (MIC50/90, 0.12/0.25 mg/L) was highly active against S. aureus isolates from skin and skin structure infection (SSSI; 99.3% susceptible [S]) including MRSA (97.7%S) and MSSA (99.9%S) (table). Similarly, OMC demonstrated potent activity against S. aureus isolates from respiratory tract infection (RTI; MIC50/90, 0.12/0.25 mg/L) including MSSA (98.2%S). All S. lugdunensis isolates from SSSI were S (100.0%) to OMC. All Streptococcus anginosus group (100.0%) and 97.6% of S. pyogenes isolates from SSSI were S to OMC as were 98.0% of S. pneumoniae from RTI. No streptococci were resistant (R) to OMC. OMC (MIC50/90 0.12/0.25 mg/L) had potent activity against E. faecalis isolates from SSSI (99.0%S). OMC S against E. cloacae and K. pneumoniae isolates from SSSI was 92.1% S and 89.4% S, respectively. Similarly, 86.2% of K. pneumoniae isolates from RTI were S to OMC. Susceptibility of H. influenzae isolates from RTI to OMC was 99.8%S (no isolates were R). ≥90.0% of E. coli (MIC50/90, 1/2 mg/L) and K. pneumoniae (MIC50/90, 2/4 mg/L) UTI isolates were inhibited by ≤4 mg/L of OMC.

Conclusion

OMC was highly active against bacterial pathogens associated with ABSSSI, CABP, and UTI including staphylococci (97.7%-100.0%S), streptococci (97.6%-100.0%S), E. faecalis (99.0%S). E. cloacae (92.1%S), K. pneumoniae (86.2%-89.4%S), and E. coli.

Disclosures

All authors: No reported disclosures.
666. Efficacy and Safety of Cefiderocol According to Renal Impairment in Patients With Complicated Urinary Tract Infection (cUTI) in a Phase 2 Study
Authors: Portsmouth Simon , Echols Roger , Machida Mitsuaki , Camilo Arjona Ferreira Juan , Ariyasu Mari , Den Nagata Tsutae
Published: July 2020

Background

Cefiderocol, a novel siderophore cephalosporin with broad activity against Gram-negative bacteria, requires dose adjustment in patients with renal impairment or augmented renal clearance, similarly to other β-lactams. The efficacy and safety of cefiderocol were assessed according to degree of renal impairment as part of a pivotal study vs. imipenem–cilastatin (IPM/CS) in patients with cUTI (NCT02321800).

Methods

A total of 448 randomized adults with cUTI received cefiderocol (2 g) or IPM/CS (1 g / 1 g), IV, q8h, for 7–14 days (safety population), with 371 patients in the microbiological intent-to-treat (Micro-ITT) population. Dose adjustments were made based on body weight (to enable IPM/CS blinding) and creatinine clearance (CrCL). The composite (clinical and microbiological) outcome at a test of cure (TOC; 7 days after treatment cessation) was analyzed by CrCL subgroup. Adverse events (AEs) according to renal subgroup were monitored throughout the study.

Results

A treatment difference in the composite outcome at TOC in favor of cefiderocol vs. IPM/CS was observed across renal subgroups (table), with greater differences in moderate and severe groups, consistent with that observed in the overall population (n = 371; 18.0%, 95% confidence interval: 7.5; 28.5). The incidence of AEs in the cefiderocol group was comparable across all renal subgroups. Conversely, AE incidence increased with the degree of impairment in the IPM/CS group (table).

Conclusion

In contrast to IPM/CS, the efficacy of cefiderocol was maintained across all renal function subgroups with no increase in the rate of AEs. These findings underscore the efficacy and safety of cefiderocol in patients with renal impairment and support the adequacy of the dose adjustment.

Disclosures

All authors: No reported disclosures.
Trade finance matters: evidence from the COVID-19 crisis
Authors: Demir Banu , Javorcik Beata
Published: July 2020

This study documents a substantial decline in the exports of major trading nations taking place in March 2020. Accounting for product-specific seasonality and annual trends, the data suggest a drop by 38 per cent in France, about a quarter in Turkey and Germany, and 12 per cent in the US, relative to their historical averages. Detailed export data from Turkey, disaggregated by financing terms, show another striking pattern. Flows using bank intermediation which eliminates or reduces the risk of non-payment or non-arrival of prepaid goods, such as letters of credit or documentary collection, appear to have been much more resilient to the current downturn relative to flows using other financing terms. These findings suggest that access to trade finance is vital during times of heightened uncertainty.
Healthy Pain-Free Individuals with a History of Distal Radius Fracture Demonstrate an Expanded Distribution of Experimental Referred Pain Toward the Wrist
Authors: Doménech-García Víctor , Palsson Thorvalur S , Boudreau Shellie A , Bellosta-López Pablo , Herrero Pablo , Graven-Nielsen Thomas
Published: July 2020

Objective

Nociception caused by injuries may sensitize central mechanisms causing expanded pain areas. After recovery, the status of such pain distribution and sensitivity mechanisms is unknown. The present study investigated whether individuals who have fully recovered from a distal radius fracture demonstrate increased pain sensitivity and expanded distribution of pressure-induced pain.

Design

Cross-sectional single-blinded study.

Setting

Clinical setting.

Subjects

Twenty-three pain-free individuals with a history of painful distal radius fracture and 22 nonfractured, age/gender-matched controls participated in two experimental sessions (day 0, day 1) 24 hours apart.

Methods

Pressure pain thresholds (PPTs) were recorded bilaterally at the extensor carpi radialis longus (ECRL), infraspinatus, and gastrocnemius muscles. Spatial distribution of pain was assessed following 60-second painful pressure stimulation at the ECRL (bilateral) and the infraspinatus muscles on the fractured or dominant side. Participants drew pain areas on a body map. After day 0 assessments, prolonged pain was induced by eccentric exercise of wrist extensors on the fractured/dominant side.

Results

Compared with controls, pressure-induced ECRL pain in the fracture group referred more frequently toward the distal forearm (P < 0.005) on day 0. Both groups showed larger pain areas on day 1 compared with day 0 (P < 0.005), although the fracture group showed a larger relative change between days (P < 0.005). The fracture group showed larger pain areas on the fracture side compared with the contralateral side on both days (P < 0.005).

Conclusions

Prolonged pain and recovered prior painful injuries like fractures may sensitize pain mechanisms manifested as expanded pain distribution. Pressure-induced referred pain can be a simple pain biomarker for clinical use.
Identification and prediction of novel classes of long-term disease trajectories for patients with juvenile dermatomyositis using growth mixture models
Authors: Deakin Claire T , Papadopoulou Charalampia , McCann Liza J , Martin Neil , Al-Obaidi Muthana , Compeyrot-Lacassagne Sandrine , Pilkington Clarissa A , Tansley Sarah L , McHugh Neil J , Wedderburn Lucy R , De Stavola Bianca L ,   for the Juvenile Dermatomyositis Research Group
Published: July 2020

Objectives

Uncertainty around clinical heterogeneity and outcomes for patients with JDM represents a major burden of disease and a challenge for clinical management. We sought to identify novel classes of patients having similar temporal patterns in disease activity and relate them to baseline clinical features.

Methods

Data were obtained for n = 519 patients, including baseline demographic and clinical features, baseline and follow-up records of physician’s global assessment of disease (PGA), and skin disease activity (modified DAS). Growth mixture models (GMMs) were fitted to identify classes of patients with similar trajectories of these variables. Baseline predictors of class membership were identified using Lasso regression.

Results

GMM analysis of PGA identified two classes of patients. Patients in class 1 (89%) tended to improve, while patients in class 2 (11%) had more persistent disease. Lasso regression identified abnormal respiration, lipodystrophy and time since diagnosis as baseline predictors of class 2 membership, with estimated odds ratios, controlling for the other two variables, of 1.91 for presence of abnormal respiration, 1.92 for lipodystrophy and 1.32 for time since diagnosis. GMM analysis of modified DAS identified three classes of patients. Patients in classes 1 (16%) and 2 (12%) had higher levels of modified DAS at diagnosis that improved or remained high, respectively. Patients in class 3 (72%) began with lower DAS levels that improved more quickly. Higher proportions of patients in PGA class 2 were in DAS class 2 (19%, compared with 16 and 10%).

Conclusion

GMM analysis identified novel JDM phenotypes based on longitudinal PGA and modified DAS.
Genetic Variation in the Microfibril Angle of Loblolly Pine From Two Test Sites
Authors: Myszewski Jennifer H. , Bridgwater Floyd E. , Lowe William J. , Byram Thomas D. , Megraw Robert A.
Published: July 2020

In recent years, several studies have examined the effect of microfibril angle (MFA) on wood quality. However, little research has been conducted upon the genetic mechanisms controlling MFA. In this study, we examined the heritability of MFA in loblolly pine, Pinus taeda L.,and its genetic relationships with height, diameter, volume, and specific gravity. Increment cores were collected at breast height from 20 to 25 progeny from each of 12 to 17 crosses (among 11 parents) in two modified partial-diallels in different locations in southern Arkansas. Specific gravitywas measured on segments containing rings 1 through 5 and on segments containing rings 6 through 20. MFA was measured on the earlywood and latewood sections of rings 4, 5, 19, and 20. Rings 4 and 5 were chosen as representative of core wood and rings 19 and 20 as representative of outer wood. Analyses of variance revealed statistically significant genetic and environmental influences on MFA. Significant general combining ability (GCA), specific combining ability (SCA), and SCA × block effects indicated that there are both additive and nonadditive genetic influences on MFA. Individual-tree, narrow-sense heritability estimates were variable, ranging from 0.17 for earlywood (ring) 4 MFA to 0.51 for earlywood (ring) 20 MFA. Genetic correlations between MFA, specific gravity, and the growth traits were nonsignificant due to large estimated standard errors. South.J. Appl. For. 28(4):196–204.
An albino mouse model of nonalcoholic fatty liver disease induced using high-fat liquid “Lieber-DeCarli” diet: a preliminary investigation
Authors: Ore Ayokanmi , Ugbaja Regina Ngozi , Adeogun Abideen Idowu , Akinloye Oluseyi Adeboye
Published: July 2020

Background:

Experimental diet models have proven to be vital to understanding the pathophysiology and management of nonalcoholic fatty liver disease (NAFLD). Lieber-DeCarli high-fat, liquid diet have been used to produce NAFLD in rat models. There is, however, currently no information on the effects of this diet in the mouse model.

Methods:

Ten (n = 10) male albino mice (27.7 ± 2.0 g) were divided into 2 diet groups (n = 5/group). Animals from group 1 were fed with standard chow diet (CD group) and those from group 2 were fed with Lieber-DeCarli high-fat, liquid diet (high-fat diet or HFD group) ad libitum for a period of 4 weeks.

Results:

Data obtained show insulin resistance in the HFD group with a significant increase in plasma lipid profile. Level of cholesterol and triglycerides in the liver and plasma increased significantly (P 
< .05) in the HFD group compared with the CD group. Plasma level of tumor necrosis factor alpha increased significantly in the HFD group compared to control. Also, indicators of oxidative stress (malondialdehyde and protein carbonyls) increased significantly coupled with a significant reduction in reduced glutathione (GSH) level and activity of glutathione peroxidase in the liver of mice in the HFD group compared to CD group. Histopathological evaluation of liver sections reveals steatosis with ballooned hepatocytes.

Conclusions:

Data from the present study suggest that the Lieber-DeCarli high-fat, liquid diet may be vital in the study of fatty liver disease in albino mouse. This model may also produce the features of NAFLD in a shorter time in albino mice.