bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of biologic response modifiers in the supernatant of conventional, refrigerated, and cryopreserved platelets
Authors: Johnson Lacey , Tan Shereen , Jenkins Emily , Wood Ben , Marks Denese C. 
Published: January 2018

BACKGROUNDAlternatives to room temperature storage of platelets (PLTs) are of interest to support blood banking logistics. The aim of this study was to compare the presence of biologic response modifiers (BRMs) in PLT concentrates stored under conventional room temperature conditions with refrigerated or cryopreserved PLTs.STUDY DESIGN AND METHODSA three‐arm pool‐and‐split study was carried out using buffy coat–derived PLTs stored in 30% plasma/70% SSP+. The three matched treatment arms were as follows: room temperature (20‐24°C), cold (2‐6°C), and cryopreserved (–80°C with DMSO). Liquid‐stored PLTs were tested over a 21‐day period, while cryopreserved PLTs were tested immediately after thawing and reconstitution in 30% plasma/70% SSP+ and after storage at room temperature.RESULTSCoagulation factor activity was comparable between room temperature and cold PLTs, with the exception of protein S, while cryopreserved PLTs had reduced Factor (F)V and FVIII activity. Cold‐stored PLTs retained α‐granule proteins better than room temperature or cryopreserved PLTs. Cryopreservation resulted in 10‐fold higher microparticle generation than cold‐stored PLTs, but both groups contained significantly more microparticles than those stored at room temperature. The supernatant from both cold and cryopreserved PLTs initiated faster clot formation and thrombin generation than room temperature PLTs.CONCLUSIONCold storage and cryopreservation alter the composition of the soluble fraction of stored PLTs. These differences in coagulation proteins, cytokines, and microparticles likely influence both the hemostatic capacity of the components and the auxiliary functions.
Reviewer Acknowledgements
Authors: Young James 
Published: January 2018

International Journal of Social Science Studies (IJSSS) would like to acknowledge the following reviewers for their assistance with peer review of manuscripts for this issue. Many authors, regardless of whether IJSSS publishes their work, appreciate the helpful feedback provided by the reviewers. Their comments and suggestions were of great help to the authors in improving the quality of their papers. Each of the reviewers listed below returned at least one review for this issue.Reviewers for Volume 6, Number 2 Agboola O. Paul, Universiti Teknologi Malaysia, MalaysiaAhmet Yıkmış, Abant Izzet Baysal Univeersity, TurkeyAmany Albert, Beni-Suef University, EgyptAnastasia Panagakos, Cosumnes River College, USAAntónio Calha, Polytechnic Institute of Portalegre, PortugalBo Li, St Ambrose University, USAE.Ozan Aksoz, Anadolu University, TurkeyJehu Onyekwere Nnaji, University of Naples II, Italy and Globe Visions Network Italy, ItalyJohn Boulard Forkuor , Kwame Nkrumah University of Science and Technology (KNUST) , GhanaJulia M. Mack, Gannon University, USAMohammad Naji Shah Mohammadi, Kuala Lumpur, MalaysiaQingzhi Huan, Peking University, ChinaRasa Poceviciene, Siauliai University, LithuaniaRemigiusz Kijak, "University of Warsaw", PolandSandro Serpa, University of the Azores, PortugalShariq aziz butt, Superior University Lahore, PakistanValentina Evangelista, G. d’Annunzio University, ItalyXian-Liang Tian, Zhongnan University of Economics and Law, ChinaYanzhe Zhang, Jilin University, China, China/Australia
Population Pharmacokinetics of Cefotaxime and Dosage Recommendations in Children with Sickle Cell Disease
Authors: Maksoud Elsa , Koehl Berengere , Facchin Aude , Ha Phuong , Zhao Wei , Kaguelidou Florentia , Benkerrou Malika , Mariani Patricia , Faye Albert , Lorrot Mathie , Jacqz-Aigrain Evelyne 
Published: January 2018

ABSTRACT
The pharmacokinetic profile of most drugs is dependent on the patient's covariates and may be influenced by the disease. Cefotaxime is frequently prescribed in pediatric patients with sickle cell disease (SCD), characterized by vaso-occlusive complications, chronic hemolytic anemia, and a defective immunological function predisposing the individual to severe infection. Data on the impact of the disease on the disposition of cefotaxime are missing. In the present study, our aims were to determine cefotaxime pharmacokinetics when prescribed to children with SCD for suspected or proven bacterial infection, identify significant covariates, and perform Monte Carlo simulations to optimize the drug dosage. Cefotaxime serum concentrations were measured in 78 pediatric SCD patients receiving cefotaxime intravenously at a daily dose of 200 mg/kg of body weight in three or four divided doses over 30 min. A total of 107 concentrations were available for pharmacokinetic analysis. A population pharmacokinetic model was developed with NONMEM software and used for Monte Carlo simulations. Cefotaxime concentrations ranged from 0.05 to 103.7 mg/liter. Cefotaxime pharmacokinetics were best described by a one-compartment model: the median estimated weight-normalized volume of distribution and clearance were 0.42 liter/kg (range, 0.2 to 1.1 liter/kg) and 0.38 liter/h/kg (range, 0.1 to 1.2 liter/h/kg). Cefotaxime clearance increased by 22% in patients with acute chest syndrome. Dosing optimization, performed using EUCAST MIC susceptibility breakpoints, showed that a dose of 100 mg/kg/6 h should be used, depending on the patient's characteristics and clinical presentation, in order to reach a value of the percentage of time that the drug concentration exceeded the MIC under steady-state pharmacokinetic conditions of 80% in 80% of the patients when targeting sensitive Gram-positive cocci and Gram-negative bacilli with MICs of 1 mg/liter or below.
Roles of Three Cryptococcus neoformans and Cryptococcus gattii Efflux Pump-Coding Genes in Response to Drug Treatment
Authors: Chang Miwha , Sionov Edward , Khanal Lamichhane Ami , Kwon-Chung Kyung J. , Chang Yun C. 
Published: January 2018

ABSTRACT

Cryptococcus neoformans
and
Cryptococcus gattii
species complexes are the etiologic agents of cryptococcosis. We have deciphered the roles of three ABC transporters, Afr1, Afr2, and Mdr1, in the representative strains of the two species,
C. neoformans
H99 and
C. gattii
R265. Deletion of
AFR1
in H99 and R265 drastically reduced the levels of resistance to three xenobiotics and three triazoles, suggesting that Afr1 is the major drug efflux pump in both strains. Fluconazole susceptibility was not affected when
AFR2
or
MDR1
was deleted in both strains. However, when these genes were deleted in combination with
AFR1
, a minor additive effect in susceptibility toward several drugs was observed. Deletion of all three genes in both strains caused further increases in susceptibility toward fluconazole and itraconazole, suggesting that Afr2 and Mdr1 augment Afr1 function in pumping these triazoles. Intracellular accumulation of Nile Red significantly increased in
afr1Δ
mutants of both strains, but rhodamine 6G accumulation increased only in the
mdr1Δ
mutant of H99. Thus, the three efflux pumps play different roles in the two strains when exposed to different azoles and xenobiotics.
AFR1
and
AFR2
expression was upregulated in H99 and R265 when treated with fluconazole. However,
MDR1
expression was upregulated only in R265 under the same conditions. We screened a library of transcription factor mutants and identified several mutants that manifested either altered fluconazole sensitivity or an increase in the frequency of fluconazole heteroresistance. Gene expression analysis suggests that the three efflux pumps are regulated independently by different transcription factors in response to fluconazole exposure.
A Multicenter, Randomized, Double-Blind, Phase 2 Study of the Efficacy and Safety of Plazomicin Compared with Levofloxacin in the Treatment of Complicated Urinary Tract Infection and Acute Pyelonephritis
Authors: Connolly Lynn E. , Riddle Valerie , Cebrik Deborah , Armstrong Eliana S. , Miller Loren G. 
Published: January 2018

ABSTRACT

Increasing antimicrobial resistance among uropathogens limits treatment options for patients with complicated urinary tract infection (cUTI). Plazomicin, a new aminoglycoside, has
in vitro
activity against multidrug-resistant
Enterobacteriaceae
, including isolates resistant to currently available aminoglycosides, as well as extended-spectrum β-lactamase-producing and carbapenem-resistant
Enterobacteriaceae
. We evaluated the efficacy and safety of plazomicin in a double-blind, comparator-controlled, phase 2 study in adults with cUTI or acute pyelonephritis. Patients were randomized 1:1:1 to receive intravenous plazomicin (10 or 15 mg/kg of body weight) or intravenous levofloxacin (750 mg) once daily for 5 days. Coprimary efficacy endpoints were microbiological eradication at the test of cure (TOC; 5 to 12 days after the last dose) in the modified intent-to-treat (MITT) and microbiologically evaluable (ME) populations. Overall, 145 patients were randomized to treatment. In the groups receiving plazomicin at 10 mg/kg, plazomicin at 15 mg/kg, and levofloxacin, microbiological eradication rates were, respectively, 50.0% (6 patients with microbiological eradication at TOC/12 patients treated [95% confidence interval {CI}, 21.1 to 78.9%]), 60.8% (31/51 [95% CI, 46.1 to 74.2%]), and 58.6% (17/29 [95% CI, 38.9 to 76.5%]) in the MITT population and 85.7% (6/7 [95% CI, 42.1 to 99.6%]), 88.6% (31/35 [95% CI, 73.3 to 96.8%]), and 81.0% (17/21 [95% CI, 58.1 to 94.6%]) in the ME population. In the MITT population, 66.7% (95% CI, 34.9 to 90.1%), 70.6% (95% CI, 56.2 to 82.5%), and 65.5% (95% CI, 45.7 to 82.1%) of the patients in the three groups, respectively, were assessed by the investigator to be clinically cured at TOC. Adverse events were reported in 31.8%, 35.1%, and 47.7% of the patients in the three groups, respectively. Serum creatinine values were generally stable over the course of the study. No plazomicin-treated patients with evaluable audiometry data had postbaseline sensorineural, conductive, or mixed hearing loss. In summary, plazomicin demonstrated microbiological and clinical success and an overall safety profile supportive of further clinical development. (This study has been registered at ClinicalTrials.gov under identifier NCT01096849.)
Antibiotic Susceptibility and Genotyping of Mycobacterium avium Strains That Cause Pulmonary and Disseminated Infection
Authors: Uchiya Kei-ichi , Asahi Shoki , Futamura Kazunori , Hamaura Hiromitsu , Nakagawa Taku , Nikai Toshiaki , Ogawa Kenji 
Published: January 2018

ABSTRACT

Mycobacterium avium
subsp.
hominissuis
mainly causes disseminated infection in immunocompromised hosts, such as individuals with human immunodeficiency virus (HIV) infection, and pulmonary infection in immunocompetent hosts. However, many aspects of the different types of
M. avium
subsp.
hominissuis
infection remain unclear. We examined the antibiotic susceptibilities and genotypes of
M. avium
subsp.
hominissuis
isolates from different hosts by performing drug susceptibility testing using eight antibiotics (clarithromycin, rifampin, ethambutol, streptomycin, kanamycin, amikacin, ethionamide, and levofloxacin) and variable-number tandem-repeat (VNTR) typing analysis for 46 isolates from the sputa of HIV-negative patients with pulmonary
M. avium
subsp.
hominissuis
disease without previous antibiotic treatment and 30 isolates from the blood of HIV-positive patients with disseminated
M. avium
subsp.
hominissuis
disease. Interestingly, isolates from pulmonary
M. avium
subsp.
hominissuis
disease patients were more resistant to seven of the eight drugs, with the exception being rifampin, than isolates from HIV-positive patients. Moreover, VNTR typing analysis showed that the strains examined in this study were roughly classified into three clusters, and the genetic distance from reference strain 104 for isolates from pulmonary
M. avium
subsp.
hominissuis
disease patients was statistically significantly different from that for isolates from HIV-positive patients (
P
= 0.0018), suggesting that
M. avium
subsp.
hominissuis
strains that cause pulmonary and disseminated disease have genetically distinct features. Significant differences in susceptibility to seven of the eight drugs, with the exception being ethambutol, were noted among the three clusters. Collectively, these results suggest that an association between the type of
M. avium
subsp.
hominissuis
infection, drug susceptibility, and the VNTR genotype and the properties of
M. avium
subsp.
hominissuis
strains associated with the development of pulmonary disease are involved in higher levels of antibiotic resistance.
Norepinephrine in Combination with Antibiotic Therapy Increases both the Bacterial Replication Rate and Bactericidal Activity
Authors: Ambrose Paul G. , VanScoy Brian D. , Adams John , Fikes Steven , Bader Justin C. , Bhavnani Sujata M. , Rubino Christopher M. 
Published: January 2018

ABSTRACT

We previously demonstrated that the rate and extent of an antimicrobial agent's bactericidal effects were coupled to the bacterial replication rate, the latter of which was modulated with the sodium chloride concentration. Herein, we describe the results from a 24-h one-compartment
in vitro
infection model study that was designed to demonstrate that an antimicrobial agent's bactericidal effects could be amplified when it is administered with a pharmaceutical agent that increases the bacterial replication rate. The antimicrobial and growth-promoting agents selected were levofloxacin and norepinephrine, respectively. The challenge isolate was
Escherichia coli
JMI 21711R (levofloxacin MIC, 8 mg/liter). Within the
in vitro
infection model, a human levofloxacin concentration-time profile (half-life, 7 h) was simulated and the challenge isolate was subjected to an ineffective monotherapy exposure (free-drug area under the concentration-time curve over 24 h divided by the MIC [AUC/MIC] ratio of 6) with and without norepinephrine as a continuous infusion (275 mg/liter). Samples were collected from the model during the course of the study for bacterial density determinations and drug concentration assay using liquid chromatography-tandem mass spectrometry (LC-MS/MS). As expected, the norepinephrine and no-treatment control arms failed immediately, followed by the levofloxacin monotherapy arm, which failed slowly over time. The levofloxacin-epinephrine regimen resulted in a 2-log
10
CFU reduction in bacterial density over the first 6 to 8 h of the study, which was followed by regrowth of a highly levofloxacin-resistant subpopulation (MIC, 64 mg/liter). These data demonstrate that increasing the rate of bacterial replication with a pharmaceutical product in combination with antimicrobial therapy represents an opportunity to increase the rate and magnitude of bactericidal effect.
A 10-Year Comparative Analysis Shows that Increasing Prevalence of Rifampin-Resistant Mycobacterium tuberculosis in China Is Associated with the Transmission of Strains Harboring Compensatory Mutations
Authors: Huo Fengmin , Luo Jingjing , Shi Jin , Zong Zhaojing , Jing Wei , Dong Wenzhu , Dong Lingling , Ma Yifeng , Liang Qian , Shang Yuanyuan , Huang Hairong , Pang Yu 
Published: January 2018

ABSTRACT

In this work, we conducted bacterial population profile studies to assess trends of rifampin (RIF) resistance of
Mycobacterium tuberculosis
isolates collected across China from 2005 to 2015. Totals of 273 and 269 randomly selected
M. tuberculosis
isolates from 2005 and 2015, respectively, were analyzed. The rates of RIF resistance (36.4%), isoniazid resistance (39.0%), and levofloxacin resistance (25.7%) in 2015 were significantly higher than those in 2005 (28.2%, 30.0%, and 15.4%, respectively;
P
< 0.05). Genotypic data revealed 256 (95.2%) Beijing-type isolates in 2015, a rate significantly higher than that in 2005 (86.4%) (
P
< 0.01). A higher proportion of mutations was identified within the rifampin resistance-determining region (RRDR) of
rpoB
in isolates from 2015 (99.0%) than in 2005 isolates (85.7%,
P
< 0.01). In addition, a significantly higher proportion of RIF-resistant isolates carrying compensatory mutations was observed in 2015 (31.6%) than in 2005 (7.8%). Notably, the great majority of these compensatory mutations (91.9%) were observed in isolates that harbored a mutation of codon 531 of the
rpoB
gene. In conclusion, our data demonstrate that resistance to RIF, isoniazid, and levofloxacin has become significantly more prevalent during the past decade. In addition, the prevalence of the Beijing genotype significantly increased from 2005 to 2015. Notably, a significantly increased frequency of strains with mutations in
rpoC
or
rpoA
is observed among those that have codon 531 mutations, which suggests that they may be compensatory and may play a role in facilitating transmission.
Evaluation of a System-Specific Function To Describe the Pharmacokinetics of Benzylpenicillin in Term Neonates Undergoing Moderate Hypothermia
Authors: Bijleveld Yuma A. , de Haan Timo R. , van der Lee Johanna H. , Groenendaal Floris , Dijk Peter H. , van Heijst Arno , de Jonge Rogier C. J. , Dijkman Koen P. , van Straaten Henrica L. M. , Rijken Monique , Zonnenberg Inge A. , Cools Filip , Zecic Alexandra , Nuytemans Debbie H. G. M. , van Kaam Anton H. , Mathôt Ron A. A. ,   PharmaCool study group, Brouwer Mieke J. , van den Broek Marcel P. , Rademaker Carin M. A. , Liem Djien , Steiner Katerina , Simons Sinno H. P. , Bos Annelies A. , Mulder-de Tollenaer S. M. , Jebbink-Akkerman L. J. M. Groot , Sonnaert Michel , Camfferman Fleur Anne 
Published: January 2018

ABSTRACT

The pharmacokinetic (PK) properties of intravenous (i.v.) benzylpenicillin in term neonates undergoing moderate hypothermia after perinatal asphyxia were evaluated, as they have been unknown until now. A system-specific modeling approach was applied, in which our recently developed covariate model describing developmental and temperature-induced changes in amoxicillin clearance (CL) in the same patient study population was incorporated into a population PK model of benzylpenicillin with
a priori
birthweight (BW)-based allometric scaling. Pediatric population covariate models describing the developmental changes in drug elimination may constitute system-specific information and may therefore be incorporated into PK models of drugs cleared through the same pathway. The performance of this system-specific model was compared to that of a reference model. Furthermore, Monte-Carlo simulations were performed to evaluate the optimal dose. The system-specific model performed as well as the reference model. Significant correlations were found between CL and postnatal age (PNA), gestational age (GA), body temperature (TEMP), urine output (UO; system-specific model), and multiorgan failure (reference model). For a typical patient with a GA of 40 weeks, BW of 3,000 g, PNA of 2 days (TEMP, 33.5°C), and normal UO (2 ml/kg/h), benzylpenicillin CL was 0.48 liter/h (interindividual variability [IIV] of 49%) and the volume of distribution of the central compartment was 0.62 liter/kg (IIV of 53%) in the system-specific model. Based on simulations, we advise a benzylpenicillin i.v. dose regimen of 75,000 IU/kg/day every 8 h (q8h), 150,000 IU/kg/day q8h, and 200,000 IU/kg/day q6h for patients with GAs of 36 to 37 weeks, 38 to 41 weeks, and ≥42 weeks, respectively. The system-specific model may be used for other drugs cleared through the same pathway accelerating model development.
Pharmacokinetics of Tedizolid in an Obese Patient after Bariatric Surgery
Authors: Grégoire Matthieu , Libois Julia Brochard , Waast Denis , Gaborit Benjamin , Dauty Marc , Deslandes Guillaume , Dailly Eric , Touchais Sophie , Boutoille David , Grégoire Nicolas , Couet William 
Published: January 2018

ABSTRACT

An obese woman was treated with oral tedizolid 200 mg once daily for pseudoarthrosis 10 years after Roux-en-Y bypass surgery. Total plasma peak concentration was 2.12 mg/liter 3 h after intake, and area under the concentration-time curve from 0 to 24 h (AUC
0–24
) was 28.3 mg/liter · h. The AUC
0–24
/MIC ratio for unbound concentrations and for sensitive
Staphylococcus
and
Streptococcus
strains was ≥10.8, higher than the target ratio of 3. These results support the use of tedizolid without adjustment after bariatric surgery.
Enhanced Ex Vivo Plasmodium vivax Intraerythrocytic Enrichment and Maturation for Rapid and Sensitive Parasite Growth Assays
Authors: Rangel Gabriel W. , Clark Martha A. , Kanjee Usheer , Lim Caeul , Shaw-Saliba Kathryn , Menezes Maria José , Mascarenhas Anjali , Chery Laura , Gomes Edwin , Rathod Pradipsinh K. , Ferreira Marcelo U. , Duraisingh Manoj T. 
Published: January 2018

ABSTRACT

Plasmodium vivax
chloroquine resistance has been documented in nearly every region where this malaria-causing parasite is endemic. Unfortunately,
P. vivax
resistance surveillance and drug discovery are challenging due to the low parasitemias of patient isolates and poor parasite survival through
ex vivo
maturation that reduce the sensitivity and scalability of current
P. vivax
antimalarial assays. Using cryopreserved patient isolates from Brazil and fresh patient isolates from India, we established a robust enrichment method for
P. vivax
parasites. We next performed a medium screen for formulations that enhance
ex vivo
survival. Finally, we optimized an isotopic metabolic labeling assay for measuring
P. vivax
maturation and its sensitivity to antimalarials. A KCl Percoll density gradient enrichment method increased parasitemias from small-volume
ex vivo
isolates by an average of >40-fold. The use of Iscove's modified Dulbecco's medium for
P. vivax ex vivo
culture approximately doubled the parasite survival through maturation. Coupling these with [
3
H]hypoxanthine metabolic labeling permitted sensitive and robust measurements of parasite maturation, which was used to measure the sensitivities of Brazilian
P. vivax
isolates to chloroquine and several novel antimalarials. These techniques can be applied to rapidly and robustly assess the
P. vivax
isolate sensitivities to antimalarials for resistance surveillance and drug discovery.