bluuebunny/crossref_metadata_2025_split huggingface dataset:
Isobolographic Analysis of Drug Combinations With Intrathecal BRL52537 (κ-Opioid Agonist), Pregabalin (Calcium Channel Modulator), AF 353 (P2X3 Receptor Antagonist), and A804598 (P2X7 Receptor Antagonist) in Neuropathic Rats
Authors: Jung Young-Hwan , Kim Yeo Ok , Han Jung Hyun , Kim Yong-Chul , Yoon Myung Ha 
Published: March 2017

BACKGROUND:
Neuropathic pain should be treated with drug combinations exhibiting multiple analgesic mechanisms of action because the mechanism of neuropathic pain involves multiple physiological causes and is mediated by multiple pathways. In this study, we defined the pharmacological interaction of BRL52537 (κ-opioid agonist), pregabalin (calcium channel modulator), AF 353 (P2X3 receptor antagonist), and A804598 (P2X7 receptor antagonist).

METHODS:
Animal models of neuropathic pain were established by spinal nerve ligation (SNL) in male Sprague-Dawley rats, and responses to the mechanical stimulation using von Frey filaments were measured. Drugs were administered by intrathecal route and were examined for antiallodynic effects, and drug interactions were evaluated using isobolographic analysis. The mRNA expression levels of pain-related receptors in each spinal cord or dorsal root ganglion of naïve, SNL, and drug-treated SNL rats were evaluated using real-time polymerase chain reaction.

RESULTS:
Intrathecal BRL52537, pregabalin, AF 353, and A804598 produced antiallodynic effects in SNL rats. In the drug combination studies, intrathecal coadministration of BRL52537 with pregabalin or A804598 exhibited synergistic interactions, and other drugs combinations showed additivity. The rank order of potency was observed as follows: BRL52537 + pregabalin > BRL52537 + A804598 > pregabalin + AF 353 > A804598 + pregabalin > BRL52537 + AF 353 > AF 353 + A804598. Real-time polymerase chain reaction indicated that alterations of P2X3 receptor and calcium channel mRNA expression levels were observed, while P2X7 receptor and κ-opioid receptor expression levels were not altered.

CONCLUSIONS:
These results demonstrated that intrathecal combination of BRL52537, pregabalin, AF 353, and A804598 synergistically or additively attenuated allodynia evoked by SNL, which suggests the possibility to improve the efficacy of single-drug administration.
Utilizing Forced Vital Capacity to Predict Low Lung Compliance and Select Intraoperative Tidal Volume During Thoracic Surgery
Authors: Hoftman Nir , Eikermann Eric , Shin John , Buckley Jack , Navab Kaveh , Abtin Fereidoun , Grogan Tristan , Cannesson Maxime , Mahajan Aman 
Published: March 2017

BACKGROUND:Tidal volume selection during mechanical ventilation utilizes dogmatic formulas that only consider a patient’s predicted body weight (PBW). In this study, we investigate whether forced vital capacity (FVC) (1) correlates better to total lung capacity (TLC) than PBW, (2) predicts low pulmonary compliance, and (3) provides an alternative method for tidal volume selection.METHODS:One hundred thirty thoracic surgery patients had their preoperative TLC calculated via 2 methods: (1) pulmonary function test (PFT; TLCPFT) and (2) computed tomography 3D reconstruction (TLCCT). We compared the correlation between TLC and PBW with the correlation between TLC and FVC to determine which was stronger. Dynamic pulmonary compliance was then calculated from intraoperative ventilator data and logistic regression models constructed to determine which clinical measure best predicted low compliance. Ratios of tidal volume/FVC plotted against peak inspiratory pressure were utilized to construct a new model for tidal volume selection. Calculated tidal volumes generated by this model were then compared with those generated by the standard lung-protective formula Vt = 7 cc/kg.RESULTS:The correlation between FVC and TLC (0.82 for TLCPFTand 0.76 for TLCCT) was stronger than the correlation between PBW and TLC (0.65 for TLCPFTand 0.58 for TLCCT). Patients with very low compliance had significantly smaller lung volumes (forced expiratory volume at 1 second, FVC, TLC) and lower diffusion capacity of the lungs for carbon monoxide when compared with patients with normal compliance. An FVC cutoff of 3470 cc was 100% sensitive and 51% specific for predicting low compliance. The proposed equation Vt = FVC/8 significantly reduced calculated tidal volume by a mean of 22.5% in patients with low pulmonary compliance without affecting the mean tidal volume in patients with normal compliance (mean difference 0.9%).CONCLUSIONS:FVC is more strongly correlated to TLC than PBW and a cutoff of about 3.5 L can be utilized to predict low pulmonary compliance. The equation Vt = FVC/8 reduced mean calculated tidal volume in patients with low pulmonary compliance and/or small lungs.
The Pathway of Injectate Spread With the Transmuscular Quadratus Lumborum Block: A Cadaver Study
Authors: Dam Mette , Moriggl Bernhard , Hansen Christian K. , Hoermann Romed , Bendtsen Thomas F. , Børglum Jens 
Published: March 2017

BACKGROUND:
The spread of injectate resulting from a transmuscular quadratus lumborum (TQL) block and a transverse oblique paramedian (TOP) TQL block has never been examined. The aim of this cadaveric study was to investigate by which pathway the injectate spreads cephalad into the thoracic paravertebral space and which nerves were dyed by the injectate cephalad and caudad to the diaphragm when performing a TQL and a TOP TQL block. We also aimed to investigate whether the thoracic and lumbar sympathetic trunks as well as the lumbar plexus were covered by the injectate.

METHODS:
Ultrasound-guided bilateral TQL and TOP TQL injections were administered in 8 cadavers. A total of 16 injections were performed. With the TQL injection, the curvilinear transducer was oriented in the transverse plane above the iliac crest at the posterior axillary line to identify the Shamrock sign. With the TOP TQL injection, the same transducer was placed with a TOP orientation 3 cm lateral to the L2 spinous process to identify the L2 transverse process and the adjoining quadratus lumborum muscle. For both techniques, the needle was advanced in-plane to the transducer, with the end point in the interfascial plane between the quadratus lumborum and psoas major muscles. Thirty milliliters of dye solution was injected bilaterally for each technique. The spread of the dye was evaluated by subsequent dissection.

RESULTS:
In all successful injections, the dye was seen to spread into the thoracic paravertebral space and the intercostal spaces to surround the somatic nerves and the thoracic sympathetic trunk. The main pathway of spread of injectate was posterior to the medial and lateral arcuate ligaments. Caudad to the diaphragm, the injected dye surrounded the subcostal, iliohypogastric, and ilioinguinal nerves in all cases, whereas the genitofemoral and lateral femoral cutaneous nerves were dyed in a varying degree. No dye was seen to surround the lumbar plexus, femoral nerve, or lumbar sympathetic trunk. The pattern of spread was similar with the TQL and TOP TQL injections.

CONCLUSIONS:
The spread of injectate with the TQL and TOP TQL approaches is cephalad from the lumbar point of administration between the quadratus lumborum and psoas major muscles, predominantly via a pathway posterior to the arcuate ligaments and into the thoracic paravertebral space to reach the somatic nerves and the thoracic sympathetic trunk in the intercostal and paravertebral spaces. The lumbar plexus and lumbar sympathetic trunk are not affected.
Crystal Structures of Bis(diphenylglyoximato)–Nickel(II) Complex with Varying Alkoxy Chain Lengths
Authors: Ueji Kan , Nomoto Kuniharu , Ichimura Shuhei , Shinozaki Satsuki , Abe Keiichi , Tomono Kazuaki , Tamaki Yoshinori , Miyamura Kazuo 
Published: March 2017

Abstract
Crystal structures of eight derivatives of bis(diphenylglyoximato)–nickel(II), bearing four alkoxy chains of different lengths, were determined by single-crystal X-ray crystallography. Sequential transition of packing structures by chain elongation was observed. The packing structures were typically one-dimensional columnar structure comprising metal wires, herringbone structures, quasi-layered structures and layered structures having an interdigitation of alkyl moieties in the alkoxy chains. Each structural characteristic depends on odd–even effect and alkoxy chain interactions. Additionally, the gauche conformation of the alkoxy chains contributes to filling the empty spaces of the structures, placing out of the molecular plane packing, and forming a clip structure of the alkoxy chains.
In silico analysis of single nucleotide polymorphisms (SNPs) in human FOXC2 gene
Authors: Nimir Mohammed , Abdelrahim Mohanad , Abdelrahim Mohamed , Abdalla Mahil , Ahmed Wala eldin , Abdullah Muhanned , Hamid Muzamil Mahdi Abdel 
Published: March 2017

Introduction: Lymphedema is abnormal accumulation of interstitial fluid, due to inefficient uptake and reduced flow, leading to swelling and disability, mostly in the extremities. Hereditary lymphedema usually occurs as an autosomal dominant trait with allelic heterogeneity. Methods:We identified single nucleotide polymorphisms (SNPs) in the FOXC2 gene using dbSNP, analyzed their effect on the resulting protein using VEP and Biomart, modelled the resulting protein using Project HOPE, identified gene – gene interactions using GeneMANIA and predicted miRNAs affected and the resulting effects of SNPs in the 5’ and 3’ regions using PolymiRTS. Results:We identified 448 SNPs - 429 were nsSNPs and 44 SNPs were in the 5’ and 3’ UTRs. In total, 2 SNPs have deleterious effects on the resulting protein, and a 3D model confirmed those effects. The gene – gene interaction network showed the involvement of FOXC2 protein in the development of the lymphatic system. hsa-miR-6886-5p, hsa-miRS-6886-5p , hsa-miR-6720-3p, which were affected by the SNPs rs201118690, rs6413505, rs201914560, respectively, were the most important miRNAs affected, due to their high conservation score. Conclusions:rs121909106 and rs121909107 were predicted to have the most harmful effects, while hsa-miR-6886-5p, hsa-miR-6886-5p and hsa-miR-6720-3p were predicted to be the most important miRNAs affected. Computational biology tools have advantages and disadvantages, and the results they provide are predictions that require confirmation.
Linguo-Didactic Features of Russian Language Teaching in Educational Organizations with Russian (Non-Mother Tongue) and Mother-Tongue (Non-Russian) Language Learning with the Use of Integrated Didactic Units
Authors: Воителева  , Voiteleva T. , Марченко  , Marchenko O. 
Published: March 2017

The article discusses the use of integrated didactic units in the process of teaching Russian as a second language. This article was written for open source
information that described the use of integrated didactic units, the specificity of the didactic training using pass-through units of the Russian language.
Venous leg ulcer healing with electric stimulation therapy: a pilot randomised controlled trial
Authors: Miller C. , McGuiness W. , Wilson S. , Cooper K. , Swanson T. , Rooney D. , Piller N. , Woodward M. 
Published: March 2017

Objective: Compression therapy is a gold standard treatment to promote venous leg ulcer (VLU) healing. Concordance with compression therapy is, however, often sub-optimal. The aim of this study was to evaluate the effectiveness of electric stimulation therapy (EST) to facilitate healing of VLUs among people who do not use moderate-to-high levels of compression (>25 mmHg). Method: A pilot multicentre, single-blinded randomised controlled trial was conducted. Participants were randomised (2:1) to the intervention group or a control group where EST or a sham device was used 4 times daily for 20 minutes per session. Participants were monitored fortnightly for eight weeks. The primary outcome measure was percentage of area (wound size) change. Results: In the 23 patients recruited, an average redution in wound size of 23.15% (standard deviation [SD]: 61.23) was observed for the control group compared with 32.67 % (SD: 42.54) for the intervention. A moderate effect size favouring the intervention group was detected from univariate [F(1,18)=1.588, p=0.224, partial eta squared=0.081] and multivariate repeated measures [F(1,18)=2.053, p=0.169, partial eta squared=0.102] analyses. Conclusion: The pilot study was not powered to detect statistical significance, however, the difference in healing outcomes are encouraging. EST may be an effective adjunct treatment among patients who have experienced difficulty adhering to moderate-to-high levels of compression therapy.
Student Preparation for PGY1 Residency Training by US Colleges of Pharmacy: Survey of the Residency Program Director Perspective
Authors: Mutz Alyssa B. , Beyer Jacob , Dickson Whitney L. , Gutman Irina , Yucebay Filiz , Lepkowsky Marcie , Chan Juliana , Carter Kristen , Shaffer Christopher L. , Fuller Patrick D. 
Published: March 2017

Purpose To evaluate current residents' level of preparation by US colleges of pharmacy for postgraduate year 1 (PGY1) residency training from the perspective of residency program directors (RPDs). Methods RPDs were asked in an electronic survey questionnaire to rate PGY1 pharmacy residents' abilities in 4 domains: communication, clinical knowledge, interpersonal/time-management skills, and professionalism/leadership. Results One hundred ninety-seven RPDs of the American Society of Health-System Pharmacists (ASHP)–accredited PGY1 programs completed the survey. The majority of RPDs strongly agreed or agreed that residents were prepared as students to effectively communicate both verbally and nonverbally, were able to appropriately respond to drug inquiries using drug resources and literature searches, and consistently displayed professionalism. Respondents were more likely to disagree or give a neutral response when asked about residents' understanding of biostatistics and their ability to provide enteral and parenteral nutritional support for patients. Conclusion Overall, RPDs agreed that residents were prepared to perform the majority of the tasks of each of the 4 domains assessed in this survey relating to PGY1 training. RPDs may use the results of this survey to provide additional support for their residents in the areas in which residents lack adequate preparation, while colleges of pharmacy may focus on incorporating more time in their curriculum for certain areas to better prepare their students for residency training.
Y-site Incompatibility between Premix Concentrations of Vancomycin and Piperacillin-Tazobactam: Do Current Compatibility Testing Methodologies Tell the Whole Story?
Authors: Kufel Wesley D. , Miller Christopher D. , Johnson Paul R. , Reid Kaleigh , Zahra James J. , Seabury Robert W. 
Published: March 2017

Background Published literature has demonstrated commercially available premix vancomycin (5 mg/mL) and piperacillin-tazobactam (67.5 mg/mL) as physically compatible via simulated Y-site methodology. Compatibility via actual Y-site infusion has yet to be established. Objective To assess and compare the compatibility of commercially available premix concentrations of vancomycin and piperacillin-tazobactam via simulated and actual Y-site evaluation. Methods Vancomycin and piperacillin-tazobactam were tested using simulated and actual Y-site infusion methodologies. Simulated Y-site compatibility was performed using previously published methods via visual inspection, turbidity evaluation, and pH evaluation. Evaluation occurred immediately, 60 minutes, 120 minutes, and 240 minutes following mixing for each mixture and control. Mixtures were considered physically incompatible if there was visual evidence of precipitation or haze, an absorbance value was greater than 0.01 A, or an absolute change of 1.0 pH unit occurred. Actual Y-site infusion was simulated to mirror antibiotic infusion in the clinical setting by nursing personnel using smart pumps and intravenous tubing. Results No evidence of physical incompatibility was observed during simulated Y-site testing via visual inspection, turbidity assessment, and pH evaluation. Conversely, physical incompatibility was observed to the unaided eye within 2 minutes during actual Y-site infusion. Conclusions Despite observed compatibility between vancomycin and piperacillin-tazobactam via simulated Y-site testing, visual evidence of physical incompatibility was observed during actual Y-site infusion. This poses a potential compromise to patient safety if these antibiotics are administered simultaneously in the clinical setting. Actual Y-site testing should be performed prior to clinical adoption of compatibility studies that are based solely on simulated methodologies.
CLIC1 null mice demonstrate a role for CLIC1 in macrophage superoxide production and tissue injury
Authors: Ulmasov Barbara , Bruno Jonathan , Oshima Kiyoko , Cheng Yao‐Wen , Holly Stephen P. , Parise Leslie V. , Egan Terrance M. , Edwards John C. 
Published: March 2017

AbstractWe generated and studied CLIC1 null (C1KO) mice to investigate the physiological role of this protein. C1KO and matched wild‐type (WT) mice were studied in two models of acute toxic tissue injury. CLIC1 expression is upregulated following acute injury of WT kidney and pancreas and is absent in C1KOs. Acute tissue injury is attenuated in the C1KOs and this correlates with an absence of the rise in tissue reactive oxygen species (ROS) that is seen in WT mice. Infiltration of injured tissue by inflammatory cells was comparable between WT and C1KOs. Absence of CLIC1 increased PMA‐induced superoxide production by isolated peritoneal neutrophils but dramatically decreased PMA‐induced superoxide production by peritoneal macrophages. CLIC1 is expressed in both neutrophils and macrophages in a peripheral pattern consistent with either plasma membrane or the cortical cytoskeleton in resting cells and redistributes away from the periphery following PMA stimulation in both cell types. Absence of CLIC1 had no effect on redistribution or dephosphorylation of Ezrin/ERM cytoskeleton in macrophages. Plasma membrane chloride conductance is altered in the absence of CLIC1, but not in a way that would be expected to block superoxide production. NADPH oxidase redistributes from an intracellular compartment to the plasma membrane when WT macrophages are stimulated to produce superoxide and this redistribution fails to occur in C1KO macrophages. We conclude that the role of CLIC1 in macrophage superoxide production is to support redistribution of NADPH oxidase to the plasma membrane, and not through major effects on ERM cytoskeleton or by acting as a plasma membrane chloride channel.
Getting a Job through Unemployed Friends: A Social Network Perspective
Authors: Zhang Rui 
Published: March 2017

AbstractWe develop a model in which unemployed workers can pass along unwanted job information to other unemployed friends within social networks. Compared with the case in the absence of social networks, we first show in an economy where networks are equal in size that unemployment rate is lower. In terms of social welfare, social planner prefers workers becoming more selective than the decentralized equilibrium. When social networks differ in size, increasing the size difference is beneficial for unemployed workers with large networks but detrimental to those with small networks; in addition, the unemployment rate decreases with the size difference. However, because of the dilution effect, as the proportion of unemployed workers with large networks increases, it eventually results in losses for all unemployed workers, and the unemployment rate may follow a non-monotonic pattern.
Mutation analysis of the NRXN1 gene in autism spectrum disorders
Authors: Onay H , Kacamak D , Kavasoglu AN , Akgun B , Yalcinli M , Kose S , Ozbaran B 
Published: March 2017

Abstract
The aim of this study was to identify the sequence mutations in the Neurexin 1 (NRXN1) gene that has been considered as one of the strong candidate genes. A total of 30 children and adolescents (aged 3-18) with non syndromic autism were enrolled this study. Sequencing of the coding exons and the exon-intron boundaries of the NRXN1 gene was performed. Two known mutations were described in two different cases. Heterozygous S14L was determined in one patient and heterozygous L748I was determined in another patient. The S14L and L748I mutations have been described in the patients with autism before. Both of these mutations were inherited from their father. In this study, two of 30 (6.7%) autism spectrum disorder (ASD) patients carrying NRXN1 gene mutations were detected. It indicates that variants in the NRXN1 gene might confer a risk of developing nonsyndromic ASD. However, due to the reduced penetrance in the gene, the causal role of the NRXN1 gene mutations must be evaluated carefully in all cases.
Polymorphism of angiotensin-converting enzyme (rs4340) and diabetic nephropathy in Caucasians with type 2 diabetes mellitus
Authors: Šeruga M , Makuc J , Završnik M , Cilenšek I , Ekart R , Petrovič D 
Published: March 2017

AbstractDiabetic nephropathy (DN) is the leading cause of endstage renal disease (ESRD) in developed countries. Several environmental and genetic factors predict the development and progression of DN. The renin-angiotensin system was demonstrated to be involved in the development of DN. We evaluated the association between rs4340 of the angiotensin-converting enzyme (ACE) gene and DN in Caucasians with type 2 diabetes mellitus (T2DM) in 276 Slovenian patients with T2DM who had DN, and 375 patients without clinical signs of DN. Genetic analysis was performed with either standard polymerase chain reaction (PCR) (for rs4340). Results were analyzed using the χ2test and multivariate logistic regression analyses. We found no association between rs4340 and DN. Cystatin C was significantly higher in the DN+ group (p<0.001) than in the DN group. Cystatin C was a better marker for the estimation of renal function than estimated glomerular filtration rate (eGFR) according to the modification diet in renal disease (MDRD) equation mL/ min. We concluded that there was no association between the rs4340 of theACEgene and DN in Caucasian patients who have T2DM.
Polymorphism of theIL13gene may be associated with Uterine leiomyomas in Slovenian women
Authors: Krsteski J , Jurgec S , Pakiž M , But I , Potočnik U 
Published: March 2017

AbstractUterine leiomyomas (ULM) are a common cause of solid pelvic tumors in women. Their etiopathogenesis remains unclear. Interleukins (ILs) and their receptors can influence tumor biology of ULM. The aim of this study was to evaluate single nucleotide polymorphisms (SNPs) exhibited in the genesIL4(rs2070874),IL4R(rs1801275),IL12RB1(rs11575934),IL12B(rs6887695),IL13(rs20541) andIL23R(rs7517847) as risk factors for ULM in Slovenian women and to identify associations between corresponding clinical parameters and the analyzed SNPs. In addition, solitary and multiple ULM were compared to identify clinical and/or genetic parameters influencing their occurrence. We conducted a case-control study that included 181 women with leiomyomas and 133 control subjects. Genotyping of selected SNPs was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and high resolution melting (HRM) techniques. The TT genotype of rs20541 (IL13) was significantly associated with decreased risk of ULM compared to both the CC and CT genotypes [p =0.018; odds ratio (OR) = 0.184; 95% confidence interval (95% CI) = 0.048-0.7121. Using genetic and clinical data to develop a predictive model with logistic regression, we found that adenomyosis, higher age at diagnosis, family history of ULM occurrence, earlier menarche, lower number of pregnancies and lower age at first sexual intercourse, the G allele and genotypes AG and GG of rs1801275 (IL4R) were associated with an increased risk of multiple ULM occurrence. We also found an association between rs20541 (IL13) and 17ß-estradiol serum levels in patients with multiple ULM (p0.003). Our study showed, for the first time, that rs20541 (IL13) may contribute to susceptibility of ULM development and that rs1801275 (IL4R) can predispose patients to develop multiple ULM.