bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cardioprotective Effects of Atorvastatin Are Mediated Through PPARγ in Paraquat-Exposed Rats
Authors: Malekinejad Mojtaba , Masoumi Verki Masoumeh , Khoramjouy Mona , Alenabi Aylar , Hallaj-Salahipour Mahsa , Malekinejad Hassan 
Published: August 2019

Background:
Paraquat poisoning is one of leading intoxication worldwide without an effective antidote and treatment protocol. Among the other organs, cardiotoxicity of paraquat has been frequently reported.

Aim:
The protective effects of atorvastatin (STN) on paraquat-induced cardiotoxicity and the role of peroxisome proliferator–activated receptors γ in the mediation of STN effects were investigated.

Methods:
Forty-two male Wistar rats were aliquoted into control or test groups. The animals in test groups in addition of paraquat received saline normal (PQ), pioglitazone (PGT), atorvastatin (STN), PGT + STN, PGT + GW9662, and/or STN + GW9662 for 14 days.

Results:
PGT and STN lowered lipid peroxidation rate, nitric oxide concentration, and activity of myeloperoxidase and CK/MB in the heart. PGT and STN protected from thiol molecules reduction and PQ-induced histopathological injuries. STN regulated the PQ-induced upregulation of COX-II expression in the heart. All STN-related protective effects were reversed by GW9662 as PPARγ antagonist.

Conclusions:
These data suggest a cardioprotective effect for STN against the PQ-induced inflammation and oxidative stress. The pharmacologic approach of these findings indicates that STN through PPARγ pathway lowered the PQ-induced cardiotoxicity.
Upregulating MicroRNA-203 Alleviates Myocardial Remodeling and Cell Apoptosis Through Downregulating Protein Tyrosine Phosphatase 1B in Rats With Myocardial Infarction
Authors: Zhang Jing , Pan Jianyuan , Yang Mengsi , Jin Xiaoqin , Feng Jun , Wang Ailing , Chen Zhenfei 
Published: August 2019

Abstract:
Myocardial infarction (MI) is one of cardiovascular diseases with high incidence and mortality. MicroRNAs, as posttranscriptional regulators of genes, are involved in many diseases, including cardiovascular diseases. The aim of the present study was to determine whether miR-203 was functional in MI therapy and how it worked. Left anterior descending artery ligation and hypoxia/reoxygenation (H/R) treatment were, respectively, performed to obtain MI rats and hypoxia-injured H9c2 cells. Western blot and quantitative real-time polymerase chain reaction were used to determine protein levels and messenger RNA of relevant genes, respectively. Lentivirus-mediated overexpression of miR-203 was performed to study the miR-203 functions on left ventricular remodeling, infarct size, and cardiomyocyte apoptosis. Compared with the sham group, miR-203 levels were significantly decreased in MI and H/R groups. However, overexpressing miR-203 greatly improved the cardiac function, reduced infarct size in rats after MI and weakened infarction-induced apoptosis by increasing Bcl-2 and reducing decreasing Bax, cleaved caspase-3, and cleaved caspase-9. In addition, Protein tyrosine phosphatase 1B (PTP1B) was proved as a target of miR-203 in cardiomyocytes, and it was negatively regulated by miR-203. Further experiments indicated that PTP1B overexpression could remarkably inhibit miR-203-mediated antiapoptosis of cardiomyocytes and alleviate protective effects of miR-203 on mitochondria after H/R treatment. Altogether, miR-203 prevented infarction-induced apoptosis by regulating PTP1B, including reducing proapoptosis proteins, inactivating caspase pathway, and protecting mitochondria. In conclusion, miR-203 had abilities to alleviate MI-caused injury on myocardium tissues and reduce mitochondria-mediated apoptosis, which might be a potential target used for MI therapy.
Synthetic Cathinones and Their Potential Interactions with Prescription Drugs
Authors: Contrucci Ramon R. , Brunt Tibor M. , Inan Funda , Franssen Eric J. F. , Hondebrink Laura 
Published: August 2019

Purpose:
Substance use disorder often coexists with other psychiatric disorders, resulting in the simultaneous use of recreational and prescription drugs. The authors aimed to identify potential pharmacokinetic and pharmacodynamic interactions between new psychoactive substances of the cathinone class and specific prescription drugs.

Methods:
The authors performed a systematic literature review on interactions between synthetic cathinones (mephedrone, methylone, methylenedioxypyrovalerone, and alpha-pyrrolidinopentiophenone) and antidepressants (citalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, and venlafaxine), attention deficit hyperactivity disorder (ADHD) medications (atomoxetine, dexamphetamine, methylphenidate, modafinil) or HIV medications.

Results:
Although no pharmacokinetic interactions have been reported in previous literatures, such interactions are likely to occur. Metabolic pathways of cathinones, antidepressants, and ADHD medications have been shown to overlap, including metabolism via cytochrome P450 enzymes and their inhibition. Consistent with this finding, interactions of bupropion (a cathinone) with antidepressants and ADHD medications have been found to increase their serum concentrations and half-lives. Additionally, limited pharmacodynamic interactions have been reported. However, as cathinones, antidepressants, and ADHD medications have been reported to increase the extracellular monoamine concentration by affecting reuptake transporters, interactions among these compounds are likely. Presumably, even higher monoamine concentrations could be observed when cathinones are combined with prescription drugs with a similar mode of action, as has been reported in animals exposed to duloxetine and bupropion. HIV medications have a different mode of action; thus, they have been reported to be less likely to have pharmacodynamic interactions with cathinones.

Conclusions:
Clinicians should be aware of possible interactions between synthetic cathinones and prescription drugs, which may increase the risk of drug toxicity or reduce the therapeutic efficacy of the drugs. Qualitative drug screening for cathinones using mass spectrometry methods may aid the early detection of these agents.
Prednisolone Concentrations in Plasma (Total and Unbound) and Saliva of Adult Kidney Transplant Recipients
Authors: Brooks Emily , Tett Susan E. , Isbel Nicole M. , McWhinney Brett , Staatz Christine E. 
Published: August 2019

Background:
Prednisolone displays significant pharmacokinetic variability and exposure–outcome relationships in renal transplant recipients, suggesting a role for drug monitoring in some scenarios. It is highly protein-bound, and the free form is pharmacologically active but cumbersome to measure. Saliva concentrations might reflect free plasma prednisolone and present an alternative measurement. The aim of this study was to examine the correlation between total and free plasma and saliva prednisolone in adult renal transplant recipients.

Methods:
Total and free plasma and saliva prednisolone concentrations were measured in 20 patients receiving oral prednisolone 1–2 months after transplant, between pre-dose and 12 hours post-dose. Prednisolone was determined using high-performance liquid chromatography mass spectrometric detection. The Pearson coefficient was used to assess the association between plasma and salivary prednisolone concentrations and area under the concentration–time curves (AUC0–12).

Results:
When considering all time points, the total and free plasma prednisolone concentrations correlated well (r2 = 0.81), but there was poor correlation between saliva and free (r2 = 0.003) and total (r2 = 0.01) plasma concentrations. When concentrations before the maximum free prednisolone plasma value were excluded, the correlation between free plasma and saliva concentrations improved (r2 = 0.57). There was a moderate correlation between free and total plasma prednisolone AUC0–12 (r2 = 0.62) using all time points, but a poor correlation between free and total plasma prednisolone AUC0–12 and saliva AUC0–12 (r2 = 0.07; r2 = 0.17).

Conclusions:
Total and free plasma prednisolone measurements correlated poorly with saliva measurements; however, correlation improved when concentrations early in the dosing interval were excluded.
Comparison of the Area Under the Curve for Vancomycin Estimated Using Compartmental and Noncompartmental Methods in Adult Patients With Normal Renal Function
Authors: Shingde Rashmi V. , Graham Garry G. , Reuter Stephanie E. , Carland Jane E. , Day Richard O. , Stocker Sophie L. 
Published: August 2019

Background:
Vancomycin pharmacokinetics are best described using a 2-compartment model. However, 1-compartment population models are commonly used as the basis for dose prediction software. Therefore, the validity of using a 1-compartment model to guide vancomycin drug dosing was examined.

Methods:
Published plasma concentration–time data from adult subjects (n = 30) with stable renal function administered a single intravenous infusion of vancomycin were extracted from previous studies. The vancomycin area under the curve (AUC0–∞) was calculated for each subject using noncompartmental methods (AUCNCA) and by fitting 1- (AUC1CMT), 2- (AUC2CMT), and 3- (AUC3CMT) compartment infusion models. The optimal model fit was determined using the Akaike information criterion and visual inspection of the residual plots. The individual compartmental AUC0–∞ values from the 1- and 2-compartment models were compared with AUCNCA values using one-way repeated measures analysis of variance.

Results:
The mean (±SD) AUC estimates were similar for the different methods: AUCNCA 180 ± 86 mg·h/L, AUC1CMT 167 ± 79 mg·h/L, and AUC2CMT 183 ± 88 mg·h/L. Despite the overlapping AUC values, AUC2CMT and AUCNCA were significantly greater than AUC1CMT (P < 0.05). The 3-compartment model was excluded from the analysis because of the failure to converge in some instances.

Conclusions:
Dose prediction software using a 1-compartment model as the basis for Bayesian forecasting underestimates drug exposure (estimated as the AUC) by less than 10%. This is unlikely to be clinically significant with respect to dose adjustment. Therefore, a 1-compartment model may be sufficient to guide vancomycin dosing in adult patients with stable renal function.
Monitoring of Thyroid Malfunction and Therapies in Pregnancy and the Postpartum Period: A Systematic Updated Critical Review of the Literature
Authors: Bohnet Heinz G. 
Published: August 2019

Purpose:
From the very beginning of pregnancy, the maternal thyroid has to adapt to increased thyroid hormone secretion of up to 50%. This is paralleled by changes in thyroid-stimulating hormone secretion and by the thyroid-topic action of human chorionic gonadotropin. Thus, hypothyroidism and hyperthyroidism may occur. Many women exhibit preexisting thyroid diseases. This review tries to add the most recently published approaches to diagnosing thyroid malfunction in pregnancy to existing guidelines.

Methods:
Different literature-based approaches to diagnosing thyroid malfunction during pregnancy and the postpartum period were applied. To diagnose thyroid malfunction in pregnancy, trimester-specific reference ranges for thyroid-stimulating hormone and T4 are used.

Results:
Definitions of thyroid malfunction are given. Treatment schedules for various thyroid diseases were reviewed and, on the basis of recent findings, were revised where necessary. For a daily clinical workup, this outline not only suggests diagnostic and therapeutic steps but also refers to frequent pitfalls and misinterpretations of laboratory data.

Conclusions:
Although the body of knowledge is increasing rapidly, the authors believe that this review is able to present new ideas concerning diagnostic and therapeutic tools for thyroid malfunction in pregnancy and the postpartum period. Nevertheless, there seems to remain room for individual approaches based on the personal experience of physicians who deal with these issues regularly.
Therapeutic Drug Monitoring of Olanzapine and Cytochrome P450 Genotyping in Nonsmoking Subjects
Authors: Miroshnichenko Igor I. , Pozhidaev Ivan V. , Ivanova Svetlana A. , Baymeeva Natalia V. 
Published: August 2019

Background:
The relationship between a daily dose of olanzapine, its serum concentration, and the genotype of young nonsmoking men treated for schizophrenia or schizophreniform disorder was investigated in day-to-day clinical practice. Pharmacogenetics was also examined for the selected patients.

Methods:
A total of 49 participants were recruited as in-patients at the Mental Health Research Center (Moscow, Russia). Inclusion criteria were patients who had been diagnosed with schizophrenia or schizoaffective disorder (following DSM-IV guidelines) and were being treated with OLZ. A prospective, observational, open-study design was implemented. In line with the literature, patients were only included if they attained steady-state OLZ concentrations lasting for at least 8 days. A liquid chromatographic–tandem mass spectrometric method was developed for analyzing OLZ in human serum. The single cytochrome P450 polymorphisms were genotyped using an amplifier real-time polymerase chain reaction system following standard protocols.

Results:
Evidence indicating that CYP2D6 polymorphism has a significant (P = 0.046) effect on the pharmacokinetics of olanzapine was obtained, confirming the beneficial effects of therapeutic drug monitoring (TDM) for olanzapine.

Conclusions:
TDM should therefore be used as a standard care during olanzapine therapy. TDM is also useful in assessing adherence and may have a role in limiting olanzapine dosage geared at minimizing the risk of long-term toxicity.
EVALUATION OF SURGICAL FACTORS AFFECTING VITREOUS HEMORRHAGE FOLLOWING PORT DELIVERY SYSTEM WITH RANIBIZUMAB IMPLANT INSERTION IN A MINIPIG MODEL
Authors: Bantseev Vladimir , Schuetz Chris , Booler Helen S. , Horvath Joshua , Hovaten Kristof , Erickson Signe , Bentley Ellison , Nork T. Michael , Freeman William R. , Stewart Jay M. , Barteselli Giulio 
Published: August 2019

Purpose:
To develop an animal model of vitreous hemorrhage (VH) to explore the impact of surgical parameters on VH associated with insertion of the Port Delivery System with ranibizumab (PDS) implant.

Methods:
Ninety eyes from 45 treatment-naive male Yucatan minipigs received PDS implant insertion or a sham procedure. The effect of prophylactic pars plana hemostasis, scleral incision length, scleral cauterization, surgical blade type/size, and viscoelastic usage on postsurgical VH was investigated.

Results:
Postsurgical VH was detected in 60.0% (54/90) of implanted eyes. A systematic effect on VH was only detected for pars plana hemostasis before the pars plana incision. The percentage of eyes with VH was 96.6% (28/29) among eyes that did not receive prophylactic pars plana hemostasis and 42.4% (24/58) among eyes that did. There was no VH in eyes that received laser ablation of the pars plana using overlapping 1,000-ms spots; pars plana cautery or diathermy was less effective. The majority of all VH cases (83.3% [45/54]) were of mild to moderate severity (involving ≤25% of the fundus).

Conclusion:
In this minipig surgical model of VH, scleral dissection followed by pars plana laser ablation before pars plana incision most effectively mitigated VH secondary to PDS implant insertion.
AN ATYPICAL CASE OF SOLAR MACULOPATHY
Authors: Bloom Steven M. , Singal Inder P. 
Published: August 2019

Purpose:
To present a case of atypical solar maculopathy.

Methods:
Case report.

Results:
A 7-year-old boy who viewed an eclipse 17 months earlier had macular findings blending features of solar and laser pointer maculopathies. The right macula clinically had a central 1,000-μm, slightly irregular round area of pigmentary changes and a tiny outer macular optical coherence tomography defect. In addition, the superior fovea had a hyperreflective mound-like retinal pigment epithelial detachment extending into the outer retina. The left macula contained several, more typical solar maculopathy lesions.

Conclusion:
We describe a unique case of solar maculopathy displaying typical optical coherence tomography findings in both eyes along with a unilateral laser pointer-like hyperreflective retinal pigment epithelial detachment.
MULTIMODAL IMAGING AND TREATMENT OF SYPHILITIC CHOROIDAL NEOVASCULARIZATION
Authors: Giuffrè Chiara , Marchese Alessandro , Cicinelli Maria Vittoria , Miserocchi Elisabetta , Querques Giuseppe , Bandello Francesco , Modorati Giulio 
Published: August 2019

Purpose:
To report a rare case of choroidal neovascularization (CNV) developed 2 years after successful treatment of ocular syphilis, identified by optical coherence tomography angiography.

Methods:
Case report.

Results:
A 31-year-old man with a history of syphilitic chorioretinitis developed a CNV 2 years after clinical remission of the infection. Structural optical coherence tomography (OCT) and optical coherence tomography angiography were helpful in providing detailed evidence of an extrafoveal CNV in an easy and noninvasive way. In comparison, the identification of CNV on fluorescein angiography was difficult because of the retinal blood barrier breakdown and intense choroidal background fluorescence for diffuse chorioretinal scarring of syphilitic chorioretinitis. The patient underwent 3 intravitreal injections of anti–vascular endothelial growth factor in addition to 25 mg/day of oral prednisone, with the restoration of previous visual acuity.

Conclusion:
Choroidal neovascularization is a rare, but sight-threatening complication of syphilitic chorioretinitis. The combination of different imaging modalities, and in particular optical coherence tomography angiography, allowed reaching a definite diagnosis of CNV. Combined treatment of systemic steroid and intravitreal anti–vascular endothelial growth factor was effective in controlling the CNV and improving the visual outcome.
XEN Gel Stent to Treat ICE Syndrome: 4 Cases
Authors: Lin Michael M. , Morgan William H. , Kolomeyer Natasha N. , Moster Stephen J. , Zheng Cindy X. , Giubilato Antonio , Moster Marlene R. 
Published: August 2019

Précis:
This case series reports safe, effective implantation of XEN gel stents to treat iridocorneal endothelial (ICE) syndrome. The stents continue to function well and have not been occluded by membranes or peripheral anterior synechiae, but continued follow-up is necessary.

Purpose:
ICE syndrome-related glaucoma is often refractory to medical treatment, and traditional surgical treatment has lower success rates than typical for other types of glaucoma. We present a series of patients who were treated with XEN gel stent implantation.

Patients and Methods:
Retrospective case series of 4 patients with ICE syndrome who underwent XEN with subconjunctival mitomycin C injection.

Results:
Average preoperative intraocular pressure was 28.5 mm Hg on 3.8 glaucoma medications, and average postoperative intraocular pressure was 10.5 mm Hg on 1.0 medication. No patients required return to the operating room for additional procedures over an average of 6.9 months of follow-up. One patient had shallow anterior chamber that resolved with conservative management. Another had shallow anterior chamber that resolved with anterior chamber reformation with viscoelastic and developed nonappositional choroidal effusions that had resolved at most recent follow-up of 7 months after surgery. No XEN implants have been occluded by membrane formation or peripheral anterior synechiae.

Conclusions:
XEN is a safe and effective option for surgical management of ICE syndrome-related glaucoma. Further follow-up surveillance is necessary.
Cell type–specific super-resolution imaging reveals an increase in calcium-permeable AMPA receptors at spinal peptidergic terminals as an anatomical correlate of inflammatory pain
Authors: Woodhams Stephen G. , Markus Robert , Gowler Peter R.W. , Self Timothy J. , Chapman Victoria 
Published: August 2019

Abstract
Spinal hyperexcitability is a key event in the development of persistent pain, and arises partly from alterations in the number and localization of α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA)-type glutamate receptors. However, determining precisely where these changes occur is challenging due to the requirement for multiplex labelling and nanoscale resolution. The recent development of super-resolution light microscopy provides new tools to address these challenges. Here, we apply combined confocal/direct STochastic Optical Reconstruction Microscopy (dSTORM) to reveal changes in calcium-permeable subunits of AMPA-type glutamate receptors (GluA1) at identified spinal cord dorsal horn (SCDH) peptidergic axon terminals in a model of inflammatory pain. L4/5 lumbar spinal cord was collected from adult male C57BL/6J mice 24 hours after unilateral hind paw injection of saline or 1% carrageenan (n = 6/group). Tissue was immunolabelled for markers of peptidergic axon terminals (substance P; SP), presynaptic active zones (Bassoon), and GluA1. Direct stochastic optical reconstruction microscopy revealed a 59% increase in total GluA1 immunolabelling in the SCDH in the carrageenan group, which was not detected by confocal microscopy. Cell type–specific analyses identified a 10-fold increase in GluA1 localized to SP+ structures, and identified GluA1 nanodomains that scaled with behavioural hypersensitivity, and were associated with synaptic release sites. These findings demonstrate that dSTORM has the sensitivity and power to detect nanoscale anatomical changes in the SCDH, and provides new evidence for synaptic insertion of GluA1+-AMPA-Rs at spinal peptidergic nociceptive terminals in a model of inflammatory pain.
Where are we now? Practice-level utilization of nurse practitioners in comparison with state-level regulations
Authors: Zwilling Jana G. , Fiandt Kathryn 
Published: August 2019

ABSTRACT

Background and purpose:
Full practice authority for nurse practitioners (NPs) is optimal for high-quality, cost-effective health care. However, a complete picture of utilization after states have adopted full practice authority needs to be determined. The purpose of this examination was to review the evidence regarding practice-level utilization (PLU) of NP PLU in comparison to state-level regulations (SLRs).

Methods:
Studies published in English and based on US populations were identified through PubMed, CINAHL, and Scopus (January 1, 1989–December 31, 2018), and bibliographies of retrieved articles. Of the 419 articles identified with these limits, 19 (5%) met all inclusion and exclusion criteria.

Conclusions:
Four categories of PLU were identified: billing practices, level of supervision, privileges, and prescriptive authority. Significant differences were seen between urban versus rural NPs and primary care versus specialty NPs. Thirteen of the 19 studies did not specifically address the SLR of the included sample.

Implications for practice:
No studies described the type of NP certification, practice specialty, and utilization, and compared all to the SLR. There is a need for more evidence concerning PLU of NPs across the tiers of SLR. Only then can health care organizations, political leaders, and other stakeholders have the information needed to proceed with beneficial practice-model changes.