bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of Cilostazol and Naftidrofuryl in an Experimental Acute Ischemia-Reperfusion Model
Authors: Gülaştı Ömer Faruk , Yavuz Şadan , Arıkan Ali Ahmet , Eraldemir Fatma Ceyla , Özbudak Ersan , Şahin Deniz , Kır Hale Maral 
Published: September 2020

Introduction: Naftidrofuryl and cilostazol are drugs with proven efficacy in the treatment of claudication in peripheral vascular disease. In this experimental study, we evaluated the effects of naftidrofuryl and cilostazol in ischemia-reperfusion (IR) injury on various tissues. Materials and Methods: 40 male albino Wistar rats (8-12 weeks old, 250-350 g.) are randomly divided into 4 groups: Control (Group 1), sham (group 2), cilostazol pre-treatment (group 3), naftidrofuryl pre-treatment (group 4). During 21 days placebo is given to group 2, 12 mg/kg/day cilostazol is given to group 3, 50 mg/kg/day naftidrofuryl is given to group 4 orally. Ischemia and reperfusion are induced at the lower hind limb in Groups 2, 3 and 4. Ischemic muscle, kidney, liver, heart, brain and blood samples are obtained. The total antioxidant capacity, oxidant levels and oxidative stress index are studied for each group. Results: Both drugs have protective effects of remote organ injury following IR. Systemic effects are similar to each other, both have protective effects of IR injury. It showed no statistical significance in the total antioxidant capacity. Total oxidant levels are significantly affected by cilostazol in the heart (p < 0.01) and by naftidrofuryl in the liver (p < 0.01). The effect on oxidative stress was only significant with cilostazol on the heart (p < 0.01). Conclusion: Cilostazol and naftidrofuryl had beneficial effects in all tissues against tissue damage caused by IR injury. In ischemic muscle, kidney and heart cilostazol had improved outcomes comparing to naftidrofuryl. Naftidrofuryl had benefits over cilostazol in liver tissue.
Electroclinical Phenotype-Genotype Homogeneity in Drug-Resistant “Generalized” Tonic-Clonic Seizures of Early Childhood
Authors: Jukkarwala Anis , Menon Ramshekhar N. , Sunesh E. R. , Radhakrishnan Ashalatha 
Published: September 2020

Purpose Children with refractory focal to bilateral tonic-clonic seizures, despite normal high-resolution imaging, are often not subjected to genetic tests due to the costs involved and instead undergo multimodality presurgical evaluation targeted at delineating a focal onset. The objective of this study was to ascertain genotype-phenotype correlations in this group of patients. Method An online hospital database search was conducted for children who presented in 2019 with drug-resistant epilepsy dominated by nonlateralizing focal-onset/rapid generalized (bilateral) tonic-clonic seizures (GTCS), subjected to presurgical evaluation and subsequent genetic testing due to absence of a clear focus hypothesis. Results Phenotypic homogeneity was apparent in 3 children who had onset in infancy with drug-resistant GTCS (predominantly unprovoked and occasionally fever provoked) and subsequent delayed development. 3-Tesla magnetic resonance imaging (MRI) scans were negative and video EEG documented a homogeneous pattern of multifocal and/or generalized epileptiform discharges with phenomenology favoring probable focal-onset/generalized-onset bilateral tonic-clonic seizures. All 3 tested positive for SCN1A gene variants (heterozygous missense substitution variants in 2 children, one of which was novel and a novel duplication in one that led to frameshift and premature truncation of the protein), suggestive of SCN1A-mediated epilepsy. This electroclinical profile constituted 3 out of 25 patients with SCN1A-epilepsy phenotypes at our center. Conclusions These cases suggest that children with early-onset drug-resistant “generalized” epilepsy are likely to have a genetic basis although the presentation may not be typical of Dravet syndrome. Hence, genetic testing for SCN1A variants is recommended in children with drug-resistant MRI negative focal-onset/generalized-onset bilateral tonic-clonic seizures before subjecting them to exhaustive presurgical workup and to guide appropriate treatment and prognostication.
The effect of using Richmond agitation and sedation scale on hospital stay, ventilator dependence, and mortality rate in ICU inpatients: a randomised clinical trial
Authors: Rashidi Mahbobeh , Molavynejad Shahram , Javadi Nasser , Adineh Mohammad , Sharhani Assad , Poursangbur Tayebeh 
Published: September 2020

Background Managing the amount of use of sedatives due to their high side effects in the intensive care unit is essential. Sedation-agitation protocols may play an important role in this regard. However, they have not been practically applied in Iran. Aims This study aimed to evaluate the effect of using the Richmond agitation and sedation scale on hospital stay duration and dependency rate on the intensive care unit ventilator system in Ahwaz City, Iran, in 2016–2017. Methods This randomised clinical trial was conducted on 74 patients. The subjects were selected by a stratified sampling method and divided into the experimental ( n = 32) and control ( n = 32) groups. Sedation and agitation levels were managed by the Richmond agitation and sedation scale as soon as the samples were anxious and agitated, and every 6 hours in the intervention group. However, the control group received routine care. The data obtained were analysed by the Statistical Package for the Social Sciences (SPSS). Results There was no significant difference between the two groups in terms of demographic variables, such as age, gender, admission diagnosis and Glasgow coma scale scores on admission. However, they differed in terms of hospital stay duration and ventilator connection ( P < 0.001), Glasgow coma scale score at the separation time from the device ( P < 0.001), Glasgow coma scale score at the discharge time from the intensive care unit ( P < 0.02) and intensive care unit death rate ( P < 0.001). In all cases mentioned previously, the intervention group’s condition was better. Conclusions Based on the results of this study, as well as the approval of validation and reliability of the Richmond agitation and sedation scale in different studies, this protocol can be very effective in optimising the use of sedatives in the intensive care unit.
Circulating metabolomics profiling reveals novel pathways associated with cognitive decline in patients with hypertension
Authors: Huang Yuli , Zheng Haoxiao , Tan Kuan , Sun Xiangdong , Ye Jinshao , Zhang Yunlong 
Published: September 2020

Background: Hypertension is a significant risk factor for cardiovascular disease, and it is associated with dementia, including Alzheimer’s disease (AD). Although it may be correlated with AD in terms of symptoms, the link between hypertension and AD pathological biomarkers, and the potential underlying mechanism of hypertension with cognitive decline, are still not well understood. Methods: The Mini-Mental State Examination (MMSE) scores were used to evaluate cognitive function. Enzyme-linked immunosorbent assays were used to examine plasma amyloid-beta (Aβ)40, Aβ42, and tau concentration in hypertensive patients. Metabolomics and metagenomics were performed to identify the significantly changed circulating metabolites and microbiota between healthy individuals and hypertensive patients. Pearson’s correlation was used to examine the association between cognitive indicators and differential metabolites. Results: We found significantly decreased MMSE scores, elevated plasma Aβ40, and decreased Aβ42/Aβ40 ratio in hypertensive patients, which are critically associated with AD pathology. Based on metabolomics, we found that significantly altered metabolites in the plasma of hypertensive patients were enriched in the benzoate degradation and phenylpropanoid biosynthesis pathways, and they were also correlated with changes in MMSE scores and Aβ42/Aβ40 ratio. In addition, metabolomics signaling pathway analysis suggested that microbial metabolism was altered in hypertensive patients. We also identified altered blood microbiota in hypertensive patients compared with the controls. Conclusions: Our study provides a novel metabolic and microbial mechanism, which may underlie the cognitive impairment in hypertensive patients.
Oral disease-modifying antirheumatic drugs and immunosuppressants with antiviral potential, including SARS-CoV-2 infection: a review
Authors: Tsai Y. C. , Tsai T. F. 
Published: September 2020

There have been several episodes of viral infection evolving into epidemics in recent decades, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the latest example. Its high infectivity and moderate mortality have resulted in an urgent need to find an effective treatment modality. Although the category of immunosuppressive drugs usually poses a risk of infection due to interference of the immune system, some of them have been found to exert antiviral properties and are already used in daily practice. Recently, hydroxychloroquine and baricitinib have been proposed as potential drugs for SARS-CoV-2. In fact, there are other immunosuppressants known with antiviral activities, including cyclosporine A, hydroxyurea, minocycline, mycophenolic acid, mycophenolate mofetil, leflunomide, tofacitinib, and thalidomide. The inherent antiviral activity could be a treatment choice for patients with coexisting rheumatological disorders and infections. Clinical evidence, their possible mode of actions and spectrum of antiviral activities are included in this review article. Lay summary Immunosuppressants often raise the concern of infection risks, especially for patients with underlying immune disorders. However, some disease-modifying antirheumatic drugs (DMARDs) with inherent antiviral activity would be a reasonable choice in the situation of concomitant viral infections and flare up of autoimmune diseases. This review covers DMARDs of treatment potential for SARS-CoV-2 in part I, and antiviral mechanisms plus trial evidence for viruses other than SARS-CoV-2 in part II.
Injectable Ketorolac and Corticosteroid Use in Athletes: A Systematic Review
Authors: Jelsema Timothy R. , Tam Anthony C. , Moeller James L. 
Published: September 2020

Context: The use of injectable medications to help athletes quickly return to the field of play after injury is common. Understanding the effects and risks of these medications will help providers make informed decisions regarding their use in this patient population. Objective: To evaluate the utilization, efficacy, and adverse effects of injectable ketorolac and corticosteroids in athletes. Data Sources: This systematic review followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A systematic search of the literature was performed using multiple databases (PubMed, Embase, Cochrane, Web of Science, and ClinicalTrials.gov). Secondary references were appraised for relevant articles. No randomized controlled trials or other prospective studies were identified. Articles included retrospective database reviews and physician survey studies. Study Selection: A total of 6 studies met the inclusion and exclusion criteria and were reviewed by 2 independent reviewers with a third consulted in the case of disagreement, which was not needed. Study Design: Systematic review. Level of Evidence: Level 5. Data Extraction: Two reviewers recorded rate of use, effectiveness of treatment, and reported side effect data. Results: Most studies centered around the football athlete, either professional or collegiate. Professional football game day use of intramuscular ketorolac declined from 93.3% (28/30) in 2002 to 48% in 2016. Collegiate football game day use of intramuscular ketorolac declined from 62% in 2008 to 26% in 2016. Game day corticosteroid injection was far lower than ketorolac usage. Both medications were reported to be effective with few adverse events. Conclusion: Use of injectable ketorolac is common but declining in professional and college football. Pain control efficacy is good, and risk of adverse events is low. The incidence of injectable corticosteroid use in athletes is unknown. Use of injectable corticosteroids in athletes allows for early return to sport activities with no reported complications.
A Provincial Survey of the Contemporary Management of Autosomal Dominant Polycystic Kidney Disease
Authors: Yi Tae Won , Levin Adeera , Bevilacqua Micheli , Canney Mark 
Published: September 2020

Background: Recent years have witnessed an encouraging expansion of knowledge and management tools in the care of patients with autosomal dominant polycystic kidney disease (ADPKD), including measurement of total kidney volume as a biomarker of disease progression, stringent blood pressure targets to slow cyst growth, and targeted treatments such as tolvaptan. Objectives: We sought to evaluate clinicians’ familiarity with, and usage of, novel evidence-based management tools for ADPKD. Design: On-line survey. Setting: British Columbia, Canada. Participants: Nephrologists in academic and community practice (excluding clinicians who practice exclusively in transplantation). Measurements: Participants answered multiple-choice questions in 6 domains: sources of information, self-identified needs for optimal care delivery, prognostication, imaging tests, blood pressure targets, and use of tolvaptan. Methods: An online survey was developed and disseminated via email to 65 nephrologists engaged in current clinical practice in British Columbia. Results: A total of 29 nephrologists (45%) completed the questionnaire. The most popular source of information was the primary literature (83% of respondents). While 86% of respondents reported assessing the risk of disease progression before the onset of kidney function decline, most were using traditional metrics such as blood pressure and proteinuria rather than validated prediction tools such as the Mayo Classification. Although 90% of respondents obtained additional imaging after diagnosis in some or all of their ADPKD patients, only 1 in 5 reported being confident in their ability to interpret kidney size. The recommended blood pressure (BP) target of <110/75 mmHg was sought by 17% of respondents. All respondents reported being familiar with the literature regarding tolvaptan; however, only half were confident in their ability to identify suitable patients for treatment. The top 3 needs identified by clinicians were better access to medications (69%), clear management protocols (66%), and easier access to imaging tests (59%). Limitations: Funding mechanisms for tolvaptan can vary; therefore, clinicians’ experience with the drug may not be generalizable. Although the response rate was acceptable, the survey is nonetheless subject to responder bias. Conclusion: This survey indicates that there is substantial variability in the usage of, and familiarity with, evidence-based ADPKD management tools among contemporary nephrologists, contributing to incomplete translation of evidence into clinical practice. Providing greater access to tolvaptan or imaging tests is unlikely to improve patient care without enhancing knowledge translation and education. Trial Registration: Not applicable as this was a survey.
The 90-Day Reoperations and Readmissions in Complex Adult Spinal Deformity Surgery
Authors: Lee Nathan J. , Lenke Lawrence G. , Cerpa Meghan , Lombardi Joseph , Ha Alex , Park Paul , Leung Eric , Sardar Zeeshan M. , Lehman Ronald A. 
Published: September 2020

Study Design: Retrospective review. Objective: Identify surgical complex adult spine deformity patients who are at increased risk for an unplanned postoperative 90-day readmission and/or reoperation. Methods: A total of 227 consecutive records of complex adult (≥18 years old) spine deformity surgeries from 2015 to 2018 were reviewed. Demographics, comorbidities, operative details, and postoperative complication data was collected. Chi-square/Fisher’s exact test and t tests were used for bivariate analysis. To determine independent predictors for readmissions/reoperations, stepwise multivariate logistic regressions were employed. The C-statistic and Hosmer-Lemeshow (HL) value was used to measure concordance and goodness of fit. Results: Average age was 50.5 ± 17.8 years and 67.8% were female. Ninety-day readmission and reoperation rates were 7.0% and 5.3%, respectively. Median number of days after index discharge date resulting in readmission and reoperation were 16.5 and 28, respectively. The multivariate regression for 90-day readmissions included pulmonary comorbidity, depression, history of deep vein thrombosis/pulmonary embolism (DVT/PE), and gastrointestinal comorbidity (C-statistic = 0.82; HL = 0.79). Pulmonary comorbidity, depression, and history of DVT/PE increased risk for 90-day readmission by 5-, 3.5-, and 10.2-fold, respectively. The multivariate regression for 90-day reoperations was similar to readmissions (C-statistic = 0.89; HL = 0.31). Operative time>7 hours and history of DVT/PE increased risk for early reoperation by 5.8- and 8.7-fold, respectively. Conclusions: An emphasis on medically optimizing patients with preexisting pulmonary comorbidities, depression, and history of DVT/PE may have a substantial impact on improving short-term outcomes in this population. The present study provides benchmark data and may serve as an initial model to predict unplanned reoperations and readmissions.
Salivary Fructosamine as a Noninvasive Glycemic Biomarker: A Systematic Review
Authors: Khoury Z.H. , Illesca P. , Sultan A.S. 
Published: September 2020

Background: Standard diagnostic and monitoring methods for glycemic status involve invasive sample collection through venous puncture or fingerstick. Recent attention has been focused on exploring noninvasive methods through oral biofluids. Specifically, serum fructosamine has been established as a short-term (2- to 3-wk) marker of disease status in patients with diabetes. Fructosamine measured through noninvasive means such as saliva has shown promise, but its clinical applicability is unknown. Objective: Evaluate the available evidence on using salivary fructosamine as a reliable noninvasive marker to screen and diagnose patients with diabetes mellitus in the clinical setting. A comparative analysis of the correlative accuracy of salivary fructosamine measurements with established blood glycemic biomarkers such as serum fructosamine, blood glucose, and HbA1c will be conducted. Methods: Six electronic databases (PubMed, PubMed Central, MEDLINE, EMBASE, Scopus, Cochrane Library) were searched for original research papers (clinical and animal studies) that were relevant to the objective of this systematic review. The search was initiated on May 28, 2020. The systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Bias risk assessment, overall quality, and level of evidence were based on the Oxford Centre for Evidence-Based Medicine, Appraisal Tool for Cross-Sectional Studies, and Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Studies tool. Heterogeneity was assessed using the National Institutes of Health quality assessment tool for cross-sectional studies. Results: A total of 174 records were identified. Full-text articles screened for eligibility (n = 21) identified only 6 original research articles relevant to the research question and were thus included in the systematic review. The types of studies identified were cross-sectional and in vivo studies. Three studies (3/6) showed positive correlation of salivary fructosamine with blood glucose levels, while 1 study (1/6) demonstrated a positive correlation with glycated hemoglobin (HbA1c). Limitations related to sample size and selection were identified along with a fair level of interstudy heterogeneity. Conclusion: Based on the evidence evaluated, the utility of salivary fructosamine as a noninvasive marker to screen and diagnose patients with diabetes is doubtful. The overall level of evidence was low (IIIB) and the risk of bias was determined to be high. Knowledge Transfer Statement: Further evidence in the form of large-scale well-controlled studies is needed prior to recommending salivary fructosamine as a noninvasive diagnostic tool for glycemic status in patients with diabetes mellitus.
The neurotransmitter receptor Gabbr1 regulates proliferation and function of hematopoietic stem and progenitor cells
Authors: Shao Lijian , Elujoba-Bridenstine Adedamola , Zink Katherine E. , Sanchez Laura M. , Cox Brian J. , Pollok Karen E. , Sinn Anthony L. , Bailey Barbara J. , Sims Emily C. , Cooper Scott H. , Broxmeyer Hal E. , Pajcini Kostandin V. , Tamplin Owen J. 
Published: September 2020

Abstract
Hematopoietic and nervous systems are linked via innervation of bone marrow (BM) niche cells. Hematopoietic stem/progenitor cells (HSPCs) express neurotransmitter receptors, such as the γ-aminobutyric acid (GABA) type B receptor subunit 1 (GABBR1), suggesting that HSPCs could be directly regulated by neurotransmitters like GABA that directly bind to GABBR1. We performed imaging mass spectrometry and found that the endogenous GABA molecule is regionally localized and concentrated near the endosteum of the BM niche. To better understand the role of GABBR1 in regulating HSPCs, we generated a constitutive Gabbr1-knockout mouse model. Analysis revealed that HSPC numbers were significantly reduced in the BM compared with wild-type littermates. Moreover, Gabbr1-null hematopoietic stem cells had diminished capacity to reconstitute irradiated recipients in a competitive transplantation model. Gabbr1-null HSPCs were less proliferative under steady-state conditions and upon stress. Colony-forming unit assays demonstrated that almost all Gabbr1-null HSPCs were in a slow or noncycling state. In vitro differentiation of Gabbr1-null HSPCs in cocultures produced fewer overall cell numbers with significant defects in differentiation and expansion of the B-cell lineage. To determine whether a GABBR1 agonist could stimulate human umbilical cord blood (UCB) HSPCs, we performed brief ex vivo treatment prior to transplant into immunodeficient mice, with significant increases in long-term engraftment of HSPCs compared with GABBR1 antagonist or vehicle treatments. Our results indicate a direct role for GABBR1 in HSPC proliferation, and identify a potential target to improve HSPC engraftment in clinical transplantation.