bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oxidative stress-induced activation of Abl and Src kinases rapidly induces P-glycoprotein internalization via phosphorylation of caveolin-1 on tyrosine-14, decreasing cortisol efflux at the blood–brain barrier
Authors: Hoshi Yutaro , Uchida Yasuo , Tachikawa Masanori , Ohtsuki Sumio , Couraud Pierre-Olivier , Suzuki Takashi , Terasaki Tetsuya 
Published: January 2019

Exposure of the brain to high levels of glucocorticoids during ischemia–reperfusion induces neuronal cell death. Oxidative stress alters blood–brain barrier (BBB) function during ischemia–reperfusion, and so we hypothesized that it might impair P-glycoprotein (P-gp)-mediated efflux transport of glucocorticoids at the BBB. Therefore, the purpose of this study was to clarify the molecular mechanism of this putative decrease of P-gp-mediated efflux function. First, we established that H2O2 treatment of a human in vitro BBB model (hCMEC/D3) reduced both P-gp efflux transport activity and protein expression on the plasma membrane within 20 min. These results suggested that the rapid decrease of efflux function might be due to internalization of P-gp. Furthermore, H2O2 treatment markedly increased tyrosine-14-phosphorylated caveolin-1, which is involved in P-gp internalization. A brain perfusion study in rats showed that cortisol efflux at the BBB was markedly decreased by H2O2 administration, and inhibitors of Abl kinase and Src kinase, which phosphorylate tyrosine-14 in caveolin-1, suppressed this decrease. Overall, these findings support the idea that oxidative stress-induced activation of Abl kinase and Src kinase induces internalization of P-gp via the phosphorylation of tyrosine-14 in caveolin-1, leading to a rapid decrease of P-gp-mediated cortisol efflux at the BBB.
An unresolved issue: The relationship between spot urine protein-to-creatinine ratio and 24-hour proteinuria
Authors: Akin Davut , Ozmen Sehmus 
Published: January 2019

Objective To investigate the relationship between spot urine protein-to-creatinine (sP/Cr) ratio and 24-h protein excretion in patients with different diagnoses. Methods This retrospective study analysed data from the medical records of patients admitted for24-h proteinuria determination who also had sP/Cr ratio data for the same day. Results A total of 1222 urine samples obtained from 694 adult outpatients were analysed. The mean ± SD age of the patients was 53.6 ± 15.9 years. The mean ± SD 24-h proteinuria and sP/Cr were 1.7 ± 2.4 g/day and 1.8 ± 2.4, respectively. The correlation between the sP/Cr and 24-h protein excretion was high (R2 = 0.89). The sP/Cr ratio accounted for 72% of the variability in 24-h proteinuria in the entire study population. Areas under the curve for 24-h proteinuria at 0.3 g/day, 1.0 g/day and 3.0 g/day were 0.940, 0.966, and 0.949, respectively. The mean + 2SD limits of agreement were between +2.99 and –2.73 g/day according to the Bland Altman analysis. Conclusion This current study found a clinically unacceptable deviation between 24-h proteinuria and sP/Cr ratio. Therefore, the sP/Cr ratio cannot replace 24-h proteinuria. A new method using spot urine protein and creatinine values that is able to minimize under or over estimation is still warranted.
TRAIL inhibits platelet-induced colorectal cancer cell invasion
Authors: Wu Li-Sha , Wang Xiao-Wei , He Wen , Ma Xiao-Ting , Wang Hai-Yue , Han Mei , Li Bing-Hui 
Published: January 2019

Objective Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a pro-apoptotic ligand that activates the extrinsic apoptosis pathway of cell death receptors. This study aimed to evaluate the relationship between TRAIL and platelet-induced tumor metastasis in colorectal cancer. Methods Platelet P-selectin (CD62P) was measured by immunohistochemistry in tumor and adjacent normal tissues from 90 patients with colorectal cancer undergoing resection. Tumor cell invasion was assessed by transwell assay in the presence of platelets with or without TRAIL. The expression of TRAIL receptors DR4 and DR5 on platelets was assessed by flow cytometry, real-time polymerase chain reaction, and western blotting. Results P-selectin (CD62P) expression was significantly increased in tumor tissues compared with adjacent normal tissues. High CD62P expression was significantly correlated with tumor stage and vascular invasion. Tumor cell migration was increased by coculture with platelets, but this effect was inhibited by TRAIL. Transforming growth factor (TGF)-β1 secretion was significantly reduced in TRAIL-treated platelets. The TRAIL receptor DR5 but not DR4 was expressed in platelets according to flow cytometry. Conclusions TRAIL could inhibit metastasis and colon cancer cell invasion by promoting platelet apoptosis and reducing the release of TGF-β1.
The effects of a multispecies probiotic supplement on inflammatory markers and episodic and chronic migraine characteristics: A randomized double-blind controlled trial
Authors: Martami Fahimeh , Togha Mansoureh , Seifishahpar Maryam , Ghorbani Zeinab , Ansari Hossein , Karimi Tahereh , Jahromi Soodeh Razeghi 
Published: January 2019

Background The current study was designed to assess the effect of supplementation with a 14-strain probiotic mixture on episodic and chronic migraine characteristics. Methods Forty episodic and 39 chronic migraine patients who completed this randomized double-blind controlled trial received two capsules of multispecies probiotic or placebo. The migraine severity was assessed by visual analog scale (VAS). The number of abortive drugs consumed, migraine days, frequency and duration of attacks were recorded on paper-based headache diaries. Serum tumor necrosis factor alpha (TNF-α) and C- reactive protein (CRP) levels were measured at baseline and the end of the intervention. Results After a 10-week intervention, among episodic migraineurs the mean frequency of migraine attacks significantly reduced in the probiotic group compare to the placebo group (mean change: −2.64 vs. 0.06; respectively, p < 0.001). A significant reduction was also evident in the migraine severity (mean decrease: −2.14 in the probiotic group and 0.11 in the placebo group; p < 0.001). Episodic migraineurs who received the probiotic also showed significant reduction in abortive drug usage per week (mean change: −0.72; p < 0.001) compare to baseline, while there was no significant changes within the placebo group. In chronic migraine patients, after an 8-week intervention, the mean frequency of migraine attacks significantly reduced in the probiotic compared to the placebo group (mean change: −9.67 vs. −0.22; p ≤ 0.001). In contrast to the placebo, probiotic supplementation significantly decreased the severity (mean changes: −2.69; p ≤ 0.001), duration (mean changes: −0.59; p ≤ 0.034) of attacks and the number of abortive drugs taken per day (mean changes: −1.02; p < 0.001), in chronic migraine patients. We failed to detect any significant differences in the serum levels of inflammatory markers at the end of the study either in chronic or in episodic migraineurs. Discussion The results of this study showed that the 14-strain probiotic mixture could be an effective and beneficial supplement to improve migraine headache in both chronic and episodic migraineurs. Further research is required to confirm our observations.
Major League Baseball Pitching Performance After Tommy John Surgery and the Effect of Tear Characteristics, Technique, and Graft Type
Authors: Marshall Nathan E. , Keller Robert , Limpisvasti Orr , Schulz Brian , ElAttrache Neal 
Published: January 2019

Background: Return to play and player satisfaction have been quite high after ulnar collateral ligament reconstruction (UCLR); however, there has been little reported on how outcomes are affected by surgical technique, graft type, and tear characteristics. Purpose: To evaluate surgical techniques, graft type, and tear characteristics on Major League Baseball (MLB) performance after UCLR. Study Design: Cohort study; Level of evidence, 2. Methods: MLB pitchers who underwent primary UCLR at a single institution were included. Tear characteristics included tear location, tear grade, and acuity. Surgical technique and graft type were also collected. Pitching performance statistics, including earned run average (ERA), walks and hits per innings pitched (WHIP), innings pitched, and fastball velocity were evaluated 3 years before and after UCLR. Results: Forty-six MLB pitchers were identified as having primary UCLR. Return to play was 96%, with 82% returning to MLB play. Technique performed showed no difference in performance. As compared with pitchers with gracilis grafts, pitchers with palmaris grafts were younger ( P = .043), played longer after surgery ( P = .012), and returned to play at 100% (35 of 35) versus 82% (9 of 11, P = .010). When compared with pitchers with proximal tears, pitchers with distal tears pitched at higher velocity (93.0 vs 90.6 mph, P = .023) and had better performance before surgery (ERA, P = .003; WHIP, P = .021); however, those with proximal tears improved to match this performance and velocity after reconstruction. As compared with those having partial tears, pitchers with complete tears played longer after surgery (5.9 vs 4.0 years, P = .033), had a better ERA before injury ( P = .041), and had better WHIP ( P = .037) and strikeouts per 9 innings ( P = .025) after reconstruction. Pitchers with chronic tears had a significant improvement in postoperative ERA, from 4.49 to 3.80 ( P = .040). Conclusion: Technique performed and graft type used did not affect performance; however, pitchers with palmaris grafts returned at a higher rate than those with gracilis grafts. Distal tears occurred in pitchers with greater velocity and better performance before injury, yet pitchers with proximal tears matched this performance after reconstruction. Pitchers with complete tears played longer after reconstruction. Pitchers who had partial tears had worse performance before injury and after reconstruction, and those with chronic tears saw a significant improvement in ERA with reconstruction.
Angiotensin II type 2 receptor gene polymorphisms and serum angiotensin-converting enzyme level in Egyptian children with systemic lupus erythematosus
Authors: Shoaib R M S , Yahia S , Elsaid A , Abdel-Malak C , Hammad A 
Published: January 2019

Background There are no reports about the association of angiotensin II type 2 receptor ( AT2R) gene polymorphisms and susceptibility to systemic lupus erythematosus (SLE) in children. Objective The objective of this research is to study AT2R gene polymorphisms in exon 3 (C1593A) and intron 1 (A1675G) in Egyptian children with SLE and its correlation with disease manifestations and serum angiotensin-converting enzyme (ACE) level. Methods Typing of AT2R gene polymorphisms was conducted in 123 children with SLE in comparison with 100 healthy controls using the restriction fragment length polymorphism method. Results Significant differences were found between SLE patients and controls for A-containing genotypes (CA + AA) and A-allele frequencies of AT2R in exon 3 (C1593A) ( p = 0.01, odds ratio (OR) = 2.5, 95% confidence interval (CI) = 1.3–5.05; p = 0.01, OR = 2.2, 95% CI = 1.2–4.1, respectively). G-containing genotypes (AG + GG) and G allele of AT2R in intron 1 (A1675G) were more frequent in SLE patients compared to controls ( p = 0.01, OR = 2.3, 95% CI = 1.2–4.5; p = 0.02, OR = 2.1, 95% CI = 1.2–3.7, respectively). Serum ACE level was significantly higher in SLE patients than in controls ( p < 0.001). There was no association between AT2R gene polymorphisms and ACE level in serum. Moreover, there was no association between AT2R gene polymorphisms and SLE clinical manifestations. Conclusion AT2R gene polymorphisms can be considered risk factors for SLE development in Egyptian children.
Key indicators of organized cancer screening programs: Results from a Delphi study
Authors: Csanádi Marcell , de Kok Inge MCM , Heijnsdijk Eveline AM , Anttila Ahti , Heinävaara Sirpa , Pitter János G , Széles György , Ivanuš Urška , Priaulx Jennifer , Veerus Piret , Senore Carlo , Koning Harry J de , Vokó Zoltán 
Published: January 2019

Objective To maximize benefits and reduce potential harms of organized cancer screening programs in Europe, monitoring, quality assurance, and evaluation of long-term impact are required. We aimed to identify the most important indicators to be collected and reported. The study was designed to establish a consensus within a European-level working group and suggest a manageable list of key indicators. Methods We conducted a Delphi study among policymakers, researchers, and program coordinators who were experts in breast, cervical, or colorectal cancer screening. Study participants evaluated the importance of screening indicators on a 5-point Likert scale. Results The top 10 indicators by study participants were interval cancer rate, detection rate, screening attendance, screening coverage, cancer incidence, cause-specific mortality, proportion of persons attending further assessment after a positive screen test result, proportion of persons attending a treatment after diagnosis, invitation coverage, and distribution of cancers by mode of detection. Performance indicators were generally considered more important than outcome indicators. Subgroup analyses by cancer types showed similar results, and only cervical cancer screening experts had slightly different preferences. Subgroup analyses by experts’ roles indicated that policymakers found different indicators important compared with researchers or program coordinators, probably because of their different point of view on screening. Conclusion The implication of our priority ranking is twofold: it serves as an initial guidance for countries that have not yet established a system to collect data, and as a checklist for those where data collection is already established, to assess the comprehensiveness of their system.
Achilles Tension Mitigates Fibular Malalignment Measured in Cadaveric Studies of Syndesmotic Clamping
Authors: Goetz Jessica E. , Szabo Nicole , Rudert M. James , Karam Matthew D. , Phisitkul Phinit 
Published: January 2019

Background: Fibular malreduction is becoming a commonly recognized complication of surgical repair of the syndesmosis when a reduction clamp is used. The goal of this work was to determine the interdependent effects of transsyndesmotic reduction clamp position and applied compression force on fibular alignment in a realistic cadaveric preparation of complete syndesmotic injury. Methods: Six through-the-knee cadaveric specimens were CT scanned intact, with the distal syndesmosis fully destabilized, and with 53, 102, and 160 N clamping forces each applied along an anteriorly, centrally, and posteriorly directed transsyndesmotic axis. Testing was repeated incorporating 178 N of Achilles tendon tension using all 3 clamping forces applied along the centrally directed axis. Fibular reduction was automatically quantified from CT scan–generated bony surfaces as rotation of the fibula around the tibia, rotation of the fibula within the incisura, medial/lateral fibular displacement, and anterior/posterior fibular displacement. Results: Transsyndesmotic clamping along the anteriorly directed axis resulted in the best reduction quality by all 4 quantified measures. Along the centrally and posteriorly directed axes, progressively greater forces caused significantly greater sagittal plane fibular malreduction. Addition of Achilles tension reduced the magnitude of fibular malreduction and overcompression. Conclusion: Placing the medial tine of a transsyndesmotic reduction clamp on the anterior medial tibia resulted in the most accurate syndesmotic reduction and provided some protection against overcompression with large reduction clamp forces. Achilles tension appeared to contribute to reduction, decreasing the magnitude of measured malreduction from clamping. Clinical relevance: Previous studies estimating fibular malpositioning in cadaveric models that lacked passive muscle tension may have overestimated expected magnitudes of malalignment in patients treated with syndesmotic clamping. However, syndesmotic malreduction, particularly in the sagittal plane, was a real complication of syndesmotic clamping that was reduced by using an anterior position of the medial tine on the tibia.
Effect of Lateral Ligament Augmentation Using Suture-Tape on Functional Ankle Instability
Authors: Cho Byung-Ki , Hong Seok-Hyun , Jeon Jae-Hyeon 
Published: January 2019

Background: Although lateral ligament augmentation using suture-tape has been effective for restoration of mechanical ankle stability, few data are available regarding changes of peroneal strength, proprioception, and postural control. The aim of this study was to determine effects of suture-tape augmentation on functional ankle instability (FAI). Methods: Twenty-four patients who underwent suture-tape augmentation were eligible and were followed more than 2 years postoperatively. Functional outcomes were evaluated with the Cumberland Ankle Instability Tool (CAIT), Foot and Ankle Ability Measure (FAAM). Changes of peroneal strength, proprioception and postural control were analyzed with an isokinetic dynamometer and a modified Romberg test. Results: CAIT and FAAM (average of daily and sports activity scores) significantly improved to average 27.2 points and 86.7 points, respectively, at final follow-up. Peak torque for eversion in 60 degrees/s angular velocity significantly improved to 10.6 Nm at final follow-up. Deficit ratio of peak torque for eversion significantly improved from mean 39.5% to 20.9%, and significant side-to-side difference was revealed ( P < .001). There were no significant differences in joint position sense. A significant improvement in balance retention time was revealed at final follow-up, and the relative deficit ratio compared to the unaffected side was 30.9%. Conclusions: Patient-reported functional outcomes significantly improved after lateral ligament augmentation using suture-tape. Although this procedure demonstrated significant effects on FAI based on improvement of isokinetic peroneal strength and postural control, recovery rates compared to the unaffected side were not significant at the intermediate-term follow-up. In addition, there was no positive effect on proprioception of the ankle. Level of Evidence: Level IV, prospective case series.
Intravitreal bevacizumab treatment for neovascular age-related macular degeneration and thromboembolic events
Authors: Weinstein Orly , Abu Tailakh Muhammad , Lifshitz Tova , Novack Victor , Levy Jaime 
Published: January 2019

Background: Systemic complications of intravitreal anti-vascular endothelial growth factor agents are relatively uncommon but highly significant. Objectives: Primary objective: To assess the risk for thromboembolic events following intravitreal bevacizumab injection in neovascular age-related macular degeneration patients by a large population-based study. Secondary objective: To analyze the association between injection frequency and the risk for thromboembolic events, the time interval between the injection and the thromboembolic events, and the influence of chronic diseases on complications rate. Design: A retrospective cohort study. Methods: Consecutive neovascular age-related macular degeneration patients receiving intravitreal bevacizumab at Soroka University Medical Center from December 2005 to December 2013 were included. Thromboembolic events analyzed included acute coronary syndrome, acute myocardial infarction, stroke, deep vein thrombosis, and pulmonary embolism. The thromboembolic event rate was compared 2 years prior and 2 years after the initial intravitreal bevacizumab injection. Results: A total of 2102 patients were included. Acute coronary syndrome and stroke rate were higher 2 years after intravitreal bevacizumab (p = 0.03 and p = 0.01, respectively). No statistical significant difference was found for the rest of thromboembolic events. Patients older than 80 years and patients receiving less than six intravitreal bevacizumab injections were more likely to experience stroke. Patients with known cardiovascular risk factors before starting injections did not develop significant more thromboembolic events. Conclusion: In our study population, patients treated with intravitreal bevacizumab were significantly more likely to experience stroke during 2 years after first injection.
Lower total cerebral arterial flow contributes to cognitive performance in multiple sclerosis patients
Authors: Jakimovski Dejan , Benedict Ralph HB , Marr Karen , Gandhi Sirin , Bergsland Niels , Weinstock-Guttman Bianca , Zivadinov Robert 
Published: January 2019

Background: The cognitive performance in multiple sclerosis (MS) patients declines with aging, longer disease duration, and possibly cardiovascular comorbidities. Objectives: We investigated whether lower total cerebral arterial blood flow (CABF) measured at the level of the carotid and vertebral arteries may contribute to worse cognitive performance in 132 MS patients and 47 healthy controls. Methods: Total CABF was evaluated with extracranial Doppler, whereas structural T2-lesion volume (LV) and gray matter volume (GMV) were measured on 3T MRI. The cognitive performance was assessed by Symbol Digit Modalities Test (SDMT), Brief Visuospatial Memory Test—Revised (BVMT-R), and California Verbal Learning Test—Second Edition (CVLT-II). Analysis of covariance, partial correlation, and regression models were used to test the differences between study groups and cognition/CABF correlations. False discovery rate (FDR)-corrected (Benjamini–Hochberg) p-values (i.e. q-values) less than 0.05 were considered significant. Results: Association between lower total CABF and the lower cognitive performance was observed only in MS patients ( r = 0.318, q < 0.001 and r = 0.244, q = 0.012 for SDMT and BVMT-R, respectively). Lower GMV, higher T2-LV, and CABF were significantly associated with poorer performance on the processing speed measure of SDMT (adjusted R2 = 0.295, t-statistics = 2.538, standardized β = 0.203, and q = 0.020), but not with memory tests. Cognitively impaired MS patients had lower total CABF compared to cognitively preserved (884.5 vs 1020.2 mL/min, q = 0.008). Conclusion: Cognitively impaired MS patients presented with lower total CABF. Altered CABF may be a result of reduced metabolic rate and might contribute to abnormal cognitive aging in MS.