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Francesco Lo Re

and 5 more

Aim The study aim is the validation of two algorithms of Limited Sampling Strategy (LSS) for the quantification of Mycophenolic Acid (MPA) Area under the plasma concentration-time curve from 0 to 12h (AUC0-12h) in a cohort of non-selected Heart Transplant (HTx) recipients treated, as standard clinical practice, with Mycophenolate Mofetil (MMF) combined with Cyclosporine (CsA), or Tacrolimus (TAC). These two LSSs were previously tested and validated by Baraldo et al. in a cohort of selected HTx recipients 1,2. The value of MPA AUC0-12h (real and estimated with LSSs) among non-rejected (NR) and rejected (R) patients were evaluated. Methods Linear regression and Bland Altman Analysis validated two LSSs methods (named LSS3 and LSS4 by number of blood samples used). The value of MPA AUC0-12h between NR and R patients were compared by Mann-Whitney test. Results The validation reports positive results for LSS3 and LSS4 according to linear regression (r=0.91 and 0.94 and R2=0.84 and 0.88, respectively) and Bland Altman Analysis (p=0.04 and 0.04). There was a difference of borderline statistically significance (p=0.06) for the median value of MPA AUC0-12h (mg×h/L) between NR and R patients (46.60; Interquartile Range (IQR): 34.80-64.10 vs 33.70; IQR: 23.60-48.25); whereas the difference was statistically significant for both LSS3 and LSS4 (p=0.03 and 0.04). Conclusion The capability of these two LSSs to estimate MPA AUC0-12h in cohort of non-selected HTx recipients and the suggestion of a significant difference on MPA AUC0-12h between NR and R patients, confirm the importance of MPA quantification in the clinical field.

Jesse Wolf

and 7 more

The usage of preprint servers in ecology and evolution is increasing, as it allows for research to be rapidly disseminated and available through open access at no cost. This is relevant for Early Career Researchers (ECRs), who must demonstrate research ability for funding opportunities, scholarships, grants, or faculty positions in short temporal windows in order to advance their careers. Concurrently, limited experience with the peer review process can make it challenging for those who are in the early stages of their research career to build publication records. Therefore, ECRs face different challenges relative to researchers with permanent positions and established research programs and have different requirements in terms of research output and timelines. These challenges might also vary according to institution size and country, which are associated with the availability of funding for open access journals. Herein, we hypothesize that career stage and institution size impact relative usage of preprint servers among researchers in ecology and evolution. Using data collected from 500 articles (100 from each of two open access journals, two closed access journals, and a preprint server), we demonstrate that ECRs generate more preprints relative to non-ECRs, for both first and last authors. We speculate that this pattern is reflective of the advantages of quick and open access research that is disproportionately beneficial to ECRs. There is also a marginal effect of first author institution size on preprint usage, whereby the number of preprints tends to increase with institution size for ECRs, although the interaction between ECR status and institution size was not significant. The United States and United Kingdom contributed the greatest number of preprints by early career researchers, whereas non-western countries contributed relatively fewer preprints. This research provides empirical evidence regarding motivations of preprint usage and barriers surrounding large-scale adoption of preprinting in ecology and evolution.

Daria Popova

and 4 more

Background: Normal mature sperm have a considerably reduced number of mitochondria which provide the energy required for progressive sperm motility. Literature suggests that disorders of sperm motility may be linked to abnormal sperm mitochondrial number and function. Objectives: To summarise the evidence from literature regarding the association of mitochondrial DNA copy numbers and semen quality with a particular emphasis on the spermatozoa motility. Search strategy: Standard methodology recommended by Cochrane. Selection criteria: All published primary research reporting on differences in mitochondrial DNA copy numbers between the sperm of males with a normal and abnormal semen analysis. Data collection and analysis: Using standard methodology recommended by Cochrane we pooled results using a random effects model and the findings were reported as a standardised mean difference. Main results: We included 10 trials. The primary outcome was sperm mitochondrial DNA copy numbers. A meta-analysis including five studies showed significantly higher mitochondrial DNA copy numbers in abnormal semen analysis as compared to normal semen analysis(SMD 1.08, 95% CI 0.74-1.43). Three other studies not included in the meta-analysis showed a significant negative correlation between mitochondrial DNA copy numbers and semen parameters. The quality of evidence was assessed as good to very good in 60% of studies. Conclusions: Our review demonstrates significantly higher mitochondrial DNA in human sperm cells of men with abnormal semen analysis in comparison to men with normal semen analysis. PROSPERO registration: CRD42019118841 Funding None received

Huseyin Erdal

and 4 more

Introduction: We aimed to measure the dynamic thiol-disulfide balance and thioredoxin reductase (TrxR) enzyme levels in patients with chronic kidney disease (CKD). Material and Methods: Thirty hemodialysis (HD), 30 CKD patients (stage3-5) and 30 controls were included in the study. The dynamic thiol-disulfide balance was determined by the colorimetric method developed by Erel et al. TrxR levels were determined by ELISA. Results: Native and total thiol levels of CKD and HD patients were significantly lower than that of the control group (p=0.001for both). However, disulfide levels were significantly higher in the HD group (p=0.001), but there was no significant difference between control and CKD groups(p=0.547). A notable negative correlation was found between the native and total thiol levels and IMA(r=-0.628;-0.631),BUN (r=-0.747;-0.747),and creatinine(r=-0.732;-0.721). There was a significant positive correlation between GFR and the thiol levels (r=0.835;0.824). TrxR levels were significantly higher in the patient groups compared to the controls (p=0.001).CRP levels of the patient groups were significantly higher compared to the controls (p=0.001). Conclusions: We have demonstrated that measurement of dynamic thiol-disulfide levels by using colorimetric method can contribute to the diagnosis and follow-up of the disease as a marker, because, it is easily applicable in routine clinical biochemistry laboratories and related with disease severity in CKD patients. Also, we showed that volume correction due to dialysis process should be consider in studies dealing with plasma thiol values and the final results should be given after the correction process.

Jiaqiong Zhang

and 3 more

Given that soil erosion is a primary cause of land degradation globally, it has been receiving increasing attention in food production regions, such as the Mollisol region in northeastern China. This study assessed soil quality under soil erosion degradation using a novel optimal data set (ODS) approach and a comparative minimum data set (MDS) approach based on soil quality indices (SQIs) within an agriculture watershed in Bin County, Heilongjiang Province, China. SQIs selection was contingent on multiple soil factors. Soil erosion rates was determined using cesium-137 technique. Relationships between soil quality and erosion or deposition rates were also analyzed. Results showed that erosion primarily drove soil redistribution, and soil quality grades were generally extremely low (approx. 80% of sampling sites), based on results from both the MDS and ODS approaches. However, soil quality varied significantly between erosion and deposition sites, it increased from upstream to midstream to downstream areas. Moreover, changes in SQIs and erosion rates exhibited spatially opposite trends, indicative of the impact that soil erosion has on soil quality, which was also confirmed by comparing representative soil properties at soil erosion and deposition sites. The good correlation between the MDS and ODS approaches indicated the feasibility of the ODS approach in estimating soil quality. Finally, the ODS approach is a cause-related method applying a relatively strict indicator selection procedure, which, compared to the MDS approach, could theoretically obtain more reliable results. Further studies are nevertheless necessary to assess the feasibility of this novel approach in other cases.

Erdi Babayiğit

and 3 more

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Huseyin Kazan

and 6 more

Objective: To investigate the factors, especially preoperative urinalysis, predicting postoperative early infection after retrograde intrarenal surgery (RIRS) in 1-2 cm renal stones. Methods: Of the 642 patients who underwent RIRS between September 2013 and July 2019, 289 patients with a total stone size of 1-2 cm were included in the study. Patients were divided into two groups as with and without postoperative urinary tract infection. The demographic data and perioperative findings of all patients were retrospectively reviewed. Sterile urine cultures were obtained in all patients during the preoperative 30-day period and urine analysis values were included in the data. Results: Urinary system infection (UTI) was seen in 20 (6.9%) of 289 patients. Patient demographics were similar between groups. There was no statistically significant difference between the two groups in terms of stone diameter and stone localization (median diameter 13.5 vs 15, p=0.285). Patients with postoperative UTI had a higher rate of UTI history (55% vs 20.5%, p=0.000) and longer operative times (62.5 vs 60 min., p=0.008). Rate of pyuria, leukocyte esterase and nitrite positivity were observed more frequently in patients with postoperative UTI. In multivariate analysis, UTI history, prolonged operative time, and nitrite positivity were found to be independent risk factors for postoperative UTI. Conclusion: Nitrite positivity in preoperative urinanalysis, history of UTI and prolonged operation time are the factors that predict the postoperative infection in RIRS for stones between 1-2 cm.

Gunter Sturm

and 38 more

Background: There is controversy whether taking β-blockers or ACE inhibitors (ACEI) is a risk factor for more severe systemic insect sting reactions (SSR) and whether it increases the number or severity of adverse events (AE) during venom immunotherapy (VIT). Methods: In this open, prospective, observational, multicenter trial, we recruited patients with a history of a SSR and indication for VIT. The primary objective of this study was to evaluate whether patients taking β-blockers or ACEI show more systemic AE during VIT compared to patients without such treatment. Results: In total, 1,425 patients were enrolled and VIT was performed in 1,342 patients. Of all patients included, 388 (27.2%) took antihypertensive (AHT) drugs (10.4% took β-blockers, 11.9% ACEI, 5.0% β-blockers and ACEI). Only 5.6% of patients under AHT treatment experienced systemic AE during VIT as compared with 7.4% of patients without these drugs (OR: 0.74, 95% CI: 0.43–1.22, p=0.25). The severity of the initial sting reaction was not affected by the intake of β-blockers or ACEI (OR: 1.14, 95% CI: 0.89–1.46, p=0.29). In total, 210 (17.7%) patients were re-stung during VIT and 191 (91.0%) tolerated the sting without systemic symptoms. Of the 19 patients with VIT treatment failure, 4 took β-blockers, none an ACEI. Conclusions: This trial provides robust evidence that taking β-blockers or ACEI does neither increase the frequency of systemic AE during VIT nor aggravate SSR. Moreover, results suggest that these drugs do not impair effectiveness of VIT. (Funded by Medical University of Graz, Austria; number, NCT04269629)

Nazanin Kermani

and 12 more

Background. Patients with severe asthma may have a greater risk of dying from COVID-19 disease. Angiotensin converting enzyme-2 (ACE2) and the enzyme proteases, transmembrane protease serine 2 (TMPRSS2) and FURIN, are needed for viral attachment and invasion into host cells. Methods. We examined microarray mRNA expression of ACE2, TMPRSS2 and FURIN in sputum, bronchial brushing and bronchial biopsies of the European U-BIOPRED cohort. Clinical parameters and molecular phenotypes, including asthma severity, sputum inflammatory cells, lung functions, oral corticosteroid (OCS) use, and transcriptomic-associated clusters, were examined in relation to gene expression levels. Results. ACE2 levels were significantly increased in sputum of severe asthma compared to mild-moderate asthma. In multivariate analyses, sputum ACE2 levels were positively associated with OCS use and male gender. Sputum FURIN levels were significantly related to neutrophils (%) and the presence of severe asthma. In bronchial brushing samples, TMPRSS2 levels were positively associated with male gender and body mass index, whereas FURIN levels with male gender and blood neutrophils. In bronchial biopsies, TMPRSS2 levels were positively related to blood neutrophils. The neutrophilic molecular phenotype characterised by high inflammasome activation expressed significantly higher FURIN levels in sputum than the eosinophilic Type 2-high or the pauci-granulocytic oxidative phosphorylation phenotypes. Conclusion. Levels of ACE2 and FURIN may differ by clinical or molecular phenotypes of asthma. Sputum FURIN expression levels were strongly associated with neutrophilic inflammation and with inflammasome activation. This might indicate the potential for a greater morbidity and mortality outcome from SARS-CoV-2 infection in neutrophilic severe asthma.

Mehmet Pehlivaoğlu

and 5 more

Aim: This study evaluated the effect of intracavitary levobupivacaine infusion diluted with locally applied isotonic solution for pain control in cystoscopy. Methods: Included in this study are 100 patients who had previously undergone transurethral tumor resection for bladder tumor and were followed up by cystoscopy. The patients were randomized into five groups (n = 20). In the first, second, third, and fourth groups, 4, 6, 8, and 10 mL of levobupivacaine HCl (5.0 mg/mL) were mixed with 26, 24, 22, and 20 mL of isotonic solution, respectively. Hence, the total mixture was 30 mL for each group. The fifth group was the control group. In this group, the standard method commonly used in most clinics was utilized. That is, a gel containing Cathejell-2% lidocaine (25 mg lidocaine) was applied. Cystoscopic interventions were performed with a 17.5 Fr rigid cystoscope and 0°, 30°, and 70° lens. During cystoscopy and 30 min later, the pain status of patients was assessed using the Visual Analogue Scale (VAS), and patient satisfaction was questioned. Results: The mean VAS score during and after the cystoscopy procedure was significantly lower in the levobupivacaine groups compared to the lidocaine group. In addition, patient satisfaction in the levobupivacaine groups was significantly higher than in the lidocaine group. No drug-related side-effects were observed in all groups. Conclusion: Thus, levobupivacaine is a more effective drug than lidocaine alone to control pain during cystoscopy. The use of levobupivacaine is recommended to prevent possible complications of general anesthesia by eliminating the need for the aforementioned as well as its cost-saving advantage.

Yanhui Dong

and 4 more

Groundwater age is often used to estimate groundwater recharge through a simplified analytical approach. This estimated recharge is thought to be representative of the mean recharge between the point of entry and the sampling point. However, given the complexity in actual recharge, whether the mean recharge is reasonable is still unclear. This study examined the validity of the method to estimate long-term average groundwater recharge and the possibility of obtaining reasonable spatial recharge pattern. We first validated our model in producing reasonable age distributions using a constant flux boundary condition. We then generated different flow fields and age patterns by using various spatially-varying flux boundary conditions with different magnitudes and wavelengths. Groundwater recharge was estimated and analyzed afterwards using the method at the spatial scale. We illustrated the main findings with a field example in the end. Our results suggest that we can estimate long-term average groundwater recharge with 10% error in many parts of an aquifer. The size of these areas decreases with the increase in both the amplitude and the wavelength. The chance of obtaining a reasonable groundwater recharge is higher if an age sample is collected from the middle of an aquifer and at downstream areas. Our study also indicates that the method can also be used to estimate local groundwater recharge if age samples are collected close to the water table. However, care must be taken to determine groundwater age regardless of conditions.

Xinyi Guan

and 4 more

Adriana Bustamante

and 3 more

Yasser Mubarak

and 1 more

Background: Small Aortic Annulus (AA) is big issue during Aortic Valve Replacement (AVR) necessitating replacement of an undersized prosthetic valve especially with Double Valve Replacement (DVR). Despite that small aortic valve prostheses can lead to Prosthesis-Patient Mismatch (PPM), there remains reluctance to perform aortic root enlargement (ARE) procedures fearing from morbidity and mortality. Objective: To evaluate clinical and echocardiographic outcomes in patients with small aortic annulus undergoing double valve replacement. Methods: The study included 100 consecutive patients underwent DVR for combined rheumatic aortic and mitral valve diseases, between Jan. 2016 and Sept. 2020. Only (50) patients had ARE with DVR. ARE was performed using an autologous or bovine pericardium or Dacron patch by Nicks or Manouguian procedures. The estimated postoperative end-points were mortality, effective orifice areas (EOA), mean aortic pressure gradient and valve-related complications. The least postoperative follow-up period was 6 months. Results: The study included 30 male and 70 female patients with mean age of 35±20 years, body surface area (BSA) of 1.7 ±0.3 m2, aortic annulus diameter was 20±1.4 mm, aortic orifice area was 0.8±0.1 cm2, and mean pressure gradient 85±2.5 mmHg. During follow-up period, there was a mild to moderate paravalvular leak (1%) with, (1%) heart block, and residual gradient on prosthetic aortic valve; that was all in DVR alone. Conclusion: Enlargement of aortic root by Nicks or Manouguian technique is safe and effective in patients with small aortic annulus undergoing double valve replacements.

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