bluuebunny/crossref_metadata_2025 huggingface dataset:
A retrospective study of open and endoscopic nephron sparing surgery in the treatment of complex renal tumors
Authors: Li Ting-ting , Feng Jia , Li Yan-ling , Sun Qian
Published: April 2021

Objective: To investigate clinical outcomes of open and retroperitoneal laparoscopic nephron-sparing surgery in the treatment of complex renal tumours.

Methods: A retrospective case study was conducted. Patients with complex renal tumours admitted to our hospital between January 2018 and September 2019 were enrolled; the included patients (n=40) were divided into the observation group (open partial nephrectomy, n=20) and control group (laparoscopic partial nephrectomy, n=20) according to operation modes. The operation time, renal warm ischaemia time, intraoperative blood loss, renal pedicle blocking time, intestinal function recovery time, postoperative hospital stay, and postoperative complications were recorded.

Results: Significant differences were noted regarding renal warm ischaemia time, renal pedicle blocking time, intraoperative blood loss, operation time, and postoperative hospital stay between the observation and control groups (P<0.05); however, no significant difference was observed in intestinal function recovery time and postoperative drainage days (P>0.05).

Conclusion: Open surgery remains the recommended surgical method for the treatment of few complex tumours in the renal hilus region and has gradually become the renal surgery of choice at present, although laparoscopic surgery has evolved tremendously.

doi: https://doi.org/10.12669/pjms.37.4.3457

How to cite this:Li TT, Feng J, Li YL, Sun Q. A retrospective study of open and endoscopic nephron sparing surgery in the treatment of complex renal tumors. Pak J Med Sci. 2021;37(4):1031-1035. doi: https://doi.org/10.12669/pjms.37.4.3457

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Team-based learning versus Traditional lecture-based learning: An investigation of students’ perceptions and academic achievements
Authors: Nawabi Shazia , Bilal Rabia , Javed Muhammad Qasim
Published: April 2021

Objectives: Evaluation of TBL from students’ perspective has been done extensively, but limited studies have analyzed the effect of TBL on students’ academic performance. Objectives of the present study were to assess students’ perceptions about team-based learning versus traditional lectures and then to compare with students’ grades in both TBL and lecture-based assessments.

Methods: Cross-sectional descriptive study which included 147 dentistry students was conducted between March and June, 2020 at Qassim University, Saudi Arabia. A self-composed 10 item closed ended instrument was administered through electronic mail. One block from each academic year was selected randomly and organizers were requested to provide grades of students in both TBL and lecture-based exams. Grades from A to F were determined as achievement indicator and were compared statistically using Kruskal Wallis, Tuckey Posthoc and Chi-square tests.

Results: A total of 120 students (81.6%) responded to the survey, and mean perception score was (3.29±0.94). Perceptions of students, regarding TBL as a learning strategy were comparatively superior as compared to the lectures. Students scored significantly higher grades in TBL exams (p<0.05) as compared to lecture-based assessments. Gender-wise analysis indicated that female students secured significantly higher grades in the TBL.

Conclusion: We conclude that dentistry students perceived TBL as superior teaching and learning strategy compared to traditional lectures. Their perception was verified by their significant higher academic achievements in the assessments for the coursework taught by utilizing team-based learning strategy.

doi: https://doi.org/10.12669/pjms.37.4.4000

How to cite this:Nawabi S, Bilal R, Javed MQ. Team-based learning versus Traditional lecture-based learning: An investigation of students’ perceptions and academic achievements. Pak J Med Sci. 2021;37(4):1080-1085. doi: https://doi.org/10.12669/pjms.37.4.4000

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
The relationship between problematic cell phone use, eating disorders and social anxiety among university students
Authors: Gokce Ayse , Ozer Ali
Published: April 2021

Objective: Problematic cell phone use is common among young age groups which include university students, and may be accompanied by social anxiety and eating disorders. We aimed to examine the relationship between problematic cell phone use, social anxiety and eating disorders among university students.

Methods: The universe of this cross-sectional study consists of 28,669 students receiving education at a Inonu University between October 2017 - November 2017. With a confidence interval of 95% and power of 80%, the sample size was calculated to be 308. The survey forms used in the study included students’ sociodemographic characteristics, data regarding cell phone usage, Problematic Mobile Phone Use Scale, Liebowitz Social Anxiety Scale and Eating Attitudes Test. The statistical analyses were conducted using Student t, One Way ANOVA, Spearman Correlation Test and Binomial Logistic Regression Analysis.

Results: The students in the study group demonstrated a 46.1% rate of problematic cell phone use. The students’ Problematic Mobile Phone Use Scale total scores showed a significant correlation with smoking, and daily duration and purpose of cell phone use (p<0.05).

Conclusion: University students demonstrate high rates of problematic cell phone use; in addition, individuals who use cell phones for increased hours or for certain purposes display higher total scores on the Problematic Mobile Phone Use Scale. Students should be educated on limiting problematic cell phone use.

doi: https://doi.org/10.12669/pjms.37.4.4124

How to cite this:Gokce A, Ozer A. The relationship between problematic cell phone use, eating disorders and social anxiety among university students. Pak J Med Sci. 2021;37(4):1201-1205. doi: https://doi.org/10.12669/pjms.37.4.4124

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Modeling of technical, economic, environmental and ergonomic parameters of forestry machines in function of the quantity of days of the working scale
Authors: Santos Diego Weslly Ferreira do Nascimento , Ribeiro Furtado Junior Marconi , Pinheiro Dadalto Juliana , Nunes do Santos Larissa , Mariano Leite Daniel
Published: April 2021

Forest machine operators work on a long scale of work, which causes physical and psychological wear and consequently reduced productivity and increased fuel consumption. The objective of this research was to verify the influence of the number of days of the work schedule of harvester and forwarder operators in low-volume forest on technical, economic, environmental and ergonomic parameters. The research was performed in forest stands with an average wood volume of 0.10 m³ tree-1. In the first, second, third and fourth day of the work schedule, productivity, energy demand, production cost, carbon dioxide emission and the occurrence of fatigue in the operators were determined. The productivity values ??of harvester operators on the third and fourth days of the work schedule decreased by 2.62 and 7.74%, respectively, in relation to the average value of the first and second days. The productivity of forwarder operators was similar in the first three days of the work schedule, with a more marked reduction in the fourth day. The reduction in the number of days in the forest machine operators’ work schedule makes the operation more sustainable from a technical, economic, environmental and ergonomic point of view.
Relationships between optical backscattering, particulate organic carbon, and phytoplankton carbon in the oligotrophic South China Sea basin
Authors: Qiu Guoqiang , Xing Xiaogang , Boss Emmanuel , Yan Xiao-Hai , Ren Rui , Xiao Wupeng , Wang Haili
Published: April 2021

The particulate backscattering coefficient (bbp) provides effective proxies for particulate organic carbon (POC) and phytoplankton carbon (Cphy); however, their bio-optical relationships in the oligotrophic ocean are rarely reported. In this work, based on the in-situ synchronous optical and biogeochemical measurements in the oligotrophic South China Sea (SCS) basin, we refined the regional relationships between POC (and Cphy) and bbp and investigated the impacts of phytoplankton community compositions and size classes on the bbp variability. The observations showed that: 1) POC and Cphy exhibited good linear relationships with bbp; 2) the relationship between Cphy and POC could also be fitted in a linear function with a positive POC intercept, and the POC contributed by phytoplankton-covarying non-algal particles was nearly two-fold of Cphy; and 3) the POC-specific bbp (b*bp) was positively correlated with the fraction of the phytoplankton groups haptophytes (Type 8) and diatoms to total Chla, but negatively correlated with the fraction of pico-phytoplankton to Chla (fpico). These findings suggest that in oligotrophic waters, the variability of b*bp was mainly determined by the variability in the relative contribution of large phytoplankton with complex structures.
Non-zero dispersion-shifted ring fiber for the orbital angular momentum mode
Authors: Zhao Wenqian , Wang Yingning , Li Si-ao , Geng Wenpu , Bao Changjing , Fang Yuxi , Wang Zhi , Liu Yan-ge , Ren Yongxiong , Pan Zhongqi , Yue Yang
Published: April 2021

As the dimension of orbital angular momentum (OAM) is orthogonal to the other degrees of freedom for photon, such as wavelength, it can be utilized to further increase data capacity in the wavelength division multiplexing (WDM) systems. However, the non-zero dispersion-shifted fiber (NZDSF) for the OAM mode has not yet been investigated or even proposed. In this work, we propose and design a ring fiber with low chromatic dispersion for the HE2,1 mode, which can serve as NZDSF for its corresponding OAM1,1 mode. A low dispersion of 3.3 ps/(nm·km) at 1550 nm and <2.9 ps/(nm·km) dispersion variation from 1530 to 1565 nm for the OAM1,1 mode is achieved in simulation, which satisfies the standard of the ITU-T G.655.C. The designed fiber with ring width from 1.5 µm to 3.5 µm can support the OAM1,1 mode within the C-band, and a large effective area of about 646 µm2 is obtained. We also note that the fiber with larger inner radius and ring width are more tolerant to the perturbations, such as fiber ellipticity and bending. In the fiber-based optical communication systems, the designed ring fiber could be used as a candidate for supporting OAM modes with low dispersion and reduced nonlinear effects.
Self-powered and high-performance all-fiber integrated photodetector based on graphene/palladium diselenide heterostructures
Authors: Yang Hongwei , Xiao Yihong , Zhang Kaimin , Chen Zefeng , Pan Jintao , Zhuo Linqing , Zhong Yongchun , Zheng Huadan , Zhu Wenguo , Yu Jianhui , Chen Zhe
Published: April 2021

An all-fiber integrated photodetector is proposed and demonstrated by assembling a graphene/palladium diselenide (PdSe2) Van der Waals heterostructure onto the endface of a standard optical fiber. A gold film is covered on the heterostructure working as an electrode and a mirror, which reflects back the unabsorbed residual light for further reusage. Owing to the low bandgap of PdSe2, the all-fiber photodetector shows a broadband photoresponse from 650 to 1550 nm with a high photoresponsivity of 6.68×104 AW−1, enabling a low light detection of 42.5 pW. And the fastest temporal response is about 660 µs. Taking advantage of heterostructures, the photodetector can work in self-powered mode with the on/off ratio about 82. These findings provide new strategies for integrating two-dimensional materials into optical fibers to realize integrated all-fiber devices with multi-function applications.
The virus of the ‘others’? Corona and discursive othering in Arab media
Authors: Richter Carola , Al-Shami Abdulrahman , Khalifa Sahar , Osman Soheir , Mundua Samuel
Published: April 2021

The spread of fear of the coronavirus and related insecurities around the pandemic have fuelled nationalist and increased exclusionary tendencies in countries all over the world. In North America, for instance, anti-Asian racism increased when former US President Donald Trump dubbed the virus the ‘Chinese virus’. A nationalist agenda has been strengthened in many places, including the Middle East and North Africa (MENA) region; and hateful narratives blaming ‘others’ for the pandemic, legitimizing a retreat to the protection of national borders and policies, are being spread in different media outlets. This article comparatively investigates processes of othering with regard to COVID-19 in four MENA countries – Egypt, Iraq, Oman and Yemen – and asks, who is held responsible for the coronavirus crisis in different countries? How is othering revealed in media coverage related to COVID-19? What (in)sensitive language can be identified? The study looks at mass media coverage at the peak of the global lockdown during the spring of 2020. The media analysis reveals a strong emphasis on mostly national identities as articulated lines of demarcation in all four cases. A homogenizing and demonizing othering was detected in particular in the cases of Yemen and Egypt, but also Iraq, when blame was attributed to political adversaries. The Omani case was characterized by a more subtle othering that focused strongly on the importance of citizenship.
Routledge Handbook on Arab Media, Noureddine Miladi and Noha Mellor (eds) (2021)
Authors: Hägglund Helena
Published: April 2021

Review of: Routledge Handbook on Arab Media, Noureddine Miladi and Noha Mellor (eds) (2021)

London: Routledge, 528 pp.,

ISBN 978-0-42942-708-4, e-book, ISBN 978-1-13838-548-1, h/bk, £190
The Role of the Social Media in Empowering Saudi Women’s Expression, Hend T. Alsudairy (2020)
Authors: Derham Reem Ali Al
Published: April 2021

Review of: The Role of the Social Media in Empowering Saudi Women’s Expression, Hend T. Alsudairy (2020)

Newcastle upon Tyne: Cambridge Scholar Publishing, 121 pp.,

ISBN 978-1-5275-4974-6, 358.30 QAR
Craig’s Anti–Platonism, Lowe’s Universals, and Christ’s Penal Substitutionary Atonement
Authors: Smith R. Scott
Published: April 2021

William Lane Craig has defended nominalism as a kind of “anti–Platonism.” To him, Platonism is inimical to God’s aseity. More recently, he also has defended the penal substitution of Christ. However, he has not brought the two subjects into dialogue with each other. In this essay, I will attempt to do that by exploring the implications of two major types of nominalism, austere nominalism and trope theory, for the penal substitution. I will argue that nominalism will undermine the penal substitution of Christ. Instead, to try to preserve both his anti–Platonism and the penal substitution, a better alternative for Craig is to embrace E. J. Lowe’s immanent universals.
The Rise of The Rising Sun: The Roots of Japanese Imperialism in Mutsuhito Era (1868-1912)
Authors: Budiarto Gema
Published: April 2021

This article aims to discuss the Japanese modernisation of the Mutsuhito Emperor Era, which focused on the developments that triggered Japan to become an imperialist country. The Bakufu government, which had been in power for more than 250 years, must finally end. After being deemed unable to handle the country's condition, the Bakufu government returned the Japanese government ultimately to Emperor Mutsuhito. During the occupation of the Empire's seat, Emperor Mutsuhito was assisted by his advisers to make changes in all fields. The main fields were built by them, such as reorganise the political bureaucracy, developing industrial-economic, and developing military technology. Supported by the progressive developments in the country, Japan was transforming into a large industrial nation. To meet its industrial needs, Japan became an imperialist country and defeated China and Russia during the Mutsuhito period of government. The method used in this research is historical and has five steps, among others determining the topic, sources collection, sources criticism, interpretation, and writing. The results showed that the aggressive development and strengthening in political bureaucracy, industrial economics, and military technology in the Meiji era were the roots of the spirit of imperialism of new Japan. Political, economic, and military are the reasons to undertake imperialism besides cultural and religious reasons
Stochastic methods defeat regular RSA exponentiation algorithms with combined blinding methods
Authors: Dugardin Margaux , Schindler Werner , Guilley Sylvain
Published: April 2021

Extra-reductions occurring in Montgomery multiplications disclose side-channel information which can be exploited even in stringent contexts. In this article, we derive stochastic attacks to defeat Rivest-Shamir-Adleman (RSA) with Montgomery ladder regular exponentiation coupled with base blinding. Namely, we leverage on precharacterized multivariate probability mass functions of extra-reductions between pairs of (multiplication, square) in one iteration of the RSA algorithm and that of the next one(s) to build a maximum likelihood distinguisher. The efficiency of our attack (in terms of required traces) is more than double compared to the state-of-the-art. In addition to this result, we also apply our method to the case of regular exponentiation, base blinding, and modulus blinding. Quite surprisingly, modulus blinding does not make our attack impossible, and so even for large sizes of the modulus randomizing element. At the cost of larger sample sizes our attacks tolerate noisy measurements. Fortunately, effective countermeasures exist.
Sensitivities and block sensitivities of elementary symmetric Boolean functions
Authors: Zhang Jing , Li Yuan , Adeyeye John O.
Published: April 2021

Boolean functions have important applications in molecular regulatory networks, engineering, cryptography, information technology, and computer science. Symmetric Boolean functions have received a lot of attention in several decades. Sensitivity and block sensitivity are important complexity measures of Boolean functions. In this paper, we study the sensitivity of elementary symmetric Boolean functions and obtain many explicit formulas. We also obtain a formula for the block sensitivity of symmetric Boolean functions and discuss its applications in elementary symmetric Boolean functions.
ONLINE GROUP PSYCHODRAMATIC PSYCHOTHERAPY: WARMING-UP REINVENTIONS
Authors: Belém Aline
Published: April 2021

This paper aims to discuss online group psychodramatic psychotherapy practices with an emphasis on warm-up. The hypothesis is that the warm-up step, specifically designed for Online care, contributes to the achievement of a more spontaneous group state. The theoretical north of the work is the warm-up stages proposed by Davoli (1999) from the experience with Spontaneous Theater. Thus, each stage is discussed taking into account the report of some experiences in conducting an online psychotherapy group. From these experiences, we affirm that the warm-up designed for this specific context provides good results in terms of group spontaneity.
DEGUSTAR PSICODRAMA ON-LINE COM PORTADORES DE OBESIDADE. VOCÊ ACEITA?
Authors: Pinto Ana Cristina Benevides
Published: April 2021

A autora partilha experiências de atendimento psicodramático on-line com pacientes obesos, como em uma degustação, que inspira a criação de recursos e reflexões sobre a prática psicoterápica em tempos de pandemia do Covid-19, bem como em novos tempos, demonstrando a viabilidade do referencial psicodramático nesta modalidade.
Symposium on Middle East and North African (MENA) conflict. Part 1: An introduction
Authors: Mansour-Ille Dina , Ali Hamid E
Published: April 2021

Since their independence, countries across the Middle East and North Africa (MENA) have witnessed subsequent waves of social and political conflicts. Armed and non-armed conflicts have almost become a defining feature of a region that has been struggling to find its own identity and a system that best represents its diverse communities and guarantees stability. Calibrated post-war power-sharing formulas of governance have produced authoritarianism, clientelism, elitism and a political post-war economy, where corruption, nepotism, injustice, and crony capitalism are rampant.
Warlord Politics and Economic Clientelism in Lebanon
Authors: Ille Sebastian , Mansour-Ille Dina
Published: April 2021

Since October 2019, Lebanon has been going through a deep economic and financial crisis that drove the country to a political meltdown. Facing a severe recession, high inflation and unemployment, nationwide protests in the aftermath of the Beirut explosion in August 2020 have led to the resignation of Hassan Diab’s cabinet – the second government to resign within the span of a few months. This article studies the interplay of the political, economic, and social factors that led to the current economic and political crisis. We show how warlord politics, and a corporate consociational system have misguided incentives and policies and consolidated a rentier economy that inevitably led to the current situation.
Did the Qatar Blockade Work? Evidence from Trade and Consumer Welfare Three Years after the Blockade
Authors: Al-Mal Hanan , Saad Ayhab F
Published: April 2021

This article examines the effects of the embargo (blockade) imposed on Qatar in June 2017 by four countries: Saudi Arabia, the United Arab Emirates, Egypt, and Bahrain. Using highly disaggregated product-destination quarterly trade datasets provided by the Qatar General Authority of Customs, we find a significant decline in Qatar’s aggregate imports and consumer welfare (with an increase in the prices of imported goods) in the short run, but not thereafter. Political relations with non-besieging countries seem to be associated with Qatar’s bilateral trade after the blockade, particularly in the first quarter. Shortly after the blockade, countries opposing the blockade experienced a sizable growth in exports to Qatar. In the medium to long run, Qatar succeeded in mitigating the impact of the blockade by diversifying its import origins and adopting new reforms to stabilize the economy and enhance the country’s food security and self-sufficiency.
Nephrogenic Diabetes Insipidus
Authors: ALBERTAZZI ELENA , ZANCHETTA DEBORAH , BARBIER PASCALINE , FARANDA SARA , FRATTINI ANNALISA , VEZZONI PAOLO , PROCACCIO MIRELLA , BETTINELLI ALBERTO , GUZZI FRANCESCA , PARENTI MARCO , CHINI BICE
Published: April 2021

The aim of this study was to identify loss-of-function mutations of the V2 vasopressin receptor gene (AVPR2) in Italian patients affected by X-linked nephrogenic diabetes insipidus (NDI). Mutations were found in 15 of the 18 unrelated families investigated: nine of these mutations were previously unknown, including two affecting residues located in regions known to be important for determining the pharmacologic properties of the receptor, which were therefore functionally investigated. The first (A84D) involves a residue located near an aspartic acid (D85) that is highly conserved in all G protein-coupled receptors and that is believed to play a role in the process of their isomerization into functionally active and inactive states. The present study indicates that this mutation not only affects receptor folding in such a way as to lead to its retention inside the intracellular compartments but, as expected, also has profound effects on its binding and coupling properties. The second was a mutation of a tryptophan located at the beginning of the first extracellular loop (W99R) that greatly impaired the binding properties of the receptor and had a minor effect on its intracellular routing. Molecular analysis of the first extracellular loop bearing this mutation suggests that this residue plays a fundamental role in stabilizing the peptide/receptor interactions responsible for the high-affinity binding of agonists to the V2 receptor.
Angiopoietin-2 Is a Site-Specific Factor in Differentiation of Mouse Renal Vasculature
Authors: YUAN HAI TAO , SURI CHITRA , LANDON DAVID N. , YANCOPOULOS GEORGE D. , WOOLF ADRIAN S.
Published: April 2021

Angiopoietin-1 (Ang-1) stimulates endothelial and vascular network differentiation through the Tie-2 receptor tyrosine kinase, while Ang-2 modulates this activation in embryo and tumor growth. The nephrogenic pattern of Ang-2 was documented in a mouse strain that expresses the LacZ reporter gene driven by the Ang-2 promoter. Heterozygous animals were healthy with morphologically normal kidneys, and they were examined after X-gal staining. At embryonic days 10.5 (E10.5) and E12.0, transgene expression was absent in the mesonephros and metanephros. At E14.0, expression was noted in the metanephric artery and its major branches. At E19.0 and in neonatal kidneys, expression was maintained in larger renal artery branches, extending to arcuate and smaller cortical vessels. Histologically, transgene expression was located in multiple layers of vessel wall cells, extending further from the endothelium than α-smooth muscle actin. The mesangium of immature glomeruli also expressed LacZ. In the first 3 postnatal weeks, a new pattern became evident, with intense X-gal staining in the inner stripe of the outer medulla, where a subset of thin descending limbs of loops of Henle expressed the transgene. This dynamic and developmentally regulated pattern indicates that Ang-2 is an early marker of the renal pericyte and vascular smooth muscle lineage and is also an epithelial-derived growth factor. Because Tie-2 is widely expressed by differentiating renal endothelia, this study is consistent with the hypothesis that Ang-2 has roles in kidney vascular maturation.
Course of Renal Injury in the Mpv17-Deficient Transgenic Mouse
Authors: O'BRYAN THOMAS , WEIHER HANS , RENNKE HELMUT G. , KREN STEFAN , HOSTETTER THOMAS H.
Published: April 2021

The mutant Mpv17 mouse is a transgenic strain that fails to express a protein that is normally expressed in the kidney and that is associated with peroxisomes. The present studies provide a quantitative examination of renal function and structure in this strain compared to its control CFW strain. By 52 wk of age, the mutant strain developed proteinuria (urinary protein to creatinine ratio: 25 ± 14 versus 3 ± 1, mutant versus control), albuminuria (urinary albumin to creatinine ratio: 23 ± 15 versus 0.1 ± 0.1, mutant versus control), and hypoalbuminemia (2.1 ± 0.4 versus 2.5 ± 0.2 G/dl, mutant versus control), but without arterial hypertension or major reduction in filtration (serum creatinine 0.14 ± 0.04 versus 0.18 ± 0.12 mg/dl, mutant versus control). The Mpv17 glomeruli were enlarged (0.98 ± 0.12 versus 0.52 ± 0.02 μm3 × 106, mutant versus control). Glomerular sclerosis became widespread (95 ± 3 versus 23 ± 32%, mutant versus control) and was preceded by mesangiolysis and microaneurysms. Tubulointerstitial disease was conspicuous by its absence. The intrarenal vasculature was normal in the mutant mice. Electron microscopy demonstrated focal foot process fusion and mesangiolysis. Thus, this mutant strain of mouse develops proteinuria and a distinct glomerulopathy including mesangiolysis but little interstitial injury all due to the loss of expression of a single gene.
Low Intraindividual Variability of Cyclosporin A Exposure Reduces Chronic Rejection Incidence and Health Care Costs
Authors: KAHAN BARRY D. , WELSH MARIA , URBAUER DIANA L. , MOSHEIM MELINDA B. , BEUSTERIEN KATHLEEN M. , WOOD MARTHA R. , SCHOENBERG LINDA P. , DICESARE JOSEPH , KATZ STEPHEN M. , VAN BUREN CHARLES T.
Published: April 2021

The present study applied a receiver operating characteristic (ROC) analysis to assess the role of intraindividual variability of cyclosporin A (CsA) drug exposure in predisposing renal transplant recipients to the occurrence of chronic rejection, as well as to increased health care costs using a resource-based economic analysis. Two hundred and four adult renal transplant recipients were treated with tapering doses of prednisone (Pred) and with a concentration-controlled strategy that selected doses of the olive oil-based formulations of CsA (Sandimmune®) that achieved target concentrations based on serial pharmacokinetic profiles. The ROC analysis revealed an inflection point of plots of the coefficient of variation (%CV) of CsA exposure versus the risk of chronic rejection at ≥28.4% for the average concentration (C
av), i.e., the dosing interval-corrected area under the concentration-time curves, and ≥36% for the trough concentration (C
0). The incidence of chronic rejection over a period of 5 yr was 24% among the less variable (LV) versus 40% among the variable (V) cohort. The economic analysis revealed that the total mean facility and physician costs per patient were $48,789 versus $60,998, respectively (P < 0.01). The degree of variability displayed by any individual could only be predicted by serial measurements of CsA concentrations, and not by demographic features, laboratory determinations, clinical characteristics, individual or mean values of any observed CsA concentration, or other pharmacokinetic parameters calculated following a single drug exposure. Thus, strategies that reduce intrapatient variability of CsA exposure over time may lead to reductions in chronic allograft loss and in treatment costs.
Differential Effects of Sera from Normotensive and Hypertensive Pregnant Women on Ca2+ Metabolism in Normal Vasular Smooth Muscle Cells
Authors: GREEN JACOB , ASSADY SUHEIR , NAKHOUL FARID , BICK TOVA , JAKOBI PETER , ABASSI ZAID
Published: April 2021

The clinical features of preeclampsia have been traditionally ascribed to a generalized vascular endothelial cell dysfunction. The present study investigates the effect of sera from preeclamptic women and normal pregnancy on the metabolism of intracellular Ca2+ concentration ([Ca2+]i) in normal cultured vascular smooth muscle cells (VSMC). Sera were obtained from normotensive pregnant women (NTP) (n = 17), preeclamptic women (PE) (n = 15), pregnant women with chronic (essential) hypertension (pregnant EHT) (n = 8), non-pregnant women with essential hypertension (non-pregnant EHT) (n = 12), and age-matched non-pregnant normotensive women (NNP) (n = 18). Serum (10%) was applied to both primary cultures of rat aortic smooth muscle cells and to the A-10 vascular muscle cell line. Levels of [Ca2+]i were determined fluorometrically. After a 4-h incubation with serum, basal [Ca2+]i was not significantly altered. However, compared with normal pregnant sera, PE sera markedly reduced hormonally induced Ca2+ transients. Thus, following acute stimulation of rat VSMC (primary cultures) with 10-8M angiotensin II, peak [Ca2+]i responses (% increment over baseline) were 443 ± 22, 184 ± 18, 259 ± 12, 274 ± 23, and 255 ± 15% in NTP, PE, pregnant EHT, non-pregnant EHT, and NNP, respectively (P <0.01 PE versus NTP, P <0.05 PE versus NNP and pregnant and non-pregnant EHT). These effects of sera on [Ca2+]i were qualitatively reproduced in platelets obtained from healthy volunteers. Also, depolarization-activated Ca2+ influx in VSMC was affected by the different sera groups in a manner similar to that seen with hormonally induced [Ca2+]i responses. The altered [Ca2+]i changes by PE sera disappeared 5 wk after delivery. The effect of the different sera groups on hormonally triggered Ca2+ transients in normal VSMC, as well as the normalization of [Ca2+]i responses after delivery, suggest the presence of a circulating serum factor in PE. Inasmuch as [Ca2+]i is the major determinant of VSMC tone, it is possible that consequent to the attenuation of [Ca2+]i responses, this putative circulating factor counterbalances the intense vasoconstriction in PE.
Vascular Endothelial Growth Factor Receptors in Human Mesangium in Vitro and in Glomerular Disease
Authors: THOMAS STEPHEN , VANUYSTEL JOHANN , GRUDEN GABRIELLA , RODRÍGUEZ VERÓNICA , BURT DAVINA , GNUDI LUIGI , HARTLEY BARRY , VIBERTI GIANCARLO
Published: April 2021

Mesangial cell proliferation and growth factor over-expression are characteristic features of several glomerular diseases. Vascular endothelial growth factor (VEGF), a potent mitogen, is expressed in podocytes in the glomerulus, and VEGF receptors (flt-1, KDR, and neuropilin-1) are present on endothelial cells and other cell types. This study examined whether human mesangial cells (HMC) express VEGF receptors in vitro and ex vivo and evaluated the effect of VEGF on HMC proliferation. All receptor types were detected in HMC in vitro by immunofluorescence and Western blotting. VEGF165 induced a dose-responsive increase in 3H-thymidine incorporation (25 ng/ml VEGF165: 2.3-fold increase; 50 ng/ml: 3.8-fold; 100 ng/ml: 4.8-fold; 200 ng/ml: 3.4-fold; P = 0.016) and in cell number (50 ng/ml VEGF165: 1.2-fold increase; 100 ng/ml: 1.6-fold; 200 ng/ml: 1.4-fold; P = 0.005), effects prevented by an anti-VEGF165 polyclonal neutralizing antibody (100 μg/ml). The proliferative effect was confirmed by a tetrazolium dye-based assay (100 ng/ml VEGF165: 1.4-fold increase). In ex vivo experiments, VEGF receptors in biopsy material from normal and diseased kidneys were detected by immunohistochemistry. No mesangial flt-1 receptor staining was seen in normal renal cortical tissue samples, and only weak mesangial KDR staining was detected. In contrast, mesangial flt-1 and KDR receptor staining were both clearly seen in biopsy samples from proliferative renal diseases. In conclusion, flt-1, KDR, and neuropilin-1 are present on cultured HMC, and VEGF165 induces HMC proliferation. In addition, the flt-1 and KDR receptors are expressed in the mesangium in mesangioproliferative disease.
Chromosomal Mapping of a Major Quantitative Trait Locus Regulating Compensatory Renal Growth in the Rat
Authors: PRAVENEC MICHAL , ZIDEK VACLAV , MUSILOVA ALENA , KR[Combining Caron]EN VLADIMIR , BILA VLASTA , NICOLANTONIO ROBERT DI
Published: April 2021

Despite extensive research conducted over the past century, the mechanisms of compensatory renal growth (CRG) remain a mystery. Insight into the mechanisms that regulate CRG might be gained by identifying genetic factors that influence this complex phenotype. In a large set of recombinant inbred strains derived from the spontaneously hypertensive rat and the Brown Norway rat, a genome scan for quantitative trait loci (QTL) that regulate CRG was performed. The CRG score was expressed as a ratio of the weight of the remnant right kidney at 8 wk of age to the weight of the left kidney at 5 wk of age, both adjusted for body weight. QTL mapping was performed using Map Manager QT and the strain distribution patterns of more than 600 genetic markers. It was found that CRG after unilateral nephrectomy is a multifactorially determined trait with a substantial genetic component. The heritability of CRG approached 40%. Genome wide scan analysis revealed significant evidence of linkage to a region of rat chromosome 4 designated Crg 1 that accounted for more than 50% of the additive genetic variance of CRG in the recombinant inbred strains. The detection of a major QTL influencing CRG in the rat should provide new opportunities for identifying mechanisms that regulate this historically enigmatic phenomenon and may also have implications for research on the pathogenesis of end-stage kidney disease.
Pharmacokinetics of Intermittent Intravenous Cefazolin and Tobramycin in Patients Treated with Automated Peritoneal Dialysis
Authors: MANLEY HAROLD J. , BAILIE GEORGE R. , FRYE REGINALD , HESS LORRAINE D. , MCGOLDRICK M. DONALD
Published: April 2021

There is increasing use of intermittent dosing of antibiotics to treat peritoneal dialysis (PD)-related peritonitis. The disposition of intravenous cefazolin and tobramycin was studied in automated PD (APD) patients. Ten patients were recruited and received a single intravenous dose of cefazolin (15 mg/kg) and tobramycin (0.6 mg/kg). Blood and dialysate samples were collected at the beginning, middle, and end of dwells 1 to 3 (on cycler), and at the end of dwells 4 to 5 (off cycler) for a 24-h period. Baseline and 24-h urine samples were collected. Pharmacokinetic parameters were calculated using a monoexponential model. Cefazolin and tobramycin half-lives were markedly different on cycler than off cycler (cefazolin on cycler: 10.67 ± 4.66 h; cefazolin off cycler: 23.09 ± 5.6 h; P = 0.001; tobramycin on cycler: 14.27 ± 4.53 h; tobramycin off cycler: 68.5 ± 26.47 h; P < 0.001). Mean serum and dialysate concentrations were above minimum inhibitory concentrations of susceptible organisms throughout the 24-h period for both drugs with intravenous administration. A model was developed to examine serum and dialysate concentrations after intermittent intraperitoneal administration of 15 mg/kg cefazolin and 0.6 mg/kg tobramycin. Model-predicted intraperitoneal cefazolin provides adequate serum and dialysate concentrations for 24 h. Intermittent intraperitoneal tobramycin doses must be 1.5 mg/kg for one exchange during the first day and then given as 0.5 mg/kg thereafter. It is concluded that the current empiric dosing recommendations for PD-related peritonitis may be adequate for cefazolin (15 to 20 mg/kg); however, tobramycin doses must be changed to 1.5 mg/kg intraperitoneally on day 1, then to 0.5 mg/kg intraperitoneally thereafter in APD patients.
Contribution of Prolonged Ischemia and Donor Age to Chronic Renal Allograft Dysfunction
Authors: TULLIUS STEFAN GU[Combining Diaeresis]NTHER , REUTZEL-SELKE ANJA , EGERMANN FRANK , NIEMINEN-KELHA[Combining Diaeresis] MELINA , JONAS SVEN , BECHSTEIN WOLF OTTO , VOLK HANS-DIETER , NEUHAUS PETER
Published: April 2021

As a consequence of an advancing discrepancy between supply of suitable grafts and demand from potential recipients, less than optimal organs are increasingly being used. Although clinical studies demonstrate the involvement of various risk factors, including donor age and duration of ischemia on long-term graft outcome, their individual contribution and correlation has not been followed experimentally. After cold ischemic times of 5, 60, and 120 min, kidney allografts of 3-, 12-, and 18-mo-old Fischer 344 donors were transplanted into 3-mo-old Lewis rats. Age-related changes were examined in matched native uninephrectomized controls. Proteinuria and creatinine clearance were determined, and histologic and immunohistologic studies were assessed and quantified at the end of the observation period (20 wk). All grafts functioned satisfactorily with the exception of one graft each from 12- and 18-mo-old donors with prolonged ischemia (120 min). Functional deterioration and structural changes progressed in parallel to increasing donor age and prolonged ischemia. The impact of expanded ischemia was particularly detrimental in grafts from older donor animals. Donor age and duration of ischemia act in a synergistic manner in our model. Brief ischemic times seem of particular relevance when grafts from older donors are being used.
Reactive Oxygen Species Stimulate p44/42 Mitogen-Activated Protein Kinase and Induce p27Kip1
Authors: HANNKEN TETE , SCHROEDER REGINE , ZAHNER GUNTHER , STAHL ROLF A. K. , WOLF GUNTER
Published: April 2021

Angiotensin II (AngII) induces G1 phase arrest and hypertrophy of cultured renal proximal tubular cells. In previous studies, it was shown that these effects depend on oxygen radical-mediated induction of p27Kip1, an inhibitor of cyclin-dependent kinases. The present study was undertaken to investigate whether mitogen-activated protein (MAP) kinases serve as signaling intermediates between AngII-induced oxidative stress and induction of p27Kip1. AngII (10-7 M) induces a biphasic phosphorylation pattern of p44/42 MAP kinase with an early phosphorylation after 2 min and a later, second phosphorylation peak after prolong incubation (12 h) in cultured proximal tubular cells from two different species (MCT and LLC-PK1 cells). Total protein expression of MAP kinase was not changed by AngII. These phosphorylation patterns of p44/42 MAP kinase caused activation of the enzyme, as detected by phosphorylated MAP substrate Elk-1 after immuno-precipitation of MAP kinase. Exogenous H2O2 also stimulates a biphasic phosphorylation of p44/42 MAP kinase. The flavoprotein inhibitor diphenylene iodinium, as well as the antioxidant N-acetylcysteine, prevented AngII-induced p44/42 MAP kinase phosphorylation, indicating involvement of reactive oxygen species generated by membrane-bound NAD(P)H oxidase. The MAP kinase kinase inhibitor PD98059 completely inhibits AngII-induced p27Kip1 expression and 3[H]leucine incorporation into proteins as a previously established marker of cell hypertrophy. PD98059 did not attenuate AngII-stimulated intracellular synthesis of oxygen radicals. Transient transfection with p44/42 MAP kinase antisense, but not sense, phosphorothioate-modified oligonucleotides also prevented AngII-induced MAP kinase phosphorylation, p27Kip1 expression, and cell hypertrophy. Furthermore, induction of p27Kip1 by H2O2 was also abolished in the presence of PD98059. Although AngII induces phosphorylation of the stress-activated p38 MAP kinase, inhibition of this enzyme with SB203580 failed to attenuate induced p27Kip1 expression and hypertrophy. These data provide evidence that AngII- mediated oxygen stress leads to the phosphorylation of p44/42 MAP kinase in proximal tubular cells. Activation of this enzyme is essential for p27Kip1 expression, G1 phase arrest, and hypertrophy of proximal tubular cells. These findings may lead to new concepts concerning interference of the development of proximal tubular hypertrophy, which may eventually turn into a maladaptive process in vivo leading ultimately to tubular atrophy and tubulointerstitial fibrosis.
Growth Hormone Increases Inducible Nitric Oxide Synthase Expression in Mesangial Cells
Authors: DOI SONIA Q. , JACOT TERRY A. , SELLITTI DONALD F. , HIRSZEL PRZEMYSLAW , HIRATA MARIO H. , STRIKER GARY E. , STRIKER LILIANE J.
Published: April 2021

Mice transgenic for bovine growth hormone (GH) develop progressive glomerulosclerosis. However, the proximal signaling events that lead to increased matrix deposition in this pathologic condition are still unclear. Components of the L-arginine metabolic pathway, especially inducible nitric oxide (NO) synthase (iNOS), ornithine aminotransferase (OAT), and ornithine decarboxylase (ODC), have been associated with glomerular scarring. In this study, mesangial cells were treated with GH, and the expression of iNOS, ODC, and OAT was determined using reverse transcription-PCR. In addition, nitrite accumulation in the conditioned media of mesangial cell cultures was measured in the presence or absence of GH. The findings revealed that GH increased iNOS transcript levels in a dose-dependent manner, with the highest levels being attained at GH concentrations of 20 to 50 ng/ml. The GH-induced increase in iNOS transcript levels was accompanied by a significant increase in nitrite concentrations in conditioned media, which was blocked by the addition of L-N
G-monomethylarginine. The effect of GH (50 ng/ml) in eliciting nitrite production was as potent as that of bacterial lipopolysaccharide (10 μg/ml). The expression of OAT and ODC, in contrast, was not altered at any of the GH concentrations tested. GH receptor mRNA was also expressed by mesangial cells, independently of the GH concentration present in the cell culture medium. These data indicate that GH may interact with its receptor to regulate the L-arginine/NO pathway in mesangial cells, by directly modulating iNOS expression and NO production, without altering the arginase/OAT/ODC pathway.
Food Restriction Prevents Advanced Glycation End Product Accumulation and Retards Kidney Aging in Lean Rats
Authors: TEILLET LAURENT , VERBEKE PHILIPPE , GOURAUD SABINE , BAKALA HILAIRE , BOROT-LALOI CAROLINE , HEUDES DIDIER , BRUNEVAL PATRICK , CORMAN BRUNO
Published: April 2021

Tissue content of advanced glycation end products (AGE) increases with age and contributes to the changes in structure and function of the renal and cardiovascular systems. The effect of chronic food restriction on this AGE accumulation was investigated in lean WAG/Rij rats. A 30% food restriction performed from 10 to 30 mo in female rats reduced their mean body weight from 240 ± 7 to 160 ± 12 g, but did not modify their survival. AGE collagen content increased from 14.3 ± 5.5 to 104.7 ± 13.0 arbitrary units per microgram (AU/μg) of hydroxyproline (OHPro) in kidney between 10 and 30 mo, and from 9.7 ± 1.2 to 310.6 ± 34.6 AU/μg OHPro in the abdominal aorta. Food restriction reduced AGE accumulation to 21.4 ± 3.3 and 74.6 ± 16.5 AU/μg OHPro in kidney and aorta of 30-mo-old animals. Similar results were found for collagen prepared from isolated glomeruli (7.8 ± 1.2, 81.2 ± 16.1, and 10.3 ± 4.3 AU/μg OHPro in 10-mo, 30-mo, and restricted 30-mo-old rats). Reduction of intrarenal and arterial AGE accumulation by food restriction was confirmed by immunostaining in optical microscopy. Age-related changes in arterial and kidney structures as polyuria and proteinuria were mainly prevented by food restriction. These data indicate that chronic food restriction reduces the accumulation of AGE and preserves the structure and function of the renal and cardiovascular systems in learn rats, although it did not affect survival of the animals between 10 and 30 mo.
Length of Stay and Costs for Hospitalized Hemodialysis Patients
Authors: KSHIRSAGAR ABHIJIT V. , HOGAN SUSAN L. , MANDELKEHR LARRY , FALK RONALD J.
Published: April 2021

The high cost of hospitalization for hemodialysis patients has become a major health care issue. To address this issue, length of hospital stay and costs for these patients were compared with services covered by nephrologists and services covered by internists. Hemodialysis patients (n = 161) were prospectively admitted 219 times on alternate days to services covered by nephrologists or by internists from July 1995 to March 1996. Admissions to nonmedical services and admissions for overnight observation were excluded. Length of stay, costs, and risk-adjusted predicted length of stay and costs, as well as the number of consultations were compared between services, using Wilcoxon rank sum tests. Readmissions and deaths were compared using χ2 tests. Mean length of stay for admissions to the nephrology service (n = 114) was 6.3 days compared with 8.1 days for admissions to internal medicine services (n = 105) (P = 0.017). The predicted length of stay was similar. Mean overall cost for admissions under the care of nephrologists was $7,925 versus $10,773 under the care of internists (P = 0.101). The internal medicine service averaged 1.5 consultations versus 0.5 consultations for the nephrology service (P = 0.001). The risk of readmission was 24% for nephrologists and 30% for internists (P = 0.328). Death within 90 days of discharge was 12% for the nephrology group and 22% for the internal medicine group (P = 0.07). The length of stay was significantly shorter for hemodialysis patients under the care of nephrologists compared with internists. The average total costs and risk of readmissions tended to be lower for nephrologists. If these results are corroborated, the care of hemodialysis patients by the nephrologist could diminish the overall expense of the ESRD program.
PRRSV type II sequencing protocol v1
Authors: Caserta Leonardo
Published: April 2021

ARTIC amplicon sequencing protocol for MinION for nCoV-2019 This one-pot native barcoding protocol was developed in conjunction with Oxford Nanopore Technologies, New England Biolabs and BCCDC.