Analysing substitutions in recent World Cups and European Championships in male and female elite football - influence of new substitution rules.

Substitutions play a key role in modern football and can substantially affect the physical and overall performance of a team, and the recent substitution rule changes are worth investigating. This study explored the characteristics of substitutions, including different substitution rules, game results, sex, competition stages, tournaments and penalty shoot-outs success rates. We analysed data from a total of 3,738 substitutions from the last 10 years (2013-2023) of European Championships and World Cups, both men's and women's games. Non-parametric tests and chi-square tests were used for statistical analysis with the significance level set at p < 0.05. With the 5-substitution rule, 48% more substitutions occurred compared to the 3-substitution rule (4.26 ± 1.07 vs. 2.87 ± 0.43, p < 0.05) with a slight increase in the average substitution time (70.6 ± 14.3 vs. 69.2 ± 14.6 min, p < 0.05), and 10% more substitutions in the men's game compared to the women's game (p < 0.05). The timing of the first substitution was slightly different in the knock-out stage compared to group stage (59.8 ± 14.7 vs. 57.2 ± 13.3 min, p < 0.05), and the timing for the winning team and drawing team was later than for the losing team (p < 0.05). A total of 13.2% goals were scored by substitutes, with no significant difference between the 5-substitution rule (15.9%) vs the 3-substition rule (12.5%) (p > 0.05). Interestingly, substitute players had a lower success rate in penalty shoot-out compared to starters (61 vs. 74%, p < 0.05). Additionally, substitute player goal scorers entered the pitch later (p < 0.05) in male games compared to female games and in knock-out stage games compared to group games. This study highlights the importance of substitution rules and timing in modern elite football matches. The timing of the first substitution, introduction of substitutes in knock-out stages, and a lower success rate of substitute players in penalty shoot-outs are crucial factors to consider. Coaches can use this information to make strategic substitution decisions to improve team performance.

The impact of social participation on the health status of the older adult: An empirical study based on CGSS 2021 data.

INTRODUCTION: With the rapid pace of population aging, the health issues of the older adult have garnered widespread attention. Social participation plays a pivotal role in the health of the older adult. This study aims to explore the impact of social participation on the health status of the older adult. METHODS: Using a binary logistic regression model, this study analyzes the influence of social participation methods on the health status of older adult individuals in China based on cross-sectional data from the "China Comprehensive Social Survey" in 2021. The study sample comprises individuals aged 60 to 99 years. RESULTS: It was found that participation in physical activities [P<0.001, OR = 1.907], social and recreational activities [P<0.001, OR = 1.387], and online activities [P<0.001, OR = 1.808] were significantly positively correlated with the health status of the older adult. CONCLUSIONS: The health of older adults is influenced by a combination of physical activities, social and recreational activities, and online activities. Good health is closely associated with high levels of physical activity. Engaging in physical exercise promotes physiological health, while participating in social and recreational activities has a significant impact on cognitive and depressive states. Additionally, involvement in online activities helps alleviate feelings of loneliness and enhances overall well-being. RECOMMENDATIONS: 1)Promote the development of physical activities for the older adult: Create an integrated environment for physical exercise. 2)Expand the social circle of the older adult: Construct diverse and structured communities to enhance well-being. 3)Develop online activities for the older adult: Facilitate their integration into the digital age. 4)Foster interdisciplinary collaboration for older adult health: Build partnerships across various domains to promote older adult health.

Improved individual identification in DNA mixtures of unrelated or related contributors through massively parallel sequencing.

DNA mixtures are a common sample type in forensic genetics, and we typically assume that contributors to the mixture are unrelated when calculating the likelihood ratio (LR). However, scenarios involving mixtures with related contributors, such as in family murder or incest cases, can also be encountered. Compared to the mixtures with unrelated contributors, the kinship within the mixture would bring additional challenges for the inference of the number of contributors (NOC) and the construction of probabilistic genotyping models. To evaluate the influence of potential kinship on the individual identification of the person of interest (POI), we conducted simulations of two-person (2 P) and three-person (3 P) DNA mixtures containing unrelated or related contributors (parent-child, full-sibling, and uncle-nephew) at different mixing ratios (for 2 P: 1:1, 4:1, 9:1, and 19:1; for 3 P: 1:1:1, 2:1:1, 5:4:1, and 10:5:1), and performed massively parallel sequencing (MPS) using MGIEasy Signature Identification Library Prep Kit on MGI platform. In addition, in silico simulations of mixtures with unrelated and related contributors were also performed. In this study, we evaluated 1): the MPS performance; 2) the influence of multiple genetic markers on determining the presence of related contributors and inferring the NOC within the mixture; 3) the probability distribution of MAC (maximum allele count) and TAC (total allele count) based on in silico mixture profiles; 4) trends in LR values with and without considering kinship in mixtures with related and unrelated contributors; 5) trends in LR values with length- and sequence-based STR genotypes. Results indicated that multiple numbers and types of genetic markers positively influenced kinship and NOC inference in a mixture. The LR values of POI were strongly dependent on the mixing ratio. Non- and correct-kinship hypotheses essentially did not affect the individual identification of the major POI; the correct kinship hypothesis yielded more conservative LR values; the incorrect kinship hypothesis did not necessarily lead to the failure of POI individual identification. However, it is noteworthy that these considerations could lead to uncertain outcomes in the identification of minor contributors. Compared to length-based STR genotyping, using sequence-based STR genotype increases the individual identification power of the POI, concurrently improving the accuracy of mixing ratio inference using EuroForMix. In conclusion, the MGIEasy Signature Identification Library Prep kit demonstrated robust individual identification power, which is a viable MPS panel for forensic DNA mixture interpretations, whether involving unrelated or related contributors.

NEATmap: a high-efficiency deep learning approach for whole mouse brain neuronal activity trace mapping.

Quantitative analysis of activated neurons in mouse brains by a specific stimulation is usually a primary step to locate the responsive neurons throughout the brain. However, it is challenging to comprehensively and consistently analyze the neuronal activity trace in whole brains of a large cohort of mice from many terabytes of volumetric imaging data. Here, we introduce NEATmap, a deep learning-based high-efficiency, high-precision and user-friendly software for whole-brain neuronal activity trace mapping by automated segmentation and quantitative analysis of immunofluorescence labeled c-Fos+ neurons. We applied NEATmap to study the brain-wide differentiated neuronal activation in response to physical and psychological stressors in cohorts of mice.

"I feel like I'm walking on eggshells": a qualitative study of moral distress among Chinese emergency doctors.

BACKGROUND: While the number of emergency patients worldwide continues to increase, emergency doctors often face moral distress. It hampers the overall efficiency of the emergency department, even leading to a reduction in human resources. AIM: This study explored the experience of moral distress among emergency department doctors and analyzed the causes of its occurrence and the strategies for addressing it. METHOD: Purposive and snowball sampling strategies were used in this study. Data were collected through in-depth, semi-structured interviews with 10 doctors working in the emergency department of a tertiary general hospital in southwest China. The interview data underwent processing using the Nvivo 14 software. The data analysis was guided by Colaizzi's phenomenological analysis method. STUDY FINDINGS: This study yielded five themes: (1) imbalance between Limited Medical Resources and High-Quality Treatment Needs; (2) Ineffective Communication with Patients; (3) Rescuing Patients With no prospect of treatment; (4) Challenges in Sustaining Optimal Treatment Measures; and (5) Strategies for Addressing Moral Distress. CONCLUSION: The moral distress faced by emergency doctors stems from various aspects. Clinical management and policymakers can alleviate this distress by enhancing the dissemination of emergency medical knowledge to the general public, improving the social and economic support systems, and strengthening multidisciplinary collaboration and doctors' communication skills.

Osteo-immunomodulatory effects of macrophage-derived extracellular vesicles treated with biphasic calcium phosphate ceramics on bone regeneration.

Literature on osteoimmunology has demonstrated that macrophages have a great influence on biomaterial-induced bone formation. However, there are almost no reports clarifying the osteo-immunomodulatory capacity of macrophage-derived extracellular vesicles (EVs). This study comprehensively investigated the effects of EVs derived from macrophages treated with biphasic calcium phosphate (BCP) ceramics (BEVs) on vital events associated with BCP-induced bone formation such as immune response, angiogenesis, and osteogenesis. It was found that compared with EVs derived from macrophages alone (control, CEVs), BEVs preferentially promoted macrophage polarization towards a wound-healing M2 phenotype, enhanced migration, angiogenic differentiation, and tube formation of human umbilical vein endothelial cells, and induced osteogenic differentiation of mesenchymal stem cells. Analysis of 15 differentially expressed microRNAs (DEMs) related to immune, angiogenesis, and osteogenesis suggested that BEVs exhibited good immunomodulatory, pro-angiogenic, and pro-osteogenic abilities, which might be attributed to their specific miRNA cargos. These findings not only deepen our understanding of biomaterial-mediated osteoinduction, but also suggest that EVs derived from biomaterial-treated macrophages hold great promise as therapeutic agents with desired immunomodulatory capacity for bone regeneration.

IFDlong: an isoform and fusion detector for accurate annotation and quantification of long-read RNA-seq data.

Advancements in long-read transcriptome sequencing (long-RNA-seq) technology have revolutionized the study of isoform diversity. These full-length transcripts enhance the detection of various transcriptome structural variations, including novel isoforms, alternative splicing events, and fusion transcripts. By shifting the open reading frame or altering gene expressions, studies have proved that these transcript alterations can serve as crucial biomarkers for disease diagnosis and therapeutic targets. In this project, we proposed IFDlong, a bioinformatics and biostatistics tool to detect isoform and fusion transcripts using bulk or single-cell long-RNA-seq data. Specifically, the software performed gene and isoform annotation for each long-read, defined novel isoforms, quantified isoform expression by a novel expectation-maximization algorithm, and profiled the fusion transcripts. For evaluation, IFDlong pipeline achieved overall the best performance when compared with several existing tools in large-scale simulation studies. In both isoform and fusion transcript quantification, IFDlong is able to reach more than 0.8 Spearman's correlation with the truth, and more than 0.9 cosine similarity when distinguishing multiple alternative splicing events. In novel isoform simulation, IFDlong can successfully balance the sensitivity (higher than 90%) and specificity (higher than 90%). Furthermore, IFDlong has proved its accuracy and robustness in diverse in-house and public datasets on healthy tissues, cell lines and multiple types of diseases. Besides bulk long-RNA-seq, IFDlong pipeline has proved its compatibility to single-cell long-RNA-seq data. This new software may hold promise for significant impact on long-read transcriptome analysis. The IFDlong software is available at https://github.com/wenjiaking/IFDlong.

Research on the impact mechanism of changes in the production of medical solid waste in China before and after COVID-19.

The changes of medical solid waste (MSW) output in recent years have had a significant impact on the spread of the virus. There is a high-risk transmission of MSW in various stages such as storage, transportation, and treatment during the COVID-19. To cope with the risks brought by the epidemic, normalized prevention consumes a large amount of protective clothing, medical masks, goggles, packaging bags, and other related medical supplies. There is a significant uncertainty in the amount of MSW output that poses a risk of COVID-19 infection in the event of an emergency, which increases the difficulty of collecting and handling epidemic prevention MSW. The analysis of MSW data from 2000 to 2022 found a stable growth trend before 2019. However, the MSW data was a sudden increase trend from 2020 to 2022, and the COVID-19 in China was characterized by an initial stage, an outbreak stage, and a stable growth stage. The range of MSW output during the epidemic was (1.19-1.75) × 106 t a-1. The amount of MSW was approximately 1.19 × 106 t a-1 during the normalized epidemic period, and its treatment cost was as high as 3.57 × 109 yuan (RMB)·a-1. The distribution of MSW output was uneven due to factors such as climate conditions, population data, and local economy. This study has important reference value for epidemic medical material reserves and MSW treatment.

Utility Analyses of AVITI Sequencing Chemistry.

Background: DNA sequencing is a critical tool in modern biology. Over the last two decades, it has been revolutionized by the advent of massively parallel sequencing, leading to significant advances in the genome and transcriptome sequencing of various organisms. Nevertheless, challenges with accuracy, lack of competitive options and prohibitive costs associated with high throughput parallel short-read sequencing persist. Results: Here, we conduct a comparative analysis using matched DNA and RNA short-reads assays between Element Biosciences' AVITI and Illumina's NextSeq 550 chemistries. Similar comparisons were evaluated for synthetic long-read sequencing for RNA and targeted single-cell transcripts between the AVITI and Illumina's NovaSeq 6000. For both DNA and RNA short-read applications, the study found that the AVITI produced significantly higher per sequence quality scores. For PCR-free DNA libraries, we observed an average 89.7% lower experimentally determined error rate when using the AVITI chemistry, compared to the NextSeq 550. For short-read RNA quantification, AVITI platform had an average of 32.5% lower error rate than that for NextSeq 550. With regards to synthetic long-read mRNA and targeted synthetic long read single cell mRNA sequencing, both platforms' respective chemistries performed comparably in quantification of genes and isoforms. The AVITI displayed a marginally lower error rate for long reads, with fewer chemistry-specific errors and a higher mutation detection rate. Conclusion: These results point to the potential of the AVITI platform as a competitive candidate in high-throughput short read sequencing analyses when juxtaposed with the Illumina NextSeq 550.

The Effect of Low HBV-DNA Viral Load on Recurrence in Hepatocellular Carcinoma Patients Who Underwent Primary Locoregional Treatment and the Development of a Nomogram Prediction Model.

(1) Background: HBV-DNA is an essential clinical indicator of primary hepatocellular carcinoma (HCC) prognosis. Our study aimed to investigate the prognostic implication of a low load of HBV-DNA in HCC patients who underwent local treatment. Additionally, we developed and validated a nomogram to predict the recurrence of patients with low (20-100 IU/mL) viral loads (L-VL). (2) Methods: A total of 475 HBV-HCC patients were enrolled, including 403 L-VL patients and 72 patients with very low (<20 IU/mL) viral loads (VL-VL). L-VL HCC patients were randomly divided into a training set (N = 282) and a validation set (N = 121) at a ratio of 7:3. Utilizing the Lasso-Cox regression analysis, we identified independent risk factors for constructing a nomogram. (3) Results: L-VL patients had significantly shorter RFS than VL-VL patients (38.2 m vs. 23.4 m, p = 0.024). The content of the nomogram included gender, BCLC stage, Glob, and MLR. The C-index (0.682 vs. 0.609); 1-, 3-, and 5-year AUCs (0.729, 0.784, and 0.783, vs. 0.631, 0.634, the 0.665); calibration curves; and decision curve analysis (DCA) curves of the training and validation cohorts proved the excellent predictive performance of the nomogram. There was a statistically significant difference in RFS between the low-, immediate-, and high-risk groups both in the training and validation cohorts (p < 0.001); (4) Conclusions: Patients with L-VL had a worse prognosis. The nomogram developed and validated in this study has the advantage of predicting patients with L-VL.

High-Voltage Cable Buffer Layer Ablation Fault Identification Based on Artificial Intelligence and Frequency Domain Impedance Spectroscopy.

In recent years, the occurrence of high-voltage cable buffer layer ablation faults has become frequent, posing a serious threat to the safe and stable operation of cables. Failure to promptly detect and address such faults may lead to cable breakdowns, impacting the normal operation of the power system. To overcome the limitations of existing methods for identifying buffer layer ablation faults in high-voltage cables, a method for identifying buffer layer ablation faults based on frequency domain impedance spectroscopy and artificial intelligence is proposed. Firstly, based on the cable distributed parameter model and frequency domain impedance spectroscopy, a mathematical model of the input impedance of a cable containing buffer layer ablation faults is derived. Through a simulation, the input impedance spectroscopy at the first end of the cables under normal conditions, buffer layer ablation, local aging, and inductive faults is performed, enabling the identification of inductive and capacitive faults through a comparative analysis. Secondly, the frequency domain amplitude spectroscopy of the buffer layer ablation and local aging faults are used as datasets and are input into a neural network model for training and validation to identify buffer layer ablation and local aging faults. Finally, using multiple evaluation metrics to assess the neural network model validates the superiority of the MLP neural network in cable fault identification models and experimentally confirms the effectiveness of the proposed method.

Sjögren's syndrome and Parkinson's Disease: A bidirectional two-sample Mendelian randomization study.

BACKGROUND: Previous observational studies have reported an association between Sjögren's syndrome (SS) and an increased risk of Parkinson's Disease (PD). However, the causal relationship between these conditions remains unclear. The objective of this study was to investigate the causal impact of SS on the risk of developing PD, utilizing the Mendelian randomization (MR) approach. METHODS: We conducted a bidirectional MR analysis using publicly available genome-wide association studies (GWAS) data. The primary analysis utilized the inverse-variance weighted (IVW) method. Complementary methods, such as MR-Egger regression, weighted mode, weighted median, and MR-pleiotropy residual sum and outlier (MR-PRESSO), were utilized to identify and correct for the presence of horizontal pleiotropy. RESULTS: The IVW MR analysis revealed no significant association between SS and PD (IVW: OR = 1.00, 95% CI = 0.94-1.07, P = 0.95). Likewise, the reverse MR analysis did not identify any significant causal relationship between PD and SS (IVW: OR = 0.98, 95% CI = 0.85-1.12, P = 0.73). The results from MR-Egger regression, weighted median, and weighted mode approaches were consistent with the IVW method. Sensitivity analyses suggested that horizontal pleiotropy is unlikely to introduce bias to the causal estimates. CONCLUSION: This study does not provide evidence to support the assertion that SS has a conclusive impact on the risk of PD, which contradicts numerous existing observational reports. Further investigation is necessary to determine the possible mechanisms behind the associations observed in these observational studies.

A Comprehensive Evaluation Algorithm of Multi-Point Relay Based on Link-State Awareness for UANETs.

The Multi-Point Relay (MPR) is one of the core technologies for Optimizing Link State Routing (OLSR) protocols, offering significant advantages in reducing network overhead, enhancing throughput, maintaining network scalability, and adaptability. However, due to the restriction that only MPR nodes can forward control messages in the network, the current evaluation criteria for selecting MPR nodes are relatively limited, making it challenging to flexibly choose MPR nodes based on current link states in dynamic networks. Therefore, the selection of MPR nodes is crucial in dynamic networks. To address issues such as unstable links, poor transmission accuracy, and lack of real-time performance caused by mobility in dynamic networks, we propose a comprehensive evaluation algorithm of MPR based on link-state awareness. This algorithm defines five state evaluation parameters from the perspectives of node mobility and load. Subsequently, we use the entropy weight method to determine weight coefficients and employing the method of Technique for Order Preference by Similarity to Ideal Solution (TOPSIS) for comprehensive evaluation to select MPR nodes. Finally, the Comprehensive Evaluation based on Link-state awareness of OLSR (CEL-OLSR) protocol is proposed, and simulated experiments are conducted using NS-3. The results indicate that, compared to PM-OLSR, ML-OLSR, LD-OLSR, and OLSR, CEL-OLSR significantly improves network performance in terms of packet delivery rate, average end-to-end delay, network throughput, and control overhead.

Feasibility of a low-cost magnet tracking device in confirming nasogastric tube placement at point of care, a clinical trial.

An affordable and reliable way of confirming the placement of nasogastric tube (NGT) at point-of-care is an unmet need. Using a novel algorithm and few sensors, we developed a low-cost magnet tracking device and showed its potential to localize the NGT preclinically. Here, we embark on a first-in-human trial. Six male and 4 female patients with NGT from the general ward of an urban hospital were recruited. We used the device to localize the NGT and compared that against chest X-ray (CXR). In 5 patients, with the sensors placed on the sternal angle, the trajectory of the NGT was reproduced by the tracking device. The tracked location of the NGT deviated from CXR by 0.55 to 1.63 cm, and a downward tracking range of 17 to 22 cm from the sternal angle was achieved. Placing the sensors on the xiphisternum, however, resulted in overt discordance between the device's localization and that on CXR. Short distance between the sternal angle and the xiphisternum, and lower body weight were observed in patients in whom tracking was feasible. Tracking was quick and well tolerated. No adverse event occurred. This device feasibly localized the NGT in 50% of patients when appropriately placed. Further refinement is anticipated.ClinicalTrials.gov identifier: NCT05204901.

eEF1A2 promotes PTEN-GSK3ß-SCF complex-dependent degradation of Aurora kinase A and is inactivated in breast cancer.

The translation elongation factor eEF1A promotes protein synthesis. Its methylation by METTL13 increases its activity, supporting tumor growth. However, in some cancers, a high abundance of eEF1A isoforms is associated with a good prognosis. Here, we found that eEF1A2 exhibited oncogenic or tumor-suppressor functions depending on its interaction with METTL13 or the phosphatase PTEN, respectively. METTL13 and PTEN competed for interaction with eEF1A2 in the same structural domain. PTEN-bound eEF1A2 promoted the ubiquitination and degradation of the mitosis-promoting Aurora kinase A in the S and G2 phases of the cell cycle. eEF1A2 bridged the interactions between the SKP1-CUL1-FBXW7 (SCF) ubiquitin ligase complex, the kinase GSK3ß, and Aurora-A, thereby facilitating the phosphorylation of Aurora-A in a degron site that was recognized by FBXW7. Genetic ablation of Eef1a2 or Pten in mice resulted in a greater abundance of Aurora-A and increased cell cycling in mammary tumors, which was corroborated in breast cancer tissues from patients. Reactivating this pathway using fimepinostat, which relieves inhibitory signaling directed at PTEN and increases FBXW7 expression, combined with inhibiting Aurora-A with alisertib, suppressed breast cancer cell proliferation in culture and tumor growth in vivo. The findings demonstrate a therapeutically exploitable, tumor-suppressive role for eEF1A2 in breast cancer.

The antioxidant activity of polysaccharides from Armillaria gallica.

The purpose of this study was to investigate the antioxidant activity of Armillaria gallica polysaccharides. It explored whether Armillaria gallica polysaccharides (AgP) could prevent HepG2 cells from H2O2-induced oxidative damage. The results demonstrated that HepG2 cells were significantly protected by AgP, and efficiently suppressed the production of reactive oxygen species (ROS) in HepG2 cells. Additionally, AgP significantly decreased the abnormal leakage of alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) caused by H2O2, protecting cell membrane integrity. It was discovered that AgP was also found to regulate the activities of antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-PX), while reducing malondialdehyde (MDA), thus protecting cells from oxidative damage. According to the flow cytometry analysis and measurement of caspase-3, caspase-8, and caspase-9 activities, AgP could modulate apoptosis-related proteins and attenuate ROS-mediated cell apoptosis.

TIM22 and TIM29 inhibit HBV replication by up-regulating SRSF1 expression.

Hepatitis B virus (HBV) infection is a serious global health problem. After the viruses infect the human body, the host can respond to the virus infection by coordinating various cellular responses, in which mitochondria play an important role. Evidence has shown that mitochondrial proteins are involved in host antiviral responses. In this study, we found that the overexpression of TIM22 and TIM29, the members of the inner membrane translocase TIM22 complex, significantly reduced the level of intracellular HBV DNA and RNA and secreted HBV surface antigens and E antigen. The effects of TIM22 and TIM29 on HBV replication and transcription is attributed to the reduction of core promoter activity mediated by the increased expression of SRSF1 which acts as a suppressor of HBV replication. This study provides new evidence for the critical role of mitochondria in the resistance of HBV infection and new targets for the development of treatment against HBV infection.

Flucloxacillin worsens while imipenem-cilastatin protects against vancomycin-induced kidney injury in a translational rat model.

BACKGROUND AND PURPOSE: Vancomycin is one of the most common clinical antibiotics, yet acute kidney injury is a major limiting factor. Common combinations of antibiotics with vancomycin have been reported to worsen and improve vancomycin-induced kidney injury. We aimed to study the impact of flucloxacillin and imipenem-cilastatin on kidney injury when combined with vancomycin in our translational rat model. EXPERIMENTAL APPROACH: Male Sprague-Dawley rats received allometrically scaled (1) vancomycin, (2) flucloxacillin, (3) vancomycin + flucloxacillin, (4) vancomycin + imipenem-cilastatin or (5) saline for 4 days. Kidney injury was evaluated via drug accumulation and urinary biomarkers including urinary output, kidney injury molecule-1 (KIM-1), clusterin and osteopontin. Relationships between vancomycin accumulation in the kidney and urinary kidney injury biomarkers were explored. KEY RESULTS: Urinary output increased every study day for vancomycin + flucloxacillin, but after the first dose only in the vancomycin group. In the vancomycin + flucloxacillin group, urinary KIM-1 increased on all days compared with vancomycin. In the vancomycin + imipenem-cilastatin group, urinary KIM-1 was decreased on Days 1 and 2 compared with vancomycin. Similar trends were observed for clusterin. More vancomycin accumulated in the kidney with vancomycin + flucloxacillin compared with vancomycin and vancomycin + imipenem-cilastatin. The accumulation of vancomycin in the kidney tissue correlated with increasing urinary KIM-1. CONCLUSIONS AND IMPLICATIONS: Vancomycin + flucloxacillin caused more kidney injury compared with vancomycin alone and vancomycin + imipenem-cilastatin in a translational rat model. The combination of vancomycin + imipenem-cilastatin was nephroprotective.