Is a randomised controlled trial of take home naloxone distributed in emergency settings likely to be feasible and acceptable? Findings from a UK qualitative study exploring perspectives of people who use opioids and emergency services staff.

OBJECTIVE: Distribution of take-home naloxone (THN) by emergency services may increase access to THN and reduce deaths and morbidity from opioid overdose. As part of a feasibility study for a randomised controlled trial (RCT) of distribution of THN kits and education within ambulance services and Emergency Departments (EDs), we used qualitative methods to explore key stakeholders' perceptions of feasibility and acceptability of delivering the trial. METHODS: We undertook semi-structured interviews and focus groups with 26 people who use opioids and with 20 paramedics and ED staff from two intervention sites between 2019 and 2021. Interviews and focus groups were recorded, transcribed verbatim and analysed using Framework Analysis. RESULTS: People using opioids reported high awareness of overdose management, including personal experience of THN use. Staff perceived emergency service provision of THN as a low-cost, low-risk intervention with potential to reduce mortality, morbidity and health service use. Staff understood the trial aims and considered it compatible with their work. All participants supported widening access to THN but reported limited trial recruitment opportunities partly due to difficulties in consenting patients during overdose. Procedural problems, restrictive recruitment protocols, limited staff buy-in and patients already owning THN limited trial recruitment. Determining trial effectiveness was challenging due to high levels of alternative community provision of THN. CONCLUSIONS: Distribution of THN in emergency settings was considered feasible and acceptable for stakeholders but an RCT to establish the effectiveness of THN delivery is unlikely to generate further useful evidence due to difficulties in recruiting patients and assessing benefits.

[Progress in epidemiological characteristics and surveillance and early warning of dengue fever in China].

Dengue fever is an acute mosquito-borne infectious disease caused by dengue virus and widely spread worldwide. Many factors, such as pathogens, vector organisms, climate, and social environment, affect its transmission and prevalence. The local dengue fever epidemic caused by imported cases in China shows a trend of increasing epidemic latitude and more widespread epidemic areas. However, the traditional monitoring and early warning models of dengue fever mainly focus on researching a single factor and a single area. Establishing a multi-factor forecast and early warning system is urgent to strengthen the early warning capability for the dengue fever epidemic. This paper mainly discusses the epidemic characteristics, the influencing factors, and the surveillance and early warning models of dengue fever in China to provide a reference for the effective prevention and control of dengue fever in China.

[Construction and preliminary validation of a risk prediction model for the recurrence of diabetic foot ulcer in diabetic patients].

Objective: To develop a risk prediction model for the recurrence of diabetic foot ulcer (DFU) in diabetic patients and primarily validate its predictive value. Methods: Meta-analysis combined with retrospective cohort study was conducted. The Chinese and English papers on risk factors related to DFU recurrence publicly published in China Biology Medicine disc, China National Knowledge Infrastructure, Wanfang Database, VIP Database, and PubMed, Embase, Cochrane Library, and Web of Science, and the search time was from the establishment date of each database until March 31st, 2022. The papers were screened and evaluated, the data were extracted, a meta-analysis was performed using RevMan 5.4.1 statistical software to screen risk factors for DFU recurrence, and Egger's linear regression was used to assess the publication bias of the study results. Risk factors for DFU recurrence mentioned in ≥3 studies and with statistically significant differences in the meta-analysis were selected as the independent variables to develop a logistic regression model for risk prediction of DFU recurrence. The medical records of 101 patients with DFU who met the inclusion criteria and were admitted to Affiliated Hospital of Guizhou Medical University from January 2019 to June 2022 were collected. There were 69 males and 32 females, aged (63±14) years. The receiver operating characteristic (ROC) curve of the predictive performance of the above constructed predictive model for DFU recurrence was drawn, and the area under the ROC curve, maximum Youden index, and sensitivity and specificity at the point were calculated. Dataset including data of 8 risk factors for DFU recurrence and the DFU recurrence rates of 10 000 cases was simulated using RStudio software and a scatter plot was drawn to determine two probabilities for risk division of DFU recurrence. Using the ß coefficients corresponding to 8 DFU recurrence risk factors ×10 and taking the integer as the score of coefficient weight of each risk factor, the total score was obtained by summing up, and the cutoff scores for risk level division were calculated based on the total score × two probabilities for risk division of DFU recurrence. Results: Finally, 20 papers were included, including 3 case-control studies and 17 cohort studies, with a total of 4 238 cases and DFU recurrence rate of 22.7% to 71.2%. Meta-analysis showed that glycosylated hemoglobin >7.5% and with plantar ulcer, diabetic peripheral neuropathy, diabetic peripheral vascular disease, smoking, osteomyelitis, history of amputation/toe amputation, and multidrug-resistant bacterial infection were risk factors for the recurrence of DFU (with odds ratios of 3.27, 3.66, 4.05, 3.94, 1.98, 7.17, 11.96, 3.61, 95% confidence intervals of 2.79-3.84, 2.06-6.50, 2.50-6.58, 2.65-5.84, 1.65-2.38, 2.29-22.47, 4.60-31.14, 3.13-4.17, respectively, P<0.05). There were no statistically significant differences in publication biases of diabetic peripheral neuropathy, diabetic peripheral vascular disease, glycosylated hemoglobin >7.5%, plantar ulcer, smoking, multidrug-resistant bacterial infection, or osteomyelitis (P>0.05), but there was a statistically significant difference in the publication bias of amputation/toe amputation (t=-30.39, P<0.05). The area under the ROC curve of the predictive model was 0.81 (with 95% confidence interval of 0.71-0.91) and the maximum Youden index was 0.59, at which the sensitivity was 72% and the specificity was 86%. Ultimately, 29.0% and 44.8% were identified respectively as the cutoff for dividing the probability of low risk and medium risk, and medium risk and high risk for DFU recurrence, while the corresponding total scores of low, medium, and high risks of DFU recurrence were <37, 37-57, and 58-118, respectively. Conclusions: Eight risk factors for DFU recurrence are screened through meta-analysis and the risk prediction model for DFU recurrence is developed, which has moderate predictive accuracy and can provide guidance for healthcare workers to take interventions for patient with DFU recurrence risk.

MS2 Virus-like Particles as a Versatile Peptide Presentation Platform: Insights into the Deterministic Abilities for Accommodating Heterologous Peptide Lengths.

Virus-like particles (VLPs) are nanostructures with the potential to present heterologous peptides at high density, thereby triggering heightened immunogenicity. RNA bacteriophage MS2 VLPs are a compelling delivery platform among them. However, a notable hurdle arises from the immune response toward MS2 coat protein, swiftly eliminating subsequent vaccinations via the same vector. Although larger inserts effectively mask carrier epitopes, current research predominantly focuses on displaying short conserved peptides (<30 aa). A systematic evaluation regarding the deterministic ability of MS2 VLPs as a platform for presenting heterologous peptides remains a gap. In light of this, we employed the "single-chain dimer" paradigm to scrutinize the tolerance of MS2 VLPs for peptide/protein insertions. The results unveiled functional MS2 VLP assembly solely for inserts smaller than 91 aa. Particularly noteworthy is the largest insertion achieved on the MS2 VLPs to date: the RNA helicase A (RHA) dsRNA-binding domains (dsRBD1). Attempts to introduce additional linkers or empty coat subunits fail to augment the expression level or assembly of the MS2 VLPs displaying dsRBD1, affirming 91 aa as the upper threshold for exogenous protein presentation. By illuminating the precise confines of MS2 VLPs in accommodating distinct peptide lengths, our study informs the selection of appropriate peptide and protein dimensions. This revelation not only underscores the scope of MS2 VLPs but also establishes a pivotal reference point, facilitating the strategic manipulation of MS2 VLPs to design next-generation epitope/antibody-based therapeutics.

PRESS survey: PREvention of surgical site infection-a global pan-specialty survey of practice protocol.

Background: Surgical site infections (SSI) complicate up to 40% of surgical procedures, leading to increased patient morbidity and mortality. Previous research identified disparities in SSI prevention guidelines and clinical practices across different institutions. The study aims to identify variations in SSI prevention practices within and between specialties and financial systems and provide a representation of existing SSI preventative measures to help improve the standardization of SSI prevention practices. Methods: This collaborative cross-sectional survey will be aimed at pan-surgical specialties internationally. The study has been designed and will be reported in line with the CROSS and CHERRIES standards. An international study steering committee will design and internally validate the survey in multiple consensus-based rounds. This will be based on SSI prevention measures outlined in the CDC (2017), WHO (2018), NICE (2019), Wounds UK (2020) and the International Surgical Wound Complications Advisory Panel (ISWCAP) guidelines. The questionnaire will include demographics, SSI surveillance, preoperative, peri-operative and postoperative SSI prevention. Data will be collected on participants' surgical specialty, operative grade, of practice and financial healthcare system of practice. The online survey will be designed and disseminated using QualtricsXM Platform™ through national and international surgical colleges and societies, in addition to social media and snowballing. Data collection will be open for 3 months with reminders, and raking will be used to ascertain the sample. Responses will be analyzed, and the chi-square test used to evaluate the impact of SSI prevention variables on responses. Discussion: Current SSI prevention practice in UK Vascular surgery varies considerably, with little consensus on many measures. Given the inconsistency in guidelines on how to prevent SSIs, there is a need for standardization. This survey will investigate the disparity in SSI preventative measures between different surgical fields and countries.

Correlation research of serum substance P, CCK-8, and 5-HT values with depression levels in stroke survivors.

OBJECTIVE: This study aimed to investigate the correlation of serum octapeptide cholecystokinin-8 (CCK-8), substance P (SP), and 5-hydroxytryptryptamine (5-HT) values with depression levels in patients with post-stroke depression (PSD). It also aimed to explore the potential approach for the early diagnosis of PSD. PATIENTS AND METHODS: A correlation research between patients' biochemical indicators and depression levels was performed among 70 stroke patients during hospitalization from June 2021 to February 2022. The 70 stroke patients were selected and divided into post-stroke depression and non-depression groups according to the Hamilton Depression Scale (HAMD) score. The concentrations of CCK-8, SP, and 5-HT in both groups were measured, and the relationship between the values of CCK-8, SP, 5-HT and the depression levels was analyzed. RESULTS: Among the 70 stroke survivors, 35 were in the depression group and 35 were in the non-depression group. Significant differences were observed in the concentration of CCK-8, SP, and 5-HT between the patients in the depression and non-depression group (p < 0.05). Accompanied by an increase in the depression level, the SP value gradually increased, but the CCK-8 and 5-HT values gradually decreased. Spearman correlation analysis indicated that the order of the correlation between CCK-8, 5-HT, SP, and the depression levels was CCK-8 > SP > 5-HT. CONCLUSIONS: All the CCK-8, SP and 5-HT values were correlated with the depression levels in stroke survivors. Furthermore, the correlation between CCK-8, SP, and post-stroke depression levels was higher than that of 5-HT, suggesting that the early diagnosis of PSD may be reflected more precisely through the detection of CCK-8, and SP values, thus providing potential priority for biochemical detection in the diagnosis of PSD.

[Methylophiopogonanone a Inhibits LPS/ATP-Induced Macrophage Pyroptosis via ROS/NLRP3 Pathway].

As a byproduct of mitochondrial respiration or metabolism, reactive oxygen species (ROS) can act as a signaling molecule to activate NLR family pyrin domain containing 3 (NLRP3) inflammasome, thereby triggering immune response. NLRP3 inflammasome acts as a sensor of various danger signals and is central to the control of pyroptosis occurrence. Macrophage pyroptosis is closely related to atherosclerosis, arthritis, pulmonary fibrosis and other inflammatory diseases. Methylophiopogonanone A (MO-A) is a main homoisoflavonoid in Chinese herb Ophiopogonis Radix, which has antioxidant effect. However, it is not clear whether MO-A can alleviate macrophage pyroptosis by inhibiting oxidative stress. Here we have shown that MO-A increases the activities of superoxide dismutase (SOD) and catalase (CAT), inhibits the production of ROS, reduces the activation of NLRP3 inflammasome and the release of lactate dehydrogenase (LDH), and inhibits pyroptosis in macrophages induced by lipopolysaccharides (LPS) and adenosine triphosphate (ATP). These effects can be reversed by the ROS promoter H2O2. Therefore, MO-A can inhibit macrophage pyroptosis through the ROS/NLRP3 pathway and may be considered as a candidate drug for the treatment of inflammatory diseases.

Low genetic diversity and predation threaten a rediscovered marine sponge.

Discovered in 1819 in the tropical waters off Singapore, the magnificent Neptune's cup sponge Cliona patera (Hardwicke, 1820) was harvested for museums and collectors until it was presumed extinct worldwide for over a century since 1907. Recently in 2011, seven living individuals were rediscovered in Singapore with six relocated to a marine protected area in an effort to better monitor and protect the population, as well as to enhance external fertilisation success. To determine genetic diversity within the population, we sequenced the complete mitochondrial genomes and nuclear ribosomal DNA of these six individuals and found extremely limited variability in their genes. The low genetic diversity of this rediscovered population is confirmed by comparisons with close relatives of C. patera and could compromise the population's ability to recover from environmental and anthropogenic pressures associated with the highly urbanised coastlines of Singapore. This lack of resilience is compounded by severe predation which has been shrinking sponge sizes by up to 5.6% every month. Recovery of this highly endangered population may require ex situ approaches and crossbreeding with other populations, which are also rare.

Comparison of open and robotic-assisted partial nephrectomy approaches using multicentric data (UroCCR-47 study).

We compared the outcomes of robotic-assisted partial nephrectomy (RPN) and open partial nephrectomy (OPN) using contemporary data to respond to unmet clinical needs. Data from patients included in the registry who underwent partial nephrectomy between January 01, 2014 and June 30, 2017 within 20 centres of the French Network for Research on Kidney Cancer UroCCR were collected (NCT03293563). Statistical methods included adjusted multivariable analyses. Rates of peri- and post-operative transfusion, and of surgical revision, were lower in the RPN (n = 1434) than the OPN (n = 571) group (2.9% vs. 6.0%, p = 0.0012; 3.8% vs. 11.5%, p < 0.0001; 2.4% vs. 6.7%, p < 0.0001, respectively). In multivariable analyses, RPN was independently associated with fewer early post-operative complications than OPN (overall: odds-ratio [95% confidence interval, CI] = 0.48 [0.35-0.66]; severe: 0.29 [0.16-0.54], p < 0.0001 for both) and shorter hospital stays (34% [30%; 37%], p < 0.0001). RPN was also a significantly associated with a decresedrisk of post-operative acute renal failure, and new-onset chronic kidney disease at 3 and 12 months post-surgery. There were no between-group differences in oncological outcomes. In comparison with OPN, RPN was associated with improved peri- and post-operative morbidity, better functional outcomes, and shorter hospital stays. Our results support the use of RPN, even for large and complex tumours.

Cellular Density in Adult Glioma, Estimated with MR Imaging Data and a Machine Learning Algorithm, Has Prognostic Power Approaching World Health Organization Histologic Grading in a Cohort of 1181 Patients.

BACKGROUND AND PURPOSE: Recent advances in machine learning have enabled image-based prediction of local tissue pathology in gliomas, but the clinical usefulness of these predictions is unknown. We aimed to evaluate the prognostic ability of imaging-based estimates of cellular density for patients with gliomas, with comparison to the gold standard reference of World Health Organization grading. MATERIALS AND METHODS: Data from 1181 (207 grade II, 246 grade III, 728 grade IV) previously untreated patients with gliomas from a single institution were analyzed. A pretrained random forest model estimated voxelwise tumor cellularity using MR imaging data. Maximum cellular density was correlated with the World Health Organization grade and actual survival, correcting for covariates of age and performance status. RESULTS: A maximum estimated cellular density of >7681 nuclei/mm2 was associated with a worse prognosis and a univariate hazard ratio of 4.21 (P < .001); the multivariate hazard ratio after adjusting for covariates of age and performance status was 2.91 (P < .001). The concordance index between maximum cellular density (adjusted for covariates) and survival was 0.734. The hazard ratio for a high World Health Organization grade (IV) was 7.57 univariate (P < .001) and 5.25 multivariate (P < .001). The concordance index for World Health Organization grading (adjusted for covariates) was 0.761. The maximum cellular density was an independent predictor of overall survival, and a Cox model using World Health Organization grade, maximum cellular density, age, and Karnofsky performance status had a higher concordance (C = 0.764; range 0.748-0.781) than the component predictors. CONCLUSIONS: Image-based estimation of glioma cellularity is a promising biomarker for predicting survival, approaching the prognostic power of World Health Organization grading, with added values of early availability, low risk, and low cost.

[Evaluation of effect based on different typing methods in Escherichia coli].

Objective: To evaluate the typing and clinical application effect based on clustered regularly interspaced short palindromic repeats (CRISPRs), serotype, and Multilocus Sequence Typing (MLST). Methods: The spacers, serotype and sequence type (ST) were obtained with CRISPRsFinder, SeroTypeFinder and MLST. PCR was used to amplify the CRISPRs, and the spacers were used to predict serotype and ST, then comparing with the serotype and ST. Results: We defined the I-E CRISPR/Cas as CT-Ⅰ, I-F CRISPR/Cas as CT-Ⅱ, and only CRISPR3-4 as CT-Ⅲ. We designated each unique arrangement spacer profile as a unique CRISPRs type. A total of 79 CT types, 76 serotypes, and 66 STs were identified. The CRISPRs typing was the most discriminating, with the Simpson index of 0.936, having the highest correlation with serology with the adjusted Rand index of 0.908. The CRISPRs type could divide the same serotype (ST) into two subtypes [O157∶H7(ST11), O104∶H4(ST678), and O26∶H11(ST21)]. The detection rates of CRISPR1, CRISPR2, CRISPR3, CRISPR4, and CRISPR3-4 were 81.1%, 94.5%, 1.4%, 1.4%, and 4.6%, with the accuracy rate of 95.0% and 100.0% according to the spacers to forecast O157∶H7 (ST11) and ST131. Conclusion: Based on the CRISPRs spacer, this method can be used as an essential molecular typing for E.coli, as it presents a good typing and clinical application effect.

Ontogenetic characteristics of the intestinal microbiota of Quasipaa spinosa revealed by 16S rRNA gene sequencing.

To analyse the correlation between the intestinal microbiota (IM) and differential development of Quasipaa spinosa across different stages of metamorphosis, we focused on four key developmental periods (15 days post-hatch [dph; Gosner stage, GS23], 60 dph [GS25], 90 dph [GS41] and 150 dph [GS25, GS41, GS42, GS46]) and used 16S rDNA amplicon sequencing. Results showed that IM diversity in Q. spinosa was related to life history. Specifically, there was a significant difference between the aquatic and terrestrial stages, and IM diversity increased with age. Proteobacteria, Bacteroidetes and Firmicutes were the dominant phyla in tadpoles, whereas Bacteroidetes, Proteobacteria, Firmicutes and Fusobacteria were the dominant phyla at the metamorphosis stages. The composition of the IM at different stages and ages varied considerably, but the changes were not substantial among different development stages at 150 dph. This was probably because age has a greater influence than growth factors, and host selective pressure increases with age. This study provides a theoretical reference for subsequent studies on the IM, as well as for the prevention of amphibian endogenous pathogenic microbial diseases.

Transcriptome analysis of blastoderms exposed to prolonged egg storage and short periods of incubation during egg storage.

BACKGROUND: Cool temperature egg storage prior to incubation is a common practice in the broiler industry; however, prolonged egg storage causes increased embryonic mortality and decreased hatchability and growth in surviving chicks. Exposing eggs to short periods of incubation during egg storage (SPIDES) reduces the adverse consequences of prolonged storage. SPIDES increases blastodermal cell viability by reducing apoptosis, though the counteracting mechanisms are unclear. To define the impact of prolonged storage and SPIDES, transcriptome analysis compared gene expression from blastoderms isolated from eggs exposed to the following treatments: control (CR, stored at 17 °C for 4 days), prolonged storage (NSR, stored at 17 °C for 21 days), SPIDES (SR, stored at 17 °C for 21 days with SPIDES), and incubated control (C2, stored at 17 °C for 4 days followed by incubation to HH (Hamburger-Hamilton) stage 2, used as the ideal standard development) (n = 3/group). Data analysis was performed using the CLC Genomics Workbench platform. Functional annotation was performed using DAVID and QIAGEN Ingenuity Pathway Analysis. RESULTS: In total, 4726 DEGs (differentially expressed genes) were identified across all experimental group comparisons (q < 0.05, FPKM> 20, |fold change| > 1.5). DEGs common across experimental comparisons were involved in cellular homeostasis and cytoskeletal protein binding. The NSR group exhibited activation of ubiquitination, apoptotic, and cell senescence processes. The SR group showed activation of cell viability, division, and metabolic processes. Through comparison analysis, cellular respiration, tRNA charging, cell cycle control, and HMBG1 signaling pathways were significantly impacted by treatment and potential regulatory roles for ribosomal protein L23a (RPL23A) and MYC proto-oncogene, BHLH transcription factor (MYC) were identified. CONCLUSIONS: Prolonged egg storage (NSR) resulted in enriched cell stress and death pathways; while SPIDES (SR) resulted in enriched basic cell and anti-apoptotic pathways. New insights into DNA repair mechanisms, RNA processing, shifts in metabolism, and chromatin dynamics in relation to egg storage treatment were obtained through this study. Although egg storage protocols have been examined through targeted gene expression approaches, this study provided a global view of the extensive molecular networks affected by prolonged storage and SPIDES and helped to identify potential upstream regulators for future experiments to optimize egg storage parameters.

Transcriptome analysis of inseminated sperm storage tubules throughout the duration of fertility in the domestic turkey, Meleagris gallopavo.

Sperm storage tubules (SST) are specialized invaginations of the oviductal epithelium that permit avian species to store spermatozoa for extended periods of time, without compromising sperm fertilization capacity. The molecular and physiological mechanisms behind sperm storage tubule differentiation, sperm protection, and regression remain largely unknown, but most likely have potential implications for substantially improving hen fertility, sperm storage, and semen cryopreservation in commercial poultry species. RNA sequencing was performed on sperm storage tubules isolated from the epithelium of the uterovaginal junction (UVJ) from hens at d 1, 7, 30, 60, and 90 postinsemination (n = 4 per timepoint). Read mapping and differential expression analysis were performed using CLC Genomics Workbench. A total of 2,340 differentially expressed genes were subjected to pathway analysis through Ingenuity Pathway Analysis (IPA). Through functional annotation of differentially expressed genes during early, peak, and late egg production, novel insights regarding the role of innate and acquired immune response to sperm, lipid synthesis and transfer, steroid hormone signalling, cytoskeletal reorganization, and regulation of ion homeostasis in SST were obtained. Additionally, potential pathways were identified that could be involved with suppressing sperm motility while sperm reside within the SST. Upstream analysis identified potential regulatory roles for 18 upstream regulators that could modulate sperm storage tubule function, including suppression of sperm motility. Understanding sperm storage tubule function throughout the laying cycle, especially with regards to sperm preservation may allow for the development of industry-based protocols for semen storage and cryopreservation that mimic the sperm preservation capabilities of SST and improve fertility.

Turkey ovarian tissue transplantation: effects of surgical technique on graft attachment and immunological status of the grafts, 6 days post-surgery.

Biobanked poultry ovaries can be revived via transplantation into a recipient female, which upon maturity will produce donor-derived progeny. Previously, a large portion of these recipients also produced recipient-derived progeny, making them gonadal chimeras. These were potentially created when portions of the recipient's ovary were inadvertently left behind. Completely removing the recipient ovary would solve this problem; however, leaving a portion of the recipient's ovary may have inadvertently increased the transplant attachment rate by providing a damaged area for attachment. To test this hypothesis in the turkey, we removed various portions (33-100%) of recipient ovarian tissue and determined the transplant attachment rate. Furthermore, the use of the abdominal air sac membrane as an additional anchoring point was tested. The overall attachment rate of transplants was 91% (27/30), while the average size of the transplants was 4.2 ± 0.6 mm2, 6 d postsurgery. There was no difference (P > 0.05) in the attachment rates, or transplant size between groups with varying amounts of recipent tissue removed, or by using the abdominal air sac membrane as an anchor. Finally, the immunological status of the grafts were evaluated by analyzing the presences of CD3 and MUM-1 (T and B cell markers). This showed that all transplants were infiltrated by large numbers of T and B cells. Shown by a high (P ≤ 0.001) percentage of CD3-positive immunostained cytoplasmic area (49.78 ± 3.90%) in transplants compared to remnant recipient tissue (0.30 ± 0.10%), as well as a high (P ≤ 0.001) percentage of MUM-1-positive immunostained nuclear area (9.85 ± 1.95%) in transplants over remnant recipient tissues (0.39 ± 0.12%). From this study we would recommend removing the entire recipient ovary, and not covering the transplants with the abdominal air sac membrane, to prevent gonadal chimeras. The high levels of lymphocytes within the grafts indicate possible tissue rejection, which could be overcome via immunosuppression with or without histocompatibility matching between donors and recipients.

Miniaturized percutaneous nephrolithotomy versus retrograde intrarenal surgery in the treatment of lower pole renal stones.

OBJECTIVES: Miniaturization of percutaneous nephrolithotomy techniques have led to their increased consideration for lower pole renal stones that can prove more challenging to reach using retrograde intrarenal surgery. The objectives of the present study were to evaluate and compare the outcomes of miniaturized percutaneous nephrolithotomy (miniPCNL) and retrograde intrarenal surgery (RIRS) for the treatment of lower pole renal stones. MATERIALS AND METHODS: A retrospective study was performed in two academic urology departments between January 2016 and June 2019. Patients presenting with one or multiple stones of the lower calyx and/or renal pelvis, between 10 and 40mm based on CT-scan treated by miniPCNL or RIRS were included. RESULTS: In all, 115 miniPCNL and 118 RIRS procedures were included. The rate of patients with no significant residual fragment (stone free rate) after the first procedure was higher in the miniPCNL group (69% vs. 52% P=0.01), especially for stones>20mm (63% vs. 24% respectively, P<0.001) and stones with a density≥1000HU (69% vs. 42% respectively, P=0.009). The higher stone free rate of miniPCNL was confirmed in multivariate analysis, adjusting for stone size and number of stones, OR 4.02 (95% CI 2.08-8.11, P<0.0001). The overall postoperative complication rate was higher in the miniPCNL group than in the RIRS group (23% vs. 11%, P=0.01). A second intervention for the treatment of residual fragments was necessary for 9.6% of patients in the miniPCNL group versus 30.5% of patients in the RIRS group (P<0.001). Pre-stenting rate and duration of ureteral drainage (2 [1-8] vs. 25 days [7-37], P<0.001) were lower in the miniPCNL group. CONCLUSIONS: The stone free rate was higher after miniPCNL, especially for stones>20mm and with a density>1000 HU, but was associated with a higher risk of postoperative complications and a longer hospital stay. RIRS resulted in fewer complications at the cost of a higher retreatment rate and longer ureteral stenting. LEVEL OF EVIDENCE: 3.

Autophagy induction regulates aquaporin 3-mediated skin fibroblast ageing.

BACKGROUND: Long- and short-term ultraviolet (UV) exposure have distinct biological effects on human fibroblasts. OBJECTIVES: To elucidate the underlying mechanisms of the biological effects of UV exposure on human skin fibroblasts. METHODS: We subjected human skin fibroblast cells with or without aquaporin 3 (AQP3), death effector domain-containing protein (DEDD) or Beclin1 manipulation to UVA treatment and evaluated autophagy and senescence in them. RESULTS: Short-term UVA irradiation induced autophagy and upregulated AQP3 but not senescence, whereas long-term UVA irradiation inhibited autophagy, AQP3 and trigger senescence in vitro and in vivo. Silencing AQP3 abolished short-term UVA irradiation-induced autophagy and led to cellular senescence, whereas AQP3 overexpression partially rescued the senescence and autophagy inhibition induced by long-term UVA exposure in vitro. Mechanistically, the transcription factor Jun was found to bind to the AQP3 promoter to activate its transcription following short-term UVA exposure. Subsequently, AQP3 interacted with DEDD to induce its ubiquitination-mediated degradation and promote autophagy, and bound to Beclin1 to directly activate autophagy. Finally, autophagy induced by AQP3 overexpression robustly prevented UVA-induced senescence in vitro and in vivo. CONCLUSIONS: Our study indicates that AQP3 controls skin fibroblast photoageing by regulating autophagy and represents a potential target for future interventions against skin ageing.

ASSOCIATION BETWEEN THE CTLA-4 EXON 1+49A/G POLYMORPHISM AND THE RELAPSE OF GRAVE'S DISEASE AFTER ATD WITHDRAWAL: A META-ANALYSIS.

Background: The cytotoxic T lymphocyte-associated molecules-4 (CTLA-4) is related to the relapse of Graves' disease (GD) after anti-thyroid drugs (ATDs) withdrawal. We performed a meta-analysis to generate large-scale evidence on whether the CTLA-4 exon 1+49A/G polymorphism can predict the relapse of GD after ATDs withdrawal. Methods and Results: The PubMed, EMBASE,the Cochrane Library and reference lists of relevant studies were searched to identify eligible studies from inception to Jan, 2021. Ten eligible studies consisting of 1450 GD patients with a total of 848 relapsed patients were included in the meta-analysis.In Caucasians patients, the CTLA-4 exon 1+49A/G polymorphism significantly elevated the relapse risk of GD in additive (OR = 2.07, 95% CI: 1.18-3.62, P=0.011), dominant (OR = 2.52, 95% CI: 1.17-5.41, P=0.02), homozygote model(OR = 3.264, 95% CI: 1.25-8.52, P=0.016), except recessive (OR = 2.18, 95% CI = 0.98-4.86, P = 0.062) and heterozygote model (OR = 2.141, 95% CI = 0.958-4.786, P = 0.064). In Asian subgroup, none of these genotypes show any associations with the relapse of GD after ATDs withdrawal. Conclusion: This meta-analysis suggests that the CTLA-4 exon1 +49A/G polymorphism is associated with the relapse risk of GD after ATDs withdrawal in Caucasians, not Asians. Compared with the AA genotype, Caucasian patients with GG genotype have 3.264 times risk of relapse. A more aggressive treatment such as radioactive iodine or thyroidectomy, or longer periods treatment of ATDs should be recommended in Caucasian patients with the GG genotype.

[Renal Parenchyma Trauma and General Trauma Recommandations]. / Traumatismes du parenchyme rénal et recommandations générales de traumatologie.

INTRODUCTION: Among trauma emergencies, kidney damage is uncommon. The urologist is frequently on the second line in the management of patients with multiple traumatic lesions. Knowledge of treatment is necessary to be able to integrate the different teams involved in an approach that is both vital in the context of damage control and functional with a concern for parenchymal preservation. METHODS: A systematic review of the literature was carried out using the Medline database in order to identify the most relevant articles in English and French. RESULTS: Kidney trauma occurs either by direct shock or by a deceleration mechanism. They are classified by severity according to the AAST classification. Management is mostly conservative by avoiding surgery and controlling bleeding by arterial embolization. Surveillance checks for complications occurrence in high-grade trauma. Traumatic dissection of the renal artery, with a poor functional prognosis requires a short delay before treatment. CONCLUSION: The prognosis for trauma to the kidney, regardless of the grade, is currently good, with improvements of effective resuscitation and embolization in the event of bleeding.