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• The presentation of urinary tract infections (UTIs) in neonates differs from that seen in older children. • The type and route of infection also differ in neonates, when compared with older children. • An appropriate urine sample for diagnosis is needed, but treatment should not be delayed. • A neonate in whom a UTI is suspected should be evaluated for sepsis, including invasive cultures. • After a documented neonatal UTI, a radiologic work-up is warranted to detect anatomic anomalies. • Vesicoureteral reflux (VUR) is diagnosed in 30%–50% of neonates with proven UTI. • Voiding cystourethrogram is the gold standard for the diagnosis of VUR and should be performed on high-risk neonates. • Treatment of VUR should be tailored to each patient's individual risk of UTI recurrence, with the goals of preventing future UTIs and renal scar formation.

Background Polycyclic triterpenoids (PTs) are common in plants, and have attracted considerable interest due to their remarkable biological activities. Currently, engineering the ergosterol synthesis pathway in Saccharomyces cerevisiae is a safe and cost-competitive way to produce triterpenoids. However, the strict regulation of ERG1 involved in the epoxidation of squalene limits the triterpenoid production. Results In this study, we found that the decrease in ERG7 protein level could dramatically boost the epoxidation of squalene by improving the protein stability of ERG1. We next explored the potential factors that affected the degradation process of ERG1 and confirmed that ERG7 was involved in the degradation process of ERG1. Subsequently, expression of four different triterpene cyclases utilizing either 2,3-oxidosqualene or 2,3:22,23-dioxidosqualene as the substrate in ERG7-degraded strains showed that the degradation of ERG7 to prompt the epoxidation of squalene could significantly increase triterpenoid production. To better display the potential of the strategy, we increased the supply of 2,3-oxidosqualene, optimized flux distribution between ergosterol synthesis pathway and β-amyrin synthesis pathway, and modified the GAL-regulation system to separate the growth stage from the production stage. The best-performing strain ultimately produced 4216.6 ± 68.4 mg/L of β-amyrin in a two-stage fed-fermentation (a 47-fold improvement over the initial strain). Conclusions This study showed that deregulation of the native restriction in ergosterol pathway was an effective strategy to increase triterpenoid production in yeast, which provided a new insight into triterpenoids biosynthesis.

Additional file 1: Fig. S1. Comparison of squalene contents in strains SquC1 and S01. Fig. S2. GC–MS analysis of SQO and SDO. Fig. S3. The concentrations of each product are provided in ERG7-modified strains. Fig. S4. The protein sequences comparison between heterologous lanosterol synthases and ERG7. Fig. S5. Removing the bottleneck to stimulate PTs production. Fig. S6. Detection of 24,25-epoxycucurbitadienol. Fig. S7. Detection of the white solids accumulated on the tank wall during the fed-batch fermentation. Fig. S8. Correlation between samples. Table S1. S. cerevisiae strains used in this work. Table S2. Plasmids used in this study. Table S3. Primers used in this study. Table S4. Heterologous lanosterol synthase sequences.

Erica Ai Li,1 Claire A Wilson,2 Jacob Davidson,2 Aaron Kwong,1 Amrit Kirpalani,3 Peter Zhan Tao Wang2,4 1Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada; 2Division of Pediatric Surgery, London Health Sciences Centre, London, Ontario, Canada; 3Division of Pediatric Nephrology, London Health Sciences Centre, London, Ontario, Canada; 4Division of Urology, London Health Sciences Center, London, Ontario, CanadaCorrespondence: Erica Ai Li, Schulich School of Medicine and Dentistry, Western University, 1151 Richmond St, London, Ontario, N6A 5C1, Canada, Email ali2024@meds.uwo.caBackground: There is limited work exploring competency-based medical education (CBME) in undergraduate medical education. We aimed to assess medical students’ and faculty’s perception of CBME in the undergraduate medicine setting after its implementation at our institution through a Content, Input, Process, Product (CIPP) program evaluation model.Methods: We explored the rationale for the transition to a CBME curriculum (Content), the changes to the curriculum and the teams involved in the transition (Input), medical students’ and faculty’s perception of the current CBME curriculum (Process), and benefits and challenges of implementing undergraduate CBME (Product). A cross-sectional online survey was delivered over 8-weeks in October 2021 to medical students and faculty as part of the Process and Product evaluation.Results: Medical students displayed greater optimism towards CBME, compared to faculty, in terms of its role in medical education (p< 0.05). Faculty were less certain about how CBME was currently implemented (p< 0.05), as well as how feedback to students should be delivered (p< 0.05). Students and faculty agreed on perceived benefits to CBME implementation. Faculty time commitment to teaching and logistical concerns were reported as perceived challenges.Conclusion: Education leaders must prioritize faculty engagement and continued professional development of faculty to facilitate the transition. This program evaluation identified strategies to aid the transition to CBME in the undergraduate setting.Keywords: competency-based medical education, competency by design, undergraduate, medical student, faculty

Postsynaptic NMDARs at spinal synapses are required for postsynaptic long-term potentiation and chronic pain. However, how presynaptic NMDARs (PreNMDARs) in spinal nociceptor terminals control presynaptic plasticity and pain hypersensitivity has remained unclear. Here we report that PreNMDARs in spinal nociceptor terminals modulate synaptic transmission in a nociceptive tone-dependent manner. PreNMDARs depresses presynaptic transmission in basal state, while paradoxically causing presynaptic potentiation upon injury. This state-dependent modulation is dependent on Ca2+ influx via PreNMDARs. Small conductance Ca2+-activated K+ (SK) channels are responsible for PreNMDARs-mediated synaptic depression. Rather, tissue inflammation induces PreNMDARs-PKG-I-dependent BDNF secretion from spinal nociceptor terminals, leading to SK channels downregulation, which in turn converts presynaptic depression to potentiation. Our findings shed light on the state-dependent characteristics of PreNMDARs in spinal nociceptor terminals on modulating nociceptive transmission and revealed a mechanism underlying state-dependent transition. Moreover, we identify PreNMDARs in spinal nociceptor terminals as key constituents of activity-dependent pain sensitization.

Harnessing mitochondria is considered as a promising method for biosynthesis of terpenes due to the adequate supply of acetyl-CoA and redox equivalents in mitochondria. However, mitochondrial engineering often causes serious metabolic burden indicated by poor cell growth. Here, we systematically analyzed the metabolic burden caused by the compartmentalization of the MVA pathway in yeast mitochondria for squalene synthesis. The phosphorylated intermediates of the MVA pathway, especially mevalonate-5-P and mevalonate-5-PP, conferred serious toxicity within mitochondria, which significantly compromised its possible advantages for squalene synthesis and was difficult to be significantly improved by routine pathway optimization. These phosphorylated intermediates were converted into ATP analogues, which strongly inhibited ATP-related cell function, such as mitochondrial oxidative respiration. Fortunately, the introduction of a partial MVA pathway from acetyl-CoA to mevalonate in mitochondria as well as the augmentation of the synthesis of mevalonate in cytosol could significantly promote the growth of yeasts. Accordingly, a combinatorial strategy of cytoplasmic and mitochondrial engineering was proposed to alleviate the metabolic burden caused by the compartmentalized MVA pathway in mitochondria and improve cell growth. The strategy also displayed the superimposed effect of cytoplasmic engineering and mitochondrial engineering on squalene production. Through a two-stage fermentation process, the squalene titer reached 21.1 g/L with a specific squalene titer of 437.1 mg/g dcw, which was the highest at present. This provides new insight into the production of squalene and other terpenes in yeasts based on the advantages of mitochondrial engineering.

The high concentration of iron and manganese in groundwater is harmful to human health, and the sources of manganese in rapidly urbanization areas are complex. Based on more than 2500 sets of hydrochemical data in different historical periods, the spatial distribution characteristics, sources, and genesis of groundwater manganese in different aquifers and areas with different urbanization levels in the Pearl River Delta were studied by using mathematical statistics and principal component analysis. The results showed that the concentration of manganese in groundwater in the pore aquifer was obviously higher than that in the fissure and karst aquifer. The proportion of high-manganese groundwater in the pore aquifer was twice that in the fissure and karst aquifer. The proportion of high-manganese groundwater in urbanized and suburban areas was significantly higher than that in non-urbanized areas. On a regional scale, the decomposition of organic matter and the reductive dissolution of Fe-Mn (oxygen) hydroxide in sedimentary strata under reductive conditions may have been the main factors controlling the increase in manganese concentration in pore aquifers. High-manganese groundwater in fissured aquifers may have been affected by low-oxygen domestic sewage leakage accompanying urbanization and industrial wastewater leakage and infiltration accompanying industrialization. The pore high-manganese groundwater was controlled by reduction conditions, and the weakly acidic environment of fissure and karst high-manganese groundwater was the important influencing factor. In the past 10 years, the groundwater environment in the study area has been improving, and the increase in groundwater redox potential and pH was not conducive to the formation of high-manganese groundwater, which was also the main cause of the overall decrease in Mn

Grinding is the main processing method for the particle-reinforced composites, where removal mechanism is of great significance to surface usability performance. In this study, Hopkinson pressure bar tests of SiCp/Al composite were carried out, and the constitutive model of SiCp/Al composite was obtained. Based on the finite element model of Hopkinson pressure bar tests, the interfacial constitute model of SiCp/Al composite was obtained. Single abrasive grain grinding experiments were designed and conducted to obtain the grinding force. Based on the interfacial constitute model, a new integrated grinding simulation model for the high volume fraction SiCp/Al composite was established and verified by the results of the single abrasive grain experiments, then the single abrasive grain grinding force prediction model was established and verified. Several grinding mechanism models for SiCp/Al composites were proposed, and the debonding between the interface of silicon carbides and aluminum alloy was observed. Finally, the multi-abrasive grain grinding forces were measured under different grinding process parameters and the influence of the grinding process parameters on the grinding force was discussed. This research about the micro-grinding mechanism of SiCp/Al composites provides a theoretical support for the study of surface quality.

Surface wear of drilling bit in the drilling process is complex, and the traditional wear index is not suitable to reflect the wear condition of drilling bit well; it is necessary to investigate on the appropriate wear testing and evaluation method. In this paper, a visual measurement system is set up to obtain the drilling bit wear characteristics based on machine vision. The wear area image is grayscale processed, and the gray image is thresholding segmentation processed, then the boundary feature is extracted based on the chain code method. A comprehensive evaluation system is established, in which the wear perimeter, the equivalent wear diameter, and maximum wear width of different areas are proposed as the wear indicators. The wear fusion feature based on the principal component analysis is proposed to characterize the drilling bit wear degree, the wear indicators of different regions are characterized and fused as the wear degree of different regions, then the prediction model of the drilling bit wear degree is established based on support vector machine. The results show that the predicted results are mainly consistent with the experimental results. The research of the drilling bit wear characteristics based on principal component analysis can provide guidance for the study of drilling bit wear mechanism.

Prompt Doppler ultrasonography to aid in diagnosis is often key to managing testicular torsion, but there may be delays in access; a faster, more widely available alternative is point-of-care ultrasonography (POCUS). The purpose of this study was to develop and evaluate a scrotal POCUS curriculum for urology and emergency medicine residents.Content experts in urology, emergency medicine and diagnostic imaging collaborated in a modified Delphi method to design a practical didactic curriculum for scrotal POCUS for the identification of testicular torsion. Training included 3 online video teaching modules and a 1-hour hands-on teaching session with standardized adult patients. We evaluated participants' competency in scrotal POCUS using a validated scale. We assessed participants' knowledge, comfort and confidence in performing scrotal POCUS before and after the intervention and at 3 months.Twenty-four urology (n = 12) and emergency medicine (n = 12) residents participated in the curriculum. After hands-on practice, 23 participants (96%) were deemed competent at scrotal POCUS. Pre-post testing showed significant improvement in knowledge (mean score 63% v. 80%, p0.001), comfort (mean Likert score 0.6 v. 3.6, p0.001) and confidence (mean Likert score 1.0 v. 2.1, p0.001) after the intervention. These effects were maintained at the 3-month assessment.The scrotal POCUS curriculum was effective and acceptable to both urology and emergency medicine residents. The findings suggest that scrotal POCUS can be learned effectively through a short hands-on session and didactic instruction.Le diagnostic rapide d’une torsion testiculaire à l’aide d’une échographie Doppler est souvent crucial à la prise en charge de ce trouble. Or, comme l’accès à cet examen peut être limité, l’échographie portable constitue une solution de rechange rapide et largement accessible. La présente étude visait la mise au point et l’évaluation d’un programme de formation sur l’échographie portable scrotale destiné aux résidents en urologie et en médecine d’urgence.Des experts en urologie, en médecine d’urgence et en imagerie diagnostique se sont servis d’une méthode Delphi modifiée pour concevoir un programme de formation sur l’échographie portable visant à faciliter le diagnostic de la torsion testiculaire. Ce programme comprenait 3 modules d’apprentissage vidéo en ligne, ainsi qu’une séance pratique d’une heure auprès de patients adultes normalisés. Nous avons évalué les compétences des participants en matière d’échographie portable scrotale au moyen d’une échelle validée. Nous avons également évalué les connaissances, l’aisance et le niveau de confiance des participants à l’égard de cet examen avant et immédiatement après la formation, puis 3 mois plus tard.Au total, 24 résidents en urologie (n = 12) et en médecine d’urgence (n = 12) ont suivi le programme de formation. Après la séance pratique, 23 participants (96 %) avaient les compétences nécessaires à la réalisation d’une échographie portable scrotale. La comparaison des résultats obtenus avant et immédiatement après la formation a montré une augmentation significative des connaissances (note moyenne : 63 % c. 80 %; p0,001), de l’aisance (moyenne à l’échelle de Likert : 0,6 c. 3,6; p0,001) et du niveau de confiance (moyenne à l’échelle de Likert : 1,0 c. 2,1; p0,001) des participants. Les effets de la formation étaient toujours présents 3 mois plus tard.Le programme de formation sur l’échographie portable scrotale s’est avéré efficace et acceptable pour les résidents en urologie et en médecine d’urgence. Les résultats obtenus laissent croire qu’une formation pédagogique et une courte séance d’apprentissage pratique permettent l’enseignement efficace de l’échographie portable scrotale.

Mastering a surgical skill requires experience and repetition, yet opportunities for surgical trainees to gain real experience are variable and limited by case load. Surgical simulators have emerged in an attempt to overcome these limitations. However, the few currently available skills simulators for flexible endoscopy are costly, have limited accessibility and versatility, lack portability, and require dedicated time for practice. The use of a portable skills simulator to teach flexible endoscopy may provide a feasible alternative. This study introduces a novel, low-cost, portable, endoscopic simulation system for training basic endoscopic skills. Using custom software, the simulator presents a virtual environment featuring 3D models of anatomy, endoscopes, and endoscopic tools. The virtual endoscope and its tools are directly controlled in the simulation by motion input from a custom-manufactured portable endoscopic controller that communicates data via a Bluetooth interface. This two-part study presents proof of concept and initial pilot data examining the face/content validity and preliminary construct validity of the portable endoscopic simulator. In part 1, experts (

Layered fracture frequently occurs in the deforming process of QStE700 medium-thickness steel plates under tensile loading. In this study, the morphology of a layered fracture was observed via scanning electron microscopy, and the mechanism of the layered fracture was also analyzed. Based on the three-dimensional digital image correlation technique, a section analysis method was adopted for determining the true stress–strain curve including the necking process. A modified Bridgeman’s equation was adopted to transform the true stress–strain curve into the equivalent stress–strain curve. At the time of layered fracture occurrence, the equivalent strain and stress triaxiality of differently shaped specimens were obtained and fitted to a linear exponential relationship equation. The equation was the layered fracture criterion function and combined with the finite element method (FEM) simulations for determining the damage criterion of the layered fracture of a certain specimen. The FEM-simulated equivalent strain was consistent with the experimental equivalent strain of the layered fracture. Summarizing, the proposed method to predict the layered fracture of a QStE700 medium-thickness steel plate is effective and can be adopted in the study and control of layered fracture.

Grinding is the main processing technique for particle-reinforced composites, in which grinding force and temperature are significant for investigating the removal mechanism and surface properties. In this study, a grinding force prediction model is established based on the response surface methodology. The energy density of surface heat source in the grinding area is calculated by combining the contact area between the grinding wheel and workpiece. Based on the integration algorithm in time and space, a theoretical ideal grinding temperature prediction model is deduced. The grinding heat energy transfer coefficient is defined as the percentage of heat energy, which is transferred from the grinding heat energy to the workpiece. According to the experimental and ideal theoretical highest grinding temperatures, a prediction model of the heat energy transfer coefficient is established, and the modified theoretical highest grinding temperature prediction model is obtained. Furthermore, a finite element model of SiCp/Al composite in grinding is established. The highest grinding temperature in the finite element model is consistent with the modified theoretical highest grinding temperature, and the grinding temperature field is analysed. The highest grinding temperature increases as the wheel speed and grinding depth increase, while it decreases as table speed increases, which differs from that of some common materials. Thus, the grinding temperature prediction model provides an important reference for the study of removal mechanism and surface properties of SiCp/Al composite.

The source of iodine in the groundwater of coastal urbanization areas is complex, and high-iodine groundwater is a potential threat to the safety of drinking water. Based on this, this study took the Pearl River Delta, which is developing rapidly in urbanization, as the research area. Additionally, the occurrence characteristics and driving factors of iodide in shallow groundwater of different aquifers and different urbanization levels in the Pearl River Delta were studied using mathematical statistics, principal component analysis, and other methods. The results showed that the concentration of iodide in the shallow groundwater was 2.34 mg·L

The supplemental information is mainly about the detailed settings of some parameters in the proposed SiamMLP model, the network design, and some complementary explanations.

Objectives Self-regulated learning has been proposed as a resource saving alternative for learning knot tying. However, this may be hindered by the Dunning-Kruger effect. A potential alternative is guided video reflection. The objectives of this study are to compare the performance and self-assessment abilities amongst medical students learning knot tying using either a traditional self-regulated approach versus guided video reflection. Design This randomized, single-blinded, controlled trial used a pre-post-retention test design. All knot tying performances were video recorded and assessed nonsequentially by blinded evaluators using a modified Objective Structured Assessment of Technical Skills tool. Participants This study recruited 31 first- and second-year medical students and 6 senior urology residents from Western University in Canada. Results At baseline, the performances of the experts were significantly higher than the experimental groups (F3,85 = 9.080, p Conclusions Students using guided video reflection were able to achieve competency and maintained their knot tying skills to the same degree as those who used the self-regulated approach. These results may be due to the positive effects of reflection on self-assessment abilities and subsequent improvement in goal setting for further practice.

Grinding is the main processing method for particle-reinforced composites, and grinding force prediction models are very important for research on removal mechanisms. In this study, single-abrasive-grain grinding experiments on SiCp/Al composites were conducted to determine the grinding forces at different grinding process parameters. In addition, a prediction model for the single-abrasive-grain grinding force was established to study the influence of the grinding process parameters and grinding grain angle on the grinding force of SiCp/Al composite. Moreover, multi-abrasive-grain grinding experiments were conducted at different grinding process parameters, which resulted in different grinding forces. The support vector machine (SVM) prediction method based on particle swarm optimisation (PSO) was used to establish a prediction model for the multi-abrasive-grain grinding force; the single-abrasive-grain grinding forces at different grinding grain angles were the input, and the average experimental grain grinding force was the output. The results show that the error between the predicted and experimental grinding forces is below 12%. Furthermore, the grinding force decreases with increasing wheel speed and increases with increasing feed velocity and grinding depth. The PSO–SVM algorithm–based grinding force prediction model can accurately predict the grinding force of SiCp/Al composite and provides theoretical support for improved surface quality.

OBJECTIVE To explore the current practice patterns for the management of renal cysts internationally among pediatric urologists and nephrologists. MATERIALS AND METHODS A survey composed of 21 questions and 4 clinical scenarios was distributed to pediatric urologists and nephrologists. Survey questions evaluated optimal imaging modality, management, and follow-up period. Interspecialty comparisons were made using chi-square analysis where appropriate. RESULTS A total of 183 respondents completed the survey (128 pediatric urologists, 37 pediatric nephrologists, and 19 other specialists). Most (57%) respondents agreed or strongly agreed with using an ultrasound based Bosniak classification to categorize renal cysts in children. The most commonly used follow-up intervals were 6-12 months for pediatric urologists and 1-2 years for pediatric nephrologists. Symptomatic mass effect (80.9%), gross hematuria (79.2%), or family history were the most common reasons for escalating surveillance. Pediatric nephrologists were more likely to increase follow-up with development of bilateral simple renal cysts (P = .008) or chronic kidney disease (P = .027) when compared to pediatric urologists. Laparoscopic marsupialization (39.4%) was the most common treatment for a simple renal cyst in a symptomatic child. Modified Bosniak III cysts had more heterogeneity in treatment based on the physician responses. CONCLUSION There is currently no consensus on the optimal protocol for the surveillance, imaging, or treatment of renal cysts in children. Most respondents agree that using an ultrasound-based Bosniak classification is reasonable. A call to action is therefore necessary for the development of registries and guidelines on the management of pediatric renal cysts and their associated malignancies.

This review focuses on the diagnosis, evaluation, and management of valve bladder syndrome (VBS) following initial treatment of posterior urethral valves (PUV). Based on current literature, we discuss the effect of PUV management in VBS and investigate the role of medications, catherization, surgery, and novel interventions. The current initial management of PUV involves valve ablation. Cutaneous urinary diversions are secondary options based on patient characteristics, PUV severity, and response to catheter drainage. VBS can independently occur as a consequence of PUV due to reduced nephron endowment leading to renal tubular dysfunction and polyuria, high bladder filling pressures secondary to a non-compliant bladder, and poor bladder emptying due to bladder neck hypertrophy. Options to mitigate the risk of upper tract deterioration include behavioral modifications and medical therapy (anticholinergics or alpha-blockers), bladder neck incision, clean intermittent catheterization and overnight catheter drainage, or more invasive approaches such as botulinum toxin injections and creation of a Mitrofanoff channel. Several experimental therapies to attenuate bladder fibrosis are currently under investigation. The management of VBS starts with initial management of PUV and is subsequently dependent on the evolving bladder filling dynamics and bladder neck hypertrophy affecting bladder filling and emptying. This requires a pre-emptive management protocol to identify VBS in boys with PUV to prevent renal damage using various therapeutic interventions. The lack of prospective studies to investigate effectiveness of available therapeutic options to treat VBS limits the development of an evidence-based approach for severity-based management of PUV-associated VBS.

Opioid analgesics remain the mainstay for managing intractable chronic pain, but their use is limited by detrimental side effects such as analgesic tolerance and hyperalgesia. Calcium-dependent synaptic plasticity is a key determinant in opiates tolerance and hyperalgesia. However, the exact substrates for this calcium-dependent synaptic plasticity in mediating these maladaptive processes are largely unknown. Canonical transient receptor potential 1, 4, and 5 (TRPC1, 4, 5) proteins assemble into heteromultimeric nonselective cation channels with high Ca2+ permeability and influence various neuronal functions. However, whether and how TRPC1/4/5 channels contribute to the development of opiates tolerance and hyperalgesia remains elusive. Here, we show that TRPC1/4/5 channels contribute to the generation of morphine tolerance and hyperalgesia. Chronic morphine exposure leads to upregulation of TRPC1/4/5 channels in the spinal cord. Spinally expressed TRPC1, TPRC4, and TRPC5 are required for chronic morphine-induced synaptic long-term potentiation (LTP) as well as remodeling of synaptic spines in the dorsal horn, thereby orchestrating functional and structural plasticity during the course of morphine-induced hyperalgesia and tolerance. These effects are attributed to TRPC1/4/5-mediated Ca2+ elevation in the spinal dorsal horn induced by chronic morphine treatment. This study identifies TRPC1/4/5 channels as a promising novel target to prevent the unwanted morphine tolerance and hyperalgesia.

Mayer-Rokitansky-Küster-Hauser syndrome is a congenital malformation disorder resulting in agenesis of the proximal vagina, absence of cervix, and variable development of the uterus. This report describes the repair of a complex iatrogenic urethrovaginal injury due to a missed diagnosis of Mayer-Rokitansky-Küster-Hauser. Our treatment utilized a primary urethroplasty through a transvaginal approach with bladder neck reconstruction and a Martius flap for secondary coverage. Urinary continence was restored postoperatively.

The study aims to enhance β-amyrin production in

Introduction: We aimed to review the trends and incidence of surgical intervention for adults with upper urinary tract stones in Ontario, Canada, and to hypothesize potential causes for the observed changes. Methods: We carried out a retrospective, population-based cohort study using administrative databases held at the Institute of Clinical Evaluative Sciences (IC/ES) to identify all adults (≥18 years) who underwent surgical treatment for urolithiasis, defined by records using a combination of both hospital and physician billing from 2002–2019. Descriptive statistics were used to summarize baseline patient demographics, and surgical trends were analyzed using the Cochrane-Armitage test for trend. Results: From 2002–2019, 140 263 patients were treated surgically for urolithiasis. During this time period, the total number of surgically treated stone disease increased by 80.5%. By type of procedure, percutaneous nephrolithotomy (PCNL) increased by 187% and ureteroscopy (URS) increased by 158%, while the number of shockwave lithotripsy (SWL) declined by 31.4%. The adult population in Ontario in the years evaluated grew by 24.4%. The number of surgical procedures per 100 000 people over this time grew by 45.3%. For every 1% increase in the population, there was a 2.6% rise in stone-related surgical procedures. Conclusions: The number of stone-related surgical procedures performed rose significantly and cannot be accounted for by population growth alone. This rise was proportionally larger in the female population, further supporting a narrowing of the gender gap in urinary stone disease. The reasons for the increase are likely multifactorial and may imply an increasing incidence of surgically treated stone disease. The change in the proportion of URS and SWL performed may demonstrate a continued shift in surgical preference or may be reflective of resource limitations and availability. The increase in PCNL volumes may also suggest a greater complexity of cases. These findings should be considered for future resource planning and require further study.

Studies indicate that learning surgical skills on low-fidelity models is equally beneficial to learning on high-fidelity models in terms of skills retention and transfer. However, it is unclear how low-fidelity simulation training impacts retention and transfer in novice learners, particularly on complex surgical tasks that incorporate multiple challenging skills. This study explores the capacity of complete novices to learn and transfer complex surgical skills from a low-fidelity model to a high-fidelity simulation after a delay.Task-naïve medical and nonmedical undergraduate students (n = 62) participated in a three-phase prospective double-arm randomized (2:1) experimental study. Participants completed two skills training sessions (end-to-side anastomosis) on a low-fidelity bench model. After a 4-week delay, participants completed the task again either using the low-fidelity model or a high-fidelity model (cadaver) and were assessed using a validated checklist.There was a significant time × fidelity group interaction (P = 0.004). Simple effects analysis indicated the high-fidelity group (MThese findings suggest that for novice populations, relying on low-fidelity simulation training as a source of teaching complex skills may not provide a reliable transfer to high-fidelity models and in turn clinical settings.

In response to rapid economic development, nitrate pollution of groundwater is becoming a serious issue in many parts of China. Urbanization and industrialization are the main drivers of NO

The objective of this study was to examine the association between learner personality and capacity to be trained (i.e., performance improvement) on a surgical task, and how instructor perceptions of the learners' capacity to be trained interact with learner personality and performance during training and feedback. There is meaningful heterogeneity in the degree of learner surgical skills acquisition despite receiving the same amount of training. While learner personality may independently contribute to skill acquisition, the instructor-learner feedback process is also important to consider. To better understand this interpersonal relationship, it is necessary to also consider instructor factors (i.e., perceptions), and how this may contribute to learner variability in skills training.This exploratory study employed a prospective two-phase design. Medical and non-medical undergraduate students (N = 62) completed measures of personality and participated in two 20-minute training sessions with expert feedback 2 weeks apart, performing an end-to-side anastomosis on a low-fidelity model. Learner performance and instructors' perceptions of a learner's capacity to be trained were assessed.Sixty-two medical and non-medical undergraduate students.There was a significant interaction between learner Extraversion and instructor's perceptions of learner capacity to be trained. Higher learner Extraversion was only associated with an increase in performance improvement for those who were considered trainable (OR = 4.83, p = 0.017). Post hoc analysis revealed a significant difference in the amount of feedback provided to participants who were considered trainable (M = 9.45) versus not trainable (M = 16.48).This study highlights the importance of both individual learner factors and instructor perceptions on surgical skill acquisition.

The antitumor immune response involves a cascade of cancer-immunity cycles. Developing a combination therapy aimed at the cancer-immunity cycle is of great importance. In this research, we designed and tested a combined therapeutic-Au nanorod (AuNR)/doxorubicin (DOX) gel (AuNR/DOX gel)-in which the sustained release of DOX was controlled by Pluronic gel. DOX served as an immunogenic tumor cell death (ICD) inducer, triggering the production of damage-associated molecular patterns (DAMPs). Mild photothermal therapy (Mild PTT) produced by 880 nm laser-irradiated AuNRs also generated tumor-associated antigens. Maleimide-modified liposomes (L-Mals), as antigen capturing agents, promoted tumor antigen uptake by DCs. Ultimately, more CD8+ T cells and fewer regulatory T cells (Tregs) infiltrated the tumor, eliciting antitumor responses from the PD-L1 antibody. Our results indicate that this combination strategy promotes a positive shift in the cancer-immunity cycle and holds much promise for combination strategy will lead to development of an antitumor drug delivery system. STATEMENT OF SIGNIFICANCE: Developing a combination therapy for cancer-immunity cycle is of great importance due to antitumor immune response involving a cascade of cancer-immunity cycles. Cancer-immunity cycle usually includes tumor antigen release, antigen presentation, immune activation, trafficking, infiltration, specific recognition of tumor cells by T cells, and finally cancer cell killing. In this research, we designed a combination strategy based on Au nanorod/doxorubicin gel via mild photothermal therapy combined with antigen-capturing liposomes and anti-PD-L1 agent promoting a positive shift in the cancer-immunity cycle. Our results indicate that this combination strategy promotes a positive shift in the cancer-immunity cycle and holds much promise for combination strategy will lead to development of an antitumor drug delivery system.

The purpose of the study was to evaluate urinary citrate/creatinine (UCi/UCr) and urinary calcium/citrate (UCa/UCi) ratios for distinguishing stone formers (SF) from non-stone formers (NSF) in an at-risk population. This was a retrospective study that included all pediatric patients who underwent urinary citrate testing from April 2017 to March 2018. The urinary levels of citrate, calcium, sodium, potassium, creatinine, oxalate, urate, pH, and specific gravity (SG) were measured in our clinical laboratory. Diagnosis of kidney stones was obtained through chart review.A total of 97 patients were included (46 NSF and 51 SF). The UCi/UCr ratio was not significantly different between NSF and SF. Median UCa/UCr ratio was higher in SF (0.67) compared with NSF (0.21, p The study has demonstrated significantly higher UCa/UCi and UCa/UCr in SF compared with NSF, while the use of urinary oxalate, urate, pH, and SG did not differentiate between SF from NSF. We also confirmed a positive correlation between UNa/UCr and UCa/UCr. While the utility of UCa/UCr is well established, our data suggest that UCa/UCi rather than UCi/UCr may be more predictive in the clinical setting when evaluating for nephrolithiasis.

OBJECTIVE Demonstrated competence through frequent assessment is an expected goal for progressive development in competency-based medical education curricula. The Objective Structured Assessment of Technical Skill (OSATS) is considered a valid method of formative assessment, but in few instances have standards been set for determining competence. The present study used borderline regression methods to examine standard setting of performance on a complex technical task with novices assessed using an OSATS checklist. METHODS This was a single institution prospective single arm experimental design study. Participants were 58 non-medical undergraduate students with no previous surgical experience, who observed a computer-based training module on end-to-side vascular anastomosis. Subsequently, participants were provided two 20-minute training sessions, two weeks apart where they received expert feedback whilst performing the task on a low-fidelity model. After each training session, participants completed the task unaided. Sessions were recorded and assessed using an OSATS checklist retrospectively by experts. RESULTS Paired t-test analyses indicate that for both the checklist total score (t(52) = 8.05, p < 0.001) and the global rating score (t(53) = 8.15, p < 0.001), individuals performed significantly better in Phase 2. Borderline regression analyses indicated that in Phase 1 (R2 = .60) and Phase 2 (R2 = .75), the OSATS checklist could adequately capture variation in performance in novices. Further, the checklist could reliably classify novices at three of the five global rating performance levels. Pass rates determined by regression equations improved from Phase 1 to Phase 2 on all global rating levels. CONCLUSIONS With the increasing focus on competency-based medical education, it is imperative that training programs have the capacity to accurately assess outcomes and set minimum performance standards. Borderline regression methods can accurately differentiate novice learners of varying performance levels before and after training on a complex technical skill task using an OSATS checklist.

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SiCp/Al is a kind of particle reinforced composites with good material properties, which can be used in the field of lightweight parts and electronic packaging. Ultrasonic- assisted grinding process is one of the processes which is suitable for machining hard and brittle materials, the surface quality can be improved by using appropriate ultrasonic-assisted process parameters. In this paper, the ultrasonic-assisted grinding process is used to improve the surface quality of SiCp/Al, meanwhile, the kinematics of abrasive particles in grinding is analysed to explain the effect of ultrasonic vibration. In addition, ultrasonic-assisted grinding experiment of SiCp/Al is conducted, it is found that the axial ultrasonic vibration can improve the surface quality of SiCp/Al in grinding, and the reduction percentage is up to 8.20% compared to the normal grinding. In addition, a regression model is proposed for surface roughness prediction, the result of t-test on the residuals shows that the model is accurate.

With the development of the local economy, the volume of groundwater production has increased continuously in the past decades in the Tacheng Basin of the Xinjiang Uygur Automous Region. Previous studies have not provided a clear pattern of the chemical composition evolution of groundwater and its driving force in this basin, which makes the future development and utilization of groundwater riskier. This study carried out systematic sampling and analysis of groundwater chemistry in this basin, and the chemical evolution of groundwater in the basin was analyzed by comparison with historical hydrochemical data. The results show that Ca

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Additional file 1: Table S1 Strains used in this study. Table S2 the properties of T7 phage. Table S3 Oligonucleotides used in this study. Figure S1 Agarose gels of cas9. Figure S2 The number of living bacterium. Figure S3 The shake flasks of cultures.

Background Galloway-Mowat syndrome (GAMOS) (OMIM #251300) is a severe autosomal recessive disease characterized by the combination of early-onset steroid-resistant nephrotic syndrome (SRNS) and microcephaly with brain anomalies caused by WDR73 as well as OSGEP, TP53RK, TPRKB, or LAGE3 mutations. Objective We report on the hitherto undescribed urological and nephrological complications of the homozygous c.974G>A (p.Arg325Gln) OSGEP mutations in a 7-year-old Caucasian girl. Case Diagnosis The patient came to the attention of pediatric nephrology at the age of 3 years and 11 months, when she presented with status epilepticus due to profound hypomagnesemia (0.31 mmol/L, normal 0.65-1.05). A 24-h urine demonstrated a magnesium loss of 0.6 mmol/kg/day with associated proteinuria suggesting renal tubulopathy. Subsequently, she developed recurrent urinary tract infections (UTIs) and was diagnosed with neurogenic bladder dysfunction. The patient continued to have UTIs associated with seizures and sequential cultures growing multi-drug-resistant organisms despite of antibiotic prophylaxis. In addition, the proteinuria (median microalbumin/creatinine ratio 647 mg/mmol) increased, and she developed partial Fanconi syndrome. At age 7, she developed a large bladder calculus (3.3 × 3.2 cm) and three left non-obstructing renal calculi associated with elevated urinary cystine, hypercalciuria, and ongoing hypomagnesemia and required surgical intervention. Glomerular filtration rate (GFR) remained normal and she never developed frank nephrotic syndrome (average albumin 31 g/L). Conclusions It is unclear if patients with OSGEP mutations with tubular symptoms rather than nephrotic syndrome should be considered a different entity. Nephrological and urological complications of OSGEP mutations can be challenging and require a multidisciplinary approach.

Objective To evaluate Thiel-embalmed cadavers (TEC) as a training model for percutaneous nephrolithotomy (PCNL), more specifically for ultrasound (US)-guided supine endoscopic combined intrarenal surgery (ECIRS). Subjects and Methods Thirteen urologists (nine experienced endourologists, four fellows/residents) performed an US-guided supine ECIRS procedure on a TEC. The model was evaluated by way of a questionnaire (5-point Likert scale). Descriptive statistical analysis was performed and results were graphically presented using divergent bar graphs. Results US images were appreciated as lifelike in all aspects. Although distention of the collecting system was not ideal in one out of three TEC, US visualisation of the distended calyces during puncture was good. Skin penetration was more difficult and less realistic in TEC, while kidney puncture and dilatation were deemed very realistic. Ureteric and collecting system anatomy and consistency were similar to real life, although the mucosa appeared paler. US needle guidance was perceived as excellent. Overall, needle puncture assessment was realistic and useful as a training tool. Overall quality and satisfaction of TEC in US-guided supine ECIRS was good to excellent and comparable to a real-life procedure. Overall appropriateness of the TEC model was considered excellent for both initial and advanced supine PCNL training. Conclusion Despite the minor drawbacks of tough skin and non-ideal collecting system dilatation during ureteroscopy, the TEC model was considered good to excellent as a training model for US-guided PCNL, in particular, US-guided needle puncture of the kidney during supine ECIRS.

Traditional training for percutaneous renal access (PCA) relies on apprenticeship, which raises concerns about patient safety, limited training opportunities, and inconsistent quality of feedback. In this study, we proposed the development of a novel augmented reality (AR) simulator for ultrasound (US)-guided PCA and evaluated its validity and efficacy as a teaching tool. Our AR simulator allows the user to practice PCA on a silicone phantom using a tracked needle and US probe emulator under the guidance of simulated US on a tablet screen. 6 Expert and 24 novice participants were recruited to evaluate the efficacy of our simulator. Experts highly rated the realism and usefulness of our simulator, reflected by the average face validity score of 4.39 and content validity score of 4.53 on a 5-point Likert scale. Comparisons with a Mann–Whitney U test revealed significant differences $$(p

Ag-doped Bi2Se3 with the formula AgxBi2Se3 and Bi2−xAgxSe3 were prepared and their electrical and magnetic transport properties have been investigated to study the influence of silver doping on transport properties of Bi2Se3 with different Ag-doped method. All samples exhibited metallic resistivity and the resistivity increased with increasing Ag concentration. The lattice parameter c of Ag-substituted and Ag-intercalated samples displays a contrary change as the Ag concentration increased. For the Ag-intercalated samples, both the resistance upturn were observed in the curves of temperature dependent of resistivity and temperature dependent of magnetoresistance, respectively, indicating that the enhanced surface effect was obtained in those samples. Monotonously, field-induced MR peaks around 200 K were also observed in those samples. Similar behaviors were not observed in the Ag-substituted samples.

Xiu-Chai Zheng,1,2,* Wei Ren,1,2,* Shuang Zhang,1,2 Ting Zhong,1,2 Xiao-Chuan Duan,1,2 Yi-Fan Yin,1,2 Mei-Qi Xu,1,2 Yan-Li Hao,1,2 Zhan-Tao Li,1,2 Hui Li,1,2 Man Liu,1,2 Zhuo-Yue Li,1,2 Xuan Zhang1,2 1Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing, People’s Republic of China; 2Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing, People’s Republic of China *These authors contributed equally to this work Background: In the present study, the tumor-specific, pH-responsive peptide H7K(R2)2 -modified, theranostic liposome-containing paclitaxel (PTX) and superparamagnetic iron oxide nanoparticles (SPIO NPs), PTX/SPIO-SSL-H7K(R2)2, was prepared by using H7K(R2)2 as the targeting ligand, SPIO NPs as the magnetic resonance imaging (MRI) agent, PTX as antitumor drug. Methods: The PTX/SPIO-SSL-H7K(R2)2 was prepared by a thin film hydration method. The characteristics of PTX/SPIO-SSL-H7K(R2)2 were evaluated. The targeting effect, MRI, and antitumor activity of PTX/SPIO-SSL-H7K(R2)2 were investigated detail in vitro and in vivo in human breast carcinoma MDA-MB-231 cell models. Results: Our results of in vitro flow cytometry, in vivo imaging, and in vivo MR imaging confirmed the pH-responsive characteristic of H7K(R2)2 in MDA-MB-231 cell line in vitro and invivo. The results of in vivo MRI and in vivo antitumor activity confirmed the theranostic effect of PTX/SPIO-SSL-H7K(R2)2 in MDA-MB-231 tumor-bearing model. Conclusion: Considering all our in vitro and in vivo results, we conclude that we developed targeting modified theranostic liposome which could achieve both role of antitumor and MRI. Keywords: tumor-specific pH-responsive peptide, paclitaxel, superparamagnetic iron oxide nanoparticles, liposome, theranostic efficiency

As one of the major carbon dioxide emitter, industrial sector has attracted considerable attention of the whole society on the energy saving and emissions reduction issue. Since the tobacco primary process has the typical characteristics of process industry, and it represents about 80% of the total energy consumption of cigarette production, this paper proposes an integrated model employing the e-p method, which is widely used in the energy consumption analysis of the process industry, to estimate the energy saving and emissions reduction potential of the tobacco primary process. Based on the energy consumption data of the three Chinese cigarette enterprises in 2015, the results show that as to the section energy intensity factor of the tobacco primary process, the changes of the tobacco leaf pre-conditioning section and the cut lamina drying section can lead to 18%–47% and 9%–36% reduction of the unit cut tobacco energy intensity, and as to the production ratio factor, the lower proportion of cut stem can lead to 15%–33% reduction of the unit cut tobacco energy intensity because of the higher energy intensity of the stem process section. In addition, scenario analysis has been used to discover the energy saving and emissions reduction potential by process optimization and products structure upgrade under the premise of the fixed total production volume, the actual production portfolio and process equipment of three enterprises. Finally, the effective measures and policy suggestions to realize the goal of energy saving and emissions reduction for three cigarette enterprises are provided.

Lipid metabolism plays an important role in the energy economy of ruminants. However, its interactions of fat, rumen fermentation, gas emission, and microorganisms are not yet clear. This study evaluated the effect of adding raw oilseeds to high-forage diets on in vitro ruminal fermentation, gas composition, and microbial profile. Three isoenergetic and isoproteic experimental diets were designed and used as fermentation substrate: control treatment (CON group) was the basal diet lacking oilseeds, the other two treatments were the basal diet supplemented by 100 g/kg dry matter (DM) raw whole soybean (S group) and 50 g/kg DM raw flaxseed (F group), respectively. Data showed that the acetate, butyrate, and total VFA concentration of culture fluids in the S group were lower (p &lt, 0.05) than in the F group. There was a tendency to a higher level (p = 0.094) of propionate concentration in the F group compared with the other two groups. The gas production in the F group was higher (p &lt, 0.05) than in the control group. There was a lower abundance of Sutterella (p &lt, 0.05) and a greater abundance of Butyrivibrio (p &lt, 0.05) in both of the two oilseed treatments. Methanobrevibacter (p = 0.078) in the F group was the lowest. Our results suggested that CH4 emission could be inhibited with flaxseed supplementation by propionate production metabolism, biohydrogenation of unsaturated fatty acid (FA), and toxicity to Methanobrevibacter, while regarding soybean seed supplementation, the emission of CH4 was more likely to be reduced through biohydrogenation of unsaturated FA modulated by Butyrivibrio.