Hypoxia-Sensitive COMMD1 Integrates Signaling and Cellular Metabolism in Human Macrophages and Suppresses Osteoclastogenesis.

Hypoxia augments inflammatory responses and osteoclastogenesis by incompletely understood mechanisms. We identified COMMD1 as a cell-intrinsic negative regulator of osteoclastogenesis that is suppressed by hypoxia. In human macrophages, COMMD1 restrained induction of NF-κB signaling and a transcription factor E2F1-dependent metabolic pathway by the cytokine RANKL. Downregulation of COMMD1 protein expression by hypoxia augmented RANKL-induced expression of inflammatory and E2F1 target genes and downstream osteoclastogenesis. E2F1 targets included glycolysis and metabolic genes including CKB that enabled cells to meet metabolic demands in challenging environments, as well as inflammatory cytokine-driven target genes. Expression quantitative trait locus analysis linked increased COMMD1 expression with decreased bone erosion in rheumatoid arthritis. Myeloid deletion of Commd1 resulted in increased osteoclastogenesis in arthritis and inflammatory osteolysis models. These results identify COMMD1 and an E2F-metabolic pathway as key regulators of osteoclastogenic responses under pathological inflammatory conditions and provide a mechanism by which hypoxia augments inflammation and bone destruction.

ß3-Adrenoceptor Agonist for the Treatment of Bladder Dysfunction in Children: A Systematic Review and Meta-Analysis.

PURPOSE: ß3-adrenergic receptor agonists (ß3 agonists) have been used in treatment of overactive bladder (OAB) and neurogenic detrusor overactivity (NDO) in adults. However, their use in children has only recently been approved by the U.S. Food and Drug Administration for patients with NDO. As in adults, the role of ß3 agonists in children may include conditions such as OAB. This systematic review and meta-analysis aims to understand the intended use, efficacy and safety of ß3 agonists in the pediatric population. MATERIALS AND METHODS: A literature search was performed in February 2021 across MEDLINE®, Embase®, Scopus®, the Cochrane Library and ClinicalTrials.gov. No language restrictions were placed. All records describing the clinical use of ß3 agonists in pediatric patients (<18 years of age) were included, regardless of the methodological design or outcomes assessed. The identified records were screened by 2 independent authors. The reporting was compliant with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. Data extraction was performed by 2 independent reviewers, blinded to each other's extractions. The data were pooled using the fixed effects model. RESULTS: Of 367 records identified, 8 studies were included in the review (3 prospective and 5 retrospective). ß3 agonists led to improvements in both urodynamics parameters and self-reported outcomes such as incontinence. Commonly reported side effects were headaches (3%‒5.9%), constipation (3.5%‒5.7%), rhinitis/nasopharyngitis (1.7%‒5.8%) and blurred vision (1.7%‒2.9%). Clinically meaningful changes in safety outcomes (blood pressure, heart rate, electrocardiogram-related changes, liver function) were rare. Before and after ß3 agonist use, pooled effect estimates for maximum cystometric capacity for 171 patients were mean difference of +98.84 ml (95% CI 74.72, 122.96); for complete dryness, assessment of 235 patients showed a Peto odds ratio of 8.68 (95% CI 5.22, 14.45). CONCLUSIONS: ß3 agonists appear to be a promising, effective and safe alternative/adjunctive therapy in management of pediatric NDO or OAB, with improvements in both objective urodynamics parameters and subjective patient-reported outcomes following their use.

Comparison of continuous and interrupted suture techniques in pyeloplasty: a systematic review and meta-analysis.

Pelvi-ureteric anastomosis is a critical step to ensure good outcome of pyeloplasty. Continuous suturing technique, especially for laparoscopic surgeries, may offer faster operative time while allowing water-tight anastomosis and remains an alternative to interrupted suturing technique. There has been mixed data on comparison of outcomes of continuous and interrupted suturing techniques. This systematic review and meta-analysis aim to assess the outcomes of pyeloplasty based on continuous and interrupted suturing techniques. Following protocol registration on PROSPERO (CRD42021269706), a systematic review was performed in accordance with Cochrane Collaboration. A literature search was performed in September 2021 across Medline, EMBASE, Scopus, Cochrane Library, and ClinicalTrials.gov. Records comparing pyeloplasty outcomes between continuous and interrupted suture techniques were included. Five studies were identified for inclusion (2 prospective, 3 retrospective). Three studies involved pediatric patients. Three studies exclusively assessed laparoscopic technique. Four outcomes were meta-analyzed: operative time, length of stay, complications, and pyeloplasty failure. Interrupted sutures had longer OR time (mean difference 33.14 min [95% CI 29.35-36.94], p < 0.0001) and length of stay (mean difference 1.08 days [95% CI 0.84-1.32], p < 0.0001). However, there were similar complication (OR 1.73 [95% CI 0.98-3.06], p = 0.06) and failure rates (OR 1.21 [95% CI 0.43-3.43], p = 0.71) between the two suture types. The overall risk of bias in the studies was high. While limited by the number of studies available, continuous sutures for pelvi-ureteric anastomosis appear to confer benefits of faster operative time and decreased length of stay without increasing complication rates or failures.

Do post-operative phone calls enhance family satisfaction and outcomes after outpatient pediatric urological surgeries? A prospective study.

INTRODUCTION: This study assesses whether post-operative check-in phone calls (POPC) performed within 48 h of outpatient pediatric urological surgeries by a non-medical professional (NMP) would increase patient/family satisfaction and minimize extraneous resource use by increasing email/telephone communication, while reducing emergency department (ED) visits within 30 days of that procedure. METHODS: Families of patients undergoing ambulatory pediatric urology surgeries were enrolled over 8 weeks. Group 1 did not receive POPC. Group 2 received a POPC within 48 h of their operation by a NMP. Both groups received a phone-call survey 2 weeks after surgery to assess families' perioperative satisfaction. RESULTS: In total, 74 families were enrolled (Group 1 = 44, Group 2 = 31). The response rates to phone surveys for Groups 1 and 2 were 59.1% and 77.4%, respectively. POPC did not improve perioperative satisfaction, nor did it significantly promote the use of nursing email/telephone communication (19.2% vs. 4.2%, p = 0.128) or reduce ED visits (15.4% vs. 0.0%, p = 0.111). However, all families in Group 2 thought POPC was timed appropriately and 79.1% perceived it to be helpful in reducing post-operative anxiety. CONCLUSION: POPC by a NMP within 48 h of surgery may not affect perioperative satisfaction of families of patients undergoing same-day pediatric urology surgery but may have an impact in reducing post-operative anxiety.

Multiscale characterization of the mineral phase at skeletal sites of breast cancer metastasis.

Skeletal metastases, the leading cause of death in advanced breast cancer patients, depend on tumor cell interactions with the mineralized bone extracellular matrix. Bone mineral is largely composed of hydroxyapatite (HA) nanocrystals with physicochemical properties that vary significantly by anatomical location, age, and pathology. However, it remains unclear whether bone regions typically targeted by metastatic breast cancer feature distinct HA materials properties. Here we combined high-resolution X-ray scattering analysis with large-area Raman imaging, backscattered electron microscopy, histopathology, and microcomputed tomography to characterize HA in mouse models of advanced breast cancer in relevant skeletal locations. The proximal tibial metaphysis served as a common metastatic site in our studies; we identified that in disease-free bones this skeletal region contained smaller and less-oriented HA nanocrystals relative to ones that constitute the diaphysis. We further observed that osteolytic bone metastasis led to a decrease in HA nanocrystal size and perfection in remnant metaphyseal trabecular bone. Interestingly, in a model of localized breast cancer, metaphyseal HA nanocrystals were also smaller and less perfect than in corresponding bone in disease-free controls. Collectively, these results suggest that skeletal sites prone to tumor cell dissemination contain less-mature HA (i.e., smaller, less-perfect, and less-oriented crystals) and that primary tumors can further increase HA immaturity even before secondary tumor formation, mimicking alterations present during tibial metastasis. Engineered tumor models recapitulating these spatiotemporal dynamics will permit assessing the functional relevance of the detected changes to the progression and treatment of breast cancer bone metastasis.

Association of two BRM promoter polymorphisms and smoking status with malignant pleural mesothelioma risk and prognosis.

Brahma (BRM), of the SWI/SNF complex, has two 6 to 7 bp insertion promoter polymorphisms (BRM-741/BRM-1321) that cause epigenetic BRM suppression, and are associated with risk of multiple cancers. BRM polymorphisms were genotyped in malignant pleural mesothelioma (MPM) cases and asbestos-exposed controls. Multivariable logistic regression (risk) and Cox regression (prognosis) were performed, including stratified analyses by smoking status to investigate the effect of polymorphisms on MPM risk and prognosis. Although there was no significant association overall between BRM-741/BRM-1321 and risk in patients with MPM, a differential effect by smoking status was observed (P-interaction < .001), where homozygous variants were protective (aOR of 0.18-0.28) in ever smokers, while never smokers had increased risk when carrying homozygous variants (aOR of 2.7-4.4). While there was no association between BRM polymorphisms and OS in ever-smokers, the aHR of carrying homozygous-variants of BRM-741, BRM-1321 or both were 4.0 to 8.6 in never-smokers when compared to wild-type carriers. Mechanistically, lower mRNA expression of BRM was associated with poorer general cancer prognosis. Electrophoretic mobility shift assays and chromatin immunoprecipitation experiments (ChIP) revealed high BRM insertion variant homology to MEF2 regulatory binding sites. ChIP experimentation confirmed MEF2 binding only occurs in the presence of insertion variants. DNA-affinity purification assays revealed YWHA scaffold proteins as vital to BRM mRNA expression. Never-smokers who carry BRM homozygous variants have an increased chance of developing MPM, which results in worse prognosis. In contrast, in ever-smokers, there may be a protective effect, with no difference in overall survival. Mechanisms for the interaction between BRM and smoking require further study.

Assessment of prophylactic heparin infusion as a safe preventative measure for thrombotic complications in pediatric kidney transplant recipients weighing <20 kg.

Small-sized kidney recipients (<20 kg) are at high risk of allograft vessel thrombosis. HP has been used to mitigate this risk but may infer an increase in bleeding risks. Therefore, we aim to determine whether HP is a safe means to prevent thrombosis in small kidney transplant patients by comparing those who have received HP and those who have NHP. A retrospective review of patients < 20 kg who underwent kidney transplant in our institution from 2000 to 2015 was performed. At our institution, unfractionated heparin 10 units/kg/hour is used as HP since 2009. Patients at increased risk of thrombosis (previous thrombosis, thrombophilia, nephrotic syndrome) and bleeding (therapeutic doses of heparin, diagnosis of coagulopathy) were excluded. Fifty-six patients were identified (HP n = 46; NHP n = 10). Baseline demographics were similar between HP and NHP. There was no statistical difference in frequency of transfusions, surgical re-exploration, or thrombotic events between HP and NHP. The HP group was more likely to have drop in Hb > 20 g/L (67.4% vs 30.0%, P = 0.038), and those who had drop in Hb > 20 g/L were more likely to also require pRBC transfusions (63.0% vs 20.0%, P = 0.017). Within the HP group, those who had bleeding complications had similar Hb levels as those who did not at baseline and post-transplant. Outcomes in the HP and NHP groups were no different with respect to thrombosis or significant bleeding complications requiring pRBC transfusions or surgical intervention. Future prospective studies are required to investigate the balance of preventing thrombosis and risks of pRBC transfusions for small-sized kidney recipients.

Variability among Canadian pediatric surgeons and pediatric urologists in the management of cryptorchidism in boys before the publication of major guidelines: a retrospective review of a single tertiary centre

Background: Before 2014, there was a lack of recommendations on managing cryptorchidism, or undescended testis (UDT), from a large pediatric urological or surgical organization. We assessed the variability in management of UDT among pediatric urologists and pediatric surgeons at a single tertiary pediatric referral centre before publication of major guidelines. Methods: We performed a retrospective review of the electronic records of patients who underwent primary unilateral or bilateral orchidopexy at our centre between January 2012 and January 2014. Results: A total of 488 patients (616 testes) were identified, of whom 405 (83.0%) and 83 (17.0%) were managed by pediatric urologists and pediatric surgeons, respectively. There was no difference in baseline characteristics, including age seen in clinic or at surgery, testis location/palpability and availability of preoperative ultrasonograms, of patients seen by the 2 groups. Pediatric surgeons ordered preoperative ultrasonography more often than pediatric urologists (25.3% v. 3.7%, p < 0.001). With palpable UDTs, although both groups used open approaches, pediatric urologists preferred a scrotal approach (56.9%), and pediatric surgeons approached most testes inguinally (98.8%). With nonpalpable UDTs, laparoscopic approaches were preferred by both groups; however, pediatric urologists used a 2-stage Fowler­Stephens approach more often than pediatric surgeons (48.4% v. 15.8%, p < 0.001). Conclusion: There was wide variation in the management of primary UDT between pediatric urologists and pediatric surgeons before the publication of guidelines. The most prominent difference between the 2 groups was in the ordering of preoperative ultrasonography. Future assessment of change in practice patterns may elucidate whether guidelines are an effective tool for standardization of practice.

Contexte: Avant 2014, on ne disposait pas de recommandations émanant d'une grande organisation urologique ou chirurgicale pédiatrique pour la prise en charge de la cryptorchidie (absence d'un ou des deux testicules dans le scrotum). Nous avons évalué les divers types de prise en charge de la cryptorchidie chez les urologues et les chirurgiens pédiatriques dans un seul centre tertiaire de référence pédiatrique avant la publication de lignes directrices majeures. Méthodes: Nous avons procédé à une revue rétrospective des dossiers électroniques de patients ayant subi une orchidopexie unilatérale ou bilatérale primaire dans notre centre entre janvier 2012 et janvier 2014. Résultats: En tout, 488 patients (616 testicules) ont été identifiés, dont 405 (83,0 %) et 83 (17,0 %) ont été traités respectivement par des urologues et des chirurgiens pédiatriques. On n'a noté aucune différence quant aux caractéristiques de départ des patients vus par les 2 groupes, telles que l'âge lors de la consultation à la clinique ou lors de la chirurgie, la localisation/palpabilité des testicules et le recours à l'échographie préopératoire. Les chirurgiens pédiatriques ont demandé une échographie préopératoire plus souvent que les urologues pédiatriques (25,3 % c. 3,7 %, p < 0,001). En présence de cryptorchidie palpable, même si les 2 groupes ont utilisé une approche ouverte, les urologues pédiatriques ont préféré l'approche scrotale (55,4 %) et les chirurgiens pédiatriques l'approche inguinale (98,8 %). En présence de cryptorchidie non palpable, les approches laparoscopiques ont été privilégiées par les 2 groupes; toutefois, les urologues pédiatriques ont utilisé une approche Fowler­Stephens en 2 temps plus souvent que les chirurgiens pédiatriques (48,4 % c. 15,8 %, p < 0,001). Conclusion: On a noté une grande variation dans la prise en charge de la cryptorchidie primaire entre les urologues et les chirurgiens pédiatriques avant la publication des lignes directrices. La principale différence entre les 2 groupes concernait le recours à l'échographie préopératoire. L'évaluation future des changements affectant la pratique permettrait de déterminer si les lignes directrices sont un outil efficace pour sa standardisation.

Cutting Edge: EZH2 Promotes Osteoclastogenesis by Epigenetic Silencing of the Negative Regulator IRF8.

Osteoclasts are resorptive cells that are important for homeostatic bone remodeling and pathological bone resorption. Emerging evidence suggests an important role for epigenetic mechanisms in osteoclastogenesis. A recent study showed that epigenetic silencing of the negative regulator of osteoclastogenesis Irf8 by DNA methylation is required for osteoclast differentiation. In this study, we investigated the role of EZH2, which epigenetically silences gene expression by histone methylation, in osteoclastogenesis. Inhibition of EZH2 by the small molecule GSK126, or decreasing its expression using antisense oligonucleotides, impeded osteoclast differentiation. Mechanistically, EZH2 was recruited to the IRF8 promoter after RANKL stimulation to deposit the negative histone mark H3K27me3 and downregulate IRF8 expression. GSK126 attenuated bone loss in the ovariectomy mouse model of postmenopausal osteoporosis. Our findings provide evidence for an additional mechanism of epigenetic IRF8 silencing during osteoclastogenesis that likely works cooperatively with DNA methylation, further emphasizing the importance of IRF8 as a negative regulator of osteoclastogenesis.

Low-Temperature Carbon Coating of Nanosized Li1.015Al0.06Mn1.925O4 and High-Density Electrode for High-Power Li-Ion Batteries.

Despite their good intrinsic rate capability, nanosized spinel cathode materials cannot fulfill the requirement of high electrode density and volumetric energy density. Standard carbon coating cannot be applied on spinel materials due to the formation of oxygen defects during the high-temperature annealing process. To overcome these problems, here we present a composite material consisting of agglomerated nanosized primary particles and well-dispersed acid-treated Super P carbon black powders, processed below 300 °C. In this structure, primary particles provide fast lithium ion diffusion in solid state due to nanosized diffusion distance. Furthermore, uniformly dispersed acid-treated Super P (ASP) in secondary particle facilitates lower charge transfer resistance and better percolation of electron. The ASPLMO material shows superior rate capability, delivering 101 mAh g-1 at 300 C-rate at 24 °C, and 75 mAh g-1 at 100 C-rate at -10 °C. Even after 5000 cycles, 86 mAh g-1 can be achieved at 30 C-rate at 24 °C, demonstrating very competitive full-cell performance.

Intravenous Immunoglobulin (IVIG) Attenuates TNF-Induced Pathologic Bone Resorption and Suppresses Osteoclastogenesis by Inducing A20 Expression.

Investigations on the therapeutic effects of intravenous immunoglobulin (IVIG) have focused on the suppression of autoantibody and immune complex-mediated inflammatory pathogenesis. Inflammatory diseases such as rheumatoid arthritis are often accompanied by excessive bone erosion but the effect of IVIG on osteoclasts, bone-resorbing cells, has not been studied. Here, we investigate whether IVIG directly regulates osteoclast differentiation and has therapeutic potential for suppressing osteoclast-mediated pathologic bone resorption. IVIG or cross-linking of Fcγ receptors with plate-bound IgG suppressed receptor activator of nuclear factor-κ B ligand (RANKL)-induced osteoclastogenesis and expression of osteoclast-related genes such as integrin ß3 and cathepsin K in a dose-dependent manner. Mechanistically, IVIG or plate-bound IgG suppressed osteoclastogenesis by downregulating RANKL-induced expression of NFATC1, the master regulator of osteoclastogenesis. IVIG suppressed NFATC1 expression by attenuating RANKL-induced NF-κB signaling, explained in part by induction of the inflammatory signaling inhibitor A20. IVIG administration attenuated in vivo osteoclastogenesis and suppressed bone resorption in the tumor necrosis factor (TNF)-induced calvarial osteolysis model. Our findings show that, in addition to suppressing inflammation, IVIG directly inhibits osteoclastogenesis through a mechanism involving suppression of RANK signaling. Direct suppression of osteoclast differentiation may provide beneficial effects on preserving bone mass when IVIG is used to treat rheumatic disorders.

Germanium Silicon Alloy Anode Material Capable of Tunable Overpotential by Nanoscale Si Segregation.

We developed the novel electrode that enables fine control of overpotential by exploiting surface segregation that is the enrichment of one component at the surface of binary alloy. To realize this approach, we controlled the proportion of Si with low Li diffusivity at the surface by annealing the SiGe nanowire in H2 environment at various temperatures. The resulting SiGe nanowires annealed at 850 °C exhibited high reversible capacity (>1031 mA·h·g(-1)), and long cycle life (400 cycles) with high capacity retention (89.0%) at 0.2 C. This superior battery performance is attributed to the remaining unlithiated part acting as support frame to prevent pulverization of anode material, which results from the fine-tuning of overpotential by controlling the degree of Si segregation.

High performance LiMn2O4 cathode materials grown with epitaxial layered nanostructure for Li-ion batteries.

Tremendous research works have been done to develop better cathode materials for a large scale battery to be used for electric vehicles (EVs). Spinel LiMn2O4 has been considered as the most promising cathode among the many candidates due to its advantages of high thermal stability, low cost, abundance, and environmental affinity. However, it still suffers from the surface dissolution of manganese in the electrolyte at elevated temperature, especially above 60 °C, which leads to a severe capacity fading. To overcome this barrier, we here report an imaginative material design; a novel heterostructure LiMn2O4 with epitaxially grown layered (R3̅m) surface phase. No defect was observed at the interface between the host spinel and layered surface phase, which provides an efficient path for the ionic and electronic mobility. In addition, the layered surface phase protects the host spinel from being directly exposed to the highly active electrolyte at 60 °C. The unique characteristics of the heterostructure LiMn2O4 phase exhibited a discharge capacity of 123 mAh g(-1) and retained 85% of its initial capacity at the elevated temperature (60 °C) after 100 cycles.

Superior long-term energy retention and volumetric energy density for Li-rich cathode materials.

Li-rich materials are considered the most promising for Li-ion battery cathodes, as high energy densities can be achieved. However, because an activation method is lacking for large particles, small particles must be used with large surface areas, a critical drawback that leads to poor long-term energy retention and low volumetric energy densities. Here we propose a new material engineering concept to overcome these difficulties. Our material is designed with 10 µm-sized secondary particles composed of submicron scaled flake-shaped primary particles that decrease the surface area without sacrificing rate capability. A novel activation method then overcomes the previous limits of Li-rich materials with large particles. As a result, we attained high average voltage and capacity retention in turn yielding excellent energy retention of 93% during 600 cycles. This novel and unique approach may furthermore open the door to new material engineering methods for high-performance cathode materials.

Hierarchical surface atomic structure of a manganese-based spinel cathode for lithium-ion batteries.

The increasing use of lithium-ion batteries (LIBs) in high-power applications requires improvement of their high-temperature electrochemical performance, including their cyclability and rate capability. Spinel lithium manganese oxide (LiMn2O4) is a promising cathode material because of its high stability and abundance. However, it exhibits poor cycling performance at high temperatures owing to Mn dissolution. Herein we show that when stoichiometric lithium manganese oxide is coated with highly doped spinels, the resulting epitaxial coating has a hierarchical atomic structure consisting of cubic-spinel, tetragonal-spinel, and layered structures, and no interfacial phase is formed. In a practical application of the coating to doped spinel, the material retained 90% of its capacity after 800 cycles at 60 °C. Thus, the formation of an epitaxial coating with a hierarchical atomic structure could enhance the electrochemical performance of LIB cathode materials while preventing large losses in capacity.

Nickel-rich layered lithium transition-metal oxide for high-energy lithium-ion batteries.

High energy-density lithium-ion batteries are in demand for portable electronic devices and electrical vehicles. Since the energy density of the batteries relies heavily on the cathode material used, major research efforts have been made to develop alternative cathode materials with a higher degree of lithium utilization and specific energy density. In particular, layered, Ni-rich, lithium transition-metal oxides can deliver higher capacity at lower cost than the conventional LiCoO2 . However, for these Ni-rich compounds there are still several problems associated with their cycle life, thermal stability, and safety. Herein the performance enhancement of Ni-rich cathode materials through structure tuning or interface engineering is summarized. The underlying mechanisms and remaining challenges will also be discussed.

The role of circumcision in preventing urinary tract infections in children with antenatal hydronephrosis: Systematic review and meta-analysis.

INTRODUCTION: Circumcision has been reported to reduce the risk of urinary tract infections (UTIs) in boys with antenatal hydronephrosis (HN). Our aim was to compare the incidence of UTIs in circumcised vs. uncircumcised boys with antenatal HN by conducting a systematic review and meta-analysis. STUDY DESIGN: A comprehensive search was performed until December 2022. Comparative studies were evaluated according to Cochrane collaboration recommendations. Assessed measures included: UTIs, continuous antibiotic prophylaxis (CAP) use, renal outcomes, and circumcision complications. Odds ratios (OR) and mean difference with 95% confidence interval (CI) were extrapolated from available data. Random-effects meta-analysis were performed. RESULTS: Twenty-three studies describing 9093 boys with antenatal HN were identified, including 4677 uncircumcised and 4416 circumcised boys. Overall effect estimates demonstrate that circumcised boys have significantly reduced odds of developing any UTI [OR 0.26, 95%CI 0.21, 0.32; p < 0.001]]. In addition, there a significantly reduced odds of developing UTI when circumcised and on CAP [OR 0.19, 95% CI 0.13, 0.30; p < 0.001]. When stratifying by etiology, circumcision reduced the odds of UTI in boys with isolated HN [OR 0.33, 95% CI 0.16, 0.68; p = 0.003], vesicoureteral reflux [OR 0.23, 95% CI 0.13, 0.42; P < 0.00001], or with posterior urethral valves [OR 0.29, 95% CI 0.13, 0.64; p = 0.002]. DISCUSSION: Circumcision reduces the incidence of UTIs in boys with antenatal HN. This review is limited by the varied definitions of UTIs and inconsistent reporting on HN etiology, renal outcomes, and circumcision complications. CONCLUSIONS: Circumcision should be considered in boys with antenatal HN to prevent the risk of developing UTI. Further research is warranted to individualize the prophylactic role of circumcision for patients with HN.

THOC5 regulates human osteoclastogenesis.

Osteoclasts are bone resorbing cells that are responsible for physiological and pathological bone resorption. Macrophage colony stimulating factor (M-CSF) binds to the M-CSF receptor (c-FMS) and plays a key role in the differentiation and survival of macrophages and osteoclasts. THOC5, a member of the THO complex, has been shown to regulate hematopoiesis and M-CSF-induced macrophage differentiation. However, the role of THOC5 in osteoclasts remains unclear. Here, our study reveals a new role of THOC5 in osteoclast formation. We found that THOC5 shuttles between nucleus and cytoplasm in an M-CSF signaling dependent manner. THOC5 bound to FICD, a proteolytic cleavage product of c-FMS, and THOC5 facilitates the nuclear translocations of FICD. Decreased expression of THOC5 by siRNA-mediated knock down suppressed osteoclast differentiation, in part, by regulating RANK, a key receptor of osteoclasts. Mechanistically, knock down of THOC5 inhibited the expression of RANKL-induced FOS and NFATc1. Our findings highlight THOC5's function as a positive regulator of osteoclasts.

The Efficacy and Safety of Tranexamic Acid in the Management of Perioperative Bleeding After Percutaneous Nephrolithotomy: A Systematic Review and Meta-Analysis of Comparative Studies.

Introduction: We performed a systematic review and meta-analysis of the current literature to assess the efficacy and safety of tranexamic acid (TXA) in the management of postoperative bleeding after percutaneous nephrolithotomy (PCNL). Methods: A systematic literature review was performed in March 2021. Two reviewers independently screened, identified, and evaluated comparative studies assessing the effectiveness of TXA in preventing bleeding after PCNL when compared with placebo or no intervention. The incidence of transfusion, complete stone clearance, and complications were extracted among TXA and control groups to generate the risk ratio (RR) and corresponding 95% confidence interval (CI). Blood loss, hemoglobin (Hb) drop, length of hospital stays, and operative (OR) time were analyzed using standard mean difference (SMD) with corresponding 95% CI. Effect estimates were pooled using the inverse-variance approach with a random-effect model. Results: A total of 11 studies (8 randomized controlled trial, 1 prospective cohort, and 2 retrospective cohort studies; total 1842 patients) of low-to-moderate-quality were included in the meta-analysis. Overall pooled effect estimates demonstrated a decreased transfusion rate (RR 0.36; 95% CI 0.25 to 0.51), blood loss (SMD -0.74; 95% CI -1.14 to -0.34), and Hb drop (SMD -0.95; 95% CI -1.51 to -0.39) among patients in the TXA group when compared with those in the control. The number needed to treat was 11 to prevent one transfusion. Patients who received TXA also had improved stone clearance (RR 1.08; 95% CI 1.02 to 1.14), lower minor (RR 0.72; 95% CI 0.58 to 0.89) and major (RR 0.38; 95% CI 0.21 to 0.69) complications, shorter hospital stays (SMD -0.52; 95% CI -1.01 to -0.04) and decreased OR time (SMD -0.89; 95% CI -1.46 to -0.31). Conclusions: TXA can effectively reduce postoperative bleeding after PCNL. Future studies should identify a subset of patients who may benefit from preoperative TXA administration for PCNL.