Biallelic variants in α-tubulin isotypes cause female infertility characterised as recurrent preimplantation embryo arrest.

BACKGROUND: Recurrent preimplantation embryo developmental arrest (RPEA) is the most common phenotype in assisted reproductive technology treatment failure associated with identified genetic abnormalities. Currently known maternal genetic variants explain only a limited number of cases. Variants of the ß-tubulin subunit gene, TUBB8, cause oocyte meiotic arrest and RPEA through a broad spectrum of spindle defects. In contrast, α-tubulin subunit genes are poorly studied in the context of preimplantation embryonic development. METHODS: Whole exome sequencing was performed on the PREA cohort. Functional characterisations of the identified candidate disease-causing variants were validated using Sanger sequencing, bioinformatics, in vitro functional analyses and single-cell RNA-sequencing of arrested embryos. RESULTS: Four homozygous variants were identified in the PREA cohort: two of TUBA1C (p.Gln358Ter and p.Asp444Metfs*42) and two of TUBA4A (p.Arg339Cys and p.Tyr440Ter). These variants cause varying degrees of spindle assembly defects. Additionally, we characterised changes in the human arrested embryo transcriptome carrying TUBA4A variants, with a particular focus on spindle organisation, chromosome segregation and mRNA decay. CONCLUSION: Our findings identified TUBA1C as a novel genetic marker and expanded the genetic and phenotypic spectrum of TUBA4A in female infertility and RPEA, which altogether highlighted the importance of α-tubulin isotypes in preimplantation embryonic development.

Interplay of kernel shape and surface structure for NIR luminescence in atomically precise gold nanorods.

It is challenging to attain strong near-infrared (NIR) emissive gold nanoclusters. Here we show a rod-shaped cluster with the composition of [Au28(p-MBT)14(Hdppa)3](SO3CF3)2 (1 for short, Hdppa is N,N-bis(diphenylphosphino)amine, p-MBT is 4-methylbenzenethiolate) has been synthesized. Single crystal X-ray structural analysis reveals that it has a rod-like face-centered cubic (fcc) Au22 kernel built from two interpenetrating bicapped cuboctahedral Au15 units. 1 features NIR luminescence with an emission maximum at 920 nm, and the photoluminescence quantum yield (PLQY) is 12%, which is 30-fold of [Au21(m-MBT)12(Hdppa)2]SO3CF3 (2, m-MBT is 3-methylbenzenethiolate) with a similar composition and 60-fold of Au30S(S­t­Bu)18 with a similar structure. time-dependent DFT(TDDFT)calculations reveal that the luminescence of 1 is associated with the Au22 kernel. The small Stokes shift of 1 indicates that it has a very small excited state structural distortion, leading to high radiative decay rate (kr) probability. The emission of cluster 1 is a mixture of phosphorescence and thermally activated delayed fluorescence(TADF), and the enhancement of the NIR emission is mainly due to the promotion of kr rather than the inhibition of knr. This work demonstrates that the metal kernel and the surface structure are both very important for cluster-based NIR luminescence materials.

Identification of novel compound heterozygous ZFP36L2 variants implicated in oocyte maturation defects and female infertility.

PURPOSE: To explore the pathogenesis of oocyte maturation defects. METHODS: Whole exome sequencing was conducted to identify potential variants, which were then confirmed within the pedigree through Sanger sequencing. The functional characterization of the identified variants responsible for the disease, including their subcellular localization, protein levels, and interactions with other proteins, was verified through transient transfection in HeLa cells in vitro. Additionally, we employed real-time RT-PCR and single-cell RNA sequencing to examine the impact of ZFP36L2 pathogenic variants on mRNA metabolism in both HeLa cells and mouse or human oocytes. RESULTS: A novel compound heterozygous variant in ZFP36L2 (c.186T > G, p.His62Gln and c.869 C > T, p.Pro290Leu) was discovered in a patient with oocyte maturation defects. Our findings indicate that these variants lead to compromised binding capacity of the ZFP36L2-CONT6L complex and impaired mRNA degradation in HeLa cells and mouse oocytes. Furthermore, we characterized the changes in the human oocyte transcriptome associated with ZFP36L2 variants, with a particular emphasis on cell division, mitochondrial function, and ribosome metabolism. CONCLUSIONS: This study broadens the mutation spectrum of ZFP36L2 and constitutes the first report of human oocyte transcriptome alterations linked to ZFP36L2 variants. In conjunction with existing knowledge of ZFP36L2, our research lays the groundwork for genetic counseling aimed at addressing female infertility.

Molecular targets and mechanisms of different aberrant alternative splicing in metastatic liver cancer.

Metastasis remains a major challenge in the successful management of malignant diseases. The liver is a major site of metastatic disease and a leading cause of death from gastrointestinal malignancies such as colon, stomach, and pancreatic cancers, as well as melanoma, breast cancer, and sarcoma. As an important factor that influences the development of metastatic liver cancer, alternative splicing drives the diversity of RNA transcripts and protein subtypes, which may provide potential to broaden the target space. In particular, the dysfunction of splicing factors and abnormal expression of splicing variants are associated with the occurrence, progression, aggressiveness, and drug resistance of cancers caused by the selective splicing of specific genes. This review is the first to provide a detailed summary of the normal splicing process and alterations that occur during metastatic liver cancer. It will cover the role of alternative splicing in the mechanisms of metastatic liver cancer by examining splicing factor changes, abnormal splicing, and the contribution of hypoxia to these changes during metastasis.

Protective Effects of Sesamol on Renal Ischemia-Reperfusion Injury Via Regulation of Nuclear Factor Erythroid 2-Related Factor 2 Pathway.

BACKGROUND: Sesamol is a natural antioxidant known for its potent antioxidant and free radical scavenging properties. This study aimed to explore the therapeutic effects and underlying mechanisms of sesamol in the development of renal ischemia-reperfusion injury (IRI) in mice. METHODS: C57BL/6J wild-type mice were divided into 3 groups: IR group, treated with normal saline after undergoing the IRI procedure; Sesamol + IR group, treated with 30 mg/kg/d of sesamol after the IRI procedure; and Sham group, treated with normal saline but not subjected to the IRI process. Renal IRI was induced by performing a right kidney nephrectomy and subjecting the left kidney to 30-minute ischemia, followed by 24-hour reperfusion. Kidney tissues and serum were collected 24 hours post-IRI to assess the impact of sesamol on renal function after IRI. Serum creatinine and blood urea nitrogen levels were assessed, and renal cell apoptosis was detected through terminal deoxynucleotidyl transferase dUTP nick-end labeling staining. The levels of interleukin 1ß and interleukin 18 in kidney tissues, as well as indicators of oxidative stress, were also measured. Furthermore, Nrf2-deficient mice were used to examine the protective function of the nuclear factor erythroid 2-related factor 2 (Nrf2)/hemeoxygenase-1 (HO-1) and NAD(P)H dehydrogenase quinone 1 (NQO1) signaling pathways induced by sesamol, as determined by western blot assay. RESULTS: Sesamol demonstrated significant improvement in renal function, along with reductions in renal tubular injury, cell necrosis, and apoptosis in mice. It also effectively lowered key inflammatory mediator levels. Sesamol exhibited antioxidant properties by reducing malondialdehyde levels and enhancing superoxide dismutase activities 24 hours after IRI. Western blot assay revealed increased Nrf2, HO-1, and NQO-1 protein levels with sesamol treatment. Notably, Nrf2-deficient mice did not exhibit the beneficial effects of sesamol. CONCLUSIONS: This study demonstrates that sesamol effectively alleviates renal IRI by enhancing antioxidant defenses and reducing inflammation potentially through the Nrf2/HO-1 and NQO1 signaling pathways.

Large-bore suction thrombectomy for sub-massive pulmonary embolism during second trimester of pregnancy: a case report.

Background: Pregnancy-associated pulmonary embolism (PAPE) remains a significant cause of maternal mortality. Anticoagulation remains the mainstay of therapy for most pulmonary embolism (PE)-related pregnancies. However, in patients with haemodynamic compromise or those refractory to anticoagulation, management is challenging. Systemic thrombolysis is associated with a substantial risk of maternal bleeding and fetal loss. In non-pregnant PE patients, large bore catheter-directed suction thrombectomy is a proven and important technique to manage intermediate or high-risk PE, allowing for normalization of pulmonary pressures, avoidance of haemodynamic deterioration, without the need for thrombolytics, major surgery, significant blood loss, or prolonged hospitalization. Case summary: A primigravid patient in her second trimester of pregnancy, initially diagnosed with a deep vein thrombosis refractory to heparin, presents with near-syncope due to sub-massive pulmonary embolism. The various management options including thrombolysis and surgical embolectomy etc. were discussed in detail by a multi-disciplinary PE team. She underwent large bore suction thrombectomy with complete thrombi removal, normalization of right heart strain, without the need for thrombolytics or surgery, minimal blood loss and was discharged after a short length of stay. She gave birth at term to a healthy infant. Conclusion: Suction thrombectomy is an important consideration for physicians managing high-risk PAPE and is likely to be associated with much a lower risk of maternal and fetal mortality compared to thrombolysis or surgery.

Effect of Early versus Delayed Use of Norepinephrine on Short-Term Outcomes in Patients with Traumatic Hemorrhagic Shock: A Propensity Score Matching Analysis.

Background: Guidelines recommend norepinephrine (NE) for the treatment of fatal hypotension caused by trauma. However, the optimal timing of treatment remains unclear. Objective: We aimed to investigate the effect of early versus delayed use of NE on survival in patients with traumatic haemorrhagic shock (HS). Materials and Methods: From March 2017 to April 2021, 356 patients with HS in the Department of Emergency Intensive Care Medicine of the Affiliated Hospital of Yangzhou University were identified using the emergency information system and inpatient electronic medical records for inclusion in the study. Our study endpoint was 24 h mortality. We used a propensity score matching (PSM) analysis to reduce bias between groups. Survival models were used to evaluate the relationship between early NE and 24 h survival. Results: After PSM, 308 patients were divided equally into an early NE (eNE) group and a delayed NE (dNE) group. Patients in the eNE group had lower 24 h mortality rates than those in the dNE group (29.9% versus 44.8%, respectively). A receiver operating characteristic analysis demonstrated that a cut-off point for NE use of 4.4 h yielded optimal predictive value for 24 h mortality, with a sensitivity of 95.52%, a specificity of 81.33% and an area under the curve value of 0.9272. Univariate and multivariate survival analyses showed that the survival rate of patients in the eNE group was higher (p < 0.01) than those in the dNE group. Conclusion: The use of NE within the first 3 h was associated with a higher 24 h survival rate. The use of eNE appears to be a safe intervention that benefits patients with traumatic HS.

Prediction of factors influencing the timing and prognosis of early tracheostomy in patients with multiple rib fractures: A propensity score matching analysis.

Objective: To investigate the factors affecting the timing and prognosis of early tracheostomy in multiple rib fracture patients. Methods: A retrospective case-control study was used to analyze the clinical data of 222 patients with multiple rib fractures who underwent tracheotomy in the Affiliated Hospital of Yangzhou University from February 2015 to October 2021. According to the time from tracheal intubation to tracheostomy after admission, the patients were divided into two groups: the early tracheostomy group (within 7 days after tracheal intubation, ET) and late tracheostomy group (after the 7th day, LT). Propensity score matching (PSM) was used to eliminate the differences in baseline characteristics Logistic regression was used to predict the independent risk factors for early tracheostomy. Kaplan-Meier and Cox survival analyses were used to analyze the influencing factors of the 28-day survival. Results: According to the propensity score matching analysis, a total of 174 patients were finally included in the study. Among them, there were 87 patients in the ET group and 87 patients in the LT group. After propensity score matching, Number of total rib fractures (NTRF) (P < 0.001), Acute respiratory distress syndrome (ARDS) (P < 0.001) and Volume of pulmonary contusion(VPC) (P < 0.000) in the ET group were higher than those in the LT group. Univariate analysis showed that the patients who underwent ET had a higher survival rate than those who underwent LT (P = 0.021). Pearson's analysis showed that there was a significant correlation between NTRF and VPC (r = 0.369, P = 0.001). A receiver operating characteristic(ROC)curve analysis showed that the areas under the curves were 0.832 and 0.804. The best cutoff-value values of the VPC and NTRF were 23.9 and 8.5, respectively. The Cox survival analysis showed that the timing of tracheostomy (HR = 2.51 95% CI, 1.12-5.57, P = 0.004) and age (HR = 1.53 95% CI, 1.00-2.05, P = 0.042) of the patients had a significant impact on the 28-day survival of patients with multiple rib fractures. In addition, The Kaplan-Meier survival analysis showed that the 28-day survival of patients in the ET group was significantly better than that of the LT group, P = 0.01. Conclusions: NTRF, ADRS and VPC are independent risk factors for the timing and prognosis of early tracheotomy. A VPC ≥ 23.9% and/or an NTRF ≥ 8.5 could be used as predictors of ET in patients with multiple rib fractures. Predicting the timing of early tracheostomy also need prediction models in the future.

Bioinformatics Analysis Screened and Identified Key Genes as Potential Biomarkers for Progression of Lung Cancer.

OBJECTIVE: To screen and identify key genes as potential biomarkers of lung cancer using bioinformatics analysis. STUDY DESIGN: Observational study. PLACE AND DURATION OF STUDY: Department of Critical Care Medicine, the First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning Province, China, from August 2018 to April 2021. METHODOLOGY: Independent microarray datasets (GSE85841 and GSE118370) were downloaded from the Gene Expression Omnibus (GEO) database and the differentially expressed genes (DEGs) were screened using GEO2R. Cytohubba was employed to identify the hub genes. Cellular component analysis, hierarchical clustering, and survival analyses of hub genes were performed via BiNGO, UCSC, and cBioPorta. A series of analyses of FGF2 and PIK3R1 were conducted using Oncomine. RESULTS: A total of 463 DEGs were identified and 11 hub genes were determined. BDNF, FGF2, JAK2, NCAM1, CAV1, TJP1, and PIK3R1 may affect the survival probability and life expectancy of lung cancer patients, but the p-values were not statistically significant. FGF2 and PIK3R1 had the highest node degrees, 40 and 32 respectively. The expression of FGF2 and PIK3R1 were significantly lower in the 4 lung cancer data sets compared with non-lung cancer tissues. And the low expression of FGF2 and PIK3R1 is related to tumor grades, family history of cancer, multiple tumors present, and prior therapy of lung cancer. CONCLUSION: Evaluation of FGF2 and PIK3R1 as potential biomarkers can contribute to the subsequent theoretical analysis of potential molecular mechanisms and development of lung cancer, so that the diagnosis of lung cancer may be more accurate, and it is possible to provide therapeutic and prognostic medicine targets. KEY WORDS: Lung neoplasms, Differentially expressed genes, Bioinformatical analysis, Microarray analysis, biomarkers.

Value of Contrast-enhanced Ultrasound in Evaluating Synovitis and Predicting Recurrent Joint Bleeding of Hemophilia.

OBJECTIVE: Contrast-enhanced ultrasound (CEUS) is advantageous for evaluating microcirculation, and has been applied to assess arthritis in previous studies. However, CEUS examinations have not been studied for hemophilia arthritis. Hemophilia arthritis is different from other arthritis, because it is induced by spontaneous joint bleeding. Hence, CEUS may have special value in evaluating hemophilia arthritis. The present study assessed the value of CEUS in evaluating synovial hypertrophy and predicting recurrent joint bleeding in severe hemophilia A patients. METHODS: From August 2016 to January 2017, 81 severe hemophilia A patients, who were referred to our hospital for ultrasound joint assessment with conventional ultrasound, were enrolled. Among these 81 patients, 46 patients consented for CEUS examinations on the same day. RESULTS: Compared to color Doppler flow imaging (CDFI), four more joints presented with a blood flow signal under CEUS mode. In addition, the synovial hypertrophy measured by CEUS was thicker than that measured by conventional ultrasound. The ultrasound scores (including the total grey-scale ultrasound score, joint effusion/hemarthrosis, synovial hypertrophy, CDFI semi-quantitative score, and CEUS semi-quantitative score) were significantly higher in the joint bleeding group than in the no joint bleeding group (P<0.05). Furthermore, these ultrasound scores were positively correlated with the joint bleeding frequency, and had the highest correlation with the CEUS score (r=0.620, P<0.05). CONCLUSION: CEUS can more accurately assess the degree of synovial hypertrophy and vascularization, and diagnose synovitis, when compared to conventional ultrasound. In addition, CEUS appears to be essential for evaluating the possibility of recurrent joint bleeding, and providing more reliable evidence for individualized treatment.

Ear microbiota and middle ear disease: a longitudinal pilot study of Aboriginal children in a remote south Australian setting.

BACKGROUND: Otitis media (OM) is a major disease burden in Australian Aboriginal children, contributing to serious long-term health outcomes. We report a pilot analysis of OM in children attending an outreach ear and hearing clinic in a remote south Australian community over a two-year period. Our study focuses on longitudinal relationships between ear canal microbiota characteristics with nasopharyngeal microbiota, and clinical and treatment variables. RESULTS: Middle ear health status were assessed in 19 children (aged 3 months to 8 years) presenting in remote western South Australia and medical interventions were recorded. Over the two-year study period, chronic suppurative OM was diagnosed at least once in 7 children (37%), acute OM with perforation in 4 children (21%), OM with effusion in 11 children (58%), while only 1 child had no ear disease. Microbiota analysis of 19 children (51 sets of left and right ear canal swabs and nasopharyngeal swabs) revealed a core group of bacterial taxa that included Corynebacterium, Alloiococcus, Staphylococcus, Haemophilus, Turicella, Streptococcus, and Pseudomonas. Within-subject microbiota similarity (between ears) was significantly greater than inter-subject similarity, regardless of differences in ear disease (p = 0.0006). Longitudinal analysis revealed changes in diagnosis to be associated with more pronounced changes in microbiota characteristics, irrespective of time interval. Ear microbiota characteristics differed significantly according to diagnosis (P (perm) = 0.0001). Diagnoses featuring inflammation with tympanic membrane perforation clustering separately to those in which the tympanic membrane was intact, and characterised by increased Proteobacteria, particularly Haemophilus influenzae, Moraxella catarrhalis, and Oligella. While nasopharyngeal microbiota differed significantly in composition to ear microbiota (P (perm) = 0.0001), inter-site similarity was significantly greater in subjects with perforated tympanic membranes, a relationship that was associated with the relative abundance of H. influenzae in ear samples (rs = - 0.71, p = 0.0003). Longitudinal changes in ear microbiology reflected changes in clinical signs and treatment. CONCLUSIONS: Children attending the ear and hearing clinic in a remote Aboriginal community present with a broad spectrum of OM conditions and severities, consistent with other remote Aboriginal communities. Ear microbiota characteristics align with OM diagnosis and change with disease course. Nasopharyngeal microbiota characteristics are consistent with the contribution of acute upper respiratory infection to OM aetiology.

Role of Rho guanine nucleotide exchange factors in non-small cell lung cancer.

Conventionally, Rho guanine nucleotide exchange factors (GEFs) are known activators of Rho guanosine triphosphatases (GTPases) that promote tumorigenesis. However, the role of Rho GEFs in non-small cell lung cancer (NSCLC) remains largely unknown. Through the screening of 81 Rho GEFs for their expression profiles and correlations with survival, four of them were identified with strong significance for predicting the prognosis of NSCLC patients. The four Rho GEFs, namely ABR, PREX1, DOCK2 and DOCK4, were downregulated in NSCLC tissues compared to normal tissues. The downregulation of ABR, PREX1, DOCK2 and DOCK4, which can be attributfed to promoter methylation, is correlated with poor prognosis. The underexpression of the four key Rho GEFs might be related to the upregulation of MYC signaling and DNA repair pathways, leading to carcinogenesis and poor prognosis. Moreover, overexpression of ABR was shown to have a tumor-suppressive effect in PC9 and H1703 cells. In conclusion, the data reveal the unprecedented role of ABR as tumor suppressor in NSCLC. The previously unnoticed functions of Rho GEFs in NSCLC will inspire researchers to investigate the distinct roles of Rho GEFs in cancers, in order to provide critical strategies in clinical practice.

Connectomes across development reveal principles of brain maturation.

An animal's nervous system changes as its body grows from birth to adulthood and its behaviours mature1-8. The form and extent of circuit remodelling across the connectome is unknown3,9-15. Here we used serial-section electron microscopy to reconstruct the full brain of eight isogenic Caenorhabditis elegans individuals across postnatal stages to investigate how it changes with age. The overall geometry of the brain is preserved from birth to adulthood, but substantial changes in chemical synaptic connectivity emerge on this consistent scaffold. Comparing connectomes between individuals reveals substantial differences in connectivity that make each brain partly unique. Comparing connectomes across maturation reveals consistent wiring changes between different neurons. These changes alter the strength of existing connections and create new connections. Collective changes in the network alter information processing. During development, the central decision-making circuitry is maintained, whereas sensory and motor pathways substantially remodel. With age, the brain becomes progressively more feedforward and discernibly modular. Thus developmental connectomics reveals principles that underlie brain maturation.

Ligand-Protected Au55 with a Novel Structure and Remarkable CO2 Electroreduction Performance.

A Au55 nanocluster with the composition of [Au55 (p-MBT)24 (Ph3 P)6 ](SbF6 )3 (p-MBT=4-methylbenzenethiolate) is synthesized via direct reduction of gold-phosphine and gold-thiolate precursors. Single-crystal X-ray diffraction reveals that this Au55 nanocluster features a face-centered cubic (fcc) Au55 kernel, different from the well-known two-shell cuboctahedral arrangement in Au55 (Ph3 P)12 Cl6 . The Au55 cluster shows a wide optical absorption band with optical energy gap (Eg =1.28 eV). It is found that the exclusion of chloride is crucial for the formation of the title cluster, otherwise rod-like [Au25 (SR)5 (PPh3 )10 Cl2 ]2+ is obtained. The strategy to run synthetic reaction in the absence of halide leads to new members of phosphine/thiolate co-protected metal nanoclusters. The Au55 nanocluster exhibits high catalytic activity and selectivity for electrochemical reduction of CO2 to CO; the Faradaic efficiency (FE) reaches 94.1 % at -0.6 V vs. reversible hydrogen electrode (RHE).

External Beam Radiation Therapy in pT4 Well-Differentiated Thyroid Cancer: A Population-Based Study of 405 Patients.

PURPOSE: The benefit of external beam radiation therapy (EBRT) in locally advanced, well- differentiated thyroid cancer (WDTC) is uncertain. The purpose of this study is to evaluate locoregional recurrence (LRR), progression-free survival, and cause-specific survival (CSS) of patients with pT4 well-differentiated thyroid carcinoma. METHODS AND MATERIALS: A population-based retrospective review was conducted of consecutive patients with pT4 WDTC (per the American Joint Committee on Cancer, 8th edition, criteria) treated provincially between 1985 and 2013. The primary endpoints were cumulative incidence of LRR and CSS. To account for the competing risks of death from other causes, a Fine-Gray's test was used. A Cox-proportional hazards model was used to analyze overall survival (OS). Multivariate models and propensity matching were used to account for the effects of covariates. RESULTS: A total of 405 patients were identified with a median follow-up time of 14.3 years for a total of 4209 person-years of follow up. The median age at the time of diagnosis was 53 years (range, 20-87). There were 211 patients (52%) who received EBRT. EBRT was associated with age ≥55 years (56% vs 35%; P < .001), airway involvement (42% vs 8%; P < .001), and R1/2 resection (81% vs 51%; P < .001). The 10-year outcomes for the non-EBRT and EBRT groups were 21.6% versus 11.4%, respectively, for LRR, 84.1% versus 93.1%, respectively, for CSS, and 85.7% versus 67.5%, respectively, for OS. On multivariate analysis, EBRT was associated with a lower rate of LRR (hazard ratio [HR]: 0.334; P < .001), but not associated with CSS (HR: 1.56; P = .142) nor OS (HR: 1.216; P = .335). After propensity score matching, the EBRT cohort had lower rates of LRR relative to the non-EBRT cohort (HR: 0.261; P = .0003), but there were no differences in CSS or OS. CONCLUSIONS: In this large, population-based analysis of patients with pT4 WDTC, EBRT was associated with lower rates of LRR, but no difference in CSS or OS.

A stable well-defined copper hydride cluster consolidated with hemilabile phosphines.

Copper hydrides are very useful in hydrogenation reactions. We report a stable Stryker-type copper hydride reagent protected by hemilabile phosphines: [Cu8H6(dppy)6](OTf)2 (Cu8-H, dppy = diphenylphosphino-2-pyridine). The metal core of this cluster has a bicapped octahedral configuration, and the copper-bound hydrides each triply bridges over a triangular face of the octahedron. This cluster is attractive due to its facile preparation and excellent stability under ambient conditions. The comparable activity and selectivity both in the stoichiometric and catalytic reactions make Cu8-H a promising alternative to Stryker's reagent.

Ultrafine Pt-Ni nanoparticles in hollow porous carbon spheres for remarkable oxygen reduction reaction catalysis.

Ultrafine bimetallic Pt-Ni nanoparticles, which catalyze the oxygen reduction reaction (ORR) efficiently, were successfully prepared in hollow porous carbon spheres (HPCSs) under the assistance of organic molecules. 2,2'-Dipyridylamine (dpa) was found to be most effective in preparing homogeneous small Pt-Ni nanoparticles (2.0 ± 0.4 nm) without the phase separation of Pt and Ni during synthesis, and the assistance of the organic molecules was investigated for the alloy nanoparticle formation. The Pt-Ni nanoparticle/HPCS catalyst synthesized in the presence of dpa exhibited remarkable electrochemical performance in the ORR showing a high mass activity of 3.25 ± 0.14 A mg-1Pt at 0.9 VRHE (13.5-fold higher relative to a commercial Pt/C catalyst), a large electrochemical surface area of 105 ± 8 m2 g-1Pt, and high durability. After 60 000 cycles of accelerated durability testing, the mass activity was still 12.3 times higher than that of the commercial Pt/C catalyst.

Cancellation of elective surgery: rates, reasons and effect on patient satisfaction.

Background: The cancellation of elective surgeries is a major problem that increases wait times, exacerbates costs and can negatively affect patients, both psychologically and physically. Our objectives were to investigate the reasons for cancellations across specialties at a single centre, to compare these reasons with previous data from the same centre between 2005 and 2009 and to examine how cancellations affected patients' lives and views of the medical system in cases when the cancellations were potentially preventable. Methods: Cancellation records of all elective surgeries scheduled between June 1, 2012, and Jan. 31, 2016, at a medium-sized, tertiary care, academic centre were retrospectively reviewed. We evaluated the rates and reasons for cancellation and interviewed a subset of patients whose surgery was cancelled for a potentially preventable reason (i.e., operating room running late, bed shortage, emergency case took place of scheduled surgery). Results: Across 11 surgical specialties, 2933 of 20 881 surgeries (14.0%) were cancelled and of these, 2448 (83.5%) were for administrative or structural reasons. Compared with the data collected previously for general, gynecological and urological procedures, cancellation rates increased from 8.1% to 11.8%. Although patients reported inconvenience, they were generally satisfied with the availability and the quality of the health care they received. Conclusion: Consistent with the previous study, our data suggest that most cancellations occur because of administrative or structural processes that are potentially preventable. Targeting these processes may help to reduce cancellations for elective surgeries and thereby improve economic efficiency and patient outcomes.

Contexte: L'annulation des chirurgies électives est un problème majeur qui allonge les temps d'attente, fait gonfler les coûts et peut affecter négativement les patients, tant psychologiquement que physiquement. Nos objectifs étaient de découvrir les raisons des annulations dans les diverses spécialités d'un seul centre, afin de comparer ces raisons à des données antérieures du même centre recueillies entre 2005 et 2009 et d'examiner en quoi les annulations affectent la vie des patients et leur perception du système médical dans les cas où les annulations auraient pu être évitées. Méthodes: Les dossiers d'annulation de toutes les chirurgies électives entre le 1er juin 2012 et le 31 janvier 2016 dans un centre hospitalier universitaire de soins tertiaires de taille moyenne ont été analysés de manière rétrospective. Nous avons évalué les taux d'annulation et les motifs, et interrogé un groupe de patients dont la chirurgie a été annulée pour des raisons potentiellement évitables (p. ex., retards au bloc opératoire, manque de lits, priorisation de cas plus urgents). Résultats: Entre les 11 spécialités chirurgicales, 2933 des 20 881 chirurgies (14,0 %) ont été annulées et parmi elles, 2448 (83,5 %) pour des raisons administratives ou structurelles. Comparativement aux données précédemment recueillies pour les interventions générales, gynécologiques et urologiques, les taux d'annulation ont augmenté de 8,1 % à 11,8 %. Même si les patients ont déploré des inconvénients, ils se sont généralement déclarés satisfaits de la qualité des soins reçus et de leur accessibilité. Conclusion: Comme lors de l'étude précédente, nos données suggèrent que les causes les plus fréquentes d'annulation sont liées à des marches à suivre administratives ou structurelles qui sont potentiellement évitables. Cibler ces marches à suivre pourrait contribuer à réduire le nombre d'annulations de chirurgies électives et améliorer de ce fait l'efficience économique et les résultats chez les patients.

Comparison of the gut microbiota of short-term and long-term medical workers and non-medical controls: a cross-sectional analysis.

OBJECTIVES: The hospital environment has been implicated in the enrichment and exchange of pathogens and antibiotic resistance, but its potential in shaping the symbiotic microbial community of hospital staff is unclear. This study was designed to evaluate the alteration of the gut microbiome in medical workers compared to non-medical controls. METHODS: A prospective cross-sectional cohort study was conducted in the intensive care unit (ICU) and other departments of a centre in north-eastern China. Faecal samples of 175 healthy medical workers-short-term (1-3 months) workers (n = 80) and long-term (>1 year) workers (n = 95)-and 80 healthy non-medical controls were analysed using 16S rRNA amplicon sequencing. The hospital environmental samples (n = 9) were also analysed. RESULTS: The gut microbiomes of medical workers exhibited marked deviations in diversity and alteration in microbial composition and function. Short-term workers showed significantly higher abundances of taxa such as Lactobacillus, Butyrivibrio, Clostridiaceae, Clostridium, Ruminococcus, Dialister, Bifidobacterium, Odoribacter, and Desulfovibrio and lower abundances of Bacteroides and Blautia than the controls. Long-term workers showed higher abundances of taxa such as Dialister, Veillonella, Clostridiaceae, Clostridium, Bilophila, Desulfovibrio, Pseudomonas, and Akkermansia and lower abundances of Bacteroides and Coprococcus than the controls. The medical workers' department (ICU versus non-ICU) and position (resident doctor versus nursing staff) also impacted their gut microbiome. Compared with the non-ICU workers, workers in the ICU showed a significant increase in the abundances of Dialister, Enterobacteriaceae, Phascolarctobacterium, Pseudomonas, Veillonella, and Streptococcus and a marked depletion of Faecalibacterium, Blautia, and Coprococcus. In contrast with the nursing staff, the resident doctors showed a significant increase in Erysipelotrichaceae and Clostridium and a decrease in Bacteroides, Blautia, and Ruminococcus in the gut microbiome. Moreover, we found that the microbiota of hospital environments potentially correlated with the workers' gut microbiota. CONCLUSIONS: Our findings demonstrated structural changes in the gut microbial community of medical workers.

Genetic Studies of Hypertrophic Cardiomyopathy in Singaporeans Identify Variants in TNNI3 and TNNT2 That Are Common in Chinese Patients.

BACKGROUND: To assess the genetic architecture of hypertrophic cardiomyopathy (HCM) in patients of predominantly Chinese ancestry. METHODS: We sequenced HCM disease genes in Singaporean patients (n=224) and Singaporean controls (n=3634), compared findings with additional populations and White HCM cohorts (n=6179), and performed in vitro functional studies. RESULTS: Singaporean HCM patients had significantly fewer confidently interpreted HCM disease variants (pathogenic/likely pathogenic: 18%, P<0.0001) but an excess of variants of uncertain significance (24%, P<0.0001), as compared to Whites (pathogenic/likely pathogenic: 31%, excess of variants of uncertain significance: 7%). Two missense variants in thin filament encoding genes were commonly seen in Singaporean HCM (TNNI3:p.R79C, disease allele frequency [AF]=0.018; TNNT2:p.R286H, disease AF=0.022) and are enriched in Singaporean HCM when compared with Asian controls (TNNI3:p.R79C, Singaporean controls AF=0.0055, P=0.0057, genome aggregation database-East Asian AF=0.0062, P=0.0086; TNNT2:p.R286H, Singaporean controls AF=0.0017, P<0.0001, genome aggregation database-East Asian AF=0.0009, P<0.0001). Both these variants have conflicting annotations in ClinVar and are of low penetrance (TNNI3:p.R79C, 0.7%; TNNT2:p.R286H, 2.7%) but are predicted to be deleterious by computational tools. In population controls, TNNI3:p.R79C carriers had significantly thicker left ventricular walls compared with noncarriers while its etiological fraction is limited (0.70 [95% CI, 0.35-0.86]) and thus TNNI3:p.R79C is considered variant of uncertain significance. Mutant TNNT2:p.R286H iPSC-CMs (induced pluripotent stem cells derived cardiomyocytes) show hypercontractility, increased metabolic requirements, and cellular hypertrophy and the etiological fraction (0.93 [95% CI, 0.83-0.97]) support the likely pathogenicity of TNNT2:p.R286H. CONCLUSIONS: As compared with Whites, Chinese HCM patients commonly have low penetrance risk alleles in TNNT2 or TNNI3 but exhibit few clinically actionable HCM variants overall. This highlights the need for greater study of HCM genetics in non-White populations.