ABSTRACT
Cell-to-cell mitochondrial transfer has recently been shown to play a role in maintaining physiological functions of cell. We previously illustrated that mitochondrial transfer within osteocyte dendritic network regulates bone tissue homeostasis. However, the mechanism of triggering this process has not been explored. Here, we showed that stressed osteocytes in mice release adenosine diphosphate (ADP), resulting in triggering mitochondrial transfer from healthy osteocytes to restore the oxygen consumption rate (OCR) and to alleviate reactive oxygen species accumulation. Furthermore, we identified that P2Y2 and P2Y6 transduced the ADP signal to regulate osteocyte mitochondrial transfer. We showed that mitochondrial metabolism is impaired in aged osteocytes, and there were more extracellular nucleotides release into the matrix in aged cortical bone due to compromised membrane integrity. Conditioned medium from aged osteocytes triggered mitochondrial transfer between osteocytes to enhance the energy metabolism. Together, using osteocyte as an example, this study showed new insights into how extracellular ADP triggers healthy cells to rescue energy metabolism crisis in stressed cells via mitochondrial transfer in tissue homeostasis.
Subject(s)
Adenosine Diphosphate , Homeostasis , Mitochondria , Osteocytes , Animals , Osteocytes/metabolism , Mitochondria/metabolism , Mice , Adenosine Diphosphate/metabolism , Reactive Oxygen Species/metabolism , Oxygen Consumption , Energy Metabolism , Mice, Inbred C57BL , Stress, PhysiologicalABSTRACT
Cell-passage-adapted strains of African swine fever virus (ASFV) typically exhibit substantial genomic alterations and attenuated virulence in pigs. We have indicated that the human embryonic kidney (HEK293T) cells-adapted ASFV strain underwent genetic alterations and the I7L gene in the right variable region was deleted compared with the ASFV HLJ/2018 strain (ASFV-WT). A recent study has revealed that the deletion of the I7L-I11L genes results in attenuation of virulent ASFV in vivo, but the underlying mechanism remains largely unknown. Therefore, we hypothesized that the deletion of the I7L gene may be related to the pathogenicity of ASFV in pigs. We generated the I7L gene-deleted ASFV mutant (ASFV-ΔI7L) and found that the I7L gene deletion does not influence the replication of ASFV in primary porcine alveolar macrophages (PAMs). Using transcriptome sequencing analysis, we identified that the differentially expressed genes in the PAMs infected with ASFV-ΔI7L were mainly involved in antiviral immune responses induced by interferon gamma (IFN-γ) compared with those in the ASFV-WT-infected PAMs. Meanwhile, we further confirmed that the I7L protein (pI7L) suppressed the IFN-γ-triggered JAK-STAT signaling pathway. Mechanistically, pI7L interacts with STAT1 and inhibits its phosphorylation and homodimerization, which depends on the tyrosine at position 98 (Y98) of pI7L, thereby preventing the nuclear translocation of STAT1 and leading to the decreased production of IFN-γ-stimulated genes. Importantly, ASFV-ΔI7L exhibited reduced replication and virulence compared with ASFV-WT in pigs, likely due to the increased production of IFN-γ-stimulated genes, indicating that pI7L is involved in the virulence of ASFV. Taken together, our findings demonstrate that pI7L is associated with pathogenicity and antagonizes the IFN-γ-triggered JAK-STAT signaling pathway via inhibiting the phosphorylation and homodimerization of STAT1 depending on the Y98 residue of pI7L and the Src homology 2 domain of STAT1, which provides more information for understanding the immunoevasion strategies and designing the live attenuated vaccines against ASFV infection.
Subject(s)
African Swine Fever Virus , African Swine Fever , Interferon-gamma , STAT1 Transcription Factor , Signal Transduction , Viral Proteins , Animals , African Swine Fever Virus/pathogenicity , Swine , African Swine Fever/virology , African Swine Fever/metabolism , STAT1 Transcription Factor/metabolism , Interferon-gamma/metabolism , Phosphorylation , Humans , Viral Proteins/metabolism , Viral Proteins/genetics , Virulence , HEK293 Cells , Virus Replication , Janus Kinases/metabolism , Macrophages, Alveolar/virology , Macrophages, Alveolar/metabolism , Macrophages, Alveolar/immunologyABSTRACT
Despite the various strategies for achieving metal-nitrogen-carbon (M-N-C) single-atom catalysts (SACs) with different microenvironments for electrochemical carbon dioxide reduction reaction (CO2RR), the synthesis-structure-performance correlation remains elusive due to the lack of well-controlled synthetic approaches. Here, we employed Ni nanoparticles as starting materials for the direct synthesis of nickel (Ni) SACs in one spot through harvesting the interaction between metallic Ni and N atoms in the precursor during the chemical vapor deposition growth of hierarchical N-doped graphene fibers. By combining with first-principle calculations, we found that the Ni-N configuration is closely correlated to the N contents in the precursor, in which the acetonitrile with a high N/C ratio favors the formation of Ni-N3, while the pyridine with a low N/C ratio is more likely to promote the evolution of Ni-N2. Moreover, we revealed that the presence of N favors the formation of H-terminated edge of sp2 carbon and consequently leads to the formation of graphene fibers consisting of vertically stacked graphene flakes, instead of the traditional growth of carbon nanotubes on Ni nanoparticles. With a high capability in balancing the *COOH formation and *CO desorption, the as-prepared hierarchical N-doped graphene nanofibers with Ni-N3 sites exhibit a superior CO2RR performance compared to that with Ni-N2 and Ni-N4 ones.
ABSTRACT
The contractile vacuole complex (CVC) is a dynamic and morphologically complex membrane organelle, comprising a large vesicle (bladder) linked with a tubular reticulum (spongiome). CVCs provide key osmoregulatory roles across diverse eukaryotic lineages, but probing the mechanisms underlying their structure and function is hampered by the limited tools available for in vivo analysis. In the experimentally tractable ciliate Tetrahymena thermophila, we describe four proteins that, as endogenously tagged constructs, localize specifically to distinct CVC zones. The DOPEY homolog Dop1p and the CORVET subunit Vps8Dp localize both to the bladder and spongiome but with different local distributions that are sensitive to osmotic perturbation, whereas the lipid scramblase Scr7p colocalizes with Vps8Dp. The H+-ATPase subunit Vma4 is spongiome specific. The live imaging permitted by these probes revealed dynamics at multiple scales including rapid exchange of CVC-localized and soluble protein pools versus lateral diffusion in the spongiome, spongiome extension and branching, and CVC formation during mitosis. Although the association with DOP1 and VPS8D implicate the CVC in endosomal trafficking, both the bladder and spongiome might be isolated from bulk endocytic input.
Subject(s)
Tetrahymena thermophila , Vacuoles , Vacuoles/metabolism , Endosomes , Proteins/metabolism , MitosisABSTRACT
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide, and the development of novel therapeutic strategies for HNSCC requires a profound understanding of tumor cells and the tumor microenvironment (TME). Additionally, HNSCC has a poor prognosis, necessitating the use of genetic markers for predicting clinical outcomes in HNSCC. In this study, we performed single-cell sequencing analysis on tumor tissues from seven HNSCC patients, along with one adjacent normal tissue. Firstly, the analysis of epithelial cell clusters revealed two clusters of malignant epithelial cells, characterized by unique gene expression patterns and dysregulated signaling pathways compared to normal epithelial cells. Secondly, the examination of the TME unveiled extensive crosstalk between fibroblasts and malignant epithelial cells, potentially mediated through ligand-receptor interactions such as COL1A1-SDC1, COL1A1-CD44, and COL1A2-SDC1. Furthermore, transcriptional heterogeneity was observed in immune cells present in the TME, including macrophages and dendritic cells. Finally, leveraging the gene expression profiles of malignant epithelial cells, we developed a prognostic model comprising six genes, which we validated using two independent datasets. These findings shed light on the heterogeneity within HNSCC tumors and the intricate interplay between malignant cells and the TME. Importantly, the developed prognostic model demonstrates high efficacy in predicting the survival outcomes of HNSCC patients.
Subject(s)
Carcinoma , Head and Neck Neoplasms , Humans , Squamous Cell Carcinoma of Head and Neck/genetics , Prognosis , Head and Neck Neoplasms/genetics , Epithelial Cells , Tumor Microenvironment/geneticsABSTRACT
Silicon (Si) is considered a promising commercial material for the next-generation of high-energy density lithium-ion battery (LIB) due to its high theoretical capacity. However, the severe volume changes and the poor conductivity hinder the practical application of Si anode. Herein, a novel core-shell heterostructure, Si as the core and V3 O4 @C as the shell (Si@V3 O4 @C), is proposed by a facile solvothermal reaction. Theoretical simulations have shown that the in-situ-formed V3 O4 layer facilitates the rapid Li+ diffusion and lowers the energy barrier of Li transport from the carbon shell to the inner core. The 3D network structure constructed by amorphous carbon can effectively improve electronic conductivity and structural stability. Benefiting from the rationally designed structure, the optimized Si@V3 O4 @C electrode exhibits an excellent cycling stability of 1061.1 mAh g-1 at 0.5 A g-1 over 700 cycles (capacity retention of 70.0%) with an average Coulombic efficiency of 99.3%. In addition, the Si@V3 O4 @C||LiFePO4 full cell shows a superior capacity retention of 78.7% after 130 cycles at 0.5 C. This study opens a novel way for designing high-performance silicon anode for advanced LIBs.
ABSTRACT
The electrochemical deintercalation method has been considered as an effective way to address the demand for lithium resources due to its environmental friendliness, high selectivity, and high efficiency. However, the performance of electrochemical lithium extraction is closely dependent on the electrode material and needs to be compatible under plateau environments with high-altitude and low-temperature. Herein, an in situ self-oxidation method is conducted to construct a hybrid conductive network on the surface of LiFePO4 (LFP-HN). The introduction of a hybrid conductive network enhanced the interfacial electron/lithium-ion transfer. In addition, structural stability is strengthened through suppressing the intercalation of impurity cations. Consequently, the LFP-HN delivered extremely high lithium extraction capacity (27.42 mg g-1), low energy consumption (4.91 Wh mol-1), and superior purity (91.05%) in Baqiancuo real brine (4788 m, -10 °C). What's more, LFP-HN-based large-scale prototypes are constructed and operated at Baqiancuo, which is calculated to extract 25 kg Lithium Carbonate Equivalent per cycle (4.55 h, 100 pairs of plates). Based on the excellent performance, the modification strategy developed in this work can be a promising solution for industrial lithium extraction under high-altitude environment.
ABSTRACT
The efficient removal of radioactive uranium from aqueous solution is of great significance for the safe and sustainable development of nuclear power. An ultrathin 2D metal-organic framework (MOF) nanosheet with cavity structures was elaborately fabricated based on a calix[4]arene ligand. Incorporating the permanent cavity structures on MOF nanosheet can fully utilize its structural characteristics of largely exposed surface area and accessible adsorption sites in pollutant removal, achieving ultrafast adsorption kinetics, and the functionalized cavity structure would endow the MOF nanosheets with the ability to achieve preconcentration and extraction of uranium from aqueous solution, affording ultrahigh removal efficiency even in ultra-low concentrations. Thus, more than 97% uranium can be removed from the concentration range of 50-500 µg L-1 within 5 min. Moreover, the 2D nano-material exhibits ultra-high anti-interference ability, which can efficiently remove uranium from groundwater and seawater. The adsorption mechanism was investigated by X-ray photoelectron spectroscopy (XPS), Fourier transform infrared (FT-IR) analysis, and density functional theory (DFT) calculations, which revealed that the cavity structure plays an important role in uranium capture. This study not only realizes highly efficient uranium removal from aqueous solution but also opens the door to achieving ultrathin MOF nanosheets with cavity structures, which will greatly expand the applications of MOF nanosheets.
ABSTRACT
OBJECTIVE(S): To evaluate whether extended dosing of antibiotics (ABX) after cytoreductive surgery (CRS) with large bowel resection for advanced ovarian cancer is associated with reduced incidence of surgical site infection (SSI) compared to standard intra-operative dosing and evaluate predictors of SSI. METHODS: A retrospective single-institution cohort study was performed in patients with stage III/IV ovarian cancer who underwent CRS from 2009 to 2017. Patients were divided into two cohorts: 1) standard intra-operative dosing ABX and 2) extended post-operative ABX. All ABX dosing was at the surgeon's discretion. The impact of antibiotic duration on SSI and other postoperative outcomes was assessed using univariate and multivariable Cox regression models. RESULTS: In total, 277 patients underwent cytoreductive surgery (CRS) with large bowel resection between 2009 and 2017. Forty-nine percent (n = 137) received standard intra-operative ABX and 50.5% (n = 140) received extended post-operative ABX. Rectosigmoid resection was the most common large bowel resection in the standard ABX (89.9%, n = 124) and extended ABX groups (90.0%, n = 126), respectively. No significant differences existed between age, BMI, hereditary predisposition, or medical comorbidities (p > 0.05). No difference was appreciated in the development of superficial incisional SSI between the standard ABX and extended ABX cohorts (10.9% vs. 12.9%, p = 0.62). Of patients who underwent a transverse colectomy, a larger percentage of patients developed a superficial SSI versus no SSI (21% vs. 6%, p = 0.004). CONCLUSION(S): In this retrospective study of patients with advanced ovarian cancer undergoing CRS with LBR, extended post-operative ABX was not associated with reduced SSI, and prolonged administration of antibiotics should be avoided unless clinically indicated.
Subject(s)
Anti-Bacterial Agents , Cytoreduction Surgical Procedures , Ovarian Neoplasms , Surgical Wound Infection , Humans , Female , Surgical Wound Infection/prevention & control , Surgical Wound Infection/epidemiology , Surgical Wound Infection/etiology , Retrospective Studies , Middle Aged , Cytoreduction Surgical Procedures/methods , Cytoreduction Surgical Procedures/adverse effects , Ovarian Neoplasms/surgery , Anti-Bacterial Agents/administration & dosage , Aged , Antibiotic Prophylaxis/methods , Cohort Studies , AdultABSTRACT
BACKGROUND: We sought to create a laparoscopic-based model to predict the ability to perform a minimally invasive (MIS) cytoreductive surgery in advanced epithelial ovarian cancer patients who have received neoadjuvant chemotherapy (NACT). METHODS: Fifty women were enrolled in a multi-institutional prospective pilot study (NCT03378128). Each patient underwent laparoscopic evaluation of 43 abdominopelvic sites followed by surgeon dictated surgical approach, either continue MIS or laparotomically. However, if the procedure continued MIS, the placement of a hand-assist port for manual palpation was mandated to emulate a laparotomic approach and all 43 sites were re-evaluated. Sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy were calculated for each site to predict MIS resectability. Each parameter was assigned a numeric value based on the strength of statistical association and a total predictive index score (PIV) was assigned for each patient. Receiver operating characteristic curve analysis was used to assess the ability of the model to predict the MIS approach. RESULTS: Twenty-seven patients (61%) underwent MIS surgery. The following abdominopelvic sites were selected for inclusion in the model: gastrosplenic ligament, rectum, left mesocolon, transverse colon, right colon, cecum, appendix, liver capsule, intrahepatic fossa/gallbladder, ileum/jejunum. Using the PIV, a ROC was generated with an AUC = 0.695. In the final model, a PIV <2 identified patients able to undergo an optimal MIS cytoreductive surgery with an accuracy of 68.2%. The specificity, or the ability to identify patients who would not be able to undergo an optimal MIS interval cytoreductive surgery, was 66.7%. CONCLUSION: This predictive index model may help to guide future inclusion criteria in randomized studies evaluating the MIS approach in advanced epithelial ovarian cancer.
Subject(s)
Carcinoma, Ovarian Epithelial , Cytoreduction Surgical Procedures , Laparoscopy , Ovarian Neoplasms , Humans , Female , Cytoreduction Surgical Procedures/methods , Ovarian Neoplasms/surgery , Ovarian Neoplasms/pathology , Ovarian Neoplasms/drug therapy , Laparoscopy/methods , Middle Aged , Prospective Studies , Carcinoma, Ovarian Epithelial/surgery , Carcinoma, Ovarian Epithelial/pathology , Carcinoma, Ovarian Epithelial/drug therapy , Pilot Projects , Neoadjuvant Therapy , Aged , Adult , Predictive Value of TestsABSTRACT
Necrotizing enterocolitis (NEC) is a common disorder in premature infants that is characterized by hyperinflammation and severe necrosis in the intestine. The pathogenesis of NEC remains to be elucidated. In this study, we demonstrate that adenosine, a metabolite more abundant in infants than in adults, plays an important role in the prevention of NEC. Administration of adenosine or its analog, adenosine-5'-N-ethyluronamide (NECA), dramatically relieved the severity of NEC in neonatal mice. Meanwhile, adenosine treatment significantly enhanced the immunosuppressive function, antibacterial activity, and migration of myeloid-derived suppressor cells (MDSCs). However, depletion of MDSCs or inhibition of their migration using the CXCR2 inhibitor SB225002 almost completely abrogated the protective effect of adenosine on NEC. Mechanistic studies showed that MDSCs in newborns expressed abundant adenosine receptor A2B (A2BR) that elicits intracellular cAMP signaling and its downstream target NF-κB. Importantly, intestinal tissues from patients with NEC showed significantly lower infiltration of A2BR-positive MDSCs than those from healthy donors. These observations revealed that adenosine-induced MDSCs represent an essential immune axis for intestinal homeostasis in newborns.
Subject(s)
Enterocolitis, Necrotizing , Myeloid-Derived Suppressor Cells , Adenosine , Animals , Enterocolitis, Necrotizing/drug therapy , Enterocolitis, Necrotizing/metabolism , Humans , Immunosuppressive Agents , Infant, Newborn , Mice , Myeloid-Derived Suppressor Cells/metabolism , NF-kappa B/metabolism , Signal Transduction/physiologyABSTRACT
The poor remediation performance of groundwater circulation well (GCW) on semi-volatile organic contaminants (such as aniline) has severely limited its practical application. To address the challenges posed by the low volatility and solubility of these contaminants, an innovative integration of GCW with in-situ thermal remediation (ISTR) was proposed to create a thermal enhanced circulation well (GCW-ISTR) in this study. Laboratory experiments and model simulations were performed to evaluate the heat transfer and enhanced remediation effect by GCW-ISTR. Results demonstrate that the heat transfer process is controlled by the water circulation around GCW-ISTR and is influenced by factors such as aeration flow rate, groundwater velocity and aquifer permeability. Heating area is directly proportional to the seepage velocity of groundwater which can be analyzed by multiplying the water head difference between the upper and lower screens with the aquifer permeability. Therefore, the heat transfer model, based on Darcy's seepage theory and the energy conservation equation, effectively simulates the heat transfer with an error margin of less than 10%. Compared to individual GCW, GCW-ISTR exhibits a 25.8% improvement in aniline remediation efficiency, resulting in a decrease in the average concentration from 97.95 mg/L to 0.168 mg/L within 48 h, effectively mitigating the occurrence of tailing phenomena. This study provides a feasible method of enhancing the remediation of GCW on semi-volatile contaminants and is anticipated to broaden the applicability of GCW in site application.
ABSTRACT
OBJECTIVE: Ovarian cancer is associated with a high rate of venous thromboembolism. Our objective is to report the incidence of venous thromboembolism in recurrent ovarian cancer, assess the impact on morbidity and mortality, and evaluate predictors of venous thromboembolism. METHODS: A retrospective single institution cohort study was performed. Patients with a diagnosis of recurrent ovarian cancer between 2007 and 2020 and no previous history of venous thromboembolism were identified. Demographic and clinical variables were collected. Univariate and multivariable analyses were performed to identify predictors of venous thromboembolism. RESULTS: Of the 345 patients included in this study, 77 (22.3%) developed a venous thromboembolism. Most (n=56, 72.7%) were actively receiving treatment at the time of diagnosis of venous thromboembolism, of whom 44 (78.6%) had received three or more lines of treatment. In total, 42 (54.5%) were admitted to hospital on diagnosis and one mortality (1.3%) occurred secondary to venous thromboembolism. An intermediate/high risk Khorana score was not predictive of venous thromboembolism (p=0.24). The risk of venous thromboembolism was significantly higher with increasing lines of chemotherapy (odds ratio 1.14, 95% confidence interval 1.02 to 1.28 per line, p=0.026). There was no significant difference in overall survival (62.9 vs 49.1 median months, p=0.29) between patients with and without venous thromboembolism. CONCLUSIONS: More than 20% of patients with recurrent ovarian cancer developed a venous thromboembolism, and most occurred after three or more lines of treatment. The risk of venous thromboembolism was higher with increasing lines of chemotherapy. While venous thromboembolism did not appear to impact survival in this population, nearly half required hospitalization, emphasizing the morbidity of venous thromboembolism and potential impact on healthcare costs. Further studies are needed to improve risk stratification for venous thromboembolism in this high risk population.
Subject(s)
Ovarian Neoplasms , Venous Thromboembolism , Humans , Female , Venous Thromboembolism/epidemiology , Venous Thromboembolism/etiology , Retrospective Studies , Ovarian Neoplasms/epidemiology , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/complications , Middle Aged , Incidence , Aged , Neoplasm Recurrence, Local/epidemiology , Adult , Cohort Studies , Risk FactorsABSTRACT
INTRODUCTION AND HYPOTHESIS: Combined surgical procedures with sacrocolpopexy (SCP) and rectopexy (RP) are more commonly being performed for treatment of multicompartment pelvic organ prolapse. This study aimed to compare healthcare resource utilization (HRU) within 6 weeks following combined surgery (SCP-RP) versus SCP alone (SCP-only). We hypothesized that concomitant RP does not impact HRU. METHODS: A retrospective cohort study of patients who underwent minimally invasive SCP from 2017 to 2022 was conducted at a tertiary referral center. Patients were grouped based on the performance of concomitant RP. HRU was defined as a composite of unscheduled office visits, emergency department visits, and readmissions before the 6-week postoperative visit. HRU was compared in the SCP-RP and SCP-only groups. Multivariable regression analysis was performed to identify factors associated with HRU. RESULTS: There were 144 patients in the SCP-RP group and 405 patients in the SCP-only group. Patient characteristics were similar between the two groups, with the following exceptions: the SCP-RP group was older, more likely to have comorbid conditions, and live >60 miles from the hospital. Of the 549 patients, 183 (33.3%) had ≥1 HRU encounter within 6 weeks after surgery. However, there was no difference between the SCP-RP and SCP-only groups in composite HRU (34.0% vs 33.1%, p = 0.84). The most common reasons for HRU were pain, urinary tract infection symptoms, and wound issues. Concomitant mid-urethral sling was associated with a two-fold increased risk of HRU after surgery. CONCLUSIONS: One in 3 patients undergoing minimally invasive SCP had at least one unanticipated encounter within 6 weeks after surgery. Concomitant RP was not associated with increased postoperative HRU.
Subject(s)
Gynecologic Surgical Procedures , Minimally Invasive Surgical Procedures , Pelvic Organ Prolapse , Humans , Female , Retrospective Studies , Middle Aged , Pelvic Organ Prolapse/surgery , Aged , Gynecologic Surgical Procedures/statistics & numerical data , Gynecologic Surgical Procedures/methods , Patient Acceptance of Health Care/statistics & numerical data , Rectum/surgery , Postoperative Complications/etiology , Postoperative Complications/epidemiology , Patient Readmission/statistics & numerical data , Sacrum/surgeryABSTRACT
OBJECTIVES: Venous thromboembolism (VTE) occurs in 0.4%-0.7% of benign hysterectomies. Pelvic vascular compression secondary to fibroids may elevate VTE risk. We aimed to evaluate the incidence and timing of VTE among individuals undergoing hysterectomy for fibroids and other benign indications. METHODS: Retrospective cohort study of patients who underwent a hysterectomy for fibroid and non-fibroid indications from January 2015 to December 2021. Main outcome measure was VTE consisting of pulmonary embolism or deep venous thrombosis diagnosed during 3 periods: (1) preoperative (1 year before surgery until day before surgery), (2) early postoperative (surgery date through 6 weeks after surgery), and (3) late postoperative (6 weeks to 1 year after surgery). Demographics, comorbidities, surgical characteristics, and VTE rates were compared by indication. RESULTS: A total of 263 844 individuals with fibroids and 203 183 without were identified. In total, 1.1% experienced VTE. On multivariable regression (adjusted demographic confounders and route of surgery), the presence of fibroids was associated with increased odds of preoperative (adjusted odds ratio [aOR] 1.12; 95% CI 1.03-1.22, P = 0.011) and reduced odds of late postoperative VTE (aOR 0.81; 95% CI 0.73-0.91, P < 0.001). For individuals with fibroids, uterine weight ≥250 g and undergoing laparotomy were independently associated with preoperative (aOR 1.29; 95% CI 1.09-1.52, P = 0.003 and aOR 2.32; 95% CI 2.10-2.56, P < 0.001) and early postoperative VTE (aOR 1.32; 95% CI 1.08-1.62, P = 0.006 and aOR 1.72; 95% CI 1.50-1.96, P < 0.001). CONCLUSIONS: Patients with fibroids were at increased odds of having VTE 1 year before hysterectomy. For those with fibroids, elevated uterine weight and laparotomy were associated with greater risk of preoperative and early postoperative VTEs.
Subject(s)
Hysterectomy , Leiomyoma , Postoperative Complications , Uterine Neoplasms , Venous Thromboembolism , Humans , Female , Hysterectomy/adverse effects , Retrospective Studies , Leiomyoma/surgery , Leiomyoma/complications , Venous Thromboembolism/epidemiology , Venous Thromboembolism/etiology , Middle Aged , Adult , Uterine Neoplasms/surgery , Uterine Neoplasms/complications , Postoperative Complications/epidemiology , Risk Factors , United States/epidemiology , Incidence , Cohort StudiesABSTRACT
OBJECTIVES: Decisional conflict and regret about prenatal genetic screening and diagnostic tests may have important consequences in the current pregnancy and for future reproductive decisions. Identifying mechanisms that reduce conflict associated with the decision to use or decline these options is necessary for optimal patient counseling. METHODS: We conducted a cluster-randomized controlled trial of a shared decision-making tool (NEST) at the beginning of prenatal care. Enrolled patients completed follow-up surveys at the time of testing (QTT) and in the second-third trimester (QFF), including the Decision Conflict Scale (DCS). Total DCS scores were analyzed using a multivariate linear mixed-effect model. RESULTS: Of the total number of participants (n=502) enrolled, 449 completed the QTT and QFF surveys. The mean age of participants was 31.6±3.8, with most parous at the time of study participation (n=321; 71.7â¯%). Both the NEST (the intervention) and control groups had lower median total DCS scores at QFF (NEST 13.3 [1.7, 25.0] vs. control 16.7 [1.7, 25.0]; p=0.24) compared to QTT (NEST 20.8 [5.0, 25.0] vs. control 18.3 [3.3, 26.7]; p=0.89). Participants exposed to NEST had lower decisional conflict at QFF compared to control (ß -3.889; [CI -7.341, -0.437]; p=0.027). CONCLUSIONS: Using a shared decision-making tool at the start of prenatal care decreased decisional conflict regarding prenatal genetic testing. Such interventions have the potential to provide an important form of decision-making support for patients facing the unique type of complex and preference-based choices about the use of prenatal genetic tests.
Subject(s)
Conflict, Psychological , Genetic Testing , Prenatal Care , Prenatal Diagnosis , Humans , Female , Pregnancy , Adult , Prenatal Care/methods , Prenatal Care/psychology , Prenatal Diagnosis/psychology , Prenatal Diagnosis/methods , Decision Making, Shared , Decision MakingABSTRACT
OBJECTIVE: Identify risk factors for postpartum readmission in class 3 obese patients undergoing unscheduled cesarean deliveries. STUDY DESIGN: Retrospective cohort study of patients with BMI ≥ 40 kg/m2 undergoing unscheduled cesarean delivery from 2017-2020 comparing patients with and without postpartum readmission (unexpected admission, emergency room/overnight observation visit, unscheduled outpatient visit, or ambulatory surgery within 30 days). Medical history, operative data, and postpartum outcomes were compared between the cohorts. RESULTS: "The electronic medical record was queried to identify cesarean deliveries documented as 'unscheduled'". 255 of 1273 identified patients (20.0%) had a postpartum readmission. Median BMI was similar between the cohorts (44.2 kg/m2, IQR [41.8, 47.9] vs. 44.8 kg/m2 [42.0, 48.9], p= 0.066). Readmitted patients were more likely to have a history of smoking during or prior to pregnancy (p= 0.046). A sub-group exploratory analysis excluding outpatient and emergency room visits demonstrated higher rates of type II diabetes mellitus in patient's with postpartum readmission (11.5% vs 4.6%, p= 0.030). Patients with readmission in comparison to those without readmissions were less likely to receive cefazolin prophylaxis (78.0% vs 84.3%, p= 0.014) in comparison to gentamicin/clindamycin prophylaxis. Patients with readmission were less likely to have had vaginal preparation (56.9% vs 64.3%, p= 0.027). On multivariable logistic regression analysis, smoking history (OR 1.44, 95% CI 1.06-1.96, p= 0.0220) and hypertensive disease (OR 1.57, 95% CI 1.18-2.09, p 0.002) were associated with readmission. Cefazolin preoperative prophylaxis (OR 0.59, 95% CI 0.41-0.84, p= 0.004) and vaginal sterile preparation (OR 0.72, 95% CI 0.54- 0.95, p= 0.022) were associated with decreased risk of readmission. CONCLUSIONS: In class 3 obese patients, a history of smoking and a diagnosis of hypertensive disease associate with increased risk of postpartum readmission. Perioperative antibiotic prophylaxis with cefazolin along with vaginal sterile preparation associate with decreased risk of postpartum readmission.
ABSTRACT
BACKGROUND: Among six extant tiger subspecies, the South China tiger (Panthera tigris amoyensis) once was widely distributed but is now the rarest one and extinct in the wild. All living South China tigers are descendants of only two male and four female wild-caught tigers and they survive solely in zoos after 60 years of effective conservation efforts. Inbreeding depression and hybridization with other tiger subspecies were believed to have occurred within the small, captive South China tiger population. It is therefore urgently needed to examine the genomic landscape of existing genetic variation among the South China tigers. RESULTS: In this study, we assembled a high-quality chromosome-level genome using long-read sequences and re-sequenced 29 high-depth genomes of the South China tigers. By combining and comparing our data with the other 40 genomes of six tiger subspecies, we identified two significantly differentiated genomic lineages among the South China tigers, which harbored some rare genetic variants introgressed from other tiger subspecies and thus maintained a moderate genetic diversity. We noticed that the South China tiger had higher FROH values for longer runs of homozygosity (ROH > 1 Mb), an indication of recent inbreeding/founder events. We also observed that the South China tiger had the least frequent homozygous genotypes of both high- and moderate-impact deleterious mutations, and lower mutation loads than both Amur and Sumatran tigers. Altogether, our analyses indicated an effective genetic purging of deleterious mutations in homozygous states from the South China tiger, following its population contraction with a controlled increase in inbreeding based on its pedigree records. CONCLUSIONS: The identification of two unique founder/genomic lineages coupled with active genetic purging of deleterious mutations in homozygous states and the genomic resources generated in our study pave the way for a genomics-informed conservation, following the real-time monitoring and rational exchange of reproductive South China tigers among zoos.
Subject(s)
Tigers , Animals , Female , Male , Tigers/genetics , Metagenomics , Genome , Genomics , China , Conservation of Natural ResourcesABSTRACT
Ciliated protozoans perform extreme forms of programmed somatic DNA rearrangement during development. The model ciliate Tetrahymena thermophila removes 34% of its germline micronuclear genome from somatic macronuclei by excising thousands of internal eliminated sequences (IESs), a process that shares features with transposon excision. Indeed, piggyBac transposon-derived genes are necessary for genome-wide IES excision in both Tetrahymena (TPB2 [Tetrahymena piggyBac-like 2] and LIA5) and Paramecium tetraurelia (PiggyMac). T. thermophila has at least three other piggyBac-derived genes: TPB1, TPB6, and TPB7 Here, we show that TPB1 and TPB6 excise a small, distinct set of 12 unusual IESs that disrupt exons. TPB1-deficient cells complete mating, but their progeny exhibit slow growth, giant vacuoles, and osmotic shock sensitivity due to retention of an IES in the vacuolar gene DOP1 (Dopey domain-containing protein). Unlike most IESs, TPB1-dependent IESs have piggyBac-like terminal inverted motifs that are necessary for excision. Transposon-like excision mediated by TPB1 and TPB6 provides direct evidence for a transposon origin of not only IES excision machinery but also IESs themselves. Our study highlights a division of labor among ciliate piggyBac-derived genes, which carry out mutually exclusive categories of excision events mediated by either transposon-like features or RNA-directed heterochromatin.
Subject(s)
DNA Transposable Elements/genetics , Gene Rearrangement/genetics , Genes, Protozoan/genetics , Genome, Protozoan/genetics , Protozoan Proteins/metabolism , Tetrahymena thermophila/genetics , Gene Expression Regulation, Developmental , Gene Knockout Techniques , Life Cycle Stages , Protozoan Proteins/genetics , Tetrahymena thermophila/growth & development , Vacuoles/geneticsABSTRACT
In this study, the oil sand was treated with an integrated process of pyrolysis and ball milling, and the obtained ball-milled carbon sand (BMCS) was utilized as peroxymonosulfate (PMS) activator to treat wastewater containing aniline (AN). Quenching experiments and electron paramagnetic resonance (EPR) confirmed the existence of sulfate radical (SO4â-), hydroxyl radical (·OH) and singlet oxygen (O12) in the BMCS/PMS system. A probe-based kinetic model was constructed to describe the degradation process of pollutants in the BMCS/PMS system, quantified the exposure of each reactive oxygen species and their contributions to AN degradation. BMCS activated PMS to quickly produce SO4â- and gradually generate ·OH. The O12 exposure showed a rapid increasing trend and the largest total exposure, while its contribution to AN degradation was small. Ball milling time and BMCS dosage demonstrated significant effect on the exposure of ·OH and O12. The main active sites for BMCS to activate PMS were iron oxides, defective carbon and oxygen-containing functional groups. This study provides a green and low-cost process for value-added transformation of pyrolytic residue of oil sand (PROS), so as to promote PROS treatment mode from harmless disposal to resource utilization.