ZWINT promotes the proliferation, migration, and invasion of cervical cancer cells by regulating the p53/p21 signaling pathway.

Cervical cancer leads to 300,000 deaths annually and the mechanism of cervical carcinogenesis remains unclear. Zeste White 10-interacting kinetochore protein (ZWINT) is uniquely elevated in malignancies, promoting proliferation, migration, and colony formation of cancer cells. To investigate the role of ZWINT in proliferation, migration, invasion of cervical cancer, and evaluate the potential ability of ZWINT as a therapeutic target. First, ZWINT expression in cervical cancer was analyzed using the bioinformatic methods and assessed in several cervical cancer cell lines. The cell viability and colony formation assays were used to evaluate cell proliferation. Then, transwell assay was performed to investigate cell migration and invasion. Moreover, western blot was used to measure the expression level of ZWINT, matrix metalloproteinase 9 (MMP-9), N-cadherin, E-cadherin, p53 and p21 in CaSki and HeLa cells with ZWINT overexpression or knockdown. The bioinformatic analysis and western blot assay revealed the expression of ZWINT was significantly increased in cervical cancer. The cell viability and colony formation analysis illustrated that cell proliferation could be promoted by ZWINT overexpression and suppressed by ZWINT knockdown. Moreover, ZWINT promoted migration and invasion of CaSki and HeLa cells, through regulating the expression of MMP-9, N-cadherin, and E-cadherin. Furthermore, ZWINT attenuated the expression of p53 and p21 in cervical cancer cells. In summary, ZWINT functions in promoting cell proliferation, migration, and invasion of cervical cancer cells by suppressing p53/p21 signaling pathway, which indicated ZWINT is a potential therapeutic target for cervical cancer treatment.

JTE-013 Alleviates Pulmonary Fibrosis by Affecting the RhoA/YAP Pathway and Mitochondrial Fusion/Fission.

Pulmonary fibrosis may be due to the proliferation of fibroblasts and the aggregation of extracellular matrix, resulting in the stimulation of inflammation damage, destroying lung tissue structure, seriously affecting the patient's respiratory function, and even leading to death. We investigated the role and mechanism of JTE-013 in attenuating bleomycin (BLM)-induced pulmonary fibrosis. BLM-induced pulmonary fibrosis was established in mice. Type 2 alveolar epithelial cells (MLE-12) were stimulated with sphingosine monophosphate (S1P) in vitro. JTE-013, an S1PR2 (sphingosine 1-phosphate receptor 2) antagonist, and Verteporfin were administered in vivo and in vitro. IL-4, IL-5, TNF-α, and IFN-γ were measured by ELISA. IL-4 and IFN-γ positive cells were detected by flow cytometry. Inhibition of S1PR2 with JTE-013 significantly ameliorated BLM-induced pathological changes and inflammatory cytokine levels. JTE-013 also significantly reduced the expression of RHOA/YAP pathway proteins and mitochondrial fission protein Drp1, apoptosis, and the colocalization of α-SMA with YAP, Drp1, and Tom20, as detected by immunohistochemistry, immunofluorescence staining, TUNEL, and Western blot. In vitro, S1PR2 and YAP knockdown downregulated RHOA/YAP pathway protein expression, Drp1 phosphorylation, and Drp1 translocation, promoted YAP phosphorylation and phenotypic transformation of MFN2, and inhibited the up-regulation of mitochondrial membrane potential, reactive oxygen species production, and cell apoptosis (7.13% vs. 18.14%), protecting the integrity of the mitochondrial dynamics. JTE-013 also inhibited the expression of fibrosis markers α-SMA, MMP-9, and COL1A1, and alleviated the symptoms of pulmonary fibrosis. Conclusively, JTE-013 has great anti-pulmonary fibrosis potential by regulating RHOA/YAP and mitochondrial fusion/fission.

Role of patient selection and trial stimulation for spinal cord stimulation therapy for chronic non-cancer pain: a comprehensive narrative review.

BACKGROUND/IMPORTANCE: Patient selection for spinal cord stimulation (SCS) therapy is crucial and is traditionally performed with clinical selection followed by a screening trial. The factors influencing patient selection and the importance of trialing have not been systematically evaluated. OBJECTIVE: We report a narrative review conducted to synthesize evidence regarding patient selection and the role of SCS trials. EVIDENCE REVIEW: Medline, EMBASE and Cochrane databases were searched for reports (any design) of SCS in adult patients, from their inception until March 30, 2022. Study selection and data extraction were carried out using DistillerSR. Data were organized into tables and narrative summaries, categorized by study design. Importance of patient variables and trialing was considered by looking at their influence on the long-term therapy success. FINDINGS: Among 7321 citations, 201 reports consisting of 60 systematic reviews, 36 randomized controlled trials (RCTs), 41 observational studies (OSs), 51 registry-based reports, and 13 case reports on complications during trialing were included. Based on RCTs and OSs, the median trial success rate was 72% and 82%, and therapy success was 65% and 61% at 12 months, respectively. Although several psychological and non-psychological determinants have been investigated, studies do not report a consistent approach to patient selection. Among psychological factors, untreated depression was associated with poor long-term outcomes, but the effect of others was inconsistent. Most RCTs except for chronic angina involved trialing and only one RCT compared patient selection with or without trial. The median (range) trial duration was 10 (0-30) and 7 (0-56) days among RCTs and OSs, respectively. CONCLUSIONS: Due to lack of a consistent approach to identify responders for SCS therapy, trialing complements patient selection to exclude patients who do not find the therapy helpful and/or intolerant of the SCS system. However, more rigorous and large studies are necessary to better evaluate its role.

High Energy Harvesting Performances Silicone Elastomer via Filling Soft Dielectric with Stretching Deformability.

Dielectric elastomer generators (DEGs) with high generated energy density and high conversion efficiency are of great interest. Among several dielectric elastomers (DEs), silicone elastomer filled with ceramic fillers have been extensively studied for their high elasticity, insulation, and permittivity. However, the stretched breakdown strength (Ebs ) of such composites decreases significantly under large strain, thus sharply reduces its energy harvesting performances. In this study, a polar rubber-based dielectric (GNBR) is synthetized and creatively used as "soft filler" for silicone elastomer. Benefiting from the deformability under stretching and its inherent strong interface bonding with silicone elastomer, this soft filler effectively avoids the formation of weak interface under large strain and reduces the local field strength of interface area. As expected, the composite filled with soft filler (GNBR/PMVS) shows enhanced Ebs of 2.8 times that of composite with traditional hard filler (TiO2 /PMVS) under equibiaxial strain of 200%. As a result, GNBR/PMVS composite exhibits maximum energy density of 130.5 mJ g-1 with up-to-date highest power conversion efficiency of reported DEG (44.5%). The findings will provide new insights in the rational design of DE composites characterized by high stretched breakdown strength for advanced energy harvesting system.

Level of Evidence of Guidelines for Perioperative Management of Patients With Obstructive Sleep Apnea: An Evaluation Using the Appraisal of Guidelines for Research and Evaluation II Tool.

Currently, the quality of guidelines for the perioperative management of patients with obstructive sleep apnea (OSA) is unknown, leaving anesthesiologists to make perioperative management decisions with some degree of uncertainty. This study evaluated the quality of clinical practice guidelines regarding the perioperative management of patients with OSA. This study was reported in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A systematic search of the MedlineALL (Ovid) database was conducted from inception to February 26, 2021, for clinical practice guidelines in the English language. Quality appraisal of guidelines was evaluated using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) framework. Descriptive statistical analysis of each of the 6 domains was expressed as a percentage using the formula: (obtained score - minimum possible score)/(maximum possible score - minimum possible score). Of 192 articles identified in the search, 41 full texts were assessed for eligibility, and 10 articles were included in this review. Intraclass correlation coefficients of the AGREE II scores across the 7 evaluators for each guideline were each >0.9, suggesting that the consistency of the scores among evaluators was high. Sixty percent of recommendations were based on evidence using validated methods to grade medical literature, while the remainder were consensus based. The median and range scores of each domain were: (1) scope and purpose, 88% (60%-95%); (2) stakeholder involvement, 52% (30%-82%); (3) rigor of development, 67% (40%-90%); (4) clarity of presentation, 74% (57%-88%); (5) applicability, 46% (20%-73%); and (6) editorial independence, 67% (19%-83%). Only 4 guidelines achieved an overall score of >70%. This critical appraisal showed that many clinical practice guidelines for perioperative management of patients with OSA used validated methods to grade medical literature, such as Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) and Oxford classification, with lower scores for stakeholder involvement due to lack of engagement of patient partners and applicability domain due to lack of focus on the complete perioperative period such as postdischarge counseling. Future efforts should be directed toward establishing higher focus on the quality of evidence, stakeholder involvement, and applicability to the wider perioperative patient experience.

Evaluating the impact of cannabinoids on sleep health and pain in patients with chronic neuropathic pain: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Chronic neuropathic pain is often debilitating and can have a significant impact on sleep health and quality of life. There is limited information on the impact of cannabinoids on sleep health when treating neuropathic pain. OBJECTIVE: The objectives of this systematic review and meta-analysis were to determine the effect of cannabinoids on sleep quality, pain intensity, and patient impression of treatment efficacy in patients with neuropathic pain. EVIDENCE REVIEW: Nine available medical literature databases were searched for randomized controlled trials comparing synthetic and natural cannabinoids to placebo in patients with neuropathic pain syndromes. Data on validated tools for sleep quality, pain intensity, patients' global impression of change (PGIC), and incidence of adverse effects of cannabinoids were extracted and synthesized. FINDINGS: Of the 3491 studies screened, eight randomized controlled trials satisfied the inclusion criteria for this review. Analyses were performed using R -4.1.2. using the metafor package and are interpreted using alpha=0.05 as the threshold for statistical significance. Validated measures for sleep health were not used in most studies. Meta-analysis of data from six studies showed that cannabinoids were associated with a significant improvement in sleep quality (standardized mean difference (SMD): 0.40; 95% CI: 0.19 to -0.61, 95% prediction interval (PI): -0.12 to 0.88, p-value=0.002, I2=55.26, τ2=0.05, Q-statistic=16.72, GRADE: moderate certainty). Meta-analysis of data from eight studies showed a significant reduction in daily pain scores in the cannabinoid (CB) group (SMD: -0.55, 95% CI:-0.69 to -0.19, 95% PI: -1.51 to 0.39, p=0.003, I2=82.49, τ2=0.20, Q-statistic=47.69, GRADE: moderate certainty). However, sleep health and analgesic benefits were associated with a higher likelihood of experiencing daytime somnolence, nausea, and dizziness. CONCLUSIONS: Cannabinoids have a role in treating chronic neuropathic pain as evidenced by significant improvements in sleep quality, pain intensity, and PGIC. More research is needed to comprehensively evaluate the impact of cannabinoids on sleep health and analgesic efficacy. PROSPERO REGISTRATION NUMBER: CRD42017074255.

Research on the Springback Behavior of 316LN Stainless Steel in Micro-Scale Bending Processes.

Hydrogen fuel cells have been used worldwide due to their high energy density and zero emissions. The metallic bipolar plate is the crucial component and has a significant effect on a cell's efficiency. However, the springback behavior of the metallic bipolar plate will greatly influence its forming accuracy in the micro-scale sheet metal forming process. Therefore, accurate calculation of the springback angle of the micro-scale metallic bipolar plate is urgent but difficult given the state of existing elastoplastic theory. In this paper, a constitutive model that simultaneously considers grain size effect and strain gradient is proposed to analyze micro-scale bending behavior and calculate springback angles. The specialized micro-scale four-point bending tool was designed to better calculate the springback angle and simplify the calculation step. A pure micro-bending experiment on a 316LN stainless steel sheet with a thickness of 0.1 mm was conducted to verify the constitutive model's accuracy.

Expression of Enhancer-Binding Protein CEBPA mRNA and Protein in Ovarian Cancer and Its Relationship With Pathobiological Characteristics.

Ovarian cancer is a common malignant tumor, its early onset is hidden, lack of specific symptoms, the location of the lesion is particularly hidden, which makes it difficult to find ovarian lesions by general detection, making it difficult to make an early clinical diagnosis. Therefore, it is still the focus and difficulty of ovarian cancer research to find the means of early diagnosis and prognosis of ovarian cancer. Cytosine-cytosine-adenosine-adenosine-thymidine (CCAAT) enhancer-binding protein α (CEBPA) has been proved to be involved in cell metabolism, proliferation, and differentiation. In this study, the expression of CEBPA mRNA and protein in normal ovary, epithelial ovarian cyst, ovarian borderline tumor, and ovarian cancer was detected, the relationship between CEBPA and pathobiological characteristics of ovarian cancer was discussed, and its influence on the prognosis of patients with ovarian cancer was analyzed. The results showed that the expression of CEBPA mRNA and protein in patients with ovarian borderline tumor and ovarian cancer is high, and the expression of CEBPA has no obvious correlation with the pathobiological characteristics of patients with ovarian cancer, and the high expression of CEBPA has an important value in the diagnosis of ovarian cancer, and it is also a poor prognostic factor of the disease.

A Novel CDK4/6 and PARP Dual Inhibitor ZC-22 Effectively Suppresses Tumor Growth and Improves the Response to Cisplatin Treatment in Breast and Ovarian Cancer.

In recent years, three PARP inhibitors and three CDK4/6 inhibitors have been approved by the FDA for the treatment of recurrent ovarian cancer and advanced ER-positive breast cancer, respectively. However, the clinical benefits of the PARPi or CDK4/6i monotherapy are not as satisfied as expected and benefit only a fraction of patients. Current studies have shown therapeutic synergy for combinations of PARPi and CDK4/6i in breast and ovarian cancers with homologous recombination (HR) proficiency, which represents a new synthetic lethal strategy for treatment of these cancers regardless HR status. Thus, any compounds or strategies that can combine PARP and CDK4/6 inhibition will likely have great potential in improving clinic outcomes and in benefiting more patients. In this study, we developed a novel compound, ZC-22, that effectively inhibited both PARP and CDK4/6. This dual-targeting compound significantly inhibited breast and ovarian cancer cells by inducing cell cycle arrest and severe DNA damage both in vitro and in vivo. Interestingly, the efficacy of ZC-22 is even higher than the combination of PARPi Olaparib and CDK4/6i Abemaciclib in most breast and ovarian cancer cells, suggesting that it may be an effective alternative for the PARPi and CDK4/6i combination therapy. Moreover, ZC-22 sensitized breast and ovarian cancer cells to cisplatin treatment, a widely used chemotherapeutic agent. Altogether, our study has demonstrated the potency of a novel CDK4/6 and PARP dual inhibitor, which can potentially be developed into a monotherapy or combinatorial therapy with cisplatin for breast and ovarian cancer patients with HR proficiency.

LncRNA Opa interacting protein 5-antisense RNA 1 (OIP5-AS1) promotes the migration, invasion and epithelial-mesenchymal transition (EMT) through targeting miR-147a/insulin-like growth factor 1 receptor (IGF1R) pathway in cervical cancer tissues and cell model.

BACKGROUND: Two factors involved in regulation, long noncoding RNA Opa interacting protein 5-antisense RNA 1 (lncRNA OIP5-AS1) and microRNA-147a, were found in cervical cancer. Therefore, the investigation of the specific regulation of miR-147a by OIP5-AS1 was performed in cervical cancer. METHOD: The cervical cancer tissues were collected from patients with cervical cancer (n = 50). The expression of OIP5-AS1, miR-147a, proteins in epithelial-mesenchymal transition (EMT) process and insulin-like growth factor 1 receptor (IGF1R) were measured by quantitative real-time polymerase chain reaction (qRT-PCT) or western blotting. Cell motility and the relationship between OIP5-AS1 and miR-147a were detected or analyzed by wound healing test, Transwell assay, dual-luciferase reporter assay, RNA binding protein immunoprecipitation assay or Pearson correlation in OIP5-AS1, or miR-147a over-expressed and/or suppressed cervical cancer cells. RESULTS: OIP5-AS1 showed the high-expression and miR-147a showed the low-expression in tumor tissues collected from patients with cervical cancer and cell lines Hela, CaSki, Siha, and ME-180. The low-expression of OIP5-AS1 suppressed the motility of Caski cells, as well as up-regulated the level of E-cadherin, which a key protein in EMT. There were targeting sites between miR-147a and OIP5-AS1. OIP5-AS1 induced the down-regulation of miR-147a, so miR-147a was inversely correlated with OIP5-AS1. The down-regulation of miR-147a increased IGF1R and E-cadherin, and these increases were alleviated by OIP5-AS1 knockdown. CONCLUSION: LncRNA OIP5-AS1 promotes the migration, invasion and EMT of cervical cancer cells via targeting miR-147a/IGF1R pathway.

Benefits of dexmedetomidine on postoperative analgesia after bariatric surgery.

INTRODUCTION: Anesthetic management of morbidly obese patients is challenging, particularly in those undergoing bariatric surgery. Dexmedetomidine is a α2-adrenergic receptor agonist that is increasingly used in the perioperative setting for its beneficial properties including sedation, anxiolysis, analgesia with opioid-sparing effects, and minimal impact on respiration. The objective of this study was to evaluate the effect of dexmedetomidine on postoperative analgesia and recovery-related outcomes among patients undergoing bariatric surgery. EVIDENCE ACQUISITION: We conducted a systematic review and meta-analysis of MEDLINE, EMBASE, and CENTRAL databases from conception to September 2021 for randomized controlled trials (RCTs) using dexmedetomidine in bariatric patients on postoperative outcomes. Outcomes were pooled using random effects model and presented as relative risks (RR) or mean differences (MD) with 95% confidence intervals (CI). EVIDENCE SYNTHESIS: In total, 20 RCTs with 665 patients in the dexmedetomidine group and 671 patients in the control groups were included. Among RCTs, the dexmedetomidine group had significantly lower opioid usage at 24-hours postoperatively (MD: -5.14, 95% CI: -10.18 to -0.10; moderate certainty), reduced pain scores on a 10-point scale at PACU arrival (MD: -1.69, 95% CI: -2.79 to -0.59; moderate certainty) and six hours postoperatively (MD: -1.82, 95% CI: -3.00 to -0.64; low certainty), and fewer instances of nausea (RR: 0.59, 95% CI: 0.45 to 0.75; moderate certainty) and vomiting (RR: 0.25, 95% CI: 0.15 to 0.43; moderate certainty), compared to control groups. CONCLUSIONS: Dexmedetomidine is an efficacious anesthesia adjunct in patients undergoing bariatric surgery. These benefits of dexmedetomidine may be considered in the multi-modal analgesic management and enhanced recovery pathways in this high-risk population.

Bariatric Surgery as a Bridge to Heart Transplantation in Morbidly Obese Patients: A Systematic Review and Meta-Analysis.

Class 2 obesity or greater [body mass index (BMI) >35 kg/m2] is a relative contraindication for heart transplant due to its associated perioperative risks and mortality. Whether bariatric surgery can act as a potential bridging procedure to heart transplantation is unknown. The aim of this systematic review and meta-analysis is to investigate the role of bariatric surgery on improving transplant candidacy in patients with end-stage heart failure (ESHF). MEDLINE, EMBASE, CENTRAL, and PubMed databases were searched up to September 2019 for studies that performed bariatric surgery on patients with severe obesity and ESHF. Outcomes of interest included incidence of patients listed for heart transplantation after bariatric surgery, proportion of patients that successfully received transplant, the change in BMI after bariatric surgery, and 30-day complications. Pooled estimates were calculated using a random-effects meta-analysis of proportions. Eleven studies with 98 patients were included. Mean preoperative BMI was 44.9 (2.1) kg/m2 and BMI after surgery was 33.2 (2.3) kg/m2 with an absolute BMI reduction of 26.1%. After bariatric surgery, 71% [95% confidence interval (CI), 55-86%] of patients with ESHF were listed for transplantation. The mean time from bariatric surgery to receiving a heart transplant was 14.9 (4.0) months. Of the listed patients, 57% (95% CI, 39-74%) successfully received heart transplant. The rate of 30-day mortality after bariatric surgery was 0%, and the 30-day major and minor complications after bariatric surgery was 28% (95% CI, 10-49%). Bariatric surgery can facilitate sustained weight loss in obese patients with ESHF, improving heart transplant candidacy and the incidence of transplantation.

Risk factors and protective measures for healthcare worker infection during highly infectious viral respiratory epidemics: A systematic review and meta-analysis.

OBJECTIVE: To investigate risk factors for healthcare worker (HCW) infection in viral respiratory pandemics: severe acute respiratory coronavirus virus 2 (SARS-CoV-2), Middle East respiratory syndrome (MERS), SARS CoV-1, influenza A H1N1, influenza H5N1. To improve understanding of HCW risk management amid the COVID-19 pandemic. DESIGN: Systematic review and meta-analysis. METHODS: We searched MEDLINE, EMBASE, CINAHL, and Cochrane CENTRAL databases from conception until July 2020 for studies comparing infected HCWs (cases) and noninfected HCWs (controls) and risk factors for infection. Outcomes included HCW types, infection prevention practices, and medical procedures. Pooled effect estimates with pathogen-specific stratified meta-analysis and inverse variance meta-regression analysis were completed. We used the GRADE framework to rate certainty of evidence. (PROSPERO no. CRD42020176232, 6 April 2020.). RESULTS: In total, 54 comparative studies were included (n = 191,004 HCWs). Compared to nonfrontline HCWs, frontline HCWs were at increased infection risk (OR, 1.66; 95% CI, 1.24-2.22), and the risk was greater for HCWs involved in endotracheal intubations (risk difference, 35.2%; 95% CI, 21.4-47.9). Use of gloves, gown, surgical mask, N95 respirator, face protection, and infection training were each strongly protective against infection. Meta-regression showed reduced infection risk in frontline HCWs working in facilities with infection designated wards (OR, -1.04; 95% CI, -1.53 to -0.33, P = .004) and performing aerosol-generating medical procedures in designated centers (OR, -1.30; 95% CI, -2.52 to -0.08; P = .037). CONCLUSIONS: During highly infectious respiratory pandemics, widely available protective measures such as use of gloves, gowns, and face masks are strongly protective against infection and should be instituted, preferably in dedicated settings, to protect frontline HCW during waves of respiratory virus pandemics.

Impact of a continuous enhanced cardio-respiratory monitoring pathway on cardio-respiratory complications after bariatric surgery: A retrospective cohort study.

STUDY OBJECTIVE: To determine the impact of an enhanced monitoring pathway consisting of continuous postoperative cardio-respiratory monitoring on adverse outcomes after bariatric. DESIGN: Single-center, retrospective cohort study. PATIENTS: Adult patients who underwent bariatric surgeries between 2009 and 2016. INTERVENTIONS: We evaluated the use of an enhanced monitoring pathway consisting of a distant, continuous, non-invasive respiratory monitoring system on postoperative cardio-respiratory complications in patients undergoing bariatric surgery. Treating physicians had the option to assign patients to enhanced monitoring (intervention group) in the postoperative period for suspected or diagnosed OSA or other clinical concerns. The control group had intermittent vital sign checks as per institutional standards. MEASUREMENTS: The primary outcome was a composite of cardio-respiratory complications (rapid response team activation, intensive care admission, respiratory complications), major adverse cardiac events, and all-cause mortality. The secondary outcome was length of stay (LOS). MAIN RESULTS: Of 1450 patients, 752 patients received enhanced monitoring (intervention) and 698 patients received standard monitoring (control). Univariate analysis showed that, compared to control, enhanced monitoring was associated with lower odds of composite cardio-respiratory complications (OR: 0.41, 95%CI: 0.32-0.53, p < 0.001) and lower odds of prolonged LOS > 2 days (OR: 0.37, 95% CI: 0.28-0.49, p < 0.001. After adjusting for potential confounders, enhanced monitoring remained associated with a reduction in composite cardio-respiratory complications (OR: 0.64, 95% CI: 0.46-0.88, p = 0.005). CONCLUSIONS: Our study demonstrates that postoperative enhanced monitoring pathway was associated with a lower incidence of cardio-respiratory composite events, compared to a standard of care, in patients undergoing bariatric surgery. As our results show association rather than causation, future prospective randomized trials are needed to confirm the benefit of enhanced monitoring. Findings of our study add to the existing literature involved in clinical management pathways to reduce the incidence of adverse postoperative outcomes in high-risk patients undergoing inpatient surgeries.

Recent cannabis use and nightly sleep duration in adults: a population analysis of the NHANES from 2005 to 2018.

BACKGROUND: While popularly consumed for its perceived benefits as a sleeping aid, the impact of cannabis on sleep-wake regulation in clinical studies is inconclusive. The purpose of this study was to determine the relationship between cannabis use and nightly sleep duration in a nationally representative dataset. METHODS: A cross-sectional analysis of adults was undertaken using the National Health and Nutrition Examination Survey data from 2005 to 2018. Respondents were dichotomized as recent users or non-users if they had used or not used cannabis in the past 30 days, respectively. The primary outcome was nightly sleep duration, categorized as short (<6 hours), optimal (6-9 hours), and long (>9 hours). Multinomial logistic regression was used to adjust for sociodemographic and health-related covariates, and survey sample weights were used in modeling. RESULTS: From a sample representing approximately 146 million adults in the USA, 14.5% reported recent cannabis use. In an adjusted analysis, recent users were more likely than non-users to report both short sleep (OR 1.34, 95% CI 1.12 to 1.59, p<0.001) and long sleep (OR 1.56, 95% CI 1.25 to 1.96, p<0.001). Heavy users (≥20 of the past 30 days) were even more likely to be at the extremes of nightly sleep duration. DISCUSSION: Recent cannabis use was associated with the extremes of nightly sleep duration in a nationally representative sample of adults, with suggestions of a dose-response relationship. Our findings highlight the need to further characterize the sleep health of regular cannabis users in the population.

Total Intravenous Anesthesia Versus Inhalation Anesthesia on Postoperative Analgesia and Nausea and Vomiting After Bariatric Surgery: A Systematic Review and Meta-Analysis.

Anesthesia for patients with morbid obesity can be challenging because of increased risk of opioid-related adverse events, postoperative nausea and vomiting (PONV), and poor pain control. We conducted a systematic review and meta-analysis to compare the safety and efficacy of total intravenous anesthesia (TIVA) with inhalation anesthesia in patients undergoing bariatric surgery. We searched MEDLINE, EMBASE, CENTRAL, and the Clinical Trials Registry database from inception to July 22, 2020. Primary outcomes were postoperative pain and PONV scores. Secondary outcomes included opioid requirements, intraoperative time, complications, and time to recovery. Grading of Recommendations Assessment, Development, and Evaluation framework was used to rate the certainty of evidence. Among 722 studies identified in our search, 7 randomized studies involving a total of 682 patients met the inclusion criteria. Bariatric surgery with TIVA resulted in a lower incidence of nausea (relative risk [RR], 0.54; 95% CI, 0.31-0.94; P = 0.03; moderate certainty) and vomiting (RR, 0.31; 95% CI, 0.13-0.74; P = 0.008; moderate certainty). There was no difference in postoperative pain at 30 minutes, 1 hour, or 24 hours, or in postoperative opioid requirements. Patients undergoing bariatric surgery with TIVA had significantly lower incidence of PONV but no difference in postoperative pain when TIVA was compared to inhalation anesthesia techniques. These benefits should be considered in order to improve the quality of care and enhance recovery for the bariatric population, who are at an increased baseline risk of perioperative complications. Future adequately powered randomized controlled trials are needed to compare the efficacy of the anesthesia regimens in patients undergoing bariatric surgery.

Benefits of Transversus Abdominis Plane Block on Postoperative Analgesia after Bariatric Surgery: A Systematic Review and Meta-Analysis.

BACKGROUND: Patients undergoing bariatric surgery present unique analgesic challenges, including poorly controlled pain, increased prevalence of obstructive sleep apnea, and opioid-induced respiratory depression. The transversus abdominis plane (TAP) has been demonstrated to be a safe and effective component of multimodal analgesia for a variety of abdominal surgeries. OBJECTIVE: To determine the benefits of the TAP block on postoperative analgesia and recovery in patients undergoing bariatric surgery. STUDY DESIGN: Systematic review and meta-analysis of randomized controlled trials (RCTs) and non-randomized studies. METHODS: We conducted a comprehensive search of MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) databases from inception to April 2020 for studies using TAP block in bariatric surgeries and reporting postoperative pain, opioid consumption, and recovery-related outcomes. Primary outcomes included postoperative pain scores, opioid consumption, and recovery-related outcomes (e.g., length of stay, time to ambulation). Outcomes were pooled using random effects model and reported as relative risks (RR) or mean differences (MD) with 95% confidence intervals (CI). RESULTS: Twenty-one studies (15 RCTs [n = 1410] and 6 nonrandomized studies [n = 1959]) were included. Among RCTs, the TAP block group required fewer opioid rescues (RR 0.28; 95% CI 0.18 to 0.42, P < 0.001) (moderate quality); reduced total opioid use over 24 hours (MD -8.33; 95% CI -14.78 to -1.89, P = 0.01); decreased time to ambulation (MD -1.12 hours; 95% CI -1.50 to -0.73, P < 0.001) (high quality); and had significantly lower pain scores at 6 hours (MD -1.52; 95% CI -1.90 to -1.13, P < 0.01) and 12 hours (MD -0.95; 95% CI -1.34 to -0.56, P < 0.001) on a 0-10 pain scale (moderate quality). No difference was observed for nausea and vomiting, or hospital length of stay. Meta-analyzed outcomes from observational studies supported these results, suggesting decreased postoperative pain and opioid consumption. LIMITATIONS: Studies varied with respect to type of surgery and components of comparator multimodal analgesia, likely contributing to heterogeneity. Subgroup analyses by type of comparator group were conducted to address these differences. We were unable to extract data from all trials included due to variability in outcomes reporting, such as non-opioid drugs for postoperative pain management or invalid dosages. Pain-related outcomes may be affected by operative differences leading to variation in visceral pain. Observational studies have their inherent limitations, such as confounding due to lack of participant randomization and intervention blinding, potentially affecting subjective outcomes, such as pain scores, as well as provider-dependent outcomes, such as hospital length of stay. Lastly, there was significant variation of TAP block technique across all studies. CONCLUSION: TAP block is an effective, safe modality that can be performed under anesthesia. It decreases pain, opioid use, and time to ambulation after bariatric surgeries and should be considered in multimodal analgesia for enhanced recovery in this high-risk surgical population.

The role of bariatric surgery on kidney transplantation: A systematic review and meta-analysis.

INTRODUCTION: Obesity (body mass index [BMI] >35 kg/m2) remains a relative contraindication for kidney transplant, while patients after kidney transplantation (KTX) are predisposed to obesity. The present study aims to investigate the role of bariatric surgery in improving transplant candidacy in patients prior to KTX, as well its safety and efficacy in KTX patients postoperatively. METHODS: A systematic search was conducted up to March 2020. Both comparative and non-comparative studies investigating the role of bariatric surgery before or after KTX were considered. Outcomes included change in BMI, rates of mortality and complications, and the rate of patients who underwent KTX following bariatric surgery. Pooled estimates were calculated using the random effects meta-analysis of proportions. RESULTS: Twenty-one studies were eligible for final review; 11 studies investigated the role of bariatric surgery before KTX. The weighted mean BMI was 43.4 (5.7) kg/m2 at baseline and 33.9 (6.3) kg/m2 at 29.1 months followup. After bariatric surgery, 83% (95% confidence interval [CI] 57-99) were successfully listed for KTX and 83% (95% CI 65-97) of patients subsequently received successful KTX. Ten studies investigated the role of bariatric surgery after kidney transplant. Weighted mean baseline BMI was 43.8 (2.2) kg/m2 and mean BMI at 19.5 months followup was 34.2 (6.7) kg/m2. Overall, all-cause 30-day mortality was 0.5% for both those who underwent bariatric surgery before or after receiving a KTX. The results of this study are limited by the inclusion of only non-randomized studies, limited followup, and high heterogeneity. CONCLUSIONS: Bariatric surgery may be safe and effective in reducing weight to improve KTX candidacy in patients with severe obesity and can also be used safely following KTX.

CCAAT enhancer binding protein α suppresses proliferation, metastasis, and epithelial-mesenchymal transition of ovarian cancer cells via suppressing the Wnt/ß-catenin signaling.

CCAAT enhancer-binding protein alpha (CEBPA, also known as C/EBPα) is a transcription factor that plays an essential role in regulating terminal differentiation and cell proliferation of many tissues. The objective of this study was to explore the potential function of CEBPA in ovarian cancer. The expression of CEBPA in ovarian cancer samples and adjacent normal tissues was evaluated by qRT-PCR. The putative role of CEBPA in ovarian cancer cells was evaluated by immunohistochemistry, western blot, cell viability assay, BrdU incorporation assay, soft agar colony formation assay, Transwell cell migration and invasion assay, tumor xenograft formation, and lung metastasis model. We found that CEBPA was downregulated in ovarian cancer samples and predicted a poor prognosis. CRISPR/Cas9-mediated CEBPA knockout promoted proliferation, anchorage-independent growth, migration, invasion, and EMT of ovarian cancer cells, while enforced CEPBA expression suppressed proliferation, anchorage-independent growth, migration, invasion, EMT, tumor xenograft growth, and lung metastasis of ovarian cancer cells. Furthermore, we found that the knockout of CEBPA activated Wnt/ß-catenin signaling in ovarian cancer cells, while CEBPA overexpression suppressed Wnt/ß-catenin activation. Our data indicated that CEBPA acted as a tumor suppressor in ovarian cancer, and might be a potential prognostic marker for ovarian cancer treatment.