FUS Selectively Facilitates circRNAs Packing into Small Extracellular Vesicles within Hypoxia Neuron.

Small extracellular vesicles (sEVs) contain abundant circular RNAs (circRNAs) and are involved in cellular processes, particularly hypoxia. However, the process that packaging of circRNAs into neuronal sEVs under hypoxia is unclear. This study revealed the spatial mechanism of the Fused in Sarcoma protein (FUS) that facilitates the loading of functional circRNAs into sEVs in hypoxia neurons. It is found that FUS translocated from the nucleus to the cytoplasm and is more enriched in hypoxic neuronal sEVs than in normal sEVs. Cytoplasmic FUS formed aggregates with the sEVs marker protein CD63 in cytoplasmic stress granules (SGs) under hypoxic stress. Meanwhile, cytoplasmic FUS recruited of functional cytoplasmic circRNAs to SGs. Upon relief of hypoxic stress and degradation of SGs, cytoplasmic FUS is transported with those circRNAs from SGs to sEVs. Validation of FUS knockout dramatically reduced the recruitment of circRNAs from SGs and led to low circRNA loading in sEVs, which is also confirmed by the accumulation of circRNAs in the cytoplasm. Furthermore, it is showed that the FUS Zf_RanBP domain regulates the transport of circRNAs to sEVs by interacting with hypoxic circRNAs in SGs. Overall, these findings have revealed a FUS-mediated transport mechanism of hypoxia-related cytoplasmic circRNAs loaded into sEVs under hypoxic conditions.

Sandblasting increases the microtensile bond strength between resin and sclerotic dentin in noncarious cervical lesions.

PURPOSE: To evaluate the effect of sandblasting on the microtensile strength between sclerotic dentin and resin composite. METHODS: 32 premolars with noncarious cervical lesions (NCCLs) were collected, and the teeth were randomly assigned to the control group (C group) and the sandblasted group (S group). Teeth in the S group were sandblasted with 110 µm Al2O3 particles at a pressure of 75 psi, while those in the C group received no further treatment. The characteristics of the tooth surface were observed by scanning electron microscopy (SEM), and the relative area of open dentin tubules (OTs) was calculated by IPP6.0 software. Surface roughness (Ra) was also assessed. The noncarious cervical lesions of all teeth were restored with a resin composite and subsequently sectioned into sticks to measure the microtensile bond strength (µTBS). RESULTS: The mean ± SD µTBS (in MPa) of the sandblasted group was 17.9 ± 0.69 and 14.23 ± 0.44 in the control group (P< 0.05). The relative area of OTs at the gingival wall of the sandblasted group was 69.74 ± 5.23%, and 47.24 ± 7.67% in the control group (P< 0.05). The average surface roughness (µm) was 1.01 ± 0.05 in the sandblasted group and 0.16 ± 0.03 in the control group. Sandblasting could increase the bond strength of sclerotic dentin and resin restorations. CLINICAL SIGNIFICANCE: After sandblasting, the microtensile strength of sclerotic dentin on the surface of noncarious cervical lesions increased, prolonging the resin adhesion longevity. Sandblasting could also alleviate the pain of patients during the treatment process and achieve a minimally invasive treatment.

Selenium-Enriched Cardamine violifolia Alleviates LPS-Induced Hepatic Damage and Inflammation by Suppressing TLR4/NODs-Necroptosis Signal Axes in Piglets.

Selenium-enriched Cardamine violifolia (SEC), a cruciferous plant, exerts excellent antioxidant and anti-inflammatory capacity, but its effect on hepatic function is unclear. This study investigated the effect and potential mechanism of SEC on hepatic injury induced by lipopolysaccharide (LPS). Twenty-four weaned piglets were randomly allotted to treatment with SEC (0.3 mg/kg Se) and/or LPS (100 µg/kg). After 28 days of the trial, pigs were injected with LPS to induce hepatic injury. These results indicated that SEC supplementation attenuated LPS-induced hepatic morphological injury and reduced aspartate aminotransferase (AST) and alkaline phosphatase (ALP) activities in plasma. SEC also inhibited the expression of pro-inflammatory cytokines such as interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF-α) after the LPS challenge. In addition, SEC improved hepatic antioxidant capacity via enhancing glutathione peroxidase (GSH-Px) activity and decreasing malondialdehyde (MDA) concentration. Moreover, SEC downregulated the mRNA expression of hepatic myeloid differentiation factor 88 (MyD88) and nucleotide-binding oligomerization domain proteins 1 (NOD1) and its adaptor molecule receptor interacting protein kinase 2 (RIPK2). SEC also alleviated LPS-induced hepatic necroptosis by inhibiting RIPK1, RIPK3, and mixed-lineage kinase domain-like (MLKL) expression. These data suggest that SEC potentially mitigates LPS-induced hepatic injury via inhibiting Toll-like receptor 4 (TLR4)/NOD2 and necroptosis signaling pathways in weaned piglets.

Bonding effect of a Zr/Si coating prepared on zirconia using a sol-gel method.

STATEMENT OF PROBLEM: Zirconia has been widely used as a dental prosthetic material. However, bonding to zirconia is challenging, and whether a Zr/Si coating would improve bonding is unclear. PURPOSE: The purpose of this in vitro study was to prepare a Zr/Si coating on zirconia ceramics using a sol-gel method and to determine whether the bonding to resin is improved. MATERIAL AND METHODS: Presintered zirconia specimens were prepared and divided into 5 groups: 4 experimental groups with ratios of the binary sol-gel precursor (zirconium oxychloride/tetraethoxysilane) set as 2:1 (Z2), 1:1 (Z1), 0.5:1 (Z0.5), and 0.25:1 (Z0.25) and Group C as the control group. In addition to surface roughness measurements, scanning electron microscopy (SEM), energy dispersion spectroscopy (EDS), and X-ray diffraction (XRD) were carried out to characterize the surface. Each group was divided into 2 subgroups according to whether a silane coupling agent was applied. Half of the bond specimens were stored in deionized water for 24 hours; the remaining half were aged using 5000 thermocycles. The shear bond strength (SBS) of resin bonded to specimens was tested for the initial and durable bond strength, and the bonding interface was also observed by SEM after debonding. Data were subjected to 1-way ANOVA and the post hoc Tukey honestly significant difference test (α=.05). RESULTS: The Zr/Si coating formed on zirconia ceramics. Z0.5 had the greatest mean ±standard deviation roughness (2.13 ±0.15 µm) and had the highest silicon content (21.7 ±0.21%). t-ZrO2, m-ZrO2, c-SiO2, and ZrSiO4 were detected by XRD in Z1. The SBS values were decreased by aging but were significantly increased by Zr/Si coating, especially for Z0.5, with the application of silane (initial: 22.92 ±2.79 MPa; aged: 9.91 ±0.92 MPa). CONCLUSIONS: The Zr/Si coating significantly improved the initial and aged bond strength, and the optimal Zr/Si ratio of the sol-gel appeared to be 0.5:1.

Application of opioid-free general anesthesia for gynecological laparoscopic surgery under ERAS protocol: a non-inferiority randomized controlled trial.

BACKGROUND: Enhanced recovery after surgery (ERAS) is now widely used in various surgical fields including gynecological laparoscopic surgery, but the advantages of opioid-free anesthesia (OFA) in gynecological laparoscopic surgery under ERAS protocol are inexact. AIMS: This study aims to assess the effectiveness and feasibility of OFA technique versus traditional opioid-based anesthesia (OA) technique in gynecological laparoscopic surgery under ERAS. METHODS: Adult female patients aged 18 ~ 65 years old undergoing gynecological laparoscopic surgery were randomly divided into OFA group (Group OFA, n = 39) with esketamine and dexmedetomidine or OA group (Group OA, n = 38) with sufentanil and remifentanil. All patients adopted ERAS protocol. The primary outcome was the area under the curve (AUC) of Visual Analogue Scale (VAS) scores (AUCVAS) postoperatively. Secondary outcomes included intraoperative hemodynamic variables, awakening and orientation recovery times, number of postoperative rescue analgesia required, incidence of postoperative nausea and vomiting (PONV) and Pittsburgh Sleep Quality Index (PSQI) perioperatively. RESULTS: AUCVAS was (Group OFA, 16.72 ± 2.50) vs (Group OA, 15.99 ± 2.72) (p = 0.223). No difference was found in the number of rescue analgesia required (p = 0.352). There were no between-group differences in mean arterial pressure (MAP) and heart rate (HR) (p = 0.211 and 0.659, respectively) except MAP at time of surgical incision immediately [(Group OFA, 84.38 ± 11.08) vs. (Group OA, 79.00 ± 8.92), p = 0.022]. Times of awakening and orientation recovery in group OFA (14.54 ± 4.22 and 20.69 ± 4.92, respectively) were both longer than which in group OA (12.63 ± 3.59 and 18.45 ± 4.08, respectively) (p = 0.036 and 0.033, respectively). The incidence of PONV in group OFA (10.1%) was lower than that in group OA (28.9%) significantly (p = 0.027). The postoperative PSQI was lower than the preoperative one in group OFA (p = 0.013). CONCLUSION: In gynecological laparoscopic surgery under ERAS protocol, OFA technique is non-inferior to OA technique in analgesic effect and intraoperative anesthesia stability. Although awakening and orientation recovery times were prolonged compared to OA, OFA had lower incidence of PONV and improved postoperative sleep quality. TRIAL REGISTRATION: ChiCTR2100052761, 05/11/2021.

A historical review of performance appraisal of public hospitals in China from the perspective of historical institutionalism.

The government performance appraisal of public hospitals serves as an effective management tool to promote high-quality development. It is also an important means of realizing the "Healthy China" initiative. Since the founding of the People's Republic of China, changes in performance appraisal have been divided into the following four periods: the early stage of performance appraisal (1949-1977), the exploration period (1978-2008), the development period (2009-2018), and the integration period (2019-present). This clarifies the regional practice of public hospital performance and identifies the institutional factors of the evolution. It also demonstrates that administrative forces, market-driving forces, and mission-driving forces combine to bring about change in the public hospital performance appraisal system. However, problems such as insufficient application of performance appraisal and coordination between health administrative departments and medical insurance departments still loom large.

Comparative Effects of Dexmedetomidine and Midazolam on Dreaming of Patients Undergoing Flexible Bronchoscopy During General Anesthesia.

BACKGROUND The aim of this study was to compare the effects of dexmedetomidine versus midazolam on the dreaming of patients undergoing flexible bronchoscopy during general anesthesia. MATERIAL AND METHODS Patients undergoing flexible bronchoscopy under general anesthesia were randomly divided into a dexmedetomidine group (Group D, n=40) and a midazolam group (Group M, n=40). In group D, patients received 0.5 µg/kg dexmedetomidine and in group M patients received 0.05 mg/kg midazolam intravenously 10 min prior to induction. After bronchoscopy and recovery, a modified Brice questionnaire was used to immediately evaluate the incidence of dreaming of patients. Dreamers were required to complete a 5-point Likert scale survey regarding the contents of their dreams (emotion, voice and movement, memorability) if dreaming was reported. Ramsay Sedation Scale score (Ramsay score) and Visual Analogue Scale (VAS) score were assessed and recorded. RESULTS Patients in group D had higher Ramsay scores and VAS scores (2.9±0.6 and 79.4±4.0, respectively) than group M (2.4±0.7 and 75.0±6.0, respectively), with a statistically significant difference (P<0.05) between groups. The incidence and memorability of dreaming were significantly lower in group D (17.5%) than group M (37.5%, P<0.05), whereas no significant difference was found in emotion, voice, and movement scores of dreaming. CONCLUSIONS Compared to midazolam, pre-injection of dexmedetomidine before induction significantly decreased the incidence of dreaming in patients undergoing flexible bronchoscopy during general anesthesia, without producing undesirable effects on the content of dreams (most of them were pleasant), produces a more efficacious sedation effect during the recovery period and improves the comfort level and satisfaction of patients.

A novel method of Uniblocker placement: extraluminal technique supported by trachea length measurement: A CONSORT-compliant article.

BACKGROUND: The use of bronchial blockers has been increased for one-lung ventilation; however, the placement of bronchial blockers is time consuming. The objective of this study was to compare the novel extraluminal technique of Uniblocker placement supported by trachea length measurement on computerized tomography images with conventional intraluminal Uniblocker placement method. METHODS: Seventy adult patients undergoing left side thoracic surgery were included in the study. All the patients were randomly assigned to one of two groups: conventional intraluminal intubation group (CV-IN group, n = 35) or extraluminal CT guided group (CT-EX group, n = 35). The primary endpoints were the optimal positions of Uniblocker and the injuries of bronchi and carina. The secondary outcomes included the time of Uniblocker placement, the adequacy of lung collapse, the incidences of Uniblocker displacement, sore throat, and hoarseness postoperative. RESULTS: In the CV-IN group, 19 of 35 Uniblockers went to the left main-stem bronchus on the initial blind insertion and 15 of 35 Uniblockers were considered as in optimal depth, whereas in the CT-EX group, 32 of 35 Uniblockers went to the left main-stem bronchus on the initial blind insertion and 31 of 35 Uniblockers were considered as in optimal depth (P < .01). The incidence of bronchi and carina injuries was obviously lower in the CT-EX group (occurred in 1 of 35 cases) than that in the CV-IN group (occurred in 8 of 35 cases) (P < .05). The time of Uniblocker placement took 145.4 s in the CV-IN group and 85.4 s in the CT-EX group (P < .01). The malpositions of Uniblocker, the degree of pulmonary collapse and the adverse events postoperative such as sore throat and hoarseness were not significantly different between the two groups (P > .05). CONCLUSION: The novel extraluminal technique of Uniblocker placement supported by trachea length measurement on computerized tomography images was proved to be more rapid, more accurate and less complications than conventional intraluminal Uniblocker placement method.

Comparative effects of fentanyl versus sufentanil on cerebral oxygen saturation and postoperative cognitive function in elderly patients undergoing open surgery.

This study was aimed to systematically evaluate the effects of fentanyl and sufentanil on intraoperative cerebral oxygen saturation changes and postoperative cognitive function in elderly patients undergoing open surgery. Ninety-six elderly patients who had undergone open surgery under general anesthesia were randomly divided into fentanyl group (F group, anesthesia by fentanyl, 4 g/kg) and sufentanil group (S group, anesthesia by sufentanil, 0.4 µg/kg). There were no significant differences between the F group and S group in the general characteristics of patients. Compared to the F group, the S group had a better effect on suppressing the stress response, maintaining a stable hemodynamic status and achieving better anesthesia effects. The anesthesia recovery time of the S group was significantly shorter than that of the F group. There was no significant difference between the two groups in the intraoperative and postoperative agitation. Patient's waking time and extubation time were significantly shorter in the S group than the F group. The VAS scores in the S group were significantly lower than those in the F group at each time point. The Ramsay scores in the S group were significantly higher than those in the F group at each time point. The cerebral oxygen saturation (SctO2) levels in both groups were significantly increased following anesthesia induction and intubation compared to that of the awake state (P < 0.05), and SctO2 was significantly decreased during the surgery in both groups. The changes in SctO2 levels were not significantly different between the two groups (P > 0.05). The SctO2 level was significantly higher during surgery than that after intubation. Compared with the F group, the relative value of SctO2 decline in the S group was smaller. Compared to the day before surgery, the Montreal Cognitive Assessment (MoCA) scores of both groups were significantly reduced after surgery. At 1 day post-surgery, the MoCA scores of the S group were significantly higher and the incidence of postoperative cognitive dysfunction (POCD) was significantly lower compared to the F group. POCD occurred in three patients (6.2%) in the S group, and the ratio was significantly lower than that in the F group (11.9%) (P < 0.05). It showed a consistent trend with the SctO2 status during the surgery. The relative value of SctO2 decline in the S group was significantly smaller than that in the F group. The reduction of cognitive function in the S group was significantly lower than that in the F group. These results indicate that the changes in SctO2 are a good prediction of the incidence of POCD.

The effect of dexmedetomidine in coracoid approach brachial plexus block under dual stimulation.

BACKGROUND: Coracoid approach brachial plexus block (CABPB) is safe and effective for clinical anesthesia and analgesia. Dual stimulation can enhance the block effect of CABPB when using nerve stimulator. Dexmedetomidine is a highly selective α-adrenoceptor agonist and it can prolong the duration of anesthesia when it is added into local anesthetics. The aim of this study was to assess the effects of dexmedetomidine on the duration of anesthesia and the effective postoperative analgesia time when it was mixed with ropivacaine for CABPB under dual stimulation. METHODS: A total of 60 patients were randomly assigned into 2 groups (groups D and C), 30 patients in each group. CABPB were guided by nerve stimulator under dual stimulation. Each patient received 40 mL of 0.375% ropivacaine (group C), or 40 mL of 0.375% ropivacaine mixed with 1 µg/kg dexmedetomidine (group D). The duration of anesthesia, the effective postoperative analgesia time, sensory and motor block onset time, visual analog scale (VAS), and the cumulative dose of rescue tramadol were recorded. RESULTS: Twenty-eight patients in each group were analyzed. The duration of anesthesia was longer in group D as compared with group C (759 vs 634 minutes, P < .05) and the effective postoperative analgesia time was longer in group D as compared with group C (986 vs 789 minutes, P < .05) too. The onset time of sensory and motor blocks were not significantly different between the 2 groups (P > .05). The VAS was similar in the 2 groups at 6 and 12 hours after block (P > .05), but it was lower in group D at 24 hours after block as compared to group C (P < .05). The cumulative dose of rescue tramadol during the first 48 hours postoperative period was significantly lower in group D as compared to group C (P < .05). No significant changes were observed in vital signs in either group. CONCLUSION: The addition of 1 µg/kg dexmedetomidine to ropivacaine extends the duration of anesthesia and the effective postoperative analgesia time for CABPB under dual stimulation. The VAS at 24 hours after block and the demand for rescue tramadol during the first 48 hours postoperative period are lower as well without side effects in the study group.(Registered in ClinicalTrials.gov id. NCT02961361).

Cuffed Versus Uncuffed Endotracheal Tubes in Pediatrics: A Meta-analysis.

BACKGROUND: Cuffed and uncuffed endotracheal tubes are commonly used for pediatric patients in surgery and emergency situations. It is still controversial which approach should be adopted. The purpose of the study was to compare the application of cuffed and uncuffed endotracheal tubes in pediatric patients. METHODS: We searched PubMed, Web of Science and Cochrane Library for clinical trials, which compared the two applications in children. The study characteristics and clinical data were summarized by two independent reviewers. Meta-analysis of the data was done using Revman 5.3 software. RESULTS: 6 studies with 4141 cases were included in this meta-analysis. The pooling analysis showed that more patients need tube changes in uncuffed than cuffed tubes (OR: 0.07, 95% CI: 0.05-0.10, P < 0.00001). However, there were no differences on intubation duration, reintubation occurrence, accidental extubation rate, croup occurrence and racemic epinephrine use during the intubation process. Also we didn't find any differences on laryngospasm and stridor occurrence after extubation. CONCLUSIONS: Our study demonstrated that uncuffed endotracheal tubes increased the need for tube changes. Other incidences or complications between the two groups had no differences. Cuffed tubes may be an optimal option for pediatric patients. But more trials are needed in the future.

Chemical and genetic inhibition of STAT3 sensitizes hepatocellular carcinoma cells to sorafenib induced cell death.

Hepatocellular carcinoma (HCC) has become the second leading cause of cancer related death, with an increasing death rate in recent years. For advanced HCC, sorafenib is the first-line FDA approved drug, with no more than 3 months' overall survival advantage. Recently, a novel strategy has been proposed to improve sorafenib efficacy through enhancing the ability of sorafenib to induce cell death. STAT3 plays a key role in cancer development and recurrence by promoting cell proliferation, survival and immune evasion through its well-established function as a transcription factor in cancer. Notably, STAT3 transcription activity, indicated by its phosphorylation on Y705 is heterogeneous in different liver cancer cell lines. And sorafenib attenuates STAT3 phosphorylation on Y705. However, the role of STAT3 in sorafenib induced cell death is still largely unknown. Here, we show that liver cancer cells also exhibit heterogeneous sensitivities to sorafenib induced cell death, which co-relates with the STAT3-Y705 phosphorylation levels and JAK1/2 expression levels in Hep3B, Huh7 and HepG2 cells. Furthermore, overexpression or knockdown of STAT3 could switch HCC cells between resistant and sensitive to sorafenib induced cell death, which could be partially due to its regulation on Mcl-1, an anti-apoptotic protein. Finally, both inhibitors of STAT3 SH2 domain (S3i-201) or STAT3 upstream kinases JAKs (JAK inhibitor I) could synergistically enhance sorafenib induced cell death. Taken together, these data strongly suggest that STAT3 is not only a downstream effector of sorafenib, but also a key regulator of cellular sensitivity to sorafenib induced cell death, which provide support for the notion to develop STAT3-targeting drugs to improve clinical efficacy of sorafenib in liver cancer.

Chest Computed Tomography Image for Accurately Predicting the Optimal Insertion Depth of Left-Sided Double-Lumen Tube.

OBJECTIVE: The main objective of this study was to assess the feasibility and accuracy of measuring the distance between the vocal cord and carina using chest computer tomography (CT) as a guide for the intubation of a left-sided double-lumen tube (LDLT). DESIGN: Single-center, prospective, randomized study. SETTING: Local hospital in China. PARTICIPANTS: Sixty adult patients undergoing elective thoracic surgery requiring an LDLT for one lung ventilation were enrolled in this study. INTERVENTIONS: Patients were randomly allocated to the following 2 groups: blind intubation group (B group, n = 30) or chest computed tomography-guided group (C group, n = 30). The placement of the LDLT was accomplished using 1 of the 2 intubation methods. After intubation, an independent anesthesiologist evaluated the position of the LDLT and carina and bronchial injuries using fiber optic bronchoscopy. The number of optimal positions, the time for LDLT intubation, the time for fiber optic bronchoscope confirmation, and carina and bronchial injuries were recorded. RESULTS: Sixteen of 30 intubations in the B group were in optimal position, whereas 27 of 30 intubations in the C group were in optimal position; the difference was statistically significant (p < 0.01). The time for intubation of the LDLT took 118.0 ± 26.2 seconds in the B group and 71.5 ± 8.7 seconds in the C group (p < 0.01). The time for position confirmation using fiber optic bronchoscope took 40.8 ± 15.8 seconds in the B group and 18.7 ± 7.9 seconds in the C group (p < 0.05). The incidences of carina and bronchial injuries were obviously lower in the C group (occurred in 3 of 30 cases) than in the B group (11 of 30 cases) p < 0.05. The incidences of postoperative sore throat and hoarseness showed no significant differences between the 2 groups (p > 0.05). CONCLUSION: This study demonstrated that the method of measuring the distance between the vocal cord and carina according to the chest CT as a guide for the intubation of LDLT is more effective and more accurate than the blind intubation method.

Role of positioning posterior cord on coracoid approach brachial plexus block guided by nerve stimulator: Compared with guided by ultrasound.

BACKGROUND: Coracoid approach is efficient and safe for brachial plexus block, and is guided by nerve stimulator or ultrasound in general. Many trials have proved that ultrasonic guidance was more efficacious than nerve stimulator guidance. We hypothesized that positioning posterior cord could enhance the anesthesia effect of coracoid approach brachial plexus block (CABPB) guided by nerve stimulator. METHODS: Eighty patients were randomized into 2 groups to receive CABPB with positioning posterior cord guided by nerve stimulator (group A) or CABPB guided by ultrasound (group B). Success rate, procedure time, and onset time of sensory or motor block were recorded. RESULTS: Success rate was similar in 2 groups (89.7% in group A vs 87.5% in group B, P > .05). Procedure time was longer in group A (8 minutes), as compared with group B (4 minutes; P < .05). The difference of onset time of sensory and motor block was not significant between the 2 groups. The onset time of sensory and motor block for musculocutaneous nerve was significantly shorter in group A, as compared with group B (P < .05). CONCLUSION: The 2 technologies are equivalent regarding success rate, safety, and onset time of sensory or motor block. Positioning posterior cord in CABPB guided by nerve stimulator is efficacious for upper extremity surgery.(URL: http://www.chictr.org.cn/listbycreater.aspx ID: ChiCTR-INR-16009091 DATE: 25/8/2016).

A multifaceted intervention to improve treatment with oral anticoagulants in atrial fibrillation (IMPACT-AF): an international, cluster-randomised trial.

BACKGROUND: Oral anticoagulation is underused in patients with atrial fibrillation. We assessed the impact of a multifaceted educational intervention, versus usual care, on oral anticoagulant use in patients with atrial fibrillation. METHODS: This study was a two-arm, prospective, international, cluster-randomised, controlled trial. Patients were included who had atrial fibrillation and an indication for oral anticoagulation. Clusters were randomised (1:1) to receive a quality improvement educational intervention (intervention group) or usual care (control group). Randomisation was carried out centrally, using the eClinicalOS electronic data capture system. The intervention involved education of providers and patients, with regular monitoring and feedback. The primary outcome was the change in the proportion of patients treated with oral anticoagulants from baseline assessment to evaluation at 1 year. The trial is registered at ClinicalTrials.gov, number NCT02082548. FINDINGS: 2281 patients from five countries (Argentina, n=343; Brazil, n=360; China, n=586; India, n=493; and Romania, n=499) were enrolled from 48 clusters between June 11, 2014, and Nov 13, 2016. Follow-up was at a median of 12·0 months (IQR 11·8-12·2). Oral anticoagulant use increased in the intervention group from 68% (804 of 1184 patients) at baseline to 80% (943 of 1184 patients) at 1 year (difference 12%), whereas in the control group it increased from 64% (703 of 1092 patients) at baseline to 67% (732 of 1092 patients) at 1 year (difference 3%). Absolute difference in the change between groups was 9·1% (95% CI 3·8-14·4); odds ratio of change in the use of oral anticoagulation between groups was 3·28 (95% CI 1·67-6·44; adjusted p value=0·0002). Kaplan-Meier estimates showed a reduction in the secondary outcome of stroke in the intervention versus control groups (HR 0·48, 95% CI 0·23-0·99; log-rank p value=0·0434). INTERPRETATION: A multifaceted and multilevel educational intervention, aimed to improve use of oral anticoagulation in patients with atrial fibrillation and at risk for stroke, resulted in a significant increase in the proportion of patients treated with oral anticoagulants. Such an intervention has the potential to improve stroke prevention around the world for patients with atrial fibrillation. FUNDING: Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, and Pfizer.

Regional differences in presentation and antithrombotic treatment of patients with atrial fibrillation: Baseline characteristics from a clustered randomized trial to IMProve treatment with AntiCoagulanTs in patients with atrial fibrillation (IMPACT-AF).

Atrial fibrillation (AF) is the most common sustained arrhythmia worldwide. However, there are few contemporary comparative data on AF from middle-income countries. METHODS: Baseline characteristics of the IMPACT-AF trial were analyzed to assess regional differences in presentation and antithrombotic treatment of AF from 5 middle-income countries (Argentina, Brazil, China, India, and Romania) and factors associated with antithrombotic treatment prescription. RESULTS: IMPACT-AF enrolled 2281 patients (69 ± 11 years, 47% women) at 48 sites. Overall, 66% of patients were on anticoagulation at baseline, ranging from 38% in China to 91% in Brazil. The top 3 reasons for not prescribing an anticoagulant were patient preference/refusal (26%); concomitant antiplatelet therapy (15%); and risks outweighing the benefits, as assessed by the physician (13%). In a multivariable model, the most significant factors associated with prescription of oral anticoagulants were no prior major bleeding (odds ratio [OR] = 4.34; 95% CI = 2.22-8.33), no alcohol abuse (OR = 2.27; 95% CI = 1.12-4.55), and history of rheumatic valvular heart disease (OR = 2.10; 95% CI = 1.36-3.26), with a strong predictive accuracy (c statistic = 0.85), whereas the most significant factors associated with prescription of a combination of oral anticoagulants and antiplatelet drugs were prior coronary revascularization (OR = 5.10; 95% CI = 2.88-9.05), prior myocardial infarction (OR = 2.24; 95% CI = 1.38-3.63), and no alcohol abuse (OR = 2.22; 95% CI = 1.11-4.55), with a good predictive accuracy (c statistic = 0.76). CONCLUSIONS: IMPACT-AF provides contemporary data from 5 middle-income countries regarding antithrombotic treatment of AF. Lack of prior major bleeding and coronary revascularization were the most important factors associated with prescription of oral anticoagulants and their combination with antiplatelet drugs, respectively.

Effects of patient load and travel distance on HIV transmission in rural China: Implications for treatment as prevention.

BACKGROUND: Sustained viral suppression through ART reduces sexual HIV transmission risk, but may require routine access to reliable and effective medical care which may be difficult to obtain in resource constrained areas. We investigated the roles of patient load and travel distance to HIV care clinic on transmission risk in HIV serodiscordant couples in Henan Province, China. METHODS: Cox proportional hazard models were used to compare HIV transmission events across couples living near, medium, or farther distances from their assigned HIV care clinics, as well as those attending clinics where clinicians bore high versus low patient loads. RESULTS: Most (84·4%) of the 3695 serodiscordant couples lived within 10 kilometers of their assigned HIV clinic, and most (73·5%) attended clinics with patient-to-provider ratios of at least 100:1. In adjusted Cox models, attending clinics where clinicians bore average patient loads of 100 or more elevated HIV transmission risk (aHR, 1·50, 95% CI, 1·00-4·84), an effect amplified in village tier clinics (aHR = 1·55; 95% CI, 1·23-6·78). Travel distance was associated with HIV transmission only after stratification; traveling medium distances to village clinics (5-10km) increased transmission risk (aHR = 1·83, 95% CI, 1·04-3·21) whereas traveling longer distances to township or county level clinics lowered transmission risk (aHR = 0·10, 95% CI, 0·01-0·75). CONCLUSION: Higher patient loads at HIV clinics was associated with risk of HIV transmission in our population, particularly at village level clinics. Farther travel distance had divergent effects based on clinic tier, suggesting unique mechanisms operating across levels of resource availability. The resource intensity of long-term HIV treatment may place significant strains on small rural clinics, for which investments in additional support staff or time-saving tools such as point-of-care laboratory testing may bring about impactful change in treatment outcomes.

A comparison of extraluminal and intraluminal use of the Uniblocker in left thoracic surgery: A CONSORT-compliant article.

BACKGROUND: The aim of this study was to assess the feasibility and safety issues concerning extraluminal use of the Uniblocker for one-lung ventilation (OLV) in the left thoracic surgery. METHODS: Forty patients undergoing elective left thoracic surgery were included in this study, and all patients were randomly allocated to extraluminal use of Uniblocker group (E group, n = 20) or intraluminal use of Uniblocker group (I group, n = 20). Time for intubation, time for verification of the correct position of Uniblocker, incidence of Uniblocker displacement, index of pulmonary collapse, mean arterial pressure, heart rate, peak airway pressure, oxygen saturation in two-lung ventilation, and 30 minutes after OLV, bronchial damage after OLV, sore throat, and hoarseness postoperative were recorded. RESULTS: The time for positioning Uniblocker was 112.6 ±â€Š31.2 seconds in intraluminal use group, whereas the time for positioning Uniblocker was significantly shorter in extraluminal use group (63.4 ±â€Š15.8 seconds). The incidence of main bronchial injury, the time of intubation, the incidence of Uniblocker malposition after initial placement, the time of OLV, the degree of pulmonary collapse, mean arterial pressure, heart rate, peak airway pressure, oxygen saturation in two-lung ventilation, and 30 minutes after OLV, the incidence of sore throat and hoarseness postoperative have no statistical significance (P > .05). CONCLUSION: Extraluminal use of the Uniblocker was proved to be a more rapid and more accurate method than conventional intraluminal use of the Uniblocker for OLV in left thoracic surgery.

Slit2/Robo1 Mediation of Synaptic Plasticity Contributes to Bone Cancer Pain.

Synaptic plasticity is fundamental to spinal sensitivity of bone cancer pain. Here, we have shown that excitatory synaptogenesis contributes to bone cancer pain. New synapse formation requires neurite outgrowth and an interaction between axons and dendrites, accompanied by the appositional organization of presynaptic and postsynaptic specializations. We have shown that Slit2, Robo1, and RhoA act as such cues that promote neurite outgrowth and guide the axon for synapse formation. Sarcoma inoculation induces excitatory synaptogenesis and bone cancer pain which are reversed by Slit2 knockdown but aggravated by Robo1 knockdown. Synaptogenesis of cultured neurons are inhibited by Slit2 knockdown but enhanced by Robo1 knockdown. Sarcoma implantation induces an increase in Slit2 and decreases Robo1 and RhoA, while Slit2 knockdown results in an increase of Robo1 and RhoA. These results have demonstrated a molecular mechanism of synaptogenesis in bone cancer pain.