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Brain-derived neurotrophic factor (BDNF) regulates neuronal plasticity by targeting the tyrosine kinase B receptor (TrkB) receptor, but limited researches concentrate on the role of BDNF/TrkB signaling in vestibular compensation. In this study, rats with unilateral vestibular dysfunction were established by unilateral labyrinthectomy (UL) and infusion with siBDNF or 7, 8-Dihydroxyflavone (7,8-DHF, a TrkB receptor agonist). The behavioral scores of rats with vestibular deficits were determined and the rotarod test was performed after UL. BDNF and TrkB levels after UL were determined by western blot and quantitative reverse transcription PCR (qRT-PCR). 5-bromo-2ʹ-deoxyuridine (BrdU)-positive cells (newly generated cells) and GAD67-positive cells (GABAergic neurons) were identified by immunohistochemistry. Glial fibrillary acidic protein (GFAP) (astrocyte marker)-positive cells were identified and GABA type A receptor (GABAAR) expression was detected by immunofluorescence. We found that after UL, BDNF and TrkB levels were up-regulated with a maximum value at 4 h, and then progressively down-regulated during 4 h ~ 7 d. Blocking BDNF/TrkB signaling inhibited the recovery from vestibular deficits, decreased the numbers of newly generated cells and astrocytes in medial vestibular nucleus (MVN), inferior vestibular nerve (IVN), superior vestibular nerve (SVN) and lateral vestibular nucleus (LVN), and disrupted the balances of GABAergic neurons and GABAAR expressions in the left (lesioned) side and right (intact) side of MVN, whereas activation of BDNF/TrkB signaling caused opposite results. The current study indicated that BDNF/TrkB signaling avails vestibular compensation, depending on the number of newly generated cells and astrocytes, the rebalance of GABAergic neurons, and GABAAR expression in bilateral MVN.

BackgroundIn this study, we proposed to use MR images at L1-L2 (lumbar) intervertebral disc level to measure abdominal fat area in patients with obesity. The quantitative results would provide evidence for the individualized assessment of the severity of obesity.MethodsAll patients in the IRB-approved database of Beijing Friendship Hospital who underwent bariatric surgery between November 2017 and November 2019 were recruited. We retrospectively reviewed upper abdominal magnetic resonance (MR) data before surgery. We analyzed the correlation and consistency of the area of abdominal subcutaneous adipose tissue (ASAT) and visceral adipose tissue (VAT) measured at the L1-L2 and L2-L3 levels on MR images. We randomly distributed the cases into prediction model training data and testing data at a ratio of 7:3.ResultsTwo hundred and forty-five subjects were included. The ASAT and VAT results within the L1-L2 and L2-L3 levels were very similar and highly correlated (maleASAT: r=0.98, femaleASAT: r=0.93; maleVAT: r=0.91, femaleVAT: r=0.88). There was no substantial systematic deviation among the results at the two levels, except for the ASAT results in males. The intraclass correlation coefficients (ICCs) were 0.91 and 0.93 for maleASAT and femaleASAT, and 0.88 and 0.87 for maleVAT and femaleVAT, respectively. The ASAT/VAT area at the L2-L3 level was well predicted. The coefficient β of linear regression that predicted L2-L3 ASAT from L1-L2 ASAT was 1.11 for males and 0.99 for females. The R-squares were 0.97 and 0.91, respectively. For VAT prediction, the coefficient β was 1.02 for males and 0.96 for females. The R-squares were 0.82 and 0.77, respectively.ConclusionFor patients with obesity, the L1-L2 intervertebral disc level can be used as the substitution of L2-L3 level in abdominal fat measurement.

Objective Delayed thrombolytic therapy with recombinant tissue plasminogen activator (tPA) may exacerbate blood‐brain barrier (BBB) breakdown after ischemic stroke and lead to catastrophic hemorrhagic transformation (HT). Rosiglitazone(RSG), a widely used antidiabetic drug that activates peroxisome proliferator‐activated receptor‐γ (PPAR‐γ), has been shown to protect against cerebral ischemia through promoting poststroke microglial polarization toward the beneficial anti‐inflammatory phenotype. However, whether RSG can alleviate HT after delayed tPA treatment remains unknown. In this study, we sort to examine the role of RSG on tPA‐induced HT after stroke. Methods and results We used the murine suture middle cerebral artery occlusion (MCAO) models of stroke followed by delayed administration of tPA (10 mg/kg, 2 hours after suture occlusion) to investigate the therapeutic potential of RSG against tPA‐induced HT. When RSG(6 mg/kg) was intraperitoneally administered 1 hour before MCAO in tPA‐treated MCAO mice, HT in the ischemic territory was significantly attenuated 1 day after stroke. In the tPA‐treated MCAO mice, we found RSG significantly mitigated BBB disruption and hemorrhage development compared to tPA‐alone‐treated stroke mice. Using flow cytometry and immunostaining, we confirmed that the expression of CD206 was significantly upregulated while the expression of iNOS was down‐regulated in microglia of the RSG‐treated mice. We further found that the expression of Arg‐1 was also upregulated in those tPA and RSG‐treated stroke mice and the protection against tPA‐induced HT and BBB disruption in these mice were abolished in the presence of PPAR‐γ antagonist GW9662 (4 mg/kg, 1 hour before dMCAO through intraperitoneal injection). Conclusions RSG treatment protects against BBB damage and ameliorates HT in delayed tPA‐treated stroke mice by activating PPAR‐γ and favoring microglial polarization toward anti‐inflammatory phenotype.

Diabetic nephropathy (DN) is one of the most serious and major renal complications of diabetes. Previously, Six-transmembrane Protein of Prostate 2 (STAMP2) was reported to contribute to nutritional stress. The purpose of this study is to investigate whether overexpression of STAMP2 attenuates diabetic renal injuries in DN rats. We induced the DN rat model by high-fat diet and low-dose streptozotocin and evaluated the metabolite and urine albumin/creatinine. Recombinant adeno-associated virus vectors were injected for overexpression of STAMP2. Pathophysiologic and ultrastructure features of DN by histochemical stain and transmission electron microscope, autophagy-related proteins and signaling pathway by western blotting were assessed. We found the expression of STAMP2 was decreased and autophagy was blunted in DN rat kidneys. Overexpressing STAMP2 significantly ameliorated metabolic disturbance, insulin resistance, and specifically restoring diabetic renal injury. Furthermore, overexpressing STAMP2 improved the autophagy deficiency in DN rats, as revealed by changes in the expressions of Beclin1, p62, and LC3. Furthermore, STAMP2 overexpressing promoted autophagy by inhibiting the mTOR and activating the AMPK/SIRT1 signaling pathway. Our results suggested that STAMP2 overexpression attenuated renal injuries via upregulating autophagy in DN rats. STAMP2 overexpressing promoted autophagy may been involved with inhibition of the mTOR/ULK1 and activation of the AMPK/SIRT1 signaling pathway.

Background Intercostal chest catheter (ICC) insertion is a common hospital procedure with attendant risks including life‐threatening complications such as pneumothorax and visceral damage. Aim To investigate the effect of a quality improvement (QI) initiative on complications associated with inpatient thoracostomy tube insertion. Methods Following an audit of ICC complications in inpatients over a 2‐year period we implemented a comprehensive QI programme. This involved formal training in and mandatory use of thoracic ultrasound, standardisation of the procedure and documentation, a dedicated procedure room with nurses trained in assisting ICC insertion and senior supervision for medical staff. An audit over 2 years post‐implementation of the QI protocol was compared with pre‐implementation results. Results A total of 103 cases were reviewed pre‐implementation and 105 cases were reviewed post‐implementation of the QI programme. All procedures following the QI initiative were image guided compared to 23.3% of cases pre‐implementation. The rate of developing a pneumothorax requiring intervention post‐implementation was less than pre‐implementation (1.9% vs 5.8% (P = 0.023). Post‐implementation, there were no instances of dry taps, viscera perforation, clinically significant bleeding or wrong side ICC insertion and documentation improved. Conclusion QI initiative applied to thoracostomy tube insertion in hospital inpatients can reduce complications and improve procedure documentation.

Depression is increasingly recognized as an inflammatory disease, with inflammatory crosstalk in the brain contributing its pathogenesis. Life stresses may up-regulate inflammatory processes and promote depression. Although cytokines are central to stress-related immune responses, their contribution to stress-induced depression remains unclear. Here, we used unpredictable chronic mild stress (UCMS) to induce depression-like behaviors in mice, as assessed through a suite of behavioral tests. C-X-C motif chemokine ligand 1 (CXCL1)-related molecular networks responsible for depression-like behaviors were assessed through intrahippocampal microinjection of lenti-CXCL1, the antidepressant fluoxetine, the C-X-C motif chemokine receptor 2 (CXCR2) inhibitor SB265610, and the glycogen synthase kinase-3β (GSK3β) inhibitor AR-A014418. Modulation of apoptosis-related pathways and neuronal plasticity were assessed via quantification of cleaved caspase-3, B-cell lymphoma 2-associated X protein, cAMP response element-binding protein (CREB), and brain-derived neurotrophic factor (BDNF) protein expression. CXCL1/CXCL2 expression was correlated with depression-like behaviors in response to chronic stress or antidepressant treatment in the UCMS depression model. Intrahippocampal microinjection of lenti-CXCL1 increased depression-like behaviors, activated GSK3β, increased apoptosis pathways, suppressed CREB activation, and decreased BDNF. Administration of the selective GSK3β inhibitor AR-A014418 abolished the effects of lenti-CXCL1, and the CXCR2 inhibitor SB265610 prevented chronic stress-induced depression-like behaviors, inhibited GSK3β activity, blocked apoptosis pathways, and restored BDNF expression. The CXCL1/CXCR2 axis appears to play a critical role in stress-induced depression, and CXCR2 is a potential novel therapeutic target for patients with depression.-Chai, H.-H., Fu, X.-C., Ma, L., Sun, H.-T., Chen, G.-Z., Song, M.-Y., Chen, W.-X., Chen, Y.-S., Tan, M.-X., Guo, Y.-W., Li, S.-P. The chemokine CXCL1 and its receptor CXCR2 contribute to chronic stress-induced depression in mice.

The anti‐inflammatory effect of sinapic acid (SA) has been reported in several studies. However, whether SA has the same effect on osteoarthritis (OA) has yet to be clearly elucidated. We designed a series of in vitro and in vivo procedures to verify the above conjecture. Compared with controls, SA‐pretreated human chondrocytes showed lower levels of interleukin (IL)‐1β‐induced IL‐6, prostaglandin E2 (PGE2), nitric oxide (NO) and tumour necrosis factor‐α (TNF‐α) in vitro. Meanwhile, SA could also reverse the degradation of type II collage and aggrecan, as well as the overproduction of matrix metalloproteinase‐9 (MMP‐9) and matrix metalloproteinase‐13 (MMP‐13), inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)‐2 and a disintegrin and metalloproteinase thrombospondin motifs (ADAMTS)‐5. Furthermore, activation of nuclear factor κB (NF‐κB), which was induced by IL‐1β, was also inhibited by SA through the pathway of nuclear factor‐erythroid 2‐related factor‐2 (Nrf2)/heme oxygenase 1. In vivo, SA could delay the progress of mice OA models. We propose that SA may be applied as a potential therapeutic drug in OA treatment.

Importance The burden of injury and costs of wrist fractures are substantial. Surgical treatment became popular without strong supporting evidence. Objective To assess whether current surgical treatment for displaced distal radius fractures provided better patient-reported wrist pain and function than nonsurgical treatment in patients 60 years and older. Design, Setting, and Participants In this multicenter randomized clinical trial and parallel observational study, 300 eligible patients were screened from 19 centers in Australia and New Zealand from December 1, 2016, until December 31, 2018. A total of 166 participants were randomized to surgical or nonsurgical treatment and followed up at 3 and 12 months by blinded assessors. Those 134 individuals who declined randomization were included in a parallel observational cohort with the same treatment options and follow-up. The primary analysis was intention to treat; sensitivity analyses included as-treated and per-protocol analyses. Intervention Surgical treatment was open reduction and internal fixation using a volar-locking plate (VLP). Nonsurgical treatment was closed reduction and cast immobilization (CR). Main Outcomes and Measures The primary outcome was the Patient-Rated Wrist Evaluation score at 12 months. Secondary outcomes were Disabilities of Arm, Shoulder, and Hand questionnaire score, health-related quality of life, pain, major complications, patient-reported treatment success, bother with appearance, and therapy use. Results In the 300 study participants (mean [SD] age, 71.2 [7.5] years; 269 [90%] female; 166 [81 VLP and 85 CR] in the randomized clinical trial sample and 134 [32 VLP and 102 CR] in the observational sample), no clinically important between-group difference in 12-month Patient-Rated Wrist Evaluation scores (mean [SD] score of 19.8 [21.1] for VLP and 21.5 [24.3] for CR; mean difference, 1.7 points; 95% CI −5.4 to 8.8) was observed. No clinically important differences were found in quality of life, wrist pain, or bother at 3 and 12 months. No significant difference was found in total complications between groups (12 of 84 [14%] for the CR group vs 6 of 80 [8%] for the VLP group; risk ratio [RR], 0.53; 95% CI, 0.21-1.33). Patient-reported treatment success favored the VLP group at 12 months (very successful or successful: 70 [89%] vs 57 [70%]; RR, 1.26; 95% CI, 1.07-1.48;P = .005). There was greater use of postoperative physical therapy in the VLP group (56 [72%] vs 44 [54%]; RR, 1.32; 95% CI, 1.04-1.69;P = 0.02). Conclusions and Relevance This randomized clinical trial found no between-group differences in improvement in wrist pain or function at 12 months from VLP fixation over CR for displaced distal radius fractures in older people. Trial Registration http://anzctr.org.auidentifier: ACTRN12616000969460

[Importance] Clinical trials assessing the efficacy of IL-6 antagonists in patients hospitalized for COVID-19 have variously reported benefit, no effect, and harm., [Objective] To estimate the association between administration of IL-6 antagonists compared with usual care or placebo and 28-day all-cause mortality and other outcomes., [Data Sources] Trials were identified through systematic searches of electronic databases between October 2020 and January 2021. Searches were not restricted by trial status or language. Additional trials were identified through contact with experts., [Study Selection] Eligible trials randomly assigned patients hospitalized for COVID-19 to a group in whom IL-6 antagonists were administered and to a group in whom neither IL-6 antagonists nor any other immunomodulators except corticosteroids were administered. Among 72 potentially eligible trials, 27 (37.5%) met study selection criteria., [Data Extraction and Synthesis] In this prospective meta-analysis, risk of bias was assessed using the Cochrane Risk of Bias Assessment Tool. Inconsistency among trial results was assessed using the I2 statistic. The primary analysis was an inverse variance–weighted fixed-effects meta-analysis of odds ratios (ORs) for 28-day all-cause mortality., [Main Outcomes and Measures] The primary outcome measure was all-cause mortality at 28 days after randomization. There were 9 secondary outcomes including progression to invasive mechanical ventilation or death and risk of secondary infection by 28 days., [Results] A total of 10 930 patients (median age, 61 years [range of medians, 52-68 years]; 3560 [33%] were women) participating in 27 trials were included. By 28 days, there were 1407 deaths among 6449 patients randomized to IL-6 antagonists and 1158 deaths among 4481 patients randomized to usual care or placebo (summary OR, 0.86 [95% CI, 0.79-0.95]; P = .003 based on a fixed-effects meta-analysis). This corresponds to an absolute mortality risk of 22% for IL-6 antagonists compared with an assumed mortality risk of 25% for usual care or placebo. The corresponding summary ORs were 0.83 (95% CI, 0.74-0.92; P, [Conclusions and Relevance] In this prospective meta-analysis of clinical trials of patients hospitalized for COVID-19, administration of IL-6 antagonists, compared with usual care or placebo, was associated with lower 28-day all-cause mortality., [Trial Registration] PROSPERO Identifier: CRD42021230155., Funding for administrative and communications support was provided by the World Health Organization.

Background Total hip and total knee replacement (THR/TKR) are common and effective surgeries to reduce the pain and disability associated with arthritis but are associated with small but significant risks of preventable complications such as surgical site infection (SSI) and venous-thrombo-embolism (VTE). This study aims to determine the degree to which hospital care was compliant with clinical guidelines for the prevention of SSI and VTE after THR/TKR; and whether non-compliant prophylaxis is associated with increased risk of complications. Methods and findings A prospective multi-centre cohort study was undertaken in consenting adults with osteoarthritis undergoing elective primary TKR/THR at one of 19 high-volume Australian public or private hospitals. Data were collected prior to surgery and for one-year post-surgery. Four adjusted logistic regression analyses were undertaken to explore associations between binary non-compliance and the risk of surgical complications: (1) composite (simultaneous) non-compliance with both (VTE and antibiotic) guidelines and composite complications [all-cause mortality, VTE, readmission/reoperation for joint-related reasons (one-year) and non-joint-related reasons (35-days)], (2) VTE non-compliance and VTE outcomes, (3) antibiotic non-compliance and any SSI, and (4) antibiotic non-compliance and deep SSI. Data were analysed for 1875 participants. Guideline non-compliance rates were high: 65% (VTE), 87% (antibiotics) and 95% (composite guideline). Composite non-compliance was not associated with composite complication (12.8% vs 8.3%, adjusted odds ratio [AOR] = 1.41, 95%CI 0.68–3.45, p = 0.40). Non-compliance with VTE guidelines was associated with VTE outcomes (5% vs 2.4%, AOR = 2.83, 95%CI 1.59–5.28,p < 0.001). Non-compliance with antibiotic guidelines was associated with any SSI (14.8% vs 6.1%, AOR = 1.98, 95%CI 1.17–3.62,p = 0.02) but not deep infection (3.7% vs 1.2%,AOR = 2.39, 95%CI 0.85–10.00, p = 0.15). Conclusions We found high rates of clinical variation and statistically significant associations between non-compliance with VTE and antibiotic guidelines and increased risk of VTE and SSI, respectively. Complications after THR/TKR surgery may be decreased by improving compliance with clinical guidelines.

Objectives Risk scoring models (RSMs) are commonly used for estimation of postoperative-mortality risk in patients undergoing cardiac surgery, but their prediction accuracy may vary in different populations and clinical situations. The prognostic accuracies of some RSMs have not yet been fully evaluated in the Australian population. In this retrospective observational study, our aims were to assess the performance of four contemporary RSMs, to identify the best RSMs for prediction of postoperative-mortality in the single-centre cohort, and to determine a statistical threshold for classification of patients with increased or “higher” mortality risk. Methods The study population included patients who underwent cardiac surgery at Liverpool Hospital between January 2013 and December 2014. Demographic information was collected, and mortality risks were estimated with the ES2 (EuroSCORE II), STS (Society of Thoracic Surgeons Score), AS (AusSCORE total) and ASMR (AusSCORE multi-risk) RSMs. (Additive EuroSCORE) (AES) and LES (logistic EuroSCORE) were included for historical interest. Discrimination, the ability to stratify patients between mortality and no mortality outcomes, and calibration, the comparison of risk score estimated and observed outcome in the population, were evaluated for each RSM, to determine their predictive accuracy in the study population. Discrimination was assessed by the AUC (area under the receiver operating characteristic curve), and acceptable calibration by the p-value greater than 0.05 for the Hosmer–Lemeshow (H-L) test. The best AUCs in contempory models were compared using the DeLong test. For ES2 and STS risk scores, cut-off points, or thresholds, for patients at increased risk of mortality were derived using Youden’s J-statistics, calculated from sensitivity and specificity of models in predicting mortality. Results From a total study population of 898 patients, 738 had scores for all six RSMs. The three EuroSCORE risk models and Youden’s J-statistics analysis included the total population. Of the models in contemporary use, ES2 had higher discrimination (AUC=0.850) in this population than ASMR (AUC=0.767, p=0.024) and AS (AUC=0.739) and non-significantly higher discrimination than STS (AUC=0.806, p=0.19). All contemporary models had acceptable calibration but the older LES (H-L p=0.024) did not. Estimated mortality was closest to observed mortality with the ES2 model. Both AES and LES over predicted mortality. The RSM with the highest discrimination in isolated coronary artery bypass graft surgery (CAGs) (AUC=0.847), isolated valves (AUC=0.830), and females (AUC=0.784) was the ES2 model. STS discrimination was highest in CAGs plus valve procedures (AUC 0.891), and males (STS AUC=0.891). Cut-off points for risk scores to define increased risk populations were 3.0% for ES2 and 1.7% for STS. Similar proportions of patients in each RSM (ES2-26% to STS-32%) were defined as higher risk by the model threshold score depending on type of procedure. Conclusion Among RSMs in contemporary use, ES2 and STS showed the best discrimination and acceptable calibration. Caution is recommended in specific subgroups. Increased mortality risk score cut-off points could be identified for these two RSMs in this single-centre cohort.

Objective Clinical grading scales used for prognostication in spontaneous intracerebral hemorrhage facilitate informed-decision making for resource-intensive interventions. Numerous clinical prognostic scores are available for spontaneous intracerebral hemorrhage. However, these have not been validated well in Asian patients, and the most appropriate scoring system remains debatable. We evaluated the utility of clinical scores in prognosticating 30-day mortality and 90-day functional outcome in patients with spontaneous intracerebral hemorrhage. Materials and Methods We conducted a retrospective review of all patients with spontaneous intracerebral hemorrhage admitted to our tertiary center from December 2014 to May 2016. Data on clinical presentation, imaging, and outcomes were extracted from electronic medical records using a standardized form. The data were analyzed for predictors of outcomes. Performance of prognostic scales was compared using receiver-operator characteristic statistics. Results A total of 297 patients were included in the study. Mean age was 60.1 (SD 15.2) years and 190 (64.0%) were male. Thirty-two (10.8%) cases died within 30 days and 177 (62.8%) cases had poor functional outcome (modified Rankin scale of 3 or more) at 90 days. Dialysis dependency (OR=33.54, 95%CI=4.21–325.26, p=0.002), Glasgow coma scale (OR=0.76, 95%CI=0.64–0.88, p=0.001), hematoma volume (OR=1.02, 95%CI=1.00–1.04, p=0.027), and surgical evacuation (OR=0.15, 95%CI=0.02–0.66, p=0.024) were independent predictors for 30-day mortality. The original ICH score (0.862) and the ICH-Grading Scale (0.781) had the highest c-statistic for 30-day mortality and 90-day poor functional outcome respectively. Conclusions Current prognostic scores performed acceptable-to-good in our patient cohort. Future studies may be useful to investigate the utility of these scores in clinical decision-making.

Liver cancer is now one of the most lethal and commonest cancers in the world, among which over 90% is hepatocellular carcinoma (HCC). Recent studies have confirmed long non-coding RNAs (lncRNAs) are implicated in carcinogenesis. It has been reported lncRNA LINC00668 serves as an oncogene in several cancers. However, the mechanism where LINC00668 regulates HCC is still unclear. qRT-PCR analysis was adopted to detect the expression of relative RNAs. Cytoplasmic and nuclear RNA fraction analysis was conducted to verify the underlying molecular mechanism. Cell colony formation was carried out to test cell colony formation ability and transwell assays were performed to testify cell migratory and invaded abilities. Relevant protein expression level was measured by Western blot assay. LINC00668 was significantly up-regulated in HCC tissues and cell lines. LINC00668 knockdown inhibited cell proliferative, migratory and invasion abilities and slowed down the epithelial–mesenchymal transition (EMT) process. Mechanistically, LINC00668 positively modulates the expression of YY1 by competitively binding to miR-532-5p. It was revealed that LINC00668 up-regulation accelerated cell proliferation and motility in HCC and suggested LINC00668 could be a potential therapeutic target for HCC.

Osteoarthritis (OA) is a degenerative joint disease characterized by destruction of articular cartilage. The inflammatory response is the most important factor affecting the disease process. As interleukin-1β (IL-1β) stimulates several key mediators in the inflammatory response, it plays a major role in the pathogenesis of OA. Maslinic acid (MA) is a natural compound distributed in olive fruit. Previous studies have found that maslinic acid has an inhibitory effect on inflammation, but its specific role in the progression of OA disease has not been studied so far. In this study, we aim to assess the protective effect of MA on OA progression by in vitro and in vivo experiments. Our results indicate that, in IL-1β-induced inflammatory response, MA is effective in attenuating some major inflammatory mediators such as nitric oxide (NO) and prostaglandin E2, and inhibits the expression of IL-6, inducible nitric oxide synthase, cyclooxygenase-2, and tumor necrosis factor-α (TNF-α) in a concentration-dependent manner. Also, MA downregulated the expression levels of thrombospondin motif 5 (ADAMTS5) and matrix metalloproteinase 13 in chondrocytes, resulting in reduced degradation of its extracellular matrix. Mechanistically, MA exhibits an anti-inflammatory effect by inactivating the PI3K/AKT/NF-κB pathway. In vivo, the protective effect of MA on OA development can be detected in a surgically induced mouse OA model. In summary, these findings suggest that MA can be used as a safe and effective potential OA therapeutic strategy.

Background Retrospective studies have found that daily opioid use pre-arthroplasty predicts worse longer-term service, clinical and patient-reported outcomes. Prospective studies are needed to confirm these observations. This prospective, exploratory study aimed to determine: the proportion of total knee or hip arthroplasty (TKA, THA) patients who use opioids regularly (daily) pre-surgery; if opioid use pre-surgery is associated with acute and sub-acute outcomes to 12-weeks post-surgery. Methods Consecutive patients undergoing primary TKA or THA were prospectively enrolled pre-surgery and followed-up by telephone to 12-weeks post-surgery. Acute-care (oral morphine equivalent dosage (OMED), length of stay, discharge to inpatient rehabilitation, complications) and 12-week outcomes (Oxford Knee or Hip Score, Euroqol ‘today’ health score, current use of opioids, and complications including readmissions) were monitored. Unadjusted and adjusted Odds Ratios (ORs) (95% Confidence Interval, CI), Rate Ratios and β coefficients (standard error) were calculated. Results Five Hundred Twenty-One patients were included (TKA n = 381). 15.7% (95%CI 12.6 to 18.9) used opioids regularly pre-surgery. 86.8% (452/521) were available for follow-up at 12-weeks. In unadjusted analyses, pre-surgical opioid use was significantly associated with higher average acute daily OMED [β 0.40 (0.07), p p Conclusion People who take daily opioids pre-surgery have significantly greater odds for greater opioid consumption acutely and ongoing use post-surgery. Adequately powered prospective studies are required to confirm whether pre-surgical opioid use is or is not associated with poorer joint and quality of life scores or a complication in the short-term.

Importance The presence of high-risk human papillomavirus (HPV) has been associated with a favorable outcome in Barrett high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC). Nevertheless, the prognostic significance of other HPV-related biomarkers (ie, retinoblastoma protein [pRb], cyclin D1 [CD1], minichromosome maintenance protein [MCM2] and Ki-67) is unknown. Objective To examine the association between HPV-related biomarkers and survival in adult patients with Barrett HGD and EAC. Design, Setting, and Participants This retrospective case-control study examined the hypothesis that the HPV-related cell cycle markers (pRb, CD1, and Ki-67) and the viral surrogate marker (MCM2) may be associated with a favorable prognosis in Barrett HGD and EAC. Pretreatment biopsies were used for HPV DNA determination via polymerase chain reaction and immunohistochemistry for the HPV-related biomarkers. Recruitment of patients occurred in secondary and tertiary referral centers, with 151 patients assessed for eligibility. The study period was from December 1, 2002, to November 28, 2017, and the dates of analysis were from September 9, 2011, to November 28, 2017. Main Outcomes and Measures Disease-free survival and overall survival. Results Of 151 patients assessed for eligibility, 9 were excluded. Among the 142 patients with Barrett HGD or EAC (126 [88.7%] men; mean [SD] age, 66.0 [12.1] years; 142 [100%] white), 37 were HPV positive and 105 were HPV negative. No association with disease-free survival was noted for pRb, CD1, Ki-67, and MCM2. In regard to overall survival, only low expression of CD1 had a favorable prognosis (hazard ratio [HR], 0.53; 95% CI, 0.30-0.95; adjustedP = .03). All the biomarkers stratified by HPV status showed significant associations with survival. Patients with HPV-positive, low-expression pRb esophageal tumors were associated with a significantly improved disease-free survival compared with the HPV-negative, high-expression Rb tumors (HR, 0.33; 95% CI, 0.12-0.93; adjustedP = .04). Similarly, HPV-positive, low-expression CD1 was associated with a significantly favorable disease-free survival (HR, 0.26; 95% CI, 0.09-0.76; adjustedP = .01), as was HPV-positive, high-expression MCM2 (HR, 0.27; 95% CI, 0.09-0.78; adjustedP = .02). In regard to overall survival, HPV was significantly associated only with low CD1 (HR, 0.38; 95% CI, 0.15-0.94; adjustedP = .04). Conclusions and Relevance This study’s findings suggest that low expression of CD1 appears to be an independent prognostic marker in Barrett HGD and EAC. Human papillomavirus positivity in combination with pRb, CD1, MCM2, and Ki-67 was associated with a survival benefit in esophageal tumors. These findings suggest the possibility of personalization of therapy for Barrett HGD and EAC based on viral status.

Purpose A proportion of TKA recipients following TKA are dissatisfied with their outcome. Our hypothesis is that patient satisfaction with TKA and perception of success of surgery are associated with patient comorbidities and overall health status, surgical and anaesthetic techniques as well as processes of post-operative care after TKA. The aims were to (i) measure the incidence of patient unfavourable outcomes—defined as dissatisfaction with the surgery or lack of joint-specific global improvement—1 year after TKA, and to explore the differences between these two outcomes of interest; (ii) assess the relationship between the development of these unfavourable outcomes and patient-reported knee function and overall quality of life; (iii) explore the associations between pre- and peri-operative variables and the development of these unfavourable outcomes 1 year after TKA. Methods This study includes analysis of data from a prospective cohort of 1017 TKA recipients. Pre-operative patient variables, surgical and acute-care data were collected. The Oxford knee score and the global perception of improvement were used to assess satisfaction and success 365 days post-surgery. Results From 1017 patients (56% female), mean age 68 years and BMI 32, 68 pts (7%) were dissatisfied with the outcome of surgery, 141 pts (14%) believed surgery was unsuccessful 1 year after TKA. A negative outcome was noted in 151 (15%) patients for either satisfaction or success, and 58 (6%) of patients reported neither good satisfaction nor success after surgery. Dissatisfied patients reported worse mean OKS (26.4 [SD 8.03] vs 42.3 [SD 5.21], p 2 and not resurfacing the patella were factors associated with the development of dissatisfaction with TKA and with patient perceived unsuccessful results of TKA. Multivariable logistic regression of patient satisfaction and success of TKA showed that compensation cases (OR 26.91, p 2 (OR 1.83, p = 0.04 for dissatisfaction and OR 1.57, p = 0.03 for unsuccessful TKA)and the development of a complication after TKA (OR 3.4, p

High-risk human papillomavirus (HPV) types 16/18 have been associated with Barrett's dysplasia (BD)/esophageal adenocarcinoma (EAC). Nevertheless, no data exist in relation to serological analysis for HPV antibodies in BD/EAC with site-specific viral DNA status. We prospectively examined antibodies to multiple HPV types in 438 patients representing hospital/reflux controls and Barrett's metaplasia (BM)/BD/intramucosal EAC. Antibody responses to HPV6/11/16/18/31/33/45/52/58 were analyzed using multiplex serology, including antibodies to E6/E7/E1/E2 and L1 antigens. Seropositivity for individual HPV proteins was infrequent in both cases and controls and was ≤10.2%. There was no difference in the seroprevalence of antibodies to any HPV antigen/antibody combination between reclassified cases (BD/EAC) and controls (hospital/reflux/BM) or between HPV16 or HPV18 DNA cases and controls, respectively. Among HPV16 DNA-positive BD/EAC cases, antibodies to HPV16 E7 were significantly more prevalent (3/26, 11.5%) than in hospital and reflux controls plus BM (5/328, 1.5%) (adjusted OR = 10.12, 95% CI: 1.61-63.73, P = 0.014). Among HPV18 DNA-positive cases, antibodies to HPV18 E1 were present in 3/6 (50%) cases versus 5/328 (1.5%) controls (adjusted OR = 44.28, 95% CI: 6.10-321.47, P = 0.0002). Although antibodies against HPV were generally uncommon in cases and controls, immune responses against two early proteins of HPV16/18 were significantly more frequent in viral DNA-positive BD/intramucosal EAC.

Use of herbal medicines is common. There is a need for education in this area. Mobile games are useful educational tools for motivating learning. A mobile game on herbal medicines can potentially enhance players' herb-related knowledge. Our objective was to develop a mobile game to motivate players to learn more about herbal medicines.Game development comprised of storyboarding, user interface design, database development, server development and distribution. A pilot usability study was conducted for the game prototype. Data was gathered through user registration, background data collection and a post-game survey containing a quiz on herbs encountered in the game. Mann-Whitney U test, chi-squared test and Spearman's correlation coefficient were used for data analysis."Herbopolis" is an in-house developed mobile game of the simulation genre. Players are tasked to manage a city specializing in the production and sale of herbal products. Nineteen out of 24 participants downloaded and played the game, and completed the post-game survey. Heuristic evaluations for usability, playability and educability were generally positive. Strong positive associations were observed between player level (r = 0.810, p 0.001) and gameplay time (r = 0.757, p 0.001) with quiz scores. Female players scored higher in the quiz (p = .044), played for more days (p = .010) and attained higher levels (p = .010) than male players.Players are motivated to learn about herb-related information through playing "Herbopolis". Our results support its use for improving knowledge on herbal medicines. Future game iterations to improve robustness and performance will likely to improve its reception and effectiveness in learning.

Objective Although angiogenesis plays an important role in coronary collateral circulation (CCC) formation and there are many determinants of coronary angiogenesis, they cannot fully explain the mechanism of CCC formation or as potent biomarker for CCC status. Therefore, there is of great clinical significance to identify the novel molecules associated with CCC. Previously, miR-503 exerts anti-angiogenesis effect via inhibition of VEGF-A and its expression is associated with many angiogenesis-related factors. Thus, we aimed to investigate the relationship of plasma miR-503 with CCC formation as well as its predictive power for CCC status in patients with coronary artery disease. Methods Among patients who underwent coronary angiography with coronary artery disease and a stenosis of ≥90% were included in our study. Collateral degree was graded according to Rentrop Cohen classification. The patients were divided to good CCC group (grade 2 or 3) and poor CCC group (grade 0 or 1) according to Rentrop grade. We investigated the plasma levels of miR-503 and VEGF-A by ELISA or q RT-PCR, respectively. In addition, we assayed the correlations of plasma miR-503 with VEGF-A or Rentrop grade using the spearman correlation test and its predictive power by receiver operating characteristic (ROC) and binary logistical regression analysis. Results Our data showed that plasma VEGF-A was significantly higher in good CCC group than that in poor group. Plasma miR-503 was lower in CAD patients with good CCC or poor CCC compared with control subjects and lowest in good CCC group. In addition, miR-503 negatively correlated with VEGF-A and Rentrop grade, respectively. Moreover, miR-503 displayed more potent predictive power for CCC status than VEGF-A, but its sensitivity and specificity for CCC status were only 72.4 or 60.9%, respectively. Conclusions Lower plasma miR-503 level was related to better CCC formation, accompanied by up-regulation of VEGF-A. In addition, miR-503 displayed potent predictive power for CCC status, but its sensitivity and specificity were not high enough, indicating that miR-503 might be as an additional prognosis biomarker for CCC.

Background/Aims: Osteoarthritis is a degenerative joint disease characterized by cartilage degeneration and a chondrocyte inflammatory response that induces an inflammatory environment closely linked to extracellular matrix (ECM) degradation. Ligustilide (LIG) is a major component of the herb Radix Angelicae Sinensis, with demonstrated anti-inflammatory effects. To confirm whether LIG has an equally inhibitory effect on inflammation in human osteoarthritis chondrocytes, we performed in vivo and in vitro experiments to validate the above conjectures and determine the relevant mechanisms. Methods: Quantitative realtime PCR and western blotting were performed to evaluate the expression of MMP-3, MMP-13, ADAMTS-5, iNOS, and COX-2 at both gene and protein levels. An enzyme-linked immunosorbent assay was used to evaluate the levels of other inflammatory factors (PGE2, TNF-α, and IL-6). The PI3K/AKT and nuclear factor kappa B (NF-κB) signaling pathways were also analyzed by western blotting, whereas immunofluorescence was used to assess the expression of collagen II and aggrecan. The in vitro effect of LIG was evaluated by intraperitoneal injection into a mouse osteoarthritis model induced by destabilization of the medial meniscus. Results: LIG lowered the phosphorylation levels of p65, IκBα, and IKKα/β and suppressed the IL-1β-induced expression of MMP-3, ADAMTS-5, iNOS, and COX-2 and the inflammatory factors PGE2, TNF-α, and IL-6. LIG markedly decreased IL-1β-induced degradation of collagen II and aggrecan. In vivo results showed that LIG-treated mouse cartilage showed less damage than the control group; the Osteoarthritis Research Society International (OARSI) score was also lower. LIG further reduced the thickness of the subchondral bone plate and alleviated the synovitis. Conclusion: LIG may act as a promising therapeutic agent for osteoarthritis by attenuating IL-1β-induced inflammation in chondrocytes and ECM degradation via suppression of NF-κB activation by the PI3K/AKT pathway.

Background: Biomechanical analysis of foot loading characteristics may provide insights into the injury mechanisms and guide orthotic prescription for basketball players. This study aimed to quantify in-shoe plantar pressure profiles in amateur players when executing typical basketball movements. Methods: Twenty male university basketball players performed four basketball-specific movement tasks—running, maximal forward sprinting, maximal 45° cutting, and layup—in a pair of standardized basketball shoes fitted with an in-shoe plantar pressure measurement system. Peak pressure (PP) and pressure-time integral (PTI) data were extracted from ten plantar regions. One-way repeated-measures analysis of variance was performed across the tasks, with significance set at P < .05. Results: Distinct plantar pressure distribution patterns were observed among the four movements. Compared with running, significantly higher (P < .05) PP and PTI of up to approximately 55% were found in sprinting and layup, particularly at the forefoot region. Similarly, significantly higher (P < .05) PPs and PTIs, ranging from approximately 23% to 90%, were observed in 45° cutting compared with running at most foot regions. Conclusions: Compared with running, sprinting and layup demonstrated higher plantar loading in the forefoot region, and 45° cutting yielded increased plantar loading in most regions of the foot. Understanding the plantar pressure characteristics of different movements may be useful in optimizing footwear designs, orthosis use, or training strategies to minimize regional plantar loading during amateur basketball play.

Cabernet Gernischt (CG) is a famous Chinese wine grape cultivar, the red wine of which is known for its green trait, especially when produced from grapes cultivated in regions with monsoon climate. To modify CG wine aroma, three enzyme preparations (H. uvarum extracellular enzyme, AR2000, and pectinase) were introduced in different winemaking stages with Saccharomyces cerevisiae. Free and bound aroma compounds in young wines were detected using headspace solid-phase micro-extraction and gas chromatography-mass spectrometry, and aroma characteristics were quantified by trained panelists. Results showed that simultaneous inoculation of enzymes and yeasts improved wine aroma. Partial least-squares regression revealed that the green trait was due mainly to varietal compounds, especially C6 compounds, and could be partly weakened by fermentative compounds. Moreover, H. uvarum enzyme treatments enriched the acid fruit note of CG wine by enhancing the synergistic effect of varietal volatiles and certain fermentative compounds, such as esters and phenylethyls.

Osteoarthritis (OA) is characterized by the degeneration and destruction of articular cartilage. Allicin, a dietary garlic active constituent, exerts anti-inflammatory effects on several diseases. However, its effects on OA have not been clearly elucidated. In this study, we explored the effects of allicin on OA in both in vitro and in vivo models. Allicin inhibited interleukin-1β (IL-1β) induced overproduction of nitric oxide, inducible nitric oxide synthase, prostaglandin E2, and cyclooxygenase-2, as well as pro-inflammatory cytokines tumor necrosis factor alpha and interleukin-6 in chondrocytes in a dose-dependent manner. Meanwhile, allicin reversed the overproduction of metalloproteinase-13 and a disintegrin and metalloproteinase with thrombospondin motifs-5 and the decrease of aggrecan and type II collagen. Furthermore, allicin dramatically suppressed IL-1β-stimulated PI3K/Akt/NF-κB activation in chondrocytes. In vivo, treatment with allicin prevented the destruction of cartilage and inhibited PI3K/Akt/NF-κB activation in the cartilage of mice OA models. Taken together, these results indicate that allicin may be a potential therapeutic agent for OA.

OBJECTIVE To compare the effectiveness of rehabilitation after total knee arthroplasty (TKA) in models with or without an inpatient rehabilitation component. DESIGN, SETTING AND PARTICIPANTS A propensity score-matched cohort of privately insured patients with osteoarthritis who underwent primary, unilateral TKA in one of 12 Australian hospitals between August 2013 and January 2015 were included. Those discharged to an inpatient facility because of poor progress or who experienced significant complications within 90 days of surgery were excluded. INTERVENTION Discharge after surgery to an inpatient rehabilitation facility or home. MAIN OUTCOME MEASURES Patient-reported knee pain and function (Oxford Knee Score; at 90 and 365 days after surgery) and health rating (EuroQol "today" health scale; at 35, 90 and 365 days). Inpatient and community-based rehabilitation provider charges were also assessed. RESULTS 258 patients (129 pairs) from a sample of 332 were matched according to their propensity scores for receiving inpatient rehabilitation; covariates used in the matching included age, sex, body mass index, and markers of health and impairment. The only significant difference in outcomes was that EuroQol health scores were better on Day 35 for patients not undergoing inpatient rehabilitation (median difference, 5; IQR, -10 to 19; P = 0.01). Median rehabilitation provider charges were significantly higher for those discharged to inpatient therapy (total costs: median difference, $9500; IQR, $7000-11 497; P < 0.001; community therapy costs: median difference, $749; IQR, $0-1980; P < 0.001). CONCLUSIONS Rehabilitation pathways incorporating inpatient rehabilitation did not achieve better joint-specific outcomes or health scores than alternatives not including inpatient rehabilitation. Given the substantial cost differences, better value alternatives should be considered for patients after uncomplicated TKA.

Objective Pre- and post-operative neutrophil to lymphocyte ratio (NLR) and prognostic nutritional index (PNI) and other prognostic clinicopathological variables were correlated with progression free survival (PFS) and overall survival (OS) of Glioblastoma Multiforme (GBM) patients. Methods GBM patients (n = 87, single-centre, recruited 2013–2019) were retrospectively divided into low and high groups using literature-derived cut-offs (NLR = 5.07, PNI = 46.97). Kaplan-Meier survival curves and log rank tests assessed PFS and OS. Univariate and multivariate analyses identified PFS and OS prognosticators. Results High vs low post-operative PNI cohort was associated with longer PFS (279 vs 136 days, p = 0.009), but significance was lost on multivariate analysis. Post-operative ECOG (p = 0.043), daily dexamethasone (p = 0.023) and IDH mutation (p = 0.046) were significant on multivariate analysis for PFS. High pre- and post-operative PNI were associated with improved OS (384 vs 114 days, p = 0.034 and 516 vs 245 days, p = 0.001, respectively). Low postoperative NLR correlated with OS (408 vs 249 days, p = 0.029). On multivariate analysis using forward selection process, extent of resection (EOR) (GTR vs biopsy, p = 0.004 and STR vs biopsy, p = 0.011), and any previous surgery (p = 0.014) were independent prognostic biomarkers for OS. On multivariate analysis of these latter variables with literature-derived prognostic biomarkers, EOR remained significantly associated with OS (p = 0.037). Conclusions EOR, followed by having any surgery prior to GBM, are the most significant independent predictors of GBM patient’s OS. Post-operative ECOG, daily dexamethasone and IDH mutation are independent prognostic biomarkers for PFS. PNI may be superior to NLR. Post- vs pre-operative serum inflammatory marker levels may be associated with survival.

Summary Background The intestinal microbiota is implicated in the pathogenesis of ulcerative colitis. Faecal microbiota transplantation is a novel form of therapeutic microbial manipulation, but its efficacy in ulcerative colitis is uncertain. We aimed to establish the efficacy of intensive-dosing, multidonor, faecal microbiota transplantation in active ulcerative colitis. Methods We conducted a multicentre, double-blind, randomised, placebo-controlled trial at three hospitals in Australia. We randomly allocated patients with active ulcerative colitis (Mayo score 4–10) in a 1:1 ratio, using a pre-established randomisation list, to either faecal microbiota transplantation or placebo colonoscopic infusion, followed by enemas 5 days per week for 8 weeks. Patients, treating clinicians, and other study staff were unaware of the assigned treatment. Faecal microbiota transplantation enemas were each derived from between three and seven unrelated donors. The primary outcome was steroid-free clinical remission with endoscopic remission or response (Mayo score ≤2, all subscores ≤1, and ≥1 point reduction in endoscopy subscore) at week 8. Analysis was by modified intention-to-treat and included all patients receiving one study dose. We performed 16S rRNA stool analysis to assess associated microbial changes. This trial is registered with ClinicalTrials.gov, number NCT01896635. The trial has ended; this report presents the final analysis. Findings From November, 2013, to May, 2015, 85 patients were enrolled to our trial, of whom 42 were randomly assigned faecal microbiota transplantation and 43 were allocated placebo. One patient assigned faecal microbiota transplantation and three allocated placebo did not receive study treatment and were excluded from the analysis. The primary outcome was achieved in 11 (27%) of 41 patients allocated faecal microbiota transplantation versus three (8%) of 40 who were assigned placebo (risk ratio 3·6, 95% CI 1·1–11·9; p=0·021). Adverse events were reported by 32 (78%) of 41 patients allocated faecal microbiota transplantation and 33 (83%) of 40 who were assigned placebo; most were self-limiting gastrointestinal complaints, with no significant difference in number or type of adverse events between treatment groups. Serious adverse events occurred in two patients assigned faecal microbiota transplantation and in one allocated placebo. Microbial diversity increased with and persisted after faecal microbiota transplantation. Several bacterial taxa were associated with clinical outcome; in particular, the presence of Fusobacterium spp was associated with lack of remission. Interpretation Intensive-dosing, multidonor, faecal microbiota transplantation induces clinical remission and endoscopic improvement in active ulcerative colitis and is associated with distinct microbial changes that relate to outcome. Faecal microbiota transplantation is, thus, a promising new therapeutic option for ulcerative colitis. Future work should focus on precisely defining the optimum treatment intensity and the role of donor–recipient matching based on microbial profiles. Funding Broad Medical Research Program, Gastroenterological Society of Australia, Mount Sinai (New York) SUCCESS fund, University of New South Wales.

Osteoarthritis (OA) is the most common form of joint disease and is widespread in the elderly population and is characterized by erosion of articular cartilage, subchondral bone sclerosis and synovitis. Oleuropein (OL), a secoiridoid, is considered as the most prevalent phenolic component in olive leaves and seeds, pulp and peel of unripe olives and has been shown to have potent anti-inflammatory effects. However, its effects on OA have not been clearly elucidated. This study aimed to assess the effect of OL on human OA chondrocytes. Human OA chondrocytes were pretreated with OL (10, 50 and 100 μM) for 2 h and subsequently stimulated with IL-1β for 24 h. The production of NO, PGE2, MMP-1, MMP-13, and ADAMTS-5 was evaluated by the Griess reaction and ELISA assays. The messenger RNA (mRNA) expression of COX-2, iNOS, MMP-1, MMP13, ADAMTS-5, aggrecan, and collagen-II was measured by using real-time PCR. The protein expressions of COX-2, iNOS, p65, IκB-α, JNK, p-JNK, ERK, p-ERK, p38, and p-p38 were tested by using western blot. We found that OL significantly inhibited the IL-1β-induced production of NO and PGE2; expression of COX-2, iNOS, MMP-1, MMP-13, and ADAMTS-5; and degradation of aggrecan and collagen-II. Furthermore, OL dramatically suppressed IL-1β-stimulated NF-κB and MAPK activation. Immunofluorescence staining demonstrated that OL could suppress IL-1β-induced phosphorylation of p65 nuclear translocation. These results indicate that the therapeutic effect of OL on OA is accomplished through the inhibition of both NF-κB and MAPK signaling pathways. Altogether, our findings provide the evidence to develop OL as a potential therapeutic agent for patients with OA.

SUMMARY There is evidence to suggest that human papillomaviruses (HPV) are associated with Barrett's dysplasia and esophageal adenocarcinoma. In other HPV-linked cancers such as cervical and oropharyngeal cancer, circulating HPV DNA is a potential biomarker to assist in tumor diagnosis and management. This study aimed to determine whether circulating HPV DNA was detectable in patients with Barrett's dysplasia and esophageal adenocarcinoma, and if so, whether there is any correlation with esophageal tissue HPV status. Plasma from 138 patients representing esophageal adenocarcinoma (N = 41), Barrett's dysplasia (N = 48) and hospital controls (N = 49) were analyzed for the presence of circulating HPV DNA using droplet-digital PCR targeting the E7 gene of HPV types 16 and 18. Circulating HPV DNA was detected in 11/138 (8.0%) study subjects including 1/49 (2.0%) hospital controls, 4/48 (8.3%) Barrett's dysplasia patients, and 6/41 (14.6%) esophageal adenocarcinoma patients. Detection of circulating HPV DNA was higher in patients with HPV-positive esophageal tissue (6/35, 17.1%) compared to those with HPV-negative specimens (5/103; 4.9%) (OR = 4.06; 95% CI 1.15–14.25; P = 0.020). The highest rates of detection occurred in esophageal adenocarcinoma patients, particularly those with invasive tumors that had breached the esophageal submucosa, had regional lymph node involvement or metastatic disease. Circulating HPV DNA was detectable in a subset of Barrett's dysplasia and esophageal adenocarcinoma patients. Detection was associated with tissue HPV positivity and possibly disease severity.

Importance Recent publication of the largest trials to date investigating rehabilitation after total knee arthroplasty (TKA) necessitate an updated evidence review. Objective To determine whether inpatient or clinic-based rehabilitation is associated with superior function and pain outcomes after TKA compared with any home-based program. Data Sources MEDLINE, Embase, CINAHL, and PubMed were searched from inception to November 5, 2018. Search terms includedknee arthroplasty,randomized controlled trial,physiotherapy, andrehabilitation. Study Selection Published randomized clinical trials of adults who underwent primary unilateral TKA and commenced rehabilitation within 6 postoperative weeks in which those receiving postacute inpatient or clinic-based rehabilitation were compared with those receiving a home-based program. Data Extraction and Synthesis Two reviewers extracted data independently and assessed data quality and validity according to the PRISMA guidelines. Data were pooled using a random-effects model. Data were analyzed from June 1, 2015, through June 4, 2018. Main Outcomes and Measures Primary outcomes were mobility (6-minute walk test [6MWT]) and patient-reported pain and function (Oxford knee score [OKS] or Western Ontario and McMaster Universities Osteoarthritis Index) reported at 10 to 12 postoperative weeks. The GRADE assessment (Grading of Recommendations, Assessment, Development, and Evaluation) was applied to the primary outcomes. Results Five unique studies involving 752 unique participants (451 [60%] female; mean [SD] age, 68.3 [8.5] years) compared clinic- and home-based rehabilitation, and 1 study involving 165 participants (112 [68%] female; mean [SD] age, 66.9 [8.0] years) compared inpatient and home-based rehabilitation. Low-quality evidence showed no clinically important difference between clinic- and home-based programs for mobility at 10 weeks (6MWT favoring home program; mean difference [MD], −11.89 m [95% CI, −35.94 to 12.16 m]) and 52 weeks (6MWT favoring home program; MD, −25.37 m [95% CI, −47.41 to −3.32 m]). Moderate-quality evidence showed no clinically important difference between clinic- and home-based programs for patient-reported pain and function at 10 weeks (OKS MD, −0.15 [95% CI, −0.35 to 0.05]) and 52 weeks (OKS MD, 0.10 [95% CI, −0.14 to 0.34]). Conclusions and Relevance Based on low- to moderate-quality evidence, no superiority of clinic-based or inpatient programs compared with home-based programs was found in the early subacute period after TKA. This evidence suggests that home-based rehabilitation is an appropriate first line of therapy after uncomplicated TKA for patients with adequate social supports.

Two new species of flatworm, collected from a beach at eastern Shenzhen, China, were studied through an integrative approach by combining morphological, histological, histochemical (acetylcholinesterase, AChE), and molecular (18S r- DNA) data. These species belong to two genera of marine triclads, previously unrecorded from China, viz. Nerpa Marcus, 1948 and Paucumara Sluys, 1989. Nerpa fistulata Wang & Chen, sp. nov. is characterized by: transparent body; principally pentamerous intestine with three distinct commissures; two very large, prepharyngeal testis follicles; a semi-circular lens in each eye cup; a penis papilla provided with a chitinized, pointed stylet; lateral bursae communicating with the oviduct and opening ventrally to the exterior via a duct. Phylogenetically N. fistulata groups with one member of the family Bdellouridae. This new, Chinese species of Nerpa introduces a major geographic disjunction, as the type species N. evelinae was described from the bay of Santos, Brazil, so that the genus is now known from both Atlantic as well as Pacific coasts. The species Paucumara falcata Wang & Li, sp. nov. is characterized by: three distinct pale yellow transverse pigmentation bands on its dorsal side, between which some snowflake-like specks are randomly distributed, and a brown transverse band anteriorly to the eyes; 8–11 testicular follicles on either side of the body, the follicles extending from immediately behind the ovaries to half-way along the pharyngeal pocket; a musculo-parenchymatic organ with a sclerotic, curved tip projecting from the anterior wall of the male atrium, ventrally to the root of the penis papilla. Phylogenetically P. falcata groups with its congener P. trigonocephala, with the genus Paucumara forming the sister taxon of the genus Ectoplana. Comparison of the nerve structure of P. falcata, as revealed by AChE histochemistry, with that of eight other species of triclad suggested that the nervous system of marine planarians is simpler than that of species of freshwater planarians, but revealed also that the nerve structure is rather variable among species. The copulatory position exhibited by two partners in Paucumara falcata is remarkable in that they intertwine, with their heads pointing downwards and the tails pointing upwards, the entire process lasting about 10 min. Such a copulatory position has never before been reported for triclad flatworms.

Objectives Following total knee or total hip arthroplasty (TKA, THA), up to 31% of recipients experience significant weight gain while up to 14% experience significant weight loss. Factors associated with significant weight change (≥5% of baseline weight) have not been comprehensively explored. This study aimed to identify pre- and post-surgical (including current) patient factors associated with significant weight change three years after surgery. Methods A pre-existing nationally-acquired cohort who underwent TKA or THA for osteoarthritis participated in 3-year telephone follow-up. Updated weight, comorbidity, and complication data were collected along with ongoing index joint problems and other patient-reported outcomes including global improvement. These data, along with body mass index (BMI) pre-surgery and post-surgery rehabilitation received, were incorporated into two multivariable logistic regression models to determine separately the factors associated with ≥5% weight gain and ≥5% loss at 3-years post-surgery. Results 73.4% (1289/1757) participated in the follow-up; 1191 (n = 663 TKA) provided updated weight data. Patterns of weight change were similar for both surgeries (TKA: 16.1% gained ≥5%, 19.6% lost ≥5%; THA: 15.8% gained ≥5%, 17.8% lost ≥5%). In multivariable modelling, younger age and lower pre-surgery BMI were significantly associated with weight gain; female gender and an absence of ongoing index joint issues were associated with weight loss. Conclusion Different mechanisms are likely associated with significant weight gain or loss at 3-years post-surgery. Cogent weight management entails consideration of both outcomes. Many post-surgical factors appear not to be importantly associated with weight change.

Diabetic cardiomyopathy (DCM) is a form of idiopathic heart disease, with signs including hypertrophy of myocardial cells, hypertension-independent fibrosis and coronary artery disease. Considering the involvement of dimethylarginine dimethylaminohydrolase 2 (DDAH2) in diabetes, it was hypothesized that DDAH2 may be beneficial to cardiac function and myocardial fibrosis during the progression of DCM with involvement of the DDAH/asymmetric NG, NGdimethyl-L-arginine (ADMA)/nitric oxide synthase (NOS)/nitric oxide (NO) signaling pathway. Following establishment of diabetic rat models, diabetes-related blood biochemical indices and cardiac function were measured in diabetic rats treated with lentivirus expressing DDAH2, short hairpin RNA against DDAH2, or L-NNA (inhibitor of NOS) to identify the roles of DDAH2 in DCM. The functional roles of DDAH2 in DCM were further determined through detection of the levels of collagen I, matrix metalloproteinase 2 (MMP2) and tissue inhibitor of metalloproteinase 2 (TIMP2). The H9C2 myocardial cell line was selected for in vitro experiments. The effects of DDAH2 on the migration of myocardial cells under high glucose conditions were also examined. To further investigate the underlying regulatory mechanism of DDAH2 in DCM, the contents of ADMA and NO, and the activities of DDAH and NOS were observed. The DCM model rats treated with DDAH2 exhibited reduced left ventricular end-diastolic pressure, and decreased blood glucose, total cholesterol, triglyceride, fasting blood glucose, and fasting insulin levels, but exhibited increased left ventricular systolic pressure and maximum rate of left ventricular pressure rise/fall levels in myocardial tissues. Myocardial cells under high glucose conditions treated with DDAH2 showed reductions in collagen I, MMP2 and TIMP2, indicating that DDAH2 reduced cell migration. Decreased levels of ADMA and NO but increased levels of DDAH and NOS were observed following treatment with DDAH2, indicating that the DDAH/ADMA/NOS/NO pathway was activated. These results reveal that the overexpression of DDAH2 attenuates myocardial fibrosis and protects against DCM through activation of the DDAH/ADMA/NOS/NO pathway in DCM rats. These results indicate that DDAH2 is a potential therapeutic candidate for the treatment of DCM.

Highlights • Providing early ECMO support due to carbon dioxide retention and on-time decannulation may be more beneficial to patients. • The duration from tracheal intubation to ECMO cannulation was more than 7 days in some patients. • The application rules of ECMO vary in different regions.

Aim 3D wound imaging has provided clinicians with even greater wound measurement options. No data is available to guide clinicians as to which 3D measurements may yield the most reflective marker of wound progression to healing. Method A prospective pilot study was undertaken to assess the accuracy of five 3D wound measurements that best reflect metrics of interest to clinicians. Twenty-one diabetic foot ulcers were enrolled from initial ulcer presentation, through to healing. The relationship between mean wound healing measurement variables was examined using linear regression and Pearsons correlation coefficient, in addition to assessing clinician inter-rater reliability of measurements using Intra-class correlation coefficients (ICC). Results Statistical analysis demonstrated a linear healing slope for each wound measurement as having a value greater than R 0.70 and a statistical significance of p = 0.0001. This suggests that all five wound measurements are useful prognostic markers of wound progression to healing. Low variability of measurements between users indicates good inter-observer reliability. Conclusion 3D wound measurements demonstrate a linear correlation between the measurement and time to healing. This suggests they could be effective prognostic markers of a wounds progression to healing and closure. It may also provide important early identification of wounds not responding to standard care. Larger studies are required to validate our results.

Given the comparable strains of high-risk human papillomavirus (HPV) present in a subset of Barrett's dysplasia and esophageal adenocarcinoma as in head and neck squamous cell carcinomas and the anatomical proximity of both lesions, we hypothesized that oral sex may increase the risk of Barrett's dysplasia/esophageal adenocarcinoma. Therefore, we compared the sexual behavior of patients with Barrett's dysplasia/esophageal adenocarcinoma and controls (hospital, reflux, and Barrett's metaplasia) to explore a plausible mechanism of viral transmission to the lower esophagus. A hospital-based case-control study involving 36 Barrett's dysplasia/esophageal adenocarcinoma subjects and 55 controls with known HPV DNA status and markers of transcriptional activity i.e p16INK4A and E6/E7 mRNA of the esophageal epithelium was conducted to evaluate differences in sexual history (if any). Barrett's dysplasia/esophageal adenocarcinoma patients were more likely than controls to be positive for HPV DNA (18 of 36, 50% vs. 6/55, 11%, p for trend

Background Inpatient rehabilitation is an expensive option following total hip arthroplasty (THA). We aimed to determine if THA patients who receive inpatient rehabilitation report better hip and quality of life scores post-surgery compared to those discharged directly home. Methods Prospective, propensity score matched cohort involving 12 private hospitals across five Australian States. Patients undergoing THA secondary to osteoarthritis were included. Those receiving inpatient rehabilitation for reasons other than choice or who experienced significant health events within 90-days post-surgery were excluded. Comparisons were made between those who did and did not receive inpatient rehabilitation for patient-reported hip pain and function (Oxford Hip Score, OHS) and ‘today’ health rating (EuroQol 0–100 scale). Rehabilitation provider charges were also estimated and compared. Results Two hundred forty-six patients (123 pairs, mean age 67 (10) yr., 66% female) were matched on 19 covariates for their propensity to receive inpatient rehabilitation. No statistically nor clinically significant between-group differences were observed [OHS median difference (IQR): 0 (− 3, 3), P = 0.60; 0 (− 1 to 1), P = 0.91, at 90 and 365-days, respectively; EuroQol scale median difference 0 (− 10, 12), P = 0.24; 0 (− 10, 10), P = 0.49; 5 (− 10, 15), P = 0.09, at 35-, 90- and 365-days, respectively]. Median rehabilitation provider charges were 10-fold higher for those who received inpatient rehabilitation [median difference $7582 (5649, 10,249), P

［摘要］

This study aimed to investigate the effects of varying midsole hardness on center of pressure (COP) and perceived stability during basketball-specific tasks, as well as the correlation between COP and perception measurements. A total of 20 male basketball players performed 45° cutting and layup while wearing basketball shoes with soft and hard midsoles. COP trajectories were obtained from the Pedar insole system. Stability perceptions at the forefoot and rearfoot were assessed using 150-mm visual analogue scales. Results indicated greater COP mediolateral deviations in soft midsole compared with hard midsole during layup (soft: 16.6 [4.7] mm, hard: 15.8 [4.6] mm, P = .03) but not 45° cutting (soft: 15.7 [5.9] mm, hard: 15.8 [5.6] mm, P = .60). While 16 out of 20 participants preferred soft midsole, no significant difference in visual analogue scale ratings was found between shoes for both tested movements. There was no significant correlation between COP and perceived stability during layup or 45° cutting. In conclusion, midsole hardness of basketball shoes did not consistently affect mediolateral stability of the foot during 45° cutting and layup. Subjective perception alone cannot be used to indicate mediolateral deviation of the foot when executing basketball-specific maneuvers.

To understand the epidemiological characteristics of malaria in Wuxi City, and explore effective strategies and measures for malaria elimination.The data on malaria cases in Wuxi from 2005 to 2014 were collected and analyzed.In Wuxi City, from 2005 to 2014, 201 malaria cases were reported, of which, there were 52 local cases and 149 imported cases. Totally 156 malaria cases were reported from 2005 to 2009, of which 6 cases were infected with Plasmodium falciparum, and 45 malaria cases were reported from 2010 to 2014, of which 23 cases were infected with P. falciparum. From 2005 to 2009, the ratio of male to female was 2.39:1. Migrant workers, farmers and workers were the major infected populations, with a proportion of 41.03%, 17.95% and 9.62%, respectively. From 2010 to 2014, the ratio of male to female was 10.25:1. Workers, farmers and migrant workers were the major infected populations, with a proportion of 37.78%, 11.11% and 6.67%, respectively. The peak of malaria incidence was observed from May to October. From 2005 to 2009, most cases were reported by CDCs, and from 2010 to 2014, most cases were reported by medical institution. There was an increase in proportion of P. falciparum.The control and prevention of malaria should focus on imported cases in the future in Wuxi. The doctors should improve the capacity of malaria diagnosis and treatment.

Objective To determine clinical outcomes in patients with diabetic foot infections receiving outpatient parenteral antimicrobial therapy (OPAT), to evaluate cost savings from the use of OPAT and to analyse demographic, clinical and laboratory data that may predict OPAT failure. Research Design and Methodology A retrospective cohort analysis was conducted between 1 January 2007 and 7 July 2012 at a tertiary referral hospital in metropolitan Sydney. Patients with diabetic foot infection were identified from the outpatient parenteral antimicrobial therapy database. Demographic, clinical, laboratory and operative report data were obtained from patient charts and electronic medical records. Potential cost savings were calculated on the estimated cost of expenditure versus the expected savings. Linear regression was used to explore outcomes associated with outpatient parenteral antimicrobial therapy failure. Results Fifty-nine patients were identified over the 5-year study period. The outpatient parenteral antimicrobial therapy success rate for diabetic foot infections was 88%. Following the resolution of the primary episode of infection, new infective episodes within the study period were high (n = 26, 44%). Regression analysis of variables for OPAT failure failed to indicate any factors reaching statistical significance. A total of 1569 days were saved by using outpatient parenteral antimicrobial therapy for an estimated total cost saving of $983 645 or $16 672 per patient. Conclusion Outpatient intravenous therapy for diabetic foot infections is an effective mode of treatment that can contribute to significant healthcare savings. High re-infection rates associated with diabetes foot ulceration in this population underline the need for close monitoring and management of these patients in multidisciplinary high-risk foot setting. Copyright © 2015 John Wiley & Sons, Ltd.

Resolvin D1 (RvD1), an endogenous lipid mediator derived from docosahexaenoic acid, has been reported to promote a biphasic activity in anti-inflammatory response and regulate inflammatory resolution. The present study aimed to determine the endogenous expression pattern of RvD1 in a rat model of self-resolution of lipopolysaccharide (LPS)-induced acute respiratory distress syndrome (ARDS) and inflammation. The ARDS model was induced by administrating LPS (2mg/kg) via tracheotomy in 138 male Sprague-Dawley rats. At specified time points, lung injury and inflammation were respectively assessed by lung histology and analysis of bronchoalveolar lavage fluid and cytokine levels. The expression of endogenous RvD1 was detected by high performance liquid chromatography and tandem mass spectrometry. The results showed that histological lung injury peaked between 6h (LPS6h) and day 3, followed by recovery over 4-10 days after LPS administration. Lung tissue polymorph nuclear cell (PMN) was significantly increased at LPS6h, and peaked between 6h to day 2. The levels of interleukin (IL)-6 and IL-10 were significantly increased at LPS6h and remained higher over day 10 as compared to baseline. Intriguingly, the endogenous RvD1 expression was decreased gradually during the first 3 days, followed by almost completely recovery over days 9-10. The finding indicated that endogenous RvD1 underwent a decrease in expression followed by gradual increase that was basically coincident with the lung injury recovery in a rat model of self-resolution LPS-induced ARDS and inflammation. Our results may help define the optimal therapeutic window for endogenous RvD1 to prevent or treat LPS-induced ARDS and inflammation.

Importance Formal rehabilitation programs, including inpatient programs, are often assumed to optimize recovery among patients after undergoing total knee arthroplasty. However, these programs have not been compared with any outpatient or home-based programs. Objective To determine whether 10 days of inpatient rehabilitation followed by a monitored home-based program after total knee arthroplasty provided greater improvements than a monitored home-based program alone in mobility, function, and quality of life. Design, Setting, and Participants In this 2-group, parallel, randomized clinical trial, including a nonrandomized observational group, conducted at 2 public, high-volume arthroplasty hospitals in Sydney, Australia (July 2012-December 2015), 940 patients with osteoarthritis undergoing primary total knee arthroplasty were screened for eligibility. Of the 525 eligible patients consecutively invited to participate, 165 were randomized either to receive inpatient hospital rehabilitation and home-based rehabilitation or to receive home-based rehabilitation alone, and 87 patients enrolled in the observation group. Interventions Eighty-one patients were randomized to receive 10 days of hospital inpatient rehabilitation followed by an 8-week clinician-monitored home-based program, 84 were randomized to receive the home-based program alone, and 87 agreed to be in the observational group, which included only the home-based program. Main Outcomes and Measures Mobility at 26 weeks after surgery, measured with the 6-minute walk test. Secondary outcomes included the Oxford Knee Score, which ranges from 0 (worst) to 48 (best) and has a minimal clinically important difference of 5 points; and EuroQol Group 5-Dimension Self-Report Questionnaire (EQ-5D) visual analog scale, which ranges from 0 (worst) to 100 (best), and has a minimal clinically important difference of 23 points. Results Among the 165 randomized participants, 68% were women, and the cohort had a mean age, 66.9 years (SD, 8.4 years). There was no significant difference in the 6-minute walk test between the inpatient rehabilitation and either of the 2 home program groups (mean difference, −1.01; 95% CI, −25.56 to 23.55), nor in patient-reported pain and function (knee score mean difference, 2.06; 95% CI, −0.59 to 4.71), or quality of life (EQ-5D visual analog scale mean difference, 1.41; 95% CI, −6.42 to 3.60). The number of postdischarge complications for the inpatient group was 12 vs 9 among the home group, and there were no adverse events reported that were a result of trial participation. Conclusions and Relevance Among adults undergoing uncomplicated total knee arthroplasty, the use of inpatient rehabilitation compared with a monitored home-based program did not improve mobility at 26 weeks after surgery. These findings do not support inpatient rehabilitation for this group of patients. Trial Registration clinicaltrials.gov Identifier:NCT01583153

We have previously demonstrated that transcriptionally active high-risk HPV (hr-HPV) is strongly incriminated in Barrett's dysplasia (BD) and oesophageal adenocarcinoma (OAC) using mainly fresh frozen tissue. This study aimed to identify biomarkers of active HPV infection in Barrett's metaplasia, (BM)/BD/OAC by immunohistochemical staining (IHC) of formalin-fixed paraffin embedded (FFPE) tissue for aberrations of p53 and the retinoblastoma (pRb) pathway, which are targets for the viral oncoproteins, E6/E7, respectively. Prospectively, BM (n = 81)/BD (n = 72)/OAC (n = 65) FFPE specimens were subjected to IHC staining for pRb, p16

Background Chronic kidney disease (CKD) is associated with increased cardiovascular morbidity and mortality; hence detection of early cardiovascular involvement in CKD is important to prevent future adverse cardiovascular events. Left atrial (LA) enlargement and dysfunction has been reported in end stage renal disease. However, there is a paucity of published data regarding the evaluation of LA function in CKD using noninvasive imaging parameters. In this study, we evaluated biplane LA volume as well as LA function (LA global systolic strain (GS) and strain rate [SR]) in stage 3 CKD patients (eGFR 30–59 mL/min per 1.73 m2) to determine if LA function parameters are more significantly altered by the presence of CKD in addition to changes due to hypertension alone. Methods Thirty-three CKD patients (eGFR 30–59 mL/min per 1.73 m2) with hypertension were compared to 33 normal controls and 34 hypertensive (HT) subjects with normal renal function; all participants underwent a detailed transthoracic echocardiogram. Indexed biplane LA volume (LAVI), LA segmental function, and GS and SR (systolic, early, and late diastole) derived from tissue Doppler imaging (TDI) were measured. Univariate predictors of LA strain were determined. Multiple logistic regression analysis was used to examine the effect of patient group (i.e. CKD) on GS and SR as well as LAVI. Results Left atrial volume indexed was significantly increased in both the HT and CKD with HT group compared to normal controls (28 ± 9 mL/m2 vs. 28 ± 9 mL/m2 vs. 23 ± 5 mL/m2, respectively, P = 0.02). However, LAVI was similar in the HT and CKD with HT group (28 ± 9 mL/m2 vs. 28 ± 9 mL/m2; P = NS). LA GS and SR were reduced in both the CKD with HT and HT group, compared to controls. However, a significantly lower LA GS was present in the CKD with HT group (Controls vs. HT vs. CKD with HT: 54.9 ± 14.5% vs. 34.5 ± 6.2% vs. 25.7 ± 9.3%, respectively; P = 0.001). To examine the effect of group, (i.e. presence of CKD) multiple logistic regression analysis was performed with univariate predictors including indexed left ventricular mass (LVMI), LV diastolic grade, LAVI, peak A-wave velocity, β-blocker therapy, GS and SR; this demonstrated that CKD had an independent effect on LA GS and SR (systolic, early, and late diastole). GS demonstrated moderate correlation with systolic blood pressure (r = −0.5, P = 0.01), diastolic grade (r = −0.5, P = 0.01), E′ velocity (r = 0.6, P = 0.0001), peak A velocity (r = −0.5, P = 0.004), and LAVI (r = −0.6, P = 0.002). Conclusions Left atrial dysfunction is evident in stage 3 CKD with associated LA enlargement. This study demonstrates that LA GS and SR were reduced in the CKD group despite similar LAVI in the CKD with HT and HT group. Hence LA GS and SR may be a more sensitive noninvasive tool to detect cardiovascular involvement in CKD.

This study examined how shoe midsole hardness influenced plantar pressure in basketball-related movements. Twenty male university basketball players wore customized shoes with hard and soft midsoles (60 and 50 Shore C) to perform four movements: running, maximal forward sprinting, maximal 45° cutting and lay-up. Plantar loading was recorded using an in-shoe pressure measuring system, with peak pressure (PP) and pressure time integral (PTI) extracted from 10 plantar regions. Compared with hard shoes, subjects exhibited lower PP in one or more plantar regions when wearing the soft shoes across all tested movements (Ps

Objective Early mobilisation is recommended following total hip arthroplasty (THA) or total knee arthroplasty (TKA) to prevent venous thromboembolism (VTE). We sought to determine the proportions of patients that first mobilised on post-operative day 0 (POD 0) and factors associated with earlier time to mobilisation. Methods A prospective cohort study was conducted involving patients with hip or knee osteoarthritis who had undergone primary unilateral THA (n = 818) and TKA (n = 989) at 19 Australian hospitals. Patient-related (e.g. age, gender, body mass index), treatment-related (e.g. hospital site, presence of indwelling catheter) and mobilisation-related variables were collected on standardised forms. Time was measured by post-operative days, where POD 0 was defined as the day of surgery ending at midnight. Multivariate Poisson regression analysis identified associations between patient- and treatment-related covariates and time to mobilisation. Results Inter-hospital variation was evident, but overall, only 9.4% of THA and 5.6% of TKA patients mobilised on POD 0. For THA patients, earlier time to mobilisation was associated with hospital site and absences of an indwelling catheter and acute complications. For TKA patients, earlier time to mobilisation was associated with hospital site and absence of donor blood transfusion. Conclusions Few THA and TKA patients mobilise POD 0, although some hospitals appear more aggressive with their mobilisation attempts than others. Treatment-related factors, not patient-related, are associated with post-operative day of mobilisation, indicating the potentially pivotal role of service providers in promoting early mobilisation to improve health outcomes and reduce rates of VTE.

Objective: To measure the prevalence of chronic obstructive pulmonary disease (COPD) among people aged 40 years or older in Australia. Design, setting and participants: A cross-sectional study of people in the community aged ≥ 40 years, selected at random using electoral rolls, in six sites chosen to reflect the sociodemographic and geographic diversity of Australia, conducted between 2006 and 2010. Standardised questionnaires were administered by interview. Forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and the FEV1/FVC ratio were measured by spirometry, before and after bronchodilator administration. Main outcome measure: Prevalence of COPD, classified according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2006 criteria. Results: Complete data were available for 1620 men (participation rate, 26%) and 1737 women (participation rate, 28%). The prevalence of GOLD Stage II or higher COPD (defined as post-bronchodilator FEV1/FVC ratio < 0.70 and FEV1 < 80% predicted) was 7.5% (95% CI, 5.7%–9.4%) among people aged ≥ 40 years, and 29.2% (95% CI, 18.1%–40.2%) among those aged ≥ 75 years. Among people aged ≥ 40 years, the prevalence of wheeze in the past 12 months was 30.0% (95% CI, 27.5%–32.5%), and prevalence of shortness of breath when hurrying on the level or climbing a slight hill was 25.2% (95% CI, 22.7%–27.6%). Conclusions: Symptoms and spirometric evidence of COPD are common among people aged 40 years or older and increase with age. Further research is needed to better understand the diagnosis and management of COPD in Australia, along with continuing efforts to prevent the disease.

Tadalafil, an oral phosphodiesterase type-5 inhibitor, induces pulmonary vasorelaxation by inhibiting the breakdown of cyclic guanosine monophosphate whereas simvastatin, an oral 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase inhibitor, has been shown to reverse pulmonary hypertension (PH) and attenuate vascular remodeling in animal models of pulmonary hypertension. We investigated whether the combination of tadalafil and simvastatin, which has different mechanisms of action, is superior to either drug alone in a rat model of monocrotaline-induced PH.Male Sprague-Dawley rats were randomized to gavage with a vehicle, tadalafil (10 mg/kg/day), simvastatin (2 mg/kg/day), or tadalafi + simvastatin 21 days after the monocrotaline (60 mg/kg) injections. The hemodynamic and histological changes in the pulmonary arterioles, right heart hypertrophy, interleukin 6 (IL-6) levels and perivascular inflammation in the lungs were measured 35 days after monocrotaline exposure.The combination of tadalafil and simvastatin showed significantly more improvement in the mean pulmonary hypertension pressure (mPAP) and right ventricular hypertrophy compared with each monotherapy (p0.05). Combination therapy had additive effects on the increases in lung IL-6 levels and the perivascular inflammation score.These results suggest that the combination of tadalafil and simvastatin bears promise as an approach to treat PH, especially PH associated with inflammation.

Background and Purpose: The diagnosis of cerebellar infarction (CBI) is often challenging due to non-specific or subtle presenting symptoms and signs. We aimed to determine whether a common syndromic cluster of symptoms, signs or vascular risk factors were associated with delayed presentation or misdiagnosis to an Emergency Department (ED). The degree of misdiagnosis between ED and neurology physicians and the influence of delayed presentation or misdiagnosis on outcome were also investigated. Methods: A prospective study of CBI patients at a large tertiary-referral hospital with a comprehensive stroke service. Data are reported with OR and 95% CIs. Results: Of 115 consecutive CBI patients (mean age ± SD 66 ± 14 years, 51% male), infarction was isolated to the cerebellum in 46%; the remainder had additional vascular territory involvement (‘mixed CBI'). Most patients (n = 79, 69%) had a mild stroke (National Institute of Health Stroke Scale score ≤4), and tended to present late to ED (>4.5 h; p = 0.05). Dysarthria (OR 3.9, 95% CI 1.6-9.6, p = 0.003) and prior history of atrial fibrillation (AF; OR 3.0, 95% CI 1.02-9.1, p = 0.047) predicted early presentation (Conclusions: Late ED presentation and misdiagnosis are common for CBI. Timely diagnosis of CBI may increase opportunity for acute stroke therapies and reduce risk of stroke-related complications.