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Distal radius fractures are common and are managed with or without surgery. Current evidence indicates surgical treatment is not superior to nonsurgical treatment at 12 months.Does surgical treatment for displaced distal radius fractures in patients 60 years or older provide better patient-reported wrist pain and function outcomes than nonsurgical treatment at 24 months?In this secondary analysis of a combined multicenter randomized clinical trial (RCT) and a parallel observational study, 300 patients were screened from 19 centers in Australia and New Zealand. Of these, 166 participants were randomized to surgical or nonsurgical treatment. Participants who declined randomization (n = 134) were included in the parallel observational group with the same treatment options and follow-up. Participants were followed up at 3, 12, and 24 months by a blinded assessor. The 24-month outcomes are reported herein. Data were collected from December 1, 2016, to December 31, 2020, and analyzed from February 4 to October 21, 2021.Surgical treatment consisting of open reduction and internal fixation using a volar-locking plate (VLP group) and nonsurgical treatment consisting of closed reduction and cast immobilization (CR group).The primary outcome was patient-reported function using the Patient-Rated Wrist Evaluation (PRWE) questionnaire. Secondary outcomes included health-related quality of life, wrist pain, patient-reported treatment success, patient-rated bother with appearance, and posttreatment complications.Among the 166 randomized and 134 observational participants (300 participants; mean [SD] age, 71.2 [7.5] years; 269 women [89.7%]), 151 (91.0%) randomized and 118 (88.1%) observational participants were followed up at 24 months. In the RCT, no clinically important difference occurred in mean PRWE scores at 24 months (13.6 [95% CI, 9.1-18.1] points for VLP fixation vs 15.8 [95% CI, 11.3-20.2] points for CR; mean difference, 2.1 [95% CI, -4.2 to 8.5]; P = .50). There were no between-group differences in all other outcomes except for patient-reported treatment success, which favored VLP fixation (33 of 74 [44.6%] in the CR group vs 54 of 72 [75.0%] in the VLP fixation group reported very successful treatment; P = .002). Rates of posttreatment complications were generally low and similar between treatment groups, including deep infection (1 of 76 [1.3%] in the CR group vs 0 of 75 in the VLP fixation group) and complex regional pain syndrome (2 of 76 [2.6%] in the CR group vs 1 of 75 [1.3%] in the VLP fixation group). The 24-month trial outcomes were consistent with 12-month outcomes and with outcomes from the observational group.Consistent with previous reports, these findings suggest that VLP fixation may not be superior to CR for displaced distal radius fractures for patient-rated wrist function in persons 60 years or older during a 2-year period. Significantly higher patient-reported treatment success at 2 years in the VLP group may be attributable to other treatment outcomes not captured in this study.ANZCTR.org Identifier: ACTRN12616000969460.

Background Given the complexity of living donor hepatectomy, it is expected that high hospital volume will better outcomes. This study aims to evaluate post-operative outcomes for living donor hepatectomy in a medium volume liver transplant centre and compare to outcomes in high volume centres. Also, it serves as a validation tool for framework of structure-process-outcome model for safe living donor hepatectomy program. Methods 204 donors who underwent donor hepatectomy between June 1996 to September 2019 were reviewed retrospectively and compared to outcomes in high volume centres. Results At 6 months, overall donor morbidity rate was 20/204 (9.8%). Wound complications were most common at 5/204 (2.5%). Majority of complications were either Clavien grade 1 or 2 and only 3 donors had Clavien grade 3 complications. There was zero donor mortality. Discussion Our centre's donor morbidity rate of 9.8% is the one of the lowest reported in the published literature. With increased experience, stringent donor selection and enhanced perioperative care by a multi-disciplinary team, outcomes in a medium volume centre can match the outcomes reported in high volume centres. The framework for quality in terms of structure, process and outcomes is presented which can be adopted for developing programs.

Introduction Pharmacy students should be eHealth literate by being skilful in searching, evaluating and applying online health information. Mobile health applications should be utilised when making clinical decisions to achieve optimal patient care with the ever-changing pharmacy practice. This study aims to explore the eHealth literacy and mobile health application utilisation amongst pharmacy undergraduates. Methods A cross-sectional study was conducted from March to April 2021. An online survey, consisting of socio-demographic characteristics, Internet use, eHealth Literacy Scale and mobile health application utilisation, was distributed amongst pharmacy undergraduates in public and private universities in Malaysia. Data analysis included descriptive statistics, one-way analysis of variance test, Mann–Whitney U test and Kruskal–Wallis test Results A total of 415 participants completed the survey (response rate = 82.5%). The median eHealth Literacy Scale score (out of 40) was 31.0 ± 3.0 (interquartile range). More than one-third of participants (34.7%) were found to have low eHealth literacy. Many lacked confidence in making health decisions from online information (42.4%) and skills in distinguishing between high-quality and low-quality health resources (35.2%). Only 70.4% of the participants had mobile health applications installed on their smartphones and/or tablets. Some students felt that they were neither knowledgeable nor skilful enough to utilise mobile health applications (24.8%), whereas 23.9% were unaware of the mobile health applications available. Conclusion In summary, the eHealth literacy of Malaysian pharmacy students can be further enhanced by incorporating eHealth literacy-focused programmes into the curriculum. Moreover, pharmacy students’ mobile health application utilisation can be improved through increased awareness and support from universities.

International audience; Although workplace incivility has received increasing attention in organizational research over the past two decades, there have been recurring questions about its construct validity, especially vis-à-vis other forms of workplace mistreatment. Also, the antecedents of experienced incivility remain understudied, leaving an incomplete understanding of its nomological network. In this meta-analysis using Schmidt and Hunter's [Methods of meta-analysis: Correcting error and bias in research findings (3rd ed.), Sage] random-effect meta-analytic methods, we validate the construct of incivility by testing its reliability, convergent and discriminant validity, as well as its incremental predictive validity over other forms of mistreatment. We also extend its nomological network by drawing on the perpetrator predation framework to systematically study the antecedents of experienced incivility. Based on 105 independent samples and 51,008 participants, we find extensive support for incivility's construct validity. Besides, we demonstrate that demographic characteristics (gender, race, rank, and tenure), personality traits (agreeableness, conscientiousness, neuroticism, negative affectivity, and self-esteem), and contextual factors (perceived uncivil climate and socially supportive climate) are important antecedents of experienced incivility, with contextual factors displaying a stronger association with incivility. In a supplementary primary study with 457 participants, we find further support for the construct validity of incivility. We discuss the theoretical and practical implications of this study. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Aims To evaluate whether biomarkers derived from fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) performed prior to (prePET) and during the third week (interim PET; iPET) of radiotherapy can predict treatment outcomes in human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPC). Materials and methods This retrospective analysis included 46 patients with newly diagnosed OPC treated with definitive (chemo)radiation and all patients had confirmed positive HPV status (HPV+OPC) based on p16 immunohistochemistry. The maximum standardised uptake value (SUVmax), metabolic tumour volume (MTV) and total lesional glycolysis (TLG) of primary, index node (node with the highest TLG) and total lymph nodes and their median percentage (≥50%) reductions in iPET were analysed, and correlated with 5-year Kaplan–Meier and multivariable analyses (smoking, T4, N2b-3 and AJCC stage IV), including local failure-free survival, regional failure-free survival, locoregional failure-free survival (LRFFS), distant metastatic failure-free survival (DMFFS), disease-free survival (DFS) and overall survival. Results There was no association of outcomes with prePET parameters observed on multivariate analysis. A complete metabolic response of primary tumour was seen in 13 patients; the negative predictive value for local failure was 100%. More than a 50% reduction in total nodal MTV provided the best predictor of outcomes, including LRFFS (88% versus 47.1%, P = 0.006, hazard ratio = 0.153) and DFS (78.2% versus 41.2%, P = 0.01, hazard ratio = 0.234). More than a 50% reduction in index node TLG was inversely related to DMFFS: a better nodal response was associated with a higher incidence of distant metastatic failure (66.7% versus 100%, P = 0.009, hazard ratio = 3.0). Conclusion The reduction (≥50%) of volumetric nodal metabolic burden can potentially identify a subgroup of HPV+OPC patients at low risk of locoregional failure but inversely at higher risk of distant metastatic failure and may have a role in individualised adaptive radiotherapy and systemic therapy.

PURPOSE The ideal location for mesh placement in minimally invasive ventral hernia repair (VHR) is still up for debate. We undertook a systematic review and meta-analysis (SRMA) to evaluate the outcomes of patients who received intraperitoneal mesh versus those that received extraperitoneal mesh in minimally invasive VHR. METHODS We searched PubMed, EMBASE, Cochrane, and Scopus from inception to May 3, 2021. We selected studies comparing intraperitoneal mesh versus extraperitoneal mesh placement in minimally invasive VHR. A meta-analysis was done for the outcomes of surgical site infection (SSI), seroma, hematoma, readmission, and recurrence. A subgroup analysis was conducted for a subset of studies comparing patients who have undergone intraperitoneal onlay mesh (IPOM) versus extended totally extraperitoneal approach (e-TEP). RESULTS A total of 11 studies (2320 patients) were identified. We found no statistically significant difference between patients who received intraperitoneal versus extraperitoneal mesh for outcomes of SSI, seroma, hematoma, readmission, and recurrence [(RR 1.60, 95% CI 0.60-4.27), (RR 1.39, 95% CI 0.68-2.81), (RR 1.29, 95% CI 0.45-3.72), (RR 1.40, 95% CI 0.69-2.86), and (RR 1.22, 95% CI 0.22-6.63), respectively]. The subgroup analysis had findings similar to the overall analysis. CONCLUSION Based on short-term results, extraperitoneal mesh does not appear to be superior to intraperitoneal mesh in minimally invasive ventral hernia repair. The choice of mesh location should be based on the current evidence, surgeon, and center experience as well as individualized to each patient.

There has not been a consensus on the superiority of a surgical approach for minimally invasive ventral hernia repair. This systematic review and meta-analysis (SRMA) aims to compare clinical, and patient-reported outcomes of robotic-assisted ventral hernia repair (rVHR) to traditional endo-laparoscopic ventral hernia repair (lapVHR). We searched PubMed, EMBASE, Cochrane and Scopus from inception to 16th March 2021. We selected randomised controlled trials and propensity score matched studies comparing rVHR to lapVHR. A meta-analysis was done for the outcomes of operative time, length of hospital stay, open conversion, recurrence, surgical site occurrence and cost. A total of 5 studies (3732 patients) were included in the qualitative and quantitative synthesis. Significantly shorter operative times were reported with the lapVHR as compared to rVHR (weighted mean difference (WMD): 62.52, 95% CI: 50.84–74.19). There was also significantly less rates of open conversion with rVHR as compared to lapVHR (WMD: 0.22, 95% CI: 0.09–0.54). No significant differences in patient-reported outcomes that was discernible from the two papers that reported them. Overall, rVHR is comparable to lapVHR with longer operative times but less open conversion. It is, therefore, important to have proper patient selection to maximise the utility of rVHR.

Background The potential protective role of eosinophils in the COVID-19 pandemic has aroused great interest, given their potential virus clearance function and the infection resistance of asthma patients to this coronavirus. However, it is unknown whether eosinophil counts could serve as a predictor of the severity of COVID-19. Methods A total of 1004 patients with confirmed COVID-19 who were admitted to Leishenshan Hospital in Wuhan, China, were enrolled in this study, including 905 patients in the general ward and 99 patients in the intensive care unit (ICU). We reviewed their medical data to analyze the association between eosinophils and ICU admission and death. Results Of our 1004 patients with COVID-19, low eosinophil counts/ratios were observed in severe cases. After adjusting for confounders that could have affected the outcome, we found that eosinophil counts might not be a predictor of ICU admission. In 99 ICU patients, 58 of whom survived and 41 of whom died, low eosinophil level was an indicator of death in severe COVID-19 patients with a cutoff value of 0.04 × 109/L, which had an area under the curve of 0.665 (95% CI = 1.089-17.839; P = .045) with sensitivity and specificity of 0.569 and 0.7317, respectively. Conclusion Our research revealed that a low eosinophil level is a predictor of death in ICU patients rather than a cause of ICU admission.

Brain perivascular macrophages (PVMs) are attracting increasing attention as this emerging cell population in the brain has multifaced roles in supporting the central nervous system structure, brain development, and maintaining physiological functions. They also widely participate in neurological diseases such as neurodegeneration and ischemic stroke. Moreover, PVMs have been reported to have both beneficial and detrimental effects under different pathological contexts. Advanced research technologies allowed the further in-depth study of PVMs and revealed novel concepts in their origins, differentiation, and regulatory mechanisms. Deepened understanding of the roles of PVMs in different brain pathological conditions can reveal novel phenotypic changes and regulatory signaling, which might pave the way for the development of novel treatment strategies targeting PVMs.

Lactic acid bacteria (LAB) are well known to elicit health benefits in humans, but their functional metabolic landscapes remain unexplored. Here, we analyze differences in growth, intestinal persistence, and postbiotic biosynthesis of six representative LAB and their interactions with 15 gut bacteria under 11 dietary regimes by combining multi-omics and in silico modeling. We confirmed predictions on short-term persistence of LAB and their interactions with commensals using cecal microbiome abundance and spent-medium experiments. Our analyses indicate that probiotic attributes are both diet and species specific and cannot be solely explained using genomics. For example, although both Lacticaseibacillus casei and Lactiplantibacillus plantarum encode similarly sized genomes with diverse capabilities, L. casei exhibits a more desirable phenotype. In addition, "high-fat/low-carb" diets more likely lead to detrimental outcomes for most LAB. Collectively, our results highlight that probiotics are not "one size fits all" health supplements and lay the foundation for personalized probiotic design.

Background Therapeutic drug monitoring (TDM) of infliximab (IFX) levels in inflammatory bowel disease (IBD) patients can help to guide dose adjustments or changes to therapy for selected patients in remission or with secondary loss of response (LOR). Aims To determine how IFX TDM is utilised in a real-life clinical setting and to quantify the potential for TDM to reduce the unnecessary use of IFX. Methods Data from all public IBD IFX level testing performed across Australia were prospectively collected from June 2016 to July 2017 to assess physician-reported for testing indications (induction, in remission or LOR) and associated results. The hypothetical influence of IFX TDM was based on an optimal therapeutic range of 6-10 mg/L for mucosal healing. Results Secondary LOR (reactive TDM) was the most common indication for TDM. These patients have consistently lower median IFX levels: 3.02 mg/L (IQR 1.14-6.67 mg/L) versus 5.22 mg/L (IQR 2.70-8.12 mg/L), P = 0.0001 compared with patients in remission (proactive TDM). TDM helped to identify unnecessary use of IFX in 30.6% of the TDM tests performed in luminal Crohn disease and ulcerative colitis patients, with an associated drug cost saving of $531.38 per IFX TDM test episode. Unnecessary IFX use was identified in 38.9% (96/247) of reactive IFX TDM tests performed and in 19.3% (35/181) of proactive testing. Conclusion Use of both reactive and proactive IFX TDM is cost-effective for IBD management as it informs the clinician where unnecessary use of IFX can be stopped.

Divalent inhibitors of the neuraminidase enzyme (NA) of the Influenza A virus were synthesized with vastly different spacers. The spacers varied from 14 to 56 atoms and were relatively rigid by way of the building blocks and their connection by CuAAC. As the ligand for these constructs, a Δ 4-β-d-glucoronide was used, which can be prepared form N-acetyl glucosamine. This ligand showed good NA inhibitory potency but with room for improvement by multivalency enhancement. The synthesized compounds showed modest potency enhancement in NA activity assays but a sizeable potency increase in a 4-day cytopathic effect assay. The demonstration that the compounds can also inhibit hemagglutinin in addition to NA may be the cause of the enhancement.

Chromatin immunoprecipitation (ChIP) is a technique that has been widely used to interrogate DNA-protein interactions in cells. In recent years, human pluripotent stem cell (hPSC)-derived 3D organoids have emerged as a powerful model to understand human development and diseases. Performing ChIP in hPSC-derived 3D organoids is a useful approach to dissect the roles of transcription factors or co-factors and to understand the epigenetic landscape in human development and diseases. However, performing ChIP in 3D organoids is more challenging than monolayer cultures, and an optimized protocol is needed for interpretable data. Hence, in this chapter, we describe in detail a protocol for performing ChIP in hPSC-derived islet-like cells as an example, from organoid harvest to ChIP-qPCR data analysis. This chapter also highlights potential pitfalls and provides recommendations for troubleshooting.

Critical aortic stenosis (AS) of the fetal heart causes a drastic change in the cardiac biomechanical environment. Consequently, a substantial proportion of such cases will lead to a single-ventricular birth outcome. However, the biomechanics of the disease is not well understood. To address this, we performed Finite Element (FE) modelling of the healthy fetal left ventricle (LV) based on patient-specific 4D ultrasound imaging, and simulated various disease features observed in clinical fetal AS to understand their biomechanical impact. These features included aortic stenosis, mitral regurgitation (MR) and LV hypertrophy, reduced contractility, and increased myocardial stiffness. AS was found to elevate LV pressures and myocardial stresses, and depending on severity, can drastically decrease stroke volume and myocardial strains. These effects are moderated by MR. AS alone did not lead to MR velocities above 3 m/s unless LV hypertrophy was included, suggesting that hypertrophy may be involved in clinical cases with high MR velocities. LV hypertrophy substantially elevated LV pressure, valve flow velocities and stroke volume, while reducing LV contractility resulted in diminished LV pressure, stroke volume and wall strains. Typical extent of hypertrophy during fetal AS in the clinic, however, led to excessive LV pressure and valve velocity in the FE model, suggesting that reduced contractility is typically associated with hypertrophy. Increased LV passive stiffness, which might represent fibroelastosis, was found to have minimal impact on LV pressures, stroke volume, and wall strain. This suggested that fibroelastosis could be a by-product of the disease progression and does not significantly impede cardiac function. Our study demonstrates that FE modelling is a valuable tool for elucidating the biomechanics of congenital heart disease and can calculate parameters which are difficult to measure, such as intraventricular pressure and myocardial stresses. Electronic supplementary material The online version of this article (10.1007/s10439-020-02683-x) contains supplementary material, which is available to authorized users.

Novel advances in the field of brain imaging have enabled the unprecedented clinical application of various imaging modalities to facilitate disease diagnosis and treatment. Electrical impedance tomography (EIT) is a functional imaging technique that measures the transfer impedances between electrodes on the body surface to estimate the spatial distribution of electrical properties of tissues. EIT offers many advantages over other neuroimaging technologies, which has led to its potential clinical use. This qualitative review provides an overview of the basic principles, algorithms, and system composition of EIT. Recent advances in the field of EIT are discussed in the context of epilepsy, stroke, brain injuries and edema, and other brain diseases. Further, we summarize factors limiting the development of brain EIT and highlight prospects for the field. In epilepsy imaging, there have been advances in EIT imaging depth, from cortical to subcortical regions. In stroke research, a bedside EIT stroke monitoring system has been developed for clinical practice, and data support the role of EIT in multi-modal imaging for diagnosing stroke. Additionally, EIT has been applied to monitor the changes in brain water content associated with cerebral edema, enabling the early identification of brain edema and the evaluation of mannitol dehydration. However, anatomically realistic geometry, inhomogeneity, cranium completeness, anisotropy and skull type, etc., must be considered to improve the accuracy of EIT modeling. Thus, the further establishment of EIT as a mature and routine diagnostic technique will necessitate the accumulation of more supporting evidence.

Erratum in Publisher Correction: Discovery of a genetic module essential for assigning left-right asymmetry in humans and ancestral vertebrates. Szenker-Ravi E, Ott T, Khatoo M, Moreau de Bellaing A, Goh WX, Chong YL, Beckers A, Kannesan D, Louvel G, Anujan P, Ravi V, Bonnard C, Moutton S, Schoen P, Fradin M, Colin E, Megarbane A, Daou L, Chehab G, Di Filippo S, Rooryck C, Deleuze JF, Boland A, Arribard N, Eker R, Tohari S, Ng AY, Rio M, Lim CT, Eisenhaber B, Eisenhaber F, Venkatesh B, Amiel J, Crollius HR, Gordon CT, Gossler A, Roy S, Attie-Bitach T, Blum M, Bouvagnet P, Reversade B.Nat Genet. 2022 Jun;54(6):906. doi: 10.1038/s41588-022-01053-8.PMID: 35304595 No abstract available.; International audience; The vertebrate left-right axis is specified during embryogenesis by a transient organ: the left-right organizer (LRO). Species including fish, amphibians, rodents and humans deploy motile cilia in the LRO to break bilateral symmetry, while reptiles, birds, even-toed mammals and cetaceans are believed to have LROs without motile cilia. We searched for genes whose loss during vertebrate evolution follows this pattern and identified five genes encoding extracellular proteins, including a putative protease with hitherto unknown functions that we named ciliated left-right organizer metallopeptide (CIROP). Here, we show that CIROP is specifically expressed in ciliated LROs. In zebrafish and Xenopus, CIROP is required solely on the left side, downstream of the leftward flow, but upstream of DAND5, the first asymmetrically expressed gene. We further ascertained 21 human patients with loss-of-function CIROP mutations presenting with recessive situs anomalies. Our findings posit the existence of an ancestral genetic module that has twice disappeared during vertebrate evolution but remains essential for distinguishing left from right in humans.

Hyaluronan (HA) is a ubiquitous extracellular matrix component playing a crucial role in the regulation of cell behaviors, including cancer. Aggressive breast cancer cells tend to proliferate, migrate and metastatize. Notably, triple-negative breast cancer cells lacking the expression of estrogen receptor (ER) as well as progesterone receptor and HER2 are more aggressive than ER-positive ones. As currently no targeted therapy is available for triple-negative breast cancer, the identification of novel therapeutic targets has a high clinical priority. In ER-negative cells, tumoral behavior can be reduced by inhibiting HA synthesis or silencing the enzymes involved in its metabolism, such as HA synthase 2 (HAS2). HAS2-AS1 is a long non-coding RNA belonging to the natural antisense transcript family which is known to favor HAS2 gene expression and HA synthesis, thus bolstering malignant progression in brain, ovary, and lung tumors. As the role of HAS2-AS1 has not yet been investigated in breast cancer, in this work we report that ER-positive breast cancers had lower HAS2-AS1 expression compared to ER-negative tumors. Moreover, the survival of patients with ER-negative tumors was higher when the expression of HAS2-AS1 was elevated. Experiments with ER-negative cell lines as MDA-MB-231 and Hs 578T revealed that the overexpression of either the full-length HAS2-AS1 or its exon 2 long or short isoforms alone, strongly reduced cell viability, migration, and invasion, whereas HAS2-AS1 silencing increased cell aggressiveness. Unexpectedly, in these ER-negative cell lines, HAS2-AS1 is involved neither in the regulation of HAS2 nor in HA deposition. Finally, transcriptome analysis revealed that HAS2-AS1 modulation affected several pathways, including apoptosis, proliferation, motility, adhesion, epithelial to mesenchymal transition, and signaling, describing this long non-coding RNA as an important regulator of breast cancer cells aggressiveness.

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.

Congenital heart malformations occur to substantial number of pregnancies. Studies showed that abnormal flow biomechanical environments could lead to malformations, making it important to understand the biomechanical environment of the developing heart. We performed 4D high-frequency ultrasound scans of chick embryonic hearts at HH25 to study the biomechanics of the whole heart (atria and ventricle). A novel and high-fidelity motion estimation technique, based on temporal motion model and non-rigid image registration algorithm, allowed automatic tracking of fluid-structure boundaries from scan images, and supported flow simulations. Results demonstrated that atrial appendages were the most contractile portion of the atria, having disproportionately high contribution to atrial blood pumping for its volume in the atria. However, the atria played a small role in blood pumping compared to the ventricle, as it had much lower ejection energy expenditure, and as the ventricle appeared to be able to draw inflow from the veins directly during late diastole. Spatially and temporally averaged wall shear stresses (WSS) for various cardiac structures were 0.062–0.068 Pa, but spatial-averaged WSS could be as high as 0.54 Pa in the RV. WSS was especially elevated at the atrial inlet, atrioventricular junction, regions near to the outflow tract, and at dividing lines between the left and right atrium and left and right side of the ventricle, where septation had begun and the lumen had narrowed. Elevated WSS could serve as biomechanics stimulation for proper growth and development.

The treatment of atypical femoral shaft fractures with abnormal bowing provides a unique challenge for surgeons. Whilst intramedullary fixation of atypical femoral shaft fractures affords both mechanical and biological benefits, the mismatch between standard intramedullary devices and the abnormal femoral bowing in these patients makes this method of fixation challenging for the surgeon. The purpose of this manuscript is to illustrate the evolution of our surgical technique through a series of four patients. The critical factors we identified include lateral positioning of the patient for reduction, the use of a piriformis-start nail, and an entry point that was anterior in the sagittal profile and lateral in the coronal profile. This technique was easily replicable, facilitated more anatomical reduction and aided in avoiding complications.

Background Distinguishing strangulated bowel obstruction (StBO) from simple bowel obstruction (SiBO) still poses a challenge for emergency surgeons. We aimed to construct a predictive model that could distinctly discriminate StBO from SiBO based on the degree of bowel ischemia. Methods The patients diagnosed with intestinal obstruction were enrolled and divided into SiBO group and StBO group. Binary logistic regression was applied to identify independent risk factors, and then predictive models based on radiological and multi-dimensional models were constructed. Receiver operating characteristic (ROC) curves and the area under the curve (AUC) were calculated to assess the accuracy of the predicted models. Via stratification analysis, we validated the multi-dimensional model in the prediction of transmural necrosis both in the training set and validation set. Results Of the 281 patients with SBO, 45 (16.0%) were found to have StBO, while 236(84.0%) with SiBO. The AUC of the radiological model was 0.706 (95%CI, 0.617–0.795). In the multivariate analysis, seven risk factors including pain duration ≤ 3 days (OR = 3.775), rebound tenderness (OR = 5.201), low-to-absent bowel sounds (OR = 5.006), low levels of potassium (OR = 3.696) and sodium (OR = 3.753), high levels of BUN (OR = 4.349), high radiological score (OR = 11.264) were identified. The AUC of the multi-dimensional model was 0.857(95%CI, 0.793–0.920). In the stratification analysis, the proportion of patients with transmural necrosis was significantly greater in the high-risk group (24%) than in the medium-risk group (3%). No transmural necrosis was found in the low-risk group. The AUC of the validation set was 0.910 (95%CI, 0.843–0.976). None of patients in the low-risk and medium-risk score group suffered with StBO. However, all patients with bowel ischemia (12%) and necrosis (24%) were resorted into high-risk score group. Conclusion The novel multi-dimensional model offers a useful tool for predicting StBO. Clinical management could be performed according to the multivariate score.

Background The volume-outcome relation for complex surgical procedures such as living donor liver transplantation (LDLT) generally favors high volume (HV) centers . It is important for low to medium volume (MV) centers to evaluate their centers’ performance against HV centers to allow early detection and correction of potential systemic issues. There is a dearth of national and international comprehensive registries for LDLT that may allow reasonable risk-adjusted comparisons for benchmarking. This study aims to evaluate the LDLT program by comparing our center's performance against HV centers of the Adult-to-Adult Living Donor Liver Transplantation cohort. Study design Patient outcomes from a MV transplant center were compared with 11 HV transplant centers from the Adult-to-Adult Living Donor Liver Transplantation cohort. Outcomes evaluated included length of hospital stay, same admission mortality, 90-day mortality, and overall survival. Results A total of 1381 patients were analzyed. HV 1 to 4, 6, 8, 9, and 11 centers had a shorter median length of hospital stay compared with the MV center (All Dunnett corrected P values all less than .05). HV 9 and 11 centers had lower same admission mortality compared with the MV center (Dunnett corrected P = .023 and .015). After adjusting for other significant predictors, the MV center had comparable 90-day mortality rates and overall survival rates to all HV centers. Conclusion This benchmarking exercise has demonstrated that the limitation of low institutional case volume can be overcome with a protocol-based framework to implement a safe LDLT program. This framework presented can be adopted for developing programs.

Tumor necrosis factor-alpha inhibitors, including infliximab and adalimumab, are effective medical treatments for perianal fistulising Crohn's disease (CD), but not all patients achieve fistula healing.To determine the correlation between perianal fistula healing and closure with infliximab and adalimumab trough levels.In this multicentre retrospective study conducted across four tertiary inflammatory bowel disease centres in Australia, we identified CD patients with perianal fistulae on maintenance infliximab or adalimumab who had a trough level within twelve weeks of clinical assessment. Data collected included demographics, serum infliximab and adalimumab trough levels (mg/L) within 12 wk before or after their most recent clinical assessment and concomitant medical or surgical therapy. The primary outcome was fistula healing, defined as cessation in fistula drainage. The secondary outcome was fistula closure, defined as healing and closure of all external fistula openings. Differences between patients who did or did not achieve fistula healing were compared using the chi-square test,One hundred and fourteen patients (66 infliximab, 48 adalimumab) were included. Forty-eight (72.7%) patients on maintenance infliximab achieved fistula healing and 18 (27.3%) achieved fistula closure. Thirty-seven (77%) patients on maintenance adalimumab achieved fistula healing and 17 (35.4%) achieved fistula closure. Patients who achieved fistula healing had significantly higher infliximab and adalimumab trough levels than patients who did not [infliximab: 6.4 (3.8-9.5)Higher maintenance infliximab and adalimumab trough levels are associated with perianal fistula healing in CD.

Left atrial ligation (LAL) of the chick embryonic heart at HH21 is a model of the hypoplastic left heart syndrome (HLHS) disease, demonstrating morphological and hemodynamic features similar to human HLHS cases. Since it relies on mechanical intervention without genetic or pharmacological manipulations, it is a good model for understanding the biomechanics origins of such HLHS malformations. To date, however, the fluid mechanical environment of this model is poorly understood. In the current study, we performed 4D ultrasound imaging of LAL and normal chick embryonic hearts and 4D cardiac flow simulations to help shed light on the mechanical environment that may lead to the HLHS morphology. Results showed that the HH25 LAL atrial function was compromised, and velocities in the ventricle were reduced. The HH25 LAL ventricles developed a more triangular shape with a sharper apex, and in some cases, the atrioventricular junction shifted medially. These changes led to more sluggish flow near the ventricular free wall and apex, where more fluid particles moved in an oscillatory manner with the motion of the ventricular wall, while slowly being washed out, resulting in lower wall shear stresses and higher oscillatory indices. Consequent to these flow conditions, at HH28, even before septation is complete, the left ventricle was found to be hypoplastic while the right ventricle was found to be larger in compensation. Our results suggest that the low and oscillatory flow near the left side of the heart may play a role in causing the HLHS morphology in the LAL model. Supplementary Information The online version contains supplementary material available at 10.1007/s10237-021-01447-3.

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.

Objectives There is an increased interest in enhanced recovery after surgery (ERAS) minimizing adverse events after orthopedic surgery. Little consensus supports the effectiveness of these interventions. The purpose of present systematic review and meta-analysis is to comprehensively analyze and evaluate the significance of ERAS interventions for postoperative outcomes after orthopedic surgery. Methods PubMed, EMBASE, and Cochrane databases were totally searched from the inception dates to May 31, 2018. Two reviewers independently extracted the data from the selected articles using a standardized form and assessed the risk of bias. The analysis was performed using STATA 12.0. Results A total of 15 published studies fulfilled the requirements of inclusion criteria. We found that the ERAS group showed a significant association with lower incidence of postoperative complications (OR, 0.70; 95% CI, 0.64 to 0.78). Meanwhile, ERAS was also associated with the decline in 30-day mortality rate and Oswestry Disability Index (ODI). However, no significant differences were identified between the two groups regarding the 30-day readmission rate (P = 0.397). Conclusions Our meta-analysis suggested that the ERAS group had more advantages in reducing incidence of postoperative complications, 30-day mortality rate, and ODI after orthopedic surgery, but not of 30-day readmission rate. However, further research with standardized, unbiased methods and larger sample sizes is required for deeper analysis. Electronic supplementary material The online version of this article (10.1186/s13018-019-1116-y) contains supplementary material, which is available to authorized users.

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.

Stroke is the world's leading cause of disability with limited brain repair treatments which effectively improve long‐term neurological deficits. The neuroinflammatory responses persist into the late repair phase of stroke and participate in all brain repair elements, including neurogenesis, angiogenesis, synaptogenesis, remyelination and axonal sprouting, shedding new light on post–stroke brain recovery. Resident brain glial cells, such as astrocytes not only contribute to neuroinflammation after stroke, but also secrete a wide range of trophic factors that can promote post–stroke brain repair. Alternatively, activated microglia, monocytes, and neutrophils in the innate immune system, traditionally considered as major damaging factors after stroke, have been suggested to be extensively involved in brain repair after stroke. The adaptive immune system may also have its bright side during the late regenerative phase, affecting the immune suppressive regulatory T cells and B cells. This review summarizes the recent findings in the evolving role of neuroinflammation in multiple post–stroke brain repair mechanisms and poses unanswered questions that may generate new directions for future research and give rise to novel therapeutic targets to improve stroke recovery.

Middle East respiratory syndrome (MERS) is a lethal respiratory disease with its first case reported back in 2012 (Jeddah, Saudi Arabia). It is a novel, single-stranded, positive-sense RNA beta coronavirus (MERS-CoV) that was isolated from a patient who died from a severe respiratory illness. Later, it was found that this patient was infected with MERS. MERS is endemic to countries in the Middle East regions, such as Saudi Arabia, Jordan, Qatar, Oman, Kuwait and the United Arab Emirates. It has been reported that the MERS virus originated from bats and dromedary camels, the natural hosts of MERS-CoV. The transmission of the virus to humans has been thought to be either direct or indirect. Few camel-to-human transmissions were reported earlier. However, the mode of transmission of how the virus affects humans remains unanswered. Moreover, outbreaks in either family-based or hospital-based settings were observed with high mortality rates, especially in individuals who did not receive proper management or those with underlying comorbidities, such as diabetes and renal failure. Since then, there have been numerous reports hypothesising complications in fatal cases of MERS. Over the years, various diagnostic methods, treatment strategies and preventive measures have been strategised in containing the MERS infection. Evidence from multiple sources implicated that no treatment options and vaccines have been developed in specific, for the direct management of MERS-CoV infection. Nevertheless, there are supportive measures outlined in response to symptom-related management. Health authorities should stress more on infection and prevention control measures, to ensure that MERS remains as a low-level threat to public health.

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.

We studied the effects of heterozygous human INS gene mutations on insulin secretion, endoplasmic reticulum (ER) stress and other mechanisms in both MIN6 and human induced pluripotent stem cells (hiPSC)-derived beta-like cells, as well as the effects of prolonged overexpression of mutant human INS in MIN6 cells.We modelled the structure of mutant C109Y and G32V proinsulin computationally to examine the in silico effects. We then overexpressed either wild-type (WT), mutant (C109Y or G32V), or both WT and mutant human preproinsulin in MIN6 cells, both transiently and stably over several weeks. We measured the levels of human and rodent insulin secreted, and examined the transcript and protein levels of several ER stress and apoptotic markers. We also reprogrammed human donor fibroblasts heterozygous for the C109Y mutation into hiPSCs and differentiated these into pancreatic beta-like cells, which were subjected to single-cell RNA-sequencing and transcript and protein analyses for ER stress and apoptotic markers.The computational modelling studies, and short-term and long-term expression studies in beta cells, revealed the presence of ER stress, organelle changes and insulin processing defects, resulting in a decreased amount of insulin secreted but not the ability to secrete insulin. By 9 weeks of expression of mutant human INS, dominant-negative effects of mutant INS were evident and beta cell insulin secretory capacity declined. INSThe results provide deeper insights into the mechanisms of beta cell failure during INS mutation-mediated diabetes disease progression. Decreasing spliced X-box binding protein 1 (sXBP1) or inflammatory response could be avenues to restore the function of the remaining WT INS allele.

Background Models of care for managing total knee or hip arthroplasty (TKA, THA) incorporating early mobilisation are associated with shorter acute length-of-stay (LOS). Few studies have examined the effect of implementing early mobilisation in isolation, however. This study aimed to determine if an accelerated mobilisation protocol implemented in isolation is associated with a reduced LOS without undermining care. Method A Before-After (quasi-experimental) study was used. Standard practice pre-implementation of the new protocol was physiotherapist-led mobilisation once per day commencing on post-operative Day 1 (Before phase). The new protocol (After phase) aimed to mobilise patients four times by end of Day 2 including an attempt to commence on Day 0; physiotherapy weekend coverage was necessarily increased. Poisson regression modelling was used to determine associations between study period and LOS. Additional outcomes to 12 weeks post-surgery were monitored to identify unintended consequences of the new protocol. Time to first mobilisation (hours) and proportion mobilising Day 0 were monitored to assess protocol compliance. An embedded qualitative component captured staff perspectives of the new protocol. Results Five hundred twenty consecutive patients (n = 278, Before; n = 242, After) were included. The new protocol was associated with no change in unadjusted LOS, a small reduction in adjusted LOS (8.1%, p = 0.046), a reduction in time to first mobilisation (28.5 (10.8) vs 22.6 (8.1) hrs, p p Conclusion Small reductions in LOS are possible utilising an early mobilisation protocol in isolation after TKA or THA although staff burden is increased likely undermining both sustainability and the magnitude of the change. Simultaneous incorporation of other changes within the pathway would likely secure larger reductions in LOS.

BACKGROUND Colonoscopy remains the gold standard for detection of colonic disease. An optimal evaluation depends on adequate bowel cleansing. Patients with inflammatory bowel disease (IBD), require frequent endoscopic assessment for both activity and dysplasia assessment. Two commonly used bowel preparations in Australia are Prep Kit-C (Pc) and Moviprep (Mp). Little is known about tolerability, efficacy and safety of split protocols of Mp and Pc in both IBD and non-IBD patients. AIM To primary aim was to compare the tolerability, efficacy and safety of split protocols of Mp and Pc in patients having a colonoscopy. The secondary aim was to compare the efficacy, tolerability and safety of either preparation in patients with or without IBD. METHODS Patients were randomized to Pc or Mp bowel preparation. Patients completed a questionnaire to assess tolerability. Efficacy was assessed using the Ottawa Bowel Preparation Score. Serum electrolytes and renal function were collected one week prior to colonoscopy and on the day of colonoscopy. RESULTS Of 338 patients met the inclusion criteria. Of 168 patients randomized to Mp and 170 to Pc. The efficacy of bowel preparation (mean Ottawa Bowel Preparation Score) was similar between Mp (5.4 ± 2.4) and Pc (5.1 ± 2.1) (P = 0.3). Mean tolerability scores were similar in Mp (11.84 ± 5.4) and Pc (10.99 ± 5.2; P = 0.17). 125 patients had IBD (73 had Crohn's Disease and 52 had Ulcerative colitis). Sixty-four IBD patients were allocated to Mp and 61 to Pc. In non-IBD patients, 104 were allocated to Mp and 109 to Pc. The mean tolerability score in the IBD group was lower than the non-IBD group (mean tolerability scores: IBD: 10.3 ± 5.1 and non-IBD: 12.0 ± 5.3; P = 0.01). IBD patients described more abdominal pain with Mp when compared with Pc; (Mp: 5.7 ± 4.4 vs Pc: 3.6 ± 2.6, P = 0.046). Serum magnesium level increased with Pc compared with Mp in all patients (mean increase in mmol/L: Mp: 0.03 ± 0.117 and Pc: 0.11 ± 0.106; P < 0.0001). CONCLUSION In this study, the efficacy, tolerability and safety of Mp and Pc were similar in all patients. However, patients with IBD reported lower tolerability with both preparations. Specifically, IBD patients had more abdominal pain with Mp. These results should be considered when recommending bowel preparation especially to IBD patients.

Objective Transdifferentiation exists between stromal cells or between stromal cells and cancer cells. Evodiamine and berberine are predominant pharmacological components of Zuojin pill, a prescription of Traditional Chinese Medicine, playing crucial functions in remolding of tumor microenvironment. This study aimed to explore the effect of combination of evodiamine with berberine (cBerEvo) on the phenotypic transition of colon epithelial cells induced by tumor-associated fibroblasts, as well as the involved mechanisms.Methods Human normal colon epithelial cell line HCoEpiC cells were treated with the prepared conditioned medium of CCD-18Co, a human colon myofibroblast line, to induce epithelial-mesenchymal transition. Phase contrast microscope was used to observe the morphological changes. Epithelial-mesenchymal transition markers including E-cadherin, vimentin and alpha-smooth muscle actin (α-SMA) were observed with immunofluorescence microscopy. Migration was assessed by wound healing assay. Western blotting was used to detect the expressions of E-cadherin, vimentin, α-SMA, Snail, ZEB1 and Smads. Results In contrast to the control, the tumor-associated fibroblasts-like CCD-18Co cells induced down-regulation of E-cadherin and up-regulation of vimentin, α-SMA, Snail and ZEB1 (P

It is important to improve echocardiography image quality, because the accuracy of echocardiographic assessment and diagnosis relies on image quality. Previous work on 2D temporal image compounding for image frames with matching cardiac phases (synchronous), and for temporally neighbouring image frames (asynchronous) over small ranges of time frames showed good improvement to image quality. Here, we extend this by performing asynchronous temporal compounding to echocardiographic images in 3D, involving all frames within a cardiac cycle, via a robust 3D cardiac motion estimation algorithm to describe the large image deformations. After compounding, the images can be reanimated via the motion model. Various methods of fusing image frames together are tested, including mean, max, and wavelet methods, and outlier rejection algorithms. The compounding algorithm is applied on 3D human adult, porcine adolescent, and human fetal echocardiography images. Results show significant improvements to contrast-to-noise ratio (CNR) and boundary clarity, and significantly decreased variability in manual quantification of cardiac chamber volumes after compounding. Interestingly, compounding can extend the field of view of the echo images, by reconstructing cardiac structures that momentarily exceeded the field of view, using the motion estimation algorithm to calculate their locations outside the field of view during these time periods. Although all compounding methods provide general improvements, the mean method led to blurred boundaries, while the max methods led to high variability of CNR. Outlier rejection algorithms were found to be useful in addressing these weaknesses.

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.

Accurate cardiac motion estimation from medical images such as ultrasound is important for clinical evaluation. We present a novel regularisation layer for cardiac motion estimation that will be applied after image registration and demonstrate its effectiveness. The regularisation utilises a spatio-temporal model of motion, b-splines of Fourier, to fit to displacement fields from pairwise image registration. In the process, it enforces spatial and temporal smoothness and consistency, cyclic nature of cardiac motion, and better adherence to the stroke volume of the heart. Flexibility is further given for inclusion of any set of registration displacement fields. The approach gave high accuracy. When applied to human adult Ultrasound data from a Cardiac Motion Analysis Challenge (CMAC), the proposed method is found to have 10% lower tracking error over CMAC participants. Satisfactory cardiac motion estimation is also demonstrated on other data sets, including human fetal echocardiography, chick embryonic heart ultrasound images, and zebrafish embryonic microscope images, with the average Dice coefficient between estimation motion and manual segmentation at 0.82–0.87. The approach of performing regularisation as an add-on layer after the completion of image registration is thus a viable option for cardiac motion estimation that can still have good accuracy. Since motion estimation algorithms are complex, dividing up regularisation and registration can simplify the process and provide flexibility. Further, owing to a large variety of existing registration algorithms, such an approach that is usable on any algorithm may be useful.

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.