Breaking prolonged sitting increases 24-h physical activity and self-perceived energy levels but does not acutely affect cognition in healthy adults.

INTRODUCTION: It is unknown whether predetermined (un)interrupted sitting within a laboratory setting will induce compensatory changes in human behaviours (energy intake and physical activity) once people return to a free-living environment. The effects of breaking up prolonged sitting on cognition are also unclear. METHODS: Twenty-four (male = 13) healthy participants [age 31 ± 8 y, BMI 22.7 ± 2.3 kg/m2 (mean ± SD)] completed 320 min mixed-feeding trials under prolonged sitting (SIT) or with 2 min walking at 6.4 km/h every 20 min (ACTIVE), in a randomised crossover design. Human behaviours were recorded post-trial under free-living conditions until midnight. Cognitive performance was evaluated before and immediately after SIT and ACTIVE trials. Self-perceived sensations (appetite, energy and mood) and finger prick blood glucose levels were collected at regular intervals throughout the trials. RESULTS: There were no differences between trials in eating behaviour and spontaneous physical activity (both, p > 0.05) in free-living conditions, resulting in greater overall total step counts [11,680 (10740,12620) versus 6049 (4845,7253) steps] and physical activity energy expenditure (PAEE) over 24-h period in ACTIVE compared to SIT (all, p < 0.05). Greater self-perceived levels of energy and lower blood glucose iAUC were found in ACTIVE trial compared to SIT trial (both, p < 0.05). No differences were found in cognitive performance between trials (all, p > 0.05). CONCLUSION: Breaking up sitting does not elicit subsequent behavioural compensation, resulting in greater 24-h step counts and PAEE in healthy adults. Breaking up sitting reduces postprandial glucose concentrations and elicits greater self-perceived energy levels, but these positive effects do not acutely translate into improved cognitive function.

Optimal reimplantation timing in two-stage exchange for periprosthetic joint infection: an observative cohort study in Asian population.

BACKGROUND: The optimal timing for reimplantation for periprosthetic joint infection (PJI) has not been established and varies from a few weeks to several months. The aim of this study was to assess the commendable time between implant removal and reimplantation in patients who underwent two-stage exchange arthroplasty for PJI. METHODS: We retrospectively reviewed 361 patients who were treated with two-stage exchange arthroplasty for hip and knee chronic PJI at our institution between January 2000 and December 2018. Patient characteristics, comorbidities, surgical variables, microbiology data, and time to reimplantation were recorded. All patients were followed for a minimum of one year. Treatment failure was defined by Delphi criteria. Logistic regression analyses were used to calculate survival rates and adjusted odds ratios (ORs) of treatment failure. RESULTS: In final analysis, 27 (7.5%) had treatment failure. Factors related to treatment failure including interim spacer exchange (OR, 3.13; confidence interval (CI), 1.04-9.09, p = 0.036), higher ESR level at reimplantation (OR, 1.85; CI, 1.05-3.57; p = 0.04), and time to reimplantation (OR, 1.00; CI, 1.003-1.005, p = 0.04). Performing revision arthroplasty surgery from 16 to 20 weeks had highest successful rate. The reimplantation over 24 weeks had a lower successful rate. However, no statistical significance in comparing each interval group. CONCLUSION: Our study emphasized the importance of timely reimplantation in achieving successful outcomes. Factors such as ESR levels, spacer exchange, and the duration of time to reimplantation influenced the likelihood of treatment failure in two-stage exchange arthroplasty for hip and knee PJI.

Automatic Detection of Two Synovial Fluid Periprosthetic Joint Infection Biomarkers on an Integrated Microfluidic System.

Post-arthroplasty periprosthetic joint infection (PJI) is a serious ailment that can be difficult to diagnose. Herein, we developed a novel integrated microfluidic system (IMS) capable of detecting two common PJI biomarkers, alpha defensin human neutrophil peptide 1 (HNP-1) and C-reactive protein (CRP), from synovial fluid (SF). A magnetic bead-based one-aptamer-one-antibody assay was carried out automatically within 45 min on a single chip for simultaneous detection of both biomarkers at concentration ranges of 0.01-50 (HNP-1) and 1-100 (CRP) mg/L. It is the first report for utilizing these two biomarkers as targets to establish the new one-aptamer-one-antibody assay to detect PJI on-chip, and the aptamers demonstrated high specificity to their SF targets. As 20 clinical samples were correctly diagnosed with our IMS (verified by a common gold standard kit), it could serve as a promising tool for PJI diagnostics.

An enigma of hypothyroidism and hyponatremia coexistence: a nationwide population-based retrospective study.

INTRODUCTION: Hypothyroidism is a rare and possible cause of hyponatremia. However, the clinical epidemiology and risk of mortality (ROM) when they coexist still remain elusive. OBJECTIVES: We assessed the epidemiology and ROM among index patients with coexisting hypothyroidism and hyponatremia via a national population database. PATIENTS AND METHODS: This retrospective cohort study utilized Taiwan's National Health Insurance program database. Distributions of definite sociodemographic factors were analyzed. The annual incidence among the overall group and sex-subgroups was investigated. In addition, potential factors influencing the ROM were also evaluated. RESULTS: Of 4,549,226 patients from 1998 to 2015, a total of 3,140 index patients with concurrent hypothyroidism and hyponatremia were analyzed. The incidence rate increased tenfold from 1998 to 2015; average annual incidence rate was 174. Among the total participants, 57.1% were women; mean age was 72.6 ± 14.7 years and 88.8% were aged > 55 years. Although average length of stay (LOS) was 13.1 ± 15.4 days, the mortality group had significantly longer LOS than that in the survival group (12.9 days vs 22.2 days). Old age, catastrophic illness, cardiac dysrhythmia, and low hospital hierarchy were independent predictors of hospital mortality. The optimal LOS cutoff value for ROM prediction was 16 days. Index patients with LOS > 16 days increased ROM by 2.3-fold. CONCLUSIONS: Coexistent hypothyroidism and hyponatremia is rare, although the incidence increased gradually. Factors influencing the ROM, such as old age, underlying catastrophic status, cardiac dysrhythmia, hospital hierarchy, and LOS should be considered in clinical care.

LncRNA HOTAIR impairs the prognosis of papillary thyroid cancer via regulating cellular malignancy and epigenetically suppressing DLX1.

PURPOSE: Papillary thyroid cancer (PTC) is the most common endocrine malignancy with a fast-growing incidence in recent decades. HOTAIR as a long non-coding RNA has been shown to be highly expressed in papillary thyroid cancer tissues with only a limited understanding of its functional roles and downstream regulatory mechanisms in papillary thyroid cancer cells. METHODS: We applied three thyroid cancer cell lines (MDA-T32, MDA-T41 and K1) to investigate the phenotypic influence after gain or loss of HOTAIR. The Cancer Genome Atlas (TCGA) database were utilised to select candidate genes possibly regulated by HOTAIR with validation in the cellular system and immunohistochemical (IHC) staining of PTC tissues. RESULTS: We observed HOTAIR was highly expressed in MDA-T32 cells but presents significantly decreased levels in MDA-T41 and K1 cells. HOTAIR knockdown in MDA-T32 cells significantly suppressed proliferation, colony formation, migration with cell cycle retardation at G1 phase. On the contrary, HOTAIR overexpression in MDA-T41 cells dramatically enhanced proliferation, colony formation, migration with cell cycle driven toward S and G2/M phases. Similar phenotypic effects were also observed as overexpressing HOTAIR in K1 cells. To explore novel HOTAIR downstream mechanisms, we analyzed TCGA transcriptome in PTC tissues and found DLX1 negatively correlated to HOTAIR, and its lower expression associated with reduced progression free survival. We further validated DLX1 gene was epigenetically suppressed by HOTAIR via performing chromatin immunoprecipitation. Moreover, IHC staining shows a significantly stepwise decrease of DLX1 protein from normal thyroid tissues to stage III PTC tissues. CONCLUSIONS: Our study pointed out that HOTAIR is a key regulator of cellular malignancy and its epigenetic suppression on DLX1 serves as a novel biomarker to evaluate the PTC disease progression.

Augmented CCL5/CCR5 signaling in brown adipose tissue inhibits adaptive thermogenesis and worsens insulin resistance in obesity.

Chemokine (C-C motif) ligand 5 (CCL5) and CCR5, one of its receptors have been reported to be highly expressed in white adipose tissue (WAT) and are associated with the progression of inflammation and the development of insulin resistance in obese humans and mice. However, the role of CCL5/CCR5 signaling in obesity-associated dysregulation of energy metabolism remains unclear. Here, we demonstrate that global CCL5/CCR5 double knockout (DKO) mice have higher cold stress-induced energy expenditure and thermogenic function in brown adipose tissue (BAT) than wildtype (WT) mice. DKO mice have higher cold stress-induced energy expenditure and thermogenic function in BAT than WT mice. KEGG pathway analysis indicated that deletion of CCL5/CCR5 further facilitated the cold-induced expression of genes related to oxidative phosphorylation (OxPhos) and lipid metabolic pathways. In primary brown adipocytes of DKO mice, the augmentation of CL-316243-stimulated thermogenic and lipolysis responses was reversed by co-treatment with AMPKα1 and α2 short interfering RNA (siRNA). Overexpression of BAT CCL5/CCR5 genes by local lentivirus injection in WT mice suppressed cold stress-induced lipolytic processes and thermogenic activities. In contrast, knockdown of BAT CCL5/CCR5 signaling further up-regulated AMPK phosphorylation as well as thermogenic and lipolysis responses to chronic adrenergic stimuli and subsequently decreased level of body weight gain. Chronic knockdown of BAT CCL5/CCR5 signaling improved high-fat diet (HFD)-induced insulin resistance in WT mice. It is suggested that obesity-induced augmentation of adipose tissue (AT) CCL5/CCR5 signaling could, at least in part, suppress energy expenditure and adaptive thermogenesis by inhibiting AMPK-mediated lipolysis and oxidative metabolism in thermogenic AT to exacerbate the development of obesity and insulin resistance.

Interruption of the long non-coding RNA HOTAIR signaling axis ameliorates chemotherapy-induced cachexia in bladder cancer.

BACKGROUND: Cisplatin-based chemotherapy is the first line of treatment for bladder cancer. However, cisplatin induces muscle wasting associated with NF-κB and cancer cachexia. HOTAIR, an oncogenic long non-coding RNA (lncRNA), promotes cancer progression in different cancers. Crosstalk between HOTAIR and NF-κB is documented. Prothymosin α (ProT) plays important roles in cancer progression and inflammation. However, the potential link between HOTAIR, ProT, and cisplatin-induced cancer cachexia remains unexplored. Here, we investigated the contribution of HOTAIR in cisplatin-induced cancer cachexia and dissected the potential signaling cascade involving the epidermal growth factor receptor (EGFR), ProT, NF-κB, and HOTAIR. MATERIALS AND METHODS: Expression of ProT and HOTAIR transcripts and their correlations in tumor tissues of bladder cancer patients and bladder cancer cell lines were determined by RT-qPCR. Next, levels of phospho-EGFR, EGFR, phospho-NF-κB, and NF-κB were examined by immunoblot analysis in human bladder cancer cells treated with cisplatin. Expression of HOTAIR in cisplatin-treated cells was also assessed by RT-qPCR. Pharmacological inhibitors and overexpression and knockdown approaches were exploited to decipher the signaling pathway. The murine C2C12 myoblasts were used as an in vitro muscle atrophy model. The syngeneic murine MBT-2 bladder tumor was used to investigate the role of mouse Hotair in cisplatin-induced cancer cachexia. RESULTS: Expression of ProT and HOTAIR was higher in bladder tumors than in normal adjacent tissues. There were positive correlations between ProT and HOTAIR expression in clinical bladder tumors and bladder cancer cell lines. Cisplatin treatment increased EGFR and NF-κB activation and upregulated ProT and HOTAIR expression in bladder cancer cells. ProT overexpression increased, whereas ProT knockdown decreased, HOTAIR expression. Notably, cisplatin-induced HOTAIR upregulation was abrogated by EGFR inhibitors or ProT knockdown. ProT-induced HOTAIR overexpression was diminished by NF-κB inhibitors. HOTAIR overexpression enhanced, whereas its knockdown reduced, cell proliferation, cachexia-associated pro-inflammatory cytokine expression, and muscle atrophy. Cachexia-associated symptoms were ameliorated in mice bearing Hotair-knockdown bladder tumors undergoing cisplatin treatment. CONCLUSIONS: We demonstrate for the first time a critical role for HOTAIR and identify the involvement of the EGFR-ProT-NF-κB-HOTAIR signaling axis in cisplatin-induced cachexia in bladder cancer and likely other cancers. Our findings also provide therapeutic targets for this disease.

Periprosthetic Joint Infection Prediction via Machine Learning: Comprehensible Personalized Decision Support for Diagnosis.

BACKGROUND: The criteria outlined in the International Consensus Meeting (ICM) in 2018, which were prespecified and fixed, have been commonly practiced by clinicians to diagnose periprosthetic joint infection (PJI). We developed a machine learning (ML) system for PJI diagnosis and compared it with the ICM scoring system to verify the feasibility of ML. METHODS: We designed an ensemble meta-learner, which combined 5 learning algorithms to achieve superior performance by optimizing their synergy. To increase the comprehensibility of ML, we developed an explanation generator that produces understandable explanations of individual predictions. We performed stratified 5-fold cross-validation on a cohort of 323 patients to compare the ML meta-learner with the ICM scoring system. RESULTS: Cross-validation demonstrated ML's superior predictive performance to that of the ICM scoring system for various metrics, including accuracy, precision, recall, F1 score, Matthews correlation coefficient, and area under receiver operating characteristic curve. Moreover, the case study showed that ML was capable of identifying personalized important features missing from ICM and providing interpretable decision support for individual diagnosis. CONCLUSION: Unlike ICM, ML could construct adaptive diagnostic models from the available patient data instead of making diagnoses based on prespecified criteria. The experimental results suggest that ML is feasible and competitive for PJI diagnosis compared with the current widely used ICM scoring criteria. The adaptive ML models can serve as an auxiliary system to ICM for diagnosing PJI.

Which Minor Criteria is the Most Accurate Predictor for the Diagnosis of Hip and Knee Periprosthetic Joint Infection in the Asian Population?

BACKGROUND: The aim of this study was to evaluate the diagnostic performance of minor criteria from the 2018 International Consensus Meeting (ICM) for the diagnosis of chronic periprosthetic joint infection (PJI) in an Asian population. METHODS: We retrospectively reviewed 76 patients who underwent a revision knee or hip arthroplasty at an academic institution between September 2018 and December 2019. All major and minor 2018 ICM criteria were available for all patients included. Cases with at least 1 major criterion or score ≥6 in minor criteria were considered as infected. The diagnostic performance was evaluated by a receiver operative characteristic curve analysis and area under the curve (AUC) for each minor criterion. An AUC value of more than 0.9 was considered outstanding and 0.8-0.9 as excellent. RESULTS: When using 2018 ICM threshold, the diagnostic performance ranked based on AUC was the following: alpha defensin (0.92), positive histology (0.83), leukocyte esterase (0.82), synovial white blood cell (0.81), serum erythrocyte sedimentation rate (0.78), synovial polymorphonuclear neutrophils (0.77), serum C-reactive protein (0.74), D-dimer (0.59), single positive culture (0.53), and positive intraoperative purulence (0.51). Alpha defensin was considered as an outstanding test among the 2018 ICM minor criteria. Positive histology, leukocyte esterase, and synovial white blood cell were considered as excellent tests. CONCLUSION: Based on our findings, alpha-defensin has the best diagnostic performance in Asian population among the minor criteria of 2018 ICM.

Impaction Bone Grafting Augmented With a Wire Coil by the Lightbulb Technique for Osteonecrosis of the Femoral Head.

BACKGROUND: Osteonecrosis of the femoral head (ONFH) is a debilitating disease that primarily affects the hips of young adults. The purpose of this study is to report the mid-term results of impaction bone grafting augmented with a wire coil using the lightbulb technique for ONFH. METHODS: From 1998 to 2016, 50 hips with late precollapsed or early postcollapsed ONFH (28 hips with Association Research Circulation Osseous [ARCO] IIC and 22 with IIIA) were treated by impaction bone grafting augmented with a wire coil using the lightbulb technique. The survival rate was analyzed with conversion to total hip arthroplasty (THA) as the end point. RESULTS: Thirty-one of the 50 hips had a successful clinical result without conversion to THA at a mean follow-up of 109.2 months. The 5-year survival rate was 68%, 82.1%, and 50% for the entire cohort, ARCO stage IIC, and ARCO stage IIIA, respectively. The 19 hips that had failed were converted to THA at an average of 52.8 months. The multivariable Cox proportional hazards model showed that an ARCO stage IIIA disease, a lateral lesion, and a necrotic index ≥0.67 were the independent risk factors for conversion to THA. CONCLUSION: As a head-preserving procedure, the lightbulb technique using impaction bone grafting augmented with a wire coil is worthwhile for patients in an earlier stage of disease and smaller lesion size to postpone the need for THA.

Outcome and Predictors of Septic Failure Following Total Joint Arthroplasty for Prior Septic Arthritis of Hip and Knee Joint.

BACKGROUND: Arthroplasty patients with prior septic arthritis are at a high risk of developing periprosthetic joint infection (PJI). The aims of this study are to investigate the outcome and predictors of septic failure following total joint arthroplasty (TJA) for prior septic arthritis. In addition, the optimal timing of TJA is also discussed. METHODS: A retrospective review of 105 TJA patients with prior septic arthritis between January 2000 and December 2019 was performed. Patient-specific and surgery-related factors, organism profiles, and other relevant variables were recorded. RESULTS: At a mean follow-up of 10.3 years, the PJI rate was 16.2%. The adjusted Cox proportional hazards model showed that male gender (HR, 9.95; P < .01), end-stage renal disease (HR, 37.34; P < .01), debridement surgery ≥3 times (HR,4.75; P = .04) and polymicrobial infection in primary septic arthritis (HR, 10.02; P = .02) were independent risk factors for PJI. Neither the types of initial debridement, nor one-stage vs two-stage arthroplasty was related to the risk of PJI. While delaying the timing of TJA did not correlate with a reduction of PJI rate, there was a higher risk of PJI re-infection by the same microorganisms isolated in prior septic arthritis if TJA was performed within 6 months after septic arthritis. CONCLUSIONS: Our study demonstrated that male gender, end-stage renal disease (ESRD), multiple debridement surgeries and polymicrobial septic arthritis predisposed septic failure of TJA following prior septic arthritis. Surgeons should counsel patients with the potential complications, and be cognizant about the risk factors pertaining to septic failure when considering TJA.

The Dynamics and Plasticity of Epigenetics in Diabetic Kidney Disease: Therapeutic Applications Vis-à-Vis.

Chronic kidney disease (CKD) refers to the phenomenon of progressive decline in the glomerular filtration rate accompanied by adverse consequences, including fluid retention, electrolyte imbalance, and an increased cardiovascular risk compared to those with normal renal function. The triggers for the irreversible renal function deterioration are multifactorial, and diabetes mellitus serves as a major contributor to the development of CKD, namely diabetic kidney disease (DKD). Recently, epigenetic dysregulation emerged as a pivotal player steering the progression of DKD, partly resulting from hyperglycemia-associated metabolic disturbances, rising oxidative stress, and/or uncontrolled inflammation. In this review, we describe the major epigenetic molecular mechanisms, followed by summarizing current understandings of the epigenetic alterations pertaining to DKD. We highlight the epigenetic regulatory processes involved in several crucial renal cell types: Mesangial cells, podocytes, tubular epithelia, and glomerular endothelial cells. Finally, we highlight epigenetic biomarkers and related therapeutic candidates that hold promising potential for the early detection of DKD and the amelioration of its progression.

Red Cell Distribution Width: Commonly Performed Test Predicts Mortality in Primary Total Joint Arthroplasty.

INTRODUCTION: Mortality after total joint arthroplasty (TJA) has been thoroughly explored. Short and long-term mortality appear to be correlated with patient comorbidities. Red Cell Distribution Width (RDW) is a commonly performed test that reflects the variation in red blood cell size. This study investigated the utility of RDW, when combined with comorbidity indices, in predicting mortality after TJA. METHODS: Using a single institutional database, 30,437 primary TJA were identified. Patient demographics (age, gender, body mass index (BMI), pre-operative hemoglobin, RDW, and Charlson Comorbidity Index(CCI)) were queried. The primary outcome was 1-year mortality after TJA. Anemia was defined as hemoglobin <12g/dL for women and <13 g/dL for men. The normal range for RDW is 11.5-14.5%. A preliminary analysis assessed the bivariate association between demographics, preoperative anemia, RDW, CCI, and all-cause mortality within 1-year after TJA. A multivariate regression model was conducted to determine independent predictors of 1-year mortality. Finally, ROC curves were used to compare AUC of RDW, CCI and the combination of both in predicting 1-year mortality. RESULTS: The mean RDW was 13.6% ± 1.2. Eighteen percent of patients had pre-operative anemia. The mean CCI was 0.4 ± 0.9. RDW, anemia, CCI, and age were significantly associated with a higher incidence of 1-year mortality. RDW, CCI, age, and male sex were found to be independent risk factors for 1-year mortality. RDW (AUC = 0.68) was a better predictor of mortality compared to CCI (AUC = 0.66). The combination of RDW and CCI (AUC = 0.76) predicted 1-year mortality more accurately than CCI or RDW alone. CONCLUSION: RDW appears to be a useful parameter that, when combined with CCI, can predict the risk for 1-year mortality after TJA.

Risk Factors for Failure and Optimal Treatment of Total Joint Arthroplasty for Septic Arthritis.

BACKGROUND: Patients with native joint septic arthritis are one of the highest risk groups for developing complications following total joint arthroplasty (TJA), especially periprosthetic joint infection(PJI). There is a paucity of information on the risk factors for developing PJI and the optimal treatment modality of the native septic joint that can mitigate that risk. This multicenter study aimed to determine these risk factors, including prior treatment. METHODS: A retrospective study of 233 TJAs performed, following prior septic arthritis at five institutions, was conducted. Comorbidities, organism profile, prior surgery, etiology of septic arthritis, and other relevant variables were reviewed. The primary outcome was the development of PJI, defined by Musculoskeletal Infection Society criteria. Bivariate and multivariate analyses were performed to identify risk factors for PJI. RESULTS: Overall, the PJI rate was 12.4% in patients who underwent TJA after native septic arthritis. Predisposing risk factors for PJI included antibiotic-resistant organisms, male gender, diabetes, and a postsurgical cause of septic arthritis eg open reduction internal fixation. When controlling for potential confounders, multivariate analysis revealed that male gender, diabetes, and a postoperative etiology were predictors of PJI. The definitive treatment modality for the septic joint did not affect the rate of PJI for both arthroscopy vs irrigation and debridement (I&D), and two-stage exchange vs single-stage procedure. DISCUSSION: This study has identified several risk factors for developing PJI in patients with prior septic joint arthritis, some of which are modifiable. The initial treatment modality of the native septic joint has no bearing on the development of PJI after TJA.

Effectiveness of Different Wound Dressings in the Reduction of Blisters and Periprosthetic Joint Infection After Total Joint Arthroplasty: A Systematic Review and Network Meta-Analysis.

BACKGROUND: The optimal type of dressing in the setting of total joint arthroplasty (TJA) remains uncertain. The aim of this network meta-analysis was to compare various wound dressings and identify the optimal type of dressings for blister reduction and prevention of periprosthetic joint infection (PJI) in patients after TJA. METHODS: Studies comparing 2 or more dressing groups after TJA (hip or knee) were systematically searched on PubMed, Embase, and Scopus. Two authors performed the study selection, risk of bias assessment, and data extraction. Both outcomes were assessed using odds ratios (OR) with 95% confidence intervals (CI) and were ranked using surface under the cumulative ranking curve (SUCRA) probabilities to determine a hierarchy of dressings. A sensitivity analysis was performed to reduce the effect of intransitivity between studies. RESULTS: A total of 21 studies, consisting of 12 dressing types in 7293 TJAs, were included in the final analysis. The highest incidence of blisters occurred when using negative-pressure wound therapy (OR 9.33, 95% CI 3.51-24.83, vs gauze). All dressings ranked better than gauze in infection rate except for hydrofiber (OR 1.46, 95% CI 0.02-112.53) and fabric dressings (OR 1.46, 95% CI 0.24-9.02). For blister reduction, alginate (SUCRA = 87.7%) and hydrofiber with hydrocolloid (SUCRA = 92.3%) were ranked as the optimal dressings before and after a sensitivity analysis, respectively. Antimicrobial dressing (SUCRA = 83.7%) demonstrated the most efficacy for preventing PJI. CONCLUSION: Based on the evidence from our analysis, an antimicrobial dressing is the optimal dressing to prevent PJI. If negative-pressure wound therapy is used, surgeons should be aware of an increased incidence of blister formation. Further studies should focus on the alginate versus hydrofiber and hydrocolloid dressing to determine the optimal dressing to reduce blisters.

High-Molecular-Weight Hyaluronic Acid Inhibits IL-1ß-Induced Synovial Inflammation and Macrophage Polarization through the GRP78-NF-κB Signaling Pathway.

Recent evidence has suggested that synovial inflammation and macrophage polarization were involved in the pathogenesis of osteoarthritis (OA). Additionally, high-molecular-weight hyaluronic acid (HMW-HA) was often used clinically to treat OA. GRP78, an endoplasmic reticulum (ER) stress chaperone, was suggested to contribute to the hyperplasia of synovial cells in OA. However, it was still unclear whether HMW-HA affected macrophage polarization through GRP78. Therefore, we aimed to identify the effect of HMW-HA in primary synovial cells and macrophage polarization and to investigate the role of GRP78 signaling. We used IL-1ß to treat primary synoviocytes to mimic OA, and then treated them with HMW-HA. We also collected conditioned medium (CM) to culture THP-1 macrophages and examine the changes in the phenotype. IL-1ß increased the expression of GRP78, NF-κB (p65 phosphorylation), IL-6, and PGE2 in primary synoviocytes, accompanied by an increased macrophage M1/M2 polarization. GRP78 knockdown significantly reversed the expression of IL-1ß-induced GRP78-related downstream molecules and macrophage polarization. HMW-HA with GRP78 knockdown had additive effects in an IL-1ß culture. Finally, the synovial fluid from OA patients revealed significantly decreased IL-6 and PGE2 levels after the HMW-HA treatment. Our study elucidated a new form of signal transduction for HMW-HA-mediated protection against synovial inflammation and macrophage polarization and highlighted the involvement of the GRP78-NF-κB signaling pathway.

Correction to: Gamma synuclein is a novel nicotine responsive protein in oral cancer malignancy.

[This corrects the article DOI: 10.1186/s12935-020-01401-w.].

Gamma synuclein is a novel nicotine responsive protein in oral cancer malignancy.

BACKGROUND: The mechanisms of neuronal protein γ-synuclein (SNCG) in the malignancy of oral squamous cell carcinoma (OSCC) are not clear. This study tested the hypothesis that SNCG is involved in nicotine-induced malignant behaviors of OSCC. The effect of nicotine on SNCG expression and epithelial-to-mesenchymal transition (EMT) markers were examined. METHODS: Short hairpin RNA (shRNA) and an antagonist specific for α7-nicotine acetylcholine receptors (α7-nAChRs) were used to examine the role of α7-nAChRs in mediating the effects of nicotine. Knockdown of SNCG in nicotine-treated cells was performed to investigate the role of SNCG in cancer malignancy. The in vivo effect of nicotine was examined using a nude mouse xenotransplantation model. RESULTS: Nicotine increased SNCG expression in a time- and dose-dependent manner. Nicotine treatment also increased E-cadherin and ZO-1 and decreased fibronectin and vimentin expression. After specific knockdown of α7-nAChRs and inhibition of the PI3/AKT signal, the effect of nicotine on SNCG expression was attenuated. Silencing of SNCG abolished nicotine-induced invasion and migration of OSCC cells. The xenotransplantation model revealed that nicotine augmented tumor growth and SNCG expression. CONCLUSION: Nicotine upregulated SNCG expression by activating the α7-nAChRs/PI3/AKT signaling that are participated in nicotine-induced oral cancer malignancy.

Use of antidiabetic medications and risk of chronic obstructive pulmonary disease exacerbation requiring hospitalization: a disease risk score-matched nested case-control study.

BACKGROUND: Exacerbation of chronic obstructive pulmonary disease (COPD) severely impacts the quality of life and causes high mortality and morbidity. COPD is involved with systemic and pulmonary inflammation, which may be attenuated with antidiabetic agents exerting anti-inflammatory effects. Real-world evidence is scant regarding the effects of antidiabetic agents on COPD exacerbation. Accordingly, we conducted a disease risk score (DRS)-matched nested case-control study to systemically assess the association between each class of oral hypoglycemic agents (OHAs) and risk of severe COPD exacerbation in a nationwide COPD population co-diagnosed with diabetes mellitus (DM). METHODS: We enrolled 23,875 COPD patients receiving at least one OHA for management of DM by analyzing the Taiwan National Health Insurance claims database between January 1, 2000, and December 31, 2015. Cases of severe exacerbation were defined as those who had the first hospital admission for COPD. Each case was individually matched with four randomly-selected controls by cohort entry date, DRS (the estimated probability of encountering a severe COPD exacerbation), and COPD medication regimens using the incidence density sampling approach. Conditional logistic regressions were performed to estimate odds ratios (OR) of severe COPD exacerbation for each type of OHAs. RESULTS: We analyzed 2700 cases of severe COPD exacerbation and 9272 corresponding controls after DRS matching. Current use of metformin versus other OHAs was associated with a 15% (adjusted OR [aOR], 0.85; 95% confidence interval [CI] 0.75-0.95) reduced risk of severe COPD exacerbation, whereas the reduced risk was not observed with other types of antidiabetic agents. When considering the duration of antidiabetic medication therapy, current use of metformin for 91-180 and 181-365 days was associated with a 28% (aOR, 0.72; 95% CI 0.58-0.89) and 37% (aOR, 0.63; 95% CI 0.51-0.77) reduced risk of severe COPD exacerbation, respectively. Similarly, 91-180 days of sulfonylureas therapy led to a 28% (aOR, 0.72; 95% CI 0.58-0.90) lower risk, and longer treatments consistently yielded 24-30% lower risks. Current use of thiazolidinediones for more than 181 days yielded an approximately 40% decreased risk. CONCLUSIONS: Duration-dependent beneficial effects of current metformin, sulfonylurea, and thiazolidinedione use on severe COPD exacerbation were observed in patients with COPD and DM.

Total Hip Arthroplasty After Prior Acetabular Fracture: Infection Is a Real Concern.

BACKGROUND: Acetabular fractures often require surgical intervention for fracture fixation and can result in premature osteoarthritis of the hip joint. This study hypothesized that total hip arthroplasty (THA) in patients with a prior acetabular fracture who had undergone open reduction and internal fixation (ORIF) is associated with a higher rate of subsequent periprosthetic joint infection (PJI). METHODS: About 72 patients with a history of acetabular fracture that required ORIF, undergoing conversion THA between 2000 and 2017 at our institution, were matched based on age, gender, body mass index, Charlson comorbidity index, and date of surgery in a 1:3 ratio with 215 patients receiving primary THA. The mean follow-up for the conversion THA cohort was 2.9 years (range, 1-12.15) and 3.06 years (range, 1-12.96) for the primary THA. RESULTS: Patients with a previous acetabular fracture, compared with the primary THA patients, had longer operative times, greater operative blood loss, and an increased need for allogeneic blood transfusion (26.4% vs 4.7%). Most notably, PJI rate was significantly higher in acetabular fracture group at 6.9% compared with 0.5% in the control group. Complications, such as aseptic revision, venous thromboembolism, and mortality, were similar between both groups. CONCLUSION: The present study demonstrates that conversion THA in patients with prior ORIF of acetabular fractures is associated with higher complication rate, in particular PJI, and less optimal outcome compared with patients undergoing primary THA. The latter findings compel us to seek and implement specific strategies that aim to reduce the risk of subsequent PJI in these patients.