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Background Although surgical treatment is considered reliable for lateral elbow tendinosis, local injection therapy may be preferable, as it avoids surgery. Among a number of local injections, platelet-rich plasma has been used successfully to treat lateral elbow tendinosis. The purpose of this study was to compare the outcomes in patients treated with either platelet-rich plasma injections or surgery for lateral elbow tendinosis using a systematic literature review and meta-analysis. Methods MEDLINE, Embase, and Cochrane Library databases were systematically searched for studies published before March 1, 2021, that compared platelet-rich plasma with operative treatment for lateral elbow tendinosis. The pooled analysis was designed to compare the visual analog scale scores and the Patient-Related Tennis Elbow Evaluation scores between the platelet-rich plasma and surgical treatment groups at serial time points. Results We included five studies involving 340 patients with lateral elbow tendinosis, comprising of 154 patients treated with platelet-rich plasma and 186 patients who underwent surgical treatment. The pooled analysis showed no statistically significant differences in the visual analog scale scores at any of the follow-up time points, namely post-intervention 2 months (mean difference = 1.11, 95% confidence interval: −2.51 to 4.74, P = 0.55, I2 = 94%), 6 months (mean difference = 0.80, 95% confidence interval: −2.83 to 4.42, P = 0.67, I2 = 92%), and 12 months (mean difference = −0.92, 95% confidence interval: −4.63 to 2.80, P = 0.63, I2 = 93%) and in the Patient-Related Tennis Elbow Evaluation scores at post-intervention 12 weeks (mean difference = −1.86, 95% confidence interval: −22.30 to 18.58, P = 0.86, I2 = 81%), 24 weeks (mean difference = −3.33, 95% confidence interval: −21.82 to 15.17, P = 0.72, I2 = 74%), and 52 weeks (mean difference = −3.64, 95% confidence interval: −19.65 to 12.37, P = 0.66, I2 = 69%). Conclusions Local platelet-rich plasma injections and surgical treatment produced equivalent pain scores and functional outcomes in patients with lateral elbow tendinosis. Thus, platelet-rich plasma injections may represent a reasonable alternative treatment for patients who are apprehensive to proceed with surgery or for poor surgical candidates.

To date, no meta-analysis of the relationship between hospital readmission after total joint arthroplasty (TJA) and preoperative depression has been conducted. Hence, this systematic review and meta-analysis aimed to evaluate the association of preoperative depression with the readmission rate following TJA.We systematically searched MEDLINE, EMBASE, and Cochrane Library for studies published before March 28, 2021, which compared readmission rates in patients with or without preoperative depression who underwent TJA. The primary outcome was the relationship between preoperative depression and 30-day and 90-day readmission rates after TJA. We also performed surgery type subgroup analyses for total hip arthroplasty, total knee arthroplasty (TKA), total shoulder arthroplasty, and total ankle arthroplasty.We included 9 studies with 395,815 TJA cases, of which 49,402 were diagnosed with preoperative depression and 346,413 were not. In pooled TJA analysis, the 30-day and 90-day readmission rates were significantly higher in the depression group than in the no-depression group (odds ratio [OR] 1.86, 95% confidence interval [CI] 1.26-2.73, P = .002 and OR 1.27, 95% CI 1.14-1.43,; P.001, respectively). In the subgroup analyses, the 90-day readmission rate was higher in the depression group than in the no-depression group after TKA (OR 1.28, 95% CI 1.15-1.42, P.001). There were no differences in other surgery types.Based on available evidence, preoperative depression increases the readmission rate after TJA, particularly TKA. As depression is a modifiable risk factor, screening for depression and referring patients for proper psychiatric management are important.Level III, meta-analysis.

The present study investigated the relationship between central hemodynamics and lung function and the response to an acute bout of exercise in COPD.Based on the severity of COPD, moderate group (MOD, n = 12) and more mild group (MLD, n = 12) underwent central hemodynamic assessments pre- and post-peak exercise.In the entire cohort (n = 24), central diastolic blood pressure (cDBP) was associated with pulmonary function. Post-exercise, cDBP remained elevated (p 0.01), however, peripheral diastolic blood pressure (pDBP) was reduced (p = 0.02). Prior to exercise, the MOD showed higher cDBP and heart rate (HR) than the MLD (p = 0.02 and p = 0.01, respectively), but no difference in central aortic/arterial stiffness (p 0.05). These findings remained similar post-exercise.Central diastolic blood pressure is linked to pulmonary function in COPD and it is elevated after exercise-induced reductions in pDBP. Central diastolic blood pressure is higher in the MOD than the MLD, however, there was no difference in central aortic/arterial stiffness between groups.

Nonthermal plasma is suitable for applications in the biomedical field because of the large amounts of active species and a low gas temperature that does not injure the human body. A plasma jet of the typical pen type is applied in most biomedical applications, but it is difficult to apply such jets to treat skin diseases that generally have wide affected areas. In this study, nonthermal multineedle dielectric barrier discharge (DBD) jet was developed for the treatment of large area lesions and used to verify its effectiveness in treating psoriasis as a representative skin disease. Stable discharge was maintained using the developed plasma jet with a multineedle electrode structure by utilizing various discharge gases. Electrical and optical analyses were performed to determine the characteristics of the plasma. The effectiveness of psoriasis treatment using this approach was confirmed by performing in vitro and in vivo experiments with the multineedle DBD jet.

Despite technological advances in cancer treatment, the survival rate of patients with head and neck cancer (HNC) has not improved significantly. Many studies have shown that endoplasmic reticulum (ER) stress-related signals are associated with mitochondrial damage and that these signals determine whether cells maintain homeostasis or activate cell death programs. The unfolded protein response (UPR) is regulated by ER membrane proteins such as double-stranded RNA-activated protein kinase R(PKR)-like ER kinase (PERK), which directly activate transcription of chaperones or genes that function in redox homeostasis, protein secretion, or cell death programs. In this study, we focused on the role of mitophagy and ER stress-mediated cell death induced by DIM-C-pPhtBu in HNC cancer. We found that DIM-C-pPhtBu, a compound that activates ER stress in many cancers, induced lysosomal dysfunction, excessive mitophagy, and cell death in HNC cells. Moreover, DIM-C-pPhtBu strongly inhibited HNC progression in a xenograft model by altering mitophagy related protein expression. Taken together, the results demonstrate that DIM-C-pPhtBu induces excessive mitophagy and eventually UPR-mediated cell death in HNC cells, suggesting that new anti-cancer drugs could be developed based on the connection between mitophagy and cancer cell death.

Background In young active patients with hip dysplasia, choosing between periacetabular osteotomy (PAO) and total hip arthroplasty (THA) is challenging. Materials and methods We systematically searched Medline, Embase, and Cochrane Library for studies published until October 10, 2019, comparing PAO and THA in patients with dysplastic hip. We compared postoperative complications’ incidences, end-stage revisions, and clinical scores. Results Five studies with 431 hips (PAO: 235; THA: 196) were included. The incidence of overall and major complications was not different between groups (PAO: OR 2.14; 95% CI, 0.58–7.96; p = 0.26; follow-up, 4–7.8 years; THA: OR 2.56; 95% CI, 0.60–10.98; p = 0.21; follow-up, 4–7.8 years). There was also no difference in end-stage revision (OR 0.95; 95% CI, 0.33–2.79; p = 0.93; follow-up, 4–7.8 years). The standard mean of Western Ontario McMasters Universities (WOMAC) pain score was higher in the THA than in the PAO group (standardized mean difference [SMD] −0.57; 95% CI, −0.93–−0.21; p = 0.002; follow-up, 4–5.5 years); however, the WOMAC functional score did not differ significantly between groups (SMD −0.16; 95% CI, −1.29–0.97; p = 0.78; follow-up, 4–5.5 years). The standard mean UCLA activity index was higher in the PAO than in the THA group (SMD 0.28; 95% CI, 0.02–0.53; p = 0.03; follow-up, 5.9–7.3 years). Conclusions The incidence of postoperative complications and revision surgery was not different between THA and PAO groups. However, postoperative pain was less in the THA group and the activity score was higher in the PAO group in the follow-up periods. Level of evidence III; meta-analysis.

Background Dilute povidone-iodine (PI) lavage, a simple disinfection method, could reduce postoperative infection risk. However, there is no clinical consensus regarding its efficacy in total joint arthroplasties (TJAs). This systematic review and meta-analysis evaluated PI lavage’s efficacy in preventing infection after TJA. Methods MEDLINE, Embase, and the Cochrane Library were systematically searched for studies published before November 22, 2019, that compared postoperative infection rates in patients who underwent TJA with or without PI lavage before wound closure. Subgroup analyses were designed to identify the differences in infection site (overall or deep), type of surgery (total hip arthroplasty or total knee arthroplasty), time until diagnosis of infection (3 or 12 months postoperatively), and primary/aseptic revision arthroplasties. Results We included 7 studies with 31,213 TJA cases, comprising 8861 patients who received PI lavage and 22,352 who did not. Pooled odds ratio for overall infection rate for the PI and non-PI lavage groups was 0.67 (95% confidence interval, 0.38-1.19, P = .17) and for the deep infection rate was 0.90 (95% confidence interval, 0.27-2.98, P = .86). Subgroup analyses revealed no differences in postoperative infection rates between the PI and non-PI lavage groups in terms of total hip arthroplasty and total knee arthroplasty, diagnosis of infection at 3 and 12 months postoperatively, or primary and aseptic revision arthroplasties. Conclusion We detected no differences in the overall postoperative infection rates between the PI and non-PI lavage groups before wound closure in TJA including all studies in the subgroup analyses.

Lipid-rich microalgae are a potential source for the bio-oil production. We isolated a novel oleaginous Thraustochytrid microalga from seawater, Schizochytrium sp. ABC101, and tested the effect of different growth conditions on its production of lipids. Batch fermentation experiments indicated that depletion of nitrogen led to lipid accumulation, and lipid accumulation led to increased cell size and decreased cell wall thickness. Based on these results, we tested three types of fed-batch fermentations (carbon and no nitrogen feeding, carbon and limited nitrogen feeding, carbon and sufficient nitrogen feeding) to examine the effect of adjusting the nitrogen supply on lipid accumulation. The limited nitrogen feeding provided the most efficient lipid production, with maxima after 60 h (dry cell weight [DCW]: 64.7 g/L, lipids: 25.4 g/L, docosahexaenoic acid [DHA]: 11.0 g/L). Use of corn steep liquor (CSL) as the sole nitrogen source also led to excellent performance, with maxima at 84 h (DCW: 86.0 g/L, lipids: 37.2 g/L, DHA: 16.7 g/L). In addition, use of CSL rather than yeast extract reduced the lipid production cost by 50%. Our results suggest that regulation of the nitrogen source improves the efficiency of microalgal lipid production and use of a low-cost nitrogen source reduces production costs.

Tension band wiring (TBW) and screw fixation (SF) are common surgical treatments for medial malleolar fractures (MMFs); however, no systematic review has identified which fixation method is superior. This study aimed to determine the most optimal MMF fixation method by comparing the clinical and radiological outcomes of TBW and SF through a systematic review and meta-analysis of the literature.We hypothesized that there may be differences in outcomes between TBW and SF for treating MMFs.MEDLINE, Embase, and the Cochrane Library were systematically searched for studies that compared TBW and SF for MMF treatment published through June 8, 2021. Fracture union, outcome scores, and postoperative complications were analyzed.We included 10 studies with 512 MMF cases; 218 and 294 patients were treated with TBW and SF, respectively. Pooled analysis revealed no significant differences between them for all outcome variables, including the time to fracture union (mean difference = -0.59 weeks; 95% confidence interval [CI], -1.82 to 0.64; P = 0.35; IBoth TBW and SF are excellent clinical and radiological methods for MMF fixation. However, an appropriate fixation method should be chosen according to the fracture type and size and bone quality considering the advantages and disadvantages of each method.III, meta-analysis.

Defects in bone are some of the most difficult injuries to treat. Biomimetic scaffolds represent a promising approach for successful bone tissue regeneration. In this study, a three-dimensional (3D) scaffold with osteo-inductive functionality was designed and assayed both in-vitro and in-vivo. Bone formation peptide-1 (BFP1), an osteo-promoting specific peptide, was covalently bound to a 3D printed polycaprolactone (PCL) scaffold using polydopamine (DOPA). The amount of BFP1 immobilized on the surface was found to increase depending on the BFP1 concentration of the loading solution. To observe the biological effects of the 3D scaffolds, human tonsil-derived mesenchymal stem cells (hTMSCs) were isolated. The cells were cultured on the scaffolds and observed to rapidly differentiate into osteoblast-like cells with osteo-promoting capabilities. The scaffolds were implanted in a rabbit calvarial defect model for 8 weeks and successfully stimulated both vessel and bone regeneration. Osteo-promoting 3D scaffolds may provide a safer and more efficient approach for bone repair and remodelling in regenerative medicine.

This study investigated whether rIPC alters the typical changes in pulmonary arterial pressure, pulmonary gas exchange associated with exercise in hypoxia. Methods 16 healthy adults were randomized to either rIPC treatment (n = 8) or control (n = 8). Afterward, subjects performed supine ergometry at constant load (30 W, 40˜50 rpm) for 25 min during hypoxia (12.5% O2). Following a 90˜120 min rest, either rIPC or sham treatment was performed, which was then followed by post-assessment exercise. Throughout exercise, pulmonary arterial systolic pressure (PASP) and mean pulmonary arterial pressure (mPAP) were measured via echocardiography, while pulmonary gas exchange was being assessed. Results The rICP group demonstrated improved PASP and mPAP (p Conclusion These data suggest that rIPC contributes to reduced pulmonary arterial pressure, and improved pulmonary gas exchange during hypoxic exercise. However, follow-up studies are needed to apply these findings to patient care settings.

Periacetabular osteotomy (PAO) is a major hip preservation surgery for developmental dysplasia of the hip. It is inevitably associated with significant blood loss, so it requires frequent transfusions and could be a cause of perioperative morbidity. However, to date, a large number of studies has not evaluated the effect of antifibrinolytic agents in PAO. Therefore we performed a systematic review and meta-analysis to assess if antifibrinolytics would be effective in reducing blood loss and transfusion rate after PAO surgery.In this systematic review and meta-analysis, MEDLINE, Embase, and Cochrane Library databases were systematically searched for studies published before April 4, 2020, that investigated the effect of antifibrinolytic agents in PAO. A pooled analysis was designed to identify differences between antifibrinolytic and control groups focusing on blood loss, transfusion, operation time, postoperative venous thromboembolism (VTE), and length of hospital stay.We included five studies involving 507 patients (antifibrinolytic group: 256; control group: 251). The pooled analysis showed that the control group had a greater total estimated blood loss (EBL) than the antifibrinolytic group (mean difference [MD]=-257.60mL, 95% confidence interval [CI] -389.68 to -125.53, p=0.0001), but there were no statistical differences in intraoperative EBL (MD=-46.46mL, 95% CI: -192.57 to 99.64, p=0.53). The allogenic transfusion rate was higher in the control group than in the antifibrinolytic group (odds ratio [OR] 0.21, 95% CI: 0.10-0.43, p0.0001), but there was no difference in the autogenic transfusion rate (OR 0.35, 95% CI: 0.09-1.43, p=0.14). The pooled result showed no difference in operation time (MD=9.13min, 95% CI: -8.54 to 26.80, p=0.31). For the VTE rate, a pooled analysis was not conducted due to the lack of data. The length of hospital stay showed no differences (MD=-0.51 days, 95% CI: -1.17 to 0.16, p=0.13).Antifibrinolytic use in PAO has positive effects in terms of reduced total EBL and allogenic transfusion rate.III; meta-analysis.

Introduction: With minimal systemic toxicity, an analgesic effect of regional nerve block (RNB) has been proved in hip fracture cases. Analgesia was expected to reduce delirium by controlling pain, a known predisposing factor for delirium. We performed a meta-analysis to investigate the effect of RNB on delirium after hip fracture surgery in elderly patients. We aimed to answer the question: Can regional nerve block reduce postoperative delirium in hip fracture patients?. Hypothesis: Our hypothesis was that RNB could reduce postoperative delirium after hip fracture surgery in elderly patients. Patients and Methods: MEDLINE, Embase, and Cochrane Library databases were searched systematically for studies published before September 9, 2020, investigating the effect of RNB on perioperative delirium after hip fracture in elderly patients. We performed synthetic analyses for overall RNB compared to a control group both in 1) overall elderly patients, including the cognitively impaired, and 2) for patients without cognitive impairment (CoI). Also, we performed subgroup analyses for each of the block techniques, such as fascia-iliac block (FIB) and femoral nerve block (FNB). Results: Eight randomized controlled trials compared the incidence of perioperative delirium between the RNB and control groups. A pooled analysis showed no differences in delirium incidence between the RNB and control groups (odds ratio [OR], 0.66; 95% confidence interval [CI], 0.36–1.22; P = 0.18; I2 = 58%) in overall elderly patients. However, there was a significant reduction of delirium in the RNB group in patients without CoI (OR, 0.44; 95% CI, 0.21–0.94; P = 0.03; I2 = 51%). In the subgroup analyses, we were unable to discern any differences in delirium incidence between the groups for FIB (OR, 0.89; 95% CI, 0.19–4.19; P = 0.88; I2 = 78%) and FNB (OR 0.61; 95% CI, 0.31–1.20, P = 0.15, I2 = 47%). Conclusions: In cases of hip fracture in elderly, RNB demonstrated a preventive effect on perioperative delirium for patients without preoperative CoI. No significant reduction in perioperative delirium was observed when cognitively impaired patients were included.

This study used a more detailed dataset approach to address the limitations of existing building energy prediction methods and to predict building energy demand more accurately. The EnergyPlus dynamic simulation program closely modeled building envelope performance, zone division, and heating, ventilation, and air conditioning systems. Building energy simulation used actual weather data and generated occupancy data. The occupancy, lighting, and equipment schedules for each zone were generated in 5-min intervals using the Lawrence Berkeley National Laboratory occupancy simulator. Summer electric power consumption based on Internet of Things information from the testbed building validated the model. When applying generated occupancy, lighting, and equipment schedules, the mean bias error of simulation similarly improved to 4.73%, and the coefficient of variation of the root-mean-squared error (Cv(RMSE]) improved to 12.26%. Subsequently, a demand prediction model was constructed as a sequence-to-sequence (seq2seq) model using long short-term memory (LSTM) cells in recurrent neural network (RNN) algorithms, then its accuracy was evaluated. In the seq2seq model, the learning performance based on the EnergyPlus data exhibited an RMSE of 4.48% and a weighted average percentage error of 3.07%. As a result of applying prediction methods while changing climate scenarios, prediction performance also satisfied statistically significant levels. The occupancy information and solar radiation were determined to exert the greatest influence on the building energy demand prediction.

Background Since its introduction in the early 1960s, the multiple cannulated screw fixation method has been developed for use in femoral neck fractures (FNFs); however, the parallelism of screws remains controversial. Materials and Methods MEDLINE, Embase, and the Cochrane Library were systematically searched for studies published before June 2, 2020, that compared the use of parallel and non-parallel screw fixation for the treatment of FNF. The pooled analysis was designed to identify differences between the two groups and focused on postoperative complications, including fracture nonunion and osteonecrosis of the femoral head (ONFH). Results Over four studies, we enrolled 445 patients, including 195 patients with fixed FNF with parallel trajectory screws and 250 patients with fixed FNF with non-parallel screws. The pooled analysis showed no difference in the nonunion rates (odds ratio (OR) = 0.91; 95 % confidence interval (CI), 0.24–3.44; P = 0.89) and no significant difference in the incidence of ONFH between parallel and non-parallel screw fixation (OR = 0.74; 95 % CI: 0.21–2.63; P = 0.64). Conclusions The results of this meta-analysis reveal that screw parallelism in multiple cannulated screw fixation of FNF has no relationship with either the fracture nonunion rate or the incidence of postoperative ONFH. Level of evidence III; meta-analysis.

Microalgae have recently attracted tremendous attention as a possible feedstock for biofuel production. In this study, the pyrolysis characteristics and kinetics of Aurantiochytrium sp. KRS101, a kind of heterotrophic oleaginous microalgae, were investigated by means of thermogravimetric analysis and pyrolysis in a micro-tubing reactor. Most biochemical components of the microalgae (carbohydrates, proteins, and lipids) were decomposed between 150 and 600 °C at heating rates of 5–20 °C/min. Derivative thermogravimetry (DTG) curves were deconvoluted to more fully understand the separate decompositions of carbohydrates, proteins, and lipids. Experimental results of pyrolysis in the micro-tubing reactor were consistent with the predictions of the proposed lumped kinetic model, and the kinetic rate constants indicated that the predominant reaction pathway under the investigated pyrolysis conditions was from biomass to bio-oil rather than from biomass to gas.

We investigated the hydrothermal liquefaction (HTL) of microalgal Aurantiochytrium sp. KRS101 at various reaction temperatures (250∼400 °C) and reaction times (10∼60 min). The product distributions of bio-oil, aqueous-phase, and gaseous products were strongly affected by reaction temperature and time. The highest bio-oil yield of 51.22 wt% was obtained at 400 °C for 10 min. A general quantitative kinetic model was applied to the hydrothermal liquefaction of microalgae, in which aqueous-phase product (AP), bio-oil, and gas were formed from the decomposition of carbohydrates, lipids, and proteins in biomass cells. The rate constants of the model were determined by minimizing the least-squares error between the experimental and calculated data using a MATLAB optimization function. The results show that the model accurately captures the trend in the experimental data. The kinetics rate constants indicate that the formations of bio-oil and aqueous-phase products from decomposition of proteins, lipids, and carbohydrates are the dominant reaction pathways. The kinetic parameters calculated from the model were utilized to explore the parameter space in order to predict liquefaction product yields.

Background In young active patients with hip dysplasia, choosing between periacetabular osteotomy (PAO) and total hip arthroplasty (THA) is challenging. Materials and methods We systematically searched MEDLINE, Embase, and Cochrane Library for studies published until October 10, 2019, comparing PAO and THA in patients with dysplastic hip. We compared postoperative complications’ incidences, end-stage revisions, and clinical scores. Results Five studies with 431 hips (PAO: 235; THA: 196) were included. The incidence of overall and major complications was not different between groups (PAO: OR 2.14; 95 % CI, 0.58–7.96; p = 0.26; follow-up, 4–7.8 years; THA: OR 2.56; 95 % CI, 0.60–10.98; p = 0.21; follow-up, 4–7.8 years). There was also no difference in end-stage revision (OR 0.95; 95 % CI, 0.33–2.79; p = 0.93; follow-up, 4–7.8 years). The standard mean of Western Ontario McMasters Universities (WOMAC) pain score was higher in the THA than in the PAO group (standardized mean difference [SMD] −0.57; 95 % CI, −0.93 – −0.21; p = 0.002; follow-up, 4–5.5 years); however, the WOMAC functional score did not differ significantly between groups (SMD −0.16; 95 % CI, −1.29–0.97; p = 0.78; follow-up, 4–5.5 years). The standard mean UCLA activity index was higher in the PAO than in the THA group (SMD 0.28; 95 % CI, 0.02–0.53; p = 0.03; follow-up, 5.9–7.3 years). Conclusions The incidence of postoperative complications and revision surgery was not different between THA and PAO groups. However, postoperative pain was less in the THA group and the activity score was higher in the PAO group in the follow-up periods. Level of evidence III; meta-analysis.

Heterotrophic microalgae, Aurantiochytrium sp. KRS101 had a large amount of lipid (56.8% total lipids). The cells in the culture medium were easily ruptured due to thin cell wall of Aurantiochytrium sp., which facilitated in-situ fatty acid methyl esters (FAMEs) production directly from biomass. The harvested biomass had a high content of free fatty acids (FFAs), which was advantageous for glycerol-free FAMEs production. FAMEs were directly produced from Aurantiochytrium sp. KRS101 biomass (48.4% saponifiable lipids) using Novozyme 435-catalyzed in-situ esterification in dimethyl carbonate (DMC). DMC was used as a lipid extraction reagent, acyl acceptor and reaction medium. A 433.09mg FAMEs/g biomass was obtained with 89.5% conversion under the optimal condition: DMC to biomass ratio of 5:1 (v/w) and enzyme to biomass ratio of 30% (w/w) at 50°C for 12h. Glycerol could not be detected in the produced FAMEs.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) represents an effective agent for the treatment of many cancers, though the majority of thyroid cancers are found to be resistant. Therefore it would be necessary to identify agents capable of increasing the sensitivity of these cancers to TRAIL-mediated cell death. Here, we examined the therapeutic effect and its underlying mechanism of combination treatment of TRAIL and histone deacetylase inhibitor, Valproic acid (VPA) in vitro using human papillary thyroid cancer (PTC) cells and in vivo using an orthotopic mouse model of PTC. TRAIL-VPA combination therapy synergistically induced apoptotic cell death in TRAIL-resistant PTC through caspase activation. In addition, downregulation of antioxidant transcription factor, Nrf2 by co-treatment of TRAIL-VPA induces cell death via suppression of Bcl-xL in vitro and in vivo; these effects were further enhanced following siRNA inhibition of these proteins in combination with TRAIL or TRAIL-VPA. Taken together, VPA sensitized TRAIL-resistant PTC cells to apoptotic cell death through involvement of Nrf2 and Bcl-xL. Thus, the combination of VPA and TRAIL may be a promising therapy for TRAIL-resistant PTC.

The term variable refrigerant flow (VRF) refers to the ability of a system to control the amount of refrigerant flow rate, which enables the use of many evaporators (indoor units) of differing capacities and configurations connected to a single condensing unit. The feature offers individualized comfort control and simultaneous heating and cooling in different zones. In this study, a performance prediction model of a DX AHU (direct expansion air handling unit)-water source VRF heat pump system was constructed based on EnergyPlus, MATLAB and BCVTB using actual measured data. Advanced control logic using an EMS function was used in EnergyPlus for outdoor unit modeling, while prediction models for a cooling tower, boiler and pump were constructed in Matlab. In order to predict the model’s quantitative energy consumption, performance curves and power consumption were calculated. The calculations were checked by comparing them with actual data and the performance curves were then calibrated. The validity test results after the calibrations showed reliable results with a Cv(RMSE) of 14.5%. Based on these results, we performed a sensitivity analysis of the DX AHU-water source VRF system’s cooling energy according to the AHU discharge air temperature, refrigerant evaporative temperature and condenser fluid temperature and flow rate.

Purpose For optimization of the pump setting, there is currently a lack of non-invasive diagnostic methods capable to sensitively reflect the altered right-to-left ventricle relationship following the Left Ventricle Assist Device (LVAD) implantation. It was hypothesized that novel measures derived from the re-breath diffusing lung capacity for carbon monoxide (DLCO) technique may become a viable alternative to invasive hemodynamic studies. The present pilot study demonstrates feasibility and quantification of dynamic pulmonary variables including lung blood flow (Q) in the face of a device derived and clinical data. Methods 6 patients with LVAD participated in the present study (tab 1). Oxygen consumption and DLCO with its components were assessed pre- and during 12-15 min of low intensity (0.3 Watts/kg) exercise on a semi-recumbent ergometer. At constant LVAD speed, nitric oxide analyzer and mass spectrometer connected to a subject via a mouthpiece were used. Results During exercise, each patient demonstrated different patterns and magnitude of alterations in respiratory gas exchange (fig 1A). Moreover, variability of alteration in DLCO measures among patients was more prominent after correction for Q (fig 2B). Conclusion Distinct inter-personal responses in DLCO components and respiratory gas exchange to low intensity exercise may indicate that the re-breath DLCO technique can be utilized for a non-invasive LVAD speed optimization.

Recapitulating the in vivo microenvironments of damaged tissues through modulation of the physicochemical properties of scaffolds can boost endogenous regenerative capacity. A series of critical events in tissue healing including immune-responses, angiogenesis, and stem cell homing and differentiation orchestrate to relay the regeneration process. Herein, we report hierarchically structured ('microchanneled') 3D printed scaffolds (named 'μCh'), in contrast to conventional 3D printed scaffolds, induce such cellular responses in a unique way that contributes to accelerated tissue repair and remodeling. The μCh reduced the extracellular trap formation of anchored neutrophils at the very beginning (24 h) of implantation while increasing the number of live cells. Among the macrophages covered the surface of μCh over 7 days a major population polarized toward alternativelly activated phase (M2) which contrasted with control scaffolds where classically activated phase (M1) being dominant. The mesenchymal stem cells (MSCs) recruited to the μCh were significantly more than those to the control, and the event was correlated with the increased level of stem cell homing cytokine, stromal derived factor 1 (SDF1) sequestered to the μCh. Furthermore, the neo-blood vessel formation was more pronounced in the μCh, which was in line with the piling up of angiogenic factor, vascular endothelial growth factor (VEGF) in the μCh. Further assays on the protein sequestration to the μCh revealed that a set of chemokines involved in early pro-inflammatory responses were less found whereas representative adhesive proteins engaged in the cell-matrix interactions were significantly more captured. Ultimately, the fibrous capsule formation on the μCh was reduced with respect to the control, when assessed for up to 21 days, indicating less severe foreign body reaction. The tissue healing and regenerative capacity of the μCh was then confirmed in a critically sized bone model, where those series of events observed are essential to relay bone regeneration. The results over 6 weeks showed that the μCh significantly enhanced the early bone matrix deposition and accelerated bone regeneration. While more in-depth studies remain as to elucidate the underlying mechanisms for each biological event, the molecular, cellular and tissue reactions to the μCh were coherently favorable for the regeneration process of tissues, supporting the engineered scaffolds as potential therapeutic 3D platforms.

Exercise intolerance is a hallmark of symptoms in patients with heart failure. In addition to reduced cardiac output, a series of impairments in pulmonary and vascular systems leads to decreases in oxygen delivery and availability in locomotor muscles. This contributes to exercise intolerance in heart failure. The oxy-hemoglobin dissociation curve is essentially a graph illustrating the relationship between the partial pressure of oxygen (PO2, X-axis) and oxygen saturation (SaO2, Y-axis) of hemoglobin. The rightward shift of the curve indicates that hemoglobin's affinity for oxygen decreases and in turn, it may allow the release of more oxygen to tissues. In the present study, we discuss the pathophysiological impairment, which causes exercise intolerance in heart failure patients and suggest a strategy to improve exercise capacity without altering cardiac output via modulating the oxy-hemoglobin dissociation curve.

Cardiac resynchronization therapy (CRT) is an accepted intervention for chronic heart failure (HF), although approximately 30% of patients are non-responders. The purpose of this study was to determine whether exercise respiratory gas exchange obtained before CRT implantation predicts early response to CRT.Before CRT implantation, patients were assigned to either a mild-moderate group (Mod G, n = 33, age 67 ± 10 years) or a moderate-severe group (Sev G, n = 31, age 67 ± 10 years), based on abnormalities in exercise gas exchange. Severity of impaired gas exchange was based on a score from the measures of VE/VCO(2) slope, resting PETCO(2) and change of PETCO(2) from resting to peak. All measurements were performed before and 3 to 4 months after CRT implantation.Although Mod G did not have improved gas exchange (p0.05), Sev G improved significantly (p0.05) post-CRT. In addition, Mod G did not show improved right ventricular systolic pressure (RSVP; pre vs post: 37 ± 14 vs 36 ± 11 mm Hg, p0.05), yet Sev G showed significantly improved RVSP, by 23% (50 ± 14 vs 42 ± 12 mm Hg, p0.05). Both groups had improved left ventricular ejection fraction (p0.05), New York Heart Association class (p0.05) and quality of life (p0.05), but no significant differences were observed between groups (p0.05). No significant changes were observed in brain natriuretic peptide in either group post-CRT.Based on pre-CRT implantation ventilatory gas exchange, subjects with the most impaired values appeared to have more improvement post-CRT, possibly associated with a decrease in RVSP.

As there is no single ideal material for dorsal augmentation in rhinoplasty, there has been a continuing need for the development of improved materials. Therefore, we aimed to evaluate the outcome of using a novel tissue-engineered construct composed of autologous chondrocytes cultured with a porcine cartilage-derived substance (PCS) scaffold as an augmentation material in rhinoplasty. A scaffold derived from decellularized and powdered porcine articular cartilage was prepared. The rabbit articular cartilage was used as the source of homologous chondrocytes, which were expanded and cultured with the PCS scaffold for 7 weeks. The chondrocyte-PCS constructs were then surgically implanted on the nasal dorsum of six rabbits. Four and eight weeks after implantation, the gross morphology, radiologic images, and histologic features of the site of implant were analyzed. The rabbits showed no signs of postoperative inflammation and infection. The degree of dorsal augmentation was maintained during the 8-week postoperative observation period. Postoperative histologic examinations showed chondrocyte proliferation without an inflammatory response. However, neo-cartilage formation from the constructs was not confirmed. The biocompatibility and structural features of tissue-engineered chondrocyte-PCS constructs indicate their potential as candidate dorsal augmentation material for use in rhinoplasty.

Hepatocyte growth factor (HGF) and its receptor, Met, regulate skeletal muscle differentiation. In the present study, we identified a novel alternatively spliced isoform of Met lacking exon 13 (designated Δ13Met), which is expressed mainly in human skeletal muscle. Alternative splicing yielded a truncated Met having extracellular domain only, suggesting an inhibitory role. Indeed, Δ13Met expression led to a decrease in HGF-induced tyrosine phosphorylation of Met and ERK phosphorylation, as well as cell proliferation and migration via sequestration of HGF. Interestingly, in human primary myoblasts undergoing differentiation, Δ13Met mRNA and protein levels were rapidly increased, concomitantly with a decrease in wild type Met mRNA and protein. Inhibition of Δ13Met with siRNA led to a decreased differentiation, whereas its overexpression potentiated differentiation of human primary myoblasts. Furthermore, in notexin-induced mouse injury model, exogenous Δ13Met expression enhanced regeneration of skeletal muscle, further confirming a stimulatory role of the isoform in muscle cell differentiation. In summary, we identified a novel alternatively spliced inhibitory isoform of Met that stimulates muscle cell differentiation, which confers a new means to control muscle differentiation and/or regeneration.

It is unclear how dynamic changes in pulmonary-capillary blood volume (Vc), alveolar lung volume (derived from end-inspiratory lung volume, EILV) and interstitial fluid (ratio of alveolar capillary membrane conductance and pulmonary capillary blood volume, Dm/Vc) influence lung impedance (Z(T)). The purpose of this study was to investigate if positional change and exercise result in increased EILV, Vc and/or lung interstitial fluid, and if Z(T) tracks these variables.12 heart failure (HF) patients underwent measurements (Z(T), EILV, Vc/Dm) at rest in the upright and supine positions, during exercise and into recovery. Inspiratory capacity was obtained to provide consistent measures of EILV while assessing Z(T).Z(T) increased with lung volume during slow vital capacity maneuvers (p0.05). Positional change (upright→supine) resulted in an increased Z(T) (p0.01), while Vc increased and EILV and Dm/Vc decreased (p0.05). Moreover, during exercise Vc and EILV increased and Dm/Vc decreased (p0.05), whereas, Z(T) did not change significantly (p0.05).Impedance appears sensitive to changes in lung volume and body position which appear to generally overwhelm small acute changes in lung fluid when assed dynamically at rest or during exercise.

For consolidated bioprocessing (CBP), components of Jerusalem artichoke ( Helianthus tuberosus L.) tubers and stalks as a potential bioenergy crop were analyzed as carbon and nutrient sources, respectively. The effectiveness of chemical pretreatment with dilute acid or alkali was evaluated to develop a CBP method. Cellulose content, delignification, and enzymatic hydrolysis efficiency of the pretreated stalks were increased more effectively by NaOH treatment than dilute H 2 SO 4 treatment. However, weight loss was greater during alkali pretreatment. Additionally, large volumes of water were required to wash the alkali-treated biomass. Therefore, CBP using the dilute acid-pretreated stalk and the ground tuber of Kluyveromyces marxianus were investigated. Fermentation of both pretreated stalks and tubers by K. marxianus with no nutrient supplementation proceeded acceptably. At 10% (w/v) stalk and 8% (w/v) tuber loading, K. marxianus produced 45.3 g/L ethanol after 30 h. The ethanol yield was 0.252 g ethanol per g dry biomass, or 0.32 g ethanol per g fermentable sugars, with a fermentable sugar conversion rate of 60%. These results suggest a cost-effective CBP strategy for bioethanol production from the whole Jerusalem artichoke plant.

Background Cardiac resynchronization therapy (CRT) has been an important treatment for heart failure. However, it is controversial as to whether an individualized approach to altering AV and VV timing intervals would improve outcomes. Changes in respiratory patterns and gas exchange are dynamic and may be influenced by timing delays. Light exercise enhances the heart and lung interactions. Thus, in this study we investigated changes in non-invasive gas exchange by altering AV and VV timing intervals during light exercise. Methods Patients ( n = 20, age 66 ± 9 years) performed two walking tests post-implantation. The protocol evaluated AV delays (100, 120, 140, 160 and 180 milliseconds), followed by VV delays (0, −20 and −40 milliseconds) while gas exchange was assessed. Results There was no consistent group pattern of change in gas exchange variables across AV and VV delays ( p > 0.05). However, there were modest changes in these variables on an individual basis with variations in VE/VCO 2 averaging 10%; O 2 pulse 11% and PETCO 2 5% across AV delays, and 4%, 8% and 2%, respectively, across VV delays. Delays that resulted in the most improved gas exchange differed from nominal in 17 of 20 subjects. Conclusion Gas exchange measures can be improved by optimization of AV and VV delays and thus could be used to individualize the approach to CRT optimization.

The present study investigates the production of mixed acids by anaerobic fermentation using non-pretreated red algae Gelidium amansii as a substrate. The production levels of mixed acids were increased 1.6-fold in enrichment cultures of anaerobic digester sludge and tidal field soil compared with fresh sludge. The enrichment culture was composed of four major groups of microbial strains belonging to Clostridium sp. and Enterococcus sp. A defined mixed culture established based on the identified isolates increased mixed acids production level by up to 50.9% (g/g). Semi-continuous fermentation with a biomass-loading rate of 2.77 g/L/d and hydraulic retention time of 30 days yielded a productivity of 1.41 g/L/d. This is the first report of the production of mixed acids from the red algae G. amansii .

Nonsteroidal anti-inflammatory drugs (NSAIDs) are usually used for the treatment of inflammatory diseases. However, certain NSAIDs also have antitumor activities in various cancers, including head and neck cancer, through cyclooxygenase-dependent or independent pathways. Nonsteroidal anti-inflammatory drug-activated gene-1 (NAG-1), a TGF-β superfamily protein, is induced by NSAIDs and has been shown to be induced by several antitumorigenic compounds and to exhibit proapoptotic and antitumorigenic activities. In this report, we demonstrate for the first time that tolfenamic acid (TA) transcriptionally induced the expression of NAG-1 during TA-induced apoptosis of anaplastic thyroid cancer (ATC) cells. TA reduced the viability of ATC cells in a dose-dependent manner and induced apoptosis, findings that were coincident with NAG-1 expression. Overexpression of the NAG-1 gene using cDNA enhanced the apoptotic effect of TA, whereas suppression of NAG-1 expression by small interfering RNA attenuated TA-induced apoptosis. Subsequently, we found that intracellular ROS generation plays an important role in activating the proapoptotic protein NAG-1. Then, we confirmed antitumorigenic effects of TA in a nude mouse orthotopic ATC model, and this result accompanied the augmentation of NAG-1 expression and ROS generation in tumor tissue. Taken together, these results demonstrate that TA induces apoptosis via NAG-1 expression and ROS generation in in vitro and in vivo ATC models, providing a novel mechanistic explanation and indicating a potential chemotherapeutic approach for treatment of ATC.

Radiation is a widely used treatment for head and neck cancers, and one of its most severe side effects is ototoxicity. Radiation-induced ototoxicity has been demonstrated to be linked to the increased production of ROS and MAPK. We intended to investigate the effect of p38 inhibition on radiation-induced ototoxicity in cochlea-derived HEI-OC1 cells and in a zebrafish model. The otoprotective effect of p38 inhibition against radiation was tested in vitro in the organ of Corti-derived cell line, HEI-OC1, and in vivo in a zebrafish model. Radiation-induced apoptosis, mitochondrial dysfunction, and an increase of intracellular NO generation were demonstrated in HEI-OC1 cells. The p38-specific inhibitor, SB203580, ameliorated radiation-induced apoptosis and mitochondrial injury in HEI-OC1 cells. p38 inhibition reduced radiation-induced activation of JNK, p38, cytochrome c, and cleavage of caspase-3 and PARP in HEI-OC1 cells. Scanning electron micrography showed that SB203580 prevented radiation-induced destruction of kinocilium and stereocilia in zebrafish neuromasts. The results of this study suggest that p38 plays an important role in mediating radiation-induced ototoxicity and inhibition of p38 could be a plausible option for preventing radiation ototoxicity.

Objectives Tracheal reconstruction with tissue-engineering technique has come into the limelight in the realm of head and neck surgery. We intended to evaluate the plausibility of allogenic chondrocytes cultured with porcine cartilage-derived substance (PCS) scaffold for partial tracheal defect reconstruction. Methods Powder made from crushed and decellularized porcine articular cartilage was formed as 5 mm × 12 mm (height × diameter) scaffold. Chondrocytes from rabbit articular cartilage were expanded and cultured with PCS scaffold. After 7 weeks culture, the scaffolds were implanted on a 5 mm × 10 mm artificial tracheal defect in six rabbits. Two, four and eight weeks postoperatively, the sites were evaluated endoscopically, radiologically, histologically and functionally. Results None of the six rabbits showed any sign of respiratory distress. Endoscopic examination did not show any collapse or blockage of the reconstructed trachea and the defects were completely covered with regenerated respiratory epithelium. Computed tomography showed good luminal contour of trachea. Postoperative histologic data showed that the implanted chondrocyte successfully formed neo-cartilage with minimal inflammatory response and granulation tissue. Ciliary beat frequency of regenerated epithelium was similar to those of normal adjacent mucosa. Conclusions The shape and function of reconstructed trachea using allogenic chondrocytes cultured with PCS scaffold was restored successfully without any graft rejection.

We isolated and characterized an oleaginous Thraustochytrid microalga. Based on 18 s rRNA sequencing, we classified this strain as Schizochytrium sp. SH103. Growth of these cells in a 5 L fermentor with a microbubble-type sparger (MTS) efficiently increased the oxygen transfer coefficient (OTC), while inducing only low external stress. For fermentation under conditions of low agitation (100 rpm) and aeration (3 L/min), the OTC was 8.6-fold higher using a MTS than a general type sparger (GTS). Under these same conditions, dry cell weight (DCW) productivity (0.54 vs. 1.26 g/L·h) and total lipid productivity (0.29 vs. 0.61 g/L·h) were each about 2.2-fold higher using a MTS than a GTS. Under conditions that optimized the OTC in a MTS fermentor (876 h−1), DCW productivity, total lipid productivity and DHA productivity were each 1.3-fold greater than non-optimized condition. Fed-batch fermentation experiments indicated the maximal DCW was 100.6 g/L at 48 h, maximal DCW productivity was 2.1 g/L·h, maximal lipid content was 48.6 g/L at 48 h, and lipid productivity was 1.0 g/L·h. Additionally, the results of experiments using a 50 L MTS fermentor (96.0 g/L DCW and 44.3 g/L total lipids at 48 h) were similar to those using the 5 L fermentor. Our results suggest that use of a MTS may help to achieve the efficient fermentation of heterotrophic microalgae for high cell densities.

Pulmonary function (PF) and diffusion capacity of lungs (DLCO) do not improve following implantation of Left Ventricle Assist Devices (LVAD) despite an increase in cardiac output. We hypothesized DLCO post-surgery may be influenced by right ventricular (RV) function assessed by echo prior to LVAD