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In endometrial cancer (EC) and colorectal cancer (CRC), in addition to microsatellite instability, tumor mutational burden (TMB) has gradually gained attention as a genomic biomarker that can be used clinically to determine which patients may benefit from immune checkpoint inhibitors. High TMB is characterized by a large number of mutated genes, which encode aberrant tumor neoantigens, and implies a better response to immunotherapy. Hence, a part of EC and CRC patients associated with high TMB may have higher chances to receive immunotherapy. TMB measurement was mainly evaluated by whole-exome sequencing or next-generation sequencing, which was costly and difficult to be widely applied in all clinical cases. Therefore, an effective, efficient, low-cost and easily accessible tool is urgently needed to distinguish the TMB status of EC and CRC patients. In this study, we present a deep learning framework, namely Ensemble Transformer-based Multiple Instance Learning with Self-Supervised Learning Vision Transformer feature encoder (ETMIL-SSLViT), to predict pathological subtype and TMB status directly from the H&E stained whole slide images (WSIs) in EC and CRC patients, which is helpful for both pathological classification and cancer treatment planning. Our framework was evaluated on two different cancer cohorts, including an EC cohort with 918 histopathology WSIs from 529 patients and a CRC cohort with 1495 WSIs from 594 patients from The Cancer Genome Atlas. The experimental results show that the proposed methods achieved excellent performance and outperforming seven state-of-the-art (SOTA) methods in cancer subtype classification and TMB prediction on both cancer datasets. Fisher's exact test further validated that the associations between the predictions of the proposed models and the actual cancer subtype or TMB status are both extremely strong (p<0.001). These promising findings show the potential of our proposed methods to guide personalized treatment decisions by accurately predicting the EC and CRC subtype and the TMB status for effective immunotherapy planning for EC and CRC patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Competing Interests: Declaration of competing interest The authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article.

Endometrial cancer (EC) diagnosis traditionally relies on tumor morphology and nuclear grade, but personalized therapy demands a deeper understanding of tumor mutational burden (TMB), i.e., a key biomarker for immune checkpoint inhibition and immunotherapy response. Traditional TMB prediction methods, such as sequencing exomes or whole genomes, are costly and often unavailable in clinical settings. We present the first TR-MAMIL deep learning framework to predict TMB status and classify the EC cancer subtype directly from H&E-stained WSIs, enabling effective personalized immunotherapy planning and prognostic refinement of EC patients. Our models were evaluated on a large dataset from The Cancer Genome Atlas. TR-MAMIL performed exceptionally well in classifying aggressive and non-aggressive EC, as well as predicting TMB, outperforming seven state-of-the-art approaches. It also performed well in classifying normal and abnormal p53 mutations in EC using H&E WSIs. Kaplan-Meier analysis further demonstrated TR-MAMIL's ability to differentiate patients with longer survival in the aggressive EC., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Whether the addition of aromatase inhibitors (AIs) to recombinant human growth hormone (rhGH) could yield additional benefit for short stature is controversial. We aimed to assess the effects of combined AIs and rhGH versus those of rhGH alone for short stature using a meta-analytic approach. The PubMed, Embase, and the Cochrane library electronic databases were searched systematically for eligible randomized controlled trials (RCTs) from inception until December 2021. The pooled effect estimates (weighted mean difference [WMD] and odds ratio [OR]) with 95% confidence intervals (CIs) were calculated using a random-effects model. Eight RCTs that provided data on 433 participants were selected. The addition of AIs to rhGH, compared with rhGH alone, resulted in higher growth velocity (WMD: 3.19 cm/year; 95% CI: 2.75-3.63; P < 0.001), higher predicted adult height (WMD: 5.50 cm; 95% CI: 3.52-7.49; P < 0.001), and younger bone age (WMD: -0.80 years; 95% CI: -1.06--0.54; P < 0.001). There were no significant differences between the groups for insulin-like growth factor I (WMD: 0.85 nmol/L; 95% CI: -2.08-3.79; P = 0.569), serum estradiol level (WMD: -19.19 pmol/L; 95% CI: -46.25-7.88; P = 0.165), and serum testosterone level (WMD: 14.88 nmol/L; 95% CI: -14.13-43.88; P = 0.315). There was no significant difference between the groups for the risk of adverse events (OR: 1.08; 95% CI: 0.44-2.66; P = 0.873). This study found that the addition of AIs to rhGH had greater benefits for growth velocity, predicted adult height, and bone age. The safety profiles were comparable., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Introduction: In the surgical treatment of pelvic ring injuries (PRIs), there is an increasing adoption of minimally invasive techniques to improve surgical outcomes. Since the introduction of endoscopic-assisted osteosynthesis for PRIs in 2019, various surgical challenges have been identified. To improve surgical and clinical outcomes, we modified the existing procedures and aimed to present the surgical outcomes of patients with pelvic fractures who underwent endoscopic-assisted surgery., Materials and Methods: We conducted a retrospective analysis of patients with PRIs treated with endoscopic technique over a 15-month period. All patients were diagnosed with diastatic symphysis, superior pubic ramus fracture, or both. The postoperative radiological and functional outcomes were assessed and reported. Details of the preoperative planning and surgical procedures were reviewed., Results: Thirteen patients with PRIs were enrolled: 10 patients for diastatic pubic symphysis (three of whom received superior ramus screw fixation) and three for isolated superior pubic ramus fractures. All surgeries were completed with endoscopic assistance, without the need for conversion to open surgery. The average surgical duration was 204.1 min, the endoscopy time was 103.7 min, and the volume of blood loss was 185.0 ml. Excellent reduction was achieved in all patients according to the Matta/Tornetta criteria and in nine patients according to the Lefaivre criteria. The mean Majeed scores were 71 and 82 and the mean Merle d'Aubigné scores 11 and 15 at 3 and 6 months postoperatively, respectively., Conclusion: Endoscopic-assisted pelvic surgery is a safe and effective treatment alternative for PRIs, particularly when focusing on the anterior pelvic ring. The advantages of this approach, including small incisions and preservation of abdominal and pelvic floor muscle integrity, contribute to improved patient recovery. Future research should focus on comparative studies of this technique with other minimally invasive techniques and open surgery., Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests. Ethical approval: This study was performed in accordance with the principles of the Declaration of Helsinki. This study was approved by the Institutional Review Board of Chang Gung Memorial Hospital (IRB No: 202401217B0). Consent to participate: The requirement for informed consent was waived owing to the retrospective nature of the study. Consent for publication: Not applicable., (© 2024. The Author(s).)

Background: There are limited data on the use of whole-exome sequencing (WES) to diagnose severe hypertriglyceridemia. Our aim was to identify candidate genes linked to triglyceride levels via a genome-wide association study (GWAS) and to recruit participants with severe hypertriglyceridemia for WES to assess allelic variants in the candidate genes., Methods and Results: A GWAS was conducted involving 120,140 participants to identify lead loci associated with blood triglyceride levels. Following the identification of these lead loci, WES was performed on DNA samples from 29 participants with hypertriglyceridemia whose triglyceride levels exceeded 800 mg/dL to assess variations in the corresponding genes. In the GWAS of 120,140 participants, the apolipoprotein A5 (APOA5) locus on chromosome 11 showed the strongest association with blood triglyceride levels (lead single nucleotide polymorphism [SNP] rs2075291; P=3.07×10 -108 ), along with 5 independent SNPs (most significant P=7.84×10 -167 ). Other key loci included BUD13 homolog (BUD13; P=2.73×10 -62 ), glucokinase regulator (GCKR; P=2.63×10 -24 ), and lipoprotein lipase (LPL; P=1.50×10 -11 ). WES in 29 hypertriglyceridemia patients identified additional genes, including ALDH1A2, APOC1, LPL, RGS7, and SIK3, showing significant allele frequency variations and potential roles in lipid metabolism., Conclusions: Our study confirms the role of known genetic loci in triglyceride metabolism and hypertriglyceridemia while uncovering novel loci, offering new perspectives on lipid regulation and potential avenues for therapeutic advancements.

Purpose: To compare the modified Hardinge approach and trochanteric flip osteotomy for the treatment of Pipkin type IV femoral head fractures., Methods:  This retrospective study included 40 patients who underwent surgical treatment for Pipkin type IV femoral head fractures between 2011 and 2020 and completed at least 1 year of follow-up. The clinical outcome of the Merle d'Aubigné-Postel score and radiological outcomes, including the quality of the fracture reduction, osteonecrosis of the femoral head, posttraumatic osteoarthritis, and heterotopic ossification, were compared between the two groups. Conversion to total hip replacement was recorded as the main outcome measure, analyzed by Kaplan-Meier curve and log-rank test., Results: Nineteen and 21 patients were treated using the modified Hardinge approach (Group A) and trochanteric flip osteotomy (Group B), respectively. The estimated surgical blood loss was significantly higher in Group B (500.00 ± 315.44 mL vs. 246.32 ± 141.35 mL; P = 0.002). Two patients in Group B complained of discomfort caused by the trochanteric screws and requested implant removal. Radiographic outcomes did not differ significantly between the two groups. Clinical outcomes assessed using the Merle d'Aubigné-Postel score 1 year after injury were nearly identical (P = 0.836). Four (21.1%) patients in Group A and three (14.3%) patients in Group B underwent conversion to total hip replacement during the follow-up period; the log-rank test showed no significant difference (P = 0.796)., Conclusions: The modified Hardinge approach resulted in reduced blood loss, with clinical and radiological outcomes similar to those of trochanteric osteotomy; thus, it is an acceptable alternative to trochanteric flip osteotomy., (© 2024. The Author(s).)

Molecular classification, particularly microsatellite instability-high (MSI-H), has gained attention for immunotherapy in endometrial cancer (EC). MSI-H is associated with DNA mismatch repair defects and is a crucial treatment predictor. The NCCN guidelines recommend pembrolizumab and nivolumab for advanced or recurrent MSI-H/mismatch repair deficient (dMMR) EC. However, evaluating MSI in all cases is impractical due to time and cost constraints. To overcome this challenge, we present an effective and efficient deep learning-based model designed to accurately and rapidly assess MSI status of EC using H&E-stained whole slide images. Our framework was evaluated on a comprehensive dataset of gigapixel histopathology images of 529 patients from the Cancer Genome Atlas (TCGA). The experimental results have shown that the proposed method achieved excellent performances in assessing MSI status, obtaining remarkably high results with 96%, 94%, 93% and 100% for endometrioid carcinoma G1G2, respectively, and 87%, 84%, 81% and 94% for endometrioid carcinoma G3, in terms of F-measure, accuracy, precision and sensitivity, respectively. Furthermore, the proposed deep learning framework outperforms four state-of-the-art benchmarked methods by a significant margin (p < 0.001) in terms of accuracy, precision, sensitivity and F-measure, respectively. Additionally, a run time analysis demonstrates that the proposed method achieves excellent quantitative results with high efficiency in AI inference time (1.03 seconds per slide), making the proposed framework viable for practical clinical usage. These results highlight the efficacy and efficiency of the proposed model to assess MSI status of EC directly from histopathological slides., (© 2024. The Author(s).)

Ganglioside GAA-7 exhibits higher neurite outgrowth than ganglioside GM1a and most echinodermatous gangliosides (EGs) when tested on neuron-like rat adrenal pheochromocytoma (PC12) cells in the presence of nerve growth factor (NGF). The unique structure of GAA-7 glycan, containing an uncommon sialic acid (8- O -methyl- N -glycolylneuraminic acid) and sialic acid-α-2,3-GalNAc linkage, makes it challenging to synthesize. We recently developed a streamlined method to chemoenzymatically synthesize GAA-7 glycan and employed this modular strategy to efficiently prepare a library of GAA-7 glycan analogues incorporating N-modified or 8-methoxyl sialic acids. Most of these synthetic glycans exhibited moderate efficacy in promoting neuronal differentiation of PC12 cells. Among them, the analogue containing common sialic acid shows greater potential than the GAA-7 glycan itself. This result reveals that methoxy modification is not essential for neurite outgrowth. Consequently, the readily available analogue presents a promising model for further biological investigations.

Addressing the critical requirement for real-time monitoring of tumor progression in cancer care, this study introduces an innovative wearable platform. This platform employs a thermoplastic polyurethane (TPU) film embedded with hafnium oxide nanoparticles (HfO 2 NPs) to facilitate dynamic tracking of tumor growth and regression in real time. Significantly, the synthesized HfO 2 NPs exhibit promising characteristics as effective sonosensitizers, holding the potential to efficiently eliminate cancer cells through ultrasound irradiation. The TPU-HfO 2 film, acting as a dielectric elastomer (DE) strain sensor, undergoes proportional deformation in response to changes in the tumor volume, thereby influencing its electrical impedance. This distinctive behavior empowers the DE strain sensor to continuously and accurately monitor alterations in tumor volume, determining the optimal timing for initiating HfO 2 NP treatment, optimizing dosages, and assessing treatment effectiveness. Seamless integration with a wireless system allows instant transmission of detected electrical impedances to a smartphone for real-time data processing and visualization, enabling immediate patient monitoring and timely intervention by remote medical staff. By combining the dynamic tumor monitoring capabilities of the TPU-HfO 2 film with the sonosensitizer potential of HfO 2 NPs, this approach propels cancer care into the realm of telemedicine, representing a significant advancement in patient treatment.

Background: Osteosynthesis for geriatric femoral pertrochanteric fractures using the linear compression integrated screw intramedullary nail system (INTERTAN™) has become popular. Nonetheless, cases of perioperative peri-implant fractures have been reported following this surgical technique. The factors responsible for this complication remain unclear. Therefore, we investigated perioperative peri-implant fracture risk factors and incidence, as well as overall outcomes, using the INTERTAN™ system for geriatric femoral pertrochanteric fractures., Methods: We retrospectively reviewed 98 consecutive patients with geriatric femoral pertrochanteric fractures after INTERTAN™ fixation, with at least a 12-month follow-up period between May 2020 and April 2022 at a single medical institute. The patients' demographic characteristics, fracture pattern, quality of reduction, quality of fixation, nail length, morphology of the femur, and perioperative complications were recorded and analyzed., Results: Among the 98 patients, 92 achieved union during follow-up. Twelve perioperative peri-implant fractures (12.2%) were recorded, all of which occurred during or within 1 month of osteosynthesis. Except for one patient who underwent re-osteosynthesis, the others underwent nonoperative treatment, and all achieved union. Multiple regression analysis revealed morphology of the femur with low-lesser trochanter width (odds ratio (OR) 0.532, 95% confidence interval (CI) 0.33-0.86, p = 0.01) to be the only factor contributing to perioperative peri-implant fractures. When the Youden index was used, the optimal cut-off value was 20.2 mm of low-lesser trochanter width. Low-lesser trochanter width < 20.2 mm was found to be a potential factor causing perioperative peri-implant fractures (OR 17.81, 95% CI 1.67-19.76, p = 0.017)., Conclusions: Morphology of the femur with a low-lesser trochanter width smaller than 20.2 mm was found to be the only potential contributor to perioperative peri-implant fractures when using INTERTAN™ for geriatric femoral pertrochanteric fractures. Care should be taken during osteosynthesis, focusing not only on the fracture site but also on the femoral cortex around the implant. Although perioperative peri-implant fractures were observed within one month following osteosynthesis, the majority of these cases were effectively treated without surgical intervention., (© 2023. The Author(s).)

Epithelial ovarian cancer (EOC) remains a significant cause of mortality among gynecologic cancers, with the majority of cases being diagnosed at an advanced stage. Before targeted therapies were available, EOC treatment relied largely on debulking surgery and platinum-based chemotherapy. Vascular endothelial growth factors have been identified as inducing tumor angiogenesis. According to several clinical trials, anti-vascular endothelial growth factor-targeted therapy with bevacizumab was effective in all phases of EOC treatment. However, there are currently no biomarkers accessible for regular therapeutic use despite the importance of patient selection. Microsatellite instability (MSI), caused by a deficiency of the DNA mismatch repair system, is a molecular abnormality observed in EOC associated with Lynch syndrome. Recent evidence suggests that angiogenesis and MSI are interconnected. Developing predictive biomarkers, which enable the selection of patients who might benefit from bevacizumab-targeted therapy or immunotherapy, is critical for realizing personalized precision medicine. In this study, we developed 2 improved deep learning methods that eliminate the need for laborious detailed image-wise annotations by pathologists and compared them with 3 state-of-the-art methods to not only predict the efficacy of bevacizumab in patients with EOC using mismatch repair protein immunostained tissue microarrays but also predict MSI status directly from histopathologic images. In prediction of therapeutic outcomes, the 2 proposed methods achieved excellent performance by obtaining the highest mean sensitivity and specificity score using MSH2 or MSH6 markers and outperformed 3 state-of-the-art deep learning methods. Moreover, both statistical analysis results, using Cox proportional hazards model analysis and Kaplan-Meier progression-free survival analysis, confirm that the 2 proposed methods successfully differentiate patients with positive therapeutic effects and lower cancer recurrence rates from patients experiencing disease progression after treatment (P < .01). In prediction of MSI status directly from histopathology images, our proposed method also achieved a decent performance in terms of mean sensitivity and specificity score even for imbalanced data sets for both internal validation using tissue microarrays from the local hospital and external validation using whole section slides from The Cancer Genome Atlas archive., (Copyright © 2023 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.)

We examined the incidence and causative factors of surgical site infection (SSI) following osteosynthesis for pelvic ring injury by reviewing the data of 97 consecutive patients with pelvic ring injuries treated between 2014 and 2019. Osteosyntheses, including internal or external skeletal fixation with plates or screws, were performed based on fracture type and patient's condition. Fractures were treated surgically, with a 36 months minimum follow-up period. Eight (8.2%) patients experienced SSI. The most common causative pathogen was Staphylococcus aureus. Patients with SSI had significantly worse functional outcomes at 3, 6, 12, 24, and 36 months than those without. For patients with SSI, the average Merle d'Aubigné and Majeed scores at 3, 6, 12, 24, and 36 months after injury were 2.4, 4.1, 8.0, 11.0, and 11.3, and 25.5, 32.1, 47.9, 61.9, and 63.3, respectively. Patients with SSI had a higher likelihood of undergoing staged operations (50.0 vs. 13.5%, p = 0.02), more surgeries for associated injuries (6.3% vs. 2.5%, p = 0.04), higher likelihood of Morel-Lavallee lesions (50.0% vs. 5.6%, p = 0.002), higher incidence of diversional colostomy (37.5% vs. 9.0%, p = 0.05), and longer intensive care unit stay (11.1 vs. 3.9 days, p = 0.001) than those without. The contributing factors for SSI were Morel-Lavallee lesions (odds ratio [OR] 4.55, 95% confidence interval [95% CI] 3.34-50.0) and other surgeries for associated injuries (OR 2.37, 95% CI 1.07-5.28). Patients with SSI after osteosynthesis for pelvic ring injuries may have worse short-term functional outcomes., (© 2023. The Author(s).)

Several modifications of the induced membrane technique (IMT) have been reported, but there is no consensus regarding their results and prognosis. Moreover, most studies have focused on tibial defects; no meta-analysis of the treatment of femoral defects using the IMT has been reported. This systematic review and meta-analysis aimed to identify the potential risk factors of post-procedural complications following the treatment of segmental femoral defects using the IMT. A comprehensive search was performed on the Cochrane Library, EBSCO, EMBASE, Ovid, PubMed, Scopus, and Web of Science databases, using the keywords "femur," "Masquelet technique," and "induced membrane technique." Original articles composed in English, having accessible individual patient data, and reporting more than two cases of bony defect or nonunion of femur or more than five cases of any body part were included. Post-procedural bone graft infections, final union status, and union time after second-stage operation were analyzed. Fourteen reports, including 90 patients, were used in this study. External fixation in second-stage surgery had an odds ratio of 9.267 for post-procedural bone graft infection (p = 0.047). The odds ratio of post-procedural bone graft infection and age >65 years for final non-union status was 51.05 (p = 0.003) and 9.18 (p = 0.042). Shorter union time was related to impregnated antibiotics in the spacer (p = 0.005), transplanting all-autologous grafts (p = 0.042), and the application of intramedullary nails as the second-stage fixation method (p = 0.050). The IMT appears to be reasonable and reproducible for femoral segmental bone defects. Several preoperative and surgical factors may affect post-procedural complications and union time., (© 2022 The Authors. Orthopaedic Surgery published by Tianjin Hospital and John Wiley & Sons Australia, Ltd.)

Background: Data on predictors and time to relapse in patients with psoriasis who discontinue therapy in a real-world setting are scarce., Objective: To investigate predictors of relapse after withdrawal of ustekinumab in patients with psoriasis., Method: This study screened 500 patients with psoriasis who received ustekinumab (669 treatment episodes) between 2011 and 2018. Overall, 202 patients (accounting for 304 treatment episodes) who had responded to therapy and were withdrawn from ustekinumab treatment were included., Results: The cumulative probabilities of being relapse-free at 6, 12, 18, 24, and 36 months after withdrawal from ustekinumab treatment were 49.3%, 12.6%, 5.3%, 4.7%, and 1.6%, respectively. Multivariate regression analyses with a generalized estimating equation showed that after adjustments, biologic-naive status, maximum improvement in Psoriasis Area and Severity Index during ustekinumab treatment, time to achieve a 50% improvement in baseline Psoriasis Area and Severity Index score after initiation of ustekinumab, family history of psoriasis, chronic kidney disease, and immunosuppressant use while not taking ustekinumab were significant predictors of time to relapse following discontinuation of ustekinumab., Limitation: Nonrandomized allocation of duration of treatment and follow-up., Conclusion: Given the high rates of relapse, withdrawal of ustekinumab from patients with well-controlled psoriasis cannot be recommended., (Copyright © 2019 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Previous studies have compared different kinds of fixations for anterior cruciate ligament reconstruction. Nevertheless, there is no optimal method to date. To the best of authors' knowledge, there is no article discussing the combination of adjustable suspensory device and interference screw for hybrid tibial fixation., Methods: In total, 66 patients (n = 34, adjustable suspensory device and interference screw; n = 32, cortical screw and interference screw) were analyzed. Their International Knee Documentation Committee score and Tegner activity level scale were evaluated before and after a 2-year follow-up. The Single Assessment Numeric Evaluation score was evaluated after a 2-year follow-up. Physical exams such as range of motion, anterior knee pain (VAS > = 3) and Lachman test were assessed before and at least 12 months after surgery. To evaluate tunnel widening, anteroposterior and lateral view radiography was conducted 1 day and at least 12 months after surgery. A more than 10% change was considered tibial tunnel widening. Mann-Whitney U test, independent t test, paired t test, Fisher's exact test and chi-squared test were used to compare the variables. Linear and logistic regression models were applied to adjust for potential confounders., Results: No variable except gender (P = 0.006) showed significant difference with regard to demographic data. After adjustment, there was no statistically significant difference between the groups regarding post-operative physical exams. Patients who used adjustable suspensory device and interference screw had lower post-operative Single Assessment Numeric Evaluation score (adjusted β - 8.194; P = 0.017), Tegner activity level scale (adjusted β - 1.295; P = 0.001) and pre-operative degrees of knee flexion (adjusted β - 2.825; P = 0.026). Less percentage of tunnel widening in the lateral view of radiographs was seen in patients in group of adjustable suspensory device and interference screw (adjusted β - 1.733; P = 0.038). No significant difference was observed in the anteroposterior view of radiographs (adjusted β - 0.667; P = 0.26)., Conclusion: In these 66 patients, we observed less tibial tunnel widening and lower post-operative functional scores in the group of adjustable suspensory device and interference screw. Both groups displayed similar outcomes of physical exams as well as improvement after operation. The proposed method may become an alternative option. Nonetheless, the quality of our study is still limited, and thus further studies are warranted to determine the efficacy and further application., Trial Registration: Joint Institutional Review Board of Taipei Medical University, Taipei, Taiwan (No: N201805094 )., Study Design: Prospective comparative cohort study; Level of evidence, II., (© 2022. The Author(s).)

Background: For hip posterior fracture-dislocation, the current consensus is to perform joint reduction within 6 h to prevent sequelae. However, whether a closed reduction (CR) should be performed at the emergency department (ED) or in the operation theater (OT) remains debatable. We aimed to assess the incidence and factors predictive of CR failure at the ED in patients with hip posterior fracture-dislocation., Methods: Patients with hip posterior fracture-dislocation between 2009 and 2019 were included. Age, sex, body mass index (BMI), injury severity score, new injury severity score, time from injury to first reduction attempt (TIR), presence of associated femoral head fracture, posterior wall marginal impaction, and posterior wall fragment size were compared between patients with CR success and patients with CR failure at the ED., Results: Fifty-five patients with hip posterior fracture-dislocation experienced CR attempts at the ED and were enrolled in the study. Thirty-eight (69.1%) hips were reduced successfully at the ED, and 17 (30.9%) experienced failure. No significant differences in age, sex, BMI, presence of femoral head fracture, marginal impaction, or size of the posterior wall fragment were found between the groups. TIR was significantly shorter in the successful CR group (2.24 vs. 4.11 h, p = 0.01). According to receiver operating characteristic curve analysis, 3.5 h was the cut-off time., Conclusions: For patients with hip posterior fracture-dislocation, TIR was a critical factor for successful CR. If the time interval exceeds 3.5 h from injury, the success rate of bedside CR at the ER is likely to decrease, and the OT should be prepared in case of failed bedside CR., (© 2022. The Author(s).)

To determine phenotype-related dupilumab response in adult patients with atopic dermatitis (AD), this multicenter, retrospective study included 111 adults with moderate-to-severe AD in Taiwan, with median age of 31.5 years (18-87) and 71 (64.0%) males. Patients received dupilumab 300 mg per two to three weeks up to 12 months. We found a significant improvement after 4 and 16 weeks of treatment in all patients for all the assessed scores, including eczema area and severity index (EASI) improvement ≥50% (EASI-50) and 75% (EASI-75), EASI reaching minimal clinically important difference (MCID), and Investigator's Global Assessment (IGA) improvement ≥2. Importantly, prior to asthma, early AD onset and 3-week drug intervals were significantly associated with a high proportion of EASI-75 at month 12, while prurigo and lichenoid phenotypes were associated with a lower proportion of EASI-75 at month 12. However, the majority of adverse events were mild in severity. In conclusion, our study results identify phenotype-related dupilumab response at month 12 in adults with moderate-to-severe AD, and we suggest that treatment should not be discontinued until reaching a satisfactory clinical response.

Background: To date, no study has compared the surgical outcomes between posterior wall acetabular fractures with and without associated femoral head fractures. Therefore, we evaluated whether an associated femoral head fracture increases the incidence of fracture sequelae, including post-traumatic osteoarthritis (PTOA) and osteonecrosis of the femoral head (ONFH), following osteosynthesis for posterior wall acetabular fractures., Methods: This retrospective clinical study enrolled 183 patients who underwent osteosynthesis for posterior wall acetabular fractures between 2009 and 2019 at a level-1 trauma center. The incidence of PTOA, ONFH, and conversion to total hip arthroplasty (THA) was reviewed., Results: The incidence of PTOA, ONFH, and conversion to THA following osteosynthesis were 20.2%, 15.9%, and 17.5%, respectively. The average time for conversion to THA was 18.76 ± 20.15 months (range, 1-82). The results for the comparison of patients with associated femoral head fractures and isolated posterior wall acetabular fractures were insignificant (PTOA: 27.3% vs. 15.7%, p = 0.13; ONFH: 18.2% vs. 14.3%, p = 0.58; conversion to THA: 20.4% vs. 15.7%, p = 0.52). Upon evaluating other variables, only marginal impaction negatively affected ONFH incidence (odds ratio: 2.90)., Conclusions: Our methods failed to demonstrate a significant difference in the rate of PTOA, ONFH, or conversion to THA in posterior wall acetabular fractures with and without an associated femoral head fracture. Beyond femoral head fractures, the marginal impaction of the acetabulum could have led to early sequelae., Level of Evidence: Level III., (© 2022. The Author(s).)

Background: Data on the functional outcomes of patients with open pelvic fractures after osteosynthesis are limited, and whether open fracture is a risk factor for worse outcomes, as compared with closed fracture, remains unclear. This study aimed to compare the functional outcomes of patients with open and closed pelvic fractures and evaluate potential factors that might affect outcomes., Methods: Overall, 19 consecutive patients with open pelvic fractures and 78 patients with closed pelvic fractures between January 2014 and June 2018 were retrospectively reviewed. All fractures were surgically treated, with a minimal follow-up period of three years. Patients' demographic profile, associated injuries, management protocol, quality of reduction, and outcomes were recorded and analyzed., Results: Patients with open pelvic fractures had higher new injury severity score, higher incidence of diverting colostomy, and longer length of stay. Both radiological and functional evaluations revealed no significant differences between the two groups at 1-year and 3-year evaluations. Multiple logistic regression analysis identified poor radiological outcomes (using Lefaivre criteria) and longer length of stay as risk factors for worse short-term functional outcomes. At 3-year evaluation, fair-to-poor radiological outcomes (using Matta/Tornetta and Lefaivre criteria) and the presence of diverting colostomy were potential risk factors., Conclusions: Compared with closed pelvic fracture, open pelvic fracture was not an indicator of worse functional outcomes. Functional outcomes may be comparable between patients with open and closed pelvic fractures at different time points within three years postoperatively. Achieving anatomical reduction in a fracture is crucial, because it might affect patient satisfaction., (© 2021. The Author(s).)

Objective: Surgical treatment of severe infectious spondylodiskitis remains challenging. Although minimally invasive percutaneous endoscopic drainage and debridement (PEDD) may yield good results in complicated cases, outcomes of patients with extensive structural damage and mechanical instability may be unsatisfactory. To address severe infectious spondylodiskitis, we have developed a surgical technique called percutaneous endoscopic interbody debridement and fusion (PEIDF), which comprises endoscopic debridement, bonegraft interbody fusion, and percutaneous posterior instrumentation., Methods: Outcomes of PEIDF in 12 patients and PEDD in 15 patients with infectious spondylodiskitis from April 2014 to July 2018 were reviewed retrospectively. Outcome were compared between 2 kinds of surgical procedures., Results: Patients in PEIDF group had significantly lower rate of revision surgery (8.3% vs. 58.3%), better kyphosis angle (-5.73° ± 8.74 vs. 1.07° ± 2.70 in postoperative; 7.09° ± 7.23 vs. 0.79° ± 4.08 in kyphosis correction at 1 year), and higher fusion rate (83.3% vs. 46.7%) than those who received PEDD., Conclusion: PEIDF is an effective approach for treating infectious spondylodiskitis, especially in patients with spinal instability and multiple medical comorbidities.

Perspiration and environmental chemicals, such as air pollutants, are two of the complicating factors of skin disease. It has not been studied how perspiration affect the skin responding to air pollutants. We applied topically artificial eccrine perspiration, sulphite or both to the mouse skin for one and two weeks to examine the influence of both factors on the shielding ability of healthy skin. Morphological examination showed apparent thickening of the epidermal layer in the skin samples with combined treatment at 1 week, and in the sections applied with sulphite and combined treatment at 2 weeks without significant difference in the extent of epidermal hyperplasia between two groups. The outcomes of immunohistochemical (IHC) analysis showed elevated percentages of dermal fibroblasts expressing interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), tumor necrosis factor β (TNF-β) and cyclooxygenase-2 (Cox-2). Results of two-way repeated measured analysis of variance (two-way RMANOVA) showed that both perspiration and sulphite, but not the interaction between them, were significant factors affecting the expression of proinflammatory cytokines. The evidences indicated that perspiration induced cytokines expressions in the dermal fibroblasts and promoted the effect of sulphite on the shielding response of the skin by inducing epidermis hyperplasia., Competing Interests: The authors declare no conflict of interest., (© 2021 The Author(s).)

In Taiwan, the incidence and prevalence of psoriatic arthritis (PsA) have risen significantly in recent years. Moreover, data from the Taiwan National Health Insurance Research Database (NHIRD) show that more than 85% of PsA patients are treated with just non-steroidal anti-inflammatory drugs (NSAIDs) and/or conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs). Taiwanese clinicians have also expressed concerns regarding uncertainties in the diagnosis of PsA and the delayed, interrupted, and/or tapered use of biologics, as well as differences in therapeutic preferences between and within dermatologists and rheumatologists. To address these issues, the Taiwan Rheumatology Association and the Taiwanese Association for Psoriasis and Skin Immunology jointly convened a committee of 28 clinicians from the fields of rheumatology, dermatology, orthopedics, and rehabilitation, to develop evidence-based consensus recommendations for the practical management of PsA in Taiwan. A total of six overarching principles and 13 recommendations were developed and approved, as well as a treatment algorithm with four separate tracks for axial PsA, peripheral PsA, enthesitis, and dactylitis. Psoriasis (PsO) management was not discussed here, as the Taiwanese Dermatological Association has recently published a comprehensive consensus statement on the management of PsO. Together, these recommendations provide an up-to-date, evidence-based framework for PsA care in Taiwan., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article., (Copyright © 2020 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Background/purpose: Atopic dermatitis (AD) is a chronic inflammatory disease commonly seen in children and increasingly recognized in adults. With recent advances in the therapeutic development for AD, the Taiwanese Dermatological Association (TDA) established a committee to update the consensus for AD management in Taiwan. This report describes the 2020 updated consensus for the management of AD., Methods: A panel of 11 core members was convened to review and discuss aspects of AD management and draft recommendation during the first two meetings. The 2015 TDA consensus and the 2017 European guideline, along with recent peer-reviewed articles, serve as the foundation for the update. In the third meeting, AD expert dermatologists selected on a national scale were invited to vote on the final statements. A total of 27 dermatologists attended the final meeting. The consensus was achieved when ratings of 7-9 (out of a total score of 9) accounted for ≥ 75% of the total votes., Results: Consensus was achieved on the therapeutic options for AD by lines of treatment. A treatment algorithm was presented to illustrate the place of each modality in terms of basic care, acute disease control, and maintenance therapy. Special considerations for the pediatric population, as well as for women during pregnancy and lactation, are discussed., Conclusion: Topical corticosteroids with long-term emollient-based therapies remain the cornerstone of AD treatment. Systemic treatments are indicated when topical therapies and phototherapy fail to control the disease. The recent approval of dupilumab and emerging targeted therapies are expected to bring significant clinical benefit for patients whose disease is inadequately managed by existing options., Competing Interests: Declaration of Competing Interest The authors declare that they have no financial or non-financial conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2020 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

To better understand the synergistic antibacterial activity between piperacillin and Lavandula angustifolia essential oil (LEO) against multidrug-resistant Escherichia coli , we performed microarray transcriptomic analysis of LEO when used alone and in combination with piperacillin against the non-treated control. In total, 90 genes were differentially expressed after the combination of LEO and piperacillin treatment. Among the up-regulated genes, nfsB, nemA , fruA, nfsB, nemA are known to control microbial metabolism and nitrotoluene degradation, which were observed only in the LEO-piperacillin combinatory treatment. Four candidate genes from the microarray result, srIA, srID, waaR and nfsB, were validated by qRT-PCR as these genes showed differential expression consistently in the two methods. Biochemical pathway analysis showed that there was upregulation of genes involved in several biological processes including fructose and mannose metabolism, phosphotransferase system (PTS), lipopolysaccharide biosynthesis and nitrotoluene degradation. Genes involved in microbial metabolism in diverse environments were found both up- and down-regulated in LEO-piperacillin combinatory treatment. Our study provides new information concerning the transcriptional changes that occur during the LEO and piperacillin interaction against the multidrug-resistant bacteria and contributes to unravel the mechanisms underlying this synergism., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest in the publication., (© King Abdulaziz City for Science and Technology 2020.)

Studying the origin of opiate and/or opiate metabolites in individual urine specimens after consumption of cold syrups is vital for patients, doctors, and law enforcement. A rapid liquid chromatography-tandem mass spectrometry method using "dilute-and-shoot" analysis without the need for extraction, hydrolysis and/or derivatization has been developed and validated. The approach provides linear ranges of 2.5-1000 ng mL -1 for 6-acetylmorphine, codeine, chlorpheniramine, and carbinoxamine, 2.5-800 ng mL -1 for morphine and morphine-3-β-d-glucuronide, and 2.5-600 ng mL -1 for morphine-6-β-d-glucuronide and codeine-6-β-d-glucuronide, with excellent correlation coefficients (R 2 > 0.995) and matrix effects (< 5%). Urine samples collected from the ten participants orally administered cold syrups were analyzed. The results concluded that participants consuming codeine-containing cold syrups did not routinely pass urine tests for opiates, and their morphine-codeine concentration ratios (M/C) were not always < 1. In addition, the distribution map of the clinical total concentration of the sum of morphine and codeine against the antihistamines (chlorpheniramine or carbinoxamine) were plotted for discrimination of people who used cold syrups. The 15 real cases have been studied by using M/C rule, cutoff value, and distribution map, further revealing a potential approach to determine opiate metabolite in urine originating from cold syrups.

Background: Percutaneous vertebroplasty has become the treatment of choice for compression fractures. Although the incidence is low, infection after vertebroplasty is a serious complication. The pathogens most often responsible for infection are bacteria. Meanwhile, mycobacterium tuberculosis-induced infection is extremely rare. In this study, we reported our treatment experience with 9 cases of tuberculous spondylitis after vertebroplasty., Methods: Between January 2001 and December 2015, 5749 patients underwent vertebroplasty or kyphoplasty in our department. Nine cases developed tuberculous spondylitis after vertebroplasty (0.16%). Data on clinical history, laboratory examinations, image, treatment and outcomes were examined., Results: One male and 8 female patients with a mean age of 75.1 years developed tuberculous spondylitis after vertebroplasty. 5 patients had a history of pulmonary tuberculosis (TB). Revision surgeries were performed from 5 days to 1124 days after vertebroplasty. Seven patients underwent anterior debridement and fusion with or without posterior instrumentation, and 2 cases received posterior decompression and instrumentation only. After operation, the diagnosis of tuberculous spondylitis was confirmed by TB polymerase chain reaction (TB-PCR) or mycobacteria culture. Mean follow-up period after revision surgery was 36.8 months. At the end of follow-up, 1 patient with paraplegia had passed away, 2 needed a wheel chair, 4 required a walker and 2 were able to walk unassisted., Conclusions: Vertebroplasty is a minimally invasive procedure but still retains some possibility of complications, including TB infection. Patients with a history of pulmonary TB or any elevation of infection parameters should be reviewed carefully to avoid infective complications., (Copyright © 2019 Chang Gung University. Published by Elsevier B.V. All rights reserved.)

Background: Atrophic nonunion of femoral shaft fracture after intramedullary (IM) nailing is uncommon. The treatment for femoral shaft aseptic atrophic non-union remained controversial. The aim of this study was to compare the surgical results between exchanging reamed nailing (ERN) and augmentative antirotational plating (AAP) for femoral shaft aseptic atrophic nonunion., Methods: We retrospectively reviewed the patients with femoral shaft nonunion between the year of 2014 and 2015. The patients with nonunion after plate osteosynthesis, septic nonunion, hypertrophic nonunion, additional surgery during revision surgery were excluded. All the patients were followed up at least 12 months., Results: Overall, the union rate after revision surgery was 70.8%. The union rate was significantly higher in the AAP group than in the ERN group. Operating time was also significantly shorter in the AAP group. Regarding the location of nonunion, the union rate was comparable between groups for isthmic nonunions. However, for non-isthmic nonunions, the union rate was significantly higher and operating time was significantly shorter in the AAP group., Conclusion: AAP showed an overall higher union rate for management of femoral shaft aseptic atrophic nonunion compared with ERN. Especially for non-isthmic femoral shaft atrophic nonunions, AAP provided a significantly higher union rate and significantly shorter operating time.

Safety data for secukinumab in patients with psoriasis and viral hepatitis are lacking. The aim of this study is to investigate the risk of reactivation of hepatitis B virus (HBV)/hepatitis C virus (HCV) in patients with psoriasis who are receiving secukinumab therapy. This multicentre study screened 284 patients with psoriasis with available HBV and HCV serological data and 63 patients with concurrent HBV/HCV infection were enrolled. In the absence of antiviral prophylaxis, 7 of 46 (15.2%) patients with HBV exhibited HBV reactivation during secukinumab therapy. The risk of reactivation was significantly higher in HBsAg-positive patients, compared with HBsAg-negative/HBcAb-positive patients (24.0% vs. 4.17%, p = 0.047). One of 14 (7.1%) HCV patients showed enhanced replication of HCV with hepatitis. No virus reactivation occurred in patients receiving antiviral prophylaxis. HBsAg-positive and HBsAg-negative/HBcAb-positive psoriasis patients can develop virus reactivation during secukinumab therapy, thus necessitating close monitoring of viral load and considering an antiviral prophylaxis for all HBsAg-positive patients with psoriasis.

Objectives: This study examines the permeability and barrier capacity of a sugar cross-linked resorbable collagen membrane ex vivo and in vivo., Materials and Methods: In an ex vivo study, injectable platelet-rich fibrin (i-PRF), a peripheral blood-derived human leukocyte-and-platelet-rich plasma was used to analyze membrane permeability. in vivo subcutaneous implantation in Wistar rats (n = 4 per time point and group) was used to investigate the barrier capacity of the membrane. The induced in vivo cellular reaction was evaluated at 3, 15, and 30 days and compared to sham OP (control) without biomaterial using histological, immunohistochemical, and histomorphometric methods., Results: Ex vivo, the membrane was impenetrable to leukocytes, platelets, and fibrin from peripheral human blood concentrate (PRF). In vivo, the membrane maintained its structure and remained impervious to cells, connective tissue, and vessels over 30 days. CD-68-positive cell (macrophage) numbers significantly decreased from 3 to 15 days, while from day 15 onwards, the number of multinucleated giant cells (MNGCs) increased significantly. Correspondingly, a rise in implantation bed vascularization from 15 to 30 days was observed. However, no signs of degradation or material breakdown were observed at any time point., Conclusion: Ex vivo and in vivo results showed material impermeability to cellular infiltration of human and murine cells, which highlights the membrane capacity to serve as a barrier over 30 days. However, whether the induced MNGCs will lead to material degradation or encapsulation over the long term requires further investigation., Clinical Relevance: The data presented are of great clinical interest, as they contribute to the ongoing discussion concerning to what extent an implanted material should be integrated versus serving only as a barrier membrane.

Judiciously tuning heart rates is critical for regular cardiovascular function. The fractal pattern of heartbeats - a multiscale regulation in instantaneous fluctuations - is well known for vertebrates. The most primitive heart system of the Drosophila provides a useful model to understand the evolutional origin of such a fractal pattern as well as the alterations of fractal pattern during diseased statuses. We developed a non-invasive visible optical heart rate recording system especially suitable for long-term recording by using principal component analysis (PCA) instead of fluorescence recording system to avoid the confounding effect from intense light irradiation. To deplete intracellular Ca(2+) levels, the expression of sarco-endoplasmic reticulum Ca(2+)-ATPase (SERCA) was tissue-specifically knocked down. The SERCA group shows longer heart beat intervals (Mean ± SD: 1009.7 ± 151.6 ms) as compared to the control group (545.5 ± 45.4 ms, p < 0.001). The multiscale correlation of SERCA group (scaling exponent: 0.77 ± 0.07), on the other hand, is weaker than that of the control Drosophila (scaling exponent: 0.85 ± 0.03) (p = 0.016).

Long inverted repeats (LIRs), often found in eukaryotic genomes, are unstable in Escherichia coli where they are recognized by the SbcCD (the bacterial Mre11/Rad50 homologue), an endonuclease/exonuclease capable of cleaving hairpin DNA. It has long been postulated that LIRs form hairpin structures exclusively on the lagging-strand template during DNA replication, and SbcCD cleaves these hairpin-containing lagging strands to generate DNA double-strand breaks. Using a reconstituted oriC plasmid DNA replication system, we have examined how a replication fork behaves when it meets a LIR on DNA. We have shown that leading-strand synthesis stalls transiently within the upstream half of the LIR. Pausing of lagging-strand synthesis at the LIR was not clearly observed, but the pattern of priming sites for Okazaki fragment synthesis was altered within the downstream half of the LIR. We have found that the LIR on a replicating plasmid was cleaved by SbcCD with almost equal frequency on both the leading- and lagging-strand templates. These data strongly suggest that the LIR is readily converted to a cruciform DNA, before the arrival of the fork, creating SbcCD-sensitive hairpin structures on both leading and lagging strands. We propose a model for the replication-dependent extrusion of LIRs to form cruciform structures that transiently impede replication fork movement., (© 2016 The Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.)

We proposed a new solid state material for hydrogen storage, which consists of a combination of both transition and alkaline earth metal atoms decorating a boron-doped graphene surface. Hydrogen adsorption and desorption on this material was investigated using density functional theory calculations. We find that the diffusion barriers for H atom migration and desorption energies are lower than for the previously designed mediums and the proposed medium can reach the gravimetric capacity of ~6.5 wt % hydrogen, which is much higher than the DOE target for the year 2015. Molecular Dynamics simulations show that metal atoms are stably adsorbed on the B doped graphene surface without clustering, which will enhance the hydrogen storage capacity.

The Mre11/Rad50 complex is a central player in various genome maintenance pathways. Here, we report a novel mode of nuclease action found for the Escherichia coli Mre11/Rad50 complex, SbcC2/D2 complex (SbcCD). SbcCD cuts off the top of a cruciform DNA by making incisions on both strands and continues cleaving the dsDNA stem at ∼10-bp intervals. Using linear-shaped DNA substrates, we observed that SbcCD cleaved dsDNA using this activity when the substrate was 110 bp long, but that on shorter substrates the cutting pattern was changed to that predicted for the activity of a 3'-5' exonuclease. Our results suggest that SbcCD processes hairpin and linear dsDNA ends with this novel DNA end-dependent binary endonuclease activity in response to substrate length rather than using previously reported activities. We propose a model for this mode of nuclease action, which provides new insight into SbcCD activity at a dsDNA end., (© The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Background: Drosophila heart tube is a feasible model for cardiac physiological research. However, obtaining Drosophila electrocardiograms (ECGs) is difficult, due to the weak signals and limited contact area to apply electrodes. This paper presents a non-invasive Gallium-Indium (GaIn) based recording system for Drosophila ECG measurement, providing the heart rate and heartbeat features to be observed. This novel, high-signal-quality system prolongs the recording time of insect ECGs, and provides a feasible platform for research on the molecular mechanisms involved in cardiovascular diseases., Methods: In this study, two types of electrode, tungsten needle probes and GaIn electrodes, were used respectively to noiselessly conduct invasive and noninvasive ECG recordings of Drosophila. To further analyze electrode properties, circuit models were established and simulated. By using electromagnetic shielded heart signal acquiring system, consisted of analog amplification and digital filtering, the ECG signals of three phenotypes that have different heart functions were recorded without dissection., Results and Discussion: The ECG waveforms of different phenotypes of Drosophila recorded invasively and repeatedly with n value (n>5) performed obvious difference in heart rate. In long period ECG recordings, non-invasive method implemented by GaIn electrodes acts relatively stable in both amplitude and period. To analyze GaIn electrode, the correctness of GaIn electrode model established by this paper was validated, presenting accuracy, stability, and reliability., Conclusions: Noninvasive ECG recording by GaIn electrodes was presented for recording Drosophila pupae ECG signals within a limited contact area and signal strength. Thus, the observation of ECG changes in normal and SERCA-depleted Drosophila over an extended period is feasible. This method prolongs insect survival time while conserving major ECG features, and provides a platform for electrophysiological signal research on the molecular mechanism involved in cardiac arrhythmia, as well as research related to drug screening and development.

Localized cutaneous nodular amyloidosis (LCNA) is the rarest type of cutaneous amyloidosis. Typically presenting as waxy nodules on the lower extremities, it demonstrates localized deposition of AL-type amyloid in immunohistologic study and is often associated with focal plasma cell proliferation. Sjögren syndrome, an autoimmune lymphoproliferative disorder, is characterized by keratoconjunctivitis sicca and xerostomia with lymphocytic infiltration of exocrine glands. As shown in case reports, the association of LCNA with Sjögren syndrome is considerable. Herein, we report a 78-year-old woman with LCNA, who was further surveyed and diagnosed with Sjögren syndrome. In light of the significant relation between these 2 diseases, further examination for coexistence of Sjögren syndrome in addition to systemic amyloidosis is well warranted. Prompt identification of an underlying Sjögren syndrome in LCNA with polyclonal immunoglobulin amyloid may have important therapeutic consequences.

This study aimed to assess the inhibitory activities of methanol extracts from the microalgae Ankistrodesmus convolutus, Synechococcus elongatus, and Spirulina platensis against Epstein-Barr virus (EBV) in three Burkitt's lymphoma (BL) cell lines, namely Akata, B95-8, and P3HR-1. The antiviral activity was assessed by quantifying the cell-free EBV DNA using real-time polymerase chain reaction (PCR) technique. The methanol extracts from Ankistrodesmus convolutus and Synechococcus elongatus displayed low cytotoxicity and potent effect in reducing cell-free EBV DNA (EC(50)<0.01 µg/ml) with a high therapeutic index (>28000). After fractionation by column chromatography, the fraction from Synechococcus elongatus (SEF1) reduced the cell-free EBV DNA most effectively (EC(50)=2.9 µg/ml, therapeutic index>69). Upon further fractionation by high performance liquid chromatography (HPLC), the sub-fraction SEF1'a was most active in reducing the cell-free EBV DNA (EC(50)=1.38 µg/ml, therapeutic index>14.5). This study suggests that microalgae could be a potential source of antiviral compounds that can be used against EBV.

To facilitate the application of plasmonic nanoparticles (PNPs) in high-throughput detection, we develop a hyperspectral imaging system (HSIS) combining dark-filed microscopy and imaging Fourier transform spectrometry to measure scattering spectra from immobilized PNPs. The current setup has acquisition time of 5 seconds and spectral resolution of 21.4 nm at 532.1 nm. We demonstrate the applicability of the HSIS in conjunction with spectral data analysis to quantify multiple types of PNPs and detect small changes in localized surface plasmon resonance wavelengths of PNPs due to changes in the environmental refractive index.

Intravenous anesthesia is commonly used during endoscopy. This approach greatly improves patient satisfaction with pain control. The risks of anesthesia are usually focused on the cardiopulmonary effects of anesthetics. The risk of pulmonary aspiration is often overlooked, unless there are other risk factors that may increase the incidence of pulmonary aspiration. Here, we report a patient with unexpected aspiration pneumonia after gastroscopy under intravenous anesthesia. We suggest that pulmonary aspiration should be taken into consideration as a risk associated with anesthesia for gastroscopy., (2010 Taiwan Society of Anesthesiologists. Published by Elsevier B.V. All rights reserved.)

Penta-acetyl geniposide [(Ac)(5)GP], an acetylated geniposide product from Gardenia fructus, has been known to have hepatoprotective properties and recent studies have revealed its anti-proliferative and apoptotic effect on C6 glioma cells. In this study, we first report the anti-metastastic effect of (Ac)(5)GP in the rat neuroblastoma line: C6 glioma cells. First (Ac)(5)GP exhibited an inhibitory effect on abilities of adhesion and motility by cell-matrix adhesion assay, wound healing assay and Boyden chamber assay. Second, the decreasing activity of matrix metalloproteinase-2 (MMP-2) was noted by gelatin zymography assay. Further analysis with semi-quantitative RT-PCR showed the mRNA levels of MMP-2 and membrane type I matrix metalloproteinase (MT1-MMP) were significantly reduced, while the tissue inhibitor of matrix metalloproteinase-2 (TIMP-2) was elevated by (Ac)(5)GP treatment. Further (Ac)(5)GP also exerted an inhibitory effect on phosphoinositide 3-kinase (PI3K) protein expression, phosphorylation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) and inhibition of activation of transcription factor nuclear factor kappa B (NF-kappaB), c-Fos, c-Jun. These findings proved (Ac)(5)GP is highly likely to be a inhibiting cancer migration agent to be further developed in the future.

Previous structural and mutational studies of bovine pancreatic deoxyribonuclease I (bpDNase I) have demonstrated that the active site His134 and His252 played critical roles in catalysis. In our present study, mutations of these two His residues to Gln, Ala or Gly reduced the DNase activity by a factor of four to five orders of magnitude. When imidazole or primary amines were added exogenously to the Ala or Gly mutants, the residual DNase activities were substantially increased by 60-120-fold. The rescue with imidazole was pH- and concentration-dependent. The pH-activity profiles showed nearly bell-shaped curves, with the maximum activity enhancement for H134A at pH 6.0 and that for H252A at pH 7.5. These findings indicated that the protonated form of imidazole was responsible for the rescue in H134A, and the unprotonated form was for that in H252A, prompting us to assign unambiguously the roles for His134 as a general acid, and His252 as a general base, in bpDNase I catalysis.