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Abstract Testicular ischemia-reperfusion induces enhanced concentration of reactive oxygen species. The increased reactive oxygen species harm cellular lipids, nucleic acids, proteins, and carbohydrates, and ultimately cause testicular injury. Sulforaphane, a kind of natural dietary isothiocyanate, exists predominantly in some cruciferous vegetables, like broccoli and cabbage. It can protect tissues from oxidative stress-induced damage. Herein, we analyzed the effectiveness of sulforaphane in treating ischemia-reperfusion injury occurring after testicular torsion-detorsion. Male rats (n = 60) were grouped as follows: sham-operated group, unilateral testicular ischemia-reperfusion group, and unilateral testicular ischemia-reperfusion group receiving sulforaphane treatment at 5 mg/kg. No testicular torsion-detorsion was performed in the sham group. Unilateral testicular ischemia-reperfusion model was created by detorsion after 2 h of left testicular torsion. In the sulforaphane-treated group, intraperitoneal sulforaphane (5 mg/kg) was administered at left testicular detorsion. Biochemical assay, Western blot, and hematoxylin and eosin staining were used to evaluate testicular malondialdehyde content (an important marker of reactive oxygen species), protein levels of superoxide dismutase and catalase (intracellular antioxidant defense mechanism), and testicular reproductive function, respectively. In testicular tissues, malondialdehyde content was significantly promoted, while protein levels of superoxide dismutase and catalase, and testicular reproductive function were significantly reduced in ipsilateral testes by testicular ischemia-reperfusion. Nevertheless, sulforaphane administration partially reversed the effect of testicular ischemia-reperfusion on these indexes. It can be concluded that sulforaphane elevates protein levels of superoxide dismutase and catalase, and suppresses reactive oxygen species content, thereby preventing ischemia-reperfusion injury in testis.

Improper acetabulum component position is a significant risk factor for postoperative dislocation after total hip arthroplasty. Several radiographic two‐dimensional methods exist for measuring acetabulum component anteversion, but they cannot distinguish between anteversion and retroversion. “Liaw's version,” initially proposed as a simple mathematical standardized two‐dimensional method, was modified to the computerized ellipse method, proving superior accuracy to traditional two‐dimensional methods. In this article, we demonstrated its application in detecting and measuring retroverted acetabulum component. We obtained anteroposterior pelvis radiographs from a patient undergoing total hip arthroplasty on the day of surgery and 2 weeks postoperatively. The computerized ellipse method was used to measure the acetabulum component orientation. Upon comparison, the difference between θ assigned to be retroverted (9.52–8.56 = 0.96) is much smaller than the difference between θ assigned to be anteverted (23.81–18.86 = 4.95), leading us to determine retroversion. This was further confirmed by computed tomography at the 6‐week follow‐up. We propose that using the computerized ellipse method to measure Liaw's version can be a valuable tool in identifying acetabulum component retroversion on anteroposterior radiographs during routine postoperative follow‐up and retrospective assessments of total hip arthroplasty patients.

Background/objective: The reduced-port approach can overcome the limitations of single-incision laparoscopic surgery while maintaining its advantages. Here, we compared the effects of robotic reduced-port surgery and conventional laparoscopic approaches for left-sided colorectal cancer. Methods: Between January 2015 and December 2016, the clinicopathological characteristics and treatment outcomes of 17 patients undergoing robotic reduced-port surgery and 49 patients undergoing laparoscopic surgery for left-sided colorectal cancer were compared. Results: The two groups were comparable in almost all outcome measures except for the distal resection margin, which was significantly longer in the laparoscopic group (P

BackgroundThe influence of recent influenza infection on perioperative outcomes is not completely understood.MethodUsing Taiwan’s National Health Insurance Research Data from 2008 to 2013, we conducted a surgical cohort study, which included 20,544 matched patients with a recent history of influenza and 10,272 matched patients without. The main outcomes were postoperative complications and mortality. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) for the complications and for mortality in patients with a history of influenza within 1–14 days or 15–30 days compared with non-influenza controls.ResultsCompared with patients who had no influenza, patients with influenza within preoperative days 1–7 had increased risks of postoperative pneumonia (OR 2.22, 95% CI 1.81–2.73), septicemia (OR 1.98, 95% CI 1.70–2.31), acute renal failure (OR 2.10, 95% CI 1.47–3.00), and urinary tract infection (OR 1.45, 95% CI 1.23–1.70). An increased risk of intensive care admission, prolonged length of stay, and higher medical expenditure was noted in patients with history of influenza within 1–14 days.ConclusionWe found that there was an association between influenza within 14 days preoperatively and the increased risk of postoperative complications, particularly with the occurrence of influenza within 7 days prior to surgery.

Abstract Sphingosine kinase 1 (SphK1) expression and activity are elevated in human osteosarcoma (OS) and is a promising target of therapy. SKI-V is a non-competitive and highly-efficient non-lipid SphK1 inhibitor. The potential anti-OS cell activity by the SphK1 inhibitor was studied here. In primary OS cells and immortalized cell lines, SKI-V robustly suppressed cell survival, growth and proliferation as well as cell mobility, and inducing profound OS cell death and apoptosis. The SphK1 inhibitor was however non-cytotoxic nor pro-apoptotic in human osteoblasts. SKI-V robustly inhibited SphK1 activation and induced accumulation of ceramides, without affecting SphK1 expression in primary OS cells. The SphK1 activator K6PC-5 or sphingosine-1-phosphate partially inhibited SKI-V-induced OS cell death. We showed that SKI-V concurrently blocked Akt-mTOR activation in primary OS cells. A constitutively-active Akt1 (ca-Akt1, S473D) construct restored Akt-mTOR activation and mitigated SKI-V-mediated cytotoxicity in primary OS cells. In vivo, daily injection of SKI-V potently suppressed OS xenograft tumor growth in nude mice. In SKI-V-administrated OS xenograft tissues, SphK1 inhibition, ceramide increase and Akt-mTOR inhibition were detected. Together, SKI-V exerts significant anti-OS activity by inhibiting SphK1 and Akt-mTOR cascades in OS cells.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic can be effectively controlled by rapid and accurate identification of SARS-CoV-2-infected cases through large-scale screening. Hypercube pooling polymerase chain reaction (PCR) is frequently used as a pooling technique because of its high speed and efficiency. We attempted to implement the hypercube pooling strategy and found it had a large quantization effect. This raised two questions: is hypercube pooling with edge = 3 actually the optimal strategy? If not, what is the best edge and dimension? We used a C++ program to calculate the expected number of PCR tests per patient for different values of prevalence, edge, and dimension. The results showed that every edge had a best performance range. Then, using C++ again, we created a program to calculate the optimal edge and dimension required for pooling samples when entering prevalence into our program. Our program will be provided as freeware in the hope that it can help governments fight the SARS-CoV-2 pandemic.

Distal radius orientation is important in evaluating Colles' fracture. In most cases, the wrist was protected by a bandage, splint, or cast. Therefore, it was difficult for the radiology technician to take perfect anteroposterior and lateral view radiographs. In this study, we build a mathematical model and calculate the pronation angle needed to produce dorsal tilt, which is a volar tilt in a perfect lateral view radiograph. The formulas are all incorporated into Excel to facilitate usage.

IntroductionFor patients undergoing THR, measuring the postoperative acetabular anteversion precisely plays a pivotal role in the prognosis. However, using elliptical methods mandates computerized equipment that is frequently in shortage in remote areas and developing countries. We invented a laser projector utilizing the ellipse method to measure the acetabular anteversion directly. The aim is to examine the consistency and validity of the laser projector as compared to our original software, Elliversion.Materials and MethodsWe retrospectively collected 50 postoperative pelvis radiographs including acetabulum from our institution. One investigator first measured the anteversion of included radiographs through Elliversion software as the control group. Subsequently, two operators independently used the laser projector for measurements in two separate periods with 1-day intervals as the experimental group. Our analysis was comprised of intra- and inter-observer comparisons and reliability, which investigated both the consistency and validity, by using two-sample student's t-test and intraclass correlation coefficient.ResultsThere was no significant difference in measuring the anteversion through laser projectors between two operators (p = 0.54), with excellent inter-observer reliability (ICC, 0.967). The estimated effect in the anteversion measurement between the Elliversion and laser projector was also comparable, with the ICC level of 0.984, indicating excellent reliability.ConclusionOur study reported the consistency and validity of this laser projector as there is no significant difference between Elliversion and Laser projector, notably with excellent intra- and inter-observer reliability. We look forward to helping elevate clinical acumen when doctors provide care to patients after THR, especially in remote areas.

This paper discusses an observer-based fuzzy control problem for uncertain nonlinear singular systems under Multi-Performance Requirements (MPRs). The approach used in the paper is to model the system using a Takagi–Sugeno (T-S) fuzzy model that can be analyzed using linear control theories. The proposed control scheme is based on the Parallel Distributed Compensation (PDC) approach and Proportional Derivative (PD) control scheme. The goal is to design an observer-based fuzzy controller that achieves stability of the system and also satisfies the Guarantee Cost Control (GCC) constraint while maintaining a desired passive constraint. The stability analysis is performed using Lyapunov theory, and the sufficient conditions are transformed into a Linear Matrix Inequality (LMI) form using a Shur Complement, free-weighting matrix method and Singular Value Decomposition (SVD) techniques. The LMI conditions are then solved using convex optimization algorithms. Finally, the proposed control method is validated using a bio-economic system to demonstrate its effectiveness.

Abstract Background The 12-lead electrocardiogram (ECG) has been adopted as an important component of preparticipation cardiovascular screening. However, there are still controversies in the screening and few studies with a large sample size have reported the results of ECGs of marathon runners. Therefore, the purpose of this study was to assess the prevalence of normal, borderline, and abnormal ECG changes in marathon runners. Methods The 12-lead ECG data of 13,079 amateur marathon runners between the ages of 18 and 35 years were included for analysis. The prevalence of ECG abnormalities among different gender groups was compared with chi-square tests. Results In terms of training-related changes, sinus bradycardia, sinus arrhythmia, and left ventricular high voltage were found in approximately 15, 5, and 3.28% of the participants, respectively. The incidence of right axis deviation in the marathon runners was 1.78%, which was slightly higher than the incidence of left axis deviation (0.88%). No more than 0.1% of the amateur marathon runners exhibited ST-segment depression, T wave inversion (TWI), premature ventricular contraction, pathologic Q waves, and prolonged QT interval. Conclusions Training-related ECG changes, including sinus bradycardia, sinus arrhythmia, and left ventricular high voltage, were common in amateur marathon runners. Most abnormal ECG changes, including ST-segment depression, TWI, premature ventricular contraction, pathologic Q waves, and prolonged QT interval, were infrequently found in amateur marathon runners. The data also suggested Chinese amateur marathon runners may have a relatively lower prevalence of ECG abnormalities than black and white runners.

Abstract Background Ankle syndesmosis injury is a common condition, and the injury mechanism can be sorted into pure syndesmosis injury, Weber-B, and Weber-C type fractures. This study aims to evaluate the treatment outcomes and stability of suture-button fixation for syndesmosis injury with different injury mechanisms. We hypothesized that injury mechanisms would alter the stability of suture-button fixation. Methods We retrospectively reviewed 63 patients with ankle syndesmosis injury who underwent surgery with TightRope (Arthrex, Naples, FL, USA) from April 2014 to February 2019. The stability of suture-button fixation with TightRope was evaluated by comparing the preoperative, postoperative, and final follow-up measurements of tibiofibular clear space (TFCS), tibiofibular overlap (TFO), and medial clear space (MCS). A subgroup analysis for each demographic group and injury type including pure syndesmosis injury, Weber-B, and Weber-C type fractures were performed. Results Syndesmosis was effectively reduced using TightRope. After the index surgery, the tibiofibular clear space was reduced from 7.73 to 4.04 mm, the tibiofibular overlap was increased from 3.05 to 6.44 mm, and the medial clear space was reduced from 8.12 to 3.54 mm. However, syndesmosis widening was noted at the final follow-up, especially in Weber-C type fractures (TFCS 3.82 to 4.45 mm, p < 0.01 and TFO 6.86 to 6.29 mm, p = 0.04). Though widened, the final follow-up values of tibiofibular clear space and tibiofibular overlap were in the acceptable range. Postoperatively and at the final follow-up, medial clear space was found to be significantly larger in the Weber-C group than in the pure syndesmosis and Weber-B groups (p < 0.05). Conclusions Suture-button fixation can offer anatomic reduction and dynamic fixation in syndesmosis injuries. However, when using this modality for Weber-C type fractures, more attention should be focused on the accuracy of reduction, especially of medial clear space, and rediastasis should be carefully monitored. Trial registration This trial was retrospectively approved by TMU-JIRB. Registration number N202004122, and the date of approval was May 06, 2020. Level of evidence III

Summary: Background: Rectal neoplasm is one of the most common malignancies worldwide. Screening programs for rectal neoplasm result in early diagnosis and a decrease in disease-related mortality and morbidity. In selected patients, early rectal cancer may be treated with local excision. Owing to poor exposure during conventional transanal excision, transanal minimally invasive surgery (TAMIS) was developed, and TAMIS is feasible for the local excision of selected rectal neoplasms. However, the limited range of motion is a major disadvantage of this operation. Therefore, robotic TAMIS was developed to resolve this issue. This paper describes the surgical outcomes of robotic TAMIS for selected rectal tumors. Methods: The eligibility criteria for robotic TAMIS were as follows: benign neoplasms, early malignancy, complete remission after concurrent chemoradiotherapy, lesions located in the middle or lower rectum, and a lesion size of less than 5 cm. To gain access to the anal canal, a transanal access platform was used, and the da Vinci robotic system was mounted for surgery. Patient characteristics and surgical outcomes were recoded. Results: A total of 23 patients were included, and the median tumor size was 2.5 cm (range: 1.1–4.5 cm) on average. The median tumor location was 5 cm (range: 2–8 cm) from the anal verge. The median length of hospital stay was 3 days (range: 1–10 days). No intraoperative complications were reported, and no patient readmission occurred. The median follow-up period was 9.6 months. No recurrent lesion was found in the follow-up period. Conclusion: Based on the short-term results, robotic TAMIS is a feasible and safe technique for the local excision of selected rectal neoplasms. Keywords: Robotic, Selected rectal neoplasms, Transanal minimally invasive surgery

This paper discusses an observer-based control problem for uncertain Takagi–Sugeno Fuzzy Singular Systems (T-SFSS) subject to passivity performance constraints. Through the Parallel Distributed Compensation (PDC) approach and the Proportional Derivative (PD) control scheme, an observer-based fuzzy controller is constructed to achieve the stability of the considered system. An unlimited positive definite matrix is utilized to construct the Lyapunov function and derive sufficient stability conditions to develop a relaxed design method. Moreover, some technologies, such as the Schur complement, projection lemma, and Singular Value Decomposition (SVD), are applied to convert the conditions to Linear Matrix Inequality (LMI) form. Therefore, the convex optimization algorithm is used to solve the LMI conditions to find feasible solutions. The observer-based fuzzy controller is established with the obtained solutions to guarantee stability and passivity performance for the uncertain nonlinear singular systems. Finally, two examples are provided to verify the availability of the proposed fuzzy control approach.

This study evaluated the mid-term (12-month) biomechanical, biocompatibility, and biological performance of additive-manufactured bioabsorbable iron-based interference screws (ISs). Two bioabsorbable iron IS types—manufactured using pure iron powder (iron_IS) and using pure iron powder with 0.2 wt% tricalcium phosphate (TCP_IS)—were compared with conventional metallic IS (control) using in vitro biocompatibility and degradation analyses and an in vivo animal study. The in vitro ultimate failure strength was significantly higher for iron_IS and TCP_IS than for control ISs at 3 months post-operatively; however, the difference between groups were nonsignificant thereafter. Moreover, at 3 months after implantation, iron_IS and TCP_IS increased bone volume fraction, bone surface area fraction, and percent intersection surface; the changes thereafter were nonsignificant. Iron_IS and TCP_IS demonstrated degradation over time with increased implant surface, decreased implant volume, and structure thickness; nevertheless, the analyses of visceral organs and biochemistry demonstrated normal results, except for time-dependent iron deposition in the spleen. Therefore, compared with conventional ISs, bioabsorbable iron-based ISs exhibit higher initial mechanical strength. Although iron-based ISs demonstrate high biocompatibility 12 months after implantation, their corrosive iron products may accumulate in the spleen. Because they demonstrate mechanical superiority along with considerable absorption capability after implantation, iron-based ISs may have potential applications in implantable medical-device development in the future.

The obesity genetic effect may play a major role in obesogenic environment. A combined case–control and an 18-month follow-up were carried out, including a total of 311 controls and 118 obese cases. All participants were aged in the range of 20–55 y/o. The body mass index (BMI) of obese cases and normal controls was in the range of 27.0–34.9 and 18.5–23.9 kg/m2, respectively. The rs712221 on Estrogen receptor1 (ESR1) and rs2016520 on Peroxisome proliferator–activated receptor delta (PPARD) showed significant associations with obesity. The TT (odds ratio (OR): 2.42; 95% confidence interval (CI): 1.46–4.01) and TT/TC (OR: 2.80; 95% CI: 1.14–6.85) genotypes on rs712221 and rs2016520 had significantly higher obesity risks, respectively. Moreover, the synergic effect of these two risk SNPs (2-RGH) exhibited an almost geometrical increase in obesity risk (OR: 7.00; 95% CI: 2.23–21.99). Obese individuals with 2-RGH had apparently higher changes in BMI increase, body weight gain and dietary fiber intake but a lower total energy intake within the 18-month follow-up.

Summary: Controversy still surrounds clinical benefits of robotic-assisted (RS) over laparoscopic surgery (LS) despite its popularity in clinical use in terms of outcomes and complication rates. The study aims to systematically review and provide the evidence concerning the risk of conversion to open laparotomy and oncological outcomes of LS vs RS rectal cancer surgery. The Cochrane Library (including the Cochrane Central Register of Controlled Trials), EMBASE, PubMed, SCOPUS, and Web of Science were searched for randomized controlled trials (RCTs) comparing LS and RS. Eight RCTs including 1305 patients were identified. Pooled conversion rate was reported in 49 (11.89%) of 412 patients who underwent LS and in 23 (5.72%) of 402 patients who underwent RS (95% CI, 1.357 to 3.613; P = .001). However, shorter operative time was noted in LS group than RS group (95% CI, −43.106 to −3.876; P = .019). No significant difference in other outcomes was observed. Finally, in further analysis, the mean age in trial-level was found to be positively associated with operative time (point estimate = 2.598; 95% CI, 1.584 to 3.612; P

Summary: Objective: Morbidity rates after living donor hepatectomy vary greatly among centers. Donor morbidity in a tertiary center over the past two decades was revisited. Methods: Clinical data and grading of complications were reviewed by a nontransplant surgeon based on Clavien 5 tier grading. Risk factors were analyzed. Results: In total, 473 consecutive living liver donors from 1997 to 2016 were included for analysis; 305 were right liver donors and 168 left liver donors, and the corresponding morbidity rates were 27.2% and 9.5%. The majority (81/99, 81.2%) of complications were grade I and II. Donors with morbidity compared with those without were significantly younger, nonoverweight body figure (BMI

Background: Stereotactic ablative radiotherapy (SABR) can deliver tumoricidal doses and achieve long-term control in early hepatocellular carcinoma (HCC). However, limited studies have investigated the safety and effectiveness of SABR in patients with advanced diseases that is unsuitable for transarterial chemoembolization (TACE). Methods: In this observational study, we reviewed the medical records of patients with Barcelona Clinic Liver Cancer (BCLC) stage C disease treated with linear accelerator-based SABR between 2008 and 2016. Their tumors were either refractory to TACE or TACE was contraindicated. Overall survival (OS), in-field progression-free survival (IFPFS), and out-field progression-free survival were calculated using Kaplan–Meier analysis. The Cox regression model was used to examine the effects of variables. Treatment-related toxicities were scored according to the Common Terminology Criteria for Adverse Events (version 4.03) and whether patients developed radiation-induced liver disease (RILD) after SABR. Results: This study included 32 patients. The mean maximal tumor diameter and tumor volumes were 4.7 cm and 135.9 ml, respectively. Patients received linear accelerator-based SABR with a median prescribed dose of 48 Gy (30–60 Gy) in three to six fractions. Based on the assessment of treatment response by using the Response Evaluation Criteria in Solid Tumors (version 1.1), 19% of patients achieved a complete response and 53% achieved a partial response. After a median follow-up of 18.1 months (4.0–65.9 months), 10, 19, and 9 patients experienced in-field failure, out-field hepatic recurrence, and extrahepatic metastases, respectively. The estimated 2-year OS and IFPFS rates were 54.4% and 62.7%, respectively. In a multivariate analysis, a pretreatment Cancer of the Liver Italian Program (CLIP) score of ⩾2 ( p = 0.01) was a prognostic factor for shorter OS, and a biologically effective dose (BED) of

This study evaluated the biocompatibility and biological performance of novel additive-manufactured bioabsorbable iron-based porous suture anchors (iron_SAs). Two types of bioabsorbable iron_SAs, with double- and triple-helical structures (iron_SA_2_helix and iron_SA_3_helix, respectively), were compared with the synthetic polymer-based bioabsorbable suture anchor (polymer_SAs). An in vitro mechanical test, MTT assay, and scanning electron microscope (SEM) analysis were performed. An in vivo animal study was also performed. The three types of suture anchors were randomly implanted in the outer cortex of the lateral femoral condyle. The ultimate in vitro pullout strength of the iron_SA_3_helix group was significantly higher than the iron_SA_2_helix and polymer_SA groups. The MTT assay findings demonstrated no significant cytotoxicity, and the SEM analysis showed cells attachment on implant surface. The ultimate failure load of the iron_SA_3_helix group was significantly higher than that of the polymer_SA group. The micro-CT analysis indicated the iron_SA_3_helix group showed a higher bone volume fraction (BV/TV) after surgery. Moreover, both iron SAs underwent degradation with time. Iron_SAs with triple-helical threads and a porous structure demonstrated better mechanical strength and high biocompatibility after short-term implantation. The combined advantages of the mechanical superiority of the iron metal and the possibility of absorption after implantation make the iron_SA a suitable candidate for further development.

Over the centuries people have always faced the deaths of their beloved ones in their families and suffer from grief over them. William Shakespeare in Hamlet offers his ideas of how a son faces his father’s death and his mother’s remarriage, ideas of whether purgatory exists and ideas of which eschatology is correct in the English Reformation, either Catholic or Protestant. In this essay, I examine two traces and one reversal in the play and ask many what-if questions through the perspective of Jacques Derrida’s deconstruction. In my argument, Shakespeare misspeaks to his readers in the atmosphere of Protestant Elizabethan England the meanings of death in Prince Hamlet’s perspective in order to reverse his readers’ way of seeing and to make them experience Prince Hamlet’s Catholicism as the form of the opposite, by which they can become theologians themselves and meet God behind His mask. In employment of Derrida’s center-freeplay structurality, I believe that it is through Prince Hamlet’s subversive character that Ghost King Hamlet is the first center into which Prince Hamlet comes as freeplay in the structurality of father and son, and Prince Hamlet is the second center into which the other characters come as freeplay in the structurality of the court, intertwined with the structurality of the religion where no existence of purgatory in Lutheranism comes as center into which the existence of purgatory in Catholicism comes as freeplay, by the structurality of authorship where author comes as center into which the play Hamlet comes as freeplay.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

MicroRNAs (miRNAs) function as the post-transcriptional factor that finetunes the gene expression by targeting to the specific candidate. Mis-regulated expression of miRNAs consequently disturbs gene expression profile, which serves as the pivotal mechanism involved in initiation or progression of human malignancy. Cancer-relevant miRNA is potentially considered the therapeutic target or biomarker toward the precise treatment of cancer. Nevertheless, the regulatory mechanism underlying the altered expression of miRNA in cancer is largely uncovered. Detailed knowledge regarding the influence of miRNAs on solid cancer is critical for exploring its potential of clinical application. Herein, we elucidate the regulatory mechanism regarding how miRNA expression is manipulated and its impact on the pathogenesis of distinct solid cancer.

Tendons are hypocellular and hypovascular tissues, and thus, their natural healing capacity is low. In this study, we sought to evaluate the efficacy of platelet-rich fibrin (PRF) to serve as a bioactive scaffold in promoting the healing of rabbit Achilles tendon injury. For in vitro study, the essence portion of PRF was determined through bioluminescent assay. Furthermore, we analyzed the time-sequential cytokines-release kinetics of PRF and evaluated their effects on tenocytes proliferation and tenogenic gene expressions. In animal study, the rabbit Achilles tendon defect was left untreated or implanted with normal/heat-denatured PRF scaffolds. Six weeks postoperatively, the specimens were evaluated through sonographic imaging and histological analysis. The results revealed significantly more activated platelets on bottom half of the PRF scaffold. Cytokine concentrations released from PRF could be detected from the first hour to six days. For the in vitro study, PRF enhanced cell viability and collagen I, collagen III, tenomodulin, and tenascin gene expression compared to the standard culture medium. For in vivo study, sonographic images revealed significantly better tendon healing in the PRF group in terms of tissue echogenicity and homogeneity. The histological analysis showed that the healing tissues in the PRF group had more organized collagen fiber, less vascularity, and minimal cartilage formation. In conclusion, bioactive PRF promotes in vitro tenocytes viability and tenogenic phenotypic differentiation. Administration of a PRF scaffold at the tendon defect promotes tissue healing as evidenced by imaging and histological outcomes.

The interference screw fixation method is used to secure a graft in the tibial tunnel during anterior cruciate ligament reconstruction surgery. However, several complications have been reported, such as biodegradable screw breakage, inflammatory or foreign body reaction, tunnel enlargement, and delayed graft healing. Using additive manufacturing (AM) technology, we developed a titanium alloy (Ti6Al4V) interference screw with chemically calcium phosphate surface modification technology to improve bone integration in the tibial tunnel. After chemical and heat treatment, the titanium screw formed a dense apatite layer on the metal surface in simulated body fluid. Twenty-seven New Zealand white rabbits were randomly divided into control and additive manufactured (AMD) screw groups. The long digital extensor tendon was detached and translated into a tibial plateau tunnel (diameter: 2.0 mm) and transfixed with an interference screw while the paw was in dorsiflexion. Biomechanical analyses, histological analyses, and an imaging study were performed at 1, 3, and 6 months. The biomechanical test showed that the ultimate pull-out load failure was significantly higher in the AMD screw group in all tested periods. Micro-computed tomography analyses revealed early woven bone formation in the AMD screw group at 1 and 3 months. In conclusion, AMD screws with bioactive surface modification improved bone ingrowth and enhanced biomechanical performance in a rabbit model.

Healing of an anterior cruciate ligament graft in bone tunnel yields weaker fibrous scar tissue, which may prolong an already prolonged healing process within the tendon−bone interface. In this study, gelatin molecules were added to thermosensitive chitosan/β-glycerol phosphate disodium salt hydrogels to form chitosan/gelatin/β-glycerol phosphate (C/G/GP) hydrogels, which were applied to 0.1 mg/mL collagenase carrier in the tendon−bone junction. New Zealand white rabbit’s long digital extensor tendon was detached and translated into a 2.5-mm diameter tibial plateau tunnel. Thirty-six rabbits underwent bilateral surgery and hydrogel injection treatment with and without collagenase. Histological analyses revealed early healing and more bone formation at the tendon−bone interface after collagenase partial digestion. The area of metachromasia significantly increased in both 4-week and 8-week groups after collagenase treatment (p < 0.01). Micro computed tomography showed a significant increase in total bone volume and bone volume/tissue volume in the 8 weeks after collagenase treatment, compared with the control group. Load-to-failure was significantly higher in the treated group at 8 weeks (23.8 ± 8.13 N vs 14.3 ± 3.9 N; p = 0.008). Treatment with collagenase digestion resulted in a 66% increase in pull-out strength. In conclusion, injection of C/G/GP hydrogel with collagenase improves tendon-to-bone healing in a rabbit model.

Human high-mobility group A2 (HMGA2) encodes for a non-histone chromatin protein which influences a variety of biological processes, including the cell cycle process, apoptosis, the DNA damage repair process, and epithelial−mesenchymal transition. The accumulated evidence suggests that high expression of HMGA2 is related to tumor progression, poor prognosis, and a poor response to therapy. Thus, HMGA2 is an important molecular target for many types of malignancies. Our recent studies revealed the positive connections between heat shock protein 90 (Hsp90) and HMGA2 and that the Hsp90 inhibitor has therapeutic potential to inhibit HMGA2-triggered tumorigenesis. However, 43% of patients suffered visual disturbances in a phase I trial of the second-generation Hsp90 inhibitor, NVP-AUY922. To identify a specific inhibitor to target HMGA2, the Gene Expression Omnibus (GEO) database and the Library of Integrated Network-based Cellular Signatures (LINCS) L1000platform were both analyzed. We identified the approved small-molecule antifungal agent ciclopirox (CPX) as a novel potential inhibitor of HMGA2. In addition, CPX induces cytotoxicity of colorectal cancer (CRC) cells by induction of cell cycle arrest and apoptosis in vitro and in vivo through direct interaction with the AT-hook motif (a small DNA-binding protein motif) of HMGA2. In conclusion, this study is the first to report that CPX is a novel potential inhibitor of HMGA2 using a drug-repurposing approach, which can provide a potential therapeutic intervention in CRC patients.

Several nuclear hormone receptors have been associated with inflammatory reactions. Particularly, liver X receptors (LXRs) have recently been identified as key transcriptional regulators of genes involved in lipid homeostasis and inflammation. LXRs are negative regulators of macrophage inflammatory gene expression. Multiple sclerosis (MS), a demyelinating disease of the central nervous system of unknown cause, is characterized by recurrent inflammation involving macrophages and their inflammatory mediators. Sweden belongs to the countries with a high MS incidence. In Italy, the MS incidence is lower, except on the island of Sardinia where the incidence is even higher than in Sweden. Subjects from Sardinia are ethnically more homogeneous, and differ from Swedes also regarding genetic background and environment. We studied mRNA expression of several nuclear hormone receptors in blood mononuclear cells (MNC) from female patients with untreated relapsing-remitting MS from Sassari, Sardinia, and Stockholm, Sweden. Sex- and age-matched healthy controls (HC) were from both areas. mRNA expression was evaluated by quantitative real-time PCR. We found altered mRNA expression of LXRs, estrogen receptors (ERs), and androgen receptor (AR) in MS. mRNA expression of both LXRα and LXRβ is lower in MS from Stockholm but not from Sassari. In particular, LXRα mRNA expression was significantly lower in MS from Stockholm as compared with all groups in the study including MS from Sassari. Low levels of ERα mRNA are seen in MS from both Stockholm and Sassari. The splice variant ERβcx showed significantly higher mRNA expression in MS from Sassari and Stockholm as compared with corresponding HC. In particular, ERβcx mRNA in MS from Sassari was remarkably higher as compared with all other groups in the study. Higher levels of AR mRNA are present in HC from Sassari. The findings indicate that the expression levels of anti-inflammatory nuclear receptor superfamily genes in MS appear to reflect both ethnic and environmental influences.

Dendritic cells (DC) are usually regarded as antigen-presenting cells (APC) involved in T cell activation, but DC also directly or indirectly affect B cell function, antibody synthesis and isotype switch. In this study, we explore potential of DC-based immunotherapy in ongoing experimental autoimmune myasthenia gravis (EAMG) in Lewis rats, which is mediated by anti-acetylcholine receptor (AChR) antibodies. Spleen DC were isolated from onset of Lewis rat EAMG on day 39 post immunization (p.i.), exposed in vitro to IL-10 and then injected intraperitoneally into ongoing EAMG Lewis rats at dose of 1 × 106 cells/rat on day 5 p.i. with AChR + complete Freund's adjuvant. IL-10-modified DC resulted in lower clinical scores, less body weight loss, lower numbers of anti-AChR IgG antibody-secreting cells and lower affinity of anti-AChR antibodies in rats receiving IL-10-modified DC, accompanied with lower expression of CD80 and CD86 and lower lymphocyte proliferation among lymph node mononuclear cells compared with control EAMG rats. Lower levels of IL-10 and IFN-γ were also found in the supernatants of AChR-stimulated lymph node MNC culture in rats receiving IL-10-modified DC. These results demonstrate that IL-10-modified DC induced hypo-responsiveness by down-regulating co-stimulatory molecules, and reduced production of anti-AChR antibodies possibly by inhibiting IL-10 production. Importantly, this procedure that autologous DC from EAMG were adopted to treat ongoing EAMG is more close to clinical trial in human, encouraging future evaluation in human myasthenia gravis.

In the title compound, C14H12ClN3O2, the acylhydrazone base [C(=O)—N—N=C] is essentially planar, with an r.m.s. deviation of 0.0095 Å, and makes a dihedral angle of 12.52 (10)°with the pyridine ring. In the crystal, molecules are linked via pairs of N—H...O hydrogen bonds, forming inversion dimers with an R22(8) graph-set motif. The dimers are linked via C—H...π interactions forming chains along [101].

The molecule of the title compound, C10H12N2O4, is located around an inversion center. The carboxylate groups are twisted slightly with respect to the pyrazine ring, making a dihedral angle of 2.76 (19)°. In the crystal, molecules are stacked along the c axis via weak C—H...O hydrogen bonds.

In the title compound, [Cu(C13H8N4O3)(H2O)]·3H2O, the complex molecule, except for the aqua ligand, is essentially planar [r.m.s. deviation = 0.034 (2) Å]. The coordination polyhedron of the Cu2+ cation is a square-pyramid, with the aqua ligand at the apex. The compound exhibits a three-dimensional structure, which is is stabilized by O—H...O and O—-H...N hydrogen bonds and π–π interactions [centroid–centroid distance = 2.987 (3) Å].

Background The author intended to clarify the therapeutic effect and prognostic factors of metastasectomy and timing of pulmonary metastases in osteosarcoma patents. Methods Data was obtained retrospectively on all consecutive osteosarcoma patients from 1985 to 2005 in author's institute. Fifty-two patients with pulmonary nodules were identified, including 24 patients undergoing pulmonary metastasectomy treatment. These patients were categorized into four groups: group 1, patients with lung metastases at the initial presentation; group 2, lung metastases identified during the period of pre-operative chemotherapy; group 3, lung metastases identified during period of the post-operative chemotherapy; group 4, lung metastases identified after therapy for the primary osteosarcoma completed. Results In our study, the 2-, 3-, and 5-year overall survival rates for 52 patients were 49%, 39% and 20%. The 2-year overall survival rates were 18% for group 1, 32% for group 3, and 70% for group 4 (p < 0.001). The 5-year overall survival rate was 34% for group 4. Patients who underwent metastesectomy showed a better survival outcome as compared with the patients not undergoing metastasectomy (p = 0.003). The 2-year and 5-year overall survival rates of only one lung metastatic nodule were 62% and 50%, and for initially multiple lung metastatic nodules, 45% and 5%, respectively. In addition, the patients presented with lung metastases had a worse prognosis as compared with those without initial lung metastases (p = 0.0001). Conclusions The patients having single metastatic nodule showed a better prognosis than those with multiple lung nodules. Furthermore, those patients who underwent metastasectomy survived longer than those not undergoing metastasectomy. Patients who had late metastases after complete chemotherapy had a better prognosis; whereas those who had metastases identified at the initial presentation predicted a poor prognosis.