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New therapeutic approaches are needed for metastatic osteosarcoma (OS), as survival rates remain low despite surgery and chemotherapy. Epigenetic changes, such as histone H3 methylation, play key roles in many cancers including OS, although the underlying mechanisms are not clear. In this study, human OS tissue and OS cell lines displayed lower levels of histone H3 lysine trimethylation compared with normal bone tissue and osteoblast cells. Treating OS cells with the histone lysine demethylase inhibitor 5-carboxy-8-hydroxyquinoline (IOX-1) dose-dependently increased histone H3 methylation and inhibited cellular migratory and invasive capabilities, suppressed matrix metalloproteinase expression, reversed epithelial-to-mesenchymal transition by increasing levels of epithelial markers E-cadherin and ZO-1 and decreasing the expression of mesenchymal markers N-cadherin, vimentin, and TWIST, and also reduced stemness properties. An analysis of cultivated MG63 cisplatin-resistant (MG63-CR) cells revealed lower histone H3 lysine trimethylation levels compared with levels in MG63 cells. Exposing MG63-CR cells to IOX-1 increased histone H3 trimethylation and ATP-binding cassette transporter expression, potentially sensitizing MG63-CR cells to cisplatin. In conclusion, our study suggests that histone H3 lysine trimethylation is associated with metastatic OS and that IOX-1 or other epigenetic modulators present promising strategies to inhibit metastatic OS progression.

Study objective Necrotizing fasciitis (NF) is an uncommon life-threatening necrotizing skin and soft tissue infection. Bullae are special skin manifestations of NF. This study was conducted to analyze the differences between different types of bullae of limbs with NF for providing the information to emergency treatment. Methods From April 2015 to August 2018, patients were initially enrolled based on surgical confirmation of limbs with NF. According to the presence of different bullae types, patients were divided into no bullae group (Group N), serous-filled bullae group (Group S), and hemorrhagic bullae group (Group H). Data such as demographics, clinical outcomes, microbiological results, presenting symptoms/signs, and laboratory findings were compared among these groups. Results In total, 187 patients were collected, with 111 (59.4%) patients in Group N, 35 (18.7%) in Group S, and 41 (21.9%) in Group H. Group H had the highest incidence of amputation, required intensive care unit care, and most patients infected with Vibrio species. In Group N, more patients were infected with Staphylococcus spp. than Group H. In Group S, more patients were infected with β-hemolytic Streptococcus than Group H. Patients with bacteremia, shock, skin necrosis, anemia, and longer prothrombin time constituted higher proportions in Group H and S than in Group N. Conclusions In southern Taiwan, patients with NF accompanied by hemorrhagic bullae appear to have more bacteremia, Vibrio infection, septic shock, and risk for amputation. If the physicians at the emergency department can detect for the early signs of NF as soon as possible, and more patient’s life and limbs may be saved.

Necrotizing fasciitis (NF) of the limbs caused by Aeromonas species is an extremely rare and life-threatening skin and soft tissue infection. The purpose of this study was to evaluate the specific characteristics and the independent predictors of mortality in patients with Aeromonas NF. Sixty-eight patients were retrospectively reviewed over an 18-year period. Differences in mortality, demographics data, comorbidities, symptoms and signs, laboratory findings, microbiological analysis, empiric antibiotics treatment and clinical outcomes were compared between the non-survival and the survival groups. Twenty patients died with the mortality rate of 29.4%. The non-survival group revealed significant differences in bacteremia, monomicrobial infection, cephalosporins resistance, initial ineffective empiric antibiotics usage, chronic kidney disease, chronic hepatic dysfunction, tachypnea, shock, hemorrhagic bullae, skin necrosis, leukopenia, band polymorphonuclear neutrophils >10%, anemia, and thrombocytopenia. The multivariate analysis identified four variables predicting mortality: bloodstream infection, shock, skin necrosis, and initial ineffective empirical antimicrobial usage against Aeromonas. NF caused by Aeromonas spp. revealed high mortality rates, even through aggressive surgical debridement and antibacterial therapies. Identifying those independent predictors, such as bacteremia, shock, progressive skin necrosis, monomicrobial infection, and application of the effective antimicrobial agents against Aeromonas under the supervision of infectious doctors, may improve clinical outcomes.

Staphylococcus aureus (S. aureus) forms biofilm that causes periprosthetic joint infections and osteomyelitis (OM) which are the intractable health problems in clinics. The silver-containing nanoparticles (AgNPs) are antibacterial nanomaterials with less cytotoxicity than the classic Ag compounds. Likewise, gold nanoparticles (AuNPs) have also been demonstrated as excellent nanomaterials for medical applications. Previous studies have showed that both AgNPs and AuNPs have anti-microbial or anti-inflammatory properties. We have developed a novel green chemistry that could generate the AuAg nanocomposites, through the reduction of tannic acid (TNA). The bioactivity of the nanocomposites was investigated in S. aureus biofilm-exposed human osteoblast cells (hFOB1.19). The current synthesis method is a simple, low-cost, eco-friendly, and green chemistry approach. Our results showed that the AuAg nanocomposites were biocompatible with low cell toxicity, and did not induce cell apoptosis nor necrosis in hFOB1.19 cells. Moreover, AuAg nanocomposites could effectively inhibited the accumulation of reactive oxygen species (ROS) in mitochondria and in rest of cellular compartments after exposing to bacterial biofilm (by reducing 0.78, 0.77-fold in the cell and mitochondria, respectively). AuAg nanocomposites also suppressed ROS-triggered inflammatory protein expression via MAPKs and Akt pathways. The current data suggest that AuAg nanocomposites have the potential to be a good therapeutic agent in treating inflammation in bacteria-infected bone diseases.

Background Necrotizing fasciitis (NF) is a rare and life-threatening necrotizing skin and soft-tissue infection. Infectious pathogens of NF must be detected early and treated rapidly to prevent loss of limb or a fatal outcome. This study aimed to detect more reliable predictors between gram-negative and gram-positive monomicrobial NF of limbs. Methods A total of 100 patients with limb monomicrobial NF were diagnosed prospectively from April 2015 to July 2018. These monomicrobial NF pathogens can be divided into gram-negative and gram-positive groups according to the result of Gram staining and final bacterial reports. Data such as demographics, seawater or seafood contact history, infectious location, comorbidities, presenting signs and symptoms, and laboratory findings were recorded and compared. Results A total of 55 patients were infected with gram-negative organisms and 45 patients with gram-positive organisms. Among the 55 cases of monomicrobial gram-negative NF, 48 (87.3%) were caused mainly by Vibrio spp. (38, 69.1%) and Aeromonas spp. (10, 18.2%). A higher incidence of chronic kidney disease, cerebrovascular accident, tachypnea, and septic shock; a higher rate of band forms of leukocytes of more than 3%, serum lactate of more than 20 mg/dL, and C-reactive protein level of less than 150 mg/dL; prolonged prothrombin time; and a lower fibrinogen level were observed in patients with gram-negative infection. In a multivariate analysis, a higher incidence of seawater or seafood contact history (odds ratio [OR]: 66.301; 95% confidence interval [CI]: 7.467–588.702), a higher rate of hyperlactatemia (OR: 7.904; 95% CI: 1.231–50.744), and a low fibrinogen level (OR: 1.013; 95% CI: 1.004–1.023) indicated gram-negative infection. Conclusions In southern Taiwan, NF of limbs mainly affected the lower limbs, exhibited monomicrobial infection, and was predominated by gram-negative bacteria. Gram-negative monomicrobial NF of limbs often occurred in individuals with the more seawater or seafood contact history, hyperlactatemia, and low fibrinogen levels.

Several diseases have been linked to particulate matter (PM) exposure. Outdoor activities, such as road running or jogging, are popular aerobic exercises due to few participatory limitations. Osteoarthritis (OA) is a progressive degenerative joint disease, usually observed at age 40, and not noticed before pain or diagnosis. Although exercise has health benefits, it is unclear whether outdoor jogging in higher PM (standard reference material 1649b, SRM 1649b) concentration environments could affect OA development or severity. Hence, a PM exposure monosodium iodoacetate (MIA)-induced OA animal jogged model was established for investigation. Results showed that high doses of PM (5 mg) significantly increased pro-inflammatory factors such as tumor necrosis factor α (TNF-α), interleukin (IL)-1β, and IL-6, and M1 macrophages in the lung region, also obtained in systemic IL-6 and TNF-α expressions in this MIA-OA rat model. Moreover, levels of osteocalcin, cartilage oligomeric matrix protein (COMP), and N-telopeptides of type I collagen were especially influenced in MIA+PM groups. Morphological and structural changes of the knee joint were detected by micro-computed tomography images (micro-CT) and immunohistochemistry. MIA + PM rats exhibited severe bone density decrease, cartilage wear, and structure damages, accompanied by lower levels of physical activity, than the sham group and groups receiving MIA or PM alone. The findings suggest that the severity of OA could be promoted by PM exposure with a PM concentration effect via systemic inflammatory mechanisms. To the best of our knowledge, this is the first study to provide direct effects of PM exposure on OA severity.

Background Although the powerful clinical effects of radiofrequency and microwave ablation have been established, such ablation is associated with several limitations, including a small ablation size, a long ablation time, the few treatment positioning, and biosafety risks. To overcome these limitations, biosafe and efficient magnetic ablation was achieved in this study by using biocompatible liquid gallium as an ablation medium and a contrast medium for imaging. Results Magnetic fields with a frequency (f) lower than 200 kHz and an amplitude (H) × f value lower than 5.0 × 109 Am−1 s−1 were generated using the proposed method. These fields could generate an ablation size of 3 cm in rat liver lobes under a temperature of approximately 300 °C and a time of 20 s. The results of this study indicate that biomedical gallium can be used as a contrast medium for the positioning of gallium injections and the evaluation of ablated tissue around a target site. Liquid gallium can be used as an ablation medium and imaging contrast medium because of its stable retention in normal tissue for at least 3 days. Besides, the high anticancer potential of gallium ions was inferred from the self-degradation of 100 µL of liquid gallium after around 21 days of immersion in acidic solutions. Conclusions The rapid wireless ablation of large or multiple lesions was achieved through the simple multi-injection of liquid gallium. This approach can replace the currently favoured procedure involving the use of multiple ablation probes, which is associated with limited benefits and several side effects. Methods Magnetic ablation was confirmed to be highly efficient by the consistent results obtained in the simulation and in vitro tests of gallium and iron oxide as well as the electromagnetic specifics and thermotherapy performance comparison detailed in this study Ultrasound imaging, X-ray imaging, and magnetic resonance imaging were found to be compatible with the proposed magnetic ablation method. Self-degradation analysis was conducted by mixing liquid gallium in acidic solutions with a pH of approximately 5–7 (to imitate a tumour-containing microenvironment). X-ray diffraction was used to identify the gallium oxides produced by degraded gallium ions.

Background: Total hip arthroplasty (THA) is a widely used and successfully performed orthopedic procedure for treating severe hip osteoarthritis, rheumatoid arthritis, and avascular necrosis. However, periprosthetic joint infection (PJI) after THA is a devastating complication for patients and orthopedic surgeons. Although surgical technology has been advanced and antibiotic-loaded cemented spacers or beads have developed, the treatment failure rate of one- or two-stage exchange arthroplasty for PJI is reported to be high, with >10% rate of incidence. Therefore, determining the possible pathogenesis and increasing the treatment success rate is a clinically important and urgent issue. Methods: A total of 256 patients with PJI who had undergone THA from 2005 to 2015 were included in this retrospective review. Seven patients required combined ilioinguinal and anterlateoal approach for debridement of iliac fossa abscess and infected hip lesion, included five patients with intraoperative pus leakage from the acetabular inner wall and the other two patients who underwent pre-operative pelvic computed tomography (CT) because of repeat PJI treatment failure. All available data from the medical records from all patients were retrospectively analyzed.Results: Of the 256 patients, seven (3.1%) patients was combined iliac fossa abscess in our cohort. For the microbiologic analysis, a total of thirteen pathogens were isolated from seven recurrent PJI patients with iliac fossa abscess, and Staphylococus aureus was the most commomly pathogen (4 out of 7 cases). The serum white blood cell (WBC) count was decreased significantly two weeks after debridement with combined the ilioinguinal and anterolateral approach compared to the day before surgery (11840/μL vs. 7370/μL; pConclusion: This result suggests that pre-operative pelvic CT and cautious identification of uncertain pus leakage from the inner wall of the acetabulum is essential for the diagnosis of recurrent PJI. Radical debridement with combined ilioinguinal and anterlateoal approach may aviod treatment failure in recurrent PJI with iliac fossa abscess.

Despite the critical role of ORF50 in the KSHV latent-to-lytic switch, the molecular mechanism by which ORF50 activates its downstream target genes, especially those that encode the viral DNA replication enzymes, is not yet fully understood. Here, we find that ORF50 can cooperate with Sp3 to synergistically activate promoters of the viral ORF56 (primase), ORF21 (thymidine kinase), and ORF60 (ribonucleotide reductase) genes via similar Sp1/Sp3-binding motifs. Additionally, the same synergistic effect can be seen on the promoter of the cellular IL-10 gene. Overall, our data reveal an important role for Sp3 in ORF50-mediated transactivation, and we propose a new subclass of ORF50-responsive elements in viral and cellular promoters., The Kaposi’s sarcoma-associated herpesvirus (KSHV)-encoded open reading frame 50 (ORF50) protein is the key transactivator responsible for the latent-to-lytic switch. Here, we investigated the transcriptional activation of the ORF56 gene (encoding a primase protein) by ORF50 and successfully identified an ORF50-responsive element located in the promoter region between positions −97 and −44 (designated 56p-RE). This 56p-RE element contains a noncanonical RBP-Jκ-binding sequence and a nonconsensus Sp1/Sp3-binding sequence. Electrophoretic mobility shift assays revealed that RBP-Jκ, Sp3, and ORF50 could form stable complexes on the 56p-RE element. Importantly, transient-reporter analysis showed that Sp3, but not RBP-Jκ or Sp1, acts in synergy with ORF50 to activate the 56p-RE-containing reporter construct, and the synergy mainly depends on the Sp1/Sp3-binding region of the 56p-RE element. Sequence similarity searches revealed that the promoters for ORF21 (thymidine kinase), ORF60 (ribonucleotide reductase, small subunit), and cellular interleukin-10 (IL-10) contain a sequence motif similar to the Sp1/Sp3-binding region of the 56p-RE element, and we found that these promoters could also be synergistically activated by ORF50 and Sp3 via the conserved motifs. Noteworthily, the conversion of the Sp1/Sp3-binding sequence of the 56p-RE element into a consensus high-affinity Sp-binding sequence completely lost the synergistic response to ORF50 and Sp3. Moreover, transcriptional synergy could not be detected through other ORF50-responsive elements from the viral PAN, K12, ORF57, and K6 promoters. Collectively, the results of our study demonstrate that ORF50 and Sp3 can act in synergy on the transcription of specific gene promoters, and we find a novel conserved cis-acting motif in these promoters essential for transcriptional synergy. IMPORTANCE Despite the critical role of ORF50 in the KSHV latent-to-lytic switch, the molecular mechanism by which ORF50 activates its downstream target genes, especially those that encode the viral DNA replication enzymes, is not yet fully understood. Here, we find that ORF50 can cooperate with Sp3 to synergistically activate promoters of the viral ORF56 (primase), ORF21 (thymidine kinase), and ORF60 (ribonucleotide reductase) genes via similar Sp1/Sp3-binding motifs. Additionally, the same synergistic effect can be seen on the promoter of the cellular IL-10 gene. Overall, our data reveal an important role for Sp3 in ORF50-mediated transactivation, and we propose a new subclass of ORF50-responsive elements in viral and cellular promoters.

Kuo-Ti Peng,1,2 Yao-Chang Chiang,3,4 Tsung-Yu Huang,5,6 Pei-Chun Chen,1 Pey-Jium Chang,6,7 Chiang-Wen Lee3,4,8,9 1Department of Orthopaedic Surgery, Chang Gung Memorial Hospital, Puzi City, Chiayi County 61363, Taiwan; 2College of Medicine, Chang Gung University, Guishan District, Taoyuan City 33303, Taiwan; 3Department of Nursing, Chang Gung University of Science and Technology, Puzi City, Chiayi County 61363, Taiwan; 4Division of Basic Medical Sciences, and Chronic Diseases and Health Promotion Research Center, Chang Gung University of Science and Technology, Puzi City, Chiayi County 61363, Taiwan; 5Division of Infectious Diseases, Department of Internal Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan; 6Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang-Gung University, Taoyuan, Taiwan; 7Department of Nephrology, Chang Gung Memorial Hospital, Chiayi, Taiwan; 8Research Center for Industry of Human Ecology and Research Center for Chinese Herbal Medicine, Chang Gung University of Science and Technology, Guishan District, Taoyuan City 33303, Taiwan; 9Department of Rehabilitation, Chang Gung Memorial Hospital, Puzi City, Chiayi County 61363, Taiwan Background: Periprosthetic joint infections (PJIs) have a high incidence of recurrence after total joint replacement and are difficult to treat by debridement or antibiotic treatment. Curcumin is a natural product with anti-inflammatory and anti-bacterial properties. The low bioactivity of curcumin in water restricts its clinical application. Curcumin nanoparticles (CURN) were developed to overcome this limitation.Methods: In this study, the therapeutic effects of CURN and their anti-inflammatory functions were investigated in a Staphylococcus aureus biofilm-induced PJIs model. Results: CURN first attenuated the biofilm-induced expansion of myeloid-derived suppressor cells (MDSCs) and then regulated M1- and M2-phenotypic MDSC expression. Down-regulation of cytokines and reactive oxygen species was considered as the mechanism of CURN in reversing the suppression of T cell proliferation. The recovery of bone permeative destruction demonstrated that CURN enhanced therapeutic potency of vancomycin in vivo. Conclusion: This is the first study to demonstrate that CURN may be useful for treating PJIs. Keywords: periprosthetic joint infections, osteomyelitis, Staphylococcus aureus, myeloid-derived suppressor cells

Microplastics (MPs) pollution has become a serious environmental issue worldwide, but its potential effects on health remain unknown. The administration of polystyrene MPs (PS-MPs) to mice for eight weeks impaired learning and memory behavior. PS-MPs were detected in the brain especially in the hippocampus of these mice. Concurrently, the hippocampus had decreased levels of immediate-early genes, aberrantly enhanced synaptic glutamate AMPA receptors, and elevated neuroinflammation, all of which are critical for synaptic plasticity and memory. Interestingly, ablation of the vagus nerve, a modulator of the gut-brain axis, improved the memory function of PS-MPs mice. These results indicate that exposure to PS-MPs in mice alters the expression of neuronal activity-dependent genes and synaptic proteins, and increases neuroinflammation in the hippocampus, subsequently causing behavioral changes through the vagus nerve-dependent pathway. Our findings shed light on the adverse impacts of PS-MPs on the brain and hippocampal learning and memory.

Background Locking plate fixation appears to be a standard treatment for proximal humeral fracture. Different locking plate designs might result in different radiographic and functional outcomes. The original version of the Proximal Humeral Internal Locking System (PHILOS; DePuy Synthes, Warsaw, IN, USA) occupied the largest volume of the humeral head by screw distribution, whereas the Zimmer Periarticular Locking Plate (ZPLP) system (Zimmer Biomet, Warsaw, IN, USA) occupied the smallest. Methods We enrolled 50 patients undergoing ZPLP treatment and 50 undergoing PHILOS treatment. Results The postoperative amount of impaction was significantly higher using the ZPLP System than using the PHILOS. Subgroup analysis showed that medial calcar support was another critical factor that affected surgical outcomes, especially when using the ZPLP System. Conclusion The amount of postoperative impaction was significantly higher when the ZPLP was used compared with the PHILOS locking plate. Medial calcar support is another critical factor that affects surgical outcomes. However, no significant differences in functional outcomes (Constant-Murley score) between the ZPLP System and the PHILOS were noted at the 12-month follow-up.

Exposure to particulate matter (PM) has been linked to pulmonary and cardiovascular dysfunctions, as well as skin diseases, etc. PM impairs the skin barrier functions and is also involved in the initiation or exacerbation of skin inflammation, which is linked to the activation of reactive oxygen species (ROS) pathways. Fullerene is a single C60 molecule which has been reported to act as a good radical scavenger. However, its poor water solubility limits its biological applications. The glyco-modification of fullerenes increases their water solubility and anti-bacterial and anti-virus functions. However, it is still unclear whether it affects their anti-inflammatory function against PM-induced skin diseases. Hence, glycofullerenes were synthesized to investigate their effects on PM-exposed HaCaT human keratinocytes. Our results showed that glycofullerenes could reduce the rate of PM-induced apoptosis and ROS production, as well as decrease the expression of downstream mitogen-activated protein kinase and Akt pathways. Moreover, PM-induced increases in inflammatory-related signals, such as cyclooxygenase-2, heme oxygenase-1, and prostaglandin E2, were also suppressed by glycofullerenes. Notably, our results suggested that PM-induced impairment of skin barrier proteins, such as filaggrin, involucrin, repetin, and loricrin, could be reduced by pre-treatment with glycofullerenes. The results of this study indicate that glycofullerenes could be potential candidates for treatments against PM-induced skin diseases and that they exert their protective effects via ROS scavenging, anti-inflammation, and maintenance of the expression of barrier proteins.

Particulate matter (PM), a widespread air pollutant, consists of a complex mixture of solid and liquid particles suspended in air. Many diseases have been linked to PM exposure, which induces an imbalance in reactive oxygen species (ROS) generated in cells, and might result in skin diseases (such as aging and atopic dermatitis). New techniques involving nanomedicine and nano-delivery systems are being rapidly developed in the medicinal field. Fullerene, a kind of nanomaterial, acts as a super radical scavenger. Lower water solubility levels limit the bio-applications of fullerene. Hence, to improve the water solubility of fullerene, while retaining its radical scavenger functions, a fullerene derivative, fullerenol C60(OH)36, was synthesized, to examine its biofunctions in PM-exposed human keratinocyte (HaCaT) cells. The PM-induced increase in ROS levels and expression of phosphorylated mitogen-activated protein kinase and Akt could be inhibited via fullerenol pre-treatment. Furthermore, the expression of inflammation-related proteins, cyclooxygenase-2, heme oxygenase-1, and prostaglandin E2 was also suppressed. Fullerenol could preserve the impaired state of skin barrier proteins (filaggrin, involucrin, repetin, and loricrin), which was attributable to PM exposure. These results suggest that fullerenol could act against PM-induced cytotoxicity via ROS scavenging and anti-inflammatory mechanisms, and the maintenance of expression of barrier proteins, and is a potential candidate compound for the treatment of skin diseases.

Methicillin-resistant Staphylococcus aureus (MRSA) causes superficial infections such as cellulitis or invasive infections such as osteomyelitis, however, differences in MRSA isolates from cellulitis (CL-MRSA) and from osteomyelitis (OM-MRSA) at the same local area remain largely unknown. A total of 221 MRSA isolates including 106 CL-MRSA strains and 115 OM-MRSA strains were collected at Chang-Gung Memorial Hospital in Taiwan between 2016 and 2018, and their genotypic and phenotypic characteristics were compared. We found that OM-MRSA isolates significantly exhibited higher rates of resistance to multiple antibiotics than CL-MRSA isolates. Genotypically, OM-MRSA isolates had higher proportions of the SCCmec type III, the sequence type ST239, and the spa type t037 than CL-MRSA isolates. Besides the multidrug-resistant lineage ST239-t037-SCCmecIII more prevalent in OM-MRSA, higher antibiotic resistance rates were also observed in several other prevalent lineages in OM-MRSA as compared to the same lineages in CL-MRSA. Furthermore, when prosthetic joint infection (PJI) associated and non-PJI-associated MRSA strains in osteomyelitis were compared, no significant differences were observed in antibiotic resistance rates between the two groups, albeit more diverse genotypes were found in non-PJI-associated MRSA. Our findings therefore suggest that deep infections may allow MRSA to evade antibiotic attack and facilitate the convergent evolution and selection of multidrug-resistant lineages.

Periprosthetic joint infections (PJIs) caused by Staphylococcus aureus infection are difficult to treat due to antibiotic resistance. It is known that the biofilms from methicillin-resistant S. aureus (MRSA) promote expansion of myeloid-derived suppressor cells (MDSCs) to suppress T-cell proliferation and benefit bacterial infections. This study finds that GMI, a fungal immunomodulatory peptide isolated from Ganoderma microsporum, suppresses MDSC expansion to promote the proliferation of cytotoxic T cells. The enhancement is likely attributed to increased expression of IL-6 and TNF-α and reduction in ROS expression. Similar beneficial effects of GMI on the suppression of MDSC expansion and IL-6 expression are also observed in the whole blood and reduces the accumulation of MDSCs in the infected bone region in a mouse PJI infection model. This study shows that GMI is potentially useful for treating S. aureus-induced PJIs.

Large-diameter head (LDH) metal-on-metal (MoM) total hip arthroplasty (THA) has lost popularity because of metal allergy or ALTRs (adverse local tissue reactions) in the past decade. Whether the surgical approach may influence the survival of LDH-MoM-THA has not been reported. From 2006 to 2009, we performed 96 LDH-MoM-THAs on 80 patients using an in situ head-neck assembly technique through a modified Watson-Jones approach. With a mean follow-up of 8.4 years (range, 6.3–10.1 years), the implant survival rate was 100%. All patients were satisfied with the results and the Harris Hip Score improved from 52 points to 98 points. No ALTRs were found, but 17.7% of the 96 hips (17 adverse events) experienced adverse events related to the cup, including 5 cases of outlier cup malposition, 11 cases of inadequate cup seating, and 1 acetabular fracture. The tissue tension that was improved by a muscle-sparing approach might lessen the chance of microseparation or edge-loading that is taken as the major risk for early implant failure. Further investigation of whether these LDH-MoM-THAs would fail or not would require a longer follow-up or even retrieval analysis in the future.

Background Anterior cruciate ligament (ACL) injury is one of the most common injuries of the area surrounding the knee. Muscle strength deficiency is observed following an ACL injury. Determining differences in muscle strength and gait between patients with acute and chronic ACL injury will provide crucial information for assessments and treatment plans. Methods We evaluated 60 patients with ACL rupture. Patients were classified into acute and chronic groups. We compared measurements of anthropometric parameters, muscle strength, gait and functional questionnaire. Findings The muscle strength of both knee extensors and flexors was higher in the chronic group than in the acute group. The muscle strength index for extensors was 57% in the acute group and 73% in the chronic group. However, the hamstring-to-quadriceps ratio for peak torque of the injured leg in the acute and chronic groups was similarly high at 98% and 101%, respectively. In gait, asymmetry in the hip and knee was observed in the acute group but not in the chronic group. The Knee Injury and Osteoarthritis Outcome Scores (KOOS) for symptoms, pain, activities of daily living, sports and recreational activities were higher in the chronic group than in the acute group. Interpretation Compared with the acute group, the gait of the chronic group is more symmetrical, and the score of KOOS is also higher. The muscle training protocols could be strategically planned according to these differences. Patients with ACL injury are characterized high hamstrings-to quadriceps peak torque ratio.

This study evaluates the sustained analgesic effect of ketorolac-eluting thermosensitive biodegradable hydrogel in the plantar incisional pain model of the rat hind-paw. A ketorolac-embedded 2, 2'-Bis (2-oxazolin) (BOX) linking methoxy-poly(ethylene glycol) and poly(lactide-co-glycolide) (mPEG-PLGA) diblock copolymer (BOX copolymer) was synthesized as keto-hydrogel based on optimal sol-gel phase transition and in vitro drug release profile. The effect of keto-hydrogel on postoperative pain (POP) was assessed using the established plantar incisional pain model in hind-paw of rats and compared to that of ketorolac solution. Pain and sensory threshold, as well as pain scoring, were evaluated with behavioral tests by means of anesthesiometer and incapacitance apparatus, respectively. Pro-inflammatory cytokine levels (TNF-α, IL-6, VEGF, and IL-1β) around incisional wounds were measured by ELISA. Tissue histology was assessed using hematoxylin and eosin and Masson’s trichrome staining. Ten mg/mL (25 wt%) keto-hydrogel showed a sol-gel transition at 26.4°C with a 10-day sustained drug release profile in vitro. Compared to ketorolac solution group, the concentration of ketorolac in tissue fluid was higher in the keto-hydrogel group during the first 18 h of application. Keto-hydrogel elevated pain and sensory threshold, increased weight-bearing capacity, and significantly reduced the levels of TNF-α, IL-6, and IL-1β while enhanced VEGF in tissue fluid. Histologic analysis reveals greater epithelialization and collagen deposition around wound treated with keto-hydrogel. In conclusion, our study suggests that keto-hydrogel is an ideal compound to treat POP with a secondary gain of improved incisional wound healing.

Malignant melanoma is developed from pigment-containing cells, melanocytes, and primarily found on the skin. Malignant melanoma still has a high mortality rate, which may imply a lack of therapeutic agents. Lakoochin A, a compound isolated from Artocarpus lakoocha and Artocarpus xanthocarpus, has an inhibitory function of tyrosinase activity and melanin production, but the anti-cancer effects are still unclear. In the current study, the therapeutic effects of lakoochin A with their apoptosis functions and possible mechanisms were investigated on A375.S2 melanoma cells. Several methods were applied, including 3-(4,5-Dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT), flow cytometry, and immunoblotting. Results suggest that lakoochin A attenuated the growth of A375.S2 melanoma cells through an apoptosis mechanism. Lakoochin A first increase the production of cellular and mitochondrial reactive oxygen species (ROSs), mitochondrial ROSs then promote mitogen-activated protein kinases (MAPKs) pathway activation and raise downstream apoptosis-related protein and caspase expression. This is the first study to demonstrate that lakoochin A, through ROS-MAPK, apoptosis-related proteins, caspases cascades, can induce melanoma cell apoptosis and may be a potential candidate compound for treating malignant melanoma.

Small wear particles (0.1-10 μm) in total joint replacement are generally considered as the major causative agent leading to periprosthetic inflammation and osteolysis. However, little is known about the roles of larger wear particles (10-100 μm) in periprosthetic inflammation and osteolysis. Additionally, although ample studies demonstrated that increased oxidative stress is critically involved in particle-induced inflammation and osteolysis, detailed changes in antioxidant enzymes expression in the disease development remain largely unclear. Herein, we used a rat knee prosthesis model to assess effects of polyethylene (PE) particles (20-60 μm) on the levels of oxidative stress markers such as malondialdehyde (MDA) and total antioxidant capacity (TAC) in blood plasma, and on the expression profiles of antioxidant enzymes in knee joint tissues. In combination with a forced-exercise intervention for all surgical rats, we found that the rat groups treated with both artificial joint and PE particles exhibited higher MDA levels and lower TAC levels, together with lower levels of physical activity and higher levels of inflammatory markers, than the sham group and the groups receiving artificial joint or PE particles alone at weeks 20-24 post-operatively. Dose-response relationships between the exposure to PE particles and the induction of oxidative stress and inflammation were also observed in the artificial joint/PE groups. Under such conditions, we unexpectedly found that most of antioxidant enzymes displayed pronounced up-regulation, with concomitant induction of inflammatory and osteoclast-inducing factors (including IL-1β, NF-κB and RANKL), in the artificial joint/PE groups as compared to the sham, artificial joint only, or PE only group. Only a few antioxidant enzymes including SOD2 and GPx2 showed down-regulation. Collectively, our findings demonstrate that implantation of artificial joint along with large PE particles synergistically trigger the induction of oxidative stress; however, down-regulation of many antioxidant enzymes may not necessarily occur during the disease development.

Background: Osteonecrosis of the femoral head can lead to destruction of the hip joint and disabling arthritis in young adults, if left untreated. Among the salvage procedures, core decompression combined with bone graft substitutes is a viable option for joint preservation. The purpose of this study was to review the outcomes of using synthetic bone graft substitute (calcium sulfate and calcium phosphate) for the treatment of late-stage osteonecrosis of the femoral head. Methods: From November 2008 to May 2009, 19 hips in 18 patients with osteonecrosis of the femoral head [6 hips in Association Research Circulation Osseous (ARCO) stage IIC and 13 hips in stage IIIA] were treated with core decompression combined with PRO-DENSE ™ (Injectable Regenerative Graft). The average age of the patients at the time of surgery was 48 years (range 25-67 years). Twelve patients (13 hips) overused alcohol, four patients (4 hips) were idiopathic, one patient (1 hip) used corticosteroids, and one patient (1 hip) was post-traumatic. The clinical failure was defined as conversion to total hip arthroplasty or progression in head collapse. Results: At the conclusion of the study, 3 in the 6 stage IIC hips and 8 in the 13 stage IIIA hips were converted to total hip arthroplasty in an average of 8.5 months (range 4-30 months) postoperatively. Advanced collapse of the femoral head awaiting for total hip arthroplasty was observed in the other six hips. Of the 19 hips, only 2 hips (10.5%) survived without further collapse in the 5-year follow-up. This resulted in 89.5% failure rate with early resorption of the grafting in an average of 5.3 months. Conclusions: Core decompression combined with an injectable calcium sulfate and calcium phosphate composite graft (PRO-DENSE) were associated high failure rates in the early postoperative period. It is not recommended for the treatment of ARCO stage IIC and IIIA osteonecrosis of the femoral head.

The risk of surgical site infections (SSIs) after total knee arthroplasty (TKA) can never be eliminated. Antimicrobial sutures containing triclosan have been used to decrease SSIs, but whether triclosan-coated sutures are effective with TKA is unclear. Between 2011 and 2012, 102 patients randomly assigned to a triclosan or a control group were prospectively assessed. The incidence of SSI within 3 months of surgery, length of hospital stay, pain scale, functional scores, wound condition, and serum inflammatory markers during hospitalization and within 3 months postoperatively were compared. At the final follow-up, there were 2 patients with superficial infections (3.9%) in the control group but none in the triclosan group. Lower serum IL-6 was detected in the triclosan group at 4 weeks and 3 months. The local skin temperature of the knees—recorded at 3 months using infrared thermography—was lower in the triclosan group than in the control group. More precise analytical measurements are needed to investigate local and systemic complications, especially in the early subclinical stage. This prospective, randomized, open-label clinical trial is in the public registry: ClinicalTrials.gov (NCT02533492).

Molecular diagnosis of biofilm-related genes (BRGs) in common bacteria that cause periprosthetic joint infections may provide crucial information for clinicians. In this study, several BRGs, including ica, fnbA, and fnbB, were rapidly detected (within 1 h) with a new integrated microfluidic system. Mannose-binding lectin (MBL)-coated magnetic beads were used to isolate these bacteria, and on-chip nucleic acid amplification (polymerase chain reaction, PCR) was then performed to detect BRGs. Both eukaryotic and prokaryotic MBLs were able to isolate common bacterial strains, regardless of their antibiotic resistance, and limits of detection were as low as 3 and 9 CFU for methicillin-resistant Staphylococcus aureus and Escherichia coli, respectively, when using a universal 16S rRNA PCR assay for bacterial identification. It is worth noting that the entire process including bacteria isolation by using MBL-coated beads for sample pre-treatment, on-chip PCR, and fluorescent signal detection could be completed on an integrated microfluidic system within 1 h. This is the first time that an integrated microfluidic system capable of detecting BRGs by using MBL as a universal capturing probe was reported. This integrated microfluidic system might therefore prove useful for monitoring profiles of BRGs and give clinicians more clues for their clinical judgments in the near future.

Background Although the loss of bone mineral density (BMD) after total hip arthroplasty (THA) is a known problem, it remains unresolved. This study prospectively examined the effect of zoledronic acid (ZA) on bone turnover and BMD after cementless THA. Methods Between January 2010 and August 2011, 60 patients who underwent cementless THA were randomly assigned to receive either ZA infusion or placebo (0.9% normal saline only) postoperatively. ZA was administered at 2 day and 1 year postoperatively. Periprosthetic BMD in seven Gruen zones was assessed preoperatively and at given time points for 2 years. Serum markers of bone turnover, functional scales, and adverse events were recorded. Results Each group contained 27 patients for the final analysis. The loss of BMD across all Gruen zones (significantly in zones 1 and 7) up to 2 years postoperatively was noted in the placebo group. BMD was significantly higher in the ZA group than in the placebo group in Gruen zones 1, 2, 6, and 7 at 1 year and in Gruen zones 1, 6, and 7 at 2 years (p

Arthritic knees with advanced valgus deformity present with soft tissue and osseous anomalies that make total knee arthroplasty (TKA) difficult. We conducted a retrospective chart review of 41 patients (51 knees) to determine whether computer-assisted surgery-TKA (CAS-TKA) is superior to TKA using conventional guiding systems. A significantly higher rate of lateral retinaculum release as well as outlier of sagittal mechanical axes and position of the femoral component (femoral flexion and femoral rotational angle) was recorded in the conventional TKA group versus the CAS-TKA group. Both groups had significant postoperative improvement in clinical performance, but results did not differ significantly between groups. Despite its radiographic benefit, CAS-TKA showed no significant benefit over TKA in short-term clinical functional outcomes when performed by an experienced surgeon.