The subacromial bursa modulates tendon healing after rotator cuff injury in rats.

Rotator cuff injuries result in more than 500,000 surgeries annually in the United States, many of which fail. These surgeries typically involve repair of the injured tendon and removal of the subacromial bursa, a synovial-like tissue that sits between the rotator cuff and the acromion. The subacromial bursa has been implicated in rotator cuff pathogenesis and healing. Using proteomic profiling of bursa samples from nine patients with rotator cuff injury, we show that the bursa responds to injury in the underlying tendon. In a rat model of supraspinatus tenotomy, we evaluated the bursa's effect on the injured supraspinatus tendon, the uninjured infraspinatus tendon, and the underlying humeral head. The bursa protected the intact infraspinatus tendon adjacent to the injured supraspinatus tendon by maintaining its mechanical properties and protected the underlying humeral head by maintaining bone morphometry. The bursa promoted an inflammatory response in injured rat tendon, initiating expression of genes associated with wound healing, including Cox2 and Il6. These results were confirmed in rat bursa organ cultures. To evaluate the potential of the bursa as a therapeutic target, polymer microspheres loaded with dexamethasone were delivered to the intact bursae of rats after tenotomy. Dexamethasone released from the bursa reduced Il1b expression in injured rat supraspinatus tendon, suggesting that the bursa could be used for drug delivery to reduce inflammation in the healing tendon. Our findings indicate that the subacromial bursa contributes to healing in underlying tissues of the shoulder joint, suggesting that its removal during rotator cuff surgery should be reconsidered.

A role for TGFß signaling in Gli1+ tendon and enthesis cells.

The development of musculoskeletal tissues such as tendon, enthesis, and bone relies on proliferation and differentiation of mesenchymal progenitor cells. Gli1+ cells have been described as putative stem cells in several tissues and are presumed to play critical roles in tissue formation and maintenance. For example, the enthesis, a fibrocartilage tissue that connects tendon to bone, is mineralized postnatally by a pool of Gli1+ progenitor cells. These cells are regulated by hedgehog signaling, but it is unclear if TGFß signaling, necessary for tenogenesis, also plays a role in their behavior. To examine the role of TGFß signaling in Gli1+ cell function, the receptor for TGFß, TbR2, was deleted in Gli1-lineage cells in mice at P5. Decreased TGFß signaling in these cells led to defects in tendon enthesis formation by P56, including defective bone morphometry underlying the enthesis and decreased mechanical properties. Immunohistochemical staining of these Gli1+ cells showed that loss of TGFß signaling reduced proliferation and increased apoptosis. In vitro experiments using Gli1+ cells isolated from mouse tail tendons demonstrated that TGFß controls cell proliferation and differentiation through canonical and non-canonical pathways and that TGFß directly controls the tendon transcription factor scleraxis by binding to its distant enhancer. These results have implications in the development of treatments for tendon and enthesis pathologies.

Hedgehog Activation for Enhanced Rotator Cuff Tendon-to-Bone Healing.

BACKGROUND: Rotator cuff repair is a common orthopaedic procedure, yet the rate of failure to heal after surgery is high. Repair site rupture is due to poor tendon-to-bone healing and lack of regeneration of the native fibrocartilaginous enthesis. During development, the enthesis is formed and mineralized by a pool of progenitors activated by hedgehog signaling. Furthermore, hedgehog signaling drives regenerative enthesis healing in young animals, in contrast to older animals, in which enthesis injuries heal via fibrovascular scar and without participation of hedgehog signaling. HYPOTHESIS: Hedgehog activation improves tendon-to-bone healing in an animal model of rotator cuff repair. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 78 adult Sprague-Dawley rats were used. Supraspinatus tendon injury and repair were completed bilaterally, with microsphere-encapsulated hedgehog agonist administered to right shoulders and control microspheres administered to left shoulders. Animals were sacrificed after 3, 14, 28, or 56 days. Gene expression and histological, biomechanical, and bone morphometric analyses were conducted. RESULTS: At 3 days, hedgehog signaling pathway genes Gli1 (1.70; P = .029) and Smo (2.06; P = .0173), as well as Runx2 (1.69; P = .0386), a transcription factor of osteogenesis, were upregulated in treated relative to control repairs. At 14 days, transcription factors of tenogenesis, Scx (4.00; P = .041), and chondrogenesis, Sox9 (2.95; P = .010), and mineralized fibrocartilage genes Col2 (3.18; P = .031) and Colx (1.85; P = .006), were upregulated in treated relative to control repairs. Treatment promoted fibrocartilage formation at the healing interface by 28 days, with improvements in tendon-bone maturity, organization, and continuity. Treatment led to improved biomechanical properties. The material property strength (2.43 vs 1.89 N/m2; P = .046) and the structural property work to failure (29.01 vs 18.09 mJ; P = .030) were increased in treated relative to control repairs at 28 days and 56 days, respectively. Treatment had a marginal effect on bone morphometry underlying the repair. Trabecular thickness (0.08 vs 0.07 mm; P = .035) was increased at 28 days. CONCLUSION: Hedgehog agonist treatment activated hedgehog signaling at the tendon-to-bone repair site and prompted increased mineralized fibrocartilage production. This extracellular matrix production and mineralization resulted in improved biomechanical properties, demonstrating the therapeutic potential of hedgehog agonism for improving tendon-to-bone healing after rotator cuff repair. CLINICAL RELEVANCE: This study demonstrates the therapeutic potential of hedgehog agonist treatment for improving tendon-to-bone healing after rotator cuff injury and repair.

The subacromial bursa is a key regulator of the rotator cuff and a new therapeutic target for improving repair.

Rotator cuff injuries result in over 500,000 surgeries performed annually, an alarmingly high number of which fail. These procedures typically involve repair of the injured tendon and removal of the subacromial bursa. However, recent identification of a resident population of mesenchymal stem cells and inflammatory responsiveness of the bursa to tendinopathy indicate an unexplored biological role of the bursa in the context of rotator cuff disease. Therefore, we aimed to understand the clinical relevance of bursa-tendon crosstalk, characterize the biologic role of the bursa within the shoulder, and test the therapeutic potential for targeting the bursa. Proteomic profiling of patient bursa and tendon samples demonstrated that the bursa is activated by tendon injury. Using a rat to model rotator cuff injury and repair, tenotomy-activated bursa protected the intact tendon adjacent to the injured tendon and maintained the morphology of the underlying bone. The bursa also promoted an early inflammatory response in the injured tendon, initiating key players in wound healing. In vivo results were supported by targeted organ culture studies of the bursa. To examine the potential to therapeutically target the bursa, dexamethasone was delivered to the bursa, prompting a shift in cellular signaling towards resolution of inflammation in the healing tendon. In conclusion, contrary to current clinical practice, the bursa should be retained to the greatest extent possible and provides a new therapeutically target for improving tendon healing outcomes. One Sentence Summary: The subacromial bursa is activated by rotator cuff injury and regulates the paracrine environment of the shoulder to maintain the properties of the underlying tendon and bone.

Solubilized curcuminoid complex prevents extensive immunosuppression through immune restoration and antioxidant activity: Therapeutic potential against SARS-CoV-2 (COVID-19).

The therapeutic benefits of curcuminoids in various diseases have been extensively reported. However, little is known regarding their preventive effects on extensive immunosuppression. We investigated the immunoregulatory effects of a curcuminoid complex (CS/M), solubilized with stevioside, using a microwave-assisted method in a cyclophosphamide (CTX)-induced immunosuppressive mouse model and identified its new pharmacological benefits. CTX-treated mice showed a decreased number of innate cells, such as dendritic cells (DCs), neutrophils, and natural killer (NK) cells, and adaptive immune cells (CD4 and CD8 T cells) in the spleen. In addition, CTX administration decreased T cell activation, especially that of Th1 and CD8 T cells, whereas it increased Th2 and regulatory T (Treg) cell activations. Pre-exposure of CS/M to CTX-induced immunosuppressed mice restored the number of innate cells (DCs, neutrophils, and NK cells) and increased their activity (including the activity of macrophages). Exposure to CS/M also led to the superior restoration of T cell numbers, including Th1, activated CD8 T cells, and multifunctional T cells, suppressed by CTX, along with a decrease in Th2 and Treg cells. Furthermore,CTX-injected mice pre-exposed to CS/M were accompanied by an increase in the levels of antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase), which play an essential role against oxidative stress. Importantly, CS/M treatment significantly reduced viral loads in severe acute respiratory syndrome coronavirus2-infected hamsters and attenuated the gross pathology in the lungs. These results provide new insights into the immunological properties of CS/M in preventing extensive immunosuppression and offer new therapeutic opportunities against various cancers and infectious diseases caused by viruses and intracellular bacteria.

Twenty-Five Year Trend Change in the Etiology of Pediatric Invasive Bacterial Infections in Korea, 1996–2020

Background@#The coronavirus disease-2019 (COVID-19) pandemic has contributed to the change in the epidemiology of many infectious diseases. This study aimed to establish the pre-pandemic epidemiology of pediatric invasive bacterial infection (IBI). @*Methods@#A retrospective multicenter-based surveillance for pediatric IBIs has been maintained from 1996 to 2020 in Korea. IBIs caused by eight bacteria (Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis, Staphylococcus aureus, Streptococcus agalactiae, Streptococcus pyogenes, Listeria monocytogenes, and Salmonella species) in immunocompetent children > 3 months of age were collected at 29 centers. The annual trend in the proportion of IBIs by each pathogen was analyzed. @*Results@#A total of 2,195 episodes were identified during the 25-year period between 1996 and 2020. S. pneumoniae (42.4%), S. aureus (22.1%), and Salmonella species (21.0%) were common in children 3 to 59 months of age. In children ≥ 5 years of age, S. aureus (58.1%), followed by Salmonella species (14.8%) and S. pneumoniae (12.2%) were common. Excluding the year 2020, there was a trend toward a decrease in the relative proportions of S. pneumoniae (rs = −0.430, P = 0.036), H. influenzae (rs = −0.922, P 3 months of age. These findings can be used as the baseline data to navigate the trend in the epidemiology of pediatric IBI in the post COVID-19 era.

Citation Activity of Journal of Korean Medical Science in 2011–2020:Reflection on the Most and Least Cited Items

Background@#The Journal of Korean Medical Science (JKMS) is a weekly periodical published by the Korean Academy of Medical Sciences. JKMS invites global researchers to submit articles covering various areas in general medicine. The present article’s aim was to analyze citations of JKMS articles in 2011–2020 for updating editorial policies. @*Methods@#Citation records of JKMS articles were tracked in Web of Science (WoS), Clarivate ®from August 2021 to June 2022. @*Results@#In 2011–2020, JKMS published 2,880 articles, including 2,757 (96.0%) ever cited. All reviews (57/57) and 96% of original research reports (2,184 out of 2,264) received at least one citation. Brief communications, opinions, and images were least cited items. Of 36 subject categories covered by JKMS, only biomedical engineering was significantly less advantageous citation-wise. Five articles published in 2012–2017 attracted more than 100 citations. Most other articles were cited less than 50 times. Article categories of nationwide epidemiology, disease or patient registries, clinical trials, and infectious diseases were distinguished as well cited. Of 378 articles published in 2020, 10 were cited at least 100 times; all these ten items were related to severe acute respiratory syndrome coronavirus 2 and coronavirus disease 2019. In the past 5 years, studies on health care laws, management, and some specific topics in clinical specialties were not cited. The citation trends in WoS, Crossref, and Scopus were similar while PubMed Central records were roughly twice less. @*Conclusion@#Most of JKMS articles are cited during 5 years post publication, with 1.4% noncitation rate. The obtained results suggest that inviting review articles in clinical sciences, research reports on hot medical topics, and nationwide database analyses may attract more author interest and related citations.

Dual therapeutic targeting of intra-articular inflammation and intracellular bacteria enhances chondroprotection in septic arthritis.

Bacterial infections involving joints and vital organs represent a challenging clinical problem because of the two concurrent therapeutic goals of bacterial eradication and tissue preservation. In the case of septic arthritis, permanent destruction of articular cartilage by intense host inflammation is commonly seen even after successful treatment of bacterial infection. Here, we provide scientific evidence of a novel treatment modality that can protect articular cartilage and enhanced eradication of causative bacteria in septic arthritis. Locally delivered cell-penetrating antibiotics such as rifampicin effectively eradicate intracellular reservoirs of methicillin-resistant Staphylococcus aureus within joint cells. Furthermore, mitigation of intra-articular inflammation by targeting the NLRP3 (nucleotide-binding oligomerization domain-, leucine-rich repeat- and pyrin domain-containing 3) inflammasome protects articular cartilage from damage in a murine model of knee septic arthritis. Together, concurrent mitigation of intra-articular inflammation and local adjuvant targeting of intracellular bacteria represents a promising new therapeutic strategy for septic arthritis.

Enhanced Tendon-to-Bone Healing via IKKß Inhibition in a Rat Rotator Cuff Model.

BACKGROUND: More than 450,000 rotator cuff repairs are performed annually, yet healing of tendon to bone often fails. This failure is rooted in the fibrovascular healing response, which does not regenerate the native attachment site. Better healing outcomes may be achieved by targeting inflammation during the early period after repair. Rather than broad inhibition of inflammation, which may impair healing, the current study utilized a molecularly targeted approach to suppress IKKß, shutting down only the inflammatory arm of the nuclear factor κB (NF-κB) signaling pathway. PURPOSE: To evaluate the therapeutic potential of IKKß inhibition in a clinically relevant model of rat rotator cuff repair. STUDY DESIGN: Controlled laboratory study. METHODS: After validating the efficacy of the IKKß inhibitor in vitro, it was administered orally once a day for 7 days after surgery in a rat rotator cuff repair model. The effect of treatment on reducing inflammation and improving repair quality was evaluated after 3 days and 2, 4, and 8 weeks of healing, using gene expression, biomechanics, bone morphometry, and histology. RESULTS: Inhibition of IKKß attenuated cytokine and chemokine production in vitro, demonstrating the potential for this inhibitor to reduce inflammation in vivo. Oral treatment with IKKß inhibitor reduced NF-κB target gene expression by up to 80% compared with a nontreated group at day 3, with a subset of these genes suppressed through 14 days. Furthermore, the IKKß inhibitor led to enhanced tenogenesis and extracellular matrix production, as demonstrated by gene expression and histological analyses. At 4 weeks, inhibitor treatment led to increased toughness, no effects on failure load and strength, and decreases in stiffness and modulus when compared with vehicle control. At 8 weeks, IKKß inhibitor treatment led to increased toughness, failure load, and strength compared with control animals. IKKß inhibitor treatment prevented the bone loss near the tendon attachment that occurred in repairs in control. CONCLUSION: Pharmacological inhibition of IKKß successfully suppressed excessive inflammation and enhanced tendon-to-bone healing after rotator cuff repair in a rat model. CLINICAL RELEVANCE: The NF-κB pathway is a promising target for enhancing outcomes after rotator cuff repair.

The effect of 4-hexylresorinol administration on NAD+ level and SIRT activity in Saos-2 cells / 대한악안면성형재건외과학회지

Background@#4-hexylresorcinol (4HR) has been shown to have anti-oxidant activity similar to that of resveratrol. As resveratrol increases sirtuin (SIRT) activity, 4HR might behave similarly to resveratrol.Method: In this study, the expression levels of SIRT1, SIRT3, and SIRT6 were evaluated after 4HR administration (1–100 μM). As NAD+ is a substrate for SIRTs, its levels with SIRT activity were also studied. @*Results@#In the results, SIRT3 (100 μM at 24 h) and SIRT6 (1–100 μM at 24 h and 10 μM at 8 h) were shown to have significantly higher expression levels compared to untreated control (p < 0.05). Pan-SIRT activity and the NAD+ level was significantly increased compared to that of the untreated control (p < 0.05; 10 and 100 μM at 24 h). @*Conclusion@#4HR administration increased SIRT activity and the NAD+ level in Saos-2 cells.

Vibraimage Characteristics of Offenders with Schizophrenia Spectrum Disorder / 생물치료정신의학

Objectives@#：The purpose of this study was to identify characteristic Vibraimage parameters in schizophrenia spectrum and other psychotic disorders. @*Methods@#：This study retrospectively analyzed subjects who were referred to the National Forensic Hospital in Gongju city for psychiatric evaluation between April 2019 and October 2019. After divided into two groups; Schizophrenia Spectrum Disorders group and non-organic non-psychotic disorders group, Vibraimage parameters and MMPI-2 items were compared between the two groups. In addition, we investigated the relations between Vibraimage parameters and MMPI-2 items characteristic of schizophrenia spectrum and other psychotic disorders by using the Correlation analysis. @*Results@#：Compared to non-organic non-psychotic disorders group, Schizophrenia Spectrum Disorders group scored low at Aggression (t=-2.752, p=0.007), Tension (t=-2.106, p=0.039), and Suspects (t=-2.617, p=0.011); high at Neuroticism (t=4,215, p<0.001) in the Vibraimage, and the group scored comparatively high at Sc (Schizophrenia) (t=-2.099, p=0.039) and low at Hy (Hysteria) (t=-2.228, p=0.029) in the MMPI-2. The Sc (Schizophrenia) item in the MMPI-2 showed a negative correlation with Suspect parameter (r=0.242 p=0.035) and positive correlation with Neuroticism parameter (r=0.267, p=0.02) in the Vibraimage. @*Conclusion@#：Our findings suggest that Suspect and Neuroticism parameters of the Vibraimage were characteristic in schizophrenia spectrum and other psychotic disorders, and showed potential as diagnostic tools, especially in psychiatric evaluations.

The Influence of Femoral Internal Rotation on Patellar Tracking in Total Knee Arthroplasty Using Gap Technique

Background@#Femoral internal rotation in total knee arthroplasty (TKA) is well known as one of the main causes of patellar maltracking. Although femoral internal rotation in TKA is considered unacceptable due to the risk of patellar maltracking, it is sometimes required for ligament balancing. We evaluated the influence of femoral internal rotation on patellar tracking in TKA performed using the gap technique. @*Methods@#From April 2008 to May 2018, 1,612 cases of TKA were done. Among them, 245 cases of TKA for osteoarthritis were followed up for at least 1 year and included in this study. We compared patellar tracking in two groups; group I consisted of 99 cases whose femoral rotation was less than 0° and group II consisted of 146 cases whose femoral rotation was 3°–5° external rotation. Preoperative femoral rotation was measured with the condylar twist angle (CTA) by using computed tomography. The patella was replaced in all cases. Patellar tracking was evaluated with patellar tilt angle (lateral tilt [+] and medial tilt [–]) in the merchant radiograph. Statistical analysis was done using Mann-Whitney U-test. Clinical assessment was performed using the Knee Society clinical rating system. @*Results@#The preoperative CTA was 5.3° ± 1.6° in group I and 5.4° ± 1.6° in group II, showing no statistically significant difference between groups (p = 0.455). Intraoperative femoral rotation was –0.5° ± 0.8° in group I and 3.9° ± 0.8° in group II when the gap technique was used (p < 0.001). The postoperative patellar tilt angle was –0.4° ± 3.6° in group I and 0.1° ± 4.1° in group II with no statistically significant difference (p = 0.251). @*Conclusions@#Compared with femoral external rotation, femoral internal rotation with ligament balance in TKA was not more associated with patellar maltracking. Therefore, patellar tracking might be related with ligament balance in flexion regardless of the anatomic femoral rotational alignment.

Vibraimage Characteristics of Offenders with Schizophrenia Spectrum Disorder / 생물치료정신의학

Objectives@#：The purpose of this study was to identify characteristic Vibraimage parameters in schizophrenia spectrum and other psychotic disorders. @*Methods@#：This study retrospectively analyzed subjects who were referred to the National Forensic Hospital in Gongju city for psychiatric evaluation between April 2019 and October 2019. After divided into two groups; Schizophrenia Spectrum Disorders group and non-organic non-psychotic disorders group, Vibraimage parameters and MMPI-2 items were compared between the two groups. In addition, we investigated the relations between Vibraimage parameters and MMPI-2 items characteristic of schizophrenia spectrum and other psychotic disorders by using the Correlation analysis. @*Results@#：Compared to non-organic non-psychotic disorders group, Schizophrenia Spectrum Disorders group scored low at Aggression (t=-2.752, p=0.007), Tension (t=-2.106, p=0.039), and Suspects (t=-2.617, p=0.011); high at Neuroticism (t=4,215, p<0.001) in the Vibraimage, and the group scored comparatively high at Sc (Schizophrenia) (t=-2.099, p=0.039) and low at Hy (Hysteria) (t=-2.228, p=0.029) in the MMPI-2. The Sc (Schizophrenia) item in the MMPI-2 showed a negative correlation with Suspect parameter (r=0.242 p=0.035) and positive correlation with Neuroticism parameter (r=0.267, p=0.02) in the Vibraimage. @*Conclusion@#：Our findings suggest that Suspect and Neuroticism parameters of the Vibraimage were characteristic in schizophrenia spectrum and other psychotic disorders, and showed potential as diagnostic tools, especially in psychiatric evaluations.

The Influence of Femoral Internal Rotation on Patellar Tracking in Total Knee Arthroplasty Using Gap Technique

Background@#Femoral internal rotation in total knee arthroplasty (TKA) is well known as one of the main causes of patellar maltracking. Although femoral internal rotation in TKA is considered unacceptable due to the risk of patellar maltracking, it is sometimes required for ligament balancing. We evaluated the influence of femoral internal rotation on patellar tracking in TKA performed using the gap technique. @*Methods@#From April 2008 to May 2018, 1,612 cases of TKA were done. Among them, 245 cases of TKA for osteoarthritis were followed up for at least 1 year and included in this study. We compared patellar tracking in two groups; group I consisted of 99 cases whose femoral rotation was less than 0° and group II consisted of 146 cases whose femoral rotation was 3°–5° external rotation. Preoperative femoral rotation was measured with the condylar twist angle (CTA) by using computed tomography. The patella was replaced in all cases. Patellar tracking was evaluated with patellar tilt angle (lateral tilt [+] and medial tilt [–]) in the merchant radiograph. Statistical analysis was done using Mann-Whitney U-test. Clinical assessment was performed using the Knee Society clinical rating system. @*Results@#The preoperative CTA was 5.3° ± 1.6° in group I and 5.4° ± 1.6° in group II, showing no statistically significant difference between groups (p = 0.455). Intraoperative femoral rotation was –0.5° ± 0.8° in group I and 3.9° ± 0.8° in group II when the gap technique was used (p < 0.001). The postoperative patellar tilt angle was –0.4° ± 3.6° in group I and 0.1° ± 4.1° in group II with no statistically significant difference (p = 0.251). @*Conclusions@#Compared with femoral external rotation, femoral internal rotation with ligament balance in TKA was not more associated with patellar maltracking. Therefore, patellar tracking might be related with ligament balance in flexion regardless of the anatomic femoral rotational alignment.

Clinical Results of Medial Unicompartmental Knee Arthroplasty in Elderly Patients Older than 70 Years of Age / 대한정형외과학회잡지

Purpose@#To evaluate the long-term clinical results and survivorship of unicompartmental knee arthroplasty (UKA) in elderly patients older than 70 years by analyzing cases that have been implanted for >10 years ago. @*Materials and Methods@#The long-term follow-up results were evaluated in 39 patients (46 cases) who underwent medial UKA from March 2002 to February 2004. The mean age of the patients at the time of surgery was 74.0 years, and the preoperative diagnosis was degenerative arthritis of the knee in all cases. @*Results@#Of the 46 cases, reoperation occurred due to the complications in four cases. In 22 cases without 14 cases of death and six cases of follow-up loss, follow-up more than 10 years was possible. The mean Knee Society knee and function scores improved significantly from 53.0 and 52.5 points pre-operatively to 89.4 and 80.9 points at the last follow-up, respectively (p<0.001). The mean range of motion of the knee recovered to 132.5°, and the mean tibiofemoral angle changed to 5.9° of valgus at the last follow-up. Complications following the UKA occurred in four cases; the most prevalent complication was mobile bearing dislocation (n=2). One case of failure occurred due to aseptic loosening and degenerative arthritis of the lateral compartment, respectively. The cumulative survival rate of the implants was 95.0% at 10 years and 85.7% at 15 years. Of the 40 cases, excluding six cases of follow-up loss, 36 cases (90.0%) could be used without reoperation until death or at the last follow-up after surgery. @*Conclusion@#These results showed the outstanding functions of the knee and satisfactory long-term survivorship after UKA. Therefore, UKA could be a useful method for the treatment of osteoarthritis of the knee in elderly patients older than 70 years of age.

Recalcitrant methicillin-resistant Staphylococcus aureus infection of bone cells: Intracellular penetration and control strategies.

AIMS: To characterize the intracellular penetration of osteoblasts and osteoclasts by methicillin-resistant Staphylococcus aureus (MRSA) and the antibiotic and detergent susceptibility of MRSA in bone. METHODS: Time-lapse confocal microscopy was used to analyze the interaction of MRSA strain USA300 with primary murine osteoblasts and osteoclasts. The effects of early and delayed antibiotic treatments on intracellular and extracellular bacterial colony formation and cell death were quantified. We tested the effects of cefazolin, gentamicin, vancomycin, tetracycline, rifampicin, and ampicillin, as well as agents used in surgical preparation and irrigation. RESULTS: MRSA infiltrated bone-resident cells within 15 to 30 minutes. Penetration was most effectively prevented with early (i.e. 30 minutes) antibiotic administration. The combined administration of rifampicin with other antibiotics potentiated their protective effects against MRSA-induced cytotoxicity and most significantly reduced extracellular bacterial bioburden. Gentamicin-containing compounds were most effective in reducing intracellular MRSA bioburden. Of the surgical preparation agents evaluated, betadine reduced in vitro MRSA growth to the greatest extent. CONCLUSION: The standard of care for open fractures involves debridement and antibiotics within the first six hours of injury but does not account for the window in which bacteria penetrate cells. Antibiotics must be administered as early as possible after injury or prior to incision to prevent intracellular infestation. Rifampicin can potentiate the capacity of antibiotic regimens to reduce MRSA-induced cytotoxicity.Cite this article: Bone Joint Res. 2020;9(2):49-59.

Diagnostic Value of SusceptibilityWeighted MRI in Differentiating Cerebellopontine Angle Schwannoma from Meningioma

Background@#Differentiation of cerebellopontine angle (CPA) schwannoma from meningioma is often a difficult process to identify.Purpose: To identify imaging features for distinguishing CPA schwannoma from meningioma and to investigate the usefulness of susceptibility-weighted imaging (SWI) in differentiating them. @*Materials and Methods@#Between March 2010 and January 2015, this study pathologically confirmed 11 meningiomas and 20 schwannomas involving CPA with preoperative SWI were retrospectively reviewed. Generally, the following MRI features were evaluated: 1) maximal diameter on axial image, 2) angle between tumor border and adjacent petrous bone, 3) presence of intratumoral dark signal intensity on SWI, 4) tumor consistency, 5) blood-fluid level, 6) involvement of internal auditory canal (IAC), 7) dural tail, and 8) involvement of adjacent intracranial space. On CT, 1) presence of dilatation of IAC, 2) intratumoral calcification, and 3) adjacent hyperostosis were evaluated. All features were compared using Chi-squared tests and Fisher’s exact tests. The univariate and multivariate logistic regression analysis were performed to identify imaging features that differentiate both tumors. @*Results@#The results noted that schwannomas more frequently demonstrated dark spots on SWI (P = 0.025), cystic consistency (P = 0.034), and globular angle (P = 0.008); schwannomas showed more dilatation of internal auditory meatus and lack of calcification (P = 0.008 and P = 0.02, respectively). However, it was shown that dural tail was more common in meningiomas (P < 0.007). In general, dark spots on SWI and dural tail remained significant in multivariate analysis (P = 0.037 and P = 0.012, respectively). In this case, the combination of two features showed a sensitivity and specificity of 80% and 100% respectively, with an area under the receiver operating characteristic curve of 0.9. @*Conclusion@#In conclusion, dark spots on SWI were found to be helpful in differentiating CPA schwannoma from meningioma. It is noted that combining dural tail with dark spots on SWI yielded strong diagnostic value in differentiating both tumors.

History and Concept of Manual Therapy / 대한정형외과학회잡지

Manual therapy has undergone parallel development throughout many parts of the world dating back to ancient times for at least 2,500 years. The earliest historical reference to the practice of manual therapy in Greece, dates back to 400 B.C. Over the centuries, manual medicines have fallen in and out of favor with the medical profession. To truly understand the principle, it is important to know that manual therapy was initially the mainstay of the three leading alternative health care systems, osteopathy, chiropractic, and most notably physical therapy. These were all founded in the latter part of the 19th century in response to the shortcomings in allopathic medicine. Although it has been around for a long time and has been used all over the world, there are a few reports on manual therapy treatment, and most papers provided a low level of evidence. Despite the controversies over manual therapy, its use appears to be increasing gradually. This article reviews the history of manual therapy from ancient times to the present including Korean history, discusses the current state of knowledge on manual therapy, and informs physicians who manage musculoskeletal pain.

Targeting the NF-κB signaling pathway in chronic tendon disease.

Tendon disorders represent the most common musculoskeletal complaint for which patients seek medical attention; inflammation drives tendon degeneration before tearing and impairs healing after repair. Clinical evidence has implicated the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway as a correlate of pain-free return to function after surgical repair. However, it is currently unknown whether this response is a reaction to or a driver of pathology. Therefore, we aimed to understand the clinically relevant involvement of the NF-κB pathway in tendinopathy, to determine its potential causative roles in tendon degeneration, and to test its potential as a therapeutic candidate. Transcriptional profiling of early rotator cuff tendinopathy identified increases in NF-κB signaling, including increased expression of the regulatory serine kinase subunit IKKß, which plays an essential role in inflammation. Using cre-mediated overexpression of IKKß in tendon fibroblasts, we observed degeneration of mouse rotator cuff tendons and the adjacent humeral head. These changes were associated with increases in proinflammatory cytokines and innate immune cells within the joint. Conversely, genetic deletion of IKKß in tendon fibroblasts partially protected mice from chronic overuse-induced tendinopathy. Furthermore, conditional knockout of IKKß improved outcomes after surgical repair, whereas overexpression impaired tendon healing. Accordingly, targeting of the IKKß/NF-κB pathway in tendon stromal cells may offer previously unidentified therapeutic approaches in the management of human tendon disorders.

Efficient and stable radiolabeling of polycyclic aromatic hydrocarbon assemblies: in vivo imaging of diesel exhaust particulates in mice.

As a robust radioanalytical method for tracking carbonaceous particulates in vivo, polycyclic aromatic hydrocarbons from diesel exhaust were labeled with a radioactive-iodine-tagged pyrene analogue. Single-photon emission computed tomography and biodistribution studies showed high uptake and slow clearance of this matter in the respiratory system, which may underlie its severe toxicity.