The Impact of Bone Marrow Stimulation on Arthroscopic Rotator Cuff Repair for Small to Large Rotator Cuff Tears: A Randomized Controlled Trial.

BACKGROUND: Bone marrow stimulation (BMS), a procedure involving the creation of multiple channels in the greater tuberosity, is often performed alongside arthroscopic rotator cuff repair (ARCR). This study evaluated the effect of BMS on clinical and structural outcomes following ARCR. METHOD: This study involved 204 patients with small, medium, and large full-thickness rotator cuff tears. In all, 103 patients who underwent BMS and ARCR made up the BMS group, while the 101 patients who only had ARCR made up the control group with randomization. Clinical and functional outcomes were assessed before and at 3 months, 6 months, 1 year, and 2 years after surgery, using parameters such as range of motion, functional scores (ASES and constant score), and clinical scores (VAS). Tendon integrity was also examined postoperatively via ultrasound at 6 months and 2 years. RESULTS: There were no significant differences between the two groups concerning range of motion, functional scores (ASES score and constant score), and clinical score (VAS) during the 2-year post-surgery period (all p>0.05). Similarly, the rotator cuff retear rate, as assessed using ultrasonographic tendon integrity checks over 2 years post-surgery, did not significantly vary between the groups (all p>0.05). CONCLUSION: There were no significant disparities in functional scores and clinical outcomes between the BMS and control groups. Further, no significant differences were observed in tendon integrity post-surgery. Therefore, the inclusion or exclusion of BMS is not anticipated to influence the postoperative outcome in ARCR for patients with small, medium, or large rotator cuff tears.

Dysfunction of NMDA receptors in neuronal models of an autism spectrum disorder patient with a DSCAM mutation and in Dscam-knockout mice.

Heterogeneity in the etiopathology of autism spectrum disorders (ASD) limits the development of generic remedies, requires individualistic and patient-specific research. Recent progress in human-induced pluripotent stem cell (iPSC) technology provides a novel platform for modeling ASDs for studying complex neuronal phenotypes. In this study, we generated telencephalic induced neuronal (iN) cells from iPSCs derived from an ASD patient with a heterozygous point mutation in the DSCAM gene. The mRNA of DSCAM and the density of DSCAM in dendrites were significantly decreased in ASD compared to control iN cells. RNA sequencing analysis revealed that several synaptic function-related genes including NMDA receptor subunits were downregulated in ASD iN cells. Moreover, NMDA receptor (R)-mediated currents were significantly reduced in ASD compared to control iN cells. Normal NMDA-R-mediated current levels were rescued by expressing wild-type DSCAM in ASD iN cells, and reduced currents were observed by truncated DSCAM expression in control iN cells. shRNA-mediated DSCAM knockdown in control iN cells resulted in the downregulation of an NMDA-R subunit, which was rescued by the overexpression of shRNA-resistant DSCAM. Furthermore, DSCAM was co-localized with NMDA-R components in the dendritic spines of iN cells whereas their co-localizations were significantly reduced in ASD iN cells. Levels of phospho-ERK1/2 were significantly lower in ASD iN cells, suggesting a potential mechanism. A neural stem cell-specific Dscam heterozygous knockout mouse model, showing deficits in social interaction and social memory with reduced NMDA-R currents. These data suggest that DSCAM mutation causes pathological symptoms of ASD by dysregulating NMDA-R function.

Cell type-restricted activity of hnRNPM promotes breast cancer metastasis via regulating alternative splicing.

Tumor metastasis remains the major cause of cancer-related death, but its molecular basis is still not well understood. Here we uncovered a splicing-mediated pathway that is essential for breast cancer metastasis. We show that the RNA-binding protein heterogeneous nuclear ribonucleoprotein M (hnRNPM) promotes breast cancer metastasis by activating the switch of alternative splicing that occurs during epithelial-mesenchymal transition (EMT). Genome-wide deep sequencing analysis suggests that hnRNPM potentiates TGFß signaling and identifies CD44 as a key downstream target of hnRNPM. hnRNPM ablation prevents TGFß-induced EMT and inhibits breast cancer metastasis in mice, whereas enforced expression of the specific CD44 standard (CD44s) splice isoform overrides the loss of hnRNPM and permits EMT and metastasis. Mechanistically, we demonstrate that the ubiquitously expressed hnRNPM acts in a mesenchymal-specific manner to precisely control CD44 splice isoform switching during EMT. This restricted cell-type activity of hnRNPM is achieved by competition with ESRP1, an epithelial splicing regulator that binds to the same cis-regulatory RNA elements as hnRNPM and is repressed during EMT. Importantly, hnRNPM is associated with aggressive breast cancer and correlates with increased CD44s in patient specimens. These findings demonstrate a novel molecular mechanism through which tumor metastasis is endowed by the hnRNPM-mediated splicing program.

SIRT1 Promotes Host Protective Immunity against Toxoplasma gondii by Controlling the FoxO-Autophagy Axis via the AMPK and PI3K/AKT Signalling Pathways.

Sirtuin 1 (SIRT1) regulates cellular processes by deacetylating non-histone targets, including transcription factors and intracellular signalling mediators; thus, its abnormal activation is closely linked to the pathophysiology of several diseases. However, its function in Toxoplasma gondii infection is unclear. We found that SIRT1 contributes to autophagy activation via the AMP-activated protein kinase (AMPK) and PI3K/AKT signalling pathways, promoting anti-Toxoplasma responses. Myeloid-specific Sirt1-/- mice exhibited an increased cyst burden in brain tissue compared to wild-type mice following infection with the avirulent ME49 strain. Consistently, the intracellular survival of T. gondii was markedly increased in Sirt1-deficient bone-marrow-derived macrophages (BMDMs). In contrast, the activation of SIRT1 by resveratrol resulted in not only the induction of autophagy but also a significantly increased anti-Toxoplasma effect. Notably, SIRT1 regulates the FoxO-autophagy axis in several human diseases. Importantly, the T. gondii-induced phosphorylation, acetylation, and cytosolic translocation of FoxO1 was enhanced in Sirt1-deficient BMDMs and the pharmacological inhibition of PI3K/AKT signalling reduced the cytosolic translocation of FoxO1 in BMDMs infected with T. gondii. Further, the CaMKK2-dependent AMPK signalling pathway is responsible for the effect of SIRT1 on the FoxO3a-autophagy axis and for its anti-Toxoplasma activity. Collectively, our findings reveal a previously unappreciated role for SIRT1 in Toxoplasma infection.

Predicting the clinically significant subscapularis tendon tear: malposition and tear of the long head of the biceps tendon on shoulder magnetic resonance imaging.

BACKGROUND: The diagnostic accuracy of magnetic resonance imaging (MRI) is low for detecting a subscapularis tendon tear. PURPOSE: To identify MRI findings that may predict the presence of a clinically significant subscapularis tendon tear requiring surgical repair. MATERIAL AND METHODS: We reviewed shoulder MR images of patients who had undergone arthroscopic rotator cuff repair at our institution between June 2018 and May 2019. Patients were divided into two groups: the study group (n = 51), with an intermediate- to high-grade partial thickness tear of the subscapularis tendon suspected on preoperative MRI and intermediate or higher grade of the tendon tear proven on arthroscopy; and the control group (n = 18), with an intermediate- to high-grade partial thickness tear of the subscapularis tendon suspected on preoperative MRI but no tear or low-grade partial thickness tear of the tendon shown on arthroscopy. Preoperative MR images were retrospectively evaluated by two readers for the size of the subscapularis tendon tear, bone reactions at the lesser tuberosity, and long head of the biceps tendon (LHBT) pathology. RESULTS: The subscapularis tendon tear measured by reader 2 was larger in the study group than in the control group. The prevalence of a tear (P = 0.006 for reader 1; P = 0.011 for reader 2) and malposition (P < 0.001 for both readers) of the LHBT were significantly greater in the study group. CONCLUSION: A tear and malposition of the LHBT on MR images may predict the presence of a clinically significant subscapularis tendon tear.

Distal chevron metatarsal osteotomy is a viable treatment option for hallux valgus with metatarsus adductus-multicentre retrospective study.

PURPOSE: The purpose of this study was to evaluate the radiographic and clinical outcomes of patients with hallux valgus (HV) with concomitant metatarsus adductus (MA) treated with distal chevron metatarsal osteotomy (DCMO), without any procedure for the second or third metatarsal. METHODS: A multicentre retrospective study involving four hospitals was conducted. A total of 45 feet from 38 patients who had received DCMO for HV with MA with at least one year post-operative follow-up were analysed. HV angle (HVâ), inter-metatarsal angle (IMâ), MA angle (MAâ), and the lateral sesamoid grade were measured. Foot function index (FFI) and visual analogue scale (VAS) were recorded. Patients were divided into mild (18° ≤ MAâ < 20°) and moderate (20° ≤ MAâ) MA groups, and results were compared. RESULTS: The mean HVâ and IMâ improved significantly from 35.1° and 14.4° pre-operatively to 10.6° and 7.1° one year post-operatively (p < 0.001). There were no differences in pre-operative HVâ, IMâ, or the sesamoid grade, and also no difference in post-operative HVâ or the sesamoid grade between mild and moderate MA groups. Only the mean post-operative IMâ showed a difference between the two groups (8.3° vs. 6.3°; p = 0.019). All clauses of FFI and VAS improved significantly (p < 0.001). When the extent of improvement was compared between the two groups, there were no significant differences in any category (p > 0.05). The total rate of recurrence (HVâ ≥ 20°) was 11.1% (5/45), and although the moderate group (4/29, 13.8%) had a higher proportion than the mild group (1/16, 6.3%), this was not statistically significant (p = 0.641). CONCLUSION: DCMO for patients with HV with MA had satisfactory radiographic and clinical outcomes with minimal recurrence. Except in cases of severe combined deformity, we recommend performing DCMO alone without any additional procedure or manipulation of the other metatarsals as a viable treatment option.

Comparative Transcriptome Analysis of Human Adipose-Derived Stem Cells Undergoing Osteogenesis in 2D and 3D Culture Conditions.

Human adipose-derived stem cells (hADSCs) are types of mesenchymal stem cells (MSCs) that have been used as tissue engineering models for bone, cartilage, muscle, marrow stroma, tendon, fat and other connective tissues. Tissue regeneration materials composed of hADSCs have the potential to play an important role in reconstituting damaged tissue or diseased mesenchymal tissue. In this study, we assessed and investigated the osteogenesis of hADSCs in both two-dimensional (2D) and three-dimensional (3D) culture conditions. We confirmed that the hADSCs successfully differentiated into bone tissues by ARS staining and quantitative RT-PCR. To gain insight into the detailed biological difference between the two culture conditions, we profiled the overall gene expression by analyzing the whole transcriptome sequencing data using various bioinformatic methods. We profiled the overall gene expression through RNA-Seq and further analyzed this using various bioinformatic methods. During differential gene expression testing, significant differences in the gene expressions between hADSCs cultured in 2D and 3D conditions were observed. The genes related to skeletal development, bone development and bone remodeling processes were overexpressed in the 3D culture condition as compared to the 2D culture condition. In summary, our RNA-Seq-based study proves effective in providing new insights that contribute toward achieving a genome-wide understanding of gene regulation in mesenchymal stem cell osteogenic differentiation and bone tissue regeneration within the 3D culture system.

Calcaneal fracture: results of earlier rehabilitation after open reduction and internal fixation.

INTRODUCTION: This study aimed to analyze the clinical and radiological outcomes of early weight-bearing and rehabilitation after open reduction and internal fixation (OR/IF) of calcaneal fracture. MATERIALS AND METHODS: This retrospective study was conducted on 78 patients with unilateral calcaneal fracture who underwent OR/IF. A mean follow-up period was 45.8 months (range 12-135). Two weeks after surgery, the range of motion (ROM) exercise was started, brace or heel off shoe was applied, and forefoot weight-bearing was allowed. Four weeks after surgery, tolerable weight-bearing ambulation without crutch was allowed. When the patient was not walking, the braces were removed to perform peritalar ROM exercises. Radiologic evaluation was performed by measuring the Böhler angle and incongruency of the subtalar joint surface. Paley grade was used to assess traumatic arthritis. Clinical evaluation was performed by measuring the foot and ankle outcome score (FAOS) and ankle ROM. RESULTS: The mean postoperative Böhler angle was 31.7° (P < 0.001) at 2 weeks, 31.2° at 3 months, and 30.1° at the last (P = 0.4). The average Paley grade of the subtalar OA was 1.12. CT imaging revealed that the average step-off of the subtalar joint was 1.26 mm in coronal and 0.84 mm in sagittal. The average ROM results were as follows (contralateral, affected side): there was no significant difference in dorsiflexion [16.9° vs. 16° (P = 0.6)], whereas plantarflexion and inversion were significantly decreased [39.5° vs. 35.3° (P = 0.049) and 50.5° vs. 34.8° (P = 0.04)]. The average FAOS score was 86.1 points, and the highest score was "function" (mean 92.5 points). CONCLUSIONS: Earlier rehabilitation after OR/IF is recommended for the treatment of calcaneal fracture.

Treatment of Recurrent Peroneal Tendon Dislocation by Peroneal Retinaculum Reattachment Without Fibular Groove Deepening.

There are numerous studies recommending fibular groove deepening in the surgical treatment of peroneal tendon dislocation; however, there are some disadvantages to fibular groove deepening procedures. In this study, we evaluated the results of anatomic reattachment of the peroneal retinaculum without fibular groove deepening as a treatment for traumatic peroneal tendon dislocation. Thirty-six patients with recurrent peroneal tendon dislocation, who underwent retinaculum repair without a fibular groove deepening procedure performed by 2 surgeons between March 2004 and March 2017, were enrolled in this study. Resubluxation of tendon, pain on inversion and eversion power of the ankle were monitored. The range of motion of inversion and eversion were measured and then compared to that of the contralateral side. American Orthopedic Foot and Ankle Society (AOFAS), visual analog scale (VAS), Foot Function Index (FFI) scores were obtained for all patients preoperatively and at the final follow-up. Postoperative complications such as infection, sural nerve injury, and recurrence were monitored. Thirty-four patients fully recovered without resubluxation of tendon. Two patients were injured again while playing soccer 6 months after the surgery and fast running 20 months after the surgery respectively. One patient had sural nerve injury. But the symptom was relieved at 6 months after the surgery. None of the patients had weakness of evertor. None of the patients had limited ankle motion. Mean AOFAS, VAS, FFI score improved significantly (p = .02, .01, .02). In conclusion, for the treatment of recurrent dislocation of the peroneal tendon reattachment of the superior retinaculum only without groove deepening followed by proper rehabilitation is sufficient.

Light Inhibits COP1-Mediated Degradation of ICE Transcription Factors to Induce Stomatal Development in Arabidopsis.

Stomata are epidermal openings that facilitate plant-atmosphere gas exchange during photosynthesis, respiration, and water evaporation. Stomatal differentiation and patterning are spatially and temporally regulated by the master regulators SPEECHLESS (SPCH), MUTE, and FAMA, which constitute a central gene regulatory network along with Inducer of CBF Expression (ICE) transcription factors for this developmental process. Stomatal development is also profoundly influenced by environmental conditions, such as light, temperature, and humidity. Light induces stomatal development, and various photoreceptors modulate this response. However, it is unknown how light is functionally linked with the master regulatory network. Here, we demonstrate that, under dark conditions, the E3 ubiquitin ligase CONSTITUTIVE PHOTOMORPHOGENIC1 (COP1) degrades ICE proteins through ubiquitination pathways in leaf abaxial epidermal cells in Arabidopsis thaliana Accordingly, the ICE proteins accumulate in the nuclei of leaf abaxial epidermal cells in COP1-defective mutants, which constitutively produce stomata. Notably, light in the blue, red, and far-red wavelength ranges suppresses the COP1-mediated degradation of the ICE proteins to induce stomatal development. These observations indicate that light is directly linked with the ICE-directed signaling module, via the COP1-mediated protein surveillance system, in the modulation of stomatal development.

Connective tissue growth factor (CTGF) regulates the fusion of osteoclast precursors by inhibiting Bcl6 in periodontitis.

Connective tissue growth factor (CTGF), an extracellular matrix protein with various biological functions, is known to be upregulated in multiple chronic diseases such as liver fibrosis and congestive heart failure, but the mechanism it undertakes to cause alveolar bone loss in periodontitis remains elusive. The present study therefore investigates the pathways involving CTGF in chronic periodontitis. RNA sequencing revealed a notable increase in the expression of CTGF in chronic periodontitis tissues. Also, TRAP staining, TRAP activity and bone resorption assays showed that osteoclast formation and function is significantly facilitated in CTGF-treated bone marrow-derived macrophages (BMMs). Interestingly, western blotting and immunofluorescence staining results displayed that CTGF had little effect on the osteoclastogenic differentiation mediated by the positive regulators of osteoclastogenesis such as nuclear factor of activated T cells 1 (NFATc1). However, following results showed that both the mRNA and protein expressions of B cell lymphoma 6 (Bcl6), a transcriptional repressor of "osteoclastic" genes, were significantly downregulated by CTGF treatment. Moreover, CTGF upregulated the expressions of v-ATPase V0 subunit d2 (ATP6v0d2) and Dendritic cell-specific transmembrane protein (DC-STAMP) which are osteoclastic genes specifically required for osteoclast cell-cell fusion in pre-osteoclasts. Findings from this study suggest that CTGF promotes the fusion of pre-osteoclasts by downregulating Bcl6 and subsequently increasing the expression of DC-STAMP in periodontitis. Understanding this novel mechanism that leads to increased osteoclastogenesis in periodontitis may be employed for the development of new therapeutic targets for preventing periodontitis-associated alveolar bone resorption.

Partial meniscectomy provides the favorable outcomes for symptomatic medial meniscus tear with an intact posterior root.

PURPOSE: This study aimed to investigate the long-term outcomes of arthroscopic partial meniscectomy for medial meniscus tear (with intact posterior root) and to analyze the risk factors for treatment failure. METHODS: The records of 165 patients who underwent partial meniscectomy for medial meniscus tear with intact posterior root with a minimum 5-year follow-up were included. Modified Lysholm score and radiologic outcomes were compared between preoperative and latest follow-up periods. The cumulative Outerbridge grade of the medial compartment was defined as follows: 0-4, low chondral wear; 5-6, intermediate wear; or 7-8, high wear. Kaplan-Meier survival and Cox hazard regression analyses were performed to assess the survivorship after partial meniscectomy. Conversion to total knee replacement arthroplasty, high tibial osteotomy or a Lysholm score of < 65 points indicated treatment failure. RESULTS: Mean Lysholm score improved from 66.3 ± 14.2 preoperatively to 81.8 ± 17.9 at the latest follow-up (p = 0.001). The postoperative 10-year survival rate of the low chondral wear group [97% (95% confidence interval (CI) 141.7-152.6 months)] was higher than that of the intermediate [83.1% (95% CI 129.6-147.9 months)] and high wear groups [76.1% (95% CI 115.2-135.0 months)]. A 1 mm joint space width narrowing led to a 37.7% increase in the failure rate [B = - 0.473; hazard ratio, 0.623 (95% CI 0.423-0.917); p = 0.016]. The high chondral wear group showed a higher failure rate compared to the low wear group [B = 1.870; hazard ratio, 6.488 (95% CI 0.853-49.333); p = 0.041]. CONCLUSION: Partial meniscectomy offers pain relief and functional improvement for medial meniscus tear with intact posterior root. Preoperative joint space narrowing and higher chondral wear at surgery were significant risk factors of treatment failure. Partial meniscectomy should be considered as an effective treatment for irreparable medial meniscus tear with intact posterior root without joint space narrowing and chondral wear. LEVEL OF EVIDENCE: Case series, Level IV.

Valgus stress ultrasound for medial ulnar collateral ligament injuries in athletes: is ultrasound alone enough for diagnosis?

BACKGROUND: We hypothesized that valgus stress ultrasound would be useful for both identifying medial ulnar collateral ligament (MUCL) tears and assessing the severity of the tears. Hence, we performed valgus stress ultrasound of the elbow in athletes with MUCL injuries, confirmed by magnetic resonance imaging (MRI), to determine whether ultrasound can be used as a diagnostic tool. METHODS: Stress ultrasound and MRI data from 146 athletes with medial elbow pain were compared prospectively. MRI findings for MUCL injuries were classified into 3 levels as follows: low-grade partial tear (≤50%), high-grade partial tear (>50%), and complete tear. The degree of joint laxity on stress ultrasound was evaluated by measuring joint gapping after applying a 2.5-kg load to the wrist. Joint gapping was measured at 30° and 90° of elbow flexion for the dominant arm and nondominant arm, and the differences between the dominant and nondominant arms were determined. RESULTS: A higher degree of MUCL injury on MRI was associated with greater joint gapping in the medial elbow on stress ultrasound. At 30° of elbow flexion, the cutoff value for complete MUCL rupture was 0.5 mm (P < .001), with a sensitivity and specificity of 88.1% and 61.5%, respectively. At 90° of elbow flexion, the cutoff value for complete MUCL rupture was 1.0 mm (P < .001), with a sensitivity and specificity of 81.0% and 66.4%, respectively. CONCLUSION: Stress ultrasound can be used to diagnose complete MUCL tears in athletes when joint gapping is greater than 0.5 mm at 30° of elbow flexion and greater than 1 mm at 90° of elbow flexion.

Does anchor insertion angle or placement of the suture anchor affect glenoid rim fracture occurrence after arthroscopic Bankart repair?

BACKGROUND: The purposes were to compare the characteristics of 2 groups of patients who underwent revision Bankart repair with and without glenoid rim fractures and to examine risk factors for glenoid rim fractures. METHODS: We retrospectively analyzed 39 patients who needed revision surgery after arthroscopic Bankart repair and identified 19 patients with and 20 patients without glenoid rim fractures. The insertion angle of the suture anchor, anchor position on the glenoid, and demographic data were compared between the groups. RESULTS: The mean anchor insertion angles in the glenoid fracture group (group F) at the 2-, 3-, 4-, and 5-o'clock positions were 64°, 58°, 55°, and 55°, respectively; those in the no-fracture group (group R) were 60°, 63°, 60°, and 55°, respectively (P = .630, P = .207, P = .166, and P = .976, respectively). At the 5-o'clock position, anchors were fixed to the glenoid face in 13 cases in group F and in 3 cases in group R (P = .040). Although age (P = .529) and sex (P = 1.0) did not differ between the groups, elite and professional athletes had a significantly higher incidence of glenoid rim fractures (P = .009). CONCLUSION: The anchor insertion angle did not affect glenoid rim fracture occurrence after arthroscopic Bankart repair. However, the placement of the suture anchor at the 5-o'clock position on the glenoid face could increase the risk of glenoid rim fracture after trauma. Athletes were more likely to have glenoid rim fractures owing to major trauma after arthroscopic Bankart repair.

Differential gene expression profiles of human periodontal ligament cells preserved in Hank's balanced salt solution and milk.

BACKGROUND/AIM: Various types of storage media have been investigated to preserve avulsed teeth. However, the efficacies of storage media mainly focus on the aspect of cell viability. The aim of this study was to evaluate and compare the gene expression profiles of human periodontal ligament cells preserved in Hank's balanced salt solution (HBSS) and milk over different storage durations. MATERIAL AND METHODS: Human periodontal ligament cells were cultured and preserved in HBSS and milk for 3 and 6 hours. Next, total RNA was isolated. QuantSeq 3' mRNA-Sequencing was used to examine differences in gene expression in HBSS- and milk-grown periodontal ligament cells. Bioinformatics analysis was also performed to predict the function of the differentially expressed genes. RESULTS: The number of differentially expressed genes shared among all groups was 101. In gene set enrichment analysis, the shared differentially expressed genes in HBSS and milk were associated with the TNF-α signaling pathway (P = 1.07E-7 ). Seven hallmark gene sets were also identified in HBSS. Moreover, hallmark gene sets associated with hypoxia (P = 7.26E-5 ) and apoptosis (P = 4.06E-4 ) were identified in HBSS. In milk, 10 hallmark gene sets along with gene sets for inflammatory response (P = 6.87E-3 ) were identified. CONCLUSIONS: Compared to those in milk, genes in HBSS were differentially expressed with increasing storage duration, suggesting that diverse and different gene expression may be involved in HBSS and milk. However, a more detailed functional analysis of these differentially expressed genes in storage solutions should be performed in the future.

Efficacy of total hip arthroplasty after operatively treated acetabular fracture.

INTRODUCTION: We evaluated the clinical and radiological outcomes of patients following total hip arthroplasty (THA) for acetabular fracture. MATERIALS AND METHODS: This was a retrospective cohort study in a single center. The medical records of patients who underwent THA from March 2002 to March 2017 were reviewed. Inclusion criteria were THA and a history of open reduction and internal fixation of acetabular fractures. Thirty-seven patients with a mean age of 56.2 years were enrolled. The Harris hip score (HHS), acetabular fracture classification, time interval between acetabular fracture and THA, cause of THA, surgical approach, implant type, complications, radiographic results, and Kaplan-Meier survival curves were analyzed. RESULTS: All patients were followed up for an average of 6.6 years. The mean preoperative HHS of 42.5 had improved to 83.5 at the final follow-up (p < 0.05). There were 29 cases of post-traumatic arthritis, 6 cases of avascular necrosis, and 4 cases of non-union. The average interval from injury to THA was 58 months (range 4-336 months). The re-admission rate was 18.9%. Patients who underwent conversion to THA due to post-traumatic arthritis combined with non-union acetabular fracture developed clinical failure more frequently than patients with post-traumatic arthritis (p = 0.037). At 12 years, 83.4% of patients were free from revision of femoral and acetabular components. CONCLUSION: THA secondary to an operatively treated acetabular fracture provides good symptomatic relief, but shows relatively inferior survival rates, and clinical failure was related to post-traumatic arthritis with acetabular non-union.

Remote Memory and Cortical Synaptic Plasticity Require Neuronal CCCTC-Binding Factor (CTCF).

The molecular mechanism of long-term memory has been extensively studied in the context of the hippocampus-dependent recent memory examined within several days. However, months-old remote memory maintained in the cortex for long-term has not been investigated much at the molecular level yet. Various epigenetic mechanisms are known to be important for long-term memory, but how the 3D chromatin architecture and its regulator molecules contribute to neuronal plasticity and systems consolidation is still largely unknown. CCCTC-binding factor (CTCF) is an 11-zinc finger protein well known for its role as a genome architecture molecule. Male conditional knock-out mice in which CTCF is lost in excitatory neurons during adulthood showed normal recent memory in the contextual fear conditioning and spatial water maze tasks. However, they showed remarkable impairments in remote memory in both tasks. Underlying the remote memory-specific phenotypes, we observed that female CTCF conditional knock-out mice exhibit disrupted cortical LTP, but not hippocampal LTP. Similarly, we observed that CTCF deletion in inhibitory neurons caused partial impairment of remote memory. Through RNA sequencing, we observed that CTCF knockdown in cortical neuron culture caused altered expression of genes that are highly involved in cell adhesion, synaptic plasticity, and memory. These results suggest that remote memory storage in the cortex requires CTCF-mediated gene regulation in neurons, whereas recent memory formation in the hippocampus does not.SIGNIFICANCE STATEMENT CCCTC-binding factor (CTCF) is a well-known 3D genome architectural protein that regulates gene expression. Here, we use two different CTCF conditional knock-out mouse lines and reveal, for the first time, that CTCF is critically involved in the regulation of remote memory. We also show that CTCF is necessary for appropriate expression of genes, many of which we found to be involved in the learning- and memory-related processes. Our study provides behavioral and physiological evidence for the involvement of CTCF-mediated gene regulation in the remote long-term memory and elucidates our understanding of systems consolidation mechanisms.

Return to play after arthroscopic treatment for shoulder instability in elite and professional baseball players.

BACKGROUND: This study evaluated the clinical outcome of arthroscopic treatment for anterior shoulder dislocation in elite and professional baseball players. METHODS: This study included 51 baseball players who underwent arthroscopic Bankart repair between 2008 and 2015. The follow-up duration was set at 24 months or longer, based on clinic visit or telephone survey. After surgery, players who played in 1 or more official games were considered to have returned to play (RTP), and those who participated in more than 10 official games were considered to have solidly returned to play (sRTP). The RTP and sRTP rates were analyzed by player position (pitcher, catcher, and in-fielder), and the period of RTP after surgery (rehabilitation period) was investigated. RESULTS: Of 51 baseball players (mean age, 20.9 years), 14 were pitchers, 6 were catchers, and 31 were in-fielders. Pitchers showed 64% RTP and 57% sRTP, catchers, 83% RTP and 83% sRTP, and in-fielders, 90% RTP and 90% sRTP. The overall RTP and sRTP rates were 82% and 80%, respectively. The average RTP period after surgery (rehabilitation period) was 8.4 months, with 9.6, 9.1, and 7.4 months for pitchers, catchers, and in-fielders, respectively. CONCLUSIONS: The RTP after arthroscopic Bankart repair shows favorable results, with the nonthrowing shoulder and in-field position yielding the best results. Players undergoing arthroscopic Bankart repair and the surgeon should be aware of the possible outcomes based on the throwing/nonthrowing arm and various positions.

Quantitative analysis of cochlear signal intensity on three-dimensional and contrast-enhanced fluid-attenuated inversion recovery images in patients with Meniere's disease: Correlation with the pure tone audiometry test.

PURPOSE: The purpose of this study was to correlate the quantitative analysis of cochlear signal intensity (SI) on 3-dimensional fluid-attenuated inversion recovery (3D-FLAIR) and contrast-enhanced (CE) 3D-FLAIR images with results of the pure tone audiometry (PTA) test in patients with Meniere's disease (MD). MATERIALS AND METHODS: Over a 3-year period, 123 patients with MD underwent 3-Tesla (3 T) temporal magnetic resonance imaging (MRI), including 3D-FLAIR and CE-FLAIR sequences. The SI of membranous labyrinth of the cochlea in both ears of each patient was measured by drawing a region of interest (ROI) with a seed growing technique. The correlation between measured cochlear SIs on 3D-FLAIR and CE-FLAIR images, contrast enhancement index (CEI), and contrast enhancement ratio (CER) and clinical findings and pre- and post-treatment PTA results were assessed. RESULTS: Cochlear signal ratios of symptomatic ears on 3D-FLAIR and CE-FLAIR images were significantly higher than those of asymptomatic ears (P < 0.001). The area under the curve, from the receiver operating characteristic curve of cochlear SIs on 3D-FLAIR and CE-FLAIR images for discrimination between symptomatic and asymptomatic ears, was 0.729 and 0.728, respectively. Cochlear SIs on 3D-FLAIR and CE-FLAIR images were significantly correlated with patients' sex (P < 0.05 and P < 0.01, respectively), symptomatic ear (both P < 0.0001), and pre-treatment PTA (P < 0.0001 and P < 0.005, respectively), but were not significantly correlated with patients' age, post-treatment PTA or hearing threshold level at 0.5, 1.0, 2.0, or 4.0 kHz. CONCLUSION: Quantitative analysis of cochlear SI on 3D-FLAIR and CE-FLAIR images may be a helpful diagnostic adjunct for MD, but may be of little value in predicting the prognosis of MD.

Global analyses of endonucleolytic cleavage in mammals reveal expanded repertoires of cleavage-inducing small RNAs and their targets.

In mammals, small RNAs are important players in post-transcriptional gene regulation. While their roles in mRNA destabilization and translational repression are well appreciated, their involvement in endonucleolytic cleavage of target RNAs is poorly understood. Very few microRNAs are known to guide RNA cleavage. Endogenous small interfering RNAs are expected to induce target cleavage, but their target genes remain largely unknown. We report a systematic study of small RNA-mediated endonucleolytic cleavage in mouse through integrative analysis of small RNA and degradome sequencing data without imposing any bias toward known small RNAs. Hundreds of small cleavage-inducing RNAs and their cognate target genes were identified, significantly expanding the repertoire of known small RNA-guided cleavage events. Strikingly, both small RNAs and their target sites demonstrated significant overlap with retrotransposons, providing evidence for the long-standing speculation that retrotransposable elements in mRNAs are leveraged as signals for gene targeting. Furthermore, our analysis showed that the RNA cleavage pathway is also present in human cells but affecting a different repertoire of retrotransposons. These results show that small RNA-guided cleavage is more widespread than previously appreciated. Their impact on retrotransposons in non-coding regions shed light on important aspects of mammalian gene regulation.