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Background: Osteochondritis dissecans (OCD) lesions are often observed in the humeral capitellum both in young baseball players and gymnasts. It is generally believed that capitellar OCD in baseball players can be seen on an anteroposterior (AP) radiograph with the elbow in 45° of flexion. However, the mechanism of injury seems to be different in baseball players and gymnasts. Repetitive valgus overload with the elbow in flexion is believed to be the cause of capitellar OCD lesions in baseball players, whereas weightbearing with the elbow in extension may be the cause of OCD in gymnasts. Purpose: To determine the difference in capitellar OCD location between baseball players and gymnasts and to propose the optimal AP radiographic angle of the elbow for visualization of early-stage OCD lesions in adolescent gymnasts. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Subjects consisted of 95 baseball players (95 elbows) and 21 gymnasts (24 elbows) with a mean age of 13.7 years (range, 11-18 years). To localize the lesion, inclination of the affected area in the humeral capitellum against the humeral axis was investigated using sagittal computed tomography images of the elbow. The inclination angle was defined as the angle between the long axis of the humerus and the line perpendicular to a line that connected the anterior and posterior margin of the lesion. The inclination angle in each group was compared and statistically analyzed. Results: The mean inclination angle was 57.6° ± 10.7° in baseball players and 28.0° ± 10.7° in gymnasts. Capitellar OCD lesions were located more anterior in baseball players when compared with gymnasts (P < .01). Conclusion: Due to differences in applied stress, capitellar OCD lesions in baseball players were located more anteriorly compared with those seen in gymnasts. Therefore, although AP radiographs with the elbow in 45° of flexion are optimal for detecting OCD lesions in baseball players, radiographs with less elbow flexion or full extension are more useful in gymnasts, especially in early-stage OCD.

Background:Osteochondritis dissecans (OCD) lesions are often observed in the humeral capitellum both in young baseball players and gymnasts. It is generally believed that capitellar OCD in baseball players can be seen on an anteroposterior (AP) radiograph with the elbow in 45° of flexion. However, the mechanism of injury seems to be different in baseball players and gymnasts. Repetitive valgus overload with the elbow in flexion is believed to be the cause of capitellar OCD lesions in baseball players, whereas weightbearing with the elbow in extension may be the cause of OCD in gymnasts.Purpose:To determine the difference in capitellar OCD location between baseball players and gymnasts and to propose the optimal AP radiographic angle of the elbow for visualization of early-stage OCD lesions in adolescent gymnasts.Study Design:Cross-sectional study; Level of evidence, 3.Methods:Subjects consisted of 95 baseball players (95 elbows) and 21 gymnasts (24 elbows) with a mean age of 13.7 years (range, 11-18 years). To localize the lesion, inclination of the affected area in the humeral capitellum against the humeral axis was investigated using sagittal computed tomography images of the elbow. The inclination angle was defined as the angle between the long axis of the humerus and the line perpendicular to a line that connected the anterior and posterior margin of the lesion. The inclination angle in each group was compared and statistically analyzed.Results:The mean inclination angle was 57.6° ± 10.7° in baseball players and 28.0° ± 10.7° in gymnasts. Capitellar OCD lesions were located more anterior in baseball players when compared with gymnasts (P < .01).Conclusion:Due to differences in applied stress, capitellar OCD lesions in baseball players were located more anteriorly compared with those seen in gymnasts. Therefore, although AP radiographs with the elbow in 45° of flexion are optimal for detecting OCD lesions in baseball players, radiographs with less elbow flexion or full extension are more useful in gymnasts, especially in early-stage OCD.

An intronic silencer, S4 , in the Cd4 gene has been shown to be responsible for the helper-lineage-specific expression of CD4; S4 requires Runx complex binding to exert its silencer function against the enhancer-mediated Cd4 activation by modulating the epigenetic state of the Cd4 gene. Here we identify a late-acting maturation enhancer. Bcl11b plays essential roles for activation of both the early-acting proximal enhancer and maturation enhancer of Cd4 . Notably, Runx complexes suppress these enhancers by distinct mechanisms. Whereas repression of the proximal enhancer depends on the S4 silencer, the maturation enhancer is repressed by Runx in the absence of S4 . Moreover, ThPOK, known to antagonize S4 -mediated Cd4 repression, assists Runx complexes to restrain maturation enhancer activation. Distinct modes of S4 silencer action upon distinct enhancers thus unravel a pathway that restricts CD4 expression to helper-lineage cells by silencer-independent and Runx-dependent repression of maturation enhancer activity in cytotoxic-lineage cells. The commitment of helper and cytotoxic lineages for CD4 and CD8 T cells, respectively, is associated with the regulation of Cd4 gene expression. Here the authors show that an intronic silencer, S4 , has differential effects and synergy with the RUNX complex to act on two enhancer elements of the CD4 gene to control T cell lineage commitment in the thymus.

Postoperative sarcopenia is associated with poor outcomes in hospitalized patients. However, few studies have focused on short-term postoperative sarcopenia. Furthermore, the influence of nutritional management using amino acids (AAs) comprising a peripheral parenteral nutrition (PPN) solution and its combination with exercise (Exc) is unclear. Hence, we established a postoperative sarcopenic rat model to evaluate the effects of parenteral AA infusion combined with Exc on skeletal muscles and investigate the underlying mechanisms involved in the amelioration of muscle atrophy. Male F344 rats underwent surgery followed by hindlimb suspension (HS) for 5 days. The rats were divided into AA (−), AA (+), AA (−)-Exc, and AA (+)-Exc groups. They were continuously administered a PPN solution with or without AA at 98 kcal/kg/day. The Exc groups were subjected to intermittent loading for 1 h per day. Postoperative sarcopenic rats exhibited decreased muscle strength and mass and an upregulated ubiquitin–proteasome system, autophagy–lysosome system, and fast-twitch fiber-related genes, especially in the AA (−) group. The AA (+)-Exc group exhibited attenuated decreased muscle strength, increased gastrocnemius mass, and a suppressed upregulation of muscle atrophy- and fast-twitch fiber-related genes. Therefore, parenteral AA infusion combined with Exc may be effective in preventing postoperative sarcopenia in hospitalized patients.

Background and aimEsophageal stenosis is a serious complication after endoscopic submucosal dissection (ESD) for thoracic esophageal cancer (TEC), and steroid has been applied for stenosis prevention. However, the rate of stenosis and effect of steroid for ESD of cervical esophageal cancer (CEC) remain unknown. The aim was to clarify the rate and managements of post-ESD stenosis for CEC.MethodsA total of 325 lesions with 272 patients who underwent ESD for esophageal cancers were enrolled and were divided to the CEC group (43 lesions) or the TEC group (282 lesions). Patient characteristics, clinicopathological features, procedure-related outcomes of esophageal ESD, stenosis rate and clinical outcome of steroid use cases were evaluated.ResultsMore patients in the CEC group received preventive steroid treatment compared to the TEC group (37.2% vs 14.5%, P = 0.001). The rate of post-ESD stenosis tended to be higher in the CEC group (11.6%) than in the TEC group (6.7%). For cases of 3/4 ≤ of circumference, local injection with oral steroid had lower stenosis rate than local injection only in both groups (CEC 40% vs 100%, TEC 30.7% vs 56.3%). More sessions and longer duration of dilation were needed to release the stenosis in the CEC group (20 times vs. 5 times, P = 0.015; 196 days vs. 55 days, P = 0.043).ConclusionThe post-ESD stenosis rate of CEC tended to be higher than that of TEC. More intensive preventive measures for post-ESD stenosis may be needed for CEC than TEC.

T-lineage committed precursor thymocytes are screened by a fate-determination process mediated via T cell receptor (TCR) signals for differentiation into distinct lineages. However, it remains unclear whether any antecedent event is required to couple TCR signals with the transcriptional program governing lineage decisions. Here we show that Bcl11b, known as a T-lineage commitment factor, is essential for proper expression of ThPOK and Runx3, central regulators for the CD4-helper/CD8-cytotoxic lineage choice. Loss of Bcl11b results in random expression of these factors and, thereby, lineage scrambling that is disconnected from TCR restriction by MHC. Initial Thpok repression by Bcl11b prior to the pre-selection stage is independent of a known silencer for Thpok , and requires the last zinc-finger motif in Bcl11b protein, which by contrast is dispensable for T-lineage commitment. Collectively, our findings shed new light on the function of Bcl11b in priming lineage-specifying genes to integrate TCR signals into subsequent transcriptional regulatory mechanisms. CD4 and CD8 T cells develop in the thymus with their transcription programs controlled by ThPOK and Runx3, respectively. Here the authors show that a pre-commitment event modulated by the transcription factor, Bcl11b, is required for the proper expression of ThPOK and Runx3 and correct CD4/CD8 lineage commitment.

Because neutrophil extracellular trap (NET) formation is involved in the pathology of a wide variety of diseases, NET-regulating compounds are expected to be useful for the therapies of these diseases. In this study, we identified sulfasalazine (SSZ) as a potent enhancer of NET formation both in vitro and in vivo . Although SSZ did not increase the amount of ROS generated, it accelerated the generation of ether-linked oxidized phospholipids, such as PE (18;1e/15-HETE) and PC (16;0e/13-HODE). Trolox, but not 2-ME, effectively suppressed lipid oxidation and NET formation that were induced by SSZ. SSZ is known as a potent inducer of ferroptosis in cancer cells by inhibiting xCT, a component of the cystine transporter. However, we found that SSZ accelerated NET formation in an xCT-independent manner. Structure-activity relationship studies revealed that the sulfapyridine moiety of SSZ plays a central role in enhancing NET formation. Furthermore, we found that two additional sulfonamide and sulfone derivatives possess NET-inducing activity by accelerating lipid oxidation. These results indicate that the hyperoxidation of ether-linked phospholipids is a key mechanism for accelerating NET formation.

How to select optimal cord blood (CB) remains an important clinical question. We developed and validated an index of CB engraftment, the cord blood index (CBI), which uses three weighted variables representing cell doses and HLA mismatches. We modeled the neutrophil engraftment time with competing events by random survival forests for competing risks as a function of the predictors: total nucleated cells, CD34, colony-forming units for granulocytes/macrophages, and the number of HLA mismatches at the antigen and allele levels. The CBI defined three groups that had different neutrophil engraftment rates at day 30 (High, 83.7% [95% CI, 79.2–88.1%]; Intermediate, 77.0% [95% CI, 73.7–80.2%]; Low, 68.4% [95% CI, 63.6–73.2%]), platelet engraftment rates at day 60 (High, 70.4% [95% CI, 64.9–75.9%]; Intermediate, 62.3% [95% CI, 58.5–66.0%]; Low, 49.3% [95% CI, 44.2–54.5%]), and non-relapse mortality at day 100 (High, 14.1% [95% CI, 9.9–18.3%]; Intermediate, 16.4% [95% CI, 13.5–19.3%]; Low, 21.3% [95% CI, 17.1–25.5%]). This novel approach is clinically beneficial and can be adopted immediately because it uses easily obtained pre-freeze data of CB.

Introduction: Eosinophils in the esophageal epithelium are unevenly distributed in eosinophilic esophagitis (EoE). Esophageal eosinophilia (EE) may be observable by endocytoscopy (EC). This study aimed to evaluate the diagnostic performance of EC for the diagnosis of EE. Methods: A total of 33 EoE patients underwent EC with methylene blue staining from March 2020 to April 2021. A total of 194 EC images with corresponding biopsies were obtained. Three findings of EC, increased squamous cells (item I), increased inflammatory cells (item II), and cells with bilobed nuclei (item III), were established. These findings were reviewed by two endoscopists to diagnose EE. Another four endoscopists reviewed the images for interobserver agreement. Results: When all three items were met by EC, the sensitivity and the accuracy for the diagnosis of EE were 88% and 76%, respectively. The integrated diagnostic odds ratios (ORs) for the diagnosis of EE of the four endoscopists were significant (OR: 3.98, 95% CI: 2.94–5.40, p < 0.001). The results were similar when only item III was met. Interobserver agreement was good for item III to diagnose EE (kappa value = 0.653). Discussion/Conclusion: The diagnostic performance of EC for EE is acceptable and has good interobserver agreement. It may be useful for targeted biopsy in EoE patients.

Background and aimsMultiple biopsies are recommended for the diagnosis of eosinophilic esophagitis (EoE) because inflammatory changes are frequently patchy. Reports on EoE using endocytoscopy (ECS) are limited. This present study aimed to assess if diagnostic yield improves by adding ECS on conventional white light imaging (WLI) in patients with esophageal eosinophilia (EE).MethodsA total of 284 biopsy specimens from 71 patients with a known diagnosis of EE were enrolled and divided into the WLI group (156 specimens) or the ECS group (128 specimens). Four biopsies from 5 and 10 cm proximal to the esophagogastric junction were taken from each patient. In the ECS group, the biopsy was performed where bilobed nuclei were observed. The biopsy sensitivity for EE, eosinophil count of a single specimen and the biopsy sensitivity of each endoscopic finding were evaluated between both groups.ResultsThe sensitivity of a single biopsy specimen was higher in the ECS group than that of the WLI group (62.5 vs. 41.7%, P < 0.001). In addition, the median eosinophil count in the ECS group was significantly higher [19 vs. 6.5/high-power field (HPF), P < 0.001]. For each endoscopic finding, ECS-based biopsy had higher sensitivity than that of WLI in the diagnosis of edema (33.1 vs. 11.3%, P = 0.007) and linear furrows (75.8 vs. 52%, P = 0.005).ConclusionThis study showed that adding ECS to WLI improved the biopsy sensitivity and eosinophil detection in patients with EE.