Cell type-specific role of CBX2 and its disordered region in spermatogenesis.

Polycomb group (PcG) proteins maintain the repressed state of lineage-inappropriate genes and are therefore essential for embryonic development and adult tissue homeostasis. One critical function of PcG complexes is modulating chromatin structure. Canonical Polycomb repressive complex 1 (cPRC1), particularly its component CBX2, can compact chromatin and phase-separate in vitro. These activities are hypothesized to be critical for forming a repressed physical environment in cells. While much has been learned by studying these PcG activities in cell culture models, it is largely unexplored how cPRC1 regulates adult stem cells and their subsequent differentiation in living animals. Here, we show in vivo evidence of a critical nonenzymatic repressive function of cPRC1 component CBX2 in the male germline. CBX2 is up-regulated as spermatogonial stem cells differentiate and is required to repress genes that were active in stem cells. CBX2 forms condensates (similar to previously described Polycomb bodies) that colocalize with target genes bound by CBX2 in differentiating spermatogonia. Single-cell analyses of mosaic Cbx2 mutant testes show that CBX2 is specifically required to produce differentiating A1 spermatogonia. Furthermore, the region of CBX2 responsible for compaction and phase separation is needed for the long-term maintenance of male germ cells in the animal. These results emphasize that the regulation of chromatin structure by CBX2 at a specific stage of spermatogenesis is critical, which distinguishes this from a mechanism that is reliant on histone modification.

Context-specific Polycomb mechanisms in development.

Polycomb group (PcG) proteins are crucial chromatin regulators that maintain repression of lineage-inappropriate genes and are therefore required for stable cell fate. Recent advances show that PcG proteins form distinct multi-protein complexes in various cellular environments, such as in early development, adult tissue maintenance and cancer. This surprising compositional diversity provides the basis for mechanistic diversity. Understanding this complexity deepens and refines the principles of PcG complex recruitment, target-gene repression and inheritance of memory. We review how the core molecular mechanism of Polycomb complexes operates in diverse developmental settings and propose that context-dependent changes in composition and mechanism are essential for proper epigenetic regulation in development.

Phase separation of Polycomb-repressive complex 1 is governed by a charged disordered region of CBX2.

Mammalian development requires effective mechanisms to repress genes whose expression would generate inappropriately specified cells. The Polycomb-repressive complex 1 (PRC1) family complexes are central to maintaining this repression. These include a set of canonical PRC1 complexes, each of which contains four core proteins, including one from the CBX family. These complexes have been shown previously to reside in membraneless organelles called Polycomb bodies, leading to speculation that canonical PRC1 might be found in a separate phase from the rest of the nucleus. We show here that reconstituted PRC1 readily phase-separates into droplets in vitro at low concentrations and physiological salt conditions. This behavior is driven by the CBX2 subunit. Point mutations in an internal domain of Cbx2 eliminate phase separation. These same point mutations eliminate the formation of puncta in cells and have been shown previously to eliminate nucleosome compaction in vitro and generate axial patterning defects in mice. Thus, the domain of CBX2 that is important for phase separation is the same domain shown previously to be important for chromatin compaction and proper development, raising the possibility of a mechanistic or evolutionary link between these activities.

Logical regulation of endogenous gene expression using programmable, multi-input processing CRISPR guide RNAs.

The CRISPR-Cas system provides a versatile RNA-guided approach for a broad range of applications. Thanks to advances in RNA synthetic biology, the engineering of guide RNAs (gRNAs) has enabled the conditional control of the CRISPR-Cas system. However, achieving precise regulation of the CRISPR-Cas system for efficient modulation of internal metabolic processes remains challenging. In this work, we developed a robust dCas9 regulator with engineered conditional gRNAs to enable tight control of endogenous genes. Our conditional gRNAs in Escherichia coli can control gene expression upon specific interaction with trigger RNAs with a dynamic range as high as 130-fold, evaluating up to a three-input logic A OR (B AND C). The conditional gRNA-mediated targeting of endogenous metabolic genes, lacZ, malT and poxB, caused differential regulation of growth in Escherichia coli via metabolic flux control. Further, conditional gRNAs could regulate essential cytoskeleton genes, ftsZ and mreB, to control cell filamentation and division. Finally, three types of two-input logic gates could be applied for the conditional control of ftsZ regulation, resulting in morphological changes. The successful operation and application of conditional gRNAs based on programmable RNA interactions suggests that our system could be compatible with other Cas-effectors and implemented in other host organisms.

Full methylation of H3K27 by PRC2 is dispensable for initial embryoid body formation but required to maintain differentiated cell identity.

Polycomb repressive complex 2 (PRC2) catalyzes methylation of histone H3 on lysine 27 and is required for normal development of complex eukaryotes. The nature of that requirement is not clear. H3K27me3 is associated with repressed genes, but the modification is not sufficient to induce repression and, in some instances, is not required. We blocked full methylation of H3K27 with both a small molecule inhibitor, GSK343, and by introducing a point mutation into EZH2, the catalytic subunit of PRC2, in the mouse CJ7 cell line. Cells with substantively decreased H3K27 methylation differentiate into embryoid bodies, which contrasts with EZH2 null cells. PRC2 targets had varied requirements for H3K27me3, with a subset that maintained normal levels of repression in the absence of methylation. The primary cellular phenotype of blocked H3K27 methylation was an inability of altered cells to maintain a differentiated state when challenged. This phenotype was determined by H3K27 methylation in embryonic stem cells through the first 4 days of differentiation. Full H3K27 methylation therefore was not necessary for formation of differentiated cell states during embryoid body formation but was required to maintain a stable differentiated state.

Automated Comprehensive CT Assessment of the Risk of Diabetes and Associated Cardiometabolic Conditions.

Background CT performed for various clinical indications has the potential to predict cardiometabolic diseases. However, the predictive ability of individual CT parameters remains underexplored. Purpose To evaluate the ability of automated CT-derived markers to predict diabetes and associated cardiometabolic comorbidities. Materials and Methods This retrospective study included Korean adults (age ≥ 25 years) who underwent health screening with fluorine 18 fluorodeoxyglucose PET/CT between January 2012 and December 2015. Fully automated CT markers included visceral and subcutaneous fat, muscle, bone density, liver fat, all normalized to height (in meters squared), and aortic calcification. Predictive performance was assessed with area under the receiver operating characteristic curve (AUC) and Harrell C-index in the cross-sectional and survival analyses, respectively. Results The cross-sectional and cohort analyses included 32166 (mean age, 45 years ± 6 [SD], 28833 men) and 27 298 adults (mean age, 44 years ± 5 [SD], 24 820 men), respectively. Diabetes prevalence and incidence was 6% at baseline and 9% during the 7.3-year median follow-up, respectively. Visceral fat index showed the highest predictive performance for prevalent and incident diabetes, yielding AUC of 0.70 (95% CI: 0.68, 0.71) for men and 0.82 (95% CI: 0.78, 0.85) for women and C-index of 0.68 (95% CI: 0.67, 0.69) for men and 0.82 (95% CI: 0.77, 0.86) for women, respectively. Combining visceral fat, muscle area, liver fat fraction, and aortic calcification improved predictive performance, yielding C-indexes of 0.69 (95% CI: 0.68, 0.71) for men and 0.83 (95% CI: 0.78, 0.87) for women. The AUC for visceral fat index in identifying metabolic syndrome was 0.81 (95% CI: 0.80, 0.81) for men and 0.90 (95% CI: 0.88, 0.91) for women. CT-derived markers also identified US-diagnosed fatty liver, coronary artery calcium scores greater than 100, sarcopenia, and osteoporosis, with AUCs ranging from 0.80 to 0.95. Conclusion Automated multiorgan CT analysis identified individuals at high risk of diabetes and other cardiometabolic comorbidities. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Pickhardt in this issue.

Active Stratification of Colloidal Mixtures for Asymmetric Multilayers.

Stratified films offer high performance and multifunctionality, yet achieving fully stratified films remains a challenge. The layer-by-layer method, involving the sequential deposition of each layer, has been commonly utilized for stratified film fabrication. However, this approach is time-consuming, labor-intensive, and prone to leaving defects within the film. Alternatively, the self-stratification process exploiting a drying binary colloidal mixture is intensively developed recently, but it relies on strict operating conditions, typically yielding a heterogeneous interlayer. In this study, an active interfacial stratification process for creating completely stratified nanoparticle (NP) films is introduced. The technique leverages NPs with varying interfacial activity at the air-water interface. With the help of depletion pressure, the lateral compression of NP mixtures at the interface induces individual desorption of less interfacial active NPs into the subphase, while more interfacial active NPs remain at the interface. This simple compression leads to nearly perfect stratified NP films with controllability, universality, and scalability. Combined with a solvent annealing process, the active stratification process enables the fabrication of stratified films comprising a polymeric layer atop a NP layer. This work provides insightful implications for designing drug encapsulation and controlled release, as well as manufacturing transparent and flexible electrodes.

Long-term control of diabetes by tofacitinib-based immunosuppressive regimen after allo islet transplantation in diabetic rhesus monkeys that rejected previously transplanted porcine islets.

Porcine islet xenotransplantation has been highlighted as an alternative to allo islet transplantation. Despite the remarkable progress that has been made in porcine-islet pre-clinical studies in nonhuman primates, immunological tolerance to porcine islets has not been achieved to date. Therefore, allo islet transplantation could be required after the failure of porcine islet xenotransplantation. Here, we report the long-term control of diabetes by allogeneic pancreatic islet transplantation in diabetic rhesus monkeys that rejected previously transplanted porcine islets. Four diabetic male rhesus monkeys received the porcine islets and then allo islets (5700-19 000 IEQ/kg) were re-transplanted for a short or long period after the first xeno islet rejection. The recipient monkeys were treated with an immunosuppressive regimen consisting of ATG, humira, and anakinra for induction, and sirolimus and tofacitinib for maintenance therapy. The graft survival days of allo islets in these monkeys were >440, 395, >273, and 127, respectively, similar to that in allo islet transplanted cynomolgus monkeys that received the same immunosuppressive regimen without xeno sensitization. Taken together, it is likely that prior islet xenotransplantation does not affect the survival of subsequent allo islets under clinically applicable immunosuppressants.

Melatonin alleviates myocardial dysfunction through inhibition of endothelial-to-mesenchymal transition via the NF-κB pathway.

Endothelial-to-mesenchymal transition (EndMT) is a complex biological process of cellular transdifferentiation by which endothelial cells (ECs) lose their characteristics and acquire mesenchymal properties, leading to cardiovascular remodeling and complications in the adult cardiovascular diseases environment. Melatonin is involved in numerous physiological and pathological processes, including aging, and has anti-inflammatory and antioxidant activities. This molecule is an effective therapeutic candidate for preventing oxidative stress, regulating endothelial function, and maintaining the EndMT balance to provide cardiovascular protection. Although recent studies have documented improved cardiac function by melatonin, the mechanism of action of melatonin on EndMT remains unclear. The present study investigated the effects of melatonin on induced EndMT by transforming growth factor-ß2/interleukin-1ß in both in vivo and in vitro models. The results revealed that melatonin reduced the migratory ability and reactive oxygen species levels of the cells and ameliorated mitochondrial dysfunction in vitro. Our findings indicate that melatonin prevents endothelial dysfunction and inhibits EndMT by activating related pathways, including nuclear factor kappa B and Smad. We also demonstrated that this molecule plays a crucial role in restoring cardiac function by regulating the EndMT process in the ischemic myocardial condition, both in vessel organoids and myocardial infarction (MI) animal models. In conclusion, melatonin is a promising agent that attenuates EC dysfunction and ameliorates cardiac damage compromising the EndMT process after MI.

Cytokine storm syndrome after anti-thymoglobulin infusion in a cynomolgus monkey with systemic lymphadenopathy caused by follicular hyperplasia: A case report.

Nonhuman primates are widely used in transplantation research as preclinical xeno- or allo-transplantation models. Rabbit anti-thymoglobulin (ATG) is often used for T-cell depletion as an immunosuppressant. T-cell depletion can cause a secondary cytokine storm syndrome that can be minimized/prevented by a prophylactic administration of systemic corticosteroids and antihistamines. We report a case of death due to CSS in a cynomolgus monkey with follicular hyperplasia-induced systemic lymphadenopathy after ATG administration. A 6-year-old female cynomolgus monkey was rendered diabetic and then transplanted with a genetically modified porcine pancreatic islets (PPI) (50 000 IEQ/kg) through the portal vein 22 days later without immunosuppressant. Because graft function was not comparable, we planned re-transplantation of PPI. For re-transplantation of the PPI, we performed an intravenous (IV) ATG infusion for inductive immunosuppression. The monkey died 3 h and 30 min after ATG administration despite cardiopulmonary resuscitation. Systemic lymphadenopathy was observed on submandibular, axillary, inguinal, foregut, colic, and hilar lymph nodes, and splenomegaly was also observed on necropsy. Histopathologic examination of the lymph node revealed follicular hyperplasia. The IL-6 level was higher after ATG infusion compared to before ATG infusion (before vs. after ATG infusion; 14.9 vs. >5000 pg/mL). The death of the cynomolgus monkey was caused by severe CSS because of apoptosis of B cells in the systemic lymph nodes caused by the ATG administration. A thorough physical examination of palpable lymph nodes and pre-ATG sonographic or computed tomographic screening could have identified lymphadenopathy, potentially preventing its infusion and reducing mortality risk.

Preoperative medial meniscus extrusion on magnetic resonance imaging is associated with a tendency toward varus shifting of open-wedge high tibial osteotomy.

PURPOSE: To investigate serial changes in postoperative alignment over 5 years after open-wedge high tibial osteotomy (OWHTO) and to identify risk factors associated with alterations in the postoperative weight-bearing line WBL ratio. METHODS: Patients who underwent OWHTO during 2011-2017 were retrospectively reviewed. Inclusion criteria were (1) follow-up duration ≥5 years and (2) serial postoperative long-standing hip-to-ankle radiographs to evaluate alignment alterations. The WBL ratio was measured preoperatively and at 3 months, 6 months, 1 year, and 5 years postoperatively to evaluate serial changes. Alterations in the WBL ratio were analyzed using a linear mixed model, considering potential risk factors including International Cartilage Repair Society (ICRS) grades of each compartment, and medial meniscus extrusion (≥3 mm). Clinical outcomes were assessed using the Knee Society (KS) objective and functional scores, and the correlations between clinical outcomes and alignment alteration were examined. RESULTS: A total of 78 knees were investigated. During the study period, the overall WBL ratio decreased by 5.5 ± 7.2%, signifying varus shifting, from 58.6 ± 11.5% at 3 months post-surgery to 51.5 ± 12.7% at 5 years post-surgery. Based on univariate regression analyses, ICRS grade of the medial compartment and medial meniscus extrusion were included in a linear mixed model regarding alignment alteration. The model identified medial meniscus extrusion as a significant risk factor after adjusting for time (p <0.001). Medial meniscus extrusion also had a significant interaction with time (p <0.001), indicating greater alignment alteration in cases of medial meniscus extrusion. The extrusion was noted in 68 out of 78 knees. CONCLUSION: In the midterm following OWHTO, the overall alignment had a tendency toward varus shifting. A linear mixed model found that preoperative medial meniscus extrusion on magnetic resonance imaging is associated with the tendency.

Lateral Distance From the Osteotomy Hinge Point to the Tibial Cortex Is Associated With Lateral Hinge Fracture Type and Fracture Occurrence Time After Medial Open-Wedge High Tibial Osteotomy.

PURPOSE: To verify whether the distance from the hinge point to the tibial cortex affects the occurrence time and characteristics of the lateral hinge fracture (LHF) in medial open-wedge high tibial osteotomy. METHODS: We retrospectively reviewed 171 knees in 171 patients (121 women, 50 men; mean age, 53.9 years; range, 36-67 years) who had undergone medial open-wedge high tibial osteotomy with locking plate fixation between January 2011 and December 2020. Osteotomy hinge point and LHFs were identified on intraoperative fluoroscopy and immediate postoperative radiographs. LHF type was classified as suggested by Takeuchi et al. Acute fracture was defined as a fracture that occurred during surgery, and delayed fracture was defined as a fracture observed after 1 month postoperatively. The nearest distances from osteotomy hinge point to lateral, distal, and proximal cortex were measured on postoperative radiographs. We compared the distance between the different types and between acute and delayed LHFs. RESULTS: There were 55 LHFs (32%) (type I, 40 knees; type II, 14 knees; type III, 1 knee) that occurred acutely in 41 knees and were found as delayed fractures in 14 knees. The patient demographics were not significantly different between non-LHFs and each type of LHFs. Proximal and distal distances were not statistically different among fracture types and between occurrence times. However, lateral distances were significantly shorter in type I LHFs (6.2 ± 1.8 mm) and longer in type II LHFs (9.3 ± 2.3 mm) than in non-LHFs (7.1 ± 2.7 mm) (P = .020 and .004, respectively). The lateral cortical distances were also different between acute LHFs (6.4 ± 1.9 mm) and delayed LHF (9.0 ± 2.7 mm) (P < .001). In the case of fracture type, the frequency of type I decreases with increase in the lateral distance, whereas that of type II increases with increase in the lateral cortical distance. In acute fracture, type I was dominant (85.4%), whereas in delayed fracture, type II was dominant (57.2%). CONCLUSIONS: The lateral cortical distance from the hinge point was significantly associated with LHF occurrence. Shorter distance increased the risk for acute type I LHF, whereas longer distance increased the risk for delayed type II LHFs. LEVEL OF EVIDENCE: Level III, retrospective comparative prognostic trial.

Variable Return to Play and Sport Performance After Elbow Ulnar Collateral Ligament Reconstruction in Baseball Players: A Systematic Review.

PURPOSE: To evaluate return to play (RTP) and return to same level of play (RTSP) rates as well as preoperative and postoperative in-game performance metrics in baseball pitchers who underwent ulnar collateral ligament reconstruction (UCLR). Secondarily, this review sought to assess outcomes based on primary versus revision UCLR as well as level of competition. METHODS: This review was performed using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed/MEDLINE, Embase, Web of Science, and Cochrane Database of Systematic Reviews were queried to identify articles evaluating UCLR in baseball players between January 2002 and October 2022. Data included RTP, RTSP, and performance metrics including earned run average, innings pitched, walks and hits per inning pitched, batting average against, strikeouts per 9 innings, walks per 9 innings, percentage of fastballs thrown, and average fastball velocity. The Methodological Index for Non-randomized Studies criteria were used for quality assessment. RESULTS: Analysis included 25 articles reporting on 2,100 elbows. After primary UCLR, RTP ranged from 336 to 615 days (57% to 100% achieved) and RTSP ranged from 330 to 513 days (61% to 95%). After revision UCLR, RTP ranged from 381 to 631 days (67% to 98%) and RTSP ranged from 518 to 575 days (42% to 78%). When stratifying primary UCLR outcomes by competitive level, RTP and RTSP ranged respectively from 417 to 615 days (75% to 100%) and 513 days (73% to 87%) for Major League Baseball only, 409 to 615 days (57% to 100%) and 470 to 513 days (61% to 95%) for Major League Baseball plus Minor League Baseball, and 336 to 516 days (73% to 85%) and 330 days (55% to 74%) for college plus high school. Heterogeneity was seen in postoperative sports performance metrics. CONCLUSIONS: Although more than half of baseball players appear able to RTP after primary and revision UCLR, RTSP rates after revision UCLR were as low as 42% in the literature. Preoperative and postoperative performance metrics varied. LEVEL OF EVIDENCE: Level IV, systematic review of Level II-IV studies.

Effect of joint-line obliquity on long-term survivorship of total knee arthroplasty: A postoperative phenotype analysis.

PURPOSE: Whether the longevity of total knee arthroplasty (TKA) differs between postoperative phenotypes has not been investigated. This study aims to examine which phenotype has a worse long-term survival rate than the reference phenotype (neutral alignment-parallel joint line), and whether joint-line obliquity (JLO) affects the survivorship of TKA. METHODS: A total of 945 knees that underwent primary TKAs for primary osteoarthritis from January 2000 to January 2009 were included. These were classified into nine postoperative phenotypes based on the combined assessment of the hip-knee-ankle (HKA) angle and JLO, measured on standing radiographs. The 5-, 10- and 15-year survival rates were analysed using Kaplan-Meier methods and log-rank tests. The long-term survival rates of each phenotype were compared with the reference phenotype. RESULTS: There were 55 aseptic mechanical failures within a period of 10.4 ± 5.0 years. The most frequently observed phenotypes were the reference phenotype (n = 527), neutral alignment-lateral joint-line inclination (n = 162), varus alignment-lateral joint-line inclination (n = 104) and varus alignment-parallel joint line (n = 101). The overall failure rate for each phenotype was 3.6%, 3.7%, 18.3% and 7.9%, respectively. Only the 10- and 15-year survival rates of the varus alignment-lateral joint-line inclination phenotype were significantly different from those of the reference phenotype (97%-93% vs. 90%-69%; p = 0.017, <0.001). CONCLUSION: The lateral joint-line inclination phenotype had an inferior long-term survival rate after varus-aligned TKA. This suggested that alignment and JLO affected the long-term survival rate of patients who underwent TKA. LEVEL OF EVIDENCE: Level III, Retrospective cohort study.

Four-Corner Fusion Versus Proximal Row Carpectomy for Scapholunate Advanced Collapse and Scaphoid Nonunion Advanced Collapse Wrist: A Systematic Review and Meta-Analysis.

PURPOSE: Although proximal row carpectomy (PRC) has increasingly been shown to have superior features to four-corner fusion (4CF), individual surgeons may remain convinced of the superiority of one procedure based on personal experience and individual biases. Hence, we sought to perform an updated meta-analysis with some of the largest studies to date to compare outcomes and complications between these procedures in the treatment of scapholunate advanced collapse and scaphoid nonunion advanced collapse wrists. METHODS: A systematic review and meta-analysis was performed per Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed/MEDLINE, Embase, Web of Science, and Cochrane were queried for articles on PRC and 4CF performed for scapholunate advanced collapse and scaphoid nonunion advanced collapse wrist. Primary outcomes included wrist range of motion; grip strength; outcome measures, including Disabilities of Arm, Shoulder, and Hand and Quick Disabilities of Arm, Shoulder, and Hand scores, Patient-Rated Wrist and Hand Evaluation, and visual analog scale pain scores; and surgical complications. RESULTS: Sixty-one studies reported on 3,174 wrists, of which 54% were treated with PRC and 46% were treated with 4CF. The weighted mean follow-up was 61 months (range, 12-216 months). Meta-analysis comparing PRC and 4CF demonstrated that PRC had significantly greater postoperative extension; ulnar deviation; postoperative improvement in extension, flexion, ulnar deviation; and visual analog scale score. No comparisons showed significant differences in grip strength. The percentage of wrists requiring arthrodesis was 5.2% for PRC and 11% for 4CF. There was an 8.9% (57/640 wrists) 4CF nonunion rate and 2.2% (17/789) hardware removal rate after 4CF. CONCLUSIONS: In the treatment of scapholunate advanced collapse and scaphoid nonunion advanced collapse wrists, PRC results in better outcomes and a lower complication rate compared to 4CF. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Graft choice and techniques used in elbow ulnar collateral ligament reconstruction over the last 20 years: a systematic review and meta-analysis.

BACKGROUND: Elbow medial ulnar collateral ligament (mUCL) injuries have become increasingly common, leading to a higher number of mUCL reconstructions (UCLR). Various techniques and graft choices have been reported. The purpose of this study was to evaluate the prevalence of each available graft choice, the surgical techniques most utilized, and the reported complications associated with each surgical method. METHODS: A systematic review was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analysesguidelines. We queried PubMed/MEDLINE, Embase, Web of Science, and Cochrane databases to identify all articles that included UCLR between January 2002 and October 2022. We included all studies that referenced UCLR graft choice, surgical technique, and/or ulnar nerve transposition. Studies were evaluated in a narrative fashion to assess demographics and report current trends in utilization and complications of UCLR as they pertain to graft choice and surgical techniques over the past 20 years. Where possible, we stratified based on graft and technique. RESULTS: Forty-seven articles were included, reporting on 6671 elbows. The cohort was 98% male, had a weighted mean age of 21 years and follow-up of 53 months. There were 6146 UCLRs (92%) performed with an autograft and 152 (2.3%) that utilized an allograft, while 373 (5.6%) were from mixed cohorts of autograft and allograft. Palmaris longus autograft was the most utilized mUCL graft choice (64%). The most utilized surgical configuration was the figure-of-8 (68%). Specifically, the most common techniques were the modified Jobe technique (37%), followed by American Sports Medicine Institute (ASMI) (22%), and the docking (22%) technique. A concomitant ulnar nerve transposition was performed in 44% of all patients, with 1.9% of these patients experiencing persistent ulnar nerve symptoms after ulnar nerve transposition. Of the total cohort, 14% experienced postoperative ulnar neuritis with no prior preoperative ulnar nerve symptoms. Further, meta-analysis revealed a significantly greater revision rate with the use of allografts compared to autograft and mixed cohorts (2.6% vs. 1.8% and 1.9%, P = .003). CONCLUSIONS: Most surgeons performed UCLR with palmaris autograft utilizing a figure-of-8 graft configuration, specifically with the modified Jobe technique. The overall rate of allograft use was 2.3%, much lower than expected. The revision rate for UCLR with allograft appears to be greater compared to UCLR with autograft, although this may be secondary to limited allograft literature.

Clinical outcomes of two-stage revision arthroplasty using a spiked tibial cement spacer in infected total knee arthroplasty.

PURPOSE: A tibial cement spacer (TCS) with spikes offers better initial stability than a conventional TCS and reduces spacer-related problems in two-stage revision total knee arthroplasty (R-TKA) for infection. We compared the clinical outcomes of two-stage revision arthroplasty for infected TKA using spiked TCS with that of conventional TCS. METHODS: This retrospective cohort study included 29 patients who underwent two-stage revision arthroplasty using an articulating cement spacer and who could be followed up for at least one year. Group S comprised 14 patients using spiked TCS, whereas Group C comprised 15 patients using conventional TCS. Demographic data, the interval from first to second stage revision, motion arc, numerical rating scale (NRS), Knee Society (KS) score, serum levels of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), and frequency of repeating the first-stage and infection recurrence after R-TKA between the groups were analyzed. RESULTS: No significant differences were observed in the female ratio and mean age between both groups. The mean interval between the first and second stage revision was significantly shorter in Group S than in Group C. The mean motion arc was significantly larger in Group S than in Group C. The mean NRS was significantly lower in Group S than in Group C. The mean KS score in Group S was significantly higher than that in Group C. Serum ESR and CRP levels did not differ between the groups. The frequency of repeating the first stage was lower in Group S than in Group C. However, the recurrence rate after R-TKA was higher in Group S than in Group C. CONCLUSION: Compared with conventional TCS, spiked TCS shortened the period until R-TKA and improved pain and function levels. However, no significant difference existed in the rate of infection recurrence after R-TKA.

Reconstruction of Segmental Bone Defect in Canine Tibia Model Utilizing Bi-Phasic Scaffold: Pilot Study.

The reunion and restoration of large segmental bone defects pose significant clinical challenges. Conventional strategies primarily involve the combination of bone scaffolds with seeded cells and/or growth factors to regulate osteogenesis and angiogenesis. However, these therapies face inherent issues related to immunogenicity, tumorigenesis, bioactivity, and off-the-shelf transplantation. The biogenic micro-environment created by implanted bone grafts plays a crucial role in initiating the bone regeneration cascade. To address this, a highly porous bi-phasic ceramic synthetic bone graft, composed of hydroxyapatite (HA) and alumina (Al), was developed. This graft was employed to repair critical segmental defects, involving the creation of a 2 cm segmental defect in a canine tibia. The assessment of bone regeneration within the synthetic bone graft post-healing was conducted using scintigraphy, micro-CT, histology, and dynamic histomorphometry. The technique yielded pore sizes in the range of 230-430 µm as primary pores, 40-70 µm as secondary inner microchannels, and 200-400 nm as tertiary submicron surface holes. These three components are designed to mimic trabecular bone networks and to provide body fluid adsorption, diffusion, a nutritional supply, communication around the cells, and cell anchorage. The overall porosity was measured at 82.61 ± 1.28%. Both micro-CT imaging and histological analysis provided substantial evidence of robust bone formation and the successful reunion of the critical defect. Furthermore, an histology revealed the presence of vascularization within the newly formed bone area, clearly demonstrating trabecular and cortical bone formation at the 8-week mark post-implantation.

Leaf angle as a leaf and canopy trait: Rejuvenating its role in ecology with new technology.

Life on Earth depends on the conversion of solar energy to chemical energy by plants through photosynthesis. A fundamental challenge in optimizing photosynthesis is to adjust leaf angles to efficiently use the intercepted sunlight under the constraints of heat stress, water loss and competition. Despite the importance of leaf angle, until recently, we have lacked data and frameworks to describe and predict leaf angle dynamics and their impacts on leaves to the globe. We review the role of leaf angle in studies of ecophysiology, ecosystem ecology and earth system science, and highlight the essential yet understudied role of leaf angle as an ecological strategy to regulate plant carbon-water-energy nexus and to bridge leaf, canopy and earth system processes. Using two models, we show that leaf angle variations have significant impacts on not only canopy-scale photosynthesis, energy balance and water use efficiency but also light competition within the forest canopy. New techniques to measure leaf angles are emerging, opening opportunities to understand the rarely-measured intraspecific, interspecific, seasonal and interannual variations of leaf angles and their implications to plant biology and earth system science. We conclude by proposing three directions for future research.

Altered Brain Glymphatic Flow at Diffusion-Tensor MRI in Rapid Eye Movement Sleep Behavior Disorder.

Background Brain glymphatic dysfunction may contribute to the development of α-synucleinopathies. Yet, noninvasive imaging and quantification remain lacking. Purpose To examine glymphatic function of the brain in isolated rapid eye movement sleep behavior disorder (RBD) and its relevance to phenoconversion with use of diffusion-tensor imaging (DTI) analysis along the perivascular space (ALPS). Materials and Methods This prospective study included consecutive participants diagnosed with RBD, age- and sex-matched control participants, and participants with Parkinson disease (PD) who were enrolled and examined between May 2017 and April 2020. All study participants underwent 3.0-T brain MRI including DTI, susceptibility-weighted and susceptibility map-weighted imaging, and/or dopamine transporter imaging using iodine 123-2ß-carbomethoxy-3ß-(4-iodophenyl)-N-(3-fluoropropyl)-nortropane SPECT at the time of participation. Phenoconversion status to α-synucleinopathies was unknown at the time of MRI. Participants were regularly followed up and monitored for any signs of α-synucleinopathies. The ALPS index reflecting glymphatic activity was calculated by a ratio of the diffusivities along the x-axis in the projection and association neural fibers to the diffusivities perpendicular to them and compared according to the groups with use of the Kruskal-Wallis and Mann-Whitney U tests. The phenoconversion risk in participants with RBD was evaluated according to the ALPS index with use of a Cox proportional hazards model. Results Twenty participants diagnosed with RBD (12 men; median age, 73 years [IQR, 66-76 years]), 20 control participants, and 20 participants with PD were included. The median ALPS index was lower in the group with RBD versus controls (1.53 vs 1.72; P = .001) but showed no evidence of a difference compared with the group with PD (1.49; P = .68). The conversion risk decreased with an increasing ALPS index (hazard ratio, 0.57 per 0.1 increase in the ALPS index [95% CI: 0.35, 0.93]; P = .03). Conclusion DTI-ALPS in RBD demonstrated a more severe reduction of glymphatic activity in individuals with phenoconversion to α-synucleinopathies. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Filippi and Balestrino in this issue.