Limitations of fluorescent timer protein maturation kinetics to isolate transcriptionally synchronized human neural progenitor cells.

Differentiation of human pluripotent stem cells (hPSCs) into subtype-specific neurons holds substantial potential for disease modeling in vitro. For successful differentiation, a detailed understanding of the transcriptional networks regulating cell fate decisions is critical. The heterochronic nature of neurodevelopment, during which distinct cells in the brain and during in vitro differentiation acquire their fates in an unsynchronized manner, hinders pooled transcriptional comparisons. One approach is to "translate" chronologic time into linear developmental and maturational time. Simple binary promotor-driven fluorescent proteins (FPs) to pool similar cells are unable to achieve this goal, due to asynchronous promotor onset in individual cells. We tested five fluorescent timer (FT) molecules expressed from the endogenous paired box 6 (PAX6) promoter in 293T and human hPSCs. Each of these FT systems faithfully reported chronologic time in 293T cells, but none of the FT constructs followed the same fluorescence kinetics in human neural progenitor cells.

Clinical and Radiological Outcomes of Meniscal Repair Versus Partial Meniscectomy for Medial Meniscus Root Tears: A Systematic Review and Meta-analysis.

BACKGROUND: Given the superiority of meniscal repair over partial meniscectomy according to biomechanical data, the clinical outcomes of meniscal repair are likely to be better than those of partial meniscectomy for a medial meniscus root tear (MMRT). PURPOSE/HYPOTHESIS: This review was designed to compare the clinical and radiological results between meniscal repair and partial meniscectomy for MMRTs. It was hypothesized that meniscal repair would result in better clinical and radiological results compared with partial meniscectomy. STUDY DESIGN: Systematic review; Level of evidence, 4. METHODS: Studies were included in the review if they (1) included patients with MMRTs who underwent primary arthroscopic meniscal repair or partial meniscectomy and (2) analyzed validated patient-reported outcomes and/or radiological evaluations. Summary odds ratios (ORs) with 95% CIs were calculated to compare partial meniscectomy with meniscal repair for each outcome. RESULTS: A total of 13 studies were included. The mean duration of follow-up was 33.5 and 47.2 months in the meniscal repair group and partial meniscectomy group, respectively. The change in the Lysholm score from preoperatively to postoperatively was statistically significantly in favor of meniscal repair (OR, 2.20 [95% CI, 1.55-3.12]), while no difference was found with respect to the change in the Tegner score between the 2 surgical approaches (OR, 1.21 [95% CI, 0.65-2.24]). The prevalence of postoperative severe knee osteoarthritis (OR, 0.31 [95% CI, 0.17-0.54]) as well as that of reoperations (OR, 0.05 [95% CI, 0.01-0.19]) were significantly in favor of meniscal repair. CONCLUSION: Better outcomes were seen after meniscal repair compared with partial meniscectomy for MMRTs, with greater improvements in Lysholm scores, and lower rates of progression to knee osteoarthritis, and lower reoperation rate.

Clinical and Radiological Outcomes After Autologous Matrix-Induced Chondrogenesis Versus Microfracture of the Knee: A Systematic Review and Meta-analysis With a Minimum 2-Year Follow-up.

BACKGROUND: Microfracture (MFx) is the most common procedure for treating chondral lesions in the knee; however, initial improvements decline after 2 years. Autologous matrix-induced chondrogenesis (AMIC) may overcome this shortcoming by combining MFx with collagen scaffolds. However, the outcomes of AMIC and MFx in the knee have not been compared. PURPOSE: To compare the clinical and radiological outcomes of AMIC and MFx over a minimum 2-year follow-up. STUDY DESIGN: Systematic review; Level of evidence, 4. METHODS: A systematic search of the MEDLINE, Embase, and Cochrane Library databases identified studies of patients who underwent AMIC or MFx and that reported validated clinical outcome measure and/or radiological evaluation findings at a follow-up of ≥2 years. There were 2 reviewers who performed study selection, a risk of bias assessment, and data extraction. RESULTS: Overall, 29 studies were included in this systematic review. The mean improvement on the Lysholm score, Tegner activity scale, and visual analog scale for pain did not differ significantly between the 2 procedures. The mean improvement on the International Knee Documentation Committee (IKDC) subjective score was significantly greater in the AMIC (45.9 [95% CI, 36.2-55.5]) than in the MFx (27.2 [95% CI, 23.3-31.1]) group (P < .001). In addition, the mean magnetic resonance observation of cartilage repair tissue score was significantly higher in the AMIC (69.3 [95% CI, 55.1-83.5]) versus MFx (41.0 [95% CI, 27.3-54.7]) group (P = .005), and the mean adequate defect filling rate on magnetic resonance imaging scans was significantly better in the AMIC (77.3% [95% CI, 66.7%-87.9%]) versus MFx (47.9% [95% CI, 29.2%-66.6%]) group (P = .008) (odds ratio, 1.58 [95% CI, 1.07-2.33]). CONCLUSION: No significant differences in clinical outcomes, except for the IKDC subjective score, were found between the AMIC and MFx groups. Greater improvement in IKDC subjective scores and magnetic resonance imaging findings were seen in patients treated with AMIC compared with MFx at a minimum 2-year follow-up.

Microstructural Evolution of Al-Zn-Mg-Cu Alloys in Accordance with Homogenization Time.

The microstructural evolution of Al-Zn-Mg-Cu alloys has been investigated for the homogenization time effect on the texture, grain orientation and dislocation density. The Al-Zn-Mg-Cu alloys were casted and homogenized for 4, 8, 16 and 24 hours. Electron backscatter diffraction (EBSD) analysis was conducted to characterize the microstructural behavior. Micropillars were fabricated using focused ion beam (FIB) milling in grains of specific crystallographic orientations. Coarse precipitations in the grain boundaries are S (Al2CuMg) and T (Al2Mg3Zn3) phases verified by scanning electron microscopy-energy dispersive spectroscopy (SEM-EDS) observation. With increasing homogenization time, equiaxed cell sizes increased. The volume fraction of S and T phases decreased with the diffusion of atomic elements into matrix. The Vickers hardness and tensile strength values decreased with homogenization temperature. The micropillar compression analysis was compared to macro tensile test results to understand the size effect and strain burst phenomenon on the mechanical properties of Al-Zn-Mg-Cu alloys.

Well-Defined Dual Light- and Thermo-Responsive Rod-Coil Block Copolymers Containing an Azobenzene, MEO2MA and OEGMA.

Here we report the dual light- and thermo-responsive behavior of well-defined rod-coil block copolymers composed of an azobenzene unit, 2-(2-methoxyethoxy)ethyl methacrylate (MEO2MA) and oligo(ethylene glycol) methacrylate (OEGMA). Azobenzene-containing rigid rod blocks prepared by chain growth condensation polymerization of the azobenzene containing monomer were used as a macroinitiator of atom transfer radical polymerization (ATRP) after attaching an α-bromoisobutyryl group as an end group. Synthesis of well-defined rod-coil block copolymers with different coil block lengths was achieved by copolymerization of MEO2MA and OEGMA monomers. The synthesized polymers exhibited amphiphilic properties and polymeric micelles were formed in aqueous solution. The light-responsive behaviors of azobenzene moieties, photoisomerization by irradiation of light, and thermo-responsive behaviors of P(MEO2MA-co-OEGMA) coil blocks, aggregation by increment of temperature over lower critical solution temperature, were investigated. A dual stimuli-responsive behavior of the rod-coil block copolymers was observed when exposed to light and heat.

Gradual change in knee extension following total knee arthroplasty using ultracongruent inserts.

BACKGROUND: Total knee arthroplasty (TKA) using an ultracongruent (UC) insert is widely performed. Lack of the posterior cruciate ligament or post-cam mechanism is a concern in terms of range of motion. The flexion angle of UC TKA had been well investigated; however, natural history and correlation factors of the postoperative extension angle have not been well documented. This study aimed to investigate time-dependent changes in extension after TKA using UC inserts, and to evaluate factors that correlated with the postoperative extension angle. METHODS: This study reviewed 388 gap-balanced UC TKAs (331 patients) without hyperextension at navigation and performed between November 2010 and December 2014. The extension angle (a positive number indicates hyperextension) was measured on full-extension lateral radiographs. The extension angles from five days post-operation to final follow-up were investigated. Factors correlated with the postoperative extension angle were evaluated using multiple regression analysis. RESULTS: Mean follow-up duration was 46.2 months. Until two years, the extension angle gradually increased; mean angles at five days/six months/one year/two years/and final follow-up were: -9.2°/-2.6°/0.6°/1.0°/1.0°, respectively. Female sex (ß = -0.15, P = 0.002) and pre-operative hyperextension (ß = 0.31, P < 0.001) were associated with postoperative hyperextension deformity. CONCLUSIONS: Following UC TKA, knees became gradually more extended until two years post-operation. Sex and pre-operative extension angle were predictive factors for the postoperative extension angle following UC TKA. LEVEL OF EVIDENCE: Level 4, Case series.

Introducing a Spectrum of Long-Range Genomic Deletions in Human Embryonic Stem Cells Using Type I CRISPR-Cas.

CRISPR-Cas systems enable microbial adaptive immunity and provide eukaryotic genome editing tools. These tools employ a single effector enzyme of type II or V CRISPR to generate RNA-guided, precise genome breaks. Here we demonstrate the feasibility of using type I CRISPR-Cas to effectively introduce a spectrum of long-range chromosomal deletions with a single RNA guide in human embryonic stem cells and HAP1 cells. Type I CRISPR systems rely on the multi-subunit ribonucleoprotein (RNP) complex Cascade to identify DNA targets and on the helicase-nuclease enzyme Cas3 to degrade DNA processively. With RNP delivery of T. fusca Cascade and Cas3, we obtained 13%-60% editing efficiency. Long-range PCR-based and high-throughput-sequencing-based lesion analyses reveal that a variety of deletions, ranging from a few hundred base pairs to 100 kilobases, are created upstream of the target site. These results highlight the potential utility of type I CRISPR-Cas for long-range genome manipulations and deletion screens in eukaryotes.

Patellar Redislocation Rates and Clinical Outcomes After Medial Patellofemoral Ligament Reconstruction: Suture Anchor Versus Double Transpatellar Tunnel Fixation.

BACKGROUND: Few studies to date have compared clinical outcomes in patients who have undergone medial patellofemoral ligament (MPFL) reconstruction using the suture anchor and double transpatellar tunnel fixation methods. This meta-analysis therefore compared the clinical results, including the patellar redislocation rate and improvement in functional scores, of suture anchor and double transpatellar tunnel fixation. HYPOTHESIS: The recurrence rate and improvement in functional outcomes after surgery would be similar using the suture anchor and double transpatellar tunnel fixation methods. STUDY DESIGN: Meta-analysis. METHODS: Studies evaluating MPFL reconstruction using either the suture anchor or double transpatellar tunnel technique for patellar site fixation were included if they reported the patellar redislocation rate after surgery and/or validated patient-reported outcomes such as the Kujala and Lysholm scores. RESULTS: Twenty-one studies were included in this meta-analysis. The mean patellar redislocation rates were similar using the suture anchor (3.2% [95% CI, 1.6%-6.2%]) and double transpatellar tunnel (3.4% [95% CI, 2.1%-5.4%]) techniques ( P = .879). The mean improvement in the Kujala score from before to after MPFL reconstruction was greater using the suture anchor (37.2 [95% CI, 31.1-43.4]) method than the double transpatellar tunnel method (28.7 [95% CI, 21.2-36.1]) ( P = .018). However, the mean improvement in the Lysholm score did not differ significantly using the 2 techniques. CONCLUSION: The patellar redislocation rate did not differ significantly in patients who underwent MPFL reconstruction using the suture anchor and double transpatellar tunnel fixation methods. The suture anchor fixation method, however, resulted in a greater degree of improvement in patient-reported outcomes.

Interpersonal Violence and Maxillofacial Fractures.

PURPOSE: Accident Compensation Corporation statistics shows that maxillofacial fracture affects 11,000 people with an approximate $90 million annual cost in New Zealand dollars (NZD). Previous studies have demonstrated interpersonal violence (IPV), road traffic accidents (RTAs), sports injury, and falls being the common causes of maxillofacial fracture. This study investigated the causes and associated alcohol and/or drug use and fracture patterns in patients presenting with maxillofacial fractures in the Wellington region. SUBJECTS AND METHODS: Demographic data of the patients, the cause of maxillofacial fracture and associated alcohol and/or drug use, and the fracture patterns were culled from our prospective maxillofacial fracture database at Hutt Hospital for a 5-year period from January 01, 2013, to December 31, 2017 and analyzed. RESULTS: A total of 1535 patients were referred with maxillofacial fractures during the study. 38% of the maxillofacial fractures were caused by IPV, followed by sports injury (24%), falls (24%), and RTA (6%), with 33.4% associated with alcohol and/or drug use. Males were six times more likely to present with IPV-related maxillofacial fractures, compared to females. The 16-30-year age group was the most prevalent in the IPV group with NZ Maori attributing to significantly more maxillofacial fractures compared to NZ European, 54.6% vs. 32.0% (P < 0.0001). CONCLUSIONS: IPV, especially involving alcohol and/or drug use, is the most common cause of maxillofacial fractures in the Wellington region, especially in NZ Maori males aged 16-30 years. Public health strategies are needed to decrease IPV as a cause of maxillofacial fractures.

Comparative postural stability in patients with lateral meniscus versus medial meniscus tears.

BACKGROUND: Types of mechanoreceptors may differ between the medial and lateral menisci, suggesting that postural stability may differ between patients with medial and lateral meniscus tears. However, to date, postural stability has not been compared in patients with medial and lateral meniscus tears. This study used stabilometry to compare postural stability in patients with medial and lateral meniscus tears. METHODS: Postural stability and thigh muscle strength were assessed in 24 patients with medial and 18 patients with lateral meniscus tears. Postural stability was determined by measuring the anteroposterior (APSI), mediolateral (MLSI), and overall (OSI) stability indices using stabilometry. Maximal torque (60°/s) of the quadriceps and hamstring was evaluated using an isokinetic testing device. RESULTS: The three stability indices, OSI, APSI, and MLSI, in both involved and uninvolved knees were all significantly greater in patients with lateral than with medial meniscus tears. (P<0.001 for all OSI, APSI, and MLSI in both involved and uninvolved knees, except for P=0.005 for MLSI of involved knees). In patients with medial meniscus tears, both OSI (1.4±0.4 vs. 1.1±0.4, P=0.037) and MLSI (0.9±0.3 vs. 0.8±0.3, P=0.041) were significantly higher on the injured than the uninjured side. In patients with lateral meniscus tears, none of the stability indices differed significantly between injured and uninjured knee joints. CONCLUSION: Postural stability of both the injured and uninjured knee joints was poorer in patients with lateral than with medial meniscus tears.

Bearing Dislocation and Progression of Osteoarthritis After Mobile-bearing Unicompartmental Knee Arthroplasty Vary Between Asian and Western Patients: A Meta-analysis.

BACKGROUND: Implant survivorship is reported to be lower and complications, particularly bearing dislocation, are reported to be more frequent in Asian than in Western patients with medial knee osteoarthritis (OA) undergoing Oxford® Phase III unicompartmental knee arthroplasty (UKA). To date, however, these complications have not been compared between these groups of patients. QUESTIONS/PURPOSES: The purpose of this study was to perform a meta-analysis comparing the standardized incidence rates of (1) all-cause reoperation; (2) reoperation related to bearing dislocation; and (3) reoperation related to progression of lateral compartment arthritis in Asian and Western patients with medial knee OA who underwent Oxford Phase III UKA. METHODS: We searched MEDLINE® (January 1, 1976, to May 31, 2017), EMBASE® (January 1, 1985, to May 31, 2017), and the Cochrane Library (January 1, 1987, to May 31, 2017) for studies that reported complications of Oxford Phase III UKAs. Studies were included if they reported reoperation rates attributable to bearing dislocation and/or progression of lateral knee OA after surgery with this implant. Twenty-seven studies were included in this systematic review and 16 studies with followups > 5 years were included in the meta-analysis. These rates were converted to standardized incidence rate (that is, reoperations per 100 observed component years) based on mean followup and number of involved knees in each study. After applying prespecified inclusion and exclusion criteria, the studies were categorized into two groups, Asian and Western, based on hospital location. Twenty-five studies, containing 3152 Asian patients and 5455 Western patients, were evaluated. Study quality was assessed by the modified Coleman Methodology score (MCMS). Although all studies were Level IV, their mean MCMS score was 66.92 (SD, 8.7; 95% confidence interval [CI], 63.5-70.3), indicating fair quality. Because the heterogeneity of all subgroup meta-analyses was high, a random-effects model was used with estimations using the restricted maximum likelihood method. RESULTS: There was no difference in the proportion of Asian patients versus Western patients undergoing reoperation for any cause calculated as 100 component observed years (1.022 of 3152 Asian patients; 95% CI, 0.810-1.235 versus 1.300 of 5455 Western patients; 95% CI, 1.067-1.534; odds ratio, 0.7839; 95% CI, 0.5323-1.1545; p = 0.178). The mean reoperation rate attributable to bearing dislocation per 100 observed years was higher in Asian than in Western patients (0.525; 95% CI, 0.407-0.643 versus 0.141; 95% CI, 0.116-0.166; odds ratio, 3.7378; 95% CI, 1.694-8.248; p = 0.001) Conversely, the mean reoperation rate attributable to lateral knee OA per 100 observed years was lower in Asian than in Western patients (0.093; 95% CI, 0.070-0.115 versus 0.298; 95% CI, 0.217-0.379; odds ratio, 0.3114; 95% CI, 0.0986-0.9840; p < 0.001). CONCLUSIONS: Although total reoperation rates did not differ in the two populations, reoperation for bearing dislocation was more likely to occur in Asian than in Western patients, whereas reoperation for lateral knee OA progression was more likely to occur in Western than in Asian patients after Oxford Phase III UKA. Although possible explanations for these findings may be hypothesized, additional randomized, prospective comparative studies are needed. However, better survival outcomes after UKA may require consideration of ethnicity and lifestyle choices in addition to traditional surgical technique and perioperative care. LEVEL OF EVIDENCE: Level III, therapeutic study.

Delocalized Plastic Flow in Proton-Irradiated Monolithic Metallic Glasses.

Creating new materials with novel properties through structural modification is the Holy Grail of materials science. The range of targetable structures for amplification of mechanical properties in metallic glasses would include types of atomic short range orders at the smallest scale through compositions or morphologies of phases in composites. Even though the usefulness of the latter approach has been successfully demonstrated in the past decades, the feasibility of the former has been incompletely proved with only marginal property improvements reported within experimentally-accessible atomic-level structural changes. Here, we report the significant enhancement of deformability in Zr-based monolithic metallic glass only through the atomic disordering by proton irradiation without altering any other structural traits. Metallic glass nanopillars that originally failed catastrophically without any notable plasticity become capable of attaining more than 30% uniaxial plastic strain accommodated by homogeneous deformation when irradiated to ~1 displacement per atom (DPA). We discuss the atomistic origin of this improved plasticity in terms of density and spatial distributions of icosahedral short range order influenced by irradiation.

Clinical and radiologic results of arthroscopic biceps tenodesis with suture anchor in the setting of rotator cuff tear.

BACKGROUND: The purpose of this study was to report clinical and radiologic results of arthroscopic biceps tenodesis with 1 suture anchor in rotator cuff tear patients. METHODS: During a 2-year period, 84 consecutive patients (45 men; 39 women) who underwent arthroscopic tenodesis were evaluated retrospectively. Mean age was 58 years. The primary indication for surgery was rotator cuff tear in 96.4%. Tenodesis was performed with 1 suture anchor placed in the bicipital groove with 2 knots, 1 lasso-type and 1 that pierced the tendon. At final follow-up at a mean of 33.2 months, visual analog scale pain (pain-VAS) score, shoulder scores (American Shoulder and Elbow Surgeons [ASES] and Constant score), Popeye deformity (PD), anterior arm pain, and elbow flexion power were evaluated. Postoperative magnetic resonance images were evaluated in 60 patients to determine the integrity of the tenodesis and the location of the suture anchor. RESULTS: The average pain-VAS decreased from 5.3 to 1.4 (P < .001). ASES and Constant scores significantly increased, from 42.9 and 56.2 to 85.2 and 82.5, respectively. PD occurred in 11 patients (12.9%), and 2 (2.3%) had self-consciousness; however, no patients complained about the deformity and the PD did not correlate with poorer clinical scores. Six patients (7.1%) complained of anterior cramping pain. Elbow flexion power was similar compared with the contralateral side. In postoperative magnetic resonance imagine analysis, 15 patients (25%) showed distal migration of tenodesed biceps tendon, although only 6 (7.1%) had clinical PD. Postoperative clinical outcomes were not influenced by the location of the suture anchor within the bicipital groove. CONCLUSIONS: Arthroscopic biceps tenodesis with 1 suture anchor resulted in good clinical outcomes at 2 years postoperatively. PD was seen in 12.9% of the patients.

Photoinduced reversible transmittance modulation of rod-coil type diblock copolymers containing azobenzene in the main chain.

Photoinduced reversible transmittance modulation was achieved with the self-assembled block copolymer micelles. A large conformational change of the well-defined rod-coil diblock copolymers containing azobenzene and ether groups in the main chain of the rod block induced a remarkable macroscopic change which can be observed with the naked eye.