Factors associated with immunological non-response after ART initiation: a retrospective observational cohort study.

BACKGROUND: Among people living with HIV (PLHIV) on antiretroviral therapy (ART), the mortality of immunological non-responders (INRs) is higher than that of immunological responders (IRs). However, factors associated with immunological non-response following ART are not well documented. METHODS: We obtained data for HIV patients from the National Free Antiretroviral Treatment Program database in China. Patients were grouped into IRs (CD4 cell count ≥ 350 cells/µl after 24 months' treatment), immunological incomplete responders (ICRs) (200-350 cells/µl) and INRs (< 200 cells/µl). Multivariable logistic regression was used to assess factors associated with immunological non-response. RESULTS: A total of 3900 PLHIV were included, among whom 2309 (59.2%) were IRs, 1206 (30.9%) ICRs and 385 (9.9%) INRs. In multivariable analysis, immunological non-response was associated with being male (2.07, 1.39-3.09), older age [40-49 years (vs. 18-29 years): 2.05, 1.29-3.25; 50-59 years: 4.04, 2.33-7.00; ≥ 60 years: 5.51, 2.84-10.67], HBV co-infection (1.63, 1.14-2.34), HCV co-infection (2.01, 1.01-4.02), lower CD4 + T cell count [50-200 cells/µl (vs. 200-350 cells/µl): 40.20, 16.83-96.01; < 50 cells/µl: 215.67, 85.62-543.26] and lower CD4/CD8 ratio (2.93, 1.98-4.34) at baseline. Compared with patients treated with non-nucleoside reverse transcriptase inhibitors (NNRTIs) based regimens, those receiving protease inhibitors (PIs) based regimens were less likely to be INRs (0.47, 0.26-0.82). CONCLUSIONS: We found a sizable immunological non-response rate among HIV-infected patients. Being male, older age, coinfection with HBV and HCV, lower CD4 + T cell count and lower CD4/CD8 ratio are risk factors of immunological non-response, whereas PIs-based regimens is a protective factor.

A new technique to implant intracorneal ring-segments from the perilimbal region: one-year prospective pilot study report.

BACKGROUND: Recently a new surgical technique for intracorneal ring-segments (ICRS) assisted by femtosecond laser (FSL) called ByLimB was developed, involving the creation of the incision from a paralimbic region. This study aims to evaluate the safety and efficacy of the ByLimb technique following one year of follow-up. METHODS: A prospective, single-center study was conducted at the Zaldivar Institute in Buenos Aires, Argentina. Keratoconus patients with indication for ICRS-FSL assisted procedure, operated with the ByLimb technique were included. By using the ByLimb technique, the ICRS are placed without affecting the tunnel's roof, and the end of the ICRS is always away from the incision area. Visual acuity, topographic astigmatism, and the occurrence of complications were evaluated. Safety index was the main outcome and efficacy indes was a complimentary outcome. RESULTS: A total of 17 eyes completed the 12-month follow-up period. The safety index was 1.10 (mean postoperative corrected distance visual acuity (CDVA) in decimal: 0.76/preoperative CDVA: 0.69), while the efficacy index was 0.89 (mean postoperative uncorrected distance visual acuity UDVA in decimal: 0.62/preoperative CDVA: 0.69). Mean preoperative astigmatism was 5.3 ± 2.3, decreasing twelve months after surgery at 2.1 ± 1.2 (p < 0.001). No eye loss lines of vision and no intraoperative complications were observed. During the first month after surgery, an improper positioning of the ICRS based on topographic assessment was detected in five cases. A second procedure was performed, which consisted of opening the incision and introducing a Sinsky hook, through which the ICRS was mobilized and placed in its correct position. No incisional alterations, signs of infection, anterior segment anomalies, or fundus alterations were observed. CONCLUSION: FSL-assisted ICRS implantation through the perilimbal region has demonstrated an adequate safety index one year post-surgery. Additionally, this technique has facilitated accurate realignment of ICRS during secondary surgical interventions within one-month post-surgery. While the current findings are promising, continued follow-up of these cases is warranted.

Late-onset distal-apical intracorneal ring-segments keratopathy: an analysis of a large sample in a multicenter study.

PURPOSE: To review the prevalence and describe the characteristics, of cases with late-onset intracorneal ring segments (ICRS) keratopathy in a multicenter study. METHODS: A retrospective multicentric case-series study was performed in a specialized keratoconus service, from Buenos Aires, Argentina. An electronic clinical chart from patients with ICRS keratopathy between January 1999 and January 2019 was reviewed. We included cases with late-onset distal-apical ICRS keratopathy, which was defined as a persistent corneal lesion developed 12 months or later after implantation, located over, around, or closer to the ICRS. All the surgeries were performed by a manual corneal tunnel creation technique. Samples were taken to rule out infectious etiology. RESULTS: From 5217 eyes that underwent ICRS implantation, 13 cases (0.24%) were detected. The keratopathy onset was 72 ± 42.98 months (29-133) after ICRS implantation. Cultures were negative in all cases. An ICRS exchange was made for five cases in stage I and four in stage II. Four cases presented with partial ICRS extrusion in stage III. ICRS exchange was possible in two of them and a penetration keratoplasty was necessary for the rest. All cases remained stable 1 year after surgical procedures. CONCLUSIONS: A late-onset distal-apical ICRS keratopathy was detected with low prevalence (0.24%) in a large sample. It was classified into three stages according to its severity. Different treatments were selected for each stage, obtaining stable results 1 year after treatment.

Arthroscopic evaluation after osteochondral autogenous transfer with osteotomy of medial malleolus for osteochondral lesion of the talar dome.

BACKGROUND: The purpose of this study was to investigate the second-look arthroscopic evaluation after osteochondral autogenous transfer (OAT) for osteochondral lesion of the talar dome (OLT) with the criteria of the International Cartilage Repair Society (ICRS). METHODS: Ten patients (twelve ankles) with OLT underwent OAT with osteotomy of the medial malleolus. Clinical outcomes were evaluated using the American Orthopedic Foot & Ankle Society (AOFAS) ankle-hindfoot scale. The condition of the transplanted cartilage was evaluated at the time of second-look arthroscopy using the ICRS Cartilage Repair Assessment. RESULTS: The AOFAS ankle-hindfoot scale was significantly improved from 65.1 ± 1.9 points before surgery to 98.1 ± 2.8 points at the time of second-look arthroscopy (p < 0.01). The ICRS Cartilage Repair Assessment was 11.4 points on average (9-12 points). CONCLUSIONS: The OAT for OLT is considered to be a useful treatment even if invasion by medial malleolus osteotomy is added. LEVEL OF EVIDENCE: Level IV, Case series.

Femtosecond Lasers in Cornea & Refractive Surgery.

Since the introduction of femtosecond laser (FS) systems for corneal flap creation in laser-assisted in-situ keratomileusis there have been numerous applications for FS laser in corneal surgery. This manuscript details the utility of FS lasers in corneal surgical procedures including refractive laser surgeries, intracorneal ring segment tunnels, presbyopic treatments, and FS-assisted keratoplasty. We also review the role of FS lasers in diagnostic procedures such as two photon excitation fluorescence and second harmonic generation.

Visual, refractive and topographic outcomes of progressive thickness intrastromal corneal ring segments for keratoconic eyes.

PURPOSE: To evaluate one-year visual, refractive, and topographic outcomes of 58 eyes of 53 keratoconus patients who underwent surgery with a progressive thickness intrastromal corneal ring segment (ICRS). METHODS: This multi-center, retrospective, observational study evaluates the one-year effects of progressive thickness ICRS implanted in keratoconus patients meeting the inclusion criteria. One or two progressive ICRS were implanted in the selected eyes after creating an intrastromal tunnel with a femtosecond laser. Pre- and postoperative uncorrected distance visual acuity, best-corrected distance visual acuity, manifest refraction (both spherical equivalent and cylindrical refractions), corneal astigmatism, maximum keratometry, corneal thickness, and corneal topography measurements and indices were evaluated. RESULTS: In this retrospective case series, 58 eyes of 53 keratoconus patients were included with a follow-up of 12 months. The mean age was 30.89 ± 11.90 years. There were improvements postoperatively in mean values of visual acuities, both uncorrected from 0.71 (preoperatively) to 0.28 (log MAR), and best-corrected from 0.28 to 0.10 (log MAR), mean cylindrical refraction from - 2.35 ± 1.51 to - 4.15 ± 2.23 D, and mean spherical equivalent from - 2.10 ± 2.25 to - 4.64 ± 3.2 D. There was also a reduction in maximal keratometry from 54.21 D preoperatively to 50.93 D postoperatively. CONCLUSION: The implantation of the progressive thickness ICRS is an effective and safe method to improve the vision of keratoconic eyes. Corneal stability was maintained at the 12-month mark.

[Methods of surgical treatment of keratectasia and analysis of postsurgical quality of vision]. / Metody khirurgicheskogo lecheniya keratektazii i analiz posleoperatsionnogo kachestva zreniya.

Keratectasias are non-inflammatory dystrophic diseases of the cornea characterized by progressive bilateral thinning of the cornea that lead to deterioration in the quantitative and qualitative characteristics of vision reducing patient's quality of life. The changes can be asymmetrical and destructive. A number of surgeries have been proposed to reduce the negative effects of keratectasia including penetrating keratoplasty and its modifications, implantation of corneal ring segments, corneal cross-linking - alone and in combination with other methods, intrastromal keratoplasty. These methods can improve visual acuity to a certain degree and help slow the progression of keratectasia. This article studies various surgical methods used for treating keratectasia and analyses possible assessment of the quality of vision before and after the treatment.

Iterative cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy for colorectal peritoneal metastases: A multi-institutional experience.

BACKGROUND AND OBJECTIVES: The aims of this multi-institutional study were to assess the feasibility of iterative cytoreductive surgery (iCRS)/hyperthermic intraperitoneal chemotherapy, iCRS in colorectal peritoneal carcinomatosis (CRPC), evaluate survival, recurrence, morbidity and mortality outcomes, and identify prognostic factors for overall survival. METHODS: Patients with CRPC that underwent an iCRS, with or without intraperitoneal chemotherapy, from June 1993 to July 2016 at 13 institutions were retrospectively analyzed from prospectively maintained databases. RESULTS: The study comprised of 231 patients, including 126 females (54.5%) with a mean age at iCRS of 51.3 years. The iterative high-grade (3/4) morbidity and mortality rates were 23.4% and 1.7%, respectively. The median recurrence-free survival was 15.0 and 10.1 months after initial and iCRS, respectively. The median and 5-year survivals were 49.1 months and 43% and 26.4 months and 26% from the initial and iCRS, respectively. Independent negative predictors of survival from the initial CRS included peritoneal carcinomatosis index (PCI) > 20 ( P = 0.02) and lymph node positivity ( P = 0.04), and from iCRS, PCI > 10 ( P = 0.03 for PCI 11-20; P < 0.001 for PCI > 20), high-grade complications ( P = 0.012), and incomplete cytoreduction ( P < 0.001). CONCLUSION: iCRS can provide long-term survival benefits to highly selected colorectal peritoneal carcinomatosis patients with comparable mortality and morbidity rates to the initial CRS procedure. Careful patient selection is necessary to improve overall outcomes.

Loss of methylation of H19-imprinted gene derived from assisted reproductive technologies can be mitigated by cleavage-stage embryo transfer in mice.

PURPOSE: Studies on rodents have shown that assisted reproductive technologies (ARTs) are associated with perturbation of genomic imprinting in blastocyst-stage embryos. However, the vulnerable developmental window for ART influence on the genomic imprinting of embryos is still undetermined. The purpose of this study was to establish the specific embryonic development stage at which the loss of methylation of H19 imprinting control regions (ICRs) was caused by ART occurrence. Additionally, we explored protocols to safeguard against possible negative impacts of ART on embryo H19 imprinting. METHODS: Mouse embryos were generated under four different experimental conditions, divided into four groups: control, in vitro culture (IVC), in vitro fertilization (IVF), and intracytoplasmic sperm injection (ICSI). The methylation levels of H19 ICR of the grouped or individual embryos were analyzed by bisulfite-sequencing PCR. RESULTS: Our data showed that the loss of methylation of H19 ICR in mouse blastocysts was inflicted to a similar extent by IVC, IVF, and ICSI. Specifically, we observed a significant loss of methylation of H19 ICR between the mouse 8-cell and morula stages. In addition, we revealed that the transfer of mouse embryos generated by ARTs in the uterus at the 8-cell stage induced the occurrence of methylation patterns in the blastocysts closer to the in vivo ones. CONCLUSIONS: Our findings indicate that the loss of methylation of H19 ICR caused by ARTs occurs between the 8-cell and the morula stages, and the transfer of cleavage embryos to the uterus mitigates the loss methylation of H19 derived by mice ARTs.

Long-term results of closed-wedge osteotomy of the lateral humeral condyle for osteochondritis dissecans of the capitellum.

BACKGROUND: Various surgical methods are used for osteochondritis dissecans of the capitellum; however, we have consistently performed a closed-wedge osteotomy of the lateral humeral condyle since 1983. The purpose of this study is to clarify the long-term results of closed-wedge osteotomy for osteochondritis dissecans of the capitellum. METHODS: Seventy-seven elbows with all lesion types of osteochondritis dissecans of the capitellum were treated with closed-wedge osteotomy. Unstable osteochondral fragments were fixed with a bone graft and bone pegs in combination with osteotomy. The mean age of the patients was 14.0 years. The patients were clinically and radiographically evaluated at a median value of 9.0 years after surgery. RESULTS: The range of elbow motion and standard deviation were increased significantly from 119° ± 22° preoperatively to 131° ± 18° postoperatively (P < .001). The Timmerman and Andrews score were improved significantly from 141 ± 26 points preoperatively to 184 ± 21 points postoperatively (P < .001). The Timmerman and Andrews score and the range of elbow motion at final examination in patients with preoperative osteoarthritic changes were significantly inferior to those in patients without preoperative osteoarthritic changes. Good remodeling of the capitellar lesions was radiographically observed in 53 elbows (69%). In the long-term follow-up evaluation, although 41 elbows (53%) had advanced osteoarthritic changes that were classified as grade II or III, disease progression was controlled in most of these cases. CONCLUSIONS: Good or excellent long-term clinical results were maintained in most of our patients. Closed-wedge osteotomy of the lateral humeral condyle is a useful method that can provide acceptable long-term clinical results.

Hip morphology influences the pattern of articular cartilage damage.

PURPOSE: The aim of this study was to obtain data on chondral damage and compare the damage patterns of various hip disorders. METHODS: Data were collected at 100 consecutive arthroscopies, and chondral lesions were recorded on anatomic articular maps divided into different anatomical zones. This geographic zone method made it possible to analyze the ICRS grade and location in relation to the hip morphology. RESULTS: The distribution and degree of the chondral defects showed a hip morphology-specific pattern. On the acetabular side, there were high incidences of full-thickness defects in the anterior-superior zone and the middle superior zone in patients with femoroacetabular impingement (FAI) (zone 2: 25.4 % grade 3, 35.5 % grade 4; zone 3: 20.3 % grade 3, 37.2 % grade 4) and borderline dysplasia (zone 2: 31.2 % grade 3, 12.5 % grade 4; zone 3: 18.7 % grade 3, 25 % grade 4). However, in patients with joint laxity, partial-thickness defects were dominant (zone 2: 50 % grade 1, 15 % grade 2; zone 3: 40 % grade 1). In patients with acetabular dysplasia, full-thickness defects extended even to the posterior superior zone (zone 4: 80 % grade 4). On the femoral head side, the incidence of full-thickness cartilage injuries was high in patients with FAI and borderline dysplasia compared to those with joint laxity and acetabular dysplasia. CONCLUSION: Evaluation of chondral damage using the geographic zone method showed that the pattern of cartilage damage was influenced by hip morphology. Understanding of hip disorder-specific chondral damage patterns may be useful for the development of arthroscopic classification of hip disorders and may lead to the establishment of treatment guidelines. LEVEL OF EVIDENCE: Diagnostic study, Level III.

Pan-cancer analysis of immune checkpoint receptors and ligands in various cells in the tumor immune microenvironment.

Drugs that target immune checkpoint have become the most popular weapon in cancer immunotherapy, yet only have practical benefits for a small percentage of patients. Tumor cells constantly interact with their microenvironment, which is made up of a variety of immune cells as well as endothelial cells and fibroblasts. Immune checkpoint expression and blocked signaling of immune cells in the tumor microenvironment (TME) are key to tumor progression. In this study, we perform deliberation convolution on the TCGA database for human lung, breast, and colorectal cancer to infer crosstalk between immune checkpoint receptors (ICRs) and ligands (ICLs) in TME of pan-carcinogenic solid tumor types, validated by flow cytometry. Analysis of immune checkpoints showed that there was little variation between different tumor types. It showed that CD160, LAG3, TIGIT were found to be highly expressed in CD8+ T cells instead of CD4+ T cells, PD-L1, PD-L2, CD86, LGALS9, TNFRSF14, LILRB4 and other ligands were highly expressed on macrophages, FVR, NECTIN2, FGL1 were highly expressed on Epithelial cells, CD200 was highly expressed in Endothelial cells, and CD80 was highly expressed in CD8 High expression on T cells. Overall, our study provides a new resource for the expression of immune checkpoints in TME on various types of cells. Significance: This study provides immune checkpoint expression of immune cells of multiple cancer types to infer immune mechanisms in the tumor microenvironment and provide ideas for the development of new immune checkpoint-blocking drugs.

Long-Term Follow-Up of a 150° Arc-Length Intrastromal Corneal Ring Segment Implantation in Post-LASIK Ectasia.

PURPOSE: To evaluate the outcomes of implanting a 150° arc-length intrastromal corneal ring segment (ICRS) using a femtosecond laser in patients with post-LASIK ectasia throughout a 5-year follow-up period. METHODS: This study enrolled 45 eyes of 45 patients diagnosed with post-LASIK ectasia who underwent a 150° arc-length Ferrara-type ICRS implantation. The uncorrected (UDVA) and corrected (CDVA) distance visual acuities, residual refractive errors, and root mean square (RMS) for coma-like aberration were evaluated preoperatively and at 6-, 12-, 36, and 60 months postoperatively. RESULTS: Mean UDVA (logMAR) ameliorated from 0.53 ± 0.33 preoperatively to 0.26 ± 0.24 at 6 months postoperatively (p < 0.0001). Mean CDVA improved from 0.12 ± 0.13 to 0.04 ± 0.06 (p < 0.0001). Mean UDVA and CDVA remained stable throughout the 5-year follow-up (p > 0.1). No eyes lost lines of CDVA at any follow-up visit compared to preoperatively, and most eyes gained lines. The eyes with a refractive cylinder ≤ 2.00 D varied from 26.7% preoperatively to more than 75% at all postoperative follow-up visits. The maximum keratometry was significantly flattened (p < 0.0001), and the RMS for corneal coma-like aberration was halved (p < 0.0001). 93.3% of the eyes did not show signs of disease progression or regression of the visual or refractive outcomes at any follow-up visits. CONCLUSION: These results suggest that implanting a single 150° arc-length Ferrara-type ICRS is a safe, effective and stable procedure for visual restoration in post-LASIK ectasia. In very few cases, visual and/or refractive instability was experienced throughout the follow-up.

Intracorneal ring segment implantation in advanced Keratoconus.

PURPOSE: To compare the clinical outcomes of intracorneal ring segment (ICRS) implantation in eyes with advanced vs. mild/moderate keratoconus (KCN). METHODS: A retrospective analysis of 141 eyes of 111 patients with KCN who underwent ICRS implantation. Preoperative maximum keratometry (Kmax) was <57 diopters (D) in 70 eyes and >57 D in 71 eyes. Postoperatively, corrected distance visual acuity (CDVA), Kmax, and intraoperative and postoperative complications were assessed at 1 day, 1 month, and 1 year. RESULTS: Corneas with a preoperative Kmax >57 D experienced greater reduction in axial curvature after ICRS implantation than corneas with a preoperative Kmax <57 D (7.0 D vs. 5.5 D, p=0.005) and gained more Snellen lines of CDVA (3 vs. 1, p<0.001) by 1 year postoperatively. The incidences of the most prevalent complications (explantation, extrusion, and infectious keratitis) did not differ significantly between the two groups (p=0.29, p=0.99, p=0.98). CONCLUSIONS: The visual and topographic effects of ICRS implantation are greater in eyes with more advanced KCN, with no increase in the incidence of the most common complications.

ByLimb: Development of a New Technique to Implant Intracorneal Ring-Segments from the Perilimbal Region.

A new technique that allows implanting intracorneal ring-segments (ICRS) from the limbal zone is described. Using a femtosecond laser (FSL), a 360° corneal tunnel is created with an internal diameter of 5.4 mm and an external diameter of 7.0 mm, with a wider area (0.2 mm inner and 0.2 mm outer) in the upper 60° of the tunnel (called landing zone). Next, a 4.36 mm-long corneal-limbal incision was created with the FSL, which connects to the bubbles created in the landing zone. The entire procedure was performed using intraoperative optical coherence tomography (OCT). Once the two incisions were connected using blunt-edged Mac Pherson forceps, the bubbles were released from the surgical plane. The programmed ICRS(s), 6 mm in diameter, are then placed in the corneal tunnel from the limbal incision with the aid of Sinskey forceps. Finally, when the ICRS is in place, the surgery is complete.

A Multi-Disciplinary MRI Assessment May Optimize the Evaluation of Chondral Lesions in Acute Ankle Fractures: A Prospective Study.

Chondral lesions (CL) in the ankle following acute fractures are frequently overlooked immediately after the injury or diagnosed at a later stage, leading to persistent symptoms despite successful surgery. The literature presents a wide range of discrepancies in the reported incidence of CLs in acute ankle fractures. The objective of this prospective study is to provide a precise assessment of the occurrence of chondral lesions (CLs) in acute ankle fractures through MRI scans conducted immediately after the trauma and prior to scheduled surgery. Furthermore, the study aims to highlight the disparities in the interpretation of these MRI scans, particularly concerning the size and extent of chondral damage, between radiologists and orthopedic surgeons. Over the period of three years, all patients presenting with an unstable ankle fracture that underwent operative treatment were consecutively included in this single-center prospective study. Preoperative MRIs were obtained for all included patients within 10 days of the trauma and were evaluated by a trauma surgeon and a radiologist specialized in musculoskeletal MRI blinded to each other's results. The location of the lesions was documented, as well as their size and ICRS classification. Correlations and kappa coefficients as well as the p-values were calculated. A total of 65 patients were included, with a mean age of 41 years. The evaluation of the orthopedic surgeon showed CLs in 52.3% of patients. CLs occurred mainly on the tibial articular surface (70.6%). Most talar lesions were located laterally (11.2%). The observed CLs were mainly ICRS grade 4. According to the radiologist, 69.2% of the patients presented with CLs. The most common location was the talar dome (48.9%), especially laterally. Most detected CLs were graded ICRS 3a. The correlation between the two observers was weak/fair regarding the detection and classification of CLs and moderate regarding the size of the detected CLs. To enhance the planning of surgical treatment for ankle chondral lesions (CLs), it may be beneficial to conduct an interdisciplinary preoperative assessment of the performed scans. This collaborative approach can optimize the evaluation of ankle CLs and improve overall treatment strategies.

Arthroscopic Electromechanical Assessment of Human Articular Cartilage Injury Correlates with ICRS Scores.

PURPOSE: This study aimed to conduct arthroscopic evaluation of cartilage electromechanical properties and establish their correlation with International Cartilage Repair Society (ICRS) grading scores. METHODS: In 18 patients, quantitative parameter (QP) measurements were taken on the weight-bearing surface of the medial femoral condyle. Adjacently, the same site was graded using ICRS scores (0-4). Electromechanical QPs for ICRS grades 0 to 3 were obtained during arthroscopy, while complete grade 4 injuries were assessed using femur cartilage-bone blocks from knee arthroplasty. The QP values for ICRS grades 0 to 2 were compared with grades 3 and 4 using Welch t test. The corresponding QP values were assigned to ICRS grades 0 to 4 and compared using Welch ANOVA (analysis of variance). Pearson's coefficient evaluated QP-ICRS grade relationship. RESULTS: Healthy grade 0 cartilage displayed a mean QP value of 10.5 (±2.8 SD, n = 4). The ICRS grade 1 and grade 2 injuries were associated with QP values of 12 (±0.7, n = 2) and 13.25 (±1.77, n = 2), respectively. The grade 3 defects had QP values of 20.43 (±4.84, n = 4), whereas complete grade 4 defects showed electromechanical values of 30.17 (±2.19, n = 6). Significant differences in QP values were observed between ICRS grades 0 to 2 (mean QP 11.56 ± 2.3, n = 8) and grades 3 and 4 (26.27 ± 6, n = 10; P < 0.0001). Pearson's correlation coefficient of 0.9 indicated a strong association between higher ICRS cartilage injury grades and elevated QP values (P < 0.0001). CONCLUSION: Arthroscopic electromechanical QP assessment robustly correlates with ICRS scores. The QP values for ICRS grades 0 to 2 are significantly lower, compared with grades 3 and 4.

Genomic analysis of a new heterotic maize group reveals key loci for pedigree breeding.

Genome-wide analyses of maize populations have clarified the genetic basis of crop domestication and improvement. However, limited information is available on how breeding improvement reshaped the genome in the process of the formation of heterotic groups. In this study, we identified a new heterotic group (X group) based on an examination of 512 Chinese maize inbred lines. The X group was clearly distinct from the other non-H&L groups, implying that X × HIL is a new heterotic pattern. We selected the core inbred lines for an analysis of yield-related traits. Almost all yield-related traits were better in the X lines than those in the parental lines, indicating that the primary genetic improvement in the X group during breeding was yield-related traits. We generated whole-genome sequences of these lines with an average coverage of 17.35× to explore genome changes further. We analyzed the identity-by-descent (IBD) segments transferred from the two parents to the X lines and identified 29 and 28 IBD conserved regions (ICRs) from the parents PH4CV and PH6WC, respectively, accounting for 28.8% and 12.8% of the genome. We also identified 103, 89, and 131 selective sweeps (SSWs) using methods that involved the π, Tajima's D, and CLR values, respectively. Notably, 96.13% of the ICRs co-localized with SSWs, indicating that SSW signals concentrated in ICRs. We identified 171 annotated genes associated with yield-related traits in maize both in ICRs and SSWs. To identify the genetic factors associated with yield improvement, we conducted QTL mapping for 240 lines from a DH population (PH4CV × PH6WC, which are the parents of X1132X) for ten key yield-related traits and identified a total of 55 QTLs. Furthermore, we detected three QTL clusters both in ICRs and SSWs. Based on the genetic evidence, we finally identified three key genes contributing to yield improvement in breeding the X group. These findings reveal key loci and genes targeted during pedigree breeding and provide new insights for future genomic breeding.

Grading cartilage damage with diffuse reflectance spectroscopy: Optical markers and mechanical properties.

Osteoarthritis (OA) is one of the most common joint diseases worldwide. Unfortunately, clinical methods lack the ability to detect OA in the early stages. Timely detection of the knee joint degradation at the level of tissue changes can prevent its progressive damage. Here, diffuse reflectance spectroscopy (DRS) in the NIR range was used to obtain optical markers of the cartilage damage grades and to assess its mechanical properties. It was observed that the water content obtained by DRS strongly correlates with the cartilage thickness (R = .82) and viscoelastic relaxation time (R = .7). Moreover, the spectral parameters, including water content (OH-band), protein content (CH-band), and scattering parameters allowed for discrimination between the cartilage damage grades (10-4 < P ≤ 10-3 ). The developed approach may become a valuable addition to arthroscopy, helping to identify lesions at the microscopic level in the early stages of OA and complement the surgical analysis.

Asymmetric intracorneal ring segments in the treatment of snowman phenotype keratoconus.

OBJECTIVE: To evaluate refractive, aberrometric, topographic, and topometric outcomes of asymmetric intracorneal ring segment (ICRS) implantation in snowman phenotype (asymmetric bow-tie) keratoconus. METHODS: This retrospective, interventional study included eyes with snowman phenotype keratoconus. Two asymmetric ICRSs (Keraring AS) were implanted after femtosecond laser-assisted tunnel formation. Visual, refractive, aberrometric, topographic, and topometric changes after asymmetric ICRS implantation were evaluated with a mean follow-up of 11 months (6-24 months). MAIN RESULTS: Seventy-one eyes were analyzed in the study. Keraring AS implantation corrected refractive errors significantly. The mean spherical error decreased from -5.06±4.23 D to -1.62±3.45 D (P=0.001), and the mean cylindrical error decreased from -5.43±2.48 D to -2.44±1.49 D (P=0.001). Uncorrected distance visual acuity improved from 0.98±0.80 to 0.46±0.46 Log MAR (P=0.001), and corrected distance visual acuity improved from 0.58±0.56 to 0.17±0.39 Log MAR (P=0.001). Keratometry (K) maximum, K1, K2, K mean, astigmatism, and corneal asphericity (Q-value) showed a significant decrease (P=0.001). Vertical coma aberration decreased significantly from -3.31±2.12µm to -2.56±1.94µm (P=0.001). All topometric indices of corneal irregularities were significantly reduced postoperatively (P=0.001). CONCLUSIONS: Keraring AS implantation in snowman phenotype keratoconus demonstrated good efficacy and safety. Clinical, topographic, topometric, and aberrometric parameters improved significantly after Keraring AS implantation.