Anatomical study and reanalysis of the nomenclature of the anterolateral complex of the knee focusing on the distal iliotibial band: identification and description of the condylar strap

Background: The capsulo-osseous layer, short lateral ligament, mid-third lateral capsular ligament, lateral capsular ligament and anterolateral ligament are terms that have been used interchangeably to describe what is probably the same structure. This has resulted in confusion regarding the anatomy and function of the anterolateral complex of the knee and its relation to the distal iliotibial band. Purpose: To characterize the macroscopic anatomy of the anterolateral complex of the knee, in particular the femoral condylar attachment of the distal iliotibial band (ITB). We identified a specific and consistent anatomical structure that was not accurately described previously, connects the deep surface of the ITB to the condylar area, and is distinct from the anterolateral ligament, the capsulo-osseous layer and the Kaplan fibers. Study Design: Descriptive laboratory study. Methods: Sixteen fresh-frozen human cadaveric knees were used to study the anterolateral complex of the knee. Standardized dissections were performed that included a qualitative and quantitative assessment of the anatomy through both anterior (n=5) and posterior (n=11) approaches. Results: The femoral condylar attachment of the distal ITB was not reliably identified by anterior dissection but was in all posterior dissections. A distinct anatomical structure, hereafter termed condylar strap (CS), was identified between the femur and the lateral gastrocnemius on one side and the deep surface of the ITB on the other, in all posteriorly dissected specimens. The structure had a mean thickness of 0.88 mm, and its femoral insertion was located between the distal Kaplan fibers and the epicondyle. The proximal femoral attachment of the structure had a mean width of 15.82 mm and the width of the distal insertion of the structure on the ITB was 13.27 mm. The mean length of the structure was 26.33 mm on its distal border and 21.88 mm on its proximal border. Qualitative evaluation of behavior in internal rotation revealed that this anatomical structure became tensioned and created a tenodesis effect on the ITB. Conclusions: There is a consistent structure that attaches to the deep ITB and the femoral epicondylar area. The orientation of fibers suggest that it may have a role in anterolateral knee stability. Clinical Relevance: This new anatomical description may help surgeons to optimize technical aspects of lateral extra-articular procedures in cases of anterolateral knee laxity

Do physical activity interventions combining self-monitoring with other components provide an additional benefit compared with self-monitoring alone? A systematic review and meta-analysis

Objective To determine the net effect of different physical activity intervention components on step counts in addition to self-monitoring. Design A systematic review with meta-analysis and meta-regression. Data sources Five databases (PubMed, Scopus, Web of Science, ProQuest and Discus) were searched from inception to May 2022. The database search was complemented with backward and forward citation searches and search of the references from relevant systematic reviews. Eligibility criteria Randomised controlled trials comparing an intervention using self-monitoring (active control arm) with an intervention comprising the same treatment PLUS any additional component (intervention arm). Data extraction and synthesis The effect measures were mean differences in daily step count. Meta-analyses were performed using random-effects models, and effect moderators were explored using univariate and multivariate meta-regression models. Results Eighty-five studies with 12 057 participants were identified, with 75 studies included in the meta-analysis at postintervention and 24 at follow-up. At postintervention, the mean difference between the intervention and active control arms was 926 steps/day (95% CI 651 to 1201). At a follow-up, the mean difference was 413 steps/day (95% CI 210 to 615). Interventions with a prescribed goal and involving human counselling, particularly via phone/video calls, were associated with a greater mean difference in the daily step count than interventions with added print materials, websites, smartphone apps or incentives. Conclusion Physical activity interventions that combine self-monitoring with other components provide an additional modest yet sustained increase in step count compared with self-monitoring alone. Some forms of counselling, particularly remote phone/video counselling, outperformed other intervention components, such as websites and smartphone apps

High-Throughput Identification of Potential Minor Histocompatibility Antigens by MHC Tetramer-Based Screening: Feasibility and Limitations

T-cell recognition of minor histocompatibility antigens (MiHA) plays an important role in the graft-versus-tumor (GVT) effect of allogeneic stem cell transplantation (allo-SCT). However, the number of MiHA identified to date remains limited, making clinical application of MiHA reactive T-cell infusion difficult. This study represents the first attempt of genome-wide prediction of MiHA, coupled to the isolation of T-cell populations that react with these antigens. In this unbiased high-throughput MiHA screen, both the possibilities and pitfalls of this approach were investigated. First, 973 polymorphic peptides expressed by hematopoietic stem cells were predicted and screened for HLA-A2 binding. Subsequently a set of 333 high affinity HLA-A2 ligands was identified and post transplantation samples from allo-SCT patients were screened for T-cell reactivity by a combination of pMHC-tetramer-based enrichment and multi-color flow cytometry. Using this approach, 71 peptide-reactive T-cell populations were generated. The isolation of a T-cell line specifically recognizing target cells expressing the MAP4K1IMA antigen demonstrates that identification of MiHA through this approach is in principle feasible. However, with the exception of the known MiHA HMHA1, none of the other T-cell populations that were generated demonstrated recognition of endogenously MiHA expressing target cells, even though recognition of peptide-loaded targets was often apparent

Heavy-light mesons in the epsilon-regime

We study the finite-size scaling of heavy-light mesons in the static limit. We compute two-point functions of chiral current densities as well as pseudoscalar densities in the epsilon-regime of heavy meson Chiral Perturbation Theory (HMChPT). As expected, finite volume dependence turns out to be significant in this regime and can be predicted in the effective theory in terms of the infinite-volume low-energy couplings. These results might be relevant for extraction of heavy-meson properties from lattice simulations.Comment: 32 pages, 4 figure

Evidence for Positive Selection on a Number of MicroRNA Regulatory Interactions during Recent Human Evolution

MicroRNA (miRNA)–mediated gene regulation is of critical functional importance in animals and is thought to be largely constrained during evolution. However, little is known regarding evolutionary changes of the miRNA network and their role in human evolution. Here we show that a number of miRNA binding sites display high levels of population differentiation in humans and thus are likely targets of local adaptation. In a subset we demonstrate that allelic differences modulate miRNA regulation in mammalian cells, including an interaction between miR-155 and TYRP1, an important melanosomal enzyme associated with human pigmentary differences. We identify alternate alleles of TYRP1 that induce or disrupt miR-155 regulation and demonstrate that these alleles are selected with different modes among human populations, causing a strong negative correlation between the frequency of miR-155 regulation of TYRP1 in human populations and their latitude of residence. We propose that local adaptation of microRNA regulation acts as a rheostat to optimize TYRP1 expression in response to differential UV radiation. Our findings illustrate the evolutionary plasticity of the microRNA regulatory network in recent human evolution

Association of Structural Magnetic Resonance Imaging Measures With Psychosis Onset in Individuals at Clinical High Risk for Developing Psychosis:An ENIGMA Working Group Mega-analysis

IMPORTANCE The ENIGMA clinical high risk (CHR) for psychosis initiative, the largest pooled neuroimaging sample of individuals at CHR to date, aims to discover robust neurobiological markers of psychosis risk.OBJECTIVE To investigate baseline structural neuroimaging differences between individuals at CHR and healthy controls as well as between participants at CHR who later developed a psychotic disorder (CHR-PS+) and those who did not (CHR-PS-).DESIGN, SETTING, AND PARTICIPANTS In this case-control study, baseline T1-weighted magnetic resonance imaging (MRI) data were pooled from 31 international sites participating in the ENIGMA Clinical High Risk for Psychosis Working Group. CHR status was assessed using the Comprehensive Assessment of At-Risk Mental States or Structured Interview for Prodromal Syndromes. MRI scans were processed using harmonized protocols and analyzed within a mega-analysis and meta-analysis framework from January to October 2020.MAIN OUTCOMES AND MEASURES Measures of regional cortical thickness (CT), surface area, and subcortical volumes were extracted from T1-weighted MRI scans. Independent variables were group (CHR group vs control group) and conversion status (CHR-PS+ group vs CHR-PS- group vs control group).RESULTS Of the 3169 included participants, 1428 (45.1%) were female, and the mean (SD; range) age was 21.1 (4.9; 9.5-39.9) years. This study included 1792 individuals at CHR and 1377 healthy controls. Using longitudinal clinical information, 253 in the CHR-PS+ group, 1234 in the CHR-PS- group, and 305 at CHR without follow-up data were identified. Compared with healthy controls, individuals at CHR exhibited widespread lower CT measures (mean [range] Cohen d = -0.13 [-0.17 to -0.09]), but not surface area or subcortical volume. Lower CT measures in the fusiform, superior temporal, and paracentral regions were associated with psychosis conversion (mean Cohen d = -0.22; 95% CI, -0.35 to 0.10). Among healthy controls, compared with those in the CHR-PS+ group, age showed a stronger negative association with left fusiform CT measures (F = 9.8; P < .001; q < .001) and left paracentral CT measures (F = 5.9; P = .005; q = .02). Effect sizes representing lower CT associated with psychosis conversion resembled patterns of CT differences observed in ENIGMA studies of schizophrenia (rho = 0.35; 95% CI, 0.12 to 0.55; P = .004) and individuals with 22q11.2 microdeletion syndrome and a psychotic disorder diagnosis (rho = 0.43; 95% CI, 0.20 to 0.61; P = .001).CONCLUSIONS AND RELEVANCE This study provides evidence for widespread subtle, lower CT measures in individuals at CHR. The pattern of CT measure differences in those in the CHR-PS+ group was similar to those reported in other large-scale investigations of psychosis. Additionally, a subset of these regions displayed abnormal age associations. Widespread disruptions in CT coupled with abnormal age associations in those at CHR may point to disruptions in postnatal brain developmental processes.Question How are brain morphometric features associated with later psychosis conversion in individuals at clinical high risk (CHR) for developing psychosis?Findings In this case-control study including 3169 participants, lower cortical thickness, but not cortical surface area or subcortical volume, was more pronounced in individuals at CHR in a manner highly consistent with thinner cortex in individuals with established psychosis. Regions that displayed lower cortical thickness in individuals at CHR who later developed a psychotic disorder additionally displayed abnormal associations with age.Meaning In this study, CHR status and later transition to psychosis was robustly associated with lower cortical thickness; abnormal age associations and specificity to cortical thickness may point to aberrant postnatal brain development in individuals at CHR, including pruning and myelination.This case-control study investigates baseline structural magnetic resonance imaging (MRI) differences between individuals at clinical high risk and healthy controls as well as between participants at clinical high risk who later developed a psychotic disorder and those who did not

Polymorphisms in the Estrogen Receptor 1 and Vitamin C and Matrix Metalloproteinase Gene Families Are Associated with Susceptibility to Lymphoma

BACKGROUND: Non-Hodgkin lymphoma (NHL) is the fifth most common cancer in the U.S. and few causes have been identified. Genetic association studies may help identify environmental risk factors and enhance our understanding of disease mechanisms. METHODOLOGY/PRINCIPAL FINDINGS: 768 coding and haplotype tagging SNPs in 146 genes were examined using Illumina GoldenGate technology in a large population-based case-control study of NHL in the San Francisco Bay Area (1,292 cases 1,375 controls are included here). Statistical analyses were restricted to HIV- participants of white non-Hispanic origin. Genes involved in steroidogenesis, immune function, cell signaling, sunlight exposure, xenobiotic metabolism/oxidative stress, energy balance, and uptake and metabolism of cholesterol, folate and vitamin C were investigated. Sixteen SNPs in eight pathways and nine haplotypes were associated with NHL after correction for multiple testing at the adjusted q<0.10 level. Eight SNPs were tested in an independent case-control study of lymphoma in Germany (494 NHL cases and 494 matched controls). Novel associations with common variants in estrogen receptor 1 (ESR1) and in the vitamin C receptor and matrix metalloproteinase gene families were observed. Four ESR1 SNPs were associated with follicular lymphoma (FL) in the U.S. study, with rs3020314 remaining associated with reduced risk of FL after multiple testing adjustments [odds ratio (OR) = 0.42, 95% confidence interval (CI) = 0.23-0.77) and replication in the German study (OR = 0.24, 95% CI = 0.06-0.94). Several SNPs and haplotypes in the matrix metalloproteinase-3 (MMP3) and MMP9 genes and in the vitamin C receptor genes, solute carrier family 23 member 1 (SLC23A1) and SLC23A2, showed associations with NHL risk. CONCLUSIONS/SIGNIFICANCE: Our findings suggest a role for estrogen, vitamin C and matrix metalloproteinases in the pathogenesis of NHL that will require further validation

Genetic linkage analysis in the age of whole-genome sequencing

For many years, linkage analysis was the primary tool used for the genetic mapping of Mendelian and complex traits with familial aggregation. Linkage analysis was largely supplanted by the wide adoption of genome-wide association studies (GWASs). However, with the recent increased use of whole-genome sequencing (WGS), linkage analysis is again emerging as an important and powerful analysis method for the identification of genes involved in disease aetiology, often in conjunction with WGS filtering approaches. Here, we review the principles of linkage analysis and provide practical guidelines for carrying out linkage studies using WGS data