RESUMEN
Insects have about 50 neuropeptide genes and about 70 genes, coding for neuropeptide G protein-coupled receptors (GPCRs). An important, but small family of evolutionarily related insect neuropeptides consists of adipokinetic hormone (AKH), corazonin, and AKH/corazonin-related peptide (ACP). Normally, insects have one specific GPCR for each of these neuropeptides. The tick Ixodes scapularis is not an insect, but belongs to the subphylum Chelicerata, which comprises ticks, scorpions, mites, spiders, and horseshoe crabs. Many of the neuropeptides and neuropeptide GPCRs occurring in insects, also occur in chelicerates, illustrating that insects and chelicerates are evolutionarily closely related. The tick I. scapularis is an ectoparasite and health risk for humans, because it infects its human host with dangerous pathogens during a blood meal. Understanding the biology of ticks will help researchers to prevent tick-borne diseases. By annotating the I. scapularis genome sequence, we previously found that ticks contain as many as five genes, coding for presumed ACP receptors. In the current paper, we cloned these receptors and expressed each of them in Chinese Hamster Ovary (CHO) cells. Each expressed receptor was activated by nanomolar concentrations of ACP, demonstrating that all five receptors were functional ACP receptors. Phylogenetic tree analyses showed that the cloned tick ACP receptors were mostly related to insect ACP receptors and, next, to insect AKH receptors, suggesting that ACP receptor genes and AKH receptor genes originated by gene duplications from a common ancestor. Similar duplications have probably occurred for the ligand genes, during a process of ligand/receptor co-evolution. Interestingly, chelicerates, in contrast to all other arthropods, do not have AKH or AKH receptor genes. Therefore, the ancestor of chelicerates might have lost AKH and AKH receptor genes and functionally replaced them by ACP and ACP receptor genes. For the small family of AKH, ACP, and corazonin receptors and their ligands, gene losses and gene gains occur frequently between the various ecdysozoan clades. Tardigrades, for example, which are well known for their survival in extreme environments, have as many as ten corazonin receptor genes and six corazonin peptide genes, while insects only have one of each, or none.
Asunto(s)
Hormonas de Insectos , Ixodes , Neuropéptidos , Oligopéptidos , Ácido Pirrolidona Carboxílico , Receptores Acoplados a Proteínas G , Animales , Neuropéptidos/metabolismo , Neuropéptidos/genética , Hormonas de Insectos/metabolismo , Hormonas de Insectos/genética , Ixodes/metabolismo , Ixodes/genética , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/genética , Oligopéptidos/metabolismo , Oligopéptidos/genética , Oligopéptidos/química , Ácido Pirrolidona Carboxílico/análogos & derivados , Ácido Pirrolidona Carboxílico/metabolismo , Filogenia , Secuencia de Aminoácidos , Cricetulus , Células CHO , Proteínas de Insectos/genética , Proteínas de Insectos/metabolismo , Receptores de Neuropéptido/metabolismo , Receptores de Neuropéptido/genéticaRESUMEN
OBJECTIVES: Patellar tendon injuries occur via various mechanisms such as overuse, or due to surgical graft harvest for anterior cruciate ligament reconstruction (ACLR). Quantified patellar tendon stiffness after injury may help guide clinical care. Continuous shear wave elastography (cSWE) allows for the assessment of viscosity and shear modulus in tendons. The reliability of the measure, however, has not been established in the patellar tendon. The purpose of this study was to investigate the interrater reliability, intrarater reliability, and between-day stability of cSWE in both healthy and pathological patellar tendons. METHODS: Participants with patellar tendinopathy (n = 13), history of ACLR using bone-patellar tendon-bone autograft (n = 9), and with no history of patellar tendon injury (n = 13) were recruited. cSWE was performed 4 times by multiple raters over 2 days. Intraclass correlations (ICC) and minimum detectable change (MDC95% ) were calculated. RESULTS: Good to excellent between-day stability were found for viscosity (ICC = 0.905, MDC95% = 8.3 Pa seconds) and shear modulus (ICC = 0.805, MDC95% = 27.4 kPa). The interrater reliability measures, however, were not as reliable (ICC = 0.591 and 0.532). CONCLUSIONS: cSWE is a reliable assessment tool for quantifying patellar tendon viscoelastic properties over time. It is recommended, however, that a single rater performs the measure as the interrater reliability was less than ideal.
Asunto(s)
Reconstrucción del Ligamento Cruzado Anterior , Diagnóstico por Imagen de Elasticidad , Ligamento Rotuliano , Traumatismos de los Tendones , Humanos , Reproducibilidad de los Resultados , Ligamento Rotuliano/diagnóstico por imagen , Tendones , Traumatismos de los Tendones/cirugíaRESUMEN
PURPOSE: Anterior cruciate ligament (ACL) injury rate is low among children, but increases during adolescence, especially in girls. Increases in the knee valgus moment within 70 ms of contact with the ground (KFM0-70) may explain the sex-specific increase in the risk of ACL injury. The purpose of the study was to investigate sex-dependent changes in the KFM0-70 from pre-adolescence to adolescence during a cutting maneuver (CM). METHODS: Kinematic and kinetic data during the CM task, performed before and after physical exertion, were recorded using a motion capture system and a force plate. A total of 293 team handball and soccer players, aged 9-12 years, were recruited. A number of those who continued sports participation (n = 103) returned five years later to repeat the test procedure. Three mixed-model analysis of variance (ANOVA) for repeated measures tests were used to determine the effects of sex and age period on the KFM0-70 (1: with no adjustment, 2: adjusted for repeated measurements, and 3: additionally adjusted with hip and knee joint frontal plane kinematics). RESULTS: Boys had significantly higher KFM0-70 than girls at both age periods (p < 0.01 for all models). Girls, not boys, demonstrated significantly increased KFM0-70 from pre-adolescence to adolescence. Importantly, this was fully explained by kinematic variables. CONCLUSION: Although the marked increase in KFM0-70 seen in girls may play a role in their risk of ACL rupture, the higher values demonstrated by boys during CM reflect the complexity of multifactorial biomechanical risk factor analysis. The role of kinematics in mediating the KFM0-70 provides means for modification of this risk factor, but as boys had higher joint moments, continued investigation into sex-dependent biomechanical risk factors is warranted. LEVEL OF EVIDENCE: II.
Asunto(s)
Lesiones del Ligamento Cruzado Anterior , Traumatismos de la Rodilla , Masculino , Femenino , Adolescente , Niño , Humanos , Articulación de la Rodilla , Rodilla , Extremidad Inferior , Lesiones del Ligamento Cruzado Anterior/etiología , Traumatismos de la Rodilla/complicacionesRESUMEN
PURPOSE: Quadriceps dysfunction is ubiquitous after anterior cruciate ligament reconstruction, especially when using bone-patellar tendon-bone (BPTB) autografts. The role of patellar tendon hypertrophy after graft harvest on knee extensor strength is unknown. The purpose of this study was to determine the predictive ability of patellar tendon (PT) and quadriceps muscle (Quad) cross-sectional area (CSA) on knee extensor strength 1-2 months after ACLR using BPTB autografts. METHODS: This is a cross-sectional analysis of a cohort 1-2 months after ACLR using BPTB autograft. Peak knee extensor torque, and PT and Quad CSA measured using ultrasound imaging, were collected in 13 males and 14 females. Simple linear regressions compared quadriceps strength index (QI) against limb symmetry index (LSI) in PT and Quad CSA. Multiple linear regressions with sequential model comparisons predicting peak knee extensor torque were performed for each limb. The base model included demographics. Quad CSA was added in the first model, then PT CSA was added in the second model. RESULTS: Both PT (p < 0.001, R2 = 0.693) and Quadriceps CSA (p = 0.013, R2 = 0.223) LSI had a positive linear relationship with QI. In the involved limb, addition of PT CSA significantly improved the model (R2 = 0.781, ΔR2 = 0.211, p for ΔR2 < 0.001). In the uninvolved limb, the addition of Quad CSA improved the model, but the addition of PT CSA did not. CONCLUSION: PT LSI was more predictive of QI than Quad CSA LSI. Involved limb PT CSA mattered more in predicting peak knee extensor torque than did Quad CSA, but in the uninvolved limb, Quad CSA was the most important predictor of peak knee extensor torque. Graft site patellar tendon hypertrophy is key for strong quadriceps early after ACLR. Early targeted loading via exercise to promote healing of the graft site patellar tendon may bring patients a step closer to winning their battle against quadriceps dysfunction. LEVEL OF EVIDENCE: Level I.
Asunto(s)
Lesiones del Ligamento Cruzado Anterior , Ligamento Rotuliano , Traumatismos de los Tendones , Masculino , Femenino , Humanos , Ligamento Rotuliano/cirugía , Autoinjertos/cirugía , Músculo Cuádriceps/cirugía , Lesiones del Ligamento Cruzado Anterior/cirugía , Traumatismos de los Tendones/cirugía , Hipertrofia/etiología , Hipertrofia/cirugía , Plastía con Hueso-Tendón Rotuliano-Hueso/efectos adversosRESUMEN
BACKGROUND: Achilles tendinopathy is a complex injury and the clinical presentation spans multiple different domains: physical and psychological symptoms, lower extremity function and tendon structure. A conceptual model of Achilles tendon health comprising these domains has been proposed in the literature. The aim of the study was to fit a model of Achilles tendinopathy using factor analysis and compare that to the conceptual model. An inclusive approach using a wide range of variables spanning multiple potential domains were included. METHODS: Participants (N = 99) with midportion Achilles tendinopathy were assessed with variables representing symptoms, physical function, tendon structure, metabolic syndrome, and psychologic symptoms. A Kaiser-Mayer-Olkin index was used to determine suitable variables for a subsequent exploratory factor analysis. RESULTS: A model emerged with an acceptable fit to the data (standardized root mean square of residuals = 0.078). Five uncorrelated factors emerged from the model and were labelled as biopsychosocial, lower extremity function, body size, load tolerance, and tendon structure. The total explained variance was 0.51 with the five factors explaining 0.14, 0.12, 0.10, 0.08, and 0.07 respectively. The results differed from the conceptual model as the factors of psychological variables and metabolic variables did not emerge from the analysis. CONCLUSION: A data driven model of Achilles tendon health supports assessment of the clinical presentation over multiple domains. As the factors are uncorrelated, the results of assessment of, for example, tendon structure should not be expected to be associated with lower extremity function or biopsychosocial limitations. The results suggest that the Patient Reported Outcomes Measurement Information System, counter-movement jump height, body mass index, pain with hopping, and the tendon cross-sectional area can evaluate the five factors, respectively. TRIAL REGISTRATION: Registered on clinicaltrials.gov (Medicine NL of. CLINICALTRIALS: gov [Internet], 2018), ID number NCT03523325.
Asunto(s)
Tendón Calcáneo , Enfermedades Musculoesqueléticas , Tendinopatía , Análisis Factorial , Humanos , Tendinopatía/diagnósticoRESUMEN
BACKGROUND: The purpose was to describe the Nordic treatment practices and to reach a Nordic consensus for the treatment of sebaceous eyelid carcinoma. METHODS: The treatment practices data was collected by a questionnaire with 37 questions to the Nordic oculoplastic surgeons and analyzed. A PubMed MEDLINE database search was done to gather data on the published treatment practices and recommendations. A working group that consisted of in minimum one senior consultant from each leading Nordic University Eye Hospital was assigned. A structured interactive method was used to establish the consensus. RESULTS: Twenty-four doctors responded to the questionnaire. 23/24 (96%) of the respondents took a biopsy before surgery. Regional lymph node scanning was routinely done by 14/23 (61%) and a systemic screening of a metastatic disease by 13/23 (57%). 6/22 (27%) never took conjunctival mapping biopsies and 12/23 (52%) never screened for Muir- Torre. Respondents used Mohs surgery, frozen section or multi-stage excision with delayed closure, and 5-6 mm was the mostly preferred margin. Sentinel lymph node biopsy was a possible option for 9/22 (41%) and cryotherapy and Mitomycin C for 6/22 (27%) respondents. 50% of respondents considered radiation as a treatment option. 15/16 (94%) respondents always followed-up their patients, most for 5 years. Two thirds scanned regional lymph nodes during the follow-up. Consensus was reached for 18 statements representing three domains: preoperative work-up, treatment and follow-up. CONCLUSION: Treatment practices differ in between the five Nordic countries which have similar public health care systems. In the article the authors present a Nordic consensus for the treatment of eyelid sebaceous carcinoma.
Asunto(s)
Adenocarcinoma Sebáceo/terapia , Consenso , Neoplasias de los Párpados/terapia , Párpados/patología , Neoplasias de las Glándulas Sebáceas/terapia , Adenocarcinoma Sebáceo/patología , Adulto , Anciano , Terapia Combinada/normas , Neoplasias de los Párpados/patología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Neoplasias de las Glándulas Sebáceas/patología , Biopsia del Ganglio Linfático Centinela , Encuestas y CuestionariosRESUMEN
PURPOSE: The anterior cruciate ligament is loaded through valgus moment, vertical ground reaction force, and internal rotation moment. The aim of this study was to compare the timing of force peaks during early stance between youth girls and boys. METHODS: One-hundred and twenty-nine team sport athletes aged 9-12 completed a total of 2540 cutting maneuvers captured with an 8-camera motion capture system. Timing of early force peaks was analyzed within 100 ms after ground contact. RESULTS: Genders showed different mean (95% CI) time to peak valgus-(32 ms (30-33 ms) vs 37 ms (36-38 ms), P < 0.001) and time to peak internal rotation moments (36 ms (35-37 ms) vs 38 ms (37-39 ms), P = 0.029) but not time to peak vertical ground reaction force [38 ms (37-40 ms) vs 37 ms (36-38 ms, n.s.)]. Girls showed a smaller time between vertical ground reaction force and valgus moment peaks (mean (95% CI) of 1 ms (1-2 ms) vs 7 ms (5-9 ms), P < 0.001), and valgus- and internal rotation moment peaks (0 ms (- 2 to 1.0 ms) vs - 5 ms (- 6 to - 3 ms), P = 0.0003) but not between internal rotation moment and vertical ground reaction force. CONCLUSIONS: Concurrent force peaks are more common for girls compared with boys, leading to more frequent multi-planar loading of the knee. Timing may explain sex-dependent risk of ACL injuries. Exposure to repeated cutting movements may result in greater ACL injury risk due to timing of knee forces as well as magnitude. Such exposure should be minimized for at-risk athletes. LEVEL OF EVIDENCE: III.
Asunto(s)
Lesiones del Ligamento Cruzado Anterior/etiología , Lesiones del Ligamento Cruzado Anterior/fisiopatología , Fenómenos Biomecánicos , Niño , Femenino , Humanos , Articulación de la Rodilla/fisiopatología , Masculino , Movimiento , Factores de Riesgo , Rotación , Factores Sexuales , Estudios de Tiempo y MovimientoRESUMEN
The Na+-HCO3- cotransporter NBCn1 (SLC4A7) is up-regulated in breast cancer, important for tumor growth, and a single nucleotide polymorphism (SNP), rs4973768, in its 3' untranslated region (3'UTR) correlates with increased breast cancer risk. We previously demonstrated that NBCn1 expression and promoter activity are strongly increased in breast cancer cells expressing a constitutively active oncogenic human epidermal growth factor receptor 2 (HER2) (p95HER2). Here, we address the roles of p95HER2 in regulating NBCn1 expression via post-transcriptional mechanisms. p95HER2 expression in MCF-7 cells reduced the rate of NBCn1 mRNA degradation. The NBCn1 3'UTR down-regulated luciferase reporter expression in control cells, and this was reversed by p95HER2, suggesting that p95HER2 counteracts 3'UTR-mediated suppression of NBCn1 expression. Truncation analyses identified three NBCn1 3'UTR regions of regulatory importance. Mutation of putative miRNA-binding sites (miR-374a/b, miR-200b/c, miR-29a/b/c, miR-488) in these regions did not have significant impact on 3'UTR activity. The NBCn1 3'UTR interacted directly with the RNA-binding protein human antigen R (HuR), and HuR knockdown reduced NBCn1 expression. Conversely, ablation of a distal AU-rich element increased 3'UTR-driven reporter activity, suggesting complex regulatory roles of these sites. The cancer-associated SNP variant decreased reporter expression in T-47D breast cancer cells, yet not in MCF-7, MDA-MB-231 and SK-BR-3 cells, arguing against a general role in regulating NBCn1 expression. Finally, p95HER2 expression increased total and plasma membrane NBCn1 protein levels and decreased the rate of NBCn1 protein degradation. Collectively, this is the first work to demonstrate 3'UTR-mediated NBCn1 regulation, shows that p95HER2 regulates NBCn1 expression at multiple levels, and substantiates the central position of p95HER2-NBCn1 signaling in breast cancer.
Asunto(s)
Regiones no Traducidas 3'/genética , Neoplasias de la Mama/metabolismo , Receptor ErbB-2/metabolismo , Simportadores de Sodio-Bicarbonato/metabolismo , Western Blotting , Neoplasias de la Mama/genética , Ensayo de Cambio de Movilidad Electroforética , Femenino , Técnica del Anticuerpo Fluorescente , Humanos , Células MCF-7 , Estabilidad del ARN/genética , Estabilidad del ARN/fisiología , Reacción en Cadena en Tiempo Real de la Polimerasa , Receptor ErbB-2/genética , Simportadores de Sodio-Bicarbonato/genéticaRESUMEN
PURPOSE: This study aimed to evaluate patient-reported outcomes as well as lower extremity and trunk muscle function in patients with long-standing hip and groin pain, in comparison with matched, healthy controls. It was hypothesized that patients with long-standing hip and groin pain would report more deficiency on the Copenhagen Hip and Groin Outcome Score (HAGOS) and have worse outcomes on performance-based measures than healthy controls. METHODS: Nineteen patients with long-standing hip and groin pain and 19 healthy, activity level-, age-, gender-, and weight-matched controls were assessed with the HAGOS for self-reported outcomes, and a parallel squat (w/kg), single-leg triple jump (cm), single-leg rise (n), barbell roll-out (% of height), and plank test (s) for performance-based measures. Independent sample t test was performed to assess between-group differences. The paired t test was used to analyse between-limb differences in unilateral performance tasks. RESULTS: The patients had worse scores than the controls in all HAGOS subscales (p ≤ 0.001), while no statistically significant differences were observed for any performance measure between groups or between symptomatic and non-symptomatic limbs. CONCLUSIONS: Despite significant self-reported functional limitations on the HAGOS, there were no significant differences between groups in performance-based strength or power measures. The results of this study highlight the need to identify performance-based measures, sensitive to functional deficiencies in patients with long-standing hip and groin pain in order to complement the clinical picture obtained by patient-reported outcomes such as the HAGOS. LEVEL OF EVIDENCE: III.
Asunto(s)
Ingle/fisiopatología , Cadera/fisiopatología , Músculo Esquelético/fisiopatología , Adulto , Enfermedad Crónica , Femenino , Ingle/lesiones , Articulación de la Cadera/fisiopatología , Humanos , Masculino , Músculo Esquelético/lesiones , Dolor/fisiopatología , Autoinforme , Análisis y Desempeño de Tareas , Adulto JovenRESUMEN
The authors present 2 children, a girl aged 9 and a boy aged 15 years, both with lower eyelid ectropion due to congenital lamellar ichthyosis.They had the same treatment protocol, insertion of inverting sutures in addition to a systemic retinoid drug and a lubrication of the eyelids. The girl had 2 separate procedures of inverting sutures, while the eyelids of the boy were corrected with 1 procedure. Both tolerate their systemic retinoid treatment nicely. Five years later, the lower eyelids are in an excellent position without any further surgical intervention. The patients are comfortable. The conventional method to treat these conditions is skin grafts. The authors offer another treatment option in this very bothersome condition.
Asunto(s)
Ectropión/cirugía , Ictiosis Lamelar/complicaciones , Lubrificación/métodos , Retinoides/farmacología , Trasplante de Piel/métodos , Técnicas de Sutura/instrumentación , Suturas , Adolescente , Niño , Ectropión/etiología , Femenino , Humanos , Ictiosis Lamelar/cirugía , MasculinoRESUMEN
OBJECTIVES: To determine the relationships between (1) Achilles tendon pain and loading symmetry, and (2) number of running bouts and symptom severity, during two weeks of outdoor running in individuals with Achilles tendinopathy. DESIGN: Prospective, observational study. SETTING: Biomechanics laboratory and outdoors. PARTICIPANTS: Seventeen runners with Achilles tendinopathy in the return-to-sport phase of rehabilitation. MAIN OUTCOME MEASURES: Symptom severity was recorded with the Victorian Institute of Sports Assessment-Achilles (VISA-A) questionnaire. Running bouts and Achilles tendon pain during runs were recorded with daily training logs. Ground contact time was collected during runs with wearable sensors. Linear mixed modeling determined if the relationship between Achilles tendon pain and ground contact time symmetry during running was moderated by consecutive run days. Multiple regression determined the relationship between number of running bouts and change in VISA-A scores over two weeks, adjusted for run distance. RESULTS: Greater ground contact time on the contralateral leg corresponded to increased ipsilateral tendon pain for each consecutive run day (b = -0.028, p < 0.001). Number of running bouts was not associated with 2-week changes in VISA-A scores (p = 0.672). CONCLUSIONS: Pain during running is associated with injured leg off-loading patterns, and this relationship strengthened with greater number of consecutive run days. Number of running bouts was not related to short-term symptom severity.
Asunto(s)
Tendón Calcáneo , Volver al Deporte , Carrera , Tendinopatía , Humanos , Tendón Calcáneo/lesiones , Tendón Calcáneo/fisiopatología , Carrera/fisiología , Carrera/lesiones , Tendinopatía/fisiopatología , Tendinopatía/rehabilitación , Estudios Prospectivos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Fenómenos Biomecánicos , Dolor/fisiopatología , Encuestas y CuestionariosRESUMEN
Graft site morbidities after bone-patellar tendon-bone (BPTB) autograft harvest for anterior cruciate ligament reconstruction (ACLR) negatively impacts rehabilitation. The purpose of this study was to establish tendon structural properties 1-month after BPTB autograft harvest compared to the uninvolved patellar tendon, and subsequently to quantify the healing trajectory of the patellar tendon over the course of rehabilitation. Patellar tendon morphology (ultrasound) and mechanical properties (continuous shear wave elastography) from 3 regions of the tendon (medial, lateral, central) were measured in 34 participants at 1 month, 3-4 months, and 6-9 months after ACLR. Mixed models were used to compare tendon structure between limbs at 1 month, and quantify healing over 3 timepoints. The involved patellar tendon had increased cross-sectional area and thickness in all regions 1-month after ACLR. Thickness reduced uniformly over time. Possible tendon elongation was observed and remained stable over time. Tendon viscosity was uniform across the three regions in the involved limb while the medial region had higher viscosity in the uninvolved limb, and shear modulus was elevated in all three regions at 1 month. Viscosity and shear modulus in only the central region reduced over time. Statement of Clinical Significance: The entire patellar tendon, and not just the central third, is altered after graft harvest. Tendon structure starts to normalize over time, but alterations remain especially in the central third at the time athletes are returning to sport. Early rehabilitation consisting of tendon loading protocols may be necessary to optimize biologic healing at the graft site tendon.
Asunto(s)
Reconstrucción del Ligamento Cruzado Anterior , Ligamento Rotuliano , Humanos , Reconstrucción del Ligamento Cruzado Anterior/rehabilitación , Reconstrucción del Ligamento Cruzado Anterior/métodos , Masculino , Adulto , Ligamento Rotuliano/trasplante , Femenino , Adulto Joven , Autoinjertos , Cicatrización de Heridas , Trasplante Autólogo , Plastía con Hueso-Tendón Rotuliano-Hueso , Adolescente , Injertos Hueso-Tendón Rotuliano-HuesoRESUMEN
Despite significant progress in the identification of genetic loci for age-related macular degeneration (AMD), not all of the heritability has been explained. To identify variants which contribute to the remaining genetic susceptibility, we performed the largest meta-analysis of genome-wide association studies to date for advanced AMD. We imputed 6 036 699 single-nucleotide polymorphisms with the 1000 Genomes Project reference genotypes on 2594 cases and 4134 controls with follow-up replication of top signals in 5640 cases and 52 174 controls. We identified two new common susceptibility alleles, rs1999930 on 6q21-q22.3 near FRK/COL10A1 [odds ratio (OR) 0.87; P = 1.1 × 10(-8)] and rs4711751 on 6p12 near VEGFA (OR 1.15; P = 8.7 × 10(-9)). In addition to the two novel loci, 10 previously reported loci in ARMS2/HTRA1 (rs10490924), CFH (rs1061170, and rs1410996), CFB (rs641153), C3 (rs2230199), C2 (rs9332739), CFI (rs10033900), LIPC (rs10468017), TIMP3 (rs9621532) and CETP (rs3764261) were confirmed with genome-wide significant signals in this large study. Loci in the recently reported genes ABCA1 and COL8A1 were also detected with suggestive evidence of association with advanced AMD. The novel variants identified in this study suggest that angiogenesis (VEGFA) and extracellular collagen matrix (FRK/COL10A1) pathways contribute to the development of advanced AMD.
Asunto(s)
Colágeno Tipo X/genética , Variación Genética , Estudio de Asociación del Genoma Completo , Degeneración Macular/genética , Proteínas de Neoplasias/genética , Proteínas Tirosina Quinasas/genética , Factor A de Crecimiento Endotelial Vascular/genética , Estudios de Casos y Controles , Estudios de Cohortes , Femenino , Genotipo , Humanos , Masculino , Polimorfismo de Nucleótido Simple , Población Blanca/genéticaRESUMEN
Patellar tendons are assumed to be uniform in morphology and mechanical properties despite a higher prevalence of tendinopathies observed in the medial region. The purpose of this study was to compare the thickness, length, viscosity, and shear modulus of the medial, central, and lateral regions of healthy patellar tendons of young males and females in vivo. B-mode ultrasound and continuous shear wave elastography were performed on 35 patellar tendons (17 females, 18 males) over three regions of interest. A linear mixed-effects model (α = 0.05) was used to determine differences between the three regions and sexes followed by pairwise comparisons for significant findings. The lateral region (mean [95% confidence interval] = 0.34 [0.31-0.37] cm) was thinner compared with the medial (0.41 [0.39-0.44] cm, p < 0.001), and central (0.41 [0.39-0.44] cm, p < 0.001) regions regardless of sex. Viscosity was lower in the lateral (19.8 [16.9-22.7] Pa-s) versus medial region (27.4 [24.7-30.2] Pa-s, p = 0.001). Length had a region-by-sex interaction (p = 0.003) characterized by a longer lateral (4.83 [4.54-5.13] cm) versus medial (4.42 [4.12-4.72] cm) region in males (p < 0.001), but not females (p = 0.992). Shear modulus was uniform between regions and sexes. The thinner, and less viscous lateral patellar tendon may reflect the lower load the tendon experiences explaining the differences in regional prevalence of developing tendon pathology. Statement of Clinical Significance: Healthy patellar tendons are not uniform in morphology or mechanical properties. Considering regional tendon properties may help guide targeted interventions for patellar tendon pathologies.
Asunto(s)
Diagnóstico por Imagen de Elasticidad , Ligamento Rotuliano , Masculino , Humanos , Ligamento Rotuliano/diagnóstico por imagen , Tendones/diagnóstico por imagen , Rótula/diagnóstico por imagen , UltrasonografíaRESUMEN
Background: The Victorian Institute of Sport Assessment-Achilles (VISA-A) questionnaire is validated and widely used in Achilles tendinopathy. How well it can evaluate treatment outcomes is not well understood. Purpose: To evaluate the responsiveness of the VISA-A in midportion Achilles tendinopathy and compare it with other patient-reported outcome measures. Study Design: Cohort study (diagnosis); Level of evidence, 2. Methods: Enrolled were 97 participants with clinically diagnosed Achilles tendinopathy (median age, 50 years [interquartile range, 18 years]; symptom duration, 10 months [interquartile range, 28.7 months). The participants underwent a baseline evaluation and completed between 1 and 6 follow-up evaluations at 8, 16, 24, 32, 40, and/or 48 weeks. Participants completed the VISA-A, the Patient Reported Outcomes Measurement Information System short form Version 2.0 (PROMIS) Physical Function and Pain Interference subscales, and the Tampa Scale for Kinesiophobia (TSK). Three thresholds were evaluated with a receiver operating characteristic analysis (minimal clinically important difference [MCID], substantial benefit [SB], and complete recovery [CR]) using an 11-point global rating of change scale as an anchor. Thresholds were evaluated on raw scores as well as changes from baseline. Results: The VISA-A was able to detect all 3 thresholds for changes over time, with raw scores >70.5, >77.5, and >89.5 representing the MCID, SB, and CR, respectively; thresholds for changes from baseline on the VISA-A were increases of 23.5, 19.5, and 37.5 points from baseline, respectively. The PROMIS subscale raw scores had identical thresholds for SB and CR (52.45 for Physical Function and 45.6 for Pain Interference). A score <34.5 on the TSK was the threshold for SB. Conclusion: The VISA-A was the most responsive outcome measure evaluated. Raw scores had increasingly higher thresholds for the MCID, SB, and CR, which were therefore logically consistent.
RESUMEN
Background: The 11+ program prevents anterior cruciate ligament (ACL) injuries in athletes through unknown mechanisms. Purpose: The aim of the current study was to evaluate the effects of The 11+ intervention program, performed by female soccer players during a single season, on the frequency of Early Peaks during athletic tasks. Methods: Three teams (69 players) of collegiate female soccer athletes (Divisions I and II) were recruited. Two teams (49 players) volunteered to perform The 11+ three times per week for one season (~22 weeks plus three weeks pre-season), and one team (20 players) served as controls. The athletes performed three repetitions of a cutting maneuver, side shuffle direction change, and forwards to backwards running direction change before and after the competitive season and were recorded using marker-based 3D motion capture. Knee valgus moment time series were calculated for each repetition with inverse kinematics and classified as either "Very Early Peak", "Early Peak" or "other" using cluster analysis. The classification was based timing of the peak relative to the timing of ACL injuries. The effect of the intervention on the frequency of Very Early Peaks and Early Peaks was evaluated with a mixed Poisson regression controlling for the movement task and pre-season frequency. Results: The 11+ intervention reduced the frequency of Early Peak knee valgus moment in one intervention team (coefficient = -1.16, p = 0.004), but not the other (coefficient = -0.01, p = 0.977). No effect was observed on the frequency of Very Early Peak knee valgus moment. Conclusions: Reduced frequency of knee valgus moment Early Peak during athletic tasks may explain the mechanism by which The 11+ program decreases risk of ACL injury. Prospective studies with a much larger sample size are required to establish a link between Early Peak knee valgus moments and risk of ACL injury. Level of evidence: 2b.
RESUMEN
Markerless motion capture (mocap) could be the future of motion analysis. The purpose of this report was to describe our team of clinicians and scientists' exploration of markerless mocap (Theia 3D) and share data for others to explore (link: https://osf.io/6vh7z/?view_only=c0e00984e94a48f28c8d987a2127339d). Simultaneous mocap was performed using markerless and marker-based systems for walking, squatting, and forward hopping. Segment lengths were more variable between trials using markerless mocap compared to marker-based mocap. Sagittal plane angles were most comparable between systems at the knee joint followed by the ankle and hip. Frontal and transverse plane angles were not comparable between systems. The data collection experience using markerless mocap was simpler, faster, and user friendly. The ease of collection was in part offset by the added data transfer and processing times, and the lack of troubleshooting flexibility. If used selectively with proper understanding of limitations, markerless mocap can be exciting technology to advance the field of motion analysis.
RESUMEN
OBJECTIVES: Fear of movement may be a source of systemic bias in studies reporting functional deficits in patients with Achilles tendinopathy. The purpose of this study was to assess the effects of kinesiophobia on completion rate and performance on tests evaluating lower extremity function, while controlling for self-reported pain. DESIGN: Cross-sectional study; SETTING: Tendon research laboratory. PARTICIPANTS: Ninety-four participants with Achilles tendinopathy. MAIN OUTCOME MEASURES: Completion (yes/no) and performance (cm) on the counter-movement jump, hopping, and drop counter-movement jump. RESULTS: The models fit the data (R^2 = 0.81, both models). TSK score did not predict completion (beta = -0.01, 95% CI = -0.13 - 0.09, P = 0.74) but pain did (beta = -0.36, 95% CI = -0.53 to -0.19, P < 0.0001). TSK score did not predict performance (beta = -0.06, 95% CI = -0.14 - 0.003, P = 0.07), but pain did (beta = -0.15, 95% CI = -0.22 to -0.07, P < 0.0001). CONCLUSIONS: Kinesiophobia did not affect the physical performance tests in patients with Achilles tendinopathy. Measures of physical performance should be interpreted alongside self-reported pain.
Asunto(s)
Tendón Calcáneo/lesiones , Miedo , Dolor/fisiopatología , Dolor/psicología , Tendinopatía/fisiopatología , Tendinopatía/psicología , Tendón Calcáneo/fisiopatología , Adulto , Estudios Transversales , Prueba de Esfuerzo/métodos , Femenino , Humanos , Extremidad Inferior/fisiopatología , Masculino , Persona de Mediana Edad , Movimiento , Dimensión del Dolor , Rendimiento Físico Funcional , AutoinformeRESUMEN
Cluster analysis of knee abduction moment waveforms may be useful to examine biomechanical data. The aim of this study was to analyze if the knee abduction moment waveform of early peaks, consistent with anterior cruciate ligament injury mechanisms, was associated with foot-trunk distance, knee kinematics, and heel strike landing posture, all of which have been observed during anterior cruciate ligament injuries. One hundred and seventy-seven adolescent athletes performed cutting maneuvers, marker-based motion capture collected kinetic and marker data and an 8-segment musculoskeletal model was constructed. Knee abduction moment waveforms were clustered as either a large early peak, or not a large early peak using a two-step process with Euclidean distances and the Ward-d2 cluster method. Mediolateral distance between foot and trunk was associated with the large early peak waveform with an odds ratio (95% confidence interval) of 3.4 (2.7-4.4). Knee flexion angle at initial contact and knee flexion excursion had odds ratios of 1.9 (1.6-2.4) and 1.6 (1.3-2.0). Knee abduction excursions had an odds ratio of 1.8 (1.1-2.4) and 1.8 (1.4-2.4), respectively. Heel strike landings and anteroposterior distance between foot and trunk were not associated with the large early peak waveform with odds ratios of 1.2 (0.9-1.7) and 1.1 (0.8-1.3), respectively. The knee abduction moment waveform is associated with several kinematic variables observed during ACL injury. The results support intervention programs that can modify these kinematics and thus reduce early stance phase knee abduction moments.
Asunto(s)
Lesiones del Ligamento Cruzado Anterior , Adolescente , Lesiones del Ligamento Cruzado Anterior/etiología , Fenómenos Biomecánicos , Humanos , Rodilla , Articulación de la Rodilla , MovimientoRESUMEN
BACKGROUND: There are 2 movement patterns associated with an anterior cruciate ligament (ACL) injury: dynamic valgus and stiff landing. Although sex-dependent differences have been identified for adults, less is known for preadolescent athletes regarding movement patterns known to load the ACL. HYPOTHESIS: We hypothesized that girls would demonstrate greater vertical ground reaction forces and knee valgus angles. We further hypothesized that the exercise intervention would affect girls more than boys and that this would primarily be demonstrated in less sagittal plane excursions, increased vertical ground reaction forces and knee valgus moments for girls than for boys. STUDY DESIGN: Controlled laboratory study. METHODS: Male and female soccer and handball players (n = 288; age range, 9-12 years) were recruited. A motion capture system synchronized to a force platform was used to record 5 trials of a cutting maneuver before and after a 5-minute fatigue intervention. Linear mixed models were constructed, and analysis of variance was used to analyze differences in outcomes associated with the sex of the athletes. RESULTS: Boys showed greater peak knee valgus moment (0.26 vs 0.22 N·m/kg, respectively; P = .048), peak knee internal rotation moment (-0.13 vs -0.10 N·m/kg, respectively; P = .021), knee rotation excursion (-7.9° vs -6.9°, respectively; P = .014), and knee extension excursion (2.7° vs 1.4°, respectively; P < .001) compared with that in girls. A significant sex × fatigue intervention interaction (F = 7.6; P = .006) was found, which was caused by a greater increase in first peak vertical ground-reaction force (vGRF) from before to after the fatigue intervention for girls (15.3 to 16.0 N/kg) compared with boys (16.4 to 16.5 N/kg). CONCLUSION: Differences detected for biomechanical factors during the cutting maneuver do not point to a greater ACL injury risk for prepubescent or early pubescent girls than for boys. Nonetheless, girls go on to develop more detrimental movement patterns in adolescence than those in boys in terms of biomechanical risk factors. CLINICAL RELEVANCE: Early adolescence is a good target age to learn and develop muscular control; balance, strength; flexibility; and jumping, running, and landing control. This time of physical and athletic growth may therefore be an appropriate period to influence biomechanical factors and thereby task execution and the injury risk.