Retinal transplant immunology and advancements.

Several gaps and barriers remain for transplanting stem cells into the eye to treat ocular disease, especially diseases of the retina. While the eye has historically been considered immune privileged, recent thinking has identified the immune system as both a barrier and an opportunity for eye stem cell transplantation. Recent approaches leveraging scaffolds or cloaking have been considered in other tissues beyond immune suppression. This perspective paper outlines approaches for transplantation and proposes opportunities to overcome barriers of the immune system in stem cell transplantation in the eye.

An extinct north American porcupine with a South American tail.

New World porcupines (Erethizontinae) originated in South America and dispersed into North America as part of the Great American Biotic Interchange (GABI) 3-4 million years ago.1 Extant prehensile-tailed porcupines (Coendou) today live in tropical forests of Central and South America.2,3 In contrast, North American porcupines (Erethizon dorsatum) are thought to be ecologically adapted to higher-latitude temperate forests, with a larger body, shorter tail, and diet that includes bark.4,5,6,7 Limited fossils8,9,10,11,12,13 have hindered our understanding of the timing of this ecological differentiation relative to intercontinental dispersal during the GABI and expansion into temperate habitats.14,15,16,17,18 Here, we describe functionally important features of the skeleton of the extinct Erethizon poyeri, the oldest nearly complete porcupine skeleton documented from North America, found in the early Pleistocene of Florida. It differs from extant E. dorsatum in having a long, prehensile tail, grasping foot, and lacking dental specializations for bark gnawing, similar to tropical Coendou. Results from phylogenetic analysis suggest that the more arboreal characteristics found in E. poyeri are ancestral for erethizontines. Only after it expanded into temperate, Nearctic habitats did Erethizon acquire the characteristic features that it is known for today. When combined with molecular estimates of divergence times, results suggest that Erethizon was ecologically similar to a larger species of Coendou when it crossed the Isthmus of Panama by the early Pleistocene. It is likely that the range of this more tropically adapted form was limited to a continuous forested biome that extended from South America through the Gulf Coast.

Clinical Course and Outcomes of Autoimmune Versus Non-Autoimmune Surgically Induced Scleral Necrosis: A Multicentric Comparative Study.

BACKGROUND: To analyze the clinical course and outcomes of autoimmune vs. non-autoimmune surgically induced scleral necrosis (SISN). METHODS: Multicentric, retrospective, comparative cohort study. Eighty-two eyes of 70 patients with SISN were classified according to pathogenic mechanism into autoimmune vs. non-autoimmune. Main outcome measures included necrosis onset, type of surgery, associated systemic disease, visual acuity, and treatment were analysed in patients followed for ≥ 6 months. RESULTS: Forty-six (65.7%) patients were women, and the median age was 66 (range: 24-90) years. Most patients (82.9%) had unilateral disease. The median time between surgery and SISN onset was 58 (1-480) months. Thirty-one (37.8%) eyes were classified as autoimmune, and 51 (62.2%) as non-autoimmune SISN. Autoimmune SISN was associated with a shorter time between the surgical procedure and SISN onset than non-autoimmune cases (median of 26 vs. 60 months, p = 0.024). Also, autoimmune SISN was associated with cataract extraction (93.5% vs. 25.5%, p < 0.001), severe scleral inflammation (58.1% vs. 17.6%, p < 0.001), and higher incidence of ocular complications (67.7% vs. 33.3%, p = 0.002) than non-autoimmune cases. Remission was achieved with medical management alone in 44 (86.3%) eyes from the non-autoimmune and in 27 (87.1%) from the autoimmune group (p = 0.916). Surgical management was required in 11 (13.4%) eyes, including two requiring enucleations due to scleral perforation and phthisis bulbi. CONCLUSIONS: Eyes with autoimmune SISN had a higher rate of cataract surgery, severe scleral inflammation, and ocular complications. Early SISN diagnosis and appropriate management, based on clinical features and pathogenic mechanisms, are critical to avoid sight-threatening complications.

Reliability of a Trunk Flexion and Extensor Muscle Strength Test with Hand-Held and Isokinetic Dynamometers in Female Athletes.

An accurate trunk muscle strength assessment seems very important to design and individualize training and rehabilitation programs in clinical and sport settings. Hand-held dynamometers (HHDs) are interesting alternatives to isokinetic dynamometers for assessing trunk isometric muscle strength because they are inexpensive instruments and easy to use. This cross-sectional observational study aimed to examine the reliability of two novel sitting tests for assessing trunk flexion and extension isometric strength using an HHD and their relationship with two other novel isometric tests that use an isokinetic dynamometer. Twenty-four female amateur athletes (age: 24.5 ± 2.64 years; body height: 164.45 ± 6.33 cm; body mass: 63.17 ± 10.35 kg) participated in this study. A test-retest design was carried out one-week apart to examine the reliability. The relationship and the degree of agreement between the HHD and the isokinetic dynamometer measurements were analysed using Pearson correlation and Bland-Altman analysis, respectively. In general, the reliability of all isometric strength tests was good, with ICCs ranging from 0.65 to 0.87 and typical error < 15%. Pearson correlations were moderate, with values of r = 0.47 (R2 = 0.22) and r = 0.42 (R2 = 0.18) for flexion and extension strength, respectively. Bland-Altman plots showed no agreement between HHDs and isokinetic measurements. All trunk isometric tests using both, an isokinetic dynamometer and HHDs, provide reliable measurements for assessing trunk flexion and extension strength. According to the comparative analysis, both measurement types are different and cannot be used interchangeably. Health and sport professionals should choose the test that best suits the biomechanical characteristics required for functional goals or success in a given sport.

Influence of the External Workload on Calf Muscle Strain Injuries in Professional Football Players: A Pilot Study.

BACKGROUND: The influence of external workload variables on the development of calf muscle strainsin football players has not been previously explored. HYPOTHESIS: Overloaded players would have an increased risk of calf muscle strain injury. STUDY DESIGN: Prospective observational study. LEVEL OF EVIDENCE: Level 4. METHODS: A total of 41 professional football players from 1 team were monitored for 2 consecutive seasons. Total distance covered (TD), and distances covered at high-intensity running, high sprint running, low (LACC) and high (HACC) acceleration, low (LDEC) and high (HDEC) deceleration, and at high metabolic load distance (HMLD) were monitored with GPS units. Accumulated players' external workload in the week before injury was compared with the weekly mean value of the 6 weeks before injury occurred for each player. RESULTS: Ten players (24.3%) suffered 16 calf muscle strain injuries (3.1 injuries per 1000 hours of match play; 0.5 injuries per 1000 hours of training exposure). Players with a calf muscle injury were older (p = 0.03), with higher body weight (p = 0.01) and height (p = 0.03). Injured players displayed substantially higher total training volume (p < 0.01), TD (p < 0.01), LACC (p < 0.01), LDEC (p < 0.01), HACC (p < 0.01), HDEC (p < 0.01), and HMLD (p = 0.03) in the week before injury, in comparison with the mean values of these variables in the 6 weeks before injury. CONCLUSION: A week with a higher-than-habitual external workload might increase the risk of calf muscle strain injury in professional football players. Calf muscle injuries were preceded by a week with unusually high workloads associated with accelerating and decelerating distances and higher training volumes. CLINICAL RELEVANCE: Monitoring external workload indicators may be helpful in determine players with a higher risk of calf muscle strain injury due to excessive workload during training/competition.

Self-reported dental pain in Mexican schoolchildren: a national ecological study.

The objective of this study was to quantify the prevalence of and identify the factors associated with dental pain among elementary- and middle-school students in Mexico. An ecological study was carried out with data from the 2008 National School-based Student-Health Survey. Information on dental pain from schoolchildren (aged 5 to 16 years) was collected from public schools across the 32 states of Mexico. In the original study, a questionnaire was used to explore various factors that affect the oral and dental health status of schoolchildren. The outcome variable was the prevalence rate (for dental pain) reported at state level. Various contextual socioeconomic variables were included, in addition to dental caries. Analyses were performed using Stata software. 52.9% of interviewees were girls; 26.9% of male and female schoolchildren in Mexico experienced gum or dental pain during the period analyzed (95% Confidence Interval = 26.02, 27.77%); according to the Spearman correlation results, self-reported dental pain was unrelated (p > 0.05) to the socioeconomic and sociodemographic variables that make up the Gross Domestic Product (GDP) and the Human Development (HDI), as well as the marginalization and the Gini indices. However, the estimated percentages of self-reported dental pain and caries were positively correlated in the elementary- (r = 0.8958, p < 0.0001), middle-school (r = 0.8958, p < 0.0001) and total populations (r = 0.8542, p < 0.0001). Prevalence of self-reported dental pain was 28%, or about one in three, of the Mexican children and adolescents in the study sample. The state-level sociodemographic and socioeconomic risk indicators were not associated with the prevalence of dental pain. Self-reported caries was positively correlated with self-reported dental pain.

Suppression of Neovascularization by Topical and Subconjunctival Bevacizumab After High-Risk Corneal Transplantation.

Purpose: To assess the effectiveness of topical and subconjunctival bevacizumab in suppressing vascularization in graft and host bed after high-risk corneal transplantation. Design: Secondary analysis of prospective, randomized, double-blind, placebo-controlled multicentric clinical trial. Participants: The study includes patients aged > 18 years who underwent high-risk penetrating keratoplasty, which was defined as corneal vascularization in ≥ 1 quadrants of the corneal graft and host bed, excluding the limbus. Methods: Patients were randomized to treatment and control groups. The patients in the treatment group received subconjunctival injection of bevacizumab (2.5 mg/0.1 ml) on the day of the procedure, followed by topical bevacizumab (10 mg/ml) 4 times per day for 4 weeks. The patients in control group received injection of vehicle (0.9% sodium chloride) on the day of procedure, followed by topical vehicle (carboxymethylcellulose sodium 1%) 4 times a day for 4 weeks. Main Outcome Measures: Vessel and invasion area of vessels in the corneal graft and host beds. Results: This study included 56 eyes of 56 patients who underwent high-risk corneal transplantation, with equal numbers in the bevacizumab and vehicle (control) treatment groups. The mean age of patients who received bevacizumab was 61.2 ± 15.9 years, and the mean age of those treated with vehicle was 60.0 ± 16.1 years. The vessel area at baseline was comparable in the bevacizumab (16.72% ± 3.19%) and control groups (15.48% ± 3.12%; P = 0.72). Similarly, the invasion areas were also similar in the treatment (35.60% ± 2.47%) and control (34.23% ± 2.64%; P = 0.9) groups at baseline. The reduction in vessel area was significantly higher in the bevacizumab-treated group (83.7%) over a period of 52 weeks compared with the control group (61.5%; P < 0.0001). In the bevacizumab-treated group, invasion area was reduced by 75.8% as compared with 46.5% in the control group. The vessel area was similar at 52 weeks postprocedure in cases of first (3.54% ± 1.21%) and repeat (3.80% ± 0.40%) corneal transplantation in patients who received bevacizumab treatment. In the vehicle-treated patients, the vessel area was significantly higher in repeat (9.76% ± 0.32%) compared with first (8.06% ± 1.02%; P < 0.0001) penetrating keratoplasty. In the bevacizumab treatment group, invasion areas at week 52 were comparable in first (11.70% ± 3.38%) and repeat (11.64% ± 1.74%) procedures, whereas invasion area was significantly higher in repeat (27.87% ± 2.57%) as compared with first (24.11% ± 2.17%) penetrating keratoplasty in vehicle-treated patients. Conclusions: In patients undergoing vascularized high-risk corneal transplantation, bevacizumab is efficacious in reducing vascularization of corneal graft and host bed, thereby reducing the risk of corneal graft rejection in vascularized host beds. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Psychometric Properties of the Spanish Clance Impostor Scale (S-CIPS) / Propiedades psicométricas de la adaptación española de la Clance Impostor Phenomenon Scale (S-CIPS)

El objetivo del presente estudio fue el de examinar la fiabilidad, validez y estructura factorial de la adaptación española de la Clance Impostor Phenomenon Scale (CIPS). Para ello, un total de 271 estudiantes españoles completaron una versión traducida de la escala original de 20 ítems. En nuestra muestra, el instrumento mostró una alta fiabilidad, medida como consistencia interna, (ωTotal =.90) y correlaciones moderadas-altas con medidas de depresión (r =.633), autoestima (r = -.754) y miedo a las evaluaciones negativas (r = .666), lo cual sugiere tanto una validez nomológica como discriminante. Aunque en la validación original se propuso una estructura de tres factores, otros estudios han encontrado ajuste a estructuras de uno y dos factores. Aquí, utilizamos un análisis factorial confirmatorio (AFC) para probar el ajuste de estos tres modelos. Nuestros resultados muestran que, en la adaptación a español, el modelo con dos factores es el preferido. Esta adaptación al español de la CIPS provee a los profesionales clínicos una de una nueva herramienta para poder investigar los mecanismos que subyacen al síndrome del impostor, así como futuros tratamientos.(AU)

The aim of this study was to examine the reliability, validity, and factorial structure of the Spanish version of the Clance Impostor Phenom-enon Scale (CIPS). A sample of 271 Spanish students was recruited to complete a translated version of the original 20-item CIPS. In our sample, the instrument showed high internal consistency reliability (ωTotal=.90) and a moderate-to-strong correlation with measures of depression (r= .633), self-esteem (r= -.754) and fear of negative evaluation (r= .666), suggesting both nomological and discriminant validity. Althoughthe original valida-tion of the CIPS proposed a factorial structure with three factors, subse-quent validations also revealed adjustment to two-and one-factor struc-tures. Here, we used confirmatory factor analysis (CFA) to test the three different models. The results showed that in our adaptation, a 2-factor structure might be preferred. This adaptation of the CIPS to Spanish pro-vides clinicians with a new method to gain insight into the psychological mechanisms behind the Impostor phenomenon and suitable treatments.(AU)

Non-fatal suicide behaviours across phases in the COVID-19 pandemic: a population-based study in a Catalan cohort.

BACKGROUND: The COVID-19 pandemic has been extensively discussed in the context of its effect on mental health. Although global suicide rates have remained stable during the pandemic, the specific effect on non-fatal suicide behaviours during and after the pandemic remains underexplored. This study aims to investigate patterns of non-fatal suicide behaviours before, during, and after the pandemic. METHODS: In this cohort study, we used data from all hospitals in Catalonia, Spain, collected through the Catalan Suicide Risk Code, which is a specifically designed suicide attempt surveillance protocol, involving a face-to-face, in-depth psychiatric evaluation, after a Catalan resident presents any suicide risk behaviour in any public health-care setting. This evaluation centralises data from suicide registries across the territory. We included non-fatal suicide behaviours, meaning suicidal ideation or attempts that did not result in death, and excluded self-harm behaviours not judged to be linked with suicidal ideation. We considered three periods: the pre-confinement period (Jan 1, 2018, to the enforcement of the lockdown in Spain on March 14, 2020); the confinement period (March 14, 2020, to the end of lockdown on June 21, 2020); and the post-confinement period (June 21, 2020, to Dec 31, 2022). We used Bayesian structural time series models to assess the effect of pandemic phases on non-fatal suicide behaviours, and we ran stratified analyses by sex and age to identify distinct patterns among demographic cohorts. FINDINGS: We obtained 26 482 records from Jan 1, 2018, to Dec 31, 2022. The mean age was 37·94 years (SD 18·07), and the sample included 17 584 (66·4%) women and 8898 (33·6%) men. Data on ethnicity were not collected. Temporal trends showed a mild increase in non-fatal suicide behaviours from Jan 1, 2018, to March 13, 2020; a reduction during the confinement period; and a subsequent rise after confinement. Bayesian models suggested a significant causal effect of lockdown easing, resulting in a 50·77% increase in non-fatal suicide behaviours (95% credible interval [CrI] 26·62-76·58; p<0·0001). Stratified analyses indicated that the easing of lockdown resulted in a significant increase in non-fatal suicide behaviours among women (25·92%; 6·71-44·72; p=0·011) and among individuals aged 18 years and younger (72·75%; 38·81-108·11; p<0·0001). INTERPRETATION: This study provides a comprehensive examination of non-fatal suicide behaviours in Catalonia, Spain, emphasising the dynamics of different COVID-19 pandemic phases. The initial reduction during strict lockdown aligns with Joiner's Interpersonal Theory of Suicide, whereas the post-confinement rise reflects complex factors, including social isolation and economic challenges. Sex-specific and age-specific analyses underscore distinct vulnerabilities, emphasising the need for targeted preventive strategies. FUNDING: Centro de Investigación Biomédica en Red de Salud Mental annual budget of G21, Agència de Gestió d'Ajuts Universitaris i de Recerca of the Generalitat de Catalunya. TRANSLATIONS: For the Catalan and Spanish translations of the abstract see Supplementary Materials section.

Variant characterisation and clinical profile in a large cohort of patients with Ellis-van Creveld syndrome and a family with Weyers acrofacial dysostosis.

BACKGROUND: Ellis-van Creveld syndrome (EvC) is a recessive disorder characterised by acromesomelic limb shortening, postaxial polydactyly, nail-teeth dysplasia and congenital cardiac defects, primarily caused by pathogenic variants in EVC or EVC2. Weyers acrofacial dysostosis (WAD) is an ultra-rare dominant condition allelic to EvC. The present work aimed to enhance current knowledge on the clinical manifestations of EvC and WAD and broaden their mutational spectrum. METHODS: We conducted molecular studies in 46 individuals from 43 unrelated families with a preliminary clinical diagnosis of EvC and 3 affected individuals from a family with WAD and retrospectively analysed clinical data. The deleterious effect of selected variants of uncertain significance was evaluated by cellular assays. MAIN RESULTS: We identified pathogenic variants in EVC/EVC2 in affected individuals from 41 of the 43 families with EvC. Patients from each of the two remaining families were found with a homozygous splicing variant in WDR35 and a de novo heterozygous frameshift variant in GLI3, respectively. The phenotype of these patients showed a remarkable overlap with EvC. A novel EVC2 C-terminal truncating variant was identified in the family with WAD. Deep phenotyping of the cohort recapitulated 'classical EvC findings' in the literature and highlighted findings previously undescribed or rarely described as part of EvC. CONCLUSIONS: This study presents the largest cohort of living patients with EvC to date, contributing to better understanding of the full clinical spectrum of EvC. We also provide comprehensive information on the EVC/EVC2 mutational landscape and add GLI3 to the list of genes associated with EvC-like phenotypes.

ACTN3 XX Genotype Negatively Affects Running Performance and Increases Muscle Injury Incidence in LaLiga Football Players.

The aim of this study was to investigate the association of the ACTN3 rs1815739 polymorphism with match running performance and injury incidence in top-level professional football players. A total of 315 top-level professional football players from the first division of Spanish football (i.e., LaLiga) participated in this prospective and descriptive study. The ACTN3 rs1815739 genotype was identified for each player using genomic DNA samples. During LaLiga 2021-2022, players' performance was obtained through a validated camera system in all official matches. Additionally, the incidence of non-contact injuries was obtained by each team's medical staff according to the International Olympic Committee (IOC) statement. From the study sample, 116 (36.8%) players had the RR genotype, 156 (49.5%) had the RX genotype, and 43 (13.7%) had the XX genotype. The anthropometric characteristics of the players were similar across genotypes. However, the total running distance (p = 0.046), the distance at 21.0-23.9 km/h (p = 0.042), and the number of sprints (p = 0.042) were associated with the ACTN3 genotype. In all these variables, XX players had lower match performance values than RR players. Additionally, total and match injury incidences were higher in XX players than in RR players (p = 0.026 and 0.009, respectively). The rate of muscle injuries was also higher in XX players (p = 0.016). LaLiga football players with the ACTN3 XX genotype had lower match running performance and a higher incidence of non-contact injuries over the season.

Lessons Learned From Ocular Graft versus Host Disease: An Ocular Surface Inflammatory Disease of Known Time of Onset.

ABSTRACT: The ocular surface inflammatory disorders (OSIDs) comprise a group of conditions characterized by persistent inflammation of the ocular surface and adnexal tissues. Systemic autoimmune diseases and hypersensitivity reactions cause them, and, if left untreated, can result in severe inflammatory dry eye, corneal damage, and vision loss. Ocular graft-versus-host disease (oGVHD) forms part of the ocular surface inflammatory disease umbrella. It is a condition occurring after allogeneic hematopoietic stem cell or bone marrow transplantation, usually in chronic graft-versus-host disease. oGVHD can virtually affect any ocular adnexal tissue, especially the meibomian glands, and cause persistent inflammation, tissue fibrosis, and subsequent chronic, severe dry eye disease. Among the OSIDs, oGVHD has the particularity that it has a "time zero," meaning we know when the disease started. As such, preclinical models have leveraged this to investigate the molecular mechanisms involved in the damage oGVHD causes to the ocular surface. In oGVHD, establishing a "time zero" allows for predicting the clinical course and establishing adequate treatment. This is also possible because the inflammatory infiltration occurs in ocular surface tissues, which are readily accessible. Using oGVHD, we might be able to understand the immune response mechanisms in other OSIDs better (i.e., Sjögren syndrome, Stevens-Johnson syndrome, among others). This review presents an up-to-date overview of the pathogenesis, clinical presentation, and treatment of oGVHD. In addition, we will discuss the value of the "time zero" concept in the study of oGVHD.

Ocular Mucous Membrane Pemphigoid: The Effect of Risk Factors at Presentation on Treatment Outcomes.

PURPOSE: Analyze the influence of risk factors at presentation in the long-term immunosuppressive therapy (IMT) outcomes of ocular mucous membrane pemphigoid (OMMP). DESIGN: Retrospective multicenter study. PARTICIPANTS: Patients with OMMP seen at the Duke Eye Center, Tecnologico de Monterrey, and Hospital Clinic of Barcelona from 1990 to 2022. METHODS: Data at presentation on demographics, direct immunofluorescence, ocular findings, sites of extraocular manifestations (EOMs), and previous treatments in patients with a clinical or laboratory diagnosis of OMMP, were analyzed with multivariable analysis and Kaplan-Meier plots to identify factors associated with adverse outcomes. MAIN OUTCOME MEASURES: (1) Inflammatory control (no conjunctival inflammation in both eyes at 3 months on IMT); (2) relapse (new-onset inflammation after absolute control in either eye); (3) progression (≥ 1 cicatrizing stage progression in either eye); and (4) vision loss (≥ 2 Snellen lines). RESULTS: A total of 117 patients (234 eyes), 61% (71/117) of whom were women, with a mean age of 66.6 (SD: 12.4) years (range: 37-97 years) and median follow-up of 34 months (interquartile range: 16-66 months; range: 3-265 months), were enrolled. Inflammatory control was achieved in 57% of patients (67/117), with high-risk EOM (HR-EOM), including esophageal, nasopharyngeal, and/or genital involvement (adjusted odds ratio [aOR]: 12.51; 95% confidence interval [CI]: 2.61-59.99; P = 0.002) and corneal scarring (aOR: 3.06; 95% CI, 1.15-8.14; P = 0.025), as significant risk factors for persistent inflammation. Disease relapse, progression, and vision loss occurred in 20% of patients (23/117), 12% of patients (14/117), and 27% of patients (32/117), respectively. Baseline corneal scarring was a risk factor for relapse (adjusted hazard ratio: 4.14; 95% CI: 1.61-10.62; P = 0.003), progression (aOR: 11.46; 95% CI: 1.78-73.75; P = 0.010), and vision loss (aOR: 3.51; 95% CI: 1.35-9.10; P = 0.010). HR-EOM was associated with stage progression (aOR, 34.57; 95% CI, 6.57-181.89; P<0.001) and vision loss (aOR, 8.42; 95% CI, 2.50-28.42; P = 0.001). No significant differences were found between IMT regimes and relapse (P = 0.169). CONCLUSIONS: Ocular mucous membrane pemphigoid presenting with HR-EOMs and corneal scarring has an increased risk of stage progression and vision loss. Corneal scarring and severe inflammation at baseline were associated with an increased risk of relapse. A disease progression staging system incorporating both the HR-EOMs and corneal involvement is required to predict the visual outcome of OMMP better. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Technical and tactical evolution of the offensive team sequences in LaLiga between 2008 and 2021. Is Spanish football now a more associative game?

The aim of this investigation was to study the technical and tactical evolution of the offensive team sequences in the Spanish football teams from 2008/09 to 2020/21. A comparative analysis including twelve variables related to the development of offensive sequences in 4940 matches was performed from 2008/09 to 2020/21 seasons of the Spanish professional football league (LaLiga). All match observations were recorded using a validated video tracking system. Multilevel linear mixed models were used to examine the differences across seasons, considering the effects of contextual variables. The number of passes per sequence (2.4 [CI: 2.2-2.5] vs 3.2 [CI: 3.0-3.4]; +33.3%), the passing accuracy (72.1 [CI: 70.6-73.5] vs 76.9 [CI: 75.4-78.3]%; +6.8%) and the average duration of the team sequences (6.4 [CI: 5.9-6.8] vs 8.3 [CI: 7.8-8.7] seconds; +25.76%) showed a small increasing trend over the seasons (P < 0.05). In contrast, variables such as the direct speed of progression (2.2 [CI: 2.1-2.3] vs 1.6 [CI: 1.5-1.7] metres/second; -24.5%), key passes (8.1 [CI: 7.6-8.5] vs 6.8 [CI: 6.3-7.2]; -15.8%), and the sequences that ended in the attacking third (64.8 [CI: 62,7-66.8] vs 57.1 [CI: 55.1-59.2]; -11.7%) or in a shot (13.0 [CI: 12.4-13.6] vs 10.2 [CI: 9.6-10.8]; -21.6%) showed a small decreasing trend from 2008/09 to 2020/21 (P < 0.05). Spanish professional football teams slightly evolved technically and tactically towards a more associative style of play that includes longer passing sequences. This evolution also involved a decreasing speed of progression and fewer technical actions such as through balls, key passes and shots.

Circadian modulation of the time course of automatic and controlled semantic processing.

We investigated whether chronotype and time-of-day modulate the time course of automatic and controlled semantic processing. Participants performed a category semantic priming task at either the optimal or non-optimal time of day. We varied the prime-target onset asynchrony (100-, 450-, 650-, and 850-ms SOAs) and kept the percentage of unrelated targets constant at 80%. Automatic processing was expected with the short SOA, and controlled processing with longer SOAs. Intermediate-types (Experiment 1) verified that our task was sensitive to capturing both types of processes and served as a reference to assess themin extreme chronotypes. Morning-type and evening-type participants (Experiment 2) differed in the influence of time of testing on priming effects. Morning-types applied control in all conditions, and no performance modulation by time-of-day was observed. In contrast, evening-types were most adversely affected by the time of day to shift from automatic-based to controlled-based responses. Also, they were considerably affected in successfully implementing controlled processing with long intervals, particularly at the non-optimal time of day, with inhibitory priming showing only a marginally significant effect at the longest SOA. These results suggest that extreme chronotypes may be associated with different styles of cognitive control. Morning-types would be driven by a proactive control style, whereas a reactive control style might be applied by evening-types.

Pharmacogenomic Analysis of Response to Topical Tumor Necrosis Factor α Antagonist Licaminlimab (OCS-02) in Dry Eye Disease.

PURPOSE: The purpose of this study was to evaluate the pharmacogenomics of response to topical ocular tumor necrosis factor α (TNFα) inhibitor licaminlimab in patients with DED. METHODS: Three single-nucleotide polymorphisms (SNPs) associated with Sjögren syndrome, 3 in the TNFα gene and 1 in the TNF receptor 1 (TNFR1) gene, were assessed for association with response to licaminlimab in participants from a randomized, vehicle-controlled, Phase 2 study in which adults with DED and severe ocular discomfort persisting despite treatment with artificial tears received licaminlimab or vehicle for 6 weeks. Response was assessed for change from baseline in Global Ocular Discomfort score at Day 29 of treatment. The pharmacogenomic analysis was a prospectively specified exploratory objective of the study. mRNA expression for TNFα, interleukin (IL) 1ß, and IL8 in conjunctival epithelium cells was determined. The relationship between SNPs and response to licaminlimab was assessed using a mixed model repeated measures analysis. RESULTS: SNP rs1800693 in the TNFR1 gene showed a significant effect on response to licaminlimab (P < 0.0001, initial association test); no effect was seen for any of the other SNPs tested. The CC genotype of rs1800693 was associated with much greater response to licaminlimab than the CT or TT genotypes: LS mean changes from baseline to Day 29 in Global Ocular Discomfort score were -29.5, -0.09, and -3.90, in patients with the CC, CT, and TT genotypes, respectively (P < 0.0001). No significant effect was observed in vehicle-treated patients. Improvements from baseline were seen in 3/4 licaminlimab-treated participants with the CC genotype. Conjunctival epithelium cell levels of mRNA for TNFα, IL1ß, and IL8 decreased from baseline in participants with the CC genotype, but not with the CT or TT genotypes. Between-genotype differences in mRNA levels were not observed in participants receiving vehicle. CONCLUSIONS: The CC genotype of rs1800693, relatively common in patients with DED, was strongly associated with response to licaminlimab and decreased inflammatory cytokine gene expression in ocular surface cells during treatment. This study is one of the first to our knowledge to investigate pharmacogenomics in the treatment of DED.

Comparison of male and female non-refugee immigrants with psychosis: clinical, sociodemographic, and migration-related differences and impact on stress.

PURPOSE: To compare social, clinical, and migration-related factors between male and female immigrants with psychotic disorders and to determine the association between these variables and stress in the last year. METHODS: We administered the Holmes and Rahe Social Readjustment Scale to evaluate psychological stress in 99 non-refugee immigrants (26 women, 73 men) who presented ≥ one psychotic episode (ICD-10 criteria). We compared the two groups in terms of sociodemographic, clinical, cultural, and migration-related variables. A multivariable analysis using a linear regression model (stepwise method) was performed to evaluate potential associations between these variables and stress. RESULTS: Women were more likely to be married and divorced, had less access to welfare payments, and lower unemployment and homeless rates than men. The most common psychiatric diagnosis was psychosis not otherwise specified with more women being affected (61.5% in women vs. 45.2% in men), but the diagnosis of schizophrenia was more common in men (38.4% vs 15.4%). Both groups exhibited very high levels of stress in the past year (mean total distress score > 300). In women, stress was significantly associated with age at first migration and be a racialized person. By contrast, among men stress was significantly associated with language barrier and comorbidity with a physical disorder. CONCLUSIONS: The results of this study reveal important differences between men and women immigrants. These findings underscore the importance of understanding how gender-specific roles and social expectations intersect with the timing and nature of migration to influence stress levels differently in immigrant women and men with psychotic disorders.