Vitreoschisis-induced vitreous cortex remnants in proliferative vitreoretinopathy: A comprehensive review from basic research to clinical practice.

Proliferative vitreoretinopathy (PVR) significantly impacts the prognosis of rhegmatogenous retinal detachment (RRD), one of the most critical and increasing causes of vision loss in the Western world. Despite advancements in surgical instruments and techniques, the failure rate due to PVR remains substantial, necessitating additional surgeries and often leading to unsatisfactory visual outcomes. This comprehensive review explores the role of vitreoschisis-induced vitreous cortex remnants (VCR) as a critical, previously under-recognised factor contributing to PVR. Vitreoschisis, a phenomenon where the inner lamellae of the posterior vitreous cortex detach while the outermost layers remain attached to the retina, creates VCR that may contain hyalocytes and serve as scaffolds for fibrocellular proliferation. These remnants are difficult to visualise without triamcinolone acetonide (TA) staining, leading to their frequent lack of recognition in clinical practice. Moreover, removing VCR can be challenging and time-consuming, often requiring meticulous surgical techniques to avoid retinal damage and ensure complete elimination. This review consolidates insights from basic research and clinical practice, emphasising the importance of complete vitreous removal and effective VCR detection and removal to mitigate PVR risks. It highlights the histopathological and clinical evidence supporting the hypothesis that VCR, containing hyalocytes, play a pivotal role in preretinal membrane formation. The review also discusses epidemiological data, surgical management strategies and potential future directions, including improved visualisation techniques and the development of new surgical tools and methods. This review aims to improve surgical outcomes and reduce the frequency and burden of RRD-related complications by addressing VCR as a critical factor in PVR.

Multi-dimensional analysis of B cells reveals the expansion of memory and regulatory B cell clusters in humans living in rural tropical areas.

B-cells play a critical role in the formation of immune responses against pathogens by acting as antigen-presenting cells, by modulating immune responses and by generating immune memory and antibody responses. Here, we studied B-cell subset distributions between regions with higher and lower microbial exposure, i.e. by comparing peripheral blood B-cells from people living in Indonesia or Ghana to those from healthy Dutch residents using a 36-marker mass cytometry panel. By applying an unbiased multidimensional approach, we observed differences in the balance between the naïve and memory compartments, with higher CD11c+ and double negative (DN-IgDnegCD27neg) memory (M)B-cells in individuals from rural tropical areas, and conversely lower naïve B-cells compared to residents from an area with less pathogen exposure. Furthermore, characterization of total B-cell populations, CD11c+, DN and Breg cells showed the emergence of specific memory clusters in individuals living in rural tropical areas. Some of these differences were more pronounced in children compared to adults and suggest that a higher microbial exposure accelerates memory B cell formation, which 'normalizes' with age.

A Scoping Review on the Influence of Contextual Factors on Training Load in Adolescent Soccer Players: What Do We Know?

This scoping review aimed to systematically explore the breadth and extent of the literature regarding the relationship between contextual factors (CFs) and training load (TL) in adolescent soccer players. Further aims included comprehending potential underlying mechanisms and identifying knowledge gaps. CFs were defined as factors not part of the main training process, such as the coach-athlete relationship and educational responsibilities. PubMed, EBSCO APA PsycINFO, Web of Science, ProQuest Dissertations & Theses A&I, and SportRxiv were searched. Studies involving adolescent soccer players that investigated the CF-TL relationship and measured TL indicators were deemed eligible. Seventeen studies were included, reflecting the limited number of articles published regarding the CF-TL relationship. CFs were mostly related to match-play (N = 13) and phase of the season (N = 7). Moreover, these factors appeared to affect TL. CF related to players' personal environment (N = 3) were underrepresented in the reviewed studies. Overall, the CF-TL relationship appears to be rarely scrutinized. A likely cause for this lack of research is the segregation of the physiological and psychological research domains, where the CF-TL relationship is often speculated upon but not measured. Therefore, a holistic approach is warranted which also investigates the effect of personal environment, such as stressful life stress events, on TL.

Early symptom-associated inflammatory responses shift to type 2 responses in controlled human schistosome infection.

Schistosomiasis is an infection caused by contact with Schistosoma-contaminated water and affects more than 230 million people worldwide with varying morbidity. The roles of T helper 2 (TH2) cells and regulatory immune responses in chronic infection are well documented, but less is known about human immune responses during acute infection. Here, we comprehensively map immune responses during controlled human Schistosoma mansoni infection using male or female cercariae. Immune responses to male or female parasite single-sex infection were comparable. An early TH1-biased inflammatory response was observed at week 4 after infection, which was particularly apparent in individuals experiencing symptoms of acute schistosomiasis. By week 8 after infection, inflammatory responses were followed by an expansion of TH2 and regulatory cell subsets. This study demonstrates the shift from TH1 to both TH2 and regulatory responses, typical of chronic schistosomiasis, in the absence of egg production and provides immunological insight into the clinical manifestations of acute schistosomiasis.

Resilience in sports: a multidisciplinary, dynamic, and personalized perspective.

Athletes are exposed to various psychological and physiological stressors, such as losing matches and high training loads. Understanding and improving the resilience of athletes is therefore crucial to prevent performance decrements and psychological or physical problems. In this review, resilience is conceptualized as a dynamic process of bouncing back to normal functioning following stressors. This process has been of wide interest in psychology, but also in the physiology and sports science literature (e.g. load and recovery). To improve our understanding of the process of resilience, we argue for a collaborative synthesis of knowledge from the domains of psychology, physiology, sports science, and data science. Accordingly, we propose a multidisciplinary, dynamic, and personalized research agenda on resilience. We explain how new technologies and data science applications are important future trends (1) to detect warning signals for resilience losses in (combinations of) psychological and physiological changes, and (2) to provide athletes and their coaches with personalized feedback about athletes' resilience.

Immune responses associated with protection induced by chemoattenuated PfSPZ vaccine in malaria-naive Europeans.

Vaccination of malaria-naive volunteers with a high dose of Plasmodium falciparum sporozoites chemoattenuated by chloroquine (CQ) (PfSPZ-CVac [CQ]) has previously demonstrated full protection against controlled human malaria infection (CHMI). However, lower doses of PfSPZ-CVac [CQ] resulted in incomplete protection. This provides the opportunity to understand the immune mechanisms needed for better vaccine-induced protection by comparing individuals who were protected with those not protected. Using mass cytometry, we characterized immune cell composition and responses of malaria-naive European volunteers who received either lower doses of PfSPZ-CVac [CQ], resulting in 50% protection irrespective of the dose, or a placebo vaccination, with everyone becoming infected following CHMI. Clusters of CD4+ and γδ T cells associated with protection were identified, consistent with their known role in malaria immunity. Additionally, EMRA CD8+ T cells and CD56+CD8+ T cell clusters were associated with protection. In a cohort from a malaria-endemic area in Gabon, these CD8+ T cell clusters were also associated with parasitemia control in individuals with lifelong exposure to malaria. Upon stimulation with P. falciparum-infected erythrocytes, CD4+, γδ, and EMRA CD8+ T cells produced IFN-γ and/or TNF, indicating their ability to mediate responses that eliminate malaria parasites.

Impact of nutritional status on vaccine-induced immunity in children living in South Africa: Investigating the B-cell repertoire and metabolic hormones.

OBJECTIVES: We explored the role of metabolic hormones and the B-cell repertoire in the association between nutritional status and vaccine responses. METHODS: In this prospective cohort study, nested within a larger randomized open-label trial, 211 South African children received two doses of measles vaccine and two or three doses of pneumococcal conjugate vaccine (PCV). Metabolic markers (leptin, ghrelin and adiponectin) and distribution of B-cell subsets (n = 106) were assessed at 18 months of age. RESULTS: Children with a weight-for-height z-score (WHZ) ≤ -1 standard deviation (SD) at booster vaccination had a decreased mean serotype-specific PCV IgG response compared with those with WHZ > -1 and <+1 SD or WHZ ≥ +1 SD at 9 months post-booster (18 months of age). (Naive) pre-germinal center B-cells were associated with pneumococcal antibody decay between one to nine months post-booster. Predictive performance of elastic net models for the combined effect of B-cell subsets, metabolic hormones and nutritional status (in addition to age, sex, and randomization group) on measles and PCV vaccine response had an average area under the receiver operating curve of 0.9 and 0.7, respectively. CONCLUSIONS: The combined effect of B-cell subsets, metabolic hormones and nutritional status correlated well with the vaccination response for measles and most PCV serotypes. CLINICALTRIALS: gov registration of parent studies: NCT02943902 and NCT03330171.

Monitoring the recovery-stress states of athletes: Psychometric properties of the acute recovery and stress scale and short recovery stress scale among Dutch and Flemish athletes.

The Acute Recovery and Stress Scale (ARSS) and the Short Recovery and Stress Scale (SRSS) are recently-introduced instruments to monitor recovery and stress processes in athletes. In this study, our aims were to replicate and extend previous psychometric assessments of the instruments, by incorporating recovery and stress dimensions into one model. Therefore, we conducted five confirmatory factor analyses (CFA) and determined structural validity, internal consistency, and construct validity. Dutch and Flemish athletes (N = 385, 213 females, 170 males, 2 others, 21.03 ± 5.44 years) completed the translated ARSS and SRSS, the Recovery Stress Questionnaire for Athletes (RESTQ-Sport-76), the Rating of Perceived Exertion (RPE) and the Total Quality of Recovery (TQR). There was a good model fit for the replicated CFA, sub-optimal model fit for the models that incorporated recovery and stress into one model, and satisfactory internal consistency (α=.75 - .87). The correlations within and between the ARSS and SRSS, as well as between the ARSS/SRSS and the RESTQ-Sport-76 (r = .31 - -.77 for the ARSS, r = .28 - -.63 for the SRSS), the RPE (r = .19 - -.23), and the TQR (r = .63 - -.63) also supported construct validity. The combined findings support the use of the ARSS and SRSS to assess stress and recovery in sports-related research and practice.

Prevalence of vitreoschisis-induced vitreous cortex remnants over the peripheral retinal surface in eyes undergoing vitrectomy for primary rhegmatogenous retinal detachment.

PURPOSE: Unremoved vitreoschisis-induced vitreous cortex remnants over the peripheral retinal surface posterior to the vitreous base (pVCR) may increase the risk of surgical failure after primary rhegmatogenous retinal detachment (RRD) repair. The purpose of this study was to validate our previous findings on pVCR prevalence during vitrectomy for RRD and to examine their association with proliferative vitreoretinopathy (PVR) and surgical failure. METHODS: Prospective observational multisurgeon study of 100 eyes of 100 consecutive patients who underwent vitrectomy for RRD by one of four vitreoretinal surgeons. Collected data included detected pVCR and known PVR risk factors. Pooled analysis with our previous retrospective study (251 eyes of 251 patients) was also performed. RESULTS: Initial PVR (≥C) was present and removed in 6/100 (6%) patients, pVCR were detected in 36/100 (36%) patients, pVCR were removed in 30/36 (83%) patients with pVCR, and 4/36 (11%) patients with pVCR were high myopes (≤-6D). Six per cent (6/100) developed a retinal redetachment, of which 3/6 (50%) had initial PVR (≥C). Surgical failure rates in eyes with and without pVCR were 17% (6/36) and 0% (0/64), respectively. In eyes with pVCR and surgical failure, pVCR were not or not completely removed during the first surgery. Overall analysis showed that pVCR were statistically significantly associated with PVR. CONCLUSIONS: This study confirms our previous findings: a pVCR prevalence of around 35% and an association between pVCR, PVR formation and surgical failure in patients undergoing vitrectomy for RRD. More research is needed to determine which patients would benefit most from pVCR removal.

Discriminative validity of summarized hip and knee angular accelerations for lower extremity training load quantification in male soccer players during a standardised training drill.

This study assessed the discriminative validity of summarized hip and knee angular accelerations during a standardized training drill. Twenty-eight soccer players performed a standardized training drill that mimics game demands. Discriminative validity was examined by assessment of between-group differences of summarized preferred kicking leg hip and knee angular accelerations, and Playerload between national and regional soccer players for the full training drill, and parts based on locomotor intensity, or additional pass and jumping header activities. Furthermore, relationships were assessed between the summarized hip and knee angular accelerations and conventional load indicators derived from a local positioning measurement system, such as high-intensity running distance and Playerload. National players had higher summarized hip (Mean difference: 62.7 A.U. ES = 0.77, p = 0.049) and knee (Mean difference: 137.1 A.U. ES = 1.06, p = 0.008) angular accelerations. Significant interaction effects were observed during high-intensity running (Hip: 0.2 A.U./m, ES = 0.98, p = 0.005; Knee: 0.61 A.U./m, ES = 1.52, p < 0.001), and sprinting (Hip: 0.3 A.U./m, ES = 1.01, p < 0.02; Knee: 0.56 A.U./m, ES = 1.57, p < 0.001). Between-group differences were not present for additional passing or jumping header activities. Compared to summarized hip and knee angular accelerations, Playerload had less ability to discriminate between players and activities. Moreover, the lower extremity training load indicators were unrelated to conventional load indicators. Together these results confirm discriminative validity of summarized hip and knee angular acceleration training load indicators during a standardised training drill.

The results in this study substantiate the use and validity of summarized hip and knee angular accelerations as external training load indicators for the lower extremities in soccer. Based on the known-group difference technique, expected differences in summarized hip and knee angular accelerations between national and regional soccer players were observed during a standardized soccer training drill. These differences were present during high intensity running and sprint activities, but not for passing or jumping header activities. The limited ability of Playerload to discriminate between players and tasks, and insignificant relationships between measurement systems in this study demonstrate that summarized hip and knee angular accelerations can be used complementary to whole-body training load indicators for evaluating soccer training and match play. The presented methodology provides insights in the training load of individual limbs, which potentially can be used to assess the effectiveness of specific training drills to under- or overload specific limbs. Trainers, coaches, and sport practitioners can use this information to balance training load and recovery in soccer, aiming to improve performance and prevent overload.

Novel Surgical Treatment of an Intraretinal Juxtapapillary Hemangioblastoma Using Intraocular Diathermy Forceps: A Case Report.

The surgical treatment of intraretinal juxtapapillary retinal hemangioblastomas (JRHs) was previously contraindicated because of the significant risk of collateral damage to the macula and optic nerve. This case report discusses the effectiveness and safety of a novel surgical technique using intraocular bipolar diathermy forceps to coagulate feeder and draining blood vessels of an intraretinal JRH. The patient suffered from bilateral retinal hemangioblastomas with loss of visual function in one eye and the development of an intraretinal JRH in the other eye. Despite intensive treatment with intravitreal bevacizumab and subconjunctival triamcinolone acetonide, growth of the intraretinal JRH continued, macular exudation worsened, and visual acuity decreased. Surgical treatment was undertaken in which, first, the feeder and draining vessels of the JRH were identified by comparing the retinal imaging of the JRH with the imaging before the emergence of the JRH 4 years earlier. Then, retinal incisions were made above the blood vessels and parallel to the nerve fibers during a pars plana vitrectomy. Lastly, these vessels were lifted above the retinal surface and coagulated using intraocular diathermy forceps. Postoperatively, macular edema reduced, and visual acuity increased and remained stable for about 6 months. Using intraocular diathermy forceps, this case report demonstrates effective and safe intraretinal JRH blood vessel coagulation above the retinal surface. This novel surgical approach was able to delay the deterioration of visual acuity due to tumor growth and exudation in this patient. This suggests that coagulation with intraocular diathermy forceps can be considered an additional surgical treatment option for JRHs, especially those with an intraretinal growth pattern.

Anaerobic methanotrophy is stimulated by graphene oxide in a brackish urban canal sediment.

Anthropogenic activities are influencing aquatic environments through increased chemical pollution and thus are greatly affecting the biogeochemical cycling of elements. This has increased greenhouse gas emissions, particularly methane, from lakes, wetlands, and canals. Most of the methane produced in anoxic sediments is converted into carbon dioxide by methanotrophs before it reaches the atmosphere. Anaerobic oxidation of methane requires an electron acceptor such as sulphate, nitrate, or metal oxides. Here, we explore the anaerobic methanotrophy in sediments of three urban canals in Amsterdam, covering a gradient from freshwater to brackish conditions. Biogeochemical analysis showed the presence of a shallow sulphate-methane transition zone in sediments of the most brackish canal, suggesting that sulphate could be a relevant electron acceptor for anaerobic methanotrophy in this setting. However, sediment incubations amended with sulphate or iron oxides (ferrihydrite) did not lead to detectable rates of methanotrophy. Despite the presence of known nitrate-dependent anaerobic methanotrophs (Methanoperedenaceae), no nitrate-driven methanotrophy was observed in any of the investigated sediments either. Interestingly, graphene oxide stimulated anaerobic methanotrophy in incubations of brackish canal sediment, possibly catalysed by anaerobic methanotrophs of the ANME-2a/b clade. We propose that natural organic matter serving as electron acceptor drives anaerobic methanotrophy in brackish sediments.

Methanotrophic potential of Dutch canal wall biofilms is driven by Methylomonadaceae.

Global urbanization of waterways over the past millennium has influenced microbial communities in these aquatic ecosystems. Increased nutrient inputs have turned most urban waters into net sources of the greenhouse gases carbon dioxide (CO2) and methane (CH4). Here, canal walls of five Dutch cities were studied for their biofilm CH4 oxidation potential, alongside field observations of water chemistry, and CO2 and CH4 emissions. Three cities showed canal wall biofilms with relatively high biological CH4 oxidation potential up to 0.48 mmol gDW-1 d-1, whereas the other two cities showed no oxidation potential. Salinity was identified as the main driver of biofilm bacterial community composition. Crenothrix and Methyloglobulus methanotrophs were observed in CH4-oxidizing biofilms. We show that microbial oxidation in canal biofilms is widespread and is likely driven by the same taxa found across cities with distinctly different canal water chemistry. The oxidation potential of the biofilms was not correlated with the amount of CH4 emitted but was related to the presence or absence of methanotrophs in the biofilms. This was controlled by whether there was enough CH4 present to sustain a methanotrophic community. These results demonstrate that canal wall biofilms can directly contribute to the mitigation of greenhouse gases from urban canals.

Inflammatory and tolerogenic myeloid cells determine outcome following human allergen challenge.

Innate mononuclear phagocytic system (MPS) cells preserve mucosal immune homeostasis. We investigated their role at nasal mucosa following allergen challenge with house dust mite. We combined single-cell proteome and transcriptome profiling on nasal immune cells from nasal biopsies cells from 30 allergic rhinitis and 27 non-allergic subjects before and after repeated nasal allergen challenge. Biopsies of patients showed infiltrating inflammatory HLA-DRhi/CD14+ and CD16+ monocytes and proallergic transcriptional changes in resident CD1C+/CD1A+ conventional dendritic cells (cDC)2 following challenge. In contrast, non-allergic individuals displayed distinct innate MPS responses to allergen challenge: predominant infiltration of myeloid-derived suppressor cells (MDSC: HLA-DRlow/CD14+ monocytes) and cDC2 expressing inhibitory/tolerogenic transcripts. These divergent patterns were confirmed in ex vivo stimulated MPS nasal biopsy cells. Thus, we identified not only MPS cell clusters involved in airway allergic inflammation but also highlight novel roles for non-inflammatory innate MPS responses by MDSC to allergens in non-allergic individuals. Future therapies should address MDSC activity as treatment for inflammatory airway diseases.

Hybrid cellular Potts and bead-spring modeling of cells in fibrous extracellular matrix.

The mechanical interaction between cells and the extracellular matrix (ECM) is fundamental to coordinate collective cell behavior in tissues. Relating individual cell-level mechanics to tissue-scale collective behavior is a challenge that cell-based models such as the cellular Potts model (CPM) are well-positioned to address. These models generally represent the ECM with mean-field approaches, which assume substrate homogeneity. This assumption breaks down with fibrous ECM, which has nontrivial structure and mechanics. Here, we extend the CPM with a bead-spring model of ECM fiber networks modeled using molecular dynamics. We model a contractile cell pulling with discrete focal adhesion-like sites on the fiber network and demonstrate agreement with experimental spatiotemporal fiber densification and displacement. We show that at high network cross-linking, contractile cell forces propagate over at least eight cell diameters, decaying with distance with power law exponent n= 0.35 - 0.65 typical of viscoelastic ECMs. Further, we use in silico atomic force microscopy to measure local cell-induced network stiffening consistent with experiments. Our model lays the foundation for investigating how local and long-ranged cell-ECM mechanobiology contributes to multicellular morphogenesis.

Characteristics of a Large, Labeled Data Set for the Training of Artificial Intelligence for Glaucoma Screening with Fundus Photographs.

Purpose: Significant visual impairment due to glaucoma is largely caused by the disease being detected too late. Objective: To build a labeled data set for training artificial intelligence (AI) algorithms for glaucoma screening by fundus photography, to assess the accuracy of the graders, and to characterize the features of all eyes with referable glaucoma (RG). Design: Cross-sectional study. Subjects: Color fundus photographs (CFPs) of 113 893 eyes of 60 357 individuals were obtained from EyePACS, California, United States, from a population screening program for diabetic retinopathy. Methods: Carefully selected graders (ophthalmologists and optometrists) graded the images. To qualify, they had to pass the European Optic Disc Assessment Trial optic disc assessment with ≥ 85% accuracy and 92% specificity. Of 90 candidates, 30 passed. Each image of the EyePACS set was then scored by varying random pairs of graders as "RG," "no referable glaucoma (NRG)," or "ungradable (UG)." In case of disagreement, a glaucoma specialist made the final grading. Referable glaucoma was scored if visual field damage was expected. In case of RG, graders were instructed to mark up to 10 relevant glaucomatous features. Main Outcome Measures: Qualitative features in eyes with RG. Results: The performance of each grader was monitored; if the sensitivity and specificity dropped below 80% and 95%, respectively (the final grade served as reference), they exited the study and their gradings were redone by other graders. In all, 20 graders qualified; their mean sensitivity and specificity (standard deviation [SD]) were 85.6% (5.7) and 96.1% (2.8), respectively. The 2 graders agreed in 92.45% of the images (Gwet's AC2, expressing the inter-rater reliability, was 0.917). Of all gradings, the sensitivity and specificity (95% confidence interval) were 86.0 (85.2-86.7)% and 96.4 (96.3-96.5)%, respectively. Of all gradable eyes (n = 111 183; 97.62%) the prevalence of RG was 4.38%. The most common features of RG were the appearance of the neuroretinal rim (NRR) inferiorly and superiorly. Conclusions: A large data set of CFPs was put together of sufficient quality to develop AI screening solutions for glaucoma. The most common features of RG were the appearance of the NRR inferiorly and superiorly. Disc hemorrhages were a rare feature of RG. Financial Disclosures: Proprietary or commercial disclosure may be found after the references.

Effectiveness of task-specific training using assistive devices and task-specific usual care on upper limb performance after stroke: a systematic review and meta-analysis.

PURPOSE: Task-specific rehabilitation is a key indicator for successful rehabilitation to improve the upper limb performance after stroke. Assistive robotic and non-robotic devices are emerging to provide rehabilitation therapy; however, the effectiveness of task-specific training programs using assistive training devices compared with task-specific usual care training has not been summarized yet. Therefore, the effectiveness of task-specific training using assistive arm devices (TST-AAD) compared with task-specific usual care (TSUC) on the upper limb performance of patients with a stroke was investigated. To assess task specificity, a set of criteria was proposed: participation, program, relevant, repeated, randomized, reconstruction and reinforced. MATERIALS AND METHODS: Out of 855 articles, 17 fulfilled the selection criteria. A meta-analysis was performed on the Fugl-Meyer Assessment scores in the subacute and chronic stages after stroke and during follow-up. RESULTS AND CONCLUSION: Both TST-AAD and TSUC improved the upper limb performance after stroke. In the sub-acute phase after stroke, TST-AAD was more effective than TSUC in reducing the upper limb impairment, although findings were based on only three studies. In the chronic phase, TST-AAD and TSUC showed similar effectiveness. No differences between the two types of training were found at the follow-up measurements. Future studies should describe training, device usage and criteria of task specificity in a standardized way to ease comparison.Implications for rehabilitationArm or hand function is often undertreated in stroke patients, assistive training devices may be able to improve the upper limb performance.Task-specific training using assistive devices is effective in improving the upper limb performance after stroke.Task-specific training using assistive devices seems to be more effective in reducing impairment compared with task specific usual care in the subacute phase after stroke, but they are equally effective in the chronic phase of stroke.