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Expert Opinion on Biological Therapy Jul 2024Neovascular age-related macular degeneration (nAMD) represents a leading cause of severe visual impairment in individuals over 50 years of age in developed nations.... (Review)
Review
INTRODUCTION
Neovascular age-related macular degeneration (nAMD) represents a leading cause of severe visual impairment in individuals over 50 years of age in developed nations. Intravitreal anti-vascular endothelial growth factor (VEGF) injections have become the standard of care for treating nAMD; however, monthly or bimonthly dosing represents significant time and cost burden due to the disease's chronic nature and limited medication half-life.
AREAS COVERED
This review summarizes innovative therapeutics and delivery methods for nAMD. Emerging methods for extended drug delivery include high molar concentration anti-VEGF drugs, intravitreal sustained release devices, reservoirs for intravitreal delivery, and gene therapy biofactories. In addition to VEGF-A, therapies targeting inhibition of VEGF-C and D, the angiopoetin-2 (Ang-2)/Tie-2 pathway, tyrosine kinases, and integrins are reviewed.
EXPERT OPINION
The evolving therapeutic landscape of nAMD is rapidly expanding our toolkit for effective and durable treatment. Recent FDA approvals of faricimab (Vabysmo) and high dose aflibercept (Eylea HD) for nAMD with potential extension of injection intervals up to four months have been promising developments for patients and providers alike. Further research and innovation, including novel delivery techniques and pharmacologic targets, is necessary to validate the efficacy of developing therapeutics and characterize real-world outcomes. demonstrating promise in expanding treatment durability.
PubMed: 38953649
DOI: 10.1080/14712598.2024.2374869 -
MBio Jul 2024Human intestinal enteroids (HIEs) are gaining recognition as physiologically relevant models of the intestinal epithelium. While HIEs from adults are used extensively in...
UNLABELLED
Human intestinal enteroids (HIEs) are gaining recognition as physiologically relevant models of the intestinal epithelium. While HIEs from adults are used extensively in biomedical research, few studies have used HIEs from infants. Considering the dramatic developmental changes that occur during infancy, it is important to establish models that represent infant intestinal characteristics and physiological responses. We established jejunal HIEs from infant surgical samples and performed comparisons to jejunal HIEs from adults using RNA sequencing (RNA-Seq) and morphologic analyses. We then validated differences in key pathways through functional studies and determined whether these cultures recapitulate known features of the infant intestinal epithelium. RNA-Seq analysis showed significant differences in the transcriptome of infant and adult HIEs, including differences in genes and pathways associated with cell differentiation and proliferation, tissue development, lipid metabolism, innate immunity, and biological adhesion. Validating these results, we observed a higher abundance of cells expressing specific enterocyte, goblet cell, and enteroendocrine cell markers in differentiated infant HIE monolayers, and greater numbers of proliferative cells in undifferentiated 3D cultures. Compared to adult HIEs, infant HIEs portray characteristics of an immature gastrointestinal epithelium including significantly shorter cell height, lower epithelial barrier integrity, and lower innate immune responses to infection with an oral poliovirus vaccine. HIEs established from infant intestinal tissues reflect characteristics of the infant gut and are distinct from adult cultures. Our data support the use of infant HIEs as an model to advance studies of infant-specific diseases and drug discovery for this population.
IMPORTANCE
Tissue or biopsy stem cell-derived human intestinal enteroids are increasingly recognized as physiologically relevant models of the human gastrointestinal epithelium. While enteroids from adults and fetal tissues have been extensively used for studying many infectious and non-infectious diseases, there are few reports on enteroids from infants. We show that infant enteroids exhibit both transcriptomic and morphological differences compared to adult cultures. They also differ in functional responses to barrier disruption and innate immune responses to infection, suggesting that infant and adult enteroids are distinct model systems. Considering the dramatic changes in body composition and physiology that begin during infancy, tools that appropriately reflect intestinal development and diseases are critical. Infant enteroids exhibit key features of the infant gastrointestinal epithelium. This study is significant in establishing infant enteroids as age-appropriate models for infant intestinal physiology, infant-specific diseases, and responses to pathogens.
PubMed: 38953637
DOI: 10.1128/mbio.01316-24 -
Muscle & Nerve Jul 2024Fatigue is a common and debilitating symptom encountered in the neuromuscular clinic. The 7-item Fatigue Severity Scale (FSS-7) is a Rasch-modified assessment validated...
INTRODUCTION/AIMS
Fatigue is a common and debilitating symptom encountered in the neuromuscular clinic. The 7-item Fatigue Severity Scale (FSS-7) is a Rasch-modified assessment validated in inflammatory neuropathies but not across a typical neuromuscular patient population. The aim of this study was to validate this measure in neuromuscular disorders and to compare between patient sex, age and diagnoses.
METHODS
The modified FSS-7 was mailed to patients recruited from a specialist neuromuscular clinic at the Walton Centre. Responses were subjected to Rasch analysis and descriptive statistics were performed on the Rasch converted data.
RESULTS
The mFSS-7 met the Rasch model expectations with an overall Chi-square probability of 0.4918, a strict unidimensional scale free from differential item functioning (DIF) that satisfied the model with substantial test-retest reliability using Lin's concordance correlation coefficient 0.71 (95% CI 0.63-0.77). A 15.7% ceiling effect was observed in this patient cohort. Post hoc analysis did not show any significant difference in fatigue between sex, age or neuromuscular diagnoses.
DISCUSSION
The self-completed Rasch mFSS-7 showed acceptable test-retest reliability across patients with varied disorders under follow-up in a specialist neuromuscular clinic. The ceiling effect constrains its use for those with the most severe fatigue. Future considerations could include assessment of the benefits of clinical interventions, particularly multidisciplinary team input or dedicated fatigue clinics.
PubMed: 38953614
DOI: 10.1002/mus.28186 -
ACS Nano Jul 2024Rechargeable aqueous batteries adopting Fe-based materials are attracting widespread attention by virtue of high-safety and low-cost. However, the present Fe-based...
Rechargeable aqueous batteries adopting Fe-based materials are attracting widespread attention by virtue of high-safety and low-cost. However, the present Fe-based anodes suffer from low electronic/ionic conductivity and unsatisfactory comprehensive performance, which greatly restrict their practicability. Concerning the principle of physical chemistry, fabricating electrodes that could simultaneously achieve ideal thermodynamics and fast kinetics is a promising issue. Herein, hierarchical FeO@Fe foam electrode with enhanced interface/grain boundary engineering is fabricated through an in situ self-regulated strategy. The electrode achieves ultrahigh areal capacity of 31.45 mA h cm (50 mA cm), good scale application potential (742.54 mA h for 25 cm electrode), satisfied antifluctuation capability, and excellent cycling stability. In/ex situ characterizations further validate the desired thermodynamic and kinetic properties of the electrode endowed with accurate interface regulation, which accounts for salient electrochemical reversibility in a two-stage phase transition and slight energy loss. This work offers a suitable strategy in designing high-performance Fe-based electrodes with comprehensive inherent characteristics for high-safety large-scale energy storage.
PubMed: 38953611
DOI: 10.1021/acsnano.4c03301 -
The Journal of the Acoustical Society... Jul 2024We derive a simple formula for the lowest natural frequencies of an infinitely long bubble plume with arbitrary cross section. Expressions are derived in terms of bubble...
We derive a simple formula for the lowest natural frequencies of an infinitely long bubble plume with arbitrary cross section. Expressions are derived in terms of bubble volume fraction and equivalent radius of the plume, and a criterion for the existence of collective modes is established. For the plume with the circular cross section, our analytical approach is validated with the results of previous studies and numerical solution.
PubMed: 38953601
DOI: 10.1121/10.0026455 -
Psychology & Health Jul 2024This research aimed to construct and psychometrically test a measure of multiple sociocultural dimensions (i.e. family, peers, media) theoretically associated with...
OBJECTIVES
This research aimed to construct and psychometrically test a measure of multiple sociocultural dimensions (i.e. family, peers, media) theoretically associated with exercise behaviours/attitudes in adolescents; the Sociocultural Influences on Exercise Behaviours in Adolescents Questionnaire (SIEBAQ).
METHODS AND MEASUREMENT
Part 1 of this study focused on measure construction and psychometric testing, involving item generation and exploratory factor analysis (EFA) to refine the item pool, with 905 adolescents (age 13.66 years (SD = 0.94); girls = 442). Part 2 sought to explore the convergent validity of the SIEBAQ ( = 846; = 414 girls).
RESULTS
EFA resulted in a 47-item measure with a nine-factor structure (including social media modelling, parent exercise expectations, peer co-participation; α = 0.72-0.92). Correlations revealed weak-moderate significant relationships between the SIEBAQ and related constructs (e.g. compulsive exercise, sociocultural attitudes towards appearance). Regression analyses with the SIEBAQ identified social media modelling of exercise as a significant predictor of compulsive exercise in boys and girls. Proving exercise ability to significant others also significantly predicted compulsive exercise outcomes.
CONCLUSION
This newly developed measure holds promise. Further psychometric testing and validation of the SIEBAQ is the recommended next step to confirm the measure's nine-factor structure identified through EFA.
PubMed: 38953588
DOI: 10.1080/08870446.2024.2372644 -
General Physiology and Biophysics Jul 2024Alzheimer's disease is currently not curable. Almost all attempts to identify disease-modifying drugs failed and the causes of disease etiology are not well understood....
Alzheimer's disease is currently not curable. Almost all attempts to identify disease-modifying drugs failed and the causes of disease etiology are not well understood. Neurofibrillary tangles composed of pathological tau protein belong to the main hallmarks of this disease. Identification of novel physiological and pathological tau interacting proteins may lead to a better understanding of Alzheimer's disease pathology and tau physiology and therefore we performed a screening of the brain library by a yeast two-hybrid system intending to identify new tau interaction partners. We identified CHORDC1 (cysteine and histidine-rich domain-containing protein 1) as a novel tau interaction partner by this approach. The CHORDC1-tau interaction was validated by co-immunoprecipitation from rat brain tissues and by in vitro co-localization in the cellular model expressing full-length human tau protein. We believe that our results can be useful for researchers studying tau protein in health and disease.
Topics: tau Proteins; Rats; Animals; Humans; Protein Binding; Brain; Protein Interaction Mapping; Two-Hybrid System Techniques
PubMed: 38953578
DOI: 10.4149/gpb_2024019 -
Journal of Cellular and Molecular... Jul 2024Both osteoporosis and tendinopathy are widely prevalent disorders, encountered in diverse medical contexts. Whilst each condition has distinct pathophysiological... (Review)
Review
Both osteoporosis and tendinopathy are widely prevalent disorders, encountered in diverse medical contexts. Whilst each condition has distinct pathophysiological characteristics, they share several risk factors and underlying causes. Notably, oxidative stress emerges as a crucial intersecting factor, playing a pivotal role in the onset and progression of both diseases. This imbalance arises from a dysregulation in generating and neutralising reactive oxygen species (ROS), leading to an abnormal oxidative environment. Elevated levels of ROS can induce multiple cellular disruptions, such as cytotoxicity, apoptosis activation and reduced cell function, contributing to tissue deterioration and weakening the structural integrity of bones and tendons. Antioxidants are substances that can prevent or slow down the oxidation process, including Vitamin C, melatonin, resveratrol, anthocyanins and so on, demonstrating potential in treating these overlapping disorders. This comprehensive review aims to elucidate the complex role of oxidative stress within the interlinked pathways of these comorbid conditions. By integrating contemporary research and empirical findings, our objective is to outline new conceptual models and innovative treatment strategies for effectively managing these prevalent diseases. This review underscores the importance of further in-depth research to validate the efficacy of antioxidants and traditional Chinese medicine in treatment plans, as well as to explore targeted interventions focused on oxidative stress as promising areas for future medical advancements.
Topics: Humans; Oxidative Stress; Osteoporosis; Antioxidants; Tendinopathy; Reactive Oxygen Species; Animals
PubMed: 38953556
DOI: 10.1111/jcmm.18508 -
Child: Care, Health and Development Jul 2024A substantial proportion of children have a physical illness; these children commonly experience physical-mental comorbidity. To assess child mental health, brief scales...
BACKGROUND
A substantial proportion of children have a physical illness; these children commonly experience physical-mental comorbidity. To assess child mental health, brief scales that can be used in clinical and research settings are needed. This study assessed the validity and reliability of parent-reported Ontario Child Health Study Emotional Behavioural Scale-Brief Version (OCHS-EBS-B) scores.
METHODS
Data come from a longitudinal study of children aged 2-16 years with a physical illness recruited from outpatient clinics at a pediatric hospital. Confirmatory factor analysis and McDonald's coefficient assessed the factor structure and internal consistency reliability of the OCHS-EBS-B, respectively. Point biserial correlations assessed agreement between the OCHS-EBS-B and Mini International Neuropsychiatric Interview for Children and Adolescents (MINI-KID), a structured diagnostic interview. The Wilcoxon rank sum test compared OCHS-EBS-B scores between children with versus without physical-mental comorbidity (known-group validity).
RESULTS
The three-factor structure of the OCHS-EBS-B was replicated in this sample of children with physical illness (χ = 196.23(272), p < 0.001; CFI = 0.98; TLI = 0.98; SRMR = 0.06; RMSEA [90% CI] = 0.034 [0.027, 0.044]). It had excellent internal consistency reliability (ω = 0.86-0.92) and was moderately correlated with the MINI-KID (baseline: r = 0.43-0.51; 6 months: r = 0.55-0.65). OCHS-EBS-B scores were significantly higher among children with versus without physical-mental comorbidity.
CONCLUSIONS
Findings confirm psychometric evidence that the OCHS-EBS-B is a valid and reliable measure of mental health in children with chronic physical illness. Its brevity and robust psychometric properties make the OCHS-EBS-B a strong candidate for routine use in integrated pediatric physical and mental health services.
Topics: Humans; Child; Male; Female; Reproducibility of Results; Child, Preschool; Chronic Disease; Adolescent; Ontario; Psychometrics; Longitudinal Studies; Factor Analysis, Statistical; Mental Disorders; Psychiatric Status Rating Scales; Comorbidity; Mental Health
PubMed: 38953538
DOI: 10.1111/cch.13300 -
Ergonomics Jul 2024This study proposes a systematic approach to address ergonomic factors, including physical, environmental and psychosocial aspects, in solving assembly line balancing...
This study proposes a systematic approach to address ergonomic factors, including physical, environmental and psychosocial aspects, in solving assembly line balancing problems. A three-stage framework is developed, starting with determining weights for ergonomic risk assessment methods using the interval-valued spherical fuzzy analytical hierarchy process. In the second stage, a fuzzy logic model for integrated ergonomic risk assessment is constructed based on these weights, and the integrated ergonomic risk score is determined. In the third stage, a mathematical model is formulated to minimise the cycle time while balancing the ergonomic risk level. A case study conducted in a wire harness factory validated the effectiveness of the proposed approach, showing a 10-11% improvement in line efficiency and a 12-25% enhancement in ergonomic risk balancing performance. These findings underscore the potential benefits of implementing this approach, which can significantly improve occupational safety and overall performance.
PubMed: 38953513
DOI: 10.1080/00140139.2024.2368270