Unveiling first report on in silico modeling of aquatic toxicity of organic chemicals to Labeo rohita (Rohu) employing QSAR and q-RASAR.

Labeo rohita, a fish species within the Carp family, holds significant dietary and aquacultural importance in South Asian countries. However, the habitats of L. rohita often face exposure to various harmful pesticides and organic compounds originating from industrial and agricultural runoff. It is challenging to individually investigate the effects of each potentially harmful compound. In such cases, in silico techniques like Quantitative Structure-Activity Relationship (QSAR) and quantitative Read-Across Structure-Activity Relationship (q-RASAR) can be employed to construct algorithmic models capable of simultaneously assessing the toxicity of numerous compounds. We utilized the US EPA's ToxValDB database to curate data regarding acute median lethal concentration (LC50) toxicity for L. rohita. The experimental variables included study type (mortality), study duration (ranging from 0.25 h to 4 h), exposure route (static, flowthrough, and renewal), exposure method (drinking water), and types of chemicals (industrial chemicals and pharmaceuticals). Using this dataset, we developed regression-based QSAR and q-RASAR models to predict chemical toxicity to L. rohita based on chemical descriptors. The key descriptors for predicting the toxicity of L. rohita in the regression-based QSAR model include F05[S-Cl], SpMax_EA(ri), s4_relPathLength_2, and SpDiam_AEA(ed). These descriptors can be employed to estimate the toxicity of untested compounds and aid in the development of compounds with lower toxicity based on the presence or absence of these descriptors. Both the QSAR and q-RASAR models serve as valuable tools for understanding the chemicals' structural features responsible for toxicity and for filling gaps in aquatic toxicity data by predicting the toxicity of newly untested compounds in relation to L. rohita. Finally, the developed best model was employed to predict 297 external chemicals, the most toxic substances to L. rohita were identified as cyhalothrin, isobornyl thiocyanatoacetate, and paclobutrzol, while the least toxic ones included ethyl acetate, ethylthiourea, and n-butyric acid.

Computational Modeling of Human Serum Albumin Binding of Per- and Polyfluoroalkyl Substances Employing QSAR, Read-Across, and Docking.

Per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals in widespread use that have been shown to be toxic to wildlife and humans. Human serum albumin (HSA) is a known transport protein that binds PFAS at various sites, leading to bioaccumulation and long-term toxicity. In silico tools like quantitative structure-activity relationship (QSAR), read-across, and quantitative read-across structure-property relationship (q-RASPR) are proven techniques for modeling chemical toxicity based on experimental data which can be used to predict the toxicity of untested and new chemicals, while at the same time, help to identify the major features responsible for toxicity. Classification-based and regression-based QSAR models are employed in the present study to predict the binding affinities of 24 PFAS to HSA. Regression-based QSAR models revealed that the packing density index (PDI) and quantitative estimation of drug-likeness (QED) descriptors were both positively correlated with higher binding affinity, while the classification-based QSAR model showed the average connectivity index of order 4 (X4A) descriptor was inversely correlated with binding affinity. Whereas molecular docking studies suggested that PFAS with the highest binding affinity to HSA create hydrogen bonds with Arg348 and salt bridges with Arg348 and Arg485, PFAS with lower binding affinity either showed no interactions with either amino acid or only interactions with Arg348. Among the studied PFAS, perfluoroalkyl acids (PFAA) with large carbon chain length (>C10) have one of the lowest binding affinities, compared to PFAA with carbon chain length ranging from 7 to 9, which showed the highest affinity to HSA. Generalized Read-Across (GenRA) was used to predict toxicity outcomes for the top five highest binding affinity PFAS based on 10 structural analogs for each and found that all are predicted as being chronic to sub-chronically toxic to HSA. The developed in silico models presented in this work can provide a framework for designing PFAS alternatives, screening compounds currently in use, and for the study of PFAS mixture toxicity, which is an area of intense research.

"Unknown world of wheelchairs" A mixed methods study exploring experiences of wheelchair and seating assistive technology provision for people with spinal cord injury in an Irish context.

AIM: This study explores people living with spinal cord injury (SCI) experiences and perspectives of wheelchair and seating assistive technology service provision within an Irish context. There are few studies that examine the process of wheelchair and seating provision and the connection between satisfaction, performance, and participation. METHOD: This mixed methods study explores participant experiences in two parts. Part one presents a thematic analysis of eight in-depth semi-structured interviews with wheelchair service users living with SCI. Part two presents the results content and frequency analysis of an on-line survey of wheelchair service user's experience and satisfaction with wheelchair and seating service provision from respondents with SCI (n = 117) taken from a larger national survey from respondents with various diagnoses (n = 273). RESULTS: Findings from the interviews and survey revealed the meaning of wheelchair and seating assistive technology provision as essential to life following SCI. Barriers within the provision system such as wait times and funding were found to impede people's rights and freedom from initial assessment through to follow up, maintenance and repair. CONCLUSIONS: The current implementation of wheelchair and seating assistive technology provision as described in this paper impacts the ability of individuals living with an SCI to participate as equal members of society. A review of wheelchair provision is essential to optimize access to services for appropriate wheelchairs.IMPLICATIONS FOR REHABILITATIONAs a basic human right, appropriate wheelchair and seating assistive technology provision facilitates people's optimal independence, health and well-being, social engagement, and participation in everyday life.The development of adequate wheelchair services should be a priority area for individuals with SCI who use wheelchair and seating assistive technology.National wheelchair and seating assistive technology provision policies in alignment with internationally developed best practice guidelines to provide equal access to services which include assessment, delivery, training, maintenance, and follow-up are essential.

Wheelchair and seating assistive technology provision: a gateway to freedom.

AIM: The meaning of wheelchair and seating assistive technology and the impact inappropriate provision has on people's lives from a service user's perspective within an Irish context is highlighted. There is a dearth in evidence examining the process of wheelchair and seating provision and the interconnectedness between satisfaction, performance and participation from an equality and human rights perspective. The purpose if the study is to investigate wheelchair service users' perspectives of wheelchair and seating provision in Ireland. METHOD: This is a mixed-methods study with an exploratory sequential design that includes two phases. During phase one, wheelchair service users were invited to take part in qualitative in-depth semi-structured interviews, which were thematically analysed and formed part of a larger ethnographic study involving multiple stakeholders in sustainable wheelchair and seating provision strategy development. In phase two, an online Survey Monkey questionnaire was distributed to obtain a wider overview of wheelchair service provision from a wheelchair service users perspective. Data obtained from the closed questions and content analysis for open comments was analysed descriptively for this phase. RESULTS: Eight wheelchair service users agreed to participate in the interviews and 273 responded to the online survey. Thematic analysis and questionnaire frequency and content analysis revealed the vital meaning of wheelchair and seating assistive technology provision. However, bottlenecks within the system affect daily living, with qualitative data highlighting the obstruction to experiences of independent living from initial appointment to wheelchair breakdowns during daily life. CONCLUSION: Appropriate wheelchair and seating assistive technology provision is a basic human right, supported by the essential and embodied nature of the wheelchair as demonstrated through the wheelchair service users' perspective throughout this study. These findings highlight the impact of ad-hoc services on individual freedoms and how the overall pace of the system affects a person's ability to organise their time as an equal member of the community across the lifespan. A national review of wheelchair and seating assistive technology provision services is called for, giving consideration to access to services, assessment and delivery, follow up and management, education and training.IMPLICATIONS FOR REHABILITATIONWheelchair and seating assistive technology provision as a basic human right is misunderstood.Appropriate wheelchair and seating assistive technology provision should be provided to meet this primary need as a pre-requisite for survival.Every aspect of the wheelchair and seating provision process impacts on occupational performance, equality of opportunity and community mobility. Wheelchair and seating assistive technology professionals and providers have a responsibility to review their practice and service provision systems.

Muscle degeneration and leukocyte infiltration caused by mutation of zebrafish Fad24.

Factor for adipocyte differentiation 24 (fad24) is a novel gene that has been implicated in adipocyte differentiation and DNA replication. In a screen for zebrafish mutants that have an abnormal tissue distribution of neutrophils, we identified an insertional allele of fad24, fad24hi1019. Homozygous fad24hi1019 larvae exhibit muscle degeneration accompanied by leukocyte infiltration. Muscle degeneration was extensive and included tissue apoptosis and disorganized, poorly striated muscle fibers. Blocking apoptosis using pan-caspase inhibitors resulted in decreased neutrophil recruitment into the body of the larva, suggesting a causative link between apoptosis and leukocyte infiltration. These findings suggest that zebrafish is a powerful genetic model system to address the interplay between muscle degeneration and leukocyte infiltration, and indicate that tissue apoptosis may contribute to neutrophil recruitment in some inflammatory states.