Dorsal-Ventral Differences in Retinal Structure in the Pigmented Royal College of Surgeons Model of Retinal Degeneration: Retinal Changes in the RCS With Age

Retinitis pigmentosa is a family of inherited retinal degenerations associated with gradual loss of photoreceptors, that ultimately leads to irreversible vision loss. The Royal College of Surgeon's (RCS) rat carries a recessive mutation affecting mer proto-oncogene tyrosine kinase (merTK), that models autosomal recessive disease. The aim of this study was to understand the glial, microglial, and photoreceptor changes that occur in different retinal locations with advancing disease. Pigmented RCS rats (RCS-p+/LAV) and age-matched isogenic control rdy (RCS-rdy +p+/LAV) rats aged postnatal day 18 to 6 months were evaluated for in vivo retinal structure and function using optical coherence tomography and electroretinography. Retinal tissues were assessed using high resolution immunohistochemistry to evaluate changes in photoreceptors, glia and microglia in the dorsal, and ventral retina. Photoreceptor dysfunction and death occurred from 1 month of age. There was a striking difference in loss of photoreceptors between the dorsal and ventral retina, with a greater number of photoreceptors surviving in the dorsal retina, despite being adjacent a layer of photoreceptor debris within the subretinal space. Loss of photoreceptors in the ventral retina was associated with fragmentation of the outer limiting membrane, extension of glial processes into the subretinal space that was accompanied by possible adhesion and migration of mononuclear phagocytes in the subretinal space. Overall, these findings highlight that breakdown of the outer limiting membrane could play an important role in exacerbating photoreceptor loss in the ventral retina. Our results also highlight the value of using the RCS rat to model sectorial retinitis pigmentosa, a disease known to predominantly effect the inferior retina

Proteomics Reveal Enhanced Oxidative Stress Responses and Metabolic Adaptation in Acidithiobacillus ferrooxidans Biofilm Cells on Pyrite

Reactive oxygen species (ROS) cause oxidative stress and growth inhibition by inactivation of essential enzymes, DNA and lipid damage in microbial cells. Acid mine drainage (AMD) ecosystems are characterized by low pH values, enhanced levels of metal ions and low species abundance. Furthermore, metal sulfides, such as pyrite and chalcopyrite, generate extracellular ROS upon exposure to acidic water. Consequently, oxidative stress management is especially important in acidophilic leaching microorganisms present in industrial biomining operations, especially when forming biofilms on metal sulfides. Several adaptive mechanisms have been described, but the molecular repertoire of responses upon exposure to pyrite and the presence of ROS are not thoroughly understood in acidophiles. In this study the impact of the addition of H2O2 on iron oxidation activity in Acidithiobacillus ferrooxidans DSM 14882T was investigated. Iron(II)- or sulfur-grown cells showed a higher sensitivity toward H2O2 than pyrite-grown ones. In order to elucidate which molecular responses may be involved, we used shot-gun proteomics and compared proteomes of cells grown with iron(II)-ions against biofilm cells, grown for 5 days in presence of pyrite as sole energy source. In total 1157 proteins were identified. 213 and 207 ones were found to have increased levels in iron(II) ion-grown or pyrite-biofilm cells, respectively. Proteins associated with inorganic sulfur compound (ISC) oxidation were among the latter. In total, 80 proteins involved in ROS degradation, thiol redox regulation, macromolecule repair mechanisms, biosynthesis of antioxidants, as well as metal and oxygen homeostasis were found. 42 of these proteins had no significant changes in abundance, while 30 proteins had increased levels in pyrite-biofilm cells. New insights in ROS mitigation strategies, such as importance of globins for oxygen homeostasis and prevention of unspecific reactions of free oxygen that generate ROS are presented for A. ferrooxidans biofilm cells. Furthermore, proteomic analyses provide insights in adaptations of carbon fixation and oxidative phosphorylation pathways under these two growth conditions

Timely Considerations of Using the de Jong Gierveld Loneliness Scale with Older Adults Living in Long-Term Care Homes: A Critical Reflection

Context: Despite being widely used with older adults in the community, there is limited literature on using the de Jong Gierveld Loneliness Scale with older adults living in long-term care (LTC). Objective: The purpose of this article is to discuss the considerations of using this scale with older adults in LTC. Method: Our team consisted of older person and family partners, a clinician, and academic researchers working together in all stages of research using the Loneliness scale to conduct individual interviews with 20 older adults in LTC in Vancouver, Canada, as part of a study exploring the experience of loneliness during the COVID-19 pandemic. Team reflection was embedded in the research process, with reflection data consisting of data transcripts, field notes, and regular team meeting notes. Thematic analysis was employed to identify lessons learned and implications. Findings: Participants had various challenges responding to the scale. Our analysis identified five themes: a) diverse meanings of loneliness, b) multi-faceted factors of loneliness, c) technical challenges, d) social desirability, and e) situational experience. We also offer five recommendations to consider when using this scale with older adults in LTC. Limitations: We used this scale with a small sample of older adults in LTC, which is a more time and labour-intensive population. Data on marital status and educational background was not collected but might help in understanding considerations for using the scale with older adults in LTC. Implications: We offer practical recommendations for using the scale with older adults in LTC, especially how qualitative open-ended questions can complement the scale by providing useful insights into context and complex experiences

Recent developments in frailty identification, management, risk factors and prevention : A narrative review of leading journals in geriatrics and gerontology

Funding The Frailty Epidemiology Research Network (EPI-FRAIL) is an international collaborative project aimed at filling knowledge gaps in the field of frailty epidemiology. The network was established as part of a NWO/ZonMw Veni fellowship awarded to E.O. Hoogendijk (Grant no. 91618067). P. Hanlon is funded through a Clinical Research Training Fellowship from the Medical Research Council (Grant reference: MR/S021949/1). Z. Liu was supported by the Soft Science Research Program of Zhejiang Province (2023KXCX-KT011). J. Jylhävä has received grant support from the Swedish Research Council (grant no. 2018-02077), the Academy of Finland (grant no. 349335), the Sigrid Jusélius Foundation, the Yrjö Jahnsson Foundation and the Instrumentarium Science Foundation. M. Sim is supported by a Royal Perth Hospital Research Foundation Career Advancement Fellowship and an Emerging Leader Fellowship from the Future Health Research and Innovation Fund (Department of Health, Western Australia). R. Ambagtsheer receives funding from the Australian Medical Research Future Fund (grant #MRF2016140). D. L. Vetrano receives financial support from the Swedish Research Council (2021-03324). S. Shi reports funding from the National Institute of Aging, R03AG078894-01. None of the funding agencies had any role in the conduct of the study; collection, management, analysis, or interpretation of the data; or preparation, review, or approval of the manuscript.Peer reviewedPublisher PD

Dorsal-Ventral Differences in Retinal Structure in the Pigmented Royal College of Surgeons Model of Retinal Degeneration

Retinitis pigmentosa is a family of inherited retinal degenerations associated with gradual loss of photoreceptors, that ultimately leads to irreversible vision loss. The Royal College of Surgeon's (RCS) rat carries a recessive mutation affecting mer proto-oncogene tyrosine kinase (merTK), that models autosomal recessive disease. The aim of this study was to understand the glial, microglial, and photoreceptor changes that occur in different retinal locations with advancing disease. Pigmented RCS rats (RCS-p+/LAV) and age-matched isogenic control rdy (RCS-rdy +p +/LAV) rats aged postnatal day 18 to 6 months were evaluated for in vivo retinal structure and function using optical coherence tomography and electroretinography. Retinal tissues were assessed using high resolution immunohistochemistry to evaluate changes in photoreceptors, glia and microglia in the dorsal, and ventral retina. Photoreceptor dysfunction and death occurred from 1 month of age. There was a striking difference in loss of photoreceptors between the dorsal and ventral retina, with a greater number of photoreceptors surviving in the dorsal retina, despite being adjacent a layer of photoreceptor debris within the subretinal space. Loss of photoreceptors in the ventral retina was associated with fragmentation of the outer limiting membrane, extension of glial processes into the subretinal space that was accompanied by possible adhesion and migration of mononuclear phagocytes in the subretinal space. Overall, these findings highlight that breakdown of the outer limiting membrane could play an important role in exacerbating photoreceptor loss in the ventral retina. Our results also highlight the value of using the RCS rat to model sectorial retinitis pigmentosa, a disease known to predominantly effect the inferior retina

Human and mouse seeds differentially affect AB aggregation by modulating the inflammatory response.

Abstract text: Alzheimer’s Disease (AD) is a neurodegenerative proteinopathy in which Aβ can misfold and aggregate into seeds that structurally corrupt native proteins, mimicking a prionlike process. These amyloid aggregation and propagation processes are influenced by three factors: the origin of the Aβ seed, time of incubation and host. However, the mechanism underlying the differential effect of each factor is poorly known. Previous studies have shown that the Aβ source is relevant for the amyloid process, since its pathogenicity is different according to its origin. Furthermore, recent evidence suggests that microglia plays a key role in the amyloidogenic event, and can modulate the propagation and aggregation process. Here, we seek to perform a comparative study to determine whether Aβ seeds from humans vs a familial AD line (the 3xTg-AD model) are more efficient to generate amyloid aggregates, as well as the role of the microglia in the propagation process. Methods: Amyloid seeds from AD patient (stage C for amyloid; from the Alzheimer’s Disease Research Center at UCI) and 25 mo-3xTg-AD mice were injected into the hippocampus of 7-8- month-old 3xTg-AD mice. They were analyzed 10 months post-surgery for amyloid and microglia markers. Results: Our findings demonstrated that amyloid seeds from the human patient seem to induce a more aggressive amyloid pathology compared to seeds from aged 3xTg-AD mice. Moreover, human and mice seeds differentially affect the presence of plaque-associated microglia in 3xTgAD mice. Conclusion: These results suggest that seeds from human patients seem to be more amyloidogenic than from aged 3xTg-AD mice, and also microglia cells may play a key role in this differential effect. Therefore, more profound understanding these factors will provide key insight on how amyloid pathology progresses in AD.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

The ENIGMA-Epilepsy working group: Mapping disease from large data sets

Epilepsy is a common and serious neurological disorder, with many different constituent conditions characterized by their electro clinical, imaging, and genetic features. MRI has been fundamental in advancing our understanding of brain processes in the epilepsies. Smaller‐scale studies have identified many interesting imaging phenomena, with implications both for understanding pathophysiology and improving clinical care. Through the infrastructure and concepts now well‐established by the ENIGMA Consortium, ENIGMA‐Epilepsy was established to strengthen epilepsy neuroscience by greatly increasing sample sizes, leveraging ideas and methods established in other ENIGMA projects, and generating a body of collaborating scientists and clinicians to drive forward robust research. Here we review published, current, and future projects, that include structural MRI, diffusion tensor imaging (DTI), and resting state functional MRI (rsfMRI), and that employ advanced methods including structural covariance, and event‐based modeling analysis. We explore age of onset‐ and duration‐related features, as well as phenomena‐specific work focusing on particular epilepsy syndromes or phenotypes, multimodal analyses focused on understanding the biology of disease progression, and deep learning approaches. We encourage groups who may be interested in participating to make contact to further grow and develop ENIGMA‐Epilepsy

Panta Rhei benchmark dataset: socio-hydrological data of paired events of floods and droughts

As the adverse impacts of hydrological extremes increase in many regions of the world, a better understanding of the drivers of changes in risk and impacts is essential for effective flood and drought risk management and climate adaptation. However, there is currently a lack of comprehensive, empirical data about the processes, interactions and feedbacks in complex human-water systems leading to flood and drought impacts. Here we present a benchmark dataset containing socio-hydrological data of paired events, i.e., two floods or two droughts that occurred in the same area. The 45 paired events occurred in 42 different study areas and cover a wide range of socio-economic and hydro-climatic conditions. The dataset is unique in covering both floods and droughts, in the number of cases assessed, and in the quantity of socio-hydrological data. The benchmark dataset comprises: 1) detailed review style reports about the events and key processes between the two events of a pair; 2) the key data table containing variables that assess the indicators which characterise management shortcomings, hazard, exposure, vulnerability and impacts of all events; 3) a table of the indicators-of-change that indicate the differences between the first and second event of a pair. The advantages of the dataset are that it enables comparative analyses across all the paired events based on the indicators-of-change and allows for detailed context- and location-specific assessments based on the extensive data and reports of the individual study areas. The dataset can be used by the scientific community for exploratory data analyses e.g. focused on causal links between risk management, changes in hazard, exposure and vulnerability and flood or drought impacts. The data can also be used for the development, calibration and validation of socio-hydrological models. The dataset is available to the public through the GFZ Data Services (Kreibich et al. 2023, link for review: https://dataservices.gfz-potsdam.de/panmetaworks/review/923c14519deb04f83815ce108b48dd2581d57b90ce069bec9c948361028b8c85/).</p