Mark Zuckerberg, the CEO of Meta, is one of the richest and most powerful men in the world. His position seems unassailable, so why does he run his business empire as though it’s under constant ...threat?
•Autistic individuals prevented from effectively participating in custody process.•Barriers to communication affect interactions between officers and autistic detainees.•The custody environment ...creates sensory difficulties for autistic detainees.•Officers are prevented from providing effective support due to demands of custody.•Changes to practice, the custody environment and policy will help improve support.
Research suggests that autistic individuals may be more likely to come into contact with police and have more negative experiences in police custody. However, limited information about the difficulties they experience during the custody process is available.
This study explores the experiences of autistic individuals and officers during a walkthrough of the custody process to identify specific difficulties in these encounters and what support is needed to overcome these.
A participative walkthrough method was developed to provide autistic individuals and officers an interactive opportunity to identify areas where further support in the custody process was needed. Two autistic participants and three officers took part in the study.
Autistic participants reported negative experiences due to: i) the emotional impact of the physical setting and custody process ii) communication barriers leading to increased anxiety and iii) exposure to sensory demands. Officers highlighted three factors which limit their ability to support autistic individuals effectively: i) the custody context ii) barriers to communication and iii) knowledge and understanding of autism.
Adjustments are needed to the custody process and environment to support interactions between autistic individuals and officers and improve the overall wellbeing of autistic individuals.
Clinical and experimental data suggest that fronto-cortical GABAergic deficits contribute to the pathophysiology of major depressive disorder (MDD). To further test this hypothesis, we used a well ...characterized rat model for depression and examined the effect of stress on GABAergic neuron numbers and GABA-mediated synaptic transmission in the medial prefrontal cortex (mPFC) of rats. Adult male Wistar rats were subjected to 9-weeks of chronic mild stress (CMS) and based on their hedonic-anhedonic behavior they were behaviorally phenotyped as being stress-susceptible (anhedonic) or stress-resilient. Post mortem quantitative histopathology was used to examine the effect of stress on parvalbumin (PV)-, calretinin- (CR), calbindin- (CB), cholecystokinin- (CCK), somatostatin-(SST) and neuropeptide Y-positive (NPY+) GABAergic neuron numbers in all cortical subareas of the mPFC (anterior cingulate (Cg1), prelimbic (PrL) and infralimbic (IL) cortexes).
, whole-cell patch-clamp recordings from layer II-III pyramidal neurons of the ventral mPFC was used to examine GABAergic neurotransmission. The cognitive performance of the animals was assessed in a hippocampal-prefrontal-cortical circuit dependent learning task. Stress exposure reduced the number of CCK-, CR- and PV-positive GABAergic neurons in the mPFC, most prominently in the IL cortex. Interestingly, in the stress-resilient animals, we found higher number of neuropeptide Y-positive neurons in the entire mPFC. The electrophysiological analysis revealed reduced frequencies of spontaneous and miniature IPSCs in the anhedonic rats and decreased release probability of perisomatic-targeting GABAergic synapses and alterations in GABA
receptor mediated signaling. In turn, pyramidal neurons showed higher excitability. Anhedonic rats were also significantly impaired in the object-place paired-associate learning task. These data demonstrate that long-term stress results in functional and structural deficits of prefrontal GABAergic networks. Our findings support the concept that fronto-limbic GABAergic dysfunctions may contribute to emotional and cognitive symptoms of MDD.
In many coastal areas, marine ecosystems have shifted into contrasting states having reduced ecosystem services (hereafter called degraded). Such degraded ecosystems may be slow to revert to their ...original state due to new ecological feedbacks that reinforce the degraded state. A better understanding of the way human actions influence the strength and direction of feedbacks, how different feedbacks could interact, and at what scales they operate, may be necessary in some cases for successful management of marine ecosystems. Here we synthesize interactions of critical feedbacks of the degraded states from six globally distinct biomes: coral reefs, kelp forests, seagrass beds, shallow soft sediments, oyster reefs, and coastal pelagic food webs. We explore to what extent current management captures these feedbacks and propose strategies for how and when (that is, windows of opportunity) to influence feedbacks in ways to break the resilience of the degraded ecosystem states. We conclude by proposing some challenges for future research that could improve our understanding of these issues and emphasize that management of degraded marine states will require a broad social—ecological approach to succeed.
•Juvenile brown trout were exposed to n-TiO2, PCB77, and n-TiO2-PCB77 mixtures via the diet.•The presence of n-TiO2 in the test diet affected PCB77 availability.•Dietary co-exposure to n-TiO2 and ...PCB77 led to combination effects on intestinal tight junction protein (zo-1) expression.•An object resembling n-TiO2 was imaged inside the Space of Disse of a liver sinusoid suggesting NP transport to the liver.•n-TiO2 had a potentiating effect on PCB77-induced biomarker responses in the liver.
Titanium dioxide nanoparticles (n-TiO2) are among the man-made nanomaterials that are predicted to be found at high concentrations in the aquatic environment. There, they likely co-exist with other chemical pollutants. Thus, n-TiO2 and other chemical pollutants can be taken up together or accumulate independently from each other in prey organisms of fish. This can lead to dietary exposure of fish to n-TiO2-chemical pollutant mixtures. In this study, we examine if simultaneous dietary exposure to n-TiO2 and 3,3’,4,4’-Tetrachlorobiphenyl (PCB77) –used as a model compound for persistent organic pollutants with dioxin-like properties– can influence the uptake and toxicological response elicited by the respective other substance. Juvenile brown trout (Salmo trutta) were fed custom-made food pellets containing n-TiO2, PCB77 or n-TiO2+PCB77 mixtures for 15 days. Ti and PCB77 concentrations in the liver were measured by ICP-MS and GC–MS, respectively. Besides, n-TiO2 uptake was assessed using TEM. Combination effects on endpoints specific for PCB77 (i.e., cytochrome P450 1A (CYP1A) induction) and endpoints shared by both PCB77 and n-TiO2 (i.e., oxidative stress-related parameters) were measured in intestine and liver using RT-qPCR and enzyme activity assays. The results show that genes encoding for proteins/enzymes essential for tight junction function (zo-1) and ROS elimination (sod-1) were significantly upregulated in the intestine of fish exposed to n-TiO2 and PCB77 mixtures, but not in the single-substance treatments. Besides, n-TiO2 had a potentiating effect on PCB77-induced CYP1A and glutathione reductase (GR) expression/enzyme activity in the liver. This study shows that simultaneous dietary exposure to nanomaterials and traditional environmental pollutants might result in effects that are larger than observed for the substances alone, but that understanding the mechanistic basis of such effects remains challenging.
Reseña bibliográfica de la obra: Diccionario Biográfico de los Diputados y Diputadas del Parlamento Vasco (1980-1984)
Enviado el (Submission Date): 30/12/2022.Aceptado el (Acceptance Date): 23/01/2023
Currently there are no effective treatments for many neurodegenerative diseases. Reliable biomarkers for identifying and stratifying these diseases will be important in the development of future ...novel therapies. Lewy Body Dementia (LBD) is considered an under diagnosed form of dementia for which markers are needed to discriminate LBD from other forms of dementia such as Alzheimer's Disease (AD). This work describes a Label-Free proteomic profiling analysis of cerebral spinal fluid (CSF) from non-neurodegenerative controls and patients with LBD. Using this technology we identified several potential novel markers for LBD. These were then combined with other biomarkers from previously published studies, to create a 10 min multiplexed targeted and translational MRM-LC-MS/MS assay. This test was used to validate our new assay in a larger cohort of samples including controls and the other neurodegenerative conditions of Alzheimer's and Parkinson's disease (PD).
Thirty eight proteins showed significantly (p < 0.05) altered expression in LBD CSF by proteomic profiling. The targeted MRM-LC-MS/MS assay revealed 4 proteins that were specific for the identification of AD from LBD: ectonucleotide pyrophosphatase/phosphodiesterase 2 (p < 0.0001), lysosome-associated membrane protein 1 (p < 0.0001), pro-orexin (p < 0.0017) and transthyretin (p < 0.0001). Nineteen proteins were elevated significantly in both AD and LBD versus the control group of which 4 proteins are novel (malate dehydrogenase 1, serum amyloid A4, GM2-activator protein, and prosaposin). Protein-DJ1 was only elevated significantly in the PD group and not in either LBD or AD samples. Correlations with Alzheimer-associated amyloid β-42 levels, determined by ELISA, were observed for transthyretin, GM2 activator protein and IGF2 in the AD disease group (r(2) ≥ 0.39, p ≤ 0.012). Cystatin C, ubiquitin and osteopontin showed a strong significant linear relationship (r(2) ≥ 0.4, p ≤ 0.03) with phosphorylated-tau levels in all groups, whilst malate dehydrogenase and apolipoprotein E demonstrated a linear relationship with phosphorylated-tau and total-tau levels in only AD and LBD disease groups.
Using proteomics we have identified several potential and novel markers of neurodegeneration and subsequently validated them using a rapid, multiplexed mass spectral test. This targeted proteomic platform can measure common markers of neurodegeneration that correlate with existing diagnostic makers as well as some that have potential to show changes between AD from LBD.
PDF
