Chronic voluntary alcohol consumption causes persistent cognitive deficits and cortical cell loss in a rodent model

Chronic alcohol use is associated with cognitive decline that impedes behavioral change during rehabilitation. Despite this, addiction therapy does not address cognitive deficits, and there is poor understanding regarding the mechanisms that underlie this decline. We established a rodent model of chronic voluntary alcohol use to measure ensuing cognitive effects and underlying pathology. Rats had intermittent access to alcohol or an isocaloric solution in their home cage under voluntary 2-bottle choice conditions. In Experiments 1 and 2 cognition was assessed using operant touchscreen chambers. We examined performance in a visual discrimination and reversal task (Experiment 1), and a 5-choice serial reaction time task (Experiment 2). For Experiment 3, rats were perfused immediately after cessation of alcohol access period, and volume, cell density and microglial populations were assessed in the prefrontal cortex and striatum. Volume was assessed using the Cavalieri probe, while cell and microglial counts were estimated using unbiased stereology with an optical fractionator. Alcohol-exposed and control rats showed comparable acquisition of pairwise discrimination; however, performance was impaired when contingencies were reversed indicating reduced behavioral flexibility. When tested in a 5-choice serial reaction time task alcohol-exposed rats showed increased compulsivity and increased attentional bias towards a reward associated cue. Consistent with these changes, we observed decreased cell density in the prefrontal cortex. These findings confirm a detrimental effect of chronic alcohol and establish a model of alcohol-induced cognitive decline following long-term voluntary intake that may be used for future intervention studies

Premature differentiation of nephron progenitor cell and dysregulation of gene pathways critical to kidney development in a model of preterm birth

Preterm birth is a leading cause of neonatal morbidity. Survivors have a greater risk for kidney dysfunction and hypertension. Little is known about the molecular changes that occur in the kidney of individuals born preterm. Here, we demonstrate that mice delivered two days prior to full term gestation undergo premature cessation of nephrogenesis, resulting in a lower glomerular density. Kidneys from preterm and term groups exhibited differences in gene expression profiles at 20- and 27-days post-conception, including significant differences in the expression of fat-soluble vitamin-related genes. Kidneys of the preterm mice exhibited decreased proportions of endothelial cells and a lower expression of genes promoting angiogenesis compared to the term group. Kidneys from the preterm mice also had altered nephron progenitor subpopulations, early Six2 depletion, and altered Jag1 expression in the nephrogenic zone, consistent with premature differentiation of nephron progenitor cells. In conclusion, preterm birth alone was sufficient to shorten the duration of nephrogenesis and cause premature differentiation of nephron progenitor cells. These candidate genes and pathways may provide targets to improve kidney health in preterm infants

Conference 2014 speaker series: an interview with Fatima El Issawi

Polis research fellow Fatima El Issawi speaks about her new report on post-uprising Egyptian Media: “Egyptian Media Under Transition: In the name of the regime… In the name of the people?

Salt Stress Causes Peroxisome Proliferation, but Inducing Peroxisome Proliferation Does Not Improve NaCl Tolerance in Arabidopsis thaliana

The PEX11 family of peroxisome membrane proteins have been shown to be involved in regulation of peroxisome size and number in plant, animals, and yeast cells. We and others have previously suggested that peroxisome proliferation as a result of abiotic stress may be important in plant stress responses, and recently it was reported that several rice PEX11 genes were up regulated in response to abiotic stress. We sought to test the hypothesis that promoting peroxisome proliferation in Arabidopsis thaliana by over expression of one PEX11 family member, PEX11e, would give increased resistance to salt stress. We could demonstrate up regulation of PEX11e by salt stress and increased peroxisome number by both PEX11e over expression and salt stress, however our experiments failed to find a correlation between PEX11e over expression and increased peroxisome metabolic activity or resistance to salt stress. This suggests that although peroxisome proliferation may be a consequence of salt stress, it does not affect the ability of Arabidopsis plants to tolerate saline conditions

Growth performance, feed utilisation and body composition of advanced nursing Nile tilapia (Oreochromis niloticus) fed diets containing Black Soldier Fly (Hermetia illucens) larvae meal

A 32-day experiment was conducted to evaluate the effects on the performance, feed utilisation efficiency and body composition of a strategic inclusion of Black Soldier Fly larvae meal (MM) in a commercially formulated diet for advance nursing Nile tilapia (Oreochromis niloticus). Four isonitrogenous and isoenergetic diets were commercially formulated and manufactured as a control and 3 test diets with strategic inclusions of MM inclusions (0, 30, 50 and 80 g kg-1) and poultry byproduct meal substituting gradually three conventional expensive feedstuffs: fish meal, fish oil and soybean meal. Fish (5.7±0.5 g fish-1) were nursed in a cage-in-lake system (Volta Lake, Ghana), under conditions similar to commercial farming practices. Control and experimental diets were fed to triplicate cages by hand to visual satiety, 6 times day-1. Growth performance (final weight; weight gain and SGR); feed utilisation efficiency indices (FCR and PER) and feed intake were not significantly different (P≥0.05) between treatments. Survival was significantly different (P<0.05) but more likely explained by the stress related to frequent handling on the smaller fish. Fish whole body composition (dry matter, crude protein, lipid, ash and fibre) was unaffected by the treatment (P≥0.05), except for the fatty acid compositions which mirrored that of the diets

Diagnosis of common health conditions among autistic adults in the UK: evidence from a matched cohort study

Background: Autistic people are disproportionately likely to experience premature mortality and most mental and physical health conditions. We measured the incidence of diagnosed conditions accounting for the most disability-adjusted life years in the UK population according to the Global Burden of Disease study (anxiety, depression, self-harm, harmful alcohol use, substance use, migraine, neck or back pain, and gynaecological conditions). Methods: Participants were aged 18 years or above and had an autism diagnosis recorded in the IQVIA Medical Research Database between 01/01/2000 and 16/01/2019. We included 15,675 autistic adults without intellectual disability, 6437 autistic adults with intellectual disability, and a comparison group matched (1:10) by age, sex, and primary care practice. We estimated crude incidences and incidence rate ratios (IRRs) adjusted for age and sex. Findings: Autistic adults without intellectual disability experienced a higher incidence (IRR, 95% CI) of self-harm (2.07, 1.79–2.40), anxiety (1.91, 1.76–2.06), depressive disorders (1.79, 1.67–1.92), and substance use (1.24, 1.02–1.51) relative to comparison participants. Incidences of harmful alcohol use (1.01, 0.85–1.18), migraine (0.99, 0.84–1.17), and gynaecological conditions (1.19, 0.95–1.49) did not differ. Neck or back pain incidence was lower (0.88, 0.82–0.95). Autistic adults with intellectual disability experienced a higher incidence of self-harm (2.08, 1.69–2.56). Incidences of anxiety (1.14, 1.00–1.30), gynaecological conditions (1.22, 0.93–1.62), and substance use (1.08, 0.80–1.47) did not differ, and lower incidences were found for depressive disorders (0.73, 0.64–0.83), harmful alcohol use (0.65, 0.50–0.84), migraine (0.55, 0.42–0.74), and neck or back pain (0.49, 0.44–0.55). Interpretation: Although our findings cannot be directly compared to previous prevalence studies, they contrast with the higher frequency of mental and physical health conditions in autistic adults reported in studies that directly assessed and/or surveyed autistic people about co-occurring conditions. The present findings may suggest under-diagnosis of common conditions in autistic people, particularly those with intellectual disability. Improved detection should be a clinical and policy priority to reduce health inequalities. Funding: Dunhill Medical Trust, Economic and Social Research Council, National Institute of Health and Care Research

Antihydrogen formation dynamics in a multipolar neutral anti-atom trap

Antihydrogen production in a neutral atom trap formed by an octupole-based magnetic field minimum is demonstrated using field-ionization of weakly bound anti-atoms. Using our unique annihilation imaging detector, we correlate antihydrogen detection by imaging and by field-ionization for the first time. We further establish how field-ionization causes radial redistribution of the antiprotons during antihydrogen formation and use this effect for the first simultaneous measurements of strongly and weakly bound antihydrogen atoms. Distinguishing between these provides critical information needed in the process of optimizing for trappable antihydrogen. These observations are of crucial importance to the ultimate goal of performing CPT tests involving antihydrogen, which likely depends upon trapping the anti-atom

Estimating life expectancy and years of life lost for autistic people in the UK: a matched cohort study

Background: Previous research has shown that people who have been diagnosed autistic are more likely to die prematurely than the general population. However, statistics on premature mortality in autistic people have often been misinterpreted. In this study we aimed to estimate the life expectancy and years of life lost experienced by autistic people living in the UK.// Methods: We studied people in the IQVIA Medical Research Database with an autism diagnosis between January 1, 1989 and January 16, 2019. For each participant diagnosed autistic, we included ten comparison participants without an autism diagnosis, matched by age, sex, and primary care practice. We calculated age- and sex-standardised mortality ratios comparing people diagnosed autistic to the reference group. We used Poisson regression to estimate age-specific mortality rates, and life tables to estimate life expectancy at age 18 and years of life lost. We analysed the data separately by sex, and for people with and without a record of intellectual disability. We discuss the findings in the light of the prevalence of recorded diagnosis of autism in primary care compared to community estimates.// Findings: From a cohort of nearly 10 million people, we identified 17,130 participants diagnosed autistic without an intellectual disability (matched with 171,300 comparison participants), and 6450 participants diagnosed autistic with an intellectual disability (matched with 64,500 comparison participants). The apparent estimates indicated that people diagnosed with autism but not intellectual disability had 1.71 (95% CI: 1.39–2.11) times the mortality rate of people without these diagnoses. People diagnosed with autism and intellectual disability had 2.83 (95% CI: 2.33–3.43) times the mortality rate of people without these diagnoses. Likewise, the apparent reduction in life expectancy for people diagnosed with autism but not intellectual disability was 6.14 years (95% CI: 2.84–9.07) for men and 6.45 years (95% CI: 1.37–11.58 years) for women. The apparent reduction in life expectancy for people diagnosed with autism and intellectual disability was 7.28 years (95% CI: 3.78–10.27) for men and 14.59 years (95% CI: 9.45–19.02 years) for women. However, these findings are likely to be subject to exposure misclassification biases: very few autistic adults and older-adults have been diagnosed, meaning that we could only study a fraction of the total autistic population. Those who have been diagnosed may well be those with greater support needs and more co-occurring health conditions than autistic people on average

A novel antiproton radial diagnostic based on octupole induced ballistic loss

We report results from a novel diagnostic that probes the outer radial profile of trapped antiproton clouds. The diagnostic allows us to determine the profile by monitoring the time-history of antiproton losses that occur as an octupole field in the antiproton confinement region is increased. We show several examples of how this diagnostic helps us to understand the radial dynamics of antiprotons in normal and nested Penning-Malmberg traps. Better understanding of these dynamics may aid current attempts to trap antihydrogen atoms

Compression of Antiproton Clouds for Antihydrogen Trapping

Control of the radial profile of trapped antiproton clouds is critical to trapping antihydrogen. We report the first detailed measurements of the radial manipulation of antiproton clouds, including areal density compressions by factors as large as ten, by manipulating spatially overlapped electron plasmas. We show detailed measurements of the near-axis antiproton radial profile and its relation to that of the electron plasma