The Local Lyman-Alpha Forest: Absorbers in Galaxy Voids

We have conducted pointed redshift surveys for galaxies in the direction of bright AGN whose HST far-UV spectra contain nearby (cz <~ 30,000 kms), low column density (12.5 <= log N_{HI} (cm s^{-2}) <= 14.5) Ly-alpha forest absorption systems. Here we present results for four lines-of-sight which contain nearby (cz <~ 3000 kms) Ly-alpha absorbers in galaxy voids. Although our data go quite deep (-13 <= M_{B}(limit) <= -14) out to impact parameters of 100-250 h_{70}^{-1} kpc, these absorbers remain isolated and thus appear to be truly intergalactic, rather than part of galaxies or their halos. Since we and others have discovered no galaxies in voids, the only baryons detected in the voids are in the Ly-alpha ``clouds''. Using a photoionization model for these clouds, the total baryonic content of the voids is 4.5% +/- 1.5% of the mean baryon density.Comment: 5 pages, 1 figure, accepted for publication in Astrophysical Journal Letter

Longitudinal osmotic and neurometabolic changes in young rats with chronic cholestatic liver disease.

Type C hepatic encephalopathy (type C HE) is increasingly suspected in children with chronic liver disease (CLD), and believed to underlie long-term neurocognitive difficulties. The molecular underpinnings of type C HE in both adults and children are incompletely understood. In the present study we combined the experimental advantages of in vivo high field &lt;sup&gt;1&lt;/sup&gt; H magnetic resonance spectroscopy with immunohistochemistry to follow longitudinally over 8 weeks the neurometabolic changes in the hippocampus of animals having undergone bile duct ligation as pups. Rats who develop CLD early in life displayed pronounced neurometabolic changes in the hippocampus characterized by a progressive increase in glutamine concentration which correlated with plasma ammonia levels and a rapid decrease in brain myo-inositol. Other neurometabolic findings included a decrease in other organic osmolytes (taurine, choline-containing compounds and creatine), ascorbate and glutamate. At the cellular level, we observed an increase in glial fibrillary acidic protein (GFAP) and aquaporin 4 (AQP4) expression in the hippocampus at 4 weeks post bile duct ligation (BDL), together with astrocytic morphological alterations. These findings differ from observations in the brain of adult rats following BDL, and are in keeping with the commonly accepted theory of age-dependent vulnerability

Neurometabolic changes in a rat pup model of type C hepatic encephalopathy depend on age at liver disease onset.

Chronic liver disease (CLD) is a serious condition where various toxins present in the blood affect the brain leading to type C hepatic encephalopathy (HE). Both adults and children are impacted, while children may display unique vulnerabilities depending on the affected window of brain development.We aimed to use the advantages of high field proton Magnetic Resonance Spectroscopy ( &lt;sup&gt;1&lt;/sup&gt; H MRS) to study longitudinally the neurometabolic and behavioural effects of Bile Duct Ligation (animal model of CLD-induced type C HE) on rats at post-natal day 15 (p15) to get closer to neonatal onset liver disease. Furthermore, we compared two sets of animals (p15 and p21-previously published) to evaluate whether the brain responds differently to CLD according to age onset.We showed for the first time that when CLD was acquired at p15, the rats presented the typical signs of CLD, i.e. rise in plasma bilirubin and ammonium, and developed the characteristic brain metabolic changes associated with type C HE (e.g. glutamine increase and osmolytes decrease). When compared to rats that acquired CLD at p21, p15 rats did not show any significant difference in plasma biochemistry, but displayed a delayed increase in brain glutamine and decrease in total-choline. The changes in neurotransmitters were milder than in p21 rats. Moreover, p15 rats showed an earlier increase in brain lactate and a different antioxidant response. These findings offer tentative pointers as to which neurodevelopmental processes may be impacted and raise the question of whether similar changes might exist in humans but are missed owing to &lt;sup&gt;1&lt;/sup&gt; H MRS methodological limitations in field strength of clinical magnet

The Galaxy Environment of O VI Absorption Systems

We combine a FUSE sample of OVI absorbers (z < 0.15) with a database of 1.07 million galaxy redshifts to explore the relationship between absorbers and galaxy environments. All 37 absorbers with N(OVI) > 10^{13.2} cm^-2 lie within 800 h_70^-1 kpc of the nearest galaxy, with no compelling evidence for OVI absorbers in voids. The OVI absorbers often appear to be associated with environments of individual galaxies. Gas with 10 +/- 5% of solar metallicity (OVI and CIII) has a median spread in distance of 350-500 kpc around L* galaxies and 200-270 kpc around 0.1 L* galaxies (ranges reflect uncertain metallicities of gas undetected in Lya absorption). In order to match the OVI line frequency, dN/dz = 20 for N(OVI) > 10^{13.2} cm^-2, galaxies with L < 0.1 L* must contribute to the cross section. The Lya absorbers with N(HI) > 10^{13.2} cm^-2 cover ~50% of the surface area of typical galaxy filaments. Two-thirds of these show OVI and/or CIII absorption, corresponding to a 33-50% covering factor at 0.1 Z_sun and suggesting that metals are spread to a maximum distance of 800 kpc, within typical galaxy supercluster filaments. Approximately 50% of the OVI absorbers have associated Lya line pairs with separations Delta V = 50-200 km/s. These pairs could represent shocks at the speeds necessary to create copious OVI, located within 100 kpc of the nearest galaxy and accounting for much of the two-point correlation function of low-z Lya forest absorbers.Comment: 14 pages, 2 figs, submitted to Ap

Probiotics improve the neurometabolic profile of rats with chronic cholestatic liver disease.

Chronic liver disease leads to neuropsychiatric complications called hepatic encephalopathy (HE). Current treatments have some limitations in their efficacy and tolerability, emphasizing the need for alternative therapies. Modulation of gut bacterial flora using probiotics is emerging as a therapeutic alternative. However, knowledge about how probiotics influence brain metabolite changes during HE is missing. In the present study, we combined the advantages of ultra-high field in vivo &lt;sup&gt;1&lt;/sup&gt; H MRS with behavioural tests to analyse whether a long-term treatment with a multistrain probiotic mixture (VIVOMIXX) in a rat model of type C HE had a positive effect on behaviour and neurometabolic changes. We showed that the prophylactic administration of this probiotic formulation led to an increase in gut Bifidobacteria and attenuated changes in locomotor activity and neurometabolic profile in a rat model of type C HE. Both the performance in behavioural tests and the neurometabolic profile of BDL + probiotic rats were improved compared to the BDL group at week 8 post-BDL. They displayed a significantly lesser increase in brain Gln, a milder decrease in brain mIns and a smaller decrease in neurotransmitter Glu than untreated animals. The clinical implications of these findings are potentially far-reaching given that probiotics are generally safe and well-tolerated by patients

Long-term modification of cortical synapses improves sensory perception

Synapses and receptive fields of the cerebral cortex are plastic. However, changes to specific inputs must be coordinated within neural networks to ensure that excitability and feature selectivity are appropriately configured for perception of the sensory environment. Long-lasting enhancements and decrements to rat primary auditory cortical excitatory synaptic strength were induced by pairing acoustic stimuli with activation of the nucleus basalis neuromodulatory system. Here we report that these synaptic modifications were approximately balanced across individual receptive fields, conserving mean excitation while reducing overall response variability. Decreased response variability should increase detection and recognition of near-threshold or previously imperceptible stimuli, as we found in behaving animals. Thus, modification of cortical inputs leads to wide-scale synaptic changes, which are related to improved sensory perception and enhanced behavioral performance

Systematic review of response criteria and endpoints in autoimmune hepatitis by the International Autoimmune Hepatitis Group

\ua9 2022 The Authors. Background &amp; Aims: Autoimmune hepatitis (AIH) has been well characterised and codified through the development of diagnostic criteria. These criteria have been adapted and simplified and are widely used in clinical practice. However, there is a need to update and precisely define the criteria for both treatment response and treatment. Methods: A systematic review was performed and a modified Delphi consensus process was used to identify and redefine the response criteria in autoimmune hepatitis. Results: The consensus process initiated by the International Autoimmune Hepatitis Group proposes that the term ‘complete biochemical response’ defined as ‘normalization of serum transaminases and IgG below the upper limit of normal’ be adopted to include a time point at 6 months after initiation of treatment. An insufficient response by 6 months was a failure to meet the above definition. Non-response was defined as ‘&lt;50% decrease of serum transaminases within 4 weeks after initiation of treatment’. Remission is defined as liver histology with a Hepatitis Activity Index &lt;4/18. Intolerance to treatment was agreed to stand for ‘any adverse event possibly related to treatment leading to potential drug discontinuation’. Conclusions: These definitions provide a simple and reproducible framework to define treatment response and non-response, irrespective of the therapeutic intervention. A consensus on endpoints is urgently required to set a global standard for the reporting of study results and to enable inter-study comparisons. Future prospective database studies are needed to validate these endpoints. Lay summary: Consensus among international experts on response criteria and endpoints in autoimmune hepatitis is lacking. A consensus on endpoints is urgently required to set a global standard for the reporting of study results and to enable the comparison of results between clinical trials. Therefore, the International Autoimmune Hepatitis Group (IAIHG) herein presents a statement on 5 agreed response criteria and endpoints: complete biochemical response, insufficient response, non-response, remission, and intolerance to treatment, which can be used to guide future reporting