Alcohol and HIV Decrease Proteasome and Immunoproteasome Function in Macrophages: Implications for Impaired Immune Function During Disease

Proteasomes (proteinase complexes, PR) and immunoproteasomes (IPR) degrade damaged proteins and affect protein processing required for antigen presentation by mononuclear phagocytes. These critical immune processes are attenuated during progressive HIV-1 infection and are affected by alcohol abuse. To investigate the mechanisms underlying these functional changes, we measured PR and CYP2E1 activities [an ethanol (EtOH) metabolizing enzyme] and reactive oxygen species (ROS) in human monocyte-derived macrophages (MDM) following HIV-1 infection and EtOH treatment. We observed progressive declines of PR activity and PR/IPR contents in HIV-1-infected MDM. PR activity and IPR expression increased after IFN-γ stimulation but reduced after HIV-1 infection. EtOH inhibited both IFN-γ -induced PR and IPR. Paradoxically, EtOH attenuated PR catalytic activity in infected MDM and suppressed viral replication. Elevated ROS followed EtOH exposure and paralleled decreased PR activity. The latter was restored by anti-oxidant. The data support the notion that HIV-1 infection and EtOH may work in concert to affect immune function including antigen presentation and thereby affect disease progression

Alimentary fluoride intake in preschool children

<p>Abstract</p> <p>Background</p> <p>The knowledge of background alimentary fluoride intake in preschool children is of utmost importance for introducing optimal and safe caries preventive measures for both individuals and communities. The aim of this study was to assess the daily fluoride intake analyzing duplicate samples of food and beverages. An attempt was made to calculate the daily intake of fluoride from food and swallowed toothpaste.</p> <p>Methods</p> <p>Daily alimentary fluoride intake was measured in a group of 36 children with an average age of 4.75 years and an average weight of 20.69 kg at baseline, by means of a double plate method. This was repeated after six months. Parents recorded their child's diet over 24 hours and collected duplicated portions of food and beverages received by children during this period. Pooled samples of food and beverages were weighed and solid food samples were homogenized. Fluoride was quantitatively extracted from solid food samples by a microdiffusion method using hexadecyldisiloxane and perchloric acid. The content of fluoride extracted from solid food samples, as well as fluoride in beverages, was measured potentiometrically by means of a fluoride ion selective electrode.</p> <p>Results</p> <p>Average daily fluoride intake at baseline was 0.389 (SD 0.054) mg per day. Six months later it was 0.378 (SD 0.084) mg per day which represents 0.020 (SD 0.010) and 0.018 (SD 0.008) mg of fluoride respectively calculated per kg bw/day.</p> <p>When adding the values of unwanted fluoride intake from the toothpaste shown in the literature (0.17-1.21 mg per day) the estimate of the total daily intake of fluoride amounted to 0.554-1.594 mg/day and recalculated to the child's body weight to 0.027-0.077 mg/kg bw/day.</p> <p>Conclusions</p> <p>In the children studied, observed daily fluoride intake reached the threshold for safe fluoride intake. When adding the potential fluoride intake from swallowed toothpaste, alimentary intake reached the optimum range for daily fluoride intake. These results showed that in preschool children, when trying to maximize the benefit of fluoride in caries prevention and to minimize its risk, caution should be exercised when giving advice on the fluoride containing components of child's diet or prescribing fluoride supplements.</p

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Search for chargino-neutralino production with mass splittings near the electroweak scale in three-lepton final states in √s=13 TeV pp collisions with the ATLAS detector

A search for supersymmetry through the pair production of electroweakinos with mass splittings near the electroweak scale and decaying via on-shell W and Z bosons is presented for a three-lepton final state. The analyzed proton-proton collision data taken at a center-of-mass energy of √s=13  TeV were collected between 2015 and 2018 by the ATLAS experiment at the Large Hadron Collider, corresponding to an integrated luminosity of 139  fb−1. A search, emulating the recursive jigsaw reconstruction technique with easily reproducible laboratory-frame variables, is performed. The two excesses observed in the 2015–2016 data recursive jigsaw analysis in the low-mass three-lepton phase space are reproduced. Results with the full data set are in agreement with the Standard Model expectations. They are interpreted to set exclusion limits at the 95% confidence level on simplified models of chargino-neutralino pair production for masses up to 345 GeV

Immunoprophylaxis of respiratory syncytial virus: global experience

Respiratory syncytial virus (RSV) infects nearly all children by age 2 years, and it causes considerable illness and death in certain high-risk pediatric populations. Historically, treatment for RSV has been symptomatic, and developing a safe and effective vaccine has been a challenge. Therefore, research efforts have turned to passive immunization as the best option to control RSV. Palivizumab, a genetically engineered humanized monoclonal antibody, has been shown to reduce RSV-related hospitalizations significantly, with few adverse effects. It was approved for use in high-risk children in the USA in 1998 and in Europe in 1999; it is now approved for use in more than 45 countries. The efficacy and safety of palivizumab continue to be supported by both clinical trial and outcomes data

Dynamic Spatial Coding within the Dorsal Frontoparietal Network during a Visual Search Task

To what extent are the left and right visual hemifields spatially coded in the dorsal frontoparietal attention network? In many experiments with neglect patients, the left hemisphere shows a contralateral hemifield preference, whereas the right hemisphere represents both hemifields. This pattern of spatial coding is often used to explain the right-hemispheric dominance of lesions causing hemispatial neglect. However, pathophysiological mechanisms of hemispatial neglect are controversial because recent experiments on healthy subjects produced conflicting results regarding the spatial coding of visual hemifields. We used an fMRI paradigm that allowed us to distinguish two attentional subprocesses during a visual search task. Either within the left or right hemifield subjects first attended to stationary locations (spatial orienting) and then shifted their attentional focus to search for a target line. Dynamic changes in spatial coding of the left and right hemifields were observed within subregions of the dorsal front-parietal network: During stationary spatial orienting, we found the well-known spatial pattern described above, with a bilateral hemifield representation in the right hemisphere and a contralateral preference in the left hemisphere. However, during search, the right hemisphere had a contralateral preference and the left hemisphere equally represented both hemifields. This finding leads to novel perspectives regarding models of visuospatial attention and hemispatial neglect