Involvement of Free Radicals in the Development and Progression of Alzheimer’s Disease

Alzheimer’s disease (AD) is a major dementia related to an overproduction of free radicals (FRs), which leads to the generation of oxidative stress in brain tissue. Amyloid beta-peptide of 42 amino acid residues (Aβ1–42) is the main source of FRs in patients with AD. βA1–42 results from hydrolysis of the amyloid precursor protein by β-secretase in a process known as the amyloidogenic pathway. During βA1–42 aggregation, the peptide interacts with various transition metals to produce hydrogen peroxide (H2O2) by the Fenton reaction, generating the hydroxyl radical (•OH), which damages lipids, proteins, and nucleic acids, thereby contributing to neurodegeneration. In addition, βA1–42 is recognized by microglial receptors; it activates these cells, causing overproduction of superoxide anion (O2•−) by NADPH oxidase; O2•− is also converted into H2O2 and finally to •OH in the Fenton reaction. Other factors that contribute to oxidative stress during microglial activation are the overproduction of nitric oxide and interleukins and the overexpression of some enzymes, including cyclooxygenase and inducible nitric oxide synthase, all of which contribute to FR production. Currently, various models in vitro and in vivo exist that permit quantification of O2•− and H2O2 and determination of the effects of these reactive oxygen species

Computational Fluid Dynamics simulations of the Late Pleistocene Lake Bonneville Flood

At approximately 18.0 ka, pluvial Lake Bonneville reached its maximum level. At its northeastern extent it was impounded by alluvium of the Marsh Creek Fan, which breached at some point north of Red Rock Pass (Idaho), leading to one of the largest floods on Earth. About 5320 km3 of water was discharged into the Snake River drainage and ultimately into the Columbia River. We use a 0D model and a 2D non-linear depth-averaged hydrodynamic model to aid understanding of outflow dynamics, specifically evaluating controls on the amount of water exiting the Lake Bonneville basin exerted by the Red Rock Pass outlet lithology and geometry as well as those imposed by the internal lake geometry of the Bonneville basin. These models are based on field evidence of prominent lake levels, hypsometry and terrain elevations corrected for post-flood isostatic deformation of the lake basin, as well as reconstructions of the topography at the outlet for both the initial and final stages of the flood. Internal flow dynamics in the northern Lake Bonneville basin during the flood were affected by the narrow passages separating the Cache Valley from the main body of Lake Bonneville. This constriction imposed a water-level drop of up to 2.7 m at the time of peak-flow conditions and likely reduced the peak discharge at the lake outlet by about 6%. The modeled peak outlet flow is 0.85·106 m3 s−1. Energy balance calculations give an estimate for the erodibility coefficient for the alluvial Marsh Creek divide of ∼0.005 m y−1 Pa−1.5, at least two orders of magnitude greater than for the underlying bedrock at the outlet. Computing quasi steady-state water flows, water elevations, water currents and shear stresses as a function of the water-level drop in the lake and for the sequential stages of erosion in the outlet gives estimates of the incision rates and an estimate of the outflow hydrograph during the Bonneville Flood: About 18 days would have been required for the outflow to grow from 10% to 100% of its peak value. At the time of peak flow, about 10% of the lake volume would have already exited; eroding about 1 km3 of alluvium from the outlet, and the lake level would have dropped by about 10.6 m

Characteristics of inmates witnessing overdose events in prison: implications for prevention in the correctional setting

<p>Abstract</p> <p>Background</p> <p>Although prevention of opiate overdose has been gaining attention as a harm reduction measure with community drug users, there is scarce information about drug overdose in prison. In correctional institutions without a drug free environment, awareness of overdose events is an important public health concern. This study explores the frequency with which inmates in a state penitentiary system report having witnessed drug overdose events in prison. It also explores whether participants who have witnessed an overdose in prison and know someone who died from an overdose in prison significantly differ from those that do not in selected sociodemographic variables and drug use history to identify a target population for prevention interventions.</p> <p>Methods</p> <p>Data comes from a cross-sectional survey of sentenced inmates in the state prisons of Puerto Rico. A complex probabilistic, multistage sampling design was used. A total of 1,179 individuals participated for an 89% response rate.</p> <p>Results</p> <p>Factors associated with witnessing an overdose event in prison include: male sex, age 25 or older, drug use during current incarceration, and drug injection in prison. Factors associated with knowing someone who died from an overdose in prison include: male sex, age between 25–35, previous incarcerations, and drug use during current incarceration.</p> <p>Conclusion</p> <p>Witnessing a drug overdose is a frequent occurrence within the prison system. The likelihood of witnessing an overdose is greater with being male, polydrug use and drug injection in prison. Findings signal an urgent public health challenge that requires prompt interventions to reduce this drug related harm within the correctional system, including adequate access to medication with opiate agonists.</p

Examination of the Feynman-Hibbs Approach in the Study of NeN_N-Coronene Clusters at Low Temperatures

Feynman-Hibbs (FH) effective potentials constitute an appealing approach for investigations of many-body systems at thermal equilibrium since they allow us to easily include quantum corrections within standard classical simulations. In this work we apply the FH formulation to the study of Ne$_N$-coronene clusters ($N=$ 1-4, 14) in the 2-14 K temperature range. Quadratic (FH2) and quartic (FH4) contributions to the effective potentials are built upon Ne-Ne and Ne-coronene analytical potentials. In particular, a new corrected expression for the FH4 effective potential is reported. FH2 and FH4 cluster energies and structures -obtained from energy optimization through a basin-hoping algorithm as well as classical Monte Carlo simulations- are reported and compared with reference path integral Monte Carlo calculations. For temperatures $T> 4$ K, both FH2 and FH4 potentials are able to correct the purely classical calculations in a consistent way. However, the FH approach fails at lower temperatures, especially the quartic correction. It is thus crucial to assess the range of applicability of this formulation and, in particular, to apply the FH4 potentials with great caution. A simple model of $N$ isotropic harmonic oscillators allows us to propose a means of estimating the cut-off temperature for the validity of the method, which is found to increase with the number of atoms adsorbed on the coronene molecule

Klebsiella pneumoniae Strains Producing Extended-Spectrum B-Lactamases in Spain: Microbiological and Clinical Features

Extended-spectrum B-lactamases (ESBL) of the CTX-M, SHV, and TEM families were recognized in 76 (67%), 31 (27%), and 6 (5%) isolates, respectively, among 162 ESBL-producing Klebsiella pneumoniae (ESBLKp) strains obtained in a multicenter study in Spain. Predisposing factors for ESBL-Kp acquisition included invasive procedures, mechanical ventilation, and previous antimicrobial use

Epidemiologic and Clinical Impact of Acinetobacter baumannii Colonization and Infection: A Reappraisal

Acinetobacter baumannii is one of the most important antibiotic-resistant nosocomial bacteria. We investigated changes in the clinical and molecular epidemiology of A. baumannii over a 10-year period. We compared the data from 2 prospective multicenter cohort studies in Spain, one performed in 2000 (183 patients) and one in 2010 (246 patients), which included consecutive patients infected or colonized by A. baumannii. Molecular typing was performed by repetitive extragenic palindromic polymerase chain reaction (REP-PCR), pulsed-field gel electrophoresis (PFGE), and multilocus sequence typing (MLST). The incidence density of A. baumannii colonization or infection increased significantly from 0.14 in 2000 to 0.52 in 2010 in medical services (p<0.001). The number of non-nosocomial health careassociated cases increased from 1.2% to 14.2%, respectively (p<0.001). Previous exposure to carbapenems increased in 2010 (16.9% in 2000 vs 27.3% in 2010, p¼0.03). The drugs most frequently used for definitive treatment of patients with infections were carbapenems in 2000 (45%) and colistin in 2010 (50.3%). There was molecular-typing evidence of an increase in the frequency of A. baumannii acquisition in non-intensive care unit wards in 2010 (7.6% in 2000 vs 19.2% in 2010, p¼0.01). By MSLT, the ST2 clonal group predominated and increased in 2010. This epidemic clonal group was more frequently resistant to imipenem and was associated with an increased risk of sepsis, although not with severe sepsis or mortality. Some significant changes were noted in the epidemiology of A. baumannii, which is increasingly affecting patients admitted to conventional wards and is also the cause of non-nosocomial health care-associated infections. Epidemic clones seem to combine antimicrobial resistance and the ability to spread, while maintaining their clinical virulence.Ministerio de Ciencia e InnovaciónInstituto de Salud Carlos IIIEuropean Development Regional Fund “A way to achieve Europe” ERDFSpanish Network for the Research in Infectious Diseases REIPI RD06/0008FIS PI 10/00056 and PI 11/0204

The orosomucoid 1 protein (α1 acid glycoprotein) is overexpressed in odontogenic myxoma

Odontogenic myxoma (OM) is a benign, but locally invasive, neoplasm occurring in the jaws. However, the molecules implicated in its development are unknown. OM as well as Dental Follicle (DF), an odontogenic tissue surrounding the enamel organ, is derived from ectomesenchymal/mesencyhmal elements. To identify some protein that could participate in the development of this neoplasm, total proteins from OM were separated by two-dimensional electrophoresis and the profiles were compared with those obtained from DF, used as a control

LanderPick, a Remote Operated Trawled Vehicle to cost-effectively deploy and recover lightweight oceanographic landers.

Landers are modular structures equipped with miscellaneous sensors and monitoring equipment which are positioned directly on the seabed to operate autonomously for a defined timeframe. A drawback of landers intended to operate for prolonged periods in the deep ocean is the high cost of recovery systems, typically depending on buoyancy modules plus expendable ballast, or requiring ROVs assistance. LanderPick concept consists of the design of a specific trawled vehicle to deploy and recover lightweight oceanographic landers not provided with recovery elements, but having a capture mesh that facilitates their hitching. The LanderPick vehicle is technically a ROTV (Remote Operated Trawled Vehicle) controlled through a standard coaxial electromechanical cable that allows real-time control from the vessel. Navigation is enabled by a low-light high-definition camera, aided by spotlights and laser pointers. Small propellers aid in the final precision approach maneuvers. A mechanical release allows the precise placement at the sea bottom of landers carried as a payload, as well as their recovery by means of a triple hook. First sea missions of the system were carried out successfully in 2021 in southern Biscay. A 4-month deployment of a lander array equipped with current-meters along an energetic canyon axis provided unprecedented detail in the progression of the internal tidal bore. Short (48-hours) deployments of a fully-instrumented lander, including lapse-time image and baits in a deep seamount summit within a marine protected area, provided insights on the biodiversity of a unique ecosystem. The LanderPick novel approach to cost-effectively and precisely deploy and recover lightweight oceanographic landers allows to conceive (i) monitoring systems based on the deployment of arrays or fleets of low-cost landers and (ii) experiments associated with deep habitats such as coral reefs in which it is necessary to locate landers with great precision

Simulation of impulse response for indoor visible light communications using 3D CAD models

n this article, a tool for simulating the channel impulse response for indoor visible light communications using 3D computer-aided design (CAD) models is presented. The simulation tool is based on a previous Monte Carlo ray-tracing algorithm for indoor infrared channel estimation, but including wavelength response evaluation. The 3D scene, or the simulation environment, can be defined using any CAD software in which the user specifies, in addition to the setting geometry, the reflection characteristics of the surface materials as well as the structures of the emitters and receivers involved in the simulation. Also, in an effort to improve the computational efficiency, two optimizations are proposed. The first one consists of dividing the setting into cubic regions of equal size, which offers a calculation improvement of approximately 50% compared to not dividing the 3D scene into sub-regions. The second one involves the parallelization of the simulation algorithm, which provides a computational speed-up proportional to the number of processors used