The pathophysiology underlying altered blood-cerebrospinal fluid barrier (BCSFB) function in Alzheimer's disease (AD) is unknown but may relate to endothelial cell activation and cytokine mediated ...inflammation.
Cerebrospinal fluid (CSF) and peripheral blood were concurrently collected from cognitively healthy controls (
= 21) and patients with mild cognitive impairment (MCI) (
= 8) or AD (
= 11). The paired serum and CSF samples were assayed for a panel of cytokines, chemokines, and related trophic factors using multiplex ELISAs. Dominance analysis models were conducted to determine the relative importance of the inflammatory factors in relationship to BCSFB permeability, as measured by CSF/serum ratios for urea, creatinine, and albumin.
BCSFB disruption to urea, a small molecule distributed by passive diffusion, had a full model coefficient of determination (
) = 0.35, and large standardized dominance weights (>0.1) for monocyte chemoattractant protein-1, interleukin (IL)-15, IL-1rα, and IL-2 in serum. BCSFB disruption to creatinine, a larger molecule governed by active transport, had a full model
= 0.78, and large standardized dominance weights for monocyte inhibitor protein-1b in CSF and tumor necrosis factor-α in serum. BCSFB disruption to albumin, a much larger molecule, had a full model
= 0.62, and large standardized dominance weights for IL-17a, interferon-gamma, IL-2, and VEGF in CSF, as well IL-4 in serum.
Inflammatory proteins have been widely documented in the AD brain. The results of the current study suggest that changes in BCSFB function resulting in altered permeability and transport are related to expression of specific inflammatory proteins, and that the shifting distribution of these proteins from serum to CSF in AD and MCI is correlated with more severe perturbations in BCSFB function.
Surface water from 38 streams nationwide was assessed using 14 target-organic methods (719 compounds). Designed-bioactive anthropogenic contaminants (biocides, pharmaceuticals) comprised 57% of 406 ...organics detected at least once. The 10 most-frequently detected anthropogenic-organics included eight pesticides (desulfinylfipronil, AMPA, chlorpyrifos, dieldrin, metolachlor, atrazine, CIAT, glyphosate) and two pharmaceuticals (caffeine, metformin) with detection frequencies ranging 66–84% of all sites. Detected contaminant concentrations varied from less than 1 ng L–1 to greater than 10 μg L–1, with 77 and 278 having median detected concentrations greater than 100 ng L–1 and 10 ng L–1, respectively. Cumulative detections and concentrations ranged 4–161 compounds (median 70) and 8.5–102 847 ng L–1, respectively, and correlated significantly with wastewater discharge, watershed development, and toxic release inventory metrics. Log10 concentrations of widely monitored HHCB, triclosan, and carbamazepine explained 71–82% of the variability in the total number of compounds detected (linear regression; p-values: < 0.001–0.012), providing a statistical inference tool for unmonitored contaminants. Due to multiple modes of action, high bioactivity, biorecalcitrance, and direct environment application (pesticides), designed-bioactive organics (median 41 per site at μg L–1 cumulative concentrations) in developed watersheds present aquatic health concerns, given their acknowledged potential for sublethal effects to sensitive species and lifecycle stages at low ng L–1.
Rock, concrete, and other engineered materials are often composed of several minerals that change volumetrically in response to variations in the moisture content of the local environment. Such ...differential shrinkage is caused by varying shrinkage rates between mineral compositions during dehydration. Using both 3D X-ray imaging of geo-architected samples and peridynamic (PD) numerical simulations, we show that the spatial distribution of the clay affects the crack network geometry with distributed clay particles yielding the most complex crack networks and percent damage (99.56%), along with a 60% reduction in material strength. We also demonstrate that crack formation, growth, coalescence, and distribution during dehydration, are controlled by the differential shrinkage rates between a highly shrinkable clay and a homogeneous mortar matrix. Sensitivity tests performed with the PD models show a clay shrinkage parameter of 0.4 yields considerable damage, and reductions in the parameter can result in a significant reduction in fracturing and an increase in material strength. Additionally, isolated clay inclusions induced localized fracturing predominantly due to debonding between the clay and matrix. These insights indicate differential shrinkage is a source of potential failure in natural and engineered barriers used to sequester anthropogenic waste.
Multicopper oxidases (MCOs) utilize an electron shuttling Type 1 Cu (T1) site in conjunction with a mononuclear Type 2 (T2) and a binuclear Type 3 (T3) site, arranged in a trinuclear copper cluster ...(TNC), to reduce O2 to H2O. Reduction of O2 occurs with limited overpotential indicating that all the coppers in the active site can be reduced via high-potential electron donors. Two forms of the resting enzyme have been observed in MCOs: the alternative resting form (AR), where only one of the three TNC Cu’s is oxidized, and the resting oxidized form (RO), where all three TNC Cu’s are oxidized. In contrast to the AR form, we show that in the RO form of a high-potential MCO, the binuclear T3 Cu(II) site can be reduced via the 700 mV T1 Cu. Systematic spectroscopic evaluation reveals that this proceeds by a two-electron process, where delivery of the first electron, forming a high energy, metastable half reduced T3 state, is followed by the rapid delivery of a second energetically favorable electron to fully reduce the T3 site. Alternatively, when this fully reduced binuclear T3 site is oxidized via the T1 Cu, a different thermodynamically favored half oxidized T3 form, i.e., the AR site, is generated. This behavior is evaluated by DFT calculations, which reveal that the protein backbone plays a significant role in controlling the environment of the active site coppers. This allows for the formation of the metastable, half reduced state and thus the complete reductive activation of the enzyme for catalysis.
Lungs undergo mechanical strain during breathing, but how these biophysical forces affect cell fate and tissue homeostasis are unclear. We show that biophysical forces through normal respiratory ...motion actively maintain alveolar type 1 (AT1) cell identity and restrict these cells from reprogramming into AT2 cells in the adult lung. AT1 cell fate is maintained at homeostasis by Cdc42- and Ptk2-mediated actin remodeling and cytoskeletal strain, and inactivation of these pathways causes a rapid reprogramming into the AT2 cell fate. This plasticity induces chromatin reorganization and changes in nuclear lamina-chromatin interactions, which can discriminate AT1 and AT2 cell identity. Unloading the biophysical forces of breathing movements leads to AT1-AT2 cell reprogramming, revealing that normal respiration is essential to maintain alveolar epithelial cell fate. These data demonstrate the integral function of mechanotransduction in maintaining lung cell fate and identifies the AT1 cell as an important mechanosensor in the alveolar niche.
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•Mechanotransduction is a key feature of alveolar type 1 (AT1) cells in the lung•Actin remodeling and integrin signaling regulate AT1 and AT2 cell fate transitions•Physical blockade of respiratory movement leads to loss of AT1 cell identity•Nuclear lamina-chromatin interactions determine alveolar epithelial cell fate
Forces elicited by respiration actively induce changes in nuclear lamina-chromatin interactions to maintain alveolar type 1 (AT1) cell identity and restrict these cells from reprogramming into AT2 cells.
Climate change and its effects on the hydrologic regime of the Amazon basin can impact biogeochemical processes, transportation, flood vulnerability, fisheries and hydropower generation. We examined ...projections of climate change on discharge and inundation extent in the Amazon basin using the regional hydrological model MGB-IPH with 1-dimensional river hydraulic and water storage simulation in floodplains. Future projections (2070–2099) were obtained from five GCMs from IPCC’s Fifth Assessment Report CMIP5. Climate projections have uncertainty and results from different climate models did not agree in total Amazon flooded area or discharge anomalies along the main stem river. Overall, model runs agree better with wetter (drier) conditions over western (eastern) Amazon. Results indicate that increased mean and maximum river discharge for large rivers draining the Andes in the northwest contributes to increased mean and maximum discharge and inundation extent over Peruvian floodplains and Solimões River (annual mean-max: +9 % - +18.3 %) in western Amazonia. Decreased river discharges (mostly dry season) are projected for eastern basins, and decreased inundation extent at low water (annual min) in the central (−15.9 %) and lower Amazon (−4.4 %).
Introduction
Screening colonoscopy is one of the few procedures that can prevent cancer. While the majority of colonoscopies in the USA are performed by gastroenterologists, general surgeons play a ...key role in at-risk, rural populations. The aim of this study was to examine geographic practice patterns in colonoscopy using a nationwide Medicare claims database.
Methods and procedures
The 2017 Medicare Provider Utilization and Payment database was used to identify physicians performing colonoscopy. Providers were classified as gastroenterologists, surgeons, ambulatory surgical centers (ASCs), or other. Rural–Urban Commuting Area classification at the zip code level was used to determine whether the practice location for an individual provider was in a rural area/small town (< 10,000 people), micropolitan area (10–50,000 people), or metropolitan area (> 50,000 people).
Results
Claims data from 3,861,187 colonoscopy procedures on Medicare patients were included. The majority of procedures were performed by gastroenterologists (57.2%) and ASCs (32.1%). Surgeons performed 6.8% of cases overall. When examined at a zip code level, surgeons performed 51.6% of procedures in small towns/rural areas and 21.7% of procedures in micropolitan areas. Individual surgeons performed fewer annual procedures as compared to gastroenterologists (median 51 vs. 187,
p
< 0.001).
Conclusions
Surgeons perform the majority of colonoscopies in rural zip codes on Medicare patients. High-quality, surgical training in endoscopy is essential to ensure access to colonoscopy for patients outside of major metropolitan areas.
Household food insecurity is associated with multiple adverse outcomes in children and adolescents, including poor school performance. U.S. federal food assistance programs such as the Food Stamp ...Program (FSP) aim to help prevent household food insecurity and its outcomes. Program participation may act as a resource either to counteract the effects of constraints such as food insecurity or to modify the effects of food insecurity on outcomes. This study aimed to determine whether FSP participation was associated with child reading and mathematics learning, weight gain, and social skills and whether these associations depended on degree of estimated need for the program. Data used were from the Early Childhood Longitudinal Study-Kindergarten cohort, a large nationally representative sample. A difference (i.e., fixed-effects) model was used to minimize bias in the estimation of association resulting from unmeasured covariates. Starting FSP participation during the 4 years from K to third grade was associated with about a 3-point greater improvement in reading and mathematics score as compared with stopping FSP participation during that period. But it was for female students only that this association was large and significant. Children in households starting FSP participation had slightly but not significantly less weight gain compared with children in households stopping FSP participation. This study provides the strongest evidence to date that FSP participation plausibly has beneficial effects for children on nonnutritional outcomes, specifically academic learning. The mechanisms for this relationship are not well understood and may be through both dietary intake and stress.
Las Crisis de Paternidad de Freud Jones, Edward A.
The International Journal of Psychoanalysis (en español),
20/7/4/, Letnik:
3, Številka:
4
Journal Article
Este artículo reexamina la interpretación del significado del olvido de Aliquis, y materiales relacionados en términos de una crisis familiar en el año 1900 que involucraba a Freud, a Anna Freud ...Bernays y a su hermana menor Paula. Se sostiene que Ernest Jones y Anna Freud más tarde ocultaron esta historia a la Historia, en gran parte, por razones familiares. Para respaldar este argumento se recurre a los archivos de la correspondencia de Ernest Jones y Anna Freud, a las memorias de Anna Freud Bernays, a la correspondencia completa de Freud con Fliess y a otras fuentes históricas, y se las compara con Los orígenes del psicoanálisis y con la biografía de Freud escrita por Ernest Jones. Así se demuestra como los sucesos dados durante la crisis se manifestaron en el ensayo "Sobre el sueño" de Freud, en el olvido de Aliquis, y en la historia del error bancario. Asimismo se rechaza la hipótesis de Peter Swales de que Freud y Minna Bernays fueran parte del olvido de Aliquis, pero se acepta la idea de Didier Anzieu de que Minna Bernays era el sujeto del relato sobre el error bancario. También se demuestra que el motivo de la represión histórica del relato empezó con Freud, pero que estuvo sobredeterminado e incluía la culpa y el sufrimiento desarrollados cuando Paula y sus otras hermanas se vieron inmersas en la invasión nazi de Austria.
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