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NAC was well-tolerated with only mild gastrointestinal adverse events associated with the treatment.
We found no evidence supporting the efficacy of the adjunctive use of NAC in OCD.
We found no evidence supporting the efficacy of the adjunctive use of NAC in OCD.
Persistent negative symptoms (PNS, e.g., avolition, anhedonia, alogia) are present in up to 30% of individuals diagnosed with a first episode of psychosis and greatly impact functional outcomes. PNS and secondary PNS (sPNS concomitant with positive, depressive, or extrapyramidal symptoms) may index distinct pathophysiologies reflected by structural brain changes, particularly in the medial temporal lobe (MTL) and basal ganglia.
We sought to characterize dynamic brain changes related to PNS over the course of 2years following a first episode of psychosis.
Longitudinal volumetric trajectories within the MTL (hippocampus, parahippocampal gyrus, entorhinal cortex, perirhinal cortex) and basal ganglia (caudate, putamen, pallidum) were investigated in 98 patients with first-episode psychosis and 86 healthy controls using generalized estimating equations.
In left hippocampus, PNS (n=25 at baseline) showed decreased volumes over time, sPNS (n=26) volumes remained stable, and non-PNS (n=47) volumes increased olighting the importance of targeted early interventions.Whereas it is well established that zooplankton can transfer various pollutants such as mercury (Hg) from primary producers to higher trophic levels, less is known on the effects of their activities on the recycling of Hg in aquatic ecosystems. Here, the impact of zooplankton grazing efficiency and excretion/egestion processes on metal concentrations in freshwater was investigated. Isotopically labeled algae (200HgCl2, Me198HgCl) was used as a food source and the transfer of the selected isotopes to the culture medium during grazing was measured. In parallel, the potential for the recycling of major ions and metals, including selected essential and non-essential metals, was investigated for this could help to track the effects of sloppy feeding. To highlight the role of feeding behavior, a large filter-feeder (Daphnia magna) was compared to a smaller selective feeder zooplankton taxon (calanoid copepods), with the latter being expected to cause more sloppy feeding than the former. The experiments demonstrated that zooplankton grazing of both taxa significantly influenced the concentrations of the particulate portion of both inorganic Hg (IHg) and monomethylmercury (MeHg) in water. In contrast, only Daphnia significantly increased the concentration of dissolved IHg, whereas the concentration of dissolved MeHg was not affected by either grazer. The results also suggested that both taxa affected the concentrations of dissolved Fe, Zn, SO42- and rare earth elements via sloppy feeding, whereas only Daphnia significantly increased the concentration of dissolved Cu via this mechanism. The effects of excretion/egestion were negligible except for dissolved IHg and Cu in Daphnia treatment. These results highlight a neglected pathway of IHg and MeHg recycling in the water column in freshwater ecosystems with potentially important consequences for trophic transfer.
Mammographic density (MD), expressed as percentage of fibroglandular breast tissue, is an important risk factor for breast cancer. Our objective is to investigate the relationship between MD and residential proximity to pollutant industries in premenopausal Spanish women.
A cross-sectional study was carried out in a sample of 1225 women extracted from the DDM-Madrid study. Multiple linear regression models were used to assess the association of MD percentage (and their 95% confidence intervals (95%CIs)) and proximity (between 1 km and 3 km) to industries included in the European Pollutant Release and Transfer Register.
Although no association was found between MD and distance to all industries as a whole, several industrial sectors showed significant association for some distances "surface treatment of metals and plastic" (β = 4.98, 95%CI = (0.85; 9.12) at ≤1.5 km, and β = 3.00, 95%CI = (0.26; 5.73) at ≤2.5 km), "organic chemical industry" (β = 6.73, 95%CI = (0.50; 12.97) at ≤1.5 km), "pharmaceutical prdiating role in breast carcinogenesis.
Our results suggest no statistically significant relationship between MD and proximity to industries as a whole, although we detected associations with various industrial sectors and some specific pollutants, which suggests that MD could have a mediating role in breast carcinogenesis.Crystalline aquifers are layered systems in which the hydrogeological path of waters extends from highly weathered, shallow and porous rocks to poorly weathered, deep and fissured rocks. This varying hydrogeological setting influences the water chemistry in different ways. The paper aims to reconstruct the water-rock interaction process in these various environments starting from a solid reactant represented by an average granite rock and several waters from the shallow aquifer. Afterwards, the water-rock interaction processes occurring in the deep environment are reconstructed, varying the geochemical conditions (primary reactants, secondary mineral phases allowed to precipitate, fO2 and fCO2), with a special focus on fluoride (F-). The evolution from the F-poor, Ca-HCO3 facies to the F-rich, Na-HCO3 water type of high pH was simulated using reaction path modelling. The obtained results show that the theoretical evolution trends well reproduce both shallow and deep water samples providing detailed information on the behavior of fluoride and other relevant constituents (i.e., Na, K, Ca, Mg, SiO2). The performed model represents a flexible and powerful tool for environmental research, applicable in other areas hosting F-rich groundwater.Karst ecosystems play a unique role as exceptional natural habitats in sustaining biodiversity. This study focuses on diatoms, a diverse group of microeukaryotes in the periphytic community of a karstic river. In a multi-microhabitat study along the Krka River (Croatia), our goal was to obtain a detailed overview of diatom diversity and community structure using morphological and molecular approaches, and to assess the applicability of eDNA metabarcoding as a reliable tool for biomonitoring assessment. The results revealed a relatively low agreement in the diatom community composition between the two approaches, but also provided complementary information, with no differences in beta diversity detected between microhabitats. The SIMPER analysis underlined the importance of the molecular approach in identifying diatom community composition, due to errors in distinguishing between deposited diatom cells that occurred in the morphological analysis. In contrast, the morphological approach indicated a clear diatom community separation along the river with a strong location effect. Despite certain differences, both approaches provided a feasible assessment of the ecological status according to the relationship to environmental pressures, classifying the Krka River as High (morphological approach) or Good (molecular approach) throughout the most of its course. Moreover, diatom diversity based on both approaches provides a reliable dataset applicable in routine monitoring assessment and offers a deeper understanding of the presented ecological status. The incompleteness of a reference database presents one major drawback of the molecular approach, which needs further updating in order to improve routine diatom metabarcoding.The combined toxic effects of nanoplastics and heavy metals on aquatic organisms have attracted widespread attention; however, the results are inconsistent and the mechanisms remain unclear. In this study, the single and combined toxicity effects of Cu and two types of polystyrene nanoplastics (PS-NPs; 50 nm PS and 55 nm PS-COOH) on Platymonas helgolandica var. tsingtaoensis were investigated, including growth inhibition, chlorophyll content, and oxidative stress. An adverse dose-response relationship on growth inhibition was found in the Cu treatment groups, which was related to the decrease in chlorophyll content and damage to cell membranes. The growth inhibitory effect of PS-NPs on microalgae increased with exposure time and concentration, and no significant difference was found in the two types of PS-NPs because of the negligible contribution of functional groups. A more significant increase in chlorophyll content was found in PS treatments than in PS-COOH treatments at 96 h because of the microscale aggregates formed by PS. Higher concentrations (≥ 50 mg/L) of PS-NPs caused membrane lipid peroxidation, which might be responsible for growth inhibition. In the combined exposure experiments, a synergistic effect on the growth inhibition rate was obtained using the independent action model and Abbott model. Combined exposure triggered more severe oxidative damage to the microalgae. Adsorption experiment results showed that there was no adsorption between PS-NPs and Cu, while the interaction of Cu and algal cells could be promoted due to the presence of the PS-NPs, which explained the increasing combined toxicity. This study could improve our understanding of the combined toxicity of nanoplastics and heavy metals and could provide a new explanation for the mechanism of combined toxicity.Forage crops are widely cultivated as livestock feed to relieve grazing pressure in agro-pastoral regions with arid climates. However, gaseous losses of soil nitrogen (N) following N fertilizer application have been considerable in response to the pursuit of increased crop yield. A two-year experiment was carried out in a typical saline field under a temperate continental arid climate to investigate the effect of N application rate on N2O emissions from barley (Hordeum vulgare L.), corngrass (Zea mays × Zea Mexicana), rye (Secale cereale L.), and sorghum-sudangrass hybrid (Sorghum bicolor × Sorghum sudanense). The dynamics of N2O emissions, hay yield, and crude protein (CP) yield were measured under four N application rates (0, 150, 200, and 250 kg ha-1) in 2016 and 2017. An N2O emission peak was observed for all crop species five days after each N application. Cumulative N2O fluxes in the growing season ranged from 0.66 to 2.40 kg ha-1 and responded exponentially to N application rate. Emission factors of N2O showed a linear increase with N application rate for all crop species, but the linear slopes significantly differed between barley or rye and corngrass and sorghum-sudangrass hybrid. The hay and CP yields of all forage grasses significantly increased with the increase of N application rate from 0 to 200 kg ha-1. Barley and rye with lower hay and CP yields showed higher N2O emission intensities. The increased level of N2O emission intensity was higher from 200 to 250 kg ha-1 than from 150 to 200 kg ha-1. At N application rates of 200 and 250 kg ha-1, CP yield had a significantly negative correlation with cumulative N2O emission and explained 50.5% and 62.9% of the variation, respectively. In conclusion, ~200 kg ha-1 is the optimal N rate for forage crops to minimize N2O emission while maintaining yield in continental arid regions.Multifunctional hydrogels with excellent comprehensive performance are essential prerequisite for the implementation of effective water resources technology with high efficiency and low energy consumption. Inspired by the water purification and self-healing properties of natural plants, and based on the synergy of photothermal and biological effects, high photothermal Fe3O4 nanoparticles and natural polyhydroxy oligomeric proanthocyanidin (OPC) are introduced into a water-active polyvinyl alcohol (PVA) hydrogel. Two new bio-hydrogels of PVA/Fe3O4/graphite and PVA/OPC with self-healing and stretchable properties are proposed and designed. The obtained hydrogels exhibit reversible covalent cross-linked water-promoted healing (chemically) and photothermal melting/recrystallization healing (physically). The double-layered hydrogel composite demonstrates a dual response function (sunlight and near-infrared light), along with water purification properties. It is prepared through a water spray triggered self-healing process. The ultimate fracture strain of the photothermal layer and purification layer hydrogel was more than 1000% and 400% respectively after self-healing.After 48 h of hydrogel composite adsorption, the color of a methylene blue solution faded, and the absorption peak at 664 nm decreased. In addition, this research adopts a phased evaporation method to concentrate local energy and provide power for seawater evaporation. The evaporation efficiency of seawater induced by near-infrared (NIR) light was up to 3.15 kg m-2 h-1, whereas that under sunlight was 1.25 kg m-2 h-1. Selection of the evaporation excitation light source allowed control of the evaporation efficiency. The proposed technology is expected to be widely applicable to the staged evaporation of seawater as well as water purification.The recovery of metals from spent LiCoO2 batteries (SLBs) is essential to avoid resource wastage and the production of hazardous waste. However, the major challenge in regard to recovering metals from SLBs using traditional bioleaching is the low Co yield. To overcome this issue, a mixed culture of Acidithiobacillus caldus and Sulfobacillus thermosulfidooxidans was designed for use in SLBs leaching in this study. With the assistance of Fe2+ as a reductant, 99% of Co and 100% of Li were leached using the above mixed-culture bioleaching (MCB) process, thus solving the problem of low metal leaching efficiency from SLBs. Analysis of the underlying mechanism revealed that the effective extraction of metals from SLBs by the Fe2+-MCB process relied on Fe2+-releasing electrons to reduce refractory Co(III) to Co(II) that can be easily bioleached. Finally, the hazardous SLBs was transformed into a non-toxic material after treatment utilizing the Fe2+-MCB process. However, effective SLBs leaching was not achieved by the addition of Fe0 to the MCB system. Only 25% Co and 31% Li yields were obtained, as the addition of Fe0 caused acid consumption and bacterial apoptosis. Overall, this study revealed that reductants that cause acid consumption and harm bacteria should be ruled out for use in reductant-assisted bioleaching processes for extracting metals from SLBs.There has been a considerable number of reports on Hg concentrations in Arctic mammals since the last Arctic Monitoring and Assessment Programme (AMAP) effort to review biological effects of the exposure to mercury (Hg) in Arctic biota in 2010 and 2018. Here, we provide an update on the state of the knowledge of health risk associated with Hg concentrations in Arctic marine and terrestrial mammal species. Using available population-specific data post-2000, our ultimate goal is to provide an updated evidence-based estimate of the risk for adverse health effects from Hg exposure in Arctic mammal species at the individual and population level. Tissue residues of Hg in 13 species across the Arctic were classified into five risk categories (from No risk to Severe risk) based on critical tissue concentrations derived from experimental studies on harp seals and mink. Exposure to Hg lead to low or no risk for health effects in most populations of marine and terrestrial mammals, however, subpopulations of polar bears, pilot whales, narwhals, beluga and hooded seals are highly exposed in geographic hotspots raising concern for Hg-induced toxicological effects. About 6% of a total of 3500 individuals, across different marine mammal species, age groups and regions, are at high or severe risk of health effects from Hg exposure. The corresponding figure for the 12 terrestrial species, regions and age groups was as low as 0.3% of a total of 731 individuals analyzed for their Hg loads. Temporal analyses indicated that the proportion of polar bears at low or moderate risk has increased in East/West Greenland and Western Hudson Bay, respectively. However, there remain numerous knowledge gaps to improve risk assessments of Hg exposure in Arctic mammalian species, including the establishment of improved concentration thresholds and upscaling to the assessment of population-level effects.Four anaerobic ammonium oxidation (anammox) immobilized filler reactors (R1 33 °C-normal, R2 seasonal temperature-normal, R3 seasonal temperature-feast, R4 seasonal temperature-starvation) were established to study the response of anammox immobilized fillers to seasonal temperature changes and different operating modes. The results showed that the anammox immobilized filler could better adapt to the seasonal temperature drop and maintain the activity potential by adjusting the hydraulic retention time (HRT). During the temperature rise phase, R2 activity increased rapidly with the highest nitrogen removal rate reaching 1.26 kgN·(m3·d)-1, which was equivalent to control sample R1 (1.33 kgN·(m3·d)-1). However, feasting and famine conditions severely impaired anammox performance and changed stoichiometric ratios; feasting, in particular, significantly lowered the nitrogen removal potential of R3. The specific anammox activity of R2, R3 and R4 was 92.2%, 52.6% and 67.9%, respectively, that of R1, respectively, whal temperature changes and different operating modes on nitrogen removal.Quinolones (QNs), dechloranes (DECs), and chlorinated paraffins (CPs) are three kinds of new halogenated organic pollutants (HOPs), which originate from the use of flame retardants, lubricants and pesticides. Since QNs, DECs, and CPs are frequently detected in waters and sediments, it is necessary to investigate the toxic effects of these HOPs with dwelling phytoplankton, especially for cyanobacteria, to explore their potential hormetic effects and contributions to algal blooms. In the present study, we investigate single and joint toxicity of QNs, DECs and CPs on Microcystis aeruginosa (M. aeruginosa), a cyanobacterium that is frequently implicated with algal blooms. The results indicate single QNs and DECs induce marked hormetic effects on the proliferation of M. aeruginosa but CPs do not. The stimulatory effect of hormesis is linked with accelerated replication of DNA, which is considered to stem from the moderate rise in intracellular reactive oxygen species (ROS). Joint toxicity tests reveal that both QNs & CPs mixtures and DECs & CPs mixtures show hormetic effects on M. aeruginosa, but QNs & DECs mixtures show no hormetic effect. QNs & DECs mixtures exhibit synergistic toxic actions, which may be caused by a sharp rise in intracellular ROS simultaneously produced by the agents. Joint toxic actions of both QNs & CPs, and DECs & CPs shift from addition to antagonism as concentration increases, and this shift may mainly depend on the influence of CPs on cell membrane hydrophobicity of M. aeruginosa. This study provides data and toxic mechanisms for the hormetic phenomenon of single and joint HOPs on M. aeruginosa. The hormetic effects of HOPs may benefit the proliferation of M. aeruginosa in the aquatic environment, aggravating the formation of algal blooms. This study also reflects the important role of hormesis in environmental risk assessment of pollutants.Sulfidated zero-valent iron (S-ZVI) is commonly used to degrade trichloroethylene (TCE). The reactivity of S-ZVI is related to not only the properties of S-ZVI but also the geochemical conditions in groundwater, such as coexisted NO3-. Therefore, the effect of NO3- on TCE degradation by S-ZVI and its mechanism were systematically studied. 95.17% of TCE was degraded to acetylene, dichloroethene, ethene, ethane and multi‑carbon products via β-elimination by fresh S-ZVI that contained 85.31% Fe0 and 14.69% FeS in the presence of NO3-, demonstrating that NO3- did not affect the degradation pathway of TCE. While high concentration of NO3- (> 10 mg/L) competed for electrons at the Fe/FeOx interface with degradation products, leading to a continuous rising of acetylene. Moreover, the rapid reduction of NO3- to NH4+ (89.79%) at the Fe0 interface contributed to the release of 5.08 mM Fe2+ from S-ZVI, which promoted the formation of Fe3O4 with excellent electron conduction properties on the surface of S-ZVI. Accordingly, NO3- improved the degradation and electron selectivity of TCE by 51.07% and 2.79 fold, respectively. This study demonstrated that S-ZVI could remediate the contamination of NO3- and TCE simultaneously and the presence of NO3- could effectively enhance the degradation of TCE in groundwater.Although interplays between plant and coevolved microorganisms are believed to drive landscape formation and ecosystem services, the relationships between the mycobiome and phytochemical evolution and the evolutionary characteristics of plant-mycobiome interaction patterns are still unclear. The present study explored fungal communities from 405 multiniche samples of three Holarctic disjunct Panax species. The overall mycobiomes showed compartment-dominated variations and dynamic universality. Neutral models were fitted for each compartment at the Panax genus (I) and species (II) levels to infer the community assembly mechanism and identify fungal subgroups potentially representing different plant-fungi interaction results, i.e., the potentially selected, opposed, and neutral taxa. Selection contributed more to the endosphere than to external compartments. The nonneutral taxa showed significant phylogenetic clustering. In Model I, the opposed subgroups could best reflect Panax saponin diversities (r = 0.69), and genera with highly positive correlations to specific saponins were identified using machine learning. Although mycobiomes in the three species differed significantly, subgroups in Model II were phylogenetically clustered based on potential interaction type rather than plant species, indicating potentially conservative plant-fungi interactions. In summary, the finding of strong links between invaders and saponin diversity can help explore the underlying mechanisms of saponin biosynthesis evolution from microbial insights, which is important to understanding the formation of the current landscape. The potential conservatism of plant-fungi interaction patterns suggests that the related genetic modules and selection pressures were convergent across Panax species, advancing our understanding of plant interplay with biotic environments.Eutrophication remains the most widespread water quality impairment globally and is commonly associated with excess nitrogen (N) and phosphorus (P) inputs to surface waters from agricultural runoff. In southern Ontario, Canada, increases in nitrate (NO3-N) concentrations as well as declines in total phosphorus (TP) concentration have been observed over the past four decades at predominantly agricultural watersheds, where major expansions in row crop production at the expense of pasture and forage have occurred. This study used a space-for-time approach to test whether 'agricultural intensification', herein defined as increases in row crop area (primarily corn-soybean-winter wheat rotation) at the expense of mixed livestock and forage/pasture, could explain increases in NO3-N and declines in TP over time. We found a clear, positive relationship between the extent of row crop area within watersheds and NO3-N losses, such that tributary NO3-N concentrations and export were predicted to increase by ~0.4 mg/L and ~130 kg/km2 respectively, for every 10% expansion in row crop area. There was also a significant positive relationship between row crop area and total dissolved phosphorus (TDP) concentration, but not export, and TP was not correlated with any form of landcover. Instead, TP was strongly associated with storm events, and was more sensitive to hydrologic condition than to landcover. These results suggest that pervasive shifts toward tile-drained corn and soybean production could explain increases in tributary NO3-N levels in this region. The relationship between changes in agriculture and P is less clear, but the significant association between dissolved P and row crop area suggests that increased adoption of reduced tillage practices and tile drainage may enhance subsurface losses of P.Nanoplastics (NPs) can be potentially accumulated by living organisms, but how they interact with cells at the cellular or subcellular level in the physiological environment is still largely unknown. In this study, time-resolved flow cytometry coupled with confocal imaging as well as other biomolecular approaches were used to investigate the cellular and subcellular responses to amine-modified polystyrene NPs of two different sizes (100 nm and 1000 nm). We first demonstrated that the two sizes of NPs displayed contrasting cytotoxicity to embryonic zebrafish fibroblast cell lines ZF4. Using the fluorescent-labeled NPs, the differentially internalized patterns between the two-sized NPs in a time-resolved manner were observed. Confocal images showed that the two sizes of NPs were deposited in lysosomes but could escape through lysosomal rupture, as evidenced by the induction of lysosomal acidification (for 1000 nm) and alkalization (for 100 nm) as well as permeabilization. Subsequent deposition of 100-NPs in the cytosol induced loss of mitochondrial membrane potential and significant reactive oxygen species production, and finally stimulated the activation of caspases, disrupted the mitochondrial mitophagy, leading to irreversible cell death. In contrast, 1000-NPs toxicity in ZF4 cells did not involve lysosomal permeabilization and loss of mitochondrial membrane potential. Lysosomal deposition of such larger sized nanoplastics mainly induced lysosome acidification, activated the autophagy as well as disrupted the integrity of cell membrane, but at the same time provoked the activation of caspases and finally triggered the apoptosis. Our study demonstrated a complicated relationship among lysosome damage, autophagy activation, and apoptosis, leading to contrasting toxicity of NPs of different sizes.Improving agricultural green total factor productivity (AGTFP) is essential to China's agricultural sustainable development. Although several studies have focused on China's AGTFP, its measurement and drivers are not fully investigated yet. More specifically, the published research examining the drivers of China's AGTFP at both the production and factor levels is still scarce. To fill this gap, this study constructs two different data envelopment analysis models combined with green Luenberger productivity indicator (GLPI), the biennial weight modified Russell model and the biennial bounded adjusted model, to measure China's AGTFP as well as check the robustness. We further decompose the AGTFP growth at both production and factor levels to investigate its drivers. The main findings are as follows. First, during 1998-2019, the central region with its GLPI at 0.0377 had the largest AGTFP growth, followed by the western (0.0281) and eastern regions (0.0254). Second, in terms of production-decomposition, technical progress was crucial driver to AGTFP growth, energy conservation and emission reduction (ECER) and market performance. Third, in terms of factors-decomposition, the contributions of these factors to the AGTFP growth were positive and the contribution rates ranged from 1.01% (pesticide) to 38.51% (agricultural carbon emissions). Additionally, ECER performance was the primary driver of AGTFP, accounting for about 51.35% of the growth. Finally, according to the decompositions, Porter effect was discovered in China's agricultural sector. ECER drove China's agriculture to achieve win-win development between the environment and economic production.
Idiopathic intracranial hypertension (IIH) is defined as elevated intracranial pressure (ICP) with normal cerebrospinal fluid content in the absence of an identifiable cause. Patients often experience symptoms related to elevated ICP (e.g., headache); however, a subgroup of patients with elevated ICP may have optic disc edema without any associated symptoms. There are limited data about this subgroup in the literature. Our aim in this study was to characterize the initial clinical findings and visual outcomes over the follow-up period in this group of asymptomatic patients.
We performed a retrospective review of all patients who were referred to the neuro-ophthalmology service at Baylor College of Medicine for evaluation of papilledema between January 2012 and June 2020. Medical records of 139 consecutive patients with papilledema were reviewed. Patients were included in the analysis if they met the criteria for the diagnosis of IIH, had bilateral optic disc edema, and did not have any symptoms of elevateng or pallor even with the use of medication to lower ICP. To our knowledge, this is the first retrospective study characterizing the clinical course of papilledema from IIH in asymptomatic individuals.
People who inject drugs and have infective endocarditis have a high risk of recurrent infective endocarditis and death. We aimed to characterize clinical factors associated with mortality and assess the probability of infective endocarditis recurrence in the presence of death as a competing risk.
A retrospective cohort study was conducted of people who inject drugs, identified between April 5, 2007 and March 15, 2018 with the Modified Duke Criteria for definite infective endocarditis. Fine-Gray sub-distribution and Cox proportional hazards modeling were conducted to determine variables associated with the rate of infective endocarditis recurrence and mortality, respectively.
Of the 310 patients with infective endocarditis who inject drugs, 236 experienced a single episode and 74 experienced recurrent episodes. Peripherally inserted central catheter misuse was associated with an increased rate of infective endocarditis recurrence (sub-distribution hazard ratio 2.41; 95% confidence interval [CI], 1.17-4.9s peripheral therapy did not reduce mortality, but oral therapy was associated with reduced risk. Inpatient addiction services referral is important.Fluoxetine (FLX) exerts its therapeutic effect by inhibiting the presynaptic reuptake of the neurotransmitter serotonin. Nonetheless, at high concentrations of this drug, adverse effects occur in the brain of exposed organisms. Bearing this into account, the objective of this study was to evaluate the neurotoxic effects of the fluoxetine through the evaluation of behavior (Novel tank test), determination of oxidative stress, and determination of acetylcholinesterase (AChE) activity in adult zebrafish Danio rerio. For this purpose, Danio rerio adults were exposed to three environmentally relevant concentrations (5, 10, 16 ng L-1) of FLX for 96 h. Our results demonstrate fish presented a significant disruption in their behavior, as they remained long-lasting time frozen at the top of the tank. Since we observed a significant reduction of AChE activity in the brain of fish, we believe the above described anxiety-like state is the result of this enzyme impairment. Moreover, as FLX-exposed fish showed a significant increase in the levels of oxidative damage biomarkers, we suggest this AChE disruption is associated with the oxidative stress response fish exhibited. Based on our findings, we believe the environmentally relevant concentration of FLX alters the redox status of the brain, impairing this way the behavior of fish and making them more vulnerable to predation.Rutin is a natural flavonoid, with typical effects including interaction with enzymes and scavenging of free radicals. However, the role of rutin in the auditory system is still unclear. In the present study, we used neonatal organ of Corti explants in vitro to investigate the effects of rutin in cisplatin-induced ototoxicity. The TUNEL assay and the cleaved caspase-3 immunohistochemistry were used to detect the apoptosis of hair cell (HCs) in cochlear explants, and the MitoSox-Red staining was used to detect the difference in mitochondrial superoxide among different groups. Western blot was used to investigate the expression of genes. Confocal microscopy showed that after pretreatment with rutin, the accumulation of reactive oxygen species in HCs caused by cisplatin exposure was significantly reduced. Furthermore, the expression levels of p-P38 and p-JNK were significantly decreased, while ratio of p-AKT/AKT was significantly upregulated. Our study showed that rutin reduced cisplatin-induced HCs death in neonatal cochlear explants in vitro. The potential mechanism involved the alleviation of mitochondrial damage, the scavenging of reactive oxygen species (ROS), the suppression of MAPK signaling pathway, and the activation of PI3K/AKT signaling pathway.Senecavirus A (SVA) is a new virus inducing porcine idiopathic vesicular disease that causes significant economic losses. Although some progress has been made in etiological research, the role of host factors in SVA infection remains unclear. This study investigated the role of the host factor, suppressor of cytokine signaling 1 (SOCS1), in SVA infection. The expression of SOCS1 was significantly upregulated with infection of SVA in a dose-dependent manner, and SOCS1 inhibited the expression of type I interferons (IFN-α, IFN-β) and the production of interferon stimulating genes (ISGs) (ISG56, ISG54, PKR), thereby facilitating viral replication. Further results showed that inhibition of antiviral responses of SOCS1 was achieved by regulating the NF-κB signaling pathway, which attenuates the production of IFNs and pro-inflammatory cytokines. These findings provide a new perspective of SVA pathogenesis and may partially explain the persistence of this infection. Moreover, the data indicate that targeting SOCS1 can help in developing new agents against SVA infection.Cuticular hydrocarbons (CHCs) are important components in the integument of insects and are required for development and survival. Insect-specific CYP4G subfamily, of the P450 enzymes, catalyze the oxidative decarbonylation step in the biosynthesis of CHCs. Here, we characterized CYP380C10 gene function in a Hemiptera rice pest, Nilaparvata lugens. We used RNA interference-mediated expression silencing to reveal that NlCYP380C10 played a key role in waterproofing and water-retention in the integument of N. lugens. Knockdown of NlCYP380C10 significantly reduced body weight and caused mortality. Scanning electron microscopy showed the loss of the lipid layer on the surface of the abdominal cuticle of the dsNlCYP380C10-injected adults. Furthermore, CHC profile analysis revealed that NlCYP380C10 knockdown significantly decreased the amounts of CHCs in adult females. This suggested that NlCYP380C10 was involved in CHC biosynthesis. Reduction of CHC content caused the loss of the intact lipid layer of the cuticle, which resulted in loss of the waterproofing and water-retention functions. This led to failure of molting and eclosion. Our findings expanded the knowledge of CHC biosynthesis in the insect integument and led to a better understanding of the functional roles of CYP450 genes involved in waterproofing and water-retention in insects.
The aim was to investigate the association of cognitive trajectories and overnight surgical hospitalization in older adults, while controlling for and comparing to the association with acute medical hospitalizations.
This is a secondary analysis of data from a population-based, longitudinal cohort study of older Australians.
Cognition was assessed with 4 biennial waves of prospective neuropsychological data from 1026 Sydney Memory and Aging Study participants age 70 to 90years at baseline. Hospitalization exposure was obtained from 10years of electronically linked data from the New South Wales Admitted Patient Data Collection.
Latent growth curve modeling estimated global cognition z-score baseline and slope over 6years, and the effects of contemporaneous surgical and medical hospitalization predictors while controlling for potential demographic and comorbidity confounders.
After controlling for confounding variables, this analysis showed that overnight surgical hospitalizations were not associated s and dementia, and importantly, how these cognitive outcomes correlate with clinically significant functional changes.
This analysis finds that surgery and anesthesia are unlikely to be risk factors for medium to long-term global cognitive decline in healthy older adults, while controlling for contemporaneous medical hospitalizations. These findings are contrary to prior conclusions from several surgical studies that may have been impeded by insufficient comparison groups. They are, however, consistent with recent population-based studies suggesting surgery has minimal association with cognitive decline in the medium to long-term. Future research needs to clarify the association of surgical hospitalization with the full spectrum of cognitive outcomes including subjective cognitive complaints and dementia, and importantly, how these cognitive outcomes correlate with clinically significant functional changes.Although outcomes for older adults undergoing elective surgery are generally comparable to younger patients, outcomes associated with emergency surgery are poor. These adverse outcomes are in part because of the physiologic changes associated with aging, increased odds of comorbidities in older adults, and a lower probability of presenting with classic "red flag" physical examination findings. Existing evidence-based perioperative best practice guidelines perform better for elective compared with emergency surgery; so, decision making for older adults undergoing emergency surgery can be challenging for surgeons and other clinicians and may rely on subjective experience. To aid surgical decision making, clinicians should assess premorbid functional status, evaluate for the presence of geriatric syndromes, and consider social determinants of health. Documentation of care preferences and a surrogate decision maker are critical. In discussing the risks and benefits of surgery, patient-centered narrative formats with inclusion of geriatric-specific outcomes are important. Use of risk calculators can be meaningful, although limitations exist. After surgery, daily evaluation for common postoperative complications should be considered, as well as early discharge planning and palliative care consultation, if appropriate. The role of the geriatrician in emergency surgery for older adults may vary based on the acuity of patient presentation, but perioperative consultation and comanagement are strongly recommended to optimize care delivery and patient outcomes.
Risk of mortality and major comorbidity remains high following hepatic resection. Given recent advancements in nonsurgical techniques to control hepatic malignancy, accurate assessment of surgical candidates, especially those considered frail, has become imperative. The present study aimed to characterize the impact of frailty on clinical and financial outcomes following hepatic resection in older individuals.
Retrospective cohort study.
All older adults (≥65years) undergoing elective hepatic resection were identified from the 2012 to 2019 National Inpatient Sample.
Frailty was defined by using the Johns Hopkins Adjusted Clinical Groups frailty-defining diagnosis indicator. Multivariable regression models were developed to assess the independent association of frailty with mortality, perioperative complications, and resource utilization. Marginal effects were tabulated to assess the impact of hospital volume on frailty-associated mortality.
Of an estimated 40,735 patients undergoing major hepatic res the Johns Hopkins Adjusted Clinical Groups, may identify patients from electronic medical records who may benefit from further geriatric assessment and targeted treatments.
As the population of the United States continues to age, surgeons are increasingly likely to encounter candidates for major hepatic resection who are frail. The present study associated frailty with inferior clinical and financial outcomes; however, frailty-associated mortality became less pronounced at centers with high hepatic resection operative volume. Coding-based instruments, such as the Johns Hopkins Adjusted Clinical Groups, may identify patients from electronic medical records who may benefit from further geriatric assessment and targeted treatments.We investigated the mechanisms and the role of autophagy in the differentiation of HL-60 human acute myeloid leukemia cells induced by protein kinase C (PKC) activator phorbol myristate acetate (PMA). PMA-triggered differentiation of HL-60 cells into macrophage-like cells was confirmed by cell-cycle arrest accompanied by elevated expression of macrophage markers CD11b, CD13, CD14, CD45, EGR1, CSF1R, and IL-8. The induction of autophagy was demonstrated by the increase in intracellular acidification, accumulation/punctuation of autophagosome marker LC3-II, and the increase in autophagic flux. PMA also increased nuclear translocation of autophagy transcription factors TFEB, FOXO1, and FOXO3, as well as the expression of several autophagy-related (ATG) genes in HL-60 cells. PMA failed to activate autophagy inducer AMP-activated protein kinase (AMPK) and inhibit autophagy suppressor mechanistic target of rapamycin complex 1 (mTORC1). On the other hand, it readily stimulated the phosphorylation of mitogen-activated protein (MAP) kinases extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) via a protein kinase C-dependent mechanism. Pharmacological or genetic inhibition of ERK or JNK suppressed PMA-triggered nuclear translocation of TFEB and FOXO1/3, ATG expression, dissociation of pro-autophagic beclin-1 from its inhibitor BCL2, autophagy induction, and differentiation of HL-60 cells into macrophage-like cells. Pharmacological or genetic inhibition of autophagy also blocked PMA-induced macrophage differentiation of HL-60 cells. Therefore, MAP kinases ERK and JNK control PMA-induced macrophage differentiation of HL-60 leukemia cells through AMPK/mTORC1-independent, TFEB/FOXO-mediated transcriptional and beclin-1-dependent post-translational activation of autophagy.
Paclitaxel-induced downregulation of two-pore domain K+ channel 1.1 (K
1.1) caused by increasing DNA methylation within its gene promoter in the dorsal root ganglion (DRG) contributes to neuropathic pain. Given that ten-eleven translocation methylcytosine dioxygenase 1 (TET1) promotes DNA demethylation and gene transcription, the present study investigated whether DRG overexpression of TET1 produces an antinociceptive effect on the paclitaxel-induced nociceptive hypersensitivity.
TET1 was overexpressed in the DRG through unilateral microinjection of the herpes simplex virus expressing full-length Tet1 mRNA into the fourth and fifth lumbar DRGs of male rats. Behavioral tests were carried out to examine the effect of this overexpression on the paclitaxel-induced nociceptive hypersensitivity. Western blot analysis, chromatin immunoprecipitation assay and 5-hydroxymethylcytosine detection assay were performed to assess the levels of TET1/K
1.1, 5-methylcytosine and 5-hydroxymethylcytosine, respectively.
Dprovide a potential avenue for the management of this disorder.
Multiple mitochondrial dysfunction (MMD) can lead to complex damage of mitochondrial structure and function, which then lead to the serious damage of various metabolic pathways including cerebral abnormalities. However, the effects of MMD on heart, a highly mitochondria-dependent tissue, are still unclear. In this study, we use iron-sulfur cluster assembly 1 (Isca1), which has been shown to cause MMD syndromes type 5 (MMDS5), to verify the above scientific question.
We generated myocardium-specific Isca1 knockout rat (Isca1
/α-MHC-Cre) using CRISPR-Cas9 technology. Echocardiography, magnetic resonance imaging (MRI), histopathological examinations and molecular markers detection demonstrated phenotypic characteristics of our model. Immunoprecipitation, immunofluorescence co-location, mitochondrial activity, ATP generation and iron ions detection were used to verify the molecular mechanism.
This study was the first to verify the effects of Isca1 deficiency on cardiac development in vivo, that is cardiomyocytes suffer from mitochondria damage and iron metabolism disorder, which leads to myocardial oncosis and eventually heart failure and body death in rat. Furthermore, forward and reverse validation experiments demonstrated that six-transmembrane epithelial antigen of prostate 3 (STEAP3), a new interacting molecule for ISCA1, plays an important role in iron metabolism and energy generation impairment induced by ISCA1 deficiency.
This result provides theoretical basis for understanding of MMDS pathogenesis, especially on heart development and the pathological process of heart diseases, and finally provides new clues for searching clinical therapeutic targets of MMDS.
This result provides theoretical basis for understanding of MMDS pathogenesis, especially on heart development and the pathological process of heart diseases, and finally provides new clues for searching clinical therapeutic targets of MMDS.The tripartite protein complex produced by anthrax bacteria (Bacillus anthracis) is a member of the AB family of β-barrel pore-forming toxins. The protective antigen (PA) component forms an oligomeric prepore that assembles on the host cell surface and serves as a scaffold for binding of lethal and edema factors. Following endocytosis, the acidic environment of the late endosome triggers a pH-induced conformational rearrangement to promote maturation of the PA prepore to a functional, membrane spanning pore that facilitates delivery of lethal and edema factors to the cytosol of the infected host. Here, we show that the dominant-negative D425A mutant of PA stalls anthrax pore maturation in an intermediate state at acidic pH. Our 2.7 Å cryo-EM structure of the intermediate state reveals structural rearrangements that involve constriction of the oligomeric pore combined with an intramolecular dissociation of the pore-forming module. In addition to defining the early stages of anthrax pore maturation, the structure identifies asymmetric conformational changes in the oligomeric pore that are influenced by the precise configuration of adjacent protomers.Leishmaniasis is a neglected disease caused by species of the protozoan Leishmania. Leishmania (Viannia) braziliensis causes the cutaneous and mucocutaneous forms of the disease. Experimental cutaneous infection of mice is one of the most important preclinical research models of leishmaniasis. Here, we investigated the course of infection in mice inoculated with two reference strains of L. (V.) braziliensis (MHOM/BR/00/BA788 strain [BA] and MHOM/BR/94/H-3227 strain [CE]). Although both parasite strains induced detectable footpad lesions, BA-infected mice developed small non-ulcerated lesions that self-healed, whereas CE-infected mice developed small non-ulcerated lesions that did not regress. The parasites were detected in the footpad lesions, lymph nodes draining the site of inoculation, spleen, and bone marrow of mice infected with BA or CE parasites at 6 and 25 weeks post-inoculation. These data indicate that L (V.) braziliensis-infected mice harbor parasites that spread, even when these animals do not display overt lesions. In addition, this is the first report of the presence of the parasite in the bone marrow of mice inoculated with L. (V.) braziliensis.The aim of this study was evaluate to seroprevalence of Toxoplasma gondii in goats worldwide and the main risk factors associated from 2000 to 2020, through meta-analysis with 55,317 goats from 75 reports published in seven electronic databases of major global importance. A global seroprevalence detected was 27.49% (95% CI 24.15-30.95; I2 = 99%), with the lowest percentage in Asia (20.74%; 95% CI 16.45-25.39) and highest in Central America (62.15%; 95% CI 57.28-66.90) and Europe (31.53%; 95% CI 21.71-42.26). The seropositivity in Africa and South America were (29.41%; 95% CI 19.11-40.89) and (29.76%; 95% CI 25.84-33.83), respectively. The seroprevalence was associated with presence of cats (OR 2.22; 95% CI 1.30-3.82), goats older than one year (OR 1.77; 95% CI 1, 37-2.29), females (OR 1.43; 95% CI 1.23-1.65), rearing system (extensive vs. intensive) (OR 4.82; 95% CI 1.96-11, 84) and rearing system (semi-intensive vs. intensive) (OR 1.48; 95% CI 1.48-6.13). The heterogeneity was evidenced in most world regions and the risk factors may play roles in varying the seroprevalence.This commentary describes a highly cited paper by Dahle, Hill, and Holman, Arch Biochem Biophys. 1962; 98 253-261. They showed that the oxidation products of polyunsaturated fatty acids reacted with thiobarbituric acid to give a colored product, which might be used to assess lipid oxidation.
To determine the maximum permissible number of missed items on the 10-item Catherine Bergego Scale administered after the Kessler Foundation Neglect Assessment Process (KF-NAP). Secondary objectives were to determine the frequency, characteristics, and most commonly cited reasons reported for missed items.
Retrospective diagnostic accuracy study.
Sixteen inpatient rehabilitation facilities in the United States.
A consecutive clinical sample of 4256 patients (N=4256) with stroke or other neurologic deficits who were assessed for spatial neglect with the KF-NAP.
Not applicable.
Catherine Bergego Scale via KF-NAP.
The majority (69.7%) of patients had at least 1 missed item on their KF-NAP. Among those with missed items, it was most common to have 2 missed items (51.4%), and few had more than 3 missed items (11.3%). The most commonly missed items were Collisions (37.2%), Cleaning After Meals (36.1%), Meals (34.0%), and Navigation (19.7%). The most commonly reported reasons for missed items included ause of patient factors and barriers inherent to the inpatient hospital setting. When missed items are necessary, clinicians can confidently interpret a prorated score when 7 or more items are scored.
To explore the effect of complexity and feedback on script training outcomes in aphasia DESIGN Randomized balanced single-blind 2×2 factorial design.
Freestanding urban rehabilitation hospital.
Adults with fluent and nonfluent aphasia (at least 6 months post onset).
Experimental treatment was AphasiaScripts, a computer-based script training program. Scripts were 10-turns long and developed at different complexity levels to allow for comparison of high vs low complexity. The program was modified to contrast high vs low feedback conditions during sentence practice. Participants were instructed to practice three 30-minute sessions per day, 6 days per week for 3 weeks.
Gains achieved from baseline in accuracy and rate of production of trained and untrained script sentences at post treatment and at 3-, 6-, and 12-weeks after the end of treatment.
Sixteen participants completed the intervention. On the trained script, gains were statistically significant for both accuracy and words per minute at post treatment and 3-, 6-, and 12-week maintenance.
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