To reduce widespread shortages, attempts are made to use more marginal livers for transplantation. Many of these grafts are discarded for fear of inferior survival rates or biliary complications. ...Recent advances in organ preservation have shown that ex vivo subnormothermic machine perfusion has the potential to improve preservation and recover marginal livers pretransplantation. To determine the feasibility in human livers, we assessed the effect of 3 h of oxygenated subnormothermic machine perfusion (21°C) on seven livers discarded for transplantation. Biochemical and microscopic assessment revealed minimal injury sustained during perfusion. Improved oxygen uptake (1.30 1.11–1.94 to 6.74 4.15–8.16 mL O2/min kg liver), lactate levels (4.04 3.70–5.99 to 2.29 1.20–3.43 mmol/L) and adenosine triphosphate content (45.0 70.6–87.5 pmol/mg preperfusion to 167.5 151.5–237.2 pmol/mg after perfusion) were observed. Liver function, reflected by urea, albumin and bile production, was seen during perfusion. Bile production increased and the composition of bile (bile salts/phospholipid ratio, pH and bicarbonate concentration) became more favorable. In conclusion, ex vivo subnormothermic machine perfusion effectively maintains liver function with minimal injury and sustains or improves various hepatobiliary parameters postischemia.
This study of human livers shows that subnormothermic machine perfusion can preserve hepatobiliary function and may be feasible for liver graft recovery pretransplantation.
Radioactive ^{27}Mg (t_{1/2}=9.5 min) was implanted into GaN of different doping types at CERN's ISOLDE facility and its lattice site determined via β^{-} emission channeling. Following ...implantations between room temperature and 800 °C, the majority of ^{27}Mg occupies the substitutional Ga sites; however, below 350 °C significant fractions were also found on interstitial positions ∼0.6 Å from ideal octahedral sites. The interstitial fraction of Mg was correlated with the GaN doping character, being highest (up to 31%) in samples doped p type with 2×10^{19} cm^{-3} stable Mg during epilayer growth, and lowest in Si-doped n-GaN, thus giving direct evidence for the amphoteric character of Mg. Implanting above 350 °C converts interstitial ^{27}Mg to substitutional Ga sites, which allows estimating the activation energy for migration of interstitial Mg as between 1.3 and 2.0 eV.
Abstract
Objectives
Gonorrhoea and antimicrobial resistance (AMR) in Neisseria gonorrhoeae are major public health concerns globally. Enhanced AMR surveillance for gonococci is essential worldwide; ...however, recent quality-assured gonococcal AMR surveillance in Latin America, including Brazil, has been limited. Our aims were to (i) establish the first nationwide gonococcal AMR surveillance, quality assured according to WHO standards, in Brazil, and (ii) describe the antimicrobial susceptibility of clinical gonococcal isolates collected from 2015 to 2016 in all five main regions (seven sentinel sites) of Brazil.
Methods
Gonococcal isolates from 550 men with urethral discharge were examined for susceptibility to ceftriaxone, cefixime, azithromycin, ciprofloxacin, benzylpenicillin and tetracycline using the agar dilution method, according to CLSI recommendations and quality assured according to WHO standards.
Results
The levels of resistance (intermediate susceptibility) to tetracycline, ciprofloxacin, benzylpenicillin and azithromycin were 61.6% (34.2%), 55.6% (0.5%), 37.1% (60.4%) and 6.9% (8.9%), respectively. All isolates were susceptible to ceftriaxone and cefixime using the US CLSI breakpoints. However, according to the European EUCAST cefixime breakpoints, 0.2% (n = 1) of isolates were cefixime resistant and 6.9% (n = 38) of isolates had a cefixime MIC bordering on resistance.
Conclusions
This study describes the first national surveillance of gonococcal AMR in Brazil, which was quality assured according to WHO standards. The high resistance to ciprofloxacin (which promptly informed a revision of the Brazilian sexually transmitted infection treatment guideline), emerging resistance to azithromycin and decreasing susceptibility to extended-spectrum cephalosporins necessitate continuous surveillance of gonococcal AMR and ideally treatment failures, and increased awareness when prescribing treatment in Brazil.
The present study aimed to evaluate the effects of ~45 nm nanoplastics (NPs) on the marine fish Dicentrarchus labrax after a short-term exposure. Animals were exposed to a concentration range of NPs ...for 96 h and liver, plasma and skin mucus were sampled. Assessed endpoints included biochemical biomarkers and expression of genes related to lipid metabolism, immune system and general cell stress. Abundance of mRNA transcripts related to lipid metabolism, pparα and pparγ, were significantly increased after exposure to NPs. Biochemical endpoints revealed decreased esterase activity levels in plasma, suggesting that the immune system of fish might be compromised by exposure to NPs. Moreover, significantly lower levels of alkaline phosphatase were found in the skin mucus of animals exposed to NPs. The present results suggest that NPs may represent a hazard to this marine fish, potentially interfering with the metabolism of lipids and the correct function of the immune response.
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•Plastic materials in the environment degrade into nano-size particles•Effects of nanoplastics (NPs) on D. labrax after short-term exposure were assessed•Molecular signaling pathways related to lipid metabolism were altered in liver•NPs might interfere with the D.labrax's immune response
This work analyses the distribution of living benthic foraminiferal assemblages of surface sediments in different intertidal areas of Ria de Aveiro (Portugal), a polihaline and anthropized coastal ...lagoon. The relationships among foraminiferal assemblages in association with environmental parameters (temperature, salinity, Eh and pH), grain size, the quantity and quality of organic matter (enrichment in carbohydrates, proteins and lipids), pollution caused by metals, and mineralogical data are studied in an attempt to identify indicators of adaptability to environmental stress. In particular, concentrations of selected metals in the surficial sediment are investigated to assess environmental pollution levels that are further synthetically parameterised by the Pollution Load Index (PLI). The PLI variations allowed the identification of five main polluted areas. Concentrations of metals were also analysed in three extracted phases to evaluate their possible mobility, bioavailability and toxicity in the surficial sediment. Polluted sediment in the form of both organic matter and metals can be found in the most confined zones. Whereas enrichment in organic matter and related biopolymers causes an increase in foraminifera density, pollution by metals leads to a decline in foraminiferal abundance and diversity in those zones. The first situation may be justified by the existence of opportunistic species (with high reproduction rate) that can live in low oxic conditions. The second is explained by the sensitivity of some species to pressure caused by metals. The quality of the organic matter found in these places and the option of a different food source should also explain the tolerance of several species to pollution caused by metals, despite their low reproductive rate in the most polluted areas. In this study, species that are sensitive and tolerant to organic matter and metal enrichment are identified, as is the differential sensitivity/tolerance of some species to metals enrichment.
Objectives
There is a growing incidence of cognitive decline and dementia associated with the ageing population. Lifestyle factors such as diet, physical activity, and cognitive activities may ...individually or collectively be undertaken to increase one’s odds of preventing cognitive decline and future dementia. This study will examine whether clinical trials using multidomain lifestyle intervention can significantly decrease the risk of cognitive decline and therefore dementia.
Design, Setting and Participants
This systematic literature review of multidomain lifestyle interventions for the prevention of cognitive decline and dementia followed the PRISMA guidelines. Clinical trials involving multidomain intervention (i.e., diet and physical activity, or without cognitive training) in older adults (≥ 49 years old) at higher risk of dementia were identified through 5 electronic databases (EMBASE, MEDLINE, CINAHL, Cochrane, and Scopus). A comprehensive search was performed to identify and retrieve publications until 15 November 2022. Trials were published in English.
Results
The included studies (n=15) assessed change in cognition in response to a multidomain lifestyle intervention. However, the cognitive outcome measures used in these studies were heterogeneous. Despite this heterogeneity, two thirds of the studies showed improvement in cognition following a multidomain intervention (n=10 with a total of 9,439 participants). However, five studies reported no improvement in cognition following the multidomain intervention. The most common form of dietary intervention included higher amount of fruit and vegetable intake; whole-grain cereal products instead of refined; low fat options in milk and meat products; and limiting sucrose intake to less than 50 g/day. Most clinical trial studies were powered to examining the effects of multidomain interventions in cognition but were not designed to test the contribution of individual domains (i.e., dietary changes, increased physical activity, or increased cognitive stimulation alone).
Conclusion
This systematic review aimed to determine the effect of multimodal lifestyle interventions on cognitive outcomes in older adults at risk of dementia. We found that participants with conditions that may increase the risk of dementia, (e.g., hypertension, cardiovascular fragility) do benefit from multi-modal lifestyle changes including diet, physical activity, and cognitive training. Two thirds of studies using multidomain lifestyle interventions showed improvements in cognitive function. Trials with a focus on cognitive training, dietary improvement, and physical activity may prevent or delay cognitive decline in older adults including those at risk of developing dementia. Future studies should consider longer follow-up periods and adequate power to be able to examine the effects of each lifestyle component in the context of multimodal interventions.
This study aimed to evaluate the desensitizing effect of a prefilled disposable tray containing potassium nitrate and fluoride on the self-reported tooth sensitivity (TS) and the bleaching efficacy ...of 40% hydrogen peroxide bleaching agent used for in-office bleaching in comparison with potassium nitrate and fluoride gel applied in a conventional-delivered tray system in an equivalence clinical trial.
Seventy-eight patients, with a right maxillary canine darker than A3, were selected for this single-blind (evaluators), randomized clinical trial. Teeth were bleached in two sessions with a one-week interval in between. Before in-office bleaching, the prefilled disposable tray or conventional tray containing potassium nitrate and fluoride was used for 15 minutes. Subsequently, the bleaching agent was applied in two 20-minute applications (per the manufacturer's directions) in each session. The color change was evaluated by subjective (Vita Classical and Vita Bleachedguide) and objective (Easyshade Advance Spectrophotometer) methods at baseline and 30 days after the first bleaching session. TS was recorded for up to 48 hours using a 0-10 visual analog scale. The absolute risk was evaluated by chi-square test, while the intensity of TS was evaluated by McNemar test (α=0.05). Color change in shade guide units and ΔE was analyzed by Student
-test for independent samples (α=0.05).
Significant whitening was observed in both groups after 30 days of clinical evaluation. The use of different methods of desensitizer in a tray did not influence the absolute risk and intensity of TS (
>0.05), although a tendency of lower risk of TS with the prefilled disposable tray containing potassium nitrate and fluoride was observed.
The use of a prefilled disposable tray containing potassium nitrate and fluoride before the application of the in-office bleaching product did not affect the whitening degree and decreased self-reported TS when compared with a conventional-delivered tray system.
Resistance to chemotherapy is a major problem facing current cancer therapy, which is continuously aiming at the development of new compounds that are capable of tackling tumors that developed ...resistance toward common chemotherapeutic agents, such as doxorubicin (DOX). Alongside the development of new generations of compounds, nanotechnology-based delivery strategies can significantly improve the in vivo drug stability and target specificity for overcoming drug resistance. In this study, multifunctional gold nanoparticles (AuNP) have been used as a nanoplatform for the targeted delivery of an original anticancer agent, a Zn(II) coordination compound Zn(DION)2Cl2 (ZnD), toward better efficacy against DOX-resistant colorectal carcinoma cells (HCT116 DR). Selective delivery of the ZnD nanosystem to cancer cells was achieved by active targeting via cetuximab, NanoZnD, which significantly inhibited cell proliferation and triggered the death of resistant tumor cells, thus improving efficacy. In vivo studies in a colorectal DOX-resistant model corroborated the capability of NanoZnD for the selective targeting of cancer cells, leading to a reduction of tumor growth without systemic toxicity. This approach highlights the potential of gold nanoformulations for the targeting of drug-resistant cancer cells.
Persistent Helicobacter pylori (H. pylori) infection is related to 90% of gastric cancers. With bacterial resistance rising and treatment inefficiency affecting 15% of the patients, alternative ...treatments urge. Chitosan microspheres (ChMics) have been proposed as an H. pylori-binding system. This work evaluates ChMics biocompatibility, mucopenetration and capacity to treat H. pylori infection in mice after oral administration. ChMics of different size (XL, ∼120 µm and XS, ∼40 µm) and degree of acetylation (6% and 16%) were developed and revealed to be able to adhere both human and mouse-adapted H. pylori strains without cytotoxicity towards human gastric cells. Ex vivo studies showed that smaller (XS) microspheres penetrate further within the gastric foveolae, suggesting their ability to reach deeply adherent bacteria. In vivo assays showed 88% reduction of infection when H. pylori-infected mice (C57BL/6) were treated with more mucoadhesive XL6 and XS6 ChMics. Overall, ChMics clearly demonstrate ability to reduce H. pylori gastric infection in mice, with chitosan degree of acetylation being a dominant factor over microspheres’ size on H. pylori removal efficiency. These results evidence the strong potential of this strategy as an antibiotic-free approach to fight H. pylori infection, where microspheres are orally administered, bind H. pylori in the stomach, and remove them through the gastrointestinal tract.
Approximately 90% of gastric cancers are caused by the carcinogenic agent Helicobacter pylori, which infects >50% of the world population. Bacterial resistance, reduced antibiotic bioavailability, and the intricate distribution of bacteria in mucus and within gastric foveolae hamper the success of most strategies to fight H. pylori. We demonstrate that an antibiotic-free therapy based on bare chitosan microspheres that bind and remove H. pylori from stomach can achieve 88% reduction of infection from H. pylori-infected mice. Changing size and mucoadhesive properties, microspheres can reach different areas of gastric mucosa: smaller and less mucoadhesive can penetrate deeper into the foveolae. This promising, simple and inexpensive strategy paves the way for a faster bench-to-bedside transition, therefore holding great potential for clinical application.
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The search for antiprion compounds has been encouraged by the fact that transmissible spongiform encephalopathies (TSEs) share molecular mechanisms with more prevalent neurodegenerative pathologies, ...such as Parkinson's and Alzheimer's diseases. Cellular prion protein (PrP
) conversion into protease-resistant forms (protease-resistant PrP PrP
or the scrapie form of PrP PrP
) is a critical step in the development of TSEs and is thus one of the main targets in the screening for antiprion compounds. In this work, three trimethoxychalcones (compounds J1, J8, and J20) and one oxadiazole (compound Y17), previously identified
to be potential antiprion compounds, were evaluated through different approaches in order to gain inferences about their mechanisms of action. None of them changed PrP
mRNA levels in N2a cells, as shown by reverse transcription-quantitative real-time PCR. Among them, J8 and Y17 were effective in real-time quaking-induced conversion reactions using rodent recombinant PrP (rPrP) from residues 23 to 231 (rPrP
) as the substrate and PrP
seeds from hamster and human brain. However, when rPrP from residues 90 to 231 (rPrP
), which lacks the N-terminal domain, was used as the substrate, only J8 remained effective, indicating that this region is important for Y17 activity, while J8 seems to interact with the PrP
globular domain. J8 also reduced the fibrillation of mouse rPrP
seeded with
-produced fibrils. Furthermore, most of the compounds decreased the amount of PrP
on the N2a cell surface by trapping this protein in the endoplasmic reticulum. On the basis of these results, we hypothesize that J8, a nontoxic compound previously shown to be a promising antiprion agent, may act by different mechanisms, since its efficacy is attributable not only to PrP conversion inhibition but also to a reduction of the PrP
content on the cell surface.
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