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The term ‘service user’ is an amorphous concept that can refer to a variety of groups. It refers to people who use or have used a service, or to the carers or parents of service users, or it can be used to refer to lay people, the public or non-professionals. It can also be used to refer to all or any combination of these. To maximise the potential of simulation, it is crucial to involve service users: their inclusion in the co-design of simulations, alongside patient educators and participatory decision-makers, provides invaluable input from a patient perspective. They also make an important contribution by portraying patients in the scenarios within which students interact, providing perspectives based on real-life experiences, offering students an insight into how patients could respond. Such an approach to designing simulations as part of nursing education will help develop professionals who are more patient-centred, culturally competent and more responsive to patient needs.

Low vitamin B12 has been associated with raised plasma homocysteines and the consumption of B vitamins has been shown to reduce homocysteines. Raised levels of homocysteines have been linked to causing symptoms of mental illness. B12 is also required in the synthesis of monoamines and is required to maintain neurological health.Aim:This study reviews research into the effects of the supplementation of B12 in the prevention and recovery of mental illness, and the potentiation of psychotropic medication.Methodology:This literature review follows a systematic approach to searching databases CINAHL, EMBASE, Medline, and PsycINFO where 287 non-duplicated articles results were received. Appropriate articles were identified through title and abstract screening and inclusion and exclusion criteria were applied. Five articles were chosen to address the research question following critical appraisal. Thematic analysis was then conducted.Findings:This review identified five randomised controlled trials into the supplementation of various doses of B12 in conjunction with folic acid and B6. The supplement was measured against post-stroke depression prevention, the reduction of symptoms of depression in woman with cardiovascular disease, the effect on negative symptoms in schizophrenia, the reduction and prevention of depression in older adults, and the potentiation of psychotropic interventions. The papers reviewed showed inconclusive results, but evidence to support sub-groups and specific high-risk groups. Strong evidence showed supplementation of B12, folic acid and B6 has high rates of preventing post-stroke depression.Conclusion:The findings show that this area of research is still to be developed. The effects of B12 supplementation with other B vitamins on mental health have shown to be inconclusive. There is a case for its use to be considered within certain patient groups to aid recovery of mental health or in some high-risk patient groups. Recommendations are made for further research into high-risk groups of people that may have symptoms or symptoms that could be improved through the supplementation of B12.

This article aims to provide an overview on loneliness in older people, with an emphasis on how insights from this body of literature can significantly contribute to the enhancement of care provided by community nurses. This review aims to provide a nuanced understanding of the factors contributing to loneliness, its impact on the physical and mental health of older individuals, and the role community nurses can play in mitigating and addressing loneliness.

Ammonia synthesis viathe catalytic Haber–Bosch process is characterized by its high pressures and low single-pass conversions, as well as by the energy-intensive production of the precursors H2and N2and their concomitant greenhouse gas emissions. Alternatively, thermochemical cycles based on metal nitrides stand as a promising pathway to green ammonia production because they can be conducted at moderate pressures without added catalysts and be further driven by concentrated solar energy as the source of high-temperature process heat. The ideal two-step cycle consists of the nitridation of a metal to form a metal nitride, followed by the hydrogenation of the metal nitride to synthetize NH3and reform the metal. Here, we perform a combined theoretical and experimental screening of mono-metallic nitrides for several candidates, namely for Sr, Ca, Cr, Mn, Fe, Co, Ni, Cu, Zn, Mo, W, Li, and Al. For the theoretical screening, Ellingham diagrams and chemical equilibrium compositions are examined with thermodynamic data derived from density function theory computations. For the experimental screening, thermogravimetric runs and mass balances supported by on-line gas analyses are performed for both steps of the cycle at ambient pressure and over the temperature ranges 100–1000 °C for nitridation and 100–500 °C for hydrogenation. The strontium-based cycle is selected as a reference for detailed examination and shown to synthetize NH3at 1 bar by effecting the nitridation at 407 °C (at peak rate) and the hydrogenation at 339 °C (at peak rate). The co-formation of metal hydrides (SrH2) and metal imides (Sr2HN) are shown to help close the material cycle.

Non-fungible tokens (NFTs) could potentially have a broader transformational effect than mere blockchain because they challenge the traditional notions of ownership and is, therefore, a more fundamental challenge to our established economic and social structures. This paper provides a systematic review of the NFT literature outlining the research opportunities for NFTs.

Peripheral nerve injuries represent a major clinical challenge, if nerve ends retract, there is no spontaneous regeneration, and grafts are required to proximate the nerve ends and give continuity to the nerve. The nerve guidance conduits (NGCs) presented in this work are silk fibroin (SF)-based, which is biocompatible and very versatile. The formation of conduits is obtained by forming a covalently cross-linked hydrogel in two concentric moulds, and the inner longitudinally aligned pattern of the SF NGCs is obtained through the use of a patterned inner mould. SF NGCs with two wall thicknesses of ~ 200 to ~ 400 μm are synthesized. Their physicochemical and mechanical characteristics have shown improved properties when the wall thickness is thicker such as resistance to kinking, which is of special importance as conduits might also be used to substitute nerves in flexible body parts. The Young modulus is higher for conduits with inner pattern, and none of the conduits has shown any salt deposition in presence of simulated body fluid, meaning they do not calcify; thus, the regeneration does not get impaired when conduits have contact with body fluids. In vitro studies demonstrated the biocompatibility of the SF NGCs; proliferation is enhanced when iSCs are cultured on top of conduits with longitudinally aligned pattern. BJ fibroblasts cannot infiltrate through the SF wall, avoiding scar tissue formation on the lumen of the graft when used in vivo. These conduits have been demonstrated to be very versatile and fulfil with the requirements for their use in PNR.

Silica nanoparticles (SiNPs) are widely used in biomedical applications, such as cancer therapy/diagnosis or tissue engineering and regenerative medicine. Herein, we synthesized SiNPs and modified them with sulfonic acid groups (by organosilylation followed by oxidation) or a sulfated polysaccharide (i.e., fucoidan, a seaweed biopolymer, by using electrostatic surface immobilization) due to the known capacity of the sulfonic/sulfate moieties to stabilize proteins and promote stem cell differentiation toward the osteogenic lineage. The developed pristine and functionalized nanoparticles were characterized by dynamic light scattering (DLS), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and X-ray photoelectron spectroscopy (XPS), showing the monodisperse size distribution (between 360 and 450 nm) and the success of the coating/functionalization with fucoidan or sulfonic groups. The developed SiNPs (at a concentration of 50 μg/mL) were assessed through their contact with SaOs2 cells evidencing their cytocompatibility. Furthermore, the osteogenic differentiation of bmMSCs was evaluated by the quantification of ALP activity, as well as the expression profile of osteogenic-related genes, such as Runx2, ALP, and OP. We found that the coating of the SiNPs with fucoidan induced the osteogenic differentiation of bmMSCs, being an effective mediator of bone regeneration.

Here, we investigate the effects of obesity induced by monosodium glutamate (MSG) on cognitive impairment and whether this model induces any alteration in the affinity, density, and subtypes of muscarinic acetylcholine receptors (mAChRs) in rat hippocampus. Healthy rats were used as controls, and MSG-obese rats were selected via the Lee index > 0.300. The effects of MSG-induced obesity on hippocampal spatial learning and memory processes were evaluated by using the working memory versions of the Morris’ water maze task and the evaluation of mAChRs by binding assay and their subtypes by immunoprecipitation assays. [3H]Quinuclidinyl benzilate specific binding analysis showed that the equilibrium dissociation constant (KD) did not differ between control and MSG, indicating that affinity is not affected by obesity induced by MSG. The maximum number of binding sites (Bmax) obtained in MSG subjects was lower than that obtained from control rats, indicating a decrease in the expression of total mAChRs. Immunoprecipitation assays reveal a decrease in the expression of M1subtype of MSG when compared with control rats (M2to M5subtypes did not differ between control and MSG). We also observed that MSG promotes a disruption of the spatial working memory which was accompanied by a decrease in the M1mAChR subtype in rat hippocampus, thus suggesting deleterious long-term effects besides the obesity. In conclusion, these findings provide new insights into how obesity can influence spatial learning and memory that is hippocampal-dependent. The data suggest that the M1mAChR subtype protein expression is a potential therapeutic target.

In the U.S., Helicoverpa zea(Boddie) is a major pest targeted by both transgenic maize and cotton expressing Bacillus thuringiensis(Bt) proteins. Resistance of insect to Bt maize and cotton containing cry1Aand cry2Agenes has widely occurred in the U.S. In this study, two trials were performed to investigate larval survival and development of a Cry1A.105/Cry2Ab2 dual-protein resistant (VT2P-RR), a susceptible, and an F1heterozygous (VT2P-RS) populations of H. zeaon ears of nine Bt and three non-Bt maize hybrids. The Bt maize hybrids evaluated represent five common pyramided traits expressing two or three of the Cry1A.105, Cry1Ab, Cry1F, Cry2Ab2, and Vip3Aa20 proteins. In the laboratory, neonates of the three H. zeapopulations were inoculated on silks of ears collected from maize at R1–R2 plant stages; and larval survivorship was checked 10 d after neonate release. All three insect populations survived normally on non-Bt maize ears. Varied numbers of VT2P-RR and VT2P-RS survived on ears of Cry1A.105/Cry2Ab2 maize, while all larvae of the three populations died or could not develop on ears of Vip3Aa20-expressing maize. The results demonstrated that the dual-protein resistant H. zeawas not cross-resistant to Vip3Aa20-expressing maize, and thus traits with vip3Aa20gene should be effective to manage Cry1A.105/Cry2Ab2-resistant H. zea. The resistance in VT2P-RR was determined to be incomplete on Cry1A.105/Cry2Ab2 maize. The effective dominance levels varied greatly, from recessive to incompletely dominant, depending on maize hybrids and trials, suggesting that proper selection of maize hybrids could be important for mitigating the Cry1A.105/Cry2Ab2 resistance. The data generated should aid in modeling multiple-protein Bt resistance in H. zea.

Heterogeneous Fenton-like reactions using O2as the sole oxidant are gaining interest for designing organic contaminant degradation in soils and groundwaters since they may provide alternatives to current processes involving strong oxidants. Indeed, several Fe(II)-bearing oxide and sulfide mineral phases have been proven to generate reactive species upon air oxidation. However, the mechanisms of these reactions and the identity of the reactive species produced upon oxygenation may deserve further research. Here, we show using electron paramagnetic resonance (EPR) spectroscopy combined with the 5,5-dimethyl-1-pyrroline N-oxide (DMPO) spin trap that air oxidation of pH 7 phosphate-buffered aqueous suspensions of magnetite (Fe3O4) or mackinawite (FeS) nanoparticles produces a reactive species that is distinct from the hydroxyl radical (•OH) and abstracts a hydrogen atom from ethanol. This reactive species grows dramatically with phosphate concentration, and ultrafiltration reveals that it occurs as both aqueous and surface species. Based on these evidence and from extant reports, we hypothesize that the nonhydroxyl reactive species produced is Fe(IV), whose formation is enhanced in the presence of phosphate ligands. Fe3O4magnetite (∼14 nm) generates about 30% more of this putative ferryl species than FeS mackinawite (∼9 nm), while FeS2(pyrite ∼12 nm + marcasite ∼4 nm) appears unreactive under these conditions.

The versatility of chitosan (Ch) biopolymer as a metallic nanoparticle stabilizing agent and excellent former of thin films on glassy carbon was explored in this work for the sustainable manufacture of novel electrochemical sensors based on carbon black (CB) and chitosan-stabilized platinum nanoparticles (Ch-PtNPs). Platinum nanoparticles highly stabilized by chitosan were easily synthesized at room temperature and characterized by HR-TEM, UV–vis, and voltammetry. Ch-PtNPs presented an average diameter of 2.7 nm, and typical voltammetric peaks of Pt in sulfuric acid medium were detected for films containing Ch-PtNPs. As a proof of concept, the CB-Ch-PtNP electrode was applied in the determination of hydrogen peroxide (H2O2) and the endocrine disruptor bisphenol A (BPA). Pronounced electrocatalytic activity towards H2O2reduction was observed in the presence of Ch-PtNPs in the films, guaranteeing the non-enzymatic determination of H2O2by chronoamperometry, with a limit of detection of 10 μmol L−1. In the determination of BPA by differential pulse adsorptive anodic stripping voltammetry (DPAdASV), under optimal experimental conditions, a wide linear response range and a limit of detection at the nanomolar level (7.9 nmol L−1) were achieved. In addition, excellent repeatabilities of sensor response and sensor fabrication, and accuracy in the analysis of natural water samples were obtained.

Rothmund-Thomson syndrome (RTS) is a rare, heterogeneous autosomal recessive genodermatosis, with poikiloderma as its hallmark. It is classified into two types: type I, with biallelic variants in ANAPC1and juvenile cataracts, and type II, with biallelic variants in RECQL4, increased cancer risk and no cataracts. We report on six Brazilian probands and two siblings of Swiss/Portuguese ancestry presenting with severe short stature, widespread poikiloderma and congenital ocular anomalies. Genomic and functional analysis revealed compound heterozygosis for a deep intronic splicing variant in trans with loss of function variants in DNA2, with reduction of the protein levels and impaired DNA double-strand break repair. The intronic variant is shared by all patients, as well as the Portuguese father of the European siblings, indicating a probable founder effect. Biallelic variants in DNA2were previously associated with microcephalic osteodysplastic primordial dwarfism. Although the individuals reported here present a similar growth pattern, the presence of poikiloderma and ocular anomalies is unique. Thus, we have broadened the phenotypical spectrum of DNA2mutations, incorporating clinical characteristics of RTS. Although a clear genotype–phenotype correlation cannot be definitively established at this moment, we speculate that the residual activity of the splicing variant allele could be responsible for the distinct manifestations of DNA2-related syndromes.

RationaleIn 2016, a new interferon-gamma release assay (IGRA) was introduced, QuantiFERON-TB Gold Plus (QFT-Plus), claimed to have improved sensitivity in active tuberculosis (TB).ObjectivesThis study aimed to determine the performance of QFT-Plus, compared with previous generation IGRAs and the tuberculin skin test (TST), in children with TB in Europe.MethodsMulticentre, ambispective cohort study within the Paediatric Tuberculosis Network European Trials Group (ptbnet), a dedicated paediatric TB research network comprising >300 members, capturing TB cases <18 years-of-age diagnosed between January 2009 and December 2019.Measurements and main results1001 TB cases from 16 countries were included (mean age (IQR) 5.6 (2.4–12.1) years). QFT-Plus was performed in 358, QFT Gold in-Tube (QFT-GIT) in 600, T-SPOT.TBin 58 and TST in 636 cases. The overall test sensitivities were: QFT-Plus 83.8% (95% CI 80.2% to 87.8%), QFT-GIT 85.5% (95% CI 82.7% to 88.3%), T-SPOT.TB77.6% (95% CI 66.9% to 88.3%) and TST (cut-off ≥10 mm) 83.3% (95% CI 83.3% to 86.2%). There was a trend for tests to have lower sensitivity in patients with miliary and/or central nervous system (CNS) TB (73.1%, 70.9%, 63.6% and 43.5%, respectively), and in immunocompromised patients (75.0%, 59.6%, 45.5% and 59.1%, respectively).ConclusionsThe results indicate that the latest generation IGRA assay, QFT-Plus, does not perform better than previous generation IGRAs or the TST in children with TB disease. Overall, tests performed worse in CNS and miliary TB, and in immunocompromised children. None of the tests evaluated had sufficiently high sensitivity to be used as a rule-out test in children with suspected TB.

Peak oxygen consumption (pVO2) is a key parameter for assessing the prognosis of heart failure with reduced ejection fraction (HFrEF). However, it is less reliable when the cardiopulmonary exercise test (CPET) is not maximal.

Decompensated heart failure (HF) is associated with poor short- and long-term prognosis. Remote invasive monitoring of pulmonary artery pressures (PAP) enables early detection of HF decompensation before symptoms occur and may improve clinical outcomes. We aimed to describe our initial experience with the use of the CardioMEMS™ remote monitoring system in patients with HF, including its safety and effectiveness.

Purpose: The proposal is to answer the following question: based on previous studies, which are the new paths and challenges related to the circular economy (CE) and Industry 4.0 (I4.0)? To answer this question, the research objective is to analyze studies approaching the interface between CE and I4.0. Design/methodology/approach: A systematic literature review (SLR) was conducted on previously published studies pertaining to Scopus and Web of Science bases, and 63 articles were found. Findings: The authors present five new paths and challenges amid the relationship between CE and I4.0: applying those technologies to clean production, using blockchain and big data in the circular supply chain, raising additive manufacturing impact on the CE, seek for a better understanding on how I4.0 technologies can properly support the CE in the stakeholders' view and discerning the factors for implementing those theoretical fields onto supply chains. Research limitations/implications: Previous studies' sample basis is still recent, lacking research depth. Search strings might have minimized the number of selected studies: there could be a bigger sample. Practical implications: Practical contributions of this study lay on the applicability of the raised propositions into several sectors' industries. Social implications: The authors suggest a transition agenda towards CE, using I4.0 technologies for operational, tactical and strategic personnel within organizations, as well as potential utilization strategies in specific study fields, like supply chain management and product manufacturing per se. Originality/value: The study presents new paths and challenges amid technologies pertaining to I4.0 and its interfaces with the CE. In the result presentation and analysis, the existing interfaces are described.

Data on urine output have not been routinely presented to define cardiac surgery-related acute kidney injury (AKI). We evaluated the incidence of AKI after cardiac surgery based on the AKIN and KDIGO criteria (considering serum creatinine concentration and urine output in the first 72 hours postoperatively) and compared the performance of the 2 criteria for AKI staging.

The increase of both arterial occlusive diseases and coronary heart diseases leads to a higher demand for small-diameter vascular grafts (<6 mm). The gold standard for small-diameter vessel replacement is the use of autologous veins. Nevertheless, up to 30% of these patients need to use vascular grafts. Although synthetic polymers have been successfully used for the replacement of large-diameter vascular grafts (>6 mm), they are associated with thrombosis, intimal hyperplasia, calcification, and chronic inflammation when used as small-diameter vascular grafts. Therefore, natural materials have been studied for this application. In this study, a decellularized human chorion membrane (dHCM) vascular graft with a 3–4 mm diameter was created. Herein, the biocompatibility of dHCM with endothelial cells was demonstrated in vitroand ex ovo. Blood biocompatibility of dHCM was also shown by studying plasma protein adsorption, platelet adhesion and activation, and its hemolytic potential. Furthermore, dHCM antibacterial properties against Staphylococcus aureuswere also studied. In summary, the dHCM reticular layer side presented all the needed characteristics to be used in the inner side of a vascular graft. Additionally, the mechanical properties of the dHCM tubular construct were studied, being similar to the ones of the saphenous vein, the gold standard for autologous small-diameter vessel replacement.

This work presents a detailed investigation aimed at understanding the key mechanisms governing nitric oxide (NO) production in N2–O2discharges by systematically comparing experimental results to modeling data. The experimental phase capitalizes on radiofrequency (13.56 MHz) discharges, sustained at 5 mbar pressure conditions, featuring varying concentrations of oxygen, ranging from pure N2plasma to air-like mixtures. On the modeling front, we adopt an integrated approach that combines the solution of the Boltzmann equation for electrons with a system of rate balance equations for heavy species. To account for ground state NO(X) generation at the reactor wall, we combine the volume chemistry with a mesoscopic description of the surface, taking into account adsorption sites and various elementary surface phenomena. Comparisons between experiments and modeling demonstrate very good agreement, extending beyond NO(X) formation to encompass other species in the plasma such as N2O(X) and atomic nitrogen N(4S). Noteworthy findings include (i) the pivotal role of surface mechanisms in NO(X) production, particularly at low oxygen content values; (ii) the significance of accurately describing the postdischarge phase, where depletion of plasma species occurs at different time scales (millisecond range); and (iii) the importance of vibrationally and electronically excited states (e.g., O2(b)) in elucidating NO(X) formation dynamics, crucial for unraveling reaction pathways and energy transfer processes. This work makes an important step toward formulating a comprehensive reaction mechanism for N2and N2–O2plasmas applied to nitrogen fixation, covering both volume and surface mechanisms, and lays a robust foundation for future research on plasma-based NO(X) production, particularly in the presence of catalysts.

Bioprinting – printing with incorporated living cells – has earned special attention on tissue engineering approaches, aiming to closer reproduce the 3D microenvironment of the target tissue. However, it raises extra complexity related to the need to use cell-friendly printing conditions that still comply with material printing fidelity. Inspired by the composite nano structural organization of mineralized tissues, this work reports the efficiency of the chemical approach followed to in situmineralize blue shark skin collagen, at a nano scale level, to ultimately produce stable inks. The influence of initial cellular density was evaluated by assessing three different concentrations (2.5, 5 and 7.5 × 106cells·ml−1) of human adipose stem cells (hASC), with the higher density of encapsulated cells presenting improved viability in a long culture term. Immunodetection of osteogenic-related markers, like RUNX2 and osteopontin, 21 days after cell culture in basal conditions confirmed the potential of the ink to be applied for osteogenic purposes, which may be associated with the success of the cell-to-ink interaction and the Ca2+ions released from the co-precipitated hydroxyapatite. A combination of mineralized shark collagen, alginate and hASC is thus proposed as a bioactive bioink with potential properties for regeneration of bone tissue.

Cancer is the major cause of morbidity and mortality worldwide. Hydroxycinnamic acids (HCAs) are naturally occurring compounds and their alkyl esters may possess enhanced biological activities. We evaluated C4, C14, C16, and C18 alkyl esters of p-coumaric, ferulic, sinapic, and caffeic acids (19 compounds) for their cytotoxic activity against four human cancer cells and also examined their effect on cell cycle alteration and apoptosis induction. The tetradecyl (1c) and hexadecyl (1d) esters of p-coumaric acid and tetradecyl ester of caffeic acid (4c), but not the parental HCAs, were selectively effective against MOLT-4 (human lymphoblastic leukemia) cells with IC50values of 0.123 ± 0.012, 0.301 ± 0.069 and 1.0 ± 0.1 μM, respectively. Compounds 1c, 1d,and 4csignificantly increased apoptotic cells in sub-G1 phase and activated the caspase-3 enzyme in MOLT-4 cells. Compound 1cwas 15.4 and 23.6 times more potent than doxorubicin and cisplatin, respectively, against the drug resistant MES-SA-DX5 uterine sarcoma cells. These p-coumarate esters were several times less effective against NIH/3T3 fibroblast cells. Docking studies showed that 1cmay cause cytotoxicity by interaction with carbonic anhydrase IX. In conclusion, long chain alkyl esters of p-coumaric acid are promising scaffolds for selective apoptosis induction in cancer cells.