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This work presents a detailed investigation aimed at understanding the key mechanisms governing nitric oxide (NO) production in N 2 -O 2 discharges 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 N 2 plasma 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 N 2 O(X) and atomic nitrogen N( 4 S). 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., O 2 (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 N 2 and N 2 -O 2 plasmas 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.

Seizures are neurological disorders triggered by an imbalance in the activity of excitatory and inhibitory neurotransmitters in the brain. When triggered chronically, this imbalance can lead to epilepsy. Critically, many of the affected individuals are refractory to treatment. Given this, anti-inflammatory drugs, in particular glucocorticoids, have been considered as a potential antiepileptogenic therapy. Glucocorticoids are currently used in the treatment of refractory patients, although there have been contradictory results in terms of their use in association with antiepileptic drugs, which reinforces the need for a more thorough investigation of their effects. In this context, the present study evaluated the effects of dexamethasone (DEX, 0.6 mg/kg) on the electroencephalographic (EEG) and histopathological parameters of male Wistar rats submitted to acute seizure induced by pentylenetetrazol (PTZ). The EEG monitoring revealed that DEX reduced the total brainwave power, in comparison with PTZ, in 12 h after the convulsive episode, exerting this effect in up to 36 h (p < 0.05 for all comparisons). An increase in the accommodation of the oscillations of the delta, alpha, and gamma frequencies was also observed from the first 12 h onwards, with the accommodation of the theta frequency occurring after 36 h, and that of the beta frequency 24 h after the seizure. The histopathological analyses showed that the CA3 region and hilum of the hippocampus suffered cell loss after the PTZ-induced seizure (control vs. PTZ, p < 0.05), although DEX was not able to protect these regions against cell death (PTZ vs. DEX + PTZ, p > 0.05). While DEX did not reverse the cell damage caused by PTZ, the data indicate that DEX has beneficial properties in the EEG analysis, which makes it a promising candidate for the attenuation of the epileptiform wave patterns that can precipitate refractory seizures., (Copyright © 2024. Published by Elsevier Inc.)

Cuniculus paca, commonly known as the paca, is a rodent of the Cuniculidae family that is widely distributed throughout the Americas, including all Brazilian territories, and is abundant in the Amazon region. It is one of the most hunted species and faces significant predation in the extreme western Amazon region of Brazil because it constitutes a staple in the diet of local communities, for subsistence and commercial purposes. Understanding the helminthic fauna of these animals is of paramount importance, given that some nematodes have zoonotic potential and may pose risks to consumer health. This study aimed to contribute to the records of the nemtodes of this highly consumed species in the Amazon region, highlighting the occurrence of gastrointestinal parasites in free-living pacas intended for human subsistence consumption. The study was conducted in the Paranã da Floresta community, located in the municipality of Guajará, Amazonas from 2022 to 2023. The community members hunted this rodent for consumption and voluntarily provided the viscera for analysis. Nematodes were extracted from each organ. The organs were opened, and the contents were processed using a sieve (0.15 mm) and subsequently evaluated separately. In total, 10,157 nematodes were found in the 14 pacas. Based on morphological analyses, the nematodes were identified as Heligmostrongylus sedecimradiatus (n = 10,068), Trichuris sp. (n = 85), and Physaloptera sp. (n = 4). This study provides insights into the nematodes diversity of free-living pacas in the extreme Western Amazon region, emphasizing the importance of sanitary surveillance and public awareness of the risks associated with bushmeat consumption., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

(1) Background: We examined the effect of the acute administration of olive oil (EVOO), linseed oil (GLO), soybean oil (SO), and palm oil (PO) on gastric motility and appetite in rats. (2) Methods: We assessed food intake, gastric retention (GR), and gene expression in all groups. (3) Results: Both EVOO and GLO were found to enhance the rate of stomach retention, leading to a decrease in hunger. On the other hand, the reduction in food intake caused by SO was accompanied by delayed effects on stomach retention. PO caused an alteration in the mRNA expression of NPY, POMC, and CART. Although PO increased stomach retention after 180 min, it did not affect food intake. It was subsequently verified that the absence of an autonomic reaction did not nullify the influence of EVOO in reducing food consumption. Moreover, in the absence of parasympathetic responses, animals that received PO exhibited a significant decrease in food consumption, probably mediated by lower NPY expression. (4) Conclusions: This study discovered that different oils induce various effects on parameters related to food consumption. Specifically, EVOO reduces food consumption primarily through its impact on the gastrointestinal tract, making it a recommended adjunct for weight loss. Conversely, the intake of PO limits food consumption in the absence of an autonomic reaction, but it is not advised due to its contribution to the development of cardiometabolic disorders.

Background: In high-resource settings, the survival of children with immunocompromise (IC) has increased and immunosuppressive therapies are increasingly being used. This study aimed to determine the clinical characteristics, performance of diagnostic tools, and outcome of IC children with tuberculosis (TB) in Europe., Methods: Multicenter, matched case-control study within the Pediatric Tuberculosis Network European Trials Group, capturing TB cases <18 years diagnosed 2000-2020., Results: A total of 417 TB cases were included, comprising 139 children who are IC (human immunodeficiency virus, inborn errors of immunity, drug-induced immunosuppression, and other immunocompromising conditions) and 278 non-IC children as controls. Nonrespiratory TB was more frequent among cases than controls (32.4% vs 21.2%; P = .013). Patients with IC had an increased likelihood of presenting with severe disease (57.6% vs 38.5%; P < .001; odds ratio [95% confidence interval], 2.073 [1.37-3.13]). Children with IC had higher rates of false-negative tuberculin skin test (31.9% vs 6.0%; P < .001) and QuantiFERON-TB Gold assay (30.0% vs 7.3%; P < .001) results at diagnosis. Overall, the microbiological confirmation rate was similar in IC and non-IC cases (58.3% vs 49.3%; P = .083). Although the mortality in children with IC was <1%, the rate of long-term sequelae was significantly higher than in non-IC cases (14.8% vs 6.1%; P = .004)., Conclusions: Children with IC and TB in Europe have increased rates of nonrespiratory TB, severe disease, and long-term sequelae. Immune-based TB tests have poor sensitivity in those children. Future research should focus on developing improved immunological TB tests that perform better in patients with IC, and determining the reasons for the increased risk of long-term sequelae, with the aim to design preventive management strategies., Competing Interests: Potential conflicts of interest . B. S. G. and M. T. have received support from Cepheid for a project on molecular tuberculosis diagnostics unrelated to the study reported here. M. T. has received QuantiFERON-TB assays at reduced pricing or free of charge for tuberculosis diagnostics projects from Cellestis/Qiagen in the past and has received support for conference attendance from Cepheid. The manufacturers had no influence on the study design, data collection, analysis or interpretation, writing of the manuscript, or the decision to submit the data for publication. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

This article examines the role of water in the body, the balance of fluids in the body and the provision of intravenous (IV) fluids to patients who are dehydrated, providing a comprehensive overview of these topics for nurses. The author details various aspects of practice in IV fluid therapy, including the types of fluids used, their indications, administration and potential side effects. The article also discusses dehydration and how nurses can identify and treat this complication, which can occur as a result of many different conditions. Drawing on the relevant research, this article aims to advance nurses' knowledge of the care of patients who are dehydrated and require IV fluid therapy., Competing Interests: None declared, (© 2024 RCN Publishing Company Ltd. All rights reserved. Not to be copied, transmitted or recorded in any way, in whole or part, without prior permission of the publishers.)

Ammonia synthesis via the 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 H 2 and N 2 and 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 NH 3 and 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 NH 3 at 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 (SrH 2 ) and metal imides (Sr 2 HN) are shown to help close the material cycle.

Organotin compounds (OTC), mainly tributyltin (TBT), have been used since the 1970s as biocides in the composition of antifouling paints. Due to its physical-chemical characteristics, TBT has high toxicity to the marine environment affecting non-target organisms. The present study aims to develop a method of direct visual identification of TBT in antifouling paints using the cyclopalladate complex, 4- (2-thiazolylazo) resorcinol (TAR-Pd), synthesized in our laboratory. Tests were performed in blank and in the paint matrix with the following OTC: TBT-O; TBT-Cl; TPT-Cl; DBT-Cl (tributyltin oxide, tributyltin chloride, triphenyltin chloride, dibutyltin chloride), in addition to the SnCl 4 and SnCl 2 compounds (tin IV chloride and tin II chloride), all at a concentration of approximately 20 g/ kg of dry paint). The test was performed by applying paint samples to test bodies and scraping a few tens of milligrams of the dry paint film. The scraped paint samples were submitted to the test, showing a different staining reaction for the TBT-Cl and SnCl 4 samples concerning blank and other samples (TBT-O, TPT, DBT-Cl, and SnCl 2 ). Solution tests were performed to characterize reaction products by spectroscopy in the visible band. The method developed has potential for application in real samples, being selective for TBT-Cl and SnCl 4 in an acid medium, obtaining a limit of detection, in the range of 1-10 mg/kg dry paint., (© 2024. The Author(s), under exclusive licence to The Japan Society for Analytical Chemistry.)

The CardioMEMS™ system remotely monitors changes in pulmonary artery pressures, which allows for early detection of heart failure worsening. It is a safe and reliable invasive monitoring system. We report a case in which there was a late migration of the device at 6 months of follow-up to the contralateral pulmonary artery. The mechanisms, consequences, and management of device migration are discussed. To our knowledge, there are very few published data on late sensor migration.

Competing Interests: Competing interests: None declared.

Impact statement This review discusses the research done using marine collagens (MCs) on biomaterials for bone, cartilage, and osteochondral tissue regenerative applications with the underlying technologies that enable their development, and explains the methodologies used to characterize MCs highlighting their importance, namely regarding the performance of derived biomaterials, and the inherent properties of such collagens. In the second part, the applicability of MCs as biomaterials for hard tissue applications was studied, focusing on the mostly applied fabrication techniques. In conclusion, this review describes the major challenges to be overcome and the forecast for the upcoming years concerning the use of MCs.

A significant and increasing number of studies have been dedicated to complex concentrated alloys (CCAs) due to the improved properties that these metallic materials can exhibit. However, while most of these studies employ melting techniques, only a few explore powder metallurgy and pressureless sintering as production methods. In this work, a microstructural characterization of AlCrCuFeMnNi CCA samples obtained by powder metallurgy and pressureless sintering using mixtures of powders with different compositions was carried out. One batch of samples (B1) was prepared using commercial powders of Al, Cr, Cu, Fe, Mn, and Ni. Another batch (B2) used mixtures of CrFeMn, AlNi, and Cu powders. A third set of samples (B3) was obtained by adding 1% at. of Mg to the B2 powder. The samples were characterized by X-ray diffraction, scanning and transmission electron microscopy, energy dispersive spectroscopy, density measurements, and hardness tests. Thermodynamic calculations were also used to complement the microstructural characterization. All the obtained samples exhibited high relative density and hardness values. However, B3 samples showed a higher hardness, attributed to the finer distribution of oxide particles, which was promoted by the presence of Mg during sintering. These last samples presented a hardness/density ratio of 62 HV/(g cm -3 ), surpassing that of some martensitic stainless steels and nickel-titanium alloys., Competing Interests: The authors declare no conflicts of interest.

In this initial study of a research project, this paper seeks to understand the thermal conditions in the cities of Lisbon and Munich, specifically focusing on Urban Heat Island intensity and on thermal comfort using the Universal Thermal Climate Index modeling data at the Local Climate Zone scale. Based on these datasets, Munich has exhibited more unfavourable thermal conditions than Lisbon. In terms of UHII, both cities have shown that low, medium, and high rise compact urban areas and bare rock or paved areas have the highest values, while sparsely built areas have the lowest. These results differ from the UTCI, which indicates that in Lisbon and Munich, these sparsely built areas as well as areas with low plants and vegetation are the most uncomfortable. In Munich, the population was exposed to very strong heat stress, while Lisbon experienced strong heat stress conditions. Conversely, low, medium, and high rise compact urban areas and densely wooded areas in Munich, and scattered trees areas and large low-rise urban areas in Lisbon, have demonstrated the lowest monthly mean and average maximum values. These results will be further explored in future studies in the city of Lisbon and cross-checked with data obtained from roving missions. This will enable a more detailed temporal and local analysis., (© 2024. The Author(s).)

The ability of human tissues to self-repair is limited, which motivates the scientific community to explore new and better therapeutic approaches to tissue regeneration. The present manuscript provides a comparative study between a marine-based composite biomaterial, and another composed of well-established counterparts for bone tissue regeneration. Blue shark skin collagen was combined with bioapatite obtained from blue shark's teeth (mColl:BAp), while bovine collagen was combined with synthetic hydroxyapatite (bColl:Ap) to produce 3D composite scaffolds by freeze-drying. Collagens showed similar profiles, while apatite particles differed in their composition, being the marine bioapatite a fluoride-enriched ceramic. The marine-sourced biomaterials presented higher porosities, improved mechanical properties, and slower degradation rates when compared to synthetic apatite-reinforced bovine collagen. The in vivo performance regarding bone tissue regeneration was evaluated in defects created in femoral condyles in New Zealand rabbits twelve weeks post-surgery. Micro-CT results showed that mColl:BAp implanted condyles had a slower degradation and an higher tissue formation (17.9 ± 6.9 %) when compared with bColl:Ap implanted ones (12.9 ± 7.6 %). The histomorphometry analysis provided supporting evidence, confirming the observed trend by quantifying 13.1 ± 7.9 % of new tissue formation for mColl:BAp composites and 10.4 ± 3.2 % for bColl:Ap composites, suggesting the potential use of marine biomaterials for bone regeneration., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Nitrocatechols are the standard pharmacophore to develop potent tight-binding inhibitors of catechol O -methyltransferase (COMT), which can be used as coadjuvant drugs to manage Parkinson's disease. Tolcapone is the most potent drug of this class, but it has raised safety concerns due to its potential to induce liver damage. Tolcapone-induced hepatotoxicity has been attributed to the nitrocatechol moiety; however, other nitrocatechol-based COMT inhibitors, such as entacapone, are safe and do not damage the liver. There is a knowledge gap concerning which mechanisms and chemical properties govern the toxicity of nitrocatechol-based COMT inhibitors. Using a vast array of cell-based assays, we found that tolcapone-induced toxicity is caused by direct interference with mitochondria that does not depend on bioactivation by P450. Our findings also suggest that (a) lipophilicity is a key property in the toxic potential of nitrocatechols; (b) the presence of a carbonyl group directly attached to the nitrocatechol ring seems to increase the reactivity of the molecule, and (c) the presence of cyano moiety in double bond stabilizes the reactivity decreasing the cytotoxicity. Altogether, the fine balance between lipophilicity and the chemical nature of the C1 substituents of the nitrocatechol ring may explain the difference in the toxicological behavior observed between tolcapone and entacapone., Competing Interests: The authors declare no competing financial interest., (© 2024 American Chemical Society.)

Hospital accreditation has become ubiquitous in developing countries. While research acknowledges that accreditation can enhance healthcare quality, efficiency, and safety, concerns persist regarding hospitals' management of conflicts stemming from the diverse institutional logic inherent in this process. Therefore, this study aimed to investigate how professional and market logic, alongside conflicts arising from institutional demands, affect compliance with hospital accreditation. To this end, we conducted a multiple-case study in four Brazilian hospitals employing in-depth interviews and on-site observations. The triangulation of narrative analysis and the outcomes of multiple correspondence analysis revealed that when professional logic predominates, there is a greater propensity to tailor accredited activities by segmenting the tasks between physicians and nurses with the intention of mitigating existing conflicts. Conversely, when conflicts occur over established goals between professionals and orientated marked logic executives, the accreditation process is impeded, resulting in non-compliance. Ultimately, the findings underscore the alignment between the pursuit of legitimacy and efficiency within the accreditation process. We conclude by delineating the theoretical and practical implications of scrutinizing the internal dynamics of institutional logic.

The effect of calorie restriction, fasting, and ketogenic diets on the treatment of liver cancer remains uncertain. Therefore, we conducted a systematic review to evaluate the effect of restrictive diets on the development and progression of liver cancer in animal models. We did a meta-analysis using the Cochrane Collaboration's Review Manager software, with the random effects model and the inverse variance technique. We examined 19 studies that were conducted between 1983 and 2020. Of these, 63.2% investigated calorie restriction, 21.0% experimented with a ketogenic diet, and 15.8% investigated the effects of fasting. The intervention lasted anything from 48 h to 221 weeks. Results showed that restrictive diets may reduce tumor incidence and progression, with a significant reduction in the risk of liver cancer development. Thereby, our results suggest that putting limits on what you eat may help treat liver cancer in more ways than one., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest that pertain to this work. PROSPERO registration: CRD42021267023., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Treatment of advanced differentiated thyroid carcinoma (DTC) remains a challenge as 25-50% of patients with locally invasive or distant metastatic disease become refractory to radioiodine (RAI) therapy. Tyrosine kinase inhibitors (TKI) are increasingly used in this setting. The SELECT trial demonstrated that lenvatinib, a multikinase inhibitor, significantly improved progression free survival (PFS) compared to placebo. Our aim was to report the effectiveness and safety of lenvatinib in our series of patients with advanced DTC., Methods: A total of 25 patients with advanced DTC followed at a single tertiary center from January of 2016 to January of 2022 were retrospectively reviewed., Results: Patients were treated with a mean daily dose of lenvatinib of 16.9 mg for a mean of 9.1 months. Median estimated PFS was 31.3 months. One patient achieved complete response. The objective response rate (ORR) was 40% and the disease control rate was 84%. The mean change in summed longest diameter of target lesions from baseline to nadir was -36.9%. Lenvatinib prolonged the tumor volume doubling time in 86.7% patients. Interestingly, we found that patients treated with a lower dose of lenvatinib (<16.9 mg daily) had a significantly higher PFS and ORR than patients treated with higher dosages (>16.9 mg). Adverse events were frequently reported., Conclusions: Our results confirm the effectiveness of lenvatinib in the management of patients with advanced DTC and support the need to adjust the dosage of lenvatinib to patient´s performance status and comorbidities.

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.

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.

The monoclonal antibody (mAb) industry is becoming increasingly digitalized. Digital twins are becoming increasingly important to test or validate processes before manufacturing. High-Throughput Process Development (HTPD) has been progressively used as a tool for process development and innovation. The combination of High-Throughput Screening with fast computational methods allows to study processes in-silico in a fast and efficient manner. This paper presents a hybrid approach for HTPD where equal importance is given to experimental, computational and decision-making stages. Equilibrium adsorption isotherms of 13 protein A and 16 Cation-Exchange resins were determined with pure mAb. The influence of other components in the clarified cell culture supernatant (harvest) has been under-investigated. This work contributes with a methodology for the study of equilibrium adsorption of mAb in harvest to different protein A resins and compares the adsorption behavior with the pure sample experiments. Column chromatography was modelled using a Lumped Kinetic Model, with an overall mass transfer coefficient parameter (k ov ). The screening results showed that the harvest solution had virtually no influence on the adsorption behavior of mAb to the different protein A resins tested. k ov was found to have a linear correlation with the sample feed concentration, which is in line with mass transfer theory. The hybrid approach for HTPD presented highlights the roles of the computational, experimental, and decision-making stages in process development, and how it can be implemented to develop a chromatographic process. The proposed white-box digital twin helps to accelerate chromatographic process development., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

The aim was to evaluate the chemical composition, carbohydrates, protein fractionation and in vitro gas production of silages composed of spineless cactus and tropical forages and their effect on sheep performance. Treatments consisted of silages: corn silage (CS), spineless cactus silage (SCS), spineless cactus + gliricidia (SCG), spineless cactus + buffel grass silage (SCBG) and spineless cactus + pornunça (SCP). Silos were opened 60 days after ensiling, and analyses were carried out. The digestibility test lasted for 36 days, with eight animals per treatment. A completely randomized design was adopted. Considering carbohydrate fractionation, CS, SCS and SCBG silages had higher total carbohydrate content ( p = 0.001). The SCS silage presented a higher A + B1 fraction ( p = 0.001). The SCBG and SCG silages showed a higher B2 fraction ( p < 0.0001) compared to the CS and SCS silages. The SCBG and SCP silages presented a higher C fraction ( p = 0.001). For protein fractionation, the SCP and SCG silages showed higher crude protein contents ( p = 0.001). The CS and SCS silages showed a higher A fraction ( p = 0.001). The SCBG silage presented a higher B1 + B2 fraction ( p = 0.001). The SCG silage showed a higher B3 fraction ( p = 0.006) compared to SCBG silage. The SCS and SCP silages showed a higher C fraction ( p = 0.001). Exclusive SCS silage showed higher in vitro dry matter digestibility ( p = 0.001), dry matter degradability ( p = 0.001) and total gas production ( p = 0.001). The use of the SCBG, SCP and SCG silages to feed sheep increased the dry matter intake ( p < 0.001). Sheep fed the SCG silage showed greater dry matter and crude protein digestibility compared to the sheep fed the CS, SCS and SCP silages ( p = 0.002). There was a higher water intake ( p < 0.001) with the use of the SCS and SCG silages to feed the sheep. The SCP and SCG silages provided a greater intake ( p < 0.001) and excretion ( p < 0.001) of nitrogen by the animals. Although there were no differences between the treatments for daily gains, lambs that received the spineless cactus-based silage associated with tropical forages showed higher gains (160-190 g/day) than lambs that received CS silage (130 g/day). Thus, the use of spineless cactus associated with buffelgrass, pornunça and gliricidia to prepare mixed silages (60:40) to feed sheep has potential use to feed sheep, with positive effects on nutrient degradation and increases in dry matter intake. Under experimental conditions, we recommend the exclusive use of spineless cactus silage associated with buffel grass, pornunça and gliricidia in feeding sheep in semi-arid regions, as it provides nutrients, water and greater daily gains compared to corn silage.

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.

Purpose: to describe a clinical case of ocular sarcoidosis in a patient with Autoimmune Polyglandular Syndrome Type 2 (APS-2)., Methods: an 86-year-old female diagnosed with APS-2 was referred to our uveitis department with rapid visual loss in her left eye during a 3-month period. Her best-corrected visual acuity (BCVA) was counting fingers in her left eye (OS) and 20/40 in her right eye (OD). Slit-lamp biomicroscopy was unremarkable OD but revealed granulomatous keratic precipitates OS. Fundoscopy revealed bilateral optic disc oedema and +2 and 4+ vitritis (SUN classification) in her OD and OS, respectively., Results: the patient underwent chest X-Ray which revealed bilateral hilar lymphadenopathy and fibrosis. On high-resolution computed tomography of the lungs, ground-glass opacities were visible, and a diagnosis of ocular sarcoidosis was presumed. After exclusion of infectious diseases, the patient was treated with methotrexate and oral corticosteroids and there was substantial improvement of the optic nerve oedema and vitritis. At the most recent visit, 2 years later, OS BCVA was 20/50., Conclusion: There may be an association between ocular sarcoidosis and APS or other autoimmune disorders.

Chondrosia reniformis is a collagen-rich marine sponge that is considered a sustainable and viable option for producing an alternative to mammalian-origin collagens. However, there is a lack of knowledge regarding the properties of collagen isolated from different sponge parts, namely the outer region, or cortex, (ectosome) and the inner region (choanosome), and how it affects the development of biomaterials. In this study, a brief histological analysis focusing on C. reniformis collagen spatial distribution and a comprehensive comparative analysis between collagen isolated from ectosome and choanosome are presented. The isolated collagen characterization was based on isolation yield, Fourier-transformed infrared spectroscopy (FTIR), circular dichroism (CD), SDS-PAGE, dot blot, and amino acid composition, as well as their cytocompatibility envisaging the development of future biomedical applications. An isolation yield of approximately 20% was similar for both sponge parts, as well as the FTIR, CD, and SDS-PAGE profiles, which demonstrated that both isolated collagens presented a high purity degree and preserved their triple helix and fibrillar conformation. Ectosome collagen had a higher OHpro content and possessed collagen type I and IV, while the choanosome was predominately constituted by collagen type IV. In vitro cytotoxicity assays using the L929 fibroblast cell line displayed a significant cytotoxic effect of choanosome collagen at 2 mg/mL, while ectosome collagen enhanced cell metabolism and proliferation, thus indicating the latter as being more suitable for the development of biomaterials. This research represents a unique comparative study of C. reniformis body parts, serving as a support for further establishing this marine sponge as a promising alternative collagen source for the future development of biomedical applications.

This work proposes a new methodology to identify and validate deep learning models for artificial oil lift systems that use submersible electric pumps. The proposed methodology allows for obtaining the models and evaluating the prediction's uncertainty jointly and systematically. The methodology employs a nonlinear model to generate training and validation data and the Markov Chain Monte Carlo algorithm to assess the neural network's epistemic uncertainty. The nonlinear model was used to overcome the limitations of the need for big datasets for training deep learning models. However, the developed models are validated against experimental data after training and validation with synthetic data. The validation is also performed through the models' uncertainty assessment and experimental data. From the implementation point of view, the method was coded in Python with Tensorflow and Keras libraries used to build the neural Networks and find the hyperparameters. The results show that the proposed methodology obtained models representing both the nonlinear model's dynamic behavior and the experimental data. It provides a most probable value close to the experimental data, and the uncertainty of the generated deep learning models has the same order of magnitude as that of the nonlinear model. This uncertainty assessment shows that the built models were adequately validated. The proposed deep learning models can be applied in several applications requiring a reliable and computationally lighter model. Hence, the obtained AI dynamic models can be employed for digital twin construction, control, and optimization., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Biodesulfurization is a biotechnological process that uses microorganisms as biocatalysts to actively remove sulfur from fuels. It has the potential to be cleaner and more efficient than the current industrial process, however several bottlenecks have prevented its implementation. Additionally, most works propose models based on direct cultivation on fuel, or batch production of biocatalysts followed by a processing step before application to batch biodesulfurization, which are difficult to replicate at a larger scale. Thus, there is a need for a model that can be adapted to a refining process, where fuel is being continuously produced to meet consumer needs. The main goal of this work was to develop the first bench-scale continuous biodesulfurization system that integrates biocatalyst production, biodesulfurization and fuel separation, into a single continuous process, taking advantage of the method for the continuous production of the biodesulfurization biocatalysts previously established. This system eliminates the need to process the biocatalysts and facilitates fuel separation, while mitigating some of the process bottlenecks. First, using the bacterium Gordonia alkanivorans strain 1B, continuous culture conditions were optimized to double biocatalyst production, and the produced biocatalysts were applied in batch biphasic biodesulfurization assays for a better understanding of the influence of different factors. Then, the novel integrated system was developed and evaluated using a model fuel ( n -heptane + dibenzothiophene) in continuous biodesulfurization assays. With this system strain 1B surpassed its highest biodesulfurization rate, reaching 21 μmol h -1 g -1 . Furthermore, by testing a recalcitrant model fuel, composed of n -heptane with dibenzothiophene and three alkylated derivatives (with 109 ppm of sulfur), 72% biodesulfurization was achieved by repeatedly passing the same fuel through the system, maintaining a constant response throughout sequential biodesulfurization cycles. Lastly, the system was also tested with real fuels (used tire/plastic pyrolysis oil; sweet and sour crude oils), revealing increased desulfurization activity. These results highlight the potential of the continuous biodesulfurization system to accelerate the transition from bench to commercial scale, contributing to the development of biodesulfurization biorefineries, centered on the valorization of sulfur-rich residues/biomasses for energy production., Competing Interests: The authors declare no competing interests., (This journal is © The Royal Society of Chemistry.)

3D bioprinting enables the fabrication of biomimetic cell-laden constructs for cartilage regeneration, offering exclusive strategies for precise pharmacological screenings in osteoarthritis (OA). Synovial inflammation plays a crucial role in OA's early stage and progression, characterized by the increased of the synovial pro-inflammatory mediators and cytokines and chondrocyte apoptosis. Therefore, there is an urgent need to develop solutions for effectively managing the primary events associated with OA. To address these issues, a phenolic-based biocompatible ionic liquid approach, combining alginate (ALG), acemannan (ACE), and cholinium caffeate (Ch[Caffeate]), was used to produce easily printable bioinks. Through the use of this strategy 3D constructs with good printing resolution and high structural integrity were obtained. The encapsulation of chondrocytes like ATDC5 cells provided structures with good cell distribution, viability, and growth, for up to 14 days. The co-culture of the constructs with THP-1 macrophages proved their ability to block pro-inflammatory cytokines (TNF-α and IL-6) and mediators (GM-CSF), released by the cultured cells. Moreover, incorporating the biocompatible ionic liquid into the system significantly improved its bioactive performance without compromising its physicochemical features. These findings demonstrate that ALG/ACE/Ch[Caffeate] bioinks have great potential for bioengineering cartilage tissue analogs. Besides, the developed ALG/ACE/Ch[Caffeate] bioinks protected encapsulated chondrocyte-like cells from the effect of the inflammation, assessed by a co-culture system with THP-1 macrophages. These results support the increasing use of Bio-ILs in the biomedical field, particularly for developing 3D bioprinting-based constructs to manage inflammatory-based changes in OA. STATEMENT OF SIGNIFICANCE: Combining natural resources with active biocompatible ionic liquids (Bio-IL) for 3D printing is herein presented as an approach for the development of tools to manage inflammatory osteoarthritis (OA). We propose combining alginate (ALG), acemannan (ACE), and cholinium caffeate (Ch[Caffeate]), a phenolic-based Bio-IL with anti-inflammatory and antioxidant features, to produce bioinks that allow to obtain 3D constructs with good printing resolution, structural integrity, and that provide encapsulated chondrocyte-like cells good viability. The establishment of a co-culture system using the printed constructs and THP-1-activated macrophages allowed us to study the encapsulated chondrocyte-like cells behaviour within an inflammatory scenario, a typical event in early-stage OA. The obtained outcomes support the beneficial use of Bio-ILs in the biomedical field, particularly for the development of 3D bioprinting-based models that allow the monitoring of inflammatory-based events in OA., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

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 ANAPC1 and 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 DNA2 were 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 DNA2 mutations, 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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: The authors have no funding or conflicts of interest to disclose.

The thermal environment is important in unit production because the perception of thermal stress can reduce fertility, and productive performance, therefore its management is necessary. The use of non-invasive methods, such as infrared thermography and real-time ultrasonography, are widely used to evaluate indicators in animal production, without the need to slaughter the animals. Thus, we aimed to assess the effect of the thermal environment on the physiological parameters and carcass characteristics of Dorper sheep with positive and negative residual feed intake (RFI) using infrared thermography and real-time ultrasonography techniques. Twenty uncastrated male Dorper sheep (17.8 ± 2.4 kg) were confined for 40 days for RFI classification. Sheep were separated into positive RFI (n = 10) and negative RFI (n = 10). The experimental design was in randomized blocks, in a 2 × 2 factorial arrangement, with 2 thermal environments (full sun or shade) and two feed efficiency groups (positive RFI or negative RFI), with 5 replications. The sheep remained in confinement for 60 days. The animals were slaughtered at the end of the experiment and the carcasses dissected for tissue separation. Rectal temperature (RT) and respiratory rate (RR) were measured at two times (14:00 h and 18:00 h) for periods of 5 days. The RR was determined by indirect auscultation of heart sounds at the level of the laryngotracheal region. The RT was measured introduced a digital clinical thermometer into the animal's rectum. Surface temperature (ST) was obtained using a thermographic infrared camera, collecting the temperatures of the eyeball and skin surface in the regions of the head, ribs, rump, flank and shin. Sheep confined in full sun showed higher RR (P = 0.0001), ST ribs (P = 0.0020), ST rumb (P = 0.0055), ST flank (P = 0.0001) and heat tolerance coefficient (HTC) (P = 0.0010). For sheep confined in full sun, a strong correlation was observed between the RR and the mean ST (MST; r = 0.6826; P = 0.0236) and between the final loin eye area (LEAf) with the real LEA (LEAr) (r = 0.9263; P = 0.0001) and slaughter body weight (SBW) (r = 0.7532; P = 0.0325). For negative RFI sheep, a positive correlation was observed between the RR and the ST rump (r = 0.7343; P = 0.0025) and ST ribs (r = 0.6560; P = 0.0178) and the MST (r = 0.7435; P = 0.0001), between the MST and the LEAr (r = 0.6837; P = 0.0025) and the final LEA (r = 0.6771; P = 0.0144), and between the final LEA and LEAr (r = 0.9942; P = 0.0001), BW (r = 0.8415; P = 0.0277) and MST (r = 0.6771; P = 0.0045). Positive RFI sheep confined to shade showed a high correlation between final LEA and LEAr (r = 0.9372; P = 0.0001). The use of shading in confined Dorper sheep, regardless of the RFI classification, reduces the effects of heat stress on physiological parameters., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Exercise testing is key in the risk stratification of patients with heart failure (HF). There are scarce data on its prognostic power in women. Our aim was to assess the predictive value of the heart transplantation (HTx) thresholds in HF in women and in men., Methods: Prospective evaluation of HF patients who underwent cardiopulmonary exercise testing (CPET) from 2009 to 2018 for the composite endpoint of cardiovascular mortality and urgent HTx., Results: A total of 458 patients underwent CPET, with a composite endpoint frequency of 10.5% in females vs. 16.0% in males in 36-month follow-up. Peak VO 2 (pVO 2 ), VE/VCO 2 slope and percent of predicted pVO 2 were independent discriminators of the composite endpoint, particularly in women. The International Society for Heart Lung Transplantation recommended values of pVO 2 ≤ 12 mL/kg/min or ≤14 if the patient is intolerant to β-blockers, VE/VCO 2 slope > 35, and percent of predicted pVO 2 ≤ 50% showed a higher diagnostic effectiveness in women. Specific pVO 2 , VE/VCO 2 slope and percent of predicted pVO 2 cut-offs in each sex group presented a higher prognostic power than the recommended thresholds., Conclusion: Individualized sex-specific thresholds may improve patient selection for HTx. More evidence is needed to address sex differences in HF risk stratification.

Background and Objectives : Cardiopulmonary exercise testing (CPET) is a cornerstone of risk stratification in heart failure with reduced ejection fraction (HFrEF). However, there is a paucity of evidence on its predictive power in older patients. The aim of this study was to evaluate the prognostic power of current heart transplantation (HTx) listing criteria in HFrEF stratified according to age groups. Materials and Methods : Consecutive patients with HFrEF undergoing CPET between 2009 and 2018 were followed-up for cardiac death and urgent HTx. Results : CPET was performed in 458 patients with HFrEF. The composite endpoint occurred in 16.8% of patients ≤50 years vs. 14.1% of patients ≥50 years in a 36-month follow-up. Peak VO 2 (pVO 2 ), VE/VCO 2 slope and percentage of predicted pVO 2 were strong independent predictors of outcomes. The International Society for Heart and Lung Transplantation thresholds of pVO 2 ≤ 12 mL/kg/min (≤14 if intolerant to β-blockers), VE/VCO 2 slope > 35 and percentage of predicted pVO 2 ≤ 50% presented a higher overall diagnostic effectiveness in younger patients (≤50 years). Specific thresholds for each age subgroup outperformed the traditional cut-offs. Conclusions : Personalized age-specific thresholds may contribute to an accurate risk stratification in HFrEF. Further studies are needed to address the gap in evidence between younger and older patients.

Objective: The clinical relevance of solid/trabecular (ST) growth in papillary thyroid carcinoma (PTC) is unclear. In this study, we investigated the impact of any amount of ST growth on tumour characteristics and patient outcomes. Furthermore, we evaluated whether ST growth per se affected patients' prognosis in the absence of aggressive features, namely vascular invasion., Design: We analysed 222 PTC patients followed up for more than 5 years in the Department of Endocrinology of the Instituto Português de Oncologia de Lisboa Francisco Gentil from 2002 to 2020. All PTC cases with any percentage of ST growth were included and compared with PTC without ST growth (1:2). Carcinomas with high-grade features were excluded., Results: There were 74 PTC cases with ST growth and 148 without ST growth (median follow-up of 9.3 years). PTC-ST was associated with larger tumour size (p = 0.001) and increased frequency of vascular invasion (p < 0.001) compared with PTC. However, PTC-ST did not exhibit a higher incidence of extrathyroidal extension (p = 1.000) or lymph node metastasis (p = 0.433). Despite the significantly higher prevalence of distant metastasis in PTC-ST compared with PTC (p = 0.043), the significance is lost when the cases with vascular invasion were excluded (p = 0.347). The total radioiodine activity was higher in PTC-ST than in PTC (p = 0.008). Recurrence rates were similar between groups (p = 0.755). The 10-year overall survival and disease-free survival rates for PTC-ST were 94.6% and 98.6%, respectively, similar to the PCT without ST growth (p = 0.097 and p = 0.333, respectively). There was no evidence of an association between the presence of an ST component (p = 0.201) with the risk of death or recurrence, whereas the presence of distant metastasis significantly increased the risk of these events (hazard ratio 10.14, p < 0.001)., Conclusions: The presence of ST growth was associated with several aggressive clinicopathological features. However, the risk of cancer recurrence and death for PTC-ST were similar to PTC. In the absence of vascular invasion, the clinical impact of ST growth alone is negligible., (© 2023 John Wiley & Sons Ltd.)

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.

In the past decade, there has been significant progress in 3D printing research for tissue engineering (TE) using biomaterial inks made from natural and synthetic compounds. These constructs can aid in the regeneration process after tissue loss or injury, but achieving high shape fidelity is a challenge as it affects the construct's physical and biological performance with cells. In parallel with the growth of 3D bioprinting approaches, some marine-origin polymers have been studied due to their biocompatibility, biodegradability, low immunogenicity, and similarities to human extracellular matrix components, making them an excellent alternative to land mammal-origin polymers with reduced disease transmission risk and ethical concerns. In this research, collagen from shark skin, chitosan from squid pens, and fucoidan from brown algae were effectively blended for the manufacturing of an adequate biomaterial ink to achieve a printable, reproducible material with a high shape fidelity and reticulated using four different approaches (phosphate-buffered saline, cell culture medium, 6% CaCl 2 , and 5 mM Genipin). Materials characterization was composed by filament collapse, fusion behavior, swelling behavior, and rheological and compressive tests, which demonstrated favorable shape fidelity resulting in a stable structure without deformations, and interesting shear recovery properties around the 80% mark. Additionally, live/dead assays were conducted in order to assess the cell viability of an immortalized human mesenchymal stem cell line, seeded directly on the 3D printed constructs, which showed over 90% viable cells. Overall, the Roswell Park Memorial Institute cell culture medium promoted the adequate crosslinking of this biopolymer blend to serve the TE approach, taking advantage of its capacity to hamper pH decrease coming from the acidic biomaterial ink. While the crosslinking occurs, the pH can be easily monitored by the presence of the indicator phenol red in the cell culture medium, which reduces costs and time., (Creative Commons Attribution license.)

Background: New therapies with prognostic benefits have been recently introduced in heart failure with reduced ejection fraction (HFrEF) management. The aim of this study was to evaluate the prognostic power of current listing criteria for heart transplantation (HT) in an HFrEF cohort submitted to cardiopulmonary exercise testing (CPET) between 2009 and 2014 (group A) and between 2015 and 2018 (group B)., Methods: Consecutive patients with HFrEF who underwent CPET were followed-up for cardiac death and urgent HT., Results: CPET was performed in 487 patients. The composite endpoint occurred in 19.4% of group A vs. 7.4% of group B in a 36-month follow-up. Peak VO 2 (pVO 2 ) and VE/VCO 2 slope were the strongest independent predictors of mortality. International Society for Heart and Lung Transplantation (ISHLT) thresholds of pVO 2 ≤ 12 mL/kg/min (≤14 if intolerant to β-blockers) and VE/VCO 2 slope > 35 presented a similar and lower Youden index, respectively, in group B compared to group A, and a lower positive predictive value. pVO 2 ≤ 10 mL/kg/min and VE/VCO 2 slope > 40 outperformed the traditional cut-offs. An ischemic etiology subanalysis showed similar results., Conclusion: ISHLT thresholds showed a lower overall prognostic effectiveness in a contemporary HFrEF population. Novel parameters may be needed to improve risk stratification.

Nineteen cases of parathyroid carcinoma in patients with multiple endocrine neoplasia type 1 have been reported in the literature, of which 11 carry an inactivating germline mutation in the MEN1 gene. Somatic genetic abnormalities in these parathyroid carcinomas have never been detected. In this paper, we aimed to describe the clinical and molecular characterization of a parathyroid carcinoma identified in a patient with MEN1. A 60-year-old man was diagnosed with primary hyperparathyroidism during the postoperative period of lung carcinoid surgery. Serum calcium and parathyroid hormone levels were 15.0 mg/dL (8.4-10.2) and 472 pg/mL (12-65), respectively. The patient underwent parathyroid surgery, and histological findings were consistent with parathyroid carcinoma. Analysis of the MEN1 gene by next-generation sequencing (NGS) identified a novel germline heterozygous nonsense pathogenic variant (c.978C>A; p.(Tyr326*)), predicted to encode a truncated protein. Genetic analysis of the parathyroid carcinoma revealed a c.307del, p.(Leu103Cysfs*16) frameshift truncating somatic MEN1 variant in the MEN1 gene, which is consistent with MEN1 tumor-suppressor role, confirming its involvement in parathyroid carcinoma etiology. Genetic analysis of CDC73, GCM2, TP53, RB1, AKT1, MTOR, PIK3CA and CCND1 genes in the parathyroid carcinoma DNA did not detect any somatic mutations. To our knowledge, this is the first report of a PC case presenting both germline (first-hit) and somatic (second-hit) inactivation of the MEN1 gene.

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. [ 3 H]Quinuclidinyl benzilate specific binding analysis showed that the equilibrium dissociation constant (K D ) did not differ between control and MSG, indicating that affinity is not affected by obesity induced by MSG. The maximum number of binding sites (B max ) 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 M 1 subtype of MSG when compared with control rats (M 2 to M 5 subtypes 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 M 1 mAChR 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 M 1 mAChR subtype protein expression is a potential therapeutic target., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Particularly in the last 2 years, due to the new coronavirus pandemic, people with depression have increasingly sought human connection and relief from depressive symptoms through playing in the world of videogames, and a small yet growing portion of researchers have been investigating the therapeutic potential of that kind of interaction. Objective: The objective of this review was to provide an exploration of the current panorama of scientific research with videogames used as therapeutic intervention tools for depression. Method: A systematic review was performed for that purpose, with a semantic field of 12 keywords around the terms "depression," "mental health," and "video games" narrowed down into a concise syntax-(games OR serious games) AND (depression) AND (treatment)-applied to relevant databases for health research; followed by the execution of a search and screening protocol based on one guiding question; and analysis of results based on four elaborative questions. Results: Twenty-six studies met the inclusion criteria and provided a set of both quantitative and qualitative data about demographics, kinds of therapeutic interventions, types of videogames used in the interventions, places, and forms of interaction. Conclusion: Important gaps were found in the review, such as a lack of research aimed at the age group most affected by the disorder, who is also the largest consumer of games; and fresh opportunities to expand the understanding of the subject as well as guide developments of game-based therapeutic interventions.

The wide occurrence of resistance to Cry1A and Cry2A insecticidal toxins from Bacillus thuringiensis ( Bt ) in the corn earworm/bollworm Helicoverpa zea (Boddie) leaves the Vip3A toxin produced during the vegetative stage of Bt as the only fully active toxin expressed in transgenic crops to control H. zea in the U.S.A. During 2021, the first unexpected survival of H. zea and injury (UXI) on a maize hybrid expressing Cry1A.105, Cry2Ab2, and Vip3Aa in Louisiana, U.S.A. were observed in two sentinel plots used for resistance monitoring. A follow-up intensive investigation was conducted with two H. zea populations established from larvae collected from the two UXI plots. The main goal of this study was to reveal if the unexpected damage was due to resistance development in the insect to the Bt toxins expressed in the maize hybrid. Diet-overlay bioassays showed that the two populations were highly resistant to Cry1A.105, moderately resistant to Cry2Ab2, but still highly susceptible to Vip3Aa when compared to a reference susceptible strain. In 10 d assays with detached ears, the larvae of the two UXI populations exhibited survival on ears expressing only Cry toxins but presented near 100% mortality on maize hybrids containing both cry and vip3A transgenes. Multiple field trials over three years demonstrated that natural H. zea populations in Louisiana were highly resistant to maize expressing only Cry toxins but remained susceptible to all tested hybrids containing cry and vip3A genes. Altogether, the results of this study suggest that the observed UXIs in Louisiana were associated with a resistance to Cry toxins but were not due to a resistance to Vip3A. The possible causes of the UXIs are discussed. The results generated and procedures adopted in this study help in determining thresholds for defining UXIs, assessing resistance risks, and documenting field resistance.

Cartilage repair after a trauma or a degenerative disease like osteoarthritis (OA) continues to be a big challenge in current medicine due to the limited self-regenerative capacity of the articular cartilage tissues. To overcome the current limitations, tissue engineering and regenerative medicine (TERM) and adjacent areas have focused their efforts on new therapeutical procedures and materials capable of restoring normal tissue functionalities through polymeric scaffolding and stem cell engineering approaches. For this, the sustainable exploration of marine origin materials has emerged in the last years as a natural alternative to mammal sources, benefiting from their biological properties (e.g., biocompatibility, biodegradability, no toxicity, among others) for the development of several types of scaffolds. In this study, marine collagen(jCOL)-chitosan(sCHT)-fucoidan(aFUC)/chondroitin sulfate(aCS) were cryo-processed (-20 °C, -80 °C, and -196 °C) and a chemical-free crosslinking approach was explored to establish cohesive and stable cryogel materials. The cryogels were intensively characterized to assess their oscillatory behavior, thermal structural stability, thixotropic properties (around 45 % for the best formulations), injectability, and surface structural organization. Additionally, the cryogels demonstrate an interesting microenvironment in in vitro studies using human adipose-derived stem cells (hASCs), supporting their viability and proliferation. In both physic-chemical and in vitro studies, the systems that contain fucoidan in their formulations, i.e., C 1 (jCOL, sCHT, aFUC) and C 3 (jCOL, sCHT, aFUC, aCS), submitted at -80 °C, are those that demonstrated most promising results for future application in articular cartilage tissues., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: DSW and AMS are Jellagen Ltd. employees, manufacturers of jellyfish collagen as used in this research., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Contributing to the development of sustainable electroanalytical chemistry, electrochemically reduced graphene oxide (ERGO) films obtained from residual graphite of discharged Zn-C batteries are proposed in this work. Graphite from the cathode of discarded Zn-C batteries was recovered and used in the synthesis of graphene oxide (GO) by the modified Hummer's method. The quality of the synthesized GO was verified using different characterization methods (FT-IR, XRD, SEM, and TEM). GO films were deposited on a glassy carbon electrode (GCE) by the drop coating method and then electrochemically reduced by cathodic potential scanning using cyclic voltammetry. The electrochemical features of the ERGO films were investigated using the ferricyanide redox probe, as well as paracetamol (PAR) and hydroquinone (HQ) molecules as model analytes. From the cyclic voltammetry assays, enhanced heterogeneous electron transfer rate constants (k 0 ) were observed for all redox systems studied. In analytical terms, the ERGO-based electrode showed higher analytical sensitivity than the bare and GO-modified GCE. Using differential pulse voltammetry, wide linear response ranges and limits of detection of 0.14 μmol L -1 and 0.65 μmol L -1 were achieved for PAR and HQ, respectively. Furthermore, the proposed sensor was successfully applied to the determination of PAR and HQ in synthetic urine and tap water samples (recoveries close to 100%). The outstanding electrochemical and analytical properties of the proposed ERGO films are added to the very low cost of the raw material, being presented as a green-based alternative for the development of electrochemical (bio)sensors with unsophisticated resources., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Non-native species are spreading at an unprecedented rate over large spatial scales, with global environmental change and growth in commerce providing novel opportunities for range expansion. Assessing the pattern and rate of spread is key to the development of strategies for safeguarding against future invasions and efficiently managing existing ones. Such assessments often depend on spatial distribution data from online repositories, which can be spatially biased, imprecise, and lacking in quantity. Here, the influence of disparities between occurrence records from online data repositories and what is known of the invasion history from peer-reviewed published literature on non-native species range expansion was evaluated using 6693 records of the Pacific oyster, Magallana gigas (Thunberg, 1793), spanning 56 years of its invasion in Europe. Two measures of spread were calculated: maximum rate of spread (distance from introduction site over time) and accumulated area (spatial expansion). Results suggest that despite discrepancies between online and peer-reviewed data sources, including a paucity of records from the early invasion history in online repositories, the use of either source does not result in significantly different estimates of spread. Our study significantly improves our understanding of the European distribution of M. gigas and suggests that a combination of short- and long-range dispersal drives range expansions. More widely, our approach provides a framework for comparison of online occurrence records and invasion histories as documented in the peer-reviewed literature, allowing critical evaluation of both data sources and improving our understanding of invasion dynamics significantly., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Current management for diabetes has stimulated the development of versatile 3D-based hydrogels as in vitro platforms for insulin release and as support for the encapsulation of pancreatic cells and islets of Langerhans. This work aimed to create agarose/fucoidan hydrogels to encapsulate pancreatic cells as a potential biomaterial for diabetes therapeutics. The hydrogels were produced by combining fucoidan (Fu) and agarose (Aga), marine polysaccharides derived from the cell wall of brown and red seaweeds, respectively, and a thermal gelation process. The agarose/fucoidan (AgaFu) blended hydrogels were obtained by dissolving Aga in 3 or 5 wt % Fu aqueous solutions to obtain different proportions (4:10; 5:10, and 7:10 wt). The rheological tests on hydrogels revealed a non-Newtonian and viscoelastic behavior, while the characterization confirmed the presence of the two polymers in the structure of the hydrogels. In addition, the mechanical behavior showed that increasing Aga concentrations resulted in hydrogels with higher Young's modulus. Further, the ability of the developed materials to sustain the viability of human pancreatic cells was assessed by encapsulation of the 1.1B4HP cell line for up to 7 days. The biological assessment of the hydrogels revealed that cultured pancreatic beta cells tended to self-organize and form pseudo-islets during the period studied.

Bio-based polyols were obtained from the thermochemical liquefaction of two biomass feedstocks, pinewood and Stipa tenacissima , with conversion rates varying between 71.9 and 79.3 wt.%, and comprehensively characterized. They exhibit phenolic and aliphatic moieties displaying hydroxyl (OH) functional groups, as confirmed by attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) and nuclear magnetic resonance spectroscopy (NMR) analysis. The biopolyols obtained were successfully employed as a green raw material to produce bio-based polyurethane (BioPU) coatings on carbon steel substrates, using, as an isocyanate source, a commercial bio-based polyisocyanate-Desmodur ® Eco N7300. The BioPU coatings were analyzed in terms of chemical structure, the extent of the reaction of the isocyanate species, thermal stability, hydrophobicity, and adhesion strength. They show moderate thermal stability at temperatures up to 100 °C, and a mild hydrophobicity, displaying contact angles between 68° and 86°. The adhesion tests reveal similar pull-off strength values (ca. 2.2 MPa) for the BioPU either prepared with pinewood and Stipa -derived biopolyols (BPUI and BPUII). Electrochemical impedance spectroscopy (EIS) measurements were carried out on the coated substrates for 60 days in 0.05 M NaCl solution. Good corrosion protection properties were achieved for the coatings, with particular emphasis on the coating prepared with the pinewood-derived polyol, which exhibited a low-frequency impedance modulus normalized for the coating thickness of 6.1 × 10 10 Ω cm at the end of the 60 days test, three times higher than for coatings prepared with Stipa -derived biopolyols. The produced BioPU formulations show great potential for application as coatings, and for further modification with bio-based fillers and corrosion inhibitors.

Fucoidan has been reported to present diverse bioactivities, but each extract has specific features from which a particular biological activity, such as immunomodulation, must be confirmed. In this study a commercially available pharmaceutical-grade fucoidan extracted from Fucus vesiculosus , FE, was characterized and its anti-inflammatory potential was investigated. Fucose was the main monosaccharide (90 mol%) present in the studied FE, followed by uronic acids, galactose, and xylose that were present at similar values (3.8-2.4 mol%). FE showed a molecular weight of 70 kDa and a sulfate content of around 10%. The expression of cytokines by mouse bone-marrow-derived macrophages (BMDMs) revealed that the addition of FE upregulated the expression of CD206 and IL-10 by about 28 and 22 fold, respectively, in respect to control. This was corroborated in a stimulated pro-inflammatory situation, with the higher expression (60 fold) of iNOS being almost completely reversed by the addition of FE. FE was also capable of reverse LPS-caused inflammation in an in vivo mouse model, including by reducing macrophage activation by LPS from 41% of positive CD11C to 9% upon fucoidan injection. Taken together, the potential of FE as an anti-inflammatory agent was validated, both in vitro and in vivo.

Gastric cancer is a dominating cause of cancer-associated mortality with limited therapeutic options. Here, we show that syndecan-4 (SDC4), a transmembrane proteoglycan, is highly expressed in intestinal subtype gastric tumors and that this signature associates with patient poor survival. Further, we mechanistically demonstrate that SDC4 is a master regulator of gastric cancer cell motility and invasion. We also find that SDC4 decorated with heparan sulfate is efficiently sorted in extracellular vesicles (EVs). Interestingly, SDC4 in EVs regulates gastric cancer cell-derived EV organ distribution, uptake, and functional effects in recipient cells. Specifically, we show that SDC4 knockout disrupts the tropism of EVs for the common gastric cancer metastatic sites. Our findings set the basis for the molecular implications of SDC4 expression in gastric cancer cells and provide broader perspectives on the development of therapeutic strategies targeting the glycan-EV axis to limit tumor progression.