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The synthesis and application of multifunctional diazirine-containing polymers for on-demand cross-linking of unfunctionalized commodity polymers through C-H bond insertion is demonstrated. While small-molecule diazirine cross-linkers have seen important applications such as plastic compatibilization and photopatterning, the high degree of functionalization of polymer-based diazirine cross-linkers offers promise for enhanced compatibility based on polymer blending and increased efficiency due to controllable multivalency. As a demonstrative example, unfunctionalized linear poly(n-butyl acrylate) (PnBA) can be cross-linked using various polymeric cross-linkers with diazirine contents as low as 0.8 wt % in 1 min under photochemical conditions. With gel fractions up to 95%, tunable rheological behavior is observed with increasing cross-linker loadings, consistent with a transition from entangled branched polymers to a cross-linked network. Moreover, the synthetic stability of the diazirine units can be exploited to prepare diazirine-containing polymers based on a variety of different backbones, from vinyl copolymers to poly(dimethylsiloxane) (PDMS), which allows successful photopatterning using a commercial 3D printer.

Surface gel layers on commercially available contact lenses have been shown to reduce frictional shear stresses and mitigate damage during sliding contact with fragile epithelial cell layers in vitro. Spencer and co-workers recently demonstrated that surface gel layers could arise from oxygen-inhibited free-radical polymerization. In this study, polyacrylamide hydrogel shell probes (7.5 wt % acrylamide, 0.3 wt % N,N'-methylenebisacrylamide) were polymerized in three hemispherical molds listed in order of decreasing surface energy and increasing oxygen permeability: borosilicate glass, polyether ether ketone (PEEK), and polytetrafluoroethylene (PTFE). Hydrogel probes polymerized in PEEK and PTFE molds exhibited 100× lower elastic moduli at the surface (EPEEK* = 80 ± 31 and EPTFE* = 106 ± 26 Pa, respectively) than those polymerized in glass molds (Eglass* = 31,560 ± 1,570 Pa), in agreement with previous investigations by Spencer and co-workers. Biotribological experiments revealed that hydrogel probes with surface gel layers reduced frictional shear stresses against cells (τPEEK = 35 ± 15 and τPTFE = 22 ± 16 Pa) more than those without (τglass = 68 ± 15 Pa) and offered greater protection against cell damage when sliding against human telomerase-immortalized corneal epithelial (hTCEpi) cell monolayers. Our work demonstrates that the "mold effect" resulting in oxygen-inhibition polymerization creates hydrogels with surface gel layers that reduce shear stresses in sliding contact with cell monolayers, similar to the protection offered by gradient mucin gel networks across epithelial cell layers.

We demonstrate the utility of block polyelectrolyte (bPE) additives to enhance viscosity and resolve challenges with the three-dimensional (3D) printability of extrusion-based biopolymer inks. The addition of oppositely charged bPEs to solutions of photocurable gelatin methacryloyl (GelMA) results in complexation-driven self-assembly of the bPEs, leading to GelMA/bPE inks that are printable at physiological temperatures, representing stark improvements over GelMA inks that suffer from low viscosity at 37 °C, leading to low printability and poor structural stability. The hierarchical microstructure of the self-assemblies (either jammed micelles or 3D networks) formed by the oppositely charged bPEs, confirmed by small-angle X-ray scattering, is attributed to the enhancements in the shear strength and printability of the GelMA/bPE inks. Varying bPE concentration in the inks is shown to enable tunability of the rheological properties to meet the criteria of pre- and postextrusion flow characteristics for 3D printing, including prominent yielding behavior, strong shear thinning, and rapid recovery upon flow cessation. Moreover, the bPE self-assemblies also contribute to the robustness of the photo-cross-linked hydrogels; photo-cross-linked GelMA/bPE hydrogels are shown to exhibit higher shear strength than photo-cross-linked GelMA hydrogels. Last, the assessment of the printability of GelMA/bPE inks indicates excellent printing performance, including minimal swelling postextrusion, satisfactory retention of the filament shape upon deposition, and satisfactory shape fidelity of the various printed constructs. We envision this study to serve as a practical guide for the printing of bespoke extrusion inks where bPEs are used as scaffolds and viscosity enhancers that can be emulated in a range of photocurable precursors.

The diversity of topics in education makes it difficult for artificial intelligence (AI) to address them all in depth. Therefore, guiding to focus efforts on specific issues is essential. The analysis of competency development by fostering collaboration should be one of them because competencies are the way to validate that the educational exercise has been successful and because collaboration has proven to be one of the most effective strategies to improve performance outcomes. This systematic review analyzes the relationship between AI, competency development, and collaborative learning (CL). PRISMA methodology is used with data from the SCOPUS database. A total of 1,233 articles were found, and 30 passed the inclusion and exclusion criteria. The analysis of the selected articles identified three categories that deserve attention: the objects of study, the way of analyzing the results, and the types of AI that could be used. In this way, it has been possible to determine the relationship offered by the studies between skill development and CL and ideas about AI's contributions to this field. Overall, however, the data from this systematic review suggest that, although AI has great potential to improve education, it should be approached with caution. More research is needed to fully understand its impact and how best to apply this technology in the classroom, minimizing its drawbacks, which may be relevant, and making truly effective and productive use of it.

Abstract Tumor metabolism is a crucial aspect of cancer development, and mitochondria plays a significant role in the aggressiveness and metastasis of tumors. As a result, mitochondria have become a promising therapeutic target in cancer treatment, leading to the development of compounds known as mitocans. In our group, we have consolidated the search of anticancer therapies based on natural products derived from plants, obtaining extracts such as P2Et from Caesalpinia spinosa and Anamu-SC from Petiveria alliacea, which have been shown to have antitumor activities in different cancer models. These extracts, due to their complex molecular composition, can interfere with multiple functions during tumor progression. To better understand how these natural products operate (P2Et and Anamu-SC), we constructed a model using 4T1 murine breast cancer cells with reduced expression of genes associated with glycolysis (Hexokinase-2) and mitochondrial function (Cqbp). The results indicate that the cells were more sensitive to the Anamu-SC extract, showing significant decreases in glucose consumption, ATP production, and oxygen consumption rate. Additionally, we observed changes in mitochondrial function, which reduced the cells’ ability to migrate, particularly when C1qbp was silenced. This triple-negative breast cancer model allows us to identify potential natural products that can modulate tumor cell metabolism.

Seasonal influenza significantly affects both health and economic costs in children and adults. This narrative review summarizes published cost-effectiveness analyses (CEAs) of cell-based influenza vaccines in children and adults

Resumen: La aparición de una complicación mecánica posterior a un infarto agudo de miocardio con elevación del ST actualmente es infrecuente, siendo las más comunes la ruptura de músculo papilar, la ruptura de la pared libre del ventrículo, la ruptura del septum ventricular o la aparición de una dilatación aneurismática del ventrículo. Presentamos un paciente con infarto agudo de miocardio con elevación del segmento ST que cursó con dos complicaciones mecánicas concomitantes a las cuales se les realizó corrección quirúrgica. Paciente masculino de 63 años con antecedentes de hipertensión y tabaquismo presentó cuadro clínico de dolor precordial con reporte de electrocardiograma con elevación del segmento ST. En el ecocardiograma transtorácico se evidencia comunicación interventricular y FEVI 51%. El cateterismo cardiaco evidencia enfermedad coronaria de dos vasos. Se decidió manejo quirúrgico para cierre de la comunicación interventricular y revascularización. Durante el procedimiento quirúrgico se evidenció una dilatación aneurismática del ventrículo izquierdo, la cual se reparó con parche del pericardio. Finalmente, después de compensación de falla cardiaca secundaria a shock séptico por infección de vías urinarias, se le dio alta médica. Las complicaciones mecánicas que se pueden presentar posterior a un infarto agudo de miocardio siguen siendo una preocupación importante debido a que pueden presentarse días o semanas después del evento coronario y pueden causar la muerte, por tal razón se debe realizar vigilancia continua de los pacientes. La decisión de intervenir quirúrgicamente al paciente para su respectiva corrección debe sopesar el riesgo-beneficio. Abstract: The occurrence of a mechanical complication following an acute myocardial infarction with ST-segment elevation is currently uncommon, with the most common being papillary muscle rupture, free wall rupture of the ventricle, ventricular septal rupture, or the development of an aneurysmal dilation of the ventricle. We present a 63-year-old male patient with acute myocardial infarction with ST-segment elevation who developed two concomitant mechanical complications, both of which underwent surgical correction. The patient had a history of hypertension and smoking, and presented with clinical symptoms of precordial pain along with an electrocardiogram showing ST-segment elevation. Transthoracic echocardiogram revealed a ventricular septal defect and an ejection fraction of 51%. Cardiac catheterization indicated two-vessel coronary disease. Surgical management was decided for closure of the ventricular septal defect and revascularization. During the surgical procedure, an aneurysmal dilation of the left ventricle was observed and repaired using a pericardial patch. Finally, after compensating for heart failure secondary to septic shock from a urinary tract infection, the patient was discharged. Mechanical complications following an acute myocardial infarction remain a significant concern as they can occur days or weeks after the coronary event and may lead to death. Therefore, continuous monitoring of patients is crucial. The decision to surgically intervene for correction should weigh the risk-benefit ratio.

This research delves into the multifaceted challenges posed to society and regional development in the wake of Russia's invasion of Ukraine, with a specific focus on the period spanning from February 2022 to February 2023 as a response to the social and entrepreneurial threats that have appeared due to the conflict. In addition, this research seeks not only to alleviate prevailing uncertainties but also to facilitate a comprehensive understanding of the economic landscape by identifying causal factors and providing a relevant contextual framework for the threats to society and regional development in the aftermath of Russia's invasion of Ukraine, which affects sustainability both economically and socially. These disruptions have given rise to unprecedented uncertainties that could potentially trigger an irreversible cascade of shortages, leading to escalating costs of critical or irreplaceable products that directly affect regional development. This paper scrutinizes this intricate process, aiming to discern underlying patterns and mitigate the prevailing uncertainty—a state that challenges rational decision-making. In this pursuit, established economic theories are deployed to provide comprehensive insights into the evolving reality. Through an in-depth analysis of the interplay between the Covid-19 pandemic, the ensuing economic crisis, and the ramifications of the Ukraine-Russia conflict, this research reveals a stark decline in economic growth. In addition, the present study explores potential solutions, emphasizing the importance of enhancing workforce skills through meticulously designed educational strategies and promoting gender diversity in science, technology, engineering and mathematics (STEM) programs.

Abstract Background The burden of antimicrobial resistance (AMR) in Latin America is high. Little is known about healthcare workers’ (HCWs) knowledge, attitudes, and perceptions of antimicrobial stewardship (AS), AMR, and antibiotic use (AU) in the region. Methods HCWs from 42 hospitals from 5 Latin American countries were invited to take an electronic, voluntary, anonymous survey regarding knowledge, attitudes, and perceptions of AS, AMR, and AU between March–April 2023. Findings Overall, 996 HCWs completed the survey (52% physicians, 32% nurses, 11% pharmacists, 3% microbiologists, and 2% “other”). More than 90% of respondents indicated optimizing AU was a priority at their healthcare facility (HCF), 69% stated the importance of AS was communicated at their HCF, and 23% were unfamiliar with the term “antibiotic stewardship”. Most (> 95%) respondents acknowledged that appropriate AU can reduce AMR; however, few thought AU (

Objetivo. Construir y comparar el ranking de los programas nacionales de inmunizaciones (PNI) de América Latina del año 2020 con el año anterior. Métodos. Se evaluaron 18 PNI con base en la información pública obtenida de sitios oficiales de los ministerios de salud de los países, la Organización Mundial de la Salud, la Organización Panamericana de la Salud, el Fondo de las Naciones Unidas para la Infancia y referentes locales. El ranking se elaboró con base en el calendario de vacunación del año 2020 en distintas etapas de la vida, situaciones especiales, vacunación antigripal, coberturas vacunales (CV) del 2019 y aspectos programáticos. Resultados. Las CV disminuyeron en la mayoría de los países. El puntaje promedio regional y de la mayoría de los países también bajó en el 2020 excepto en Chile y Colombia. Chile lidera el ranking, seguido por Uruguay, Panamá y Costa Rica, y se destaca por su calendario completo, mayores CV y logros programáticos. Conclusiones. El menor puntaje global del 2020 resalta que es necesario recuperar la CV en la Región. Este análisis busca motivar a los países a abordar los desafíos pendientes.

Abstract Background Dual point-of-care tests (POCTs) for the simultaneous detection of antibodies to HIV and syphilis have been developed. Since community-based organisations (CBO) are effective providers of HIV and syphilis testing among men who have sex with men (MSM), evaluation of the utility of these dual tests at CBO testing services is a high priority. The aim of this study is to determine the feasibility of performing dual HIV-syphilis POCT testing among both users and providers at these non-clinical sites. Methods This evaluation assessed the utility of two lateral flow immunochromatographic antibody technologies for dual screening for HIV/syphilis among MSM seeking testing in four CBO testing services in Spain, Slovenia, Latvia, and Ukraine. The study’s conceptual framework divides the concept of feasibility into two inter-related domains, acceptability, and usability and further breaks it down into six subdomains: learnability, willingness, suitability, satisfaction, efficacy, and effectiveness. The feasibility analysis was performed by calculating the median score in 3 stages (for individual questions, subdomains, and domains), using a summated scores method. Results The final sample included 844 participants, 60 of which were found to be HIV test positive (7.1%) and 61 (7.2%) positive on testing for syphilis. There was a small difference (1.1%) when comparing the results of the two dual POCTs under evaluation to the tests routinely used at each site. The inter-rater agreement showed a high concordance between two independent readings. The analysis of the feasibility for the users of the services indicated good satisfaction, suitability, and willingness. In addition, among 18 providers the total mean score showed good acceptability and usability, good willingness, easy learnability, high suitability, and good efficacy, but lower satisfaction and effectiveness. The operational characteristics of both dual study POCTs were well evaluated by providers. Conclusions The introduction of dual HIV and syphilis POCTs in CBO testing services for screening of MSM is feasible, with a high acceptability and usability both for users and providers. Implementation of dual POCTs for HIV and syphilis in CBO testing services is an opportunity for scaling up integrated HIV/syphilis testing for MSM.

Introducing an innovation does not end, but rather starts, with adoption. In fact, some innovations display network elements and require more than one firm to take them up in order to be successful and deliver the intended results. Such is the case of NDC (new distribution capability), an airline-fostered enhancement of the way air travel services are conveyed and distributed from carriers to travel agents. The promise behind NDC is that travel services will be sold more richly and within a more open and inclusive framework. We draw on the diffusion of innovations, institutional theory, and agency theory to review the determinants of adoption and its effects on performance for service providers. We use the International Air Transport Association (IATA) ticket database to establish the role that institutional pressure plays on innovation behaviours and firms’ results. We find that institutional pressure, not just innovation attributes, influence outcomes. Also, given each player's different incentives and the asymmetry of information, ticket sales are selectively distributed in ways that fit the agent and only occasionally the airline principal. Thus, we conclude that travel intermediaries assess outcomes wholistically and that the innovation's revenue uplift depends on such assessment.

The formation of metamorphic zircon after baddeleyite is a well-known reaction that can be used to date the metamorphism of igneous silica-undersaturated rocks. By contrast, metamorphic minerals formed after igneous zirconolite have rarely been reported. In this paper, we document metamorphic titanite + zircon pseudomorphs formed from the metamorphic breakdown of igneous zirconolite in syenodiorite and syenite, in the southeastern Sveconorwegian Province, Sweden. Water-rich fluid influx during tectonometamorphism in epidote–amphibolite-facies metamorphic conditions caused the release of silica during a metamorphic reaction involving igneous feldspar and pyroxene and the simultaneous breakdown of igneous Zr-bearing phases. Typical titanite + zircon intergrowths are elongated or platy titanite crystals speckled with tiny inclusions of zircon. Most intergrowths are smaller than 15 µm; some are subrounded in shape. Locally, bead-like grains of titanite and zircon are intergrown with silicate minerals. The precursor igneous zirconolite was found preserved only in a sample of near-pristine igneous syenodiorite, as remnant grains of mainly < 2 µm in size. Two somewhat larger crystals, 8 and 12 µm, allowed semiquantitative confirmation using microprobe analysis. Analogous with zircon pseudomorphs after baddeleyite, titanite + zircon pseudomorphs after zirconolite potentially offer dating of the metamorphic reaction, although the small size of the crystals makes dating with today's techniques challenging. The scarcity of reports of zirconolite and pseudomorphs reflects that they are either rare or possibly overlooked.

Abstract Background Chemotherapy in breast cancer is effective but can generate significant toxicity and lead to tumor resistance. Joint treatment with standardized plant extracts can be an alternative to improve the response and allow an effective activation of the antitumor immune response that favors recovery in the short and long term. The P2Et extract of Caesalpinia spinosa presents antitumor activity in cells and animal models of breast cancer, improves the tumor microenvironment, and induces activation of the specific immune response against the tumor and is synergistic when used together with anthracyclines, which makes it a good candidate for evaluation in patients. Methods Conducted at a single center, this phase II study is a randomized, double-blind, placebo-controlled trial aimed at assessing the safety and efficacy of P2Et extract in patients diagnosed with stage II and III breast cancer, who are eligible for neoadjuvant treatment. The study aims to determine the safety profile at the previously established optimal biological dose from phase I trial while investigating various efficacy outcomes. These outcomes include improvements in quality of life, immunomodulation, metabolic profile, microbiome, as well as clinical indicators such as tumor reduction, disease-free survival, and pathological response, assessed at different stages of the treatment regimen. Discussion Treatment with the P2Et extract in breast cancer patients is hypothesized to enhance overall well-being, positively influencing their quality of life, while also triggering an antitumor immune response and enhancing immune infiltration. These combined effects have the potential to contribute to improved long-term survival outcomes for patients receiving the phytomedicine alongside neoadjuvant chemotherapy treatment. Trial registration This trial was registered in the US National Library of Medicine with identifier NCT05007444. First Registered August 16th, 2021. Last Updated: August 9th, 2022.

La utilización de redes sociales por los estudiantes de educación media de los colegios de la Policía Nacional en Bogotá, incluye, la identificación de posibles vacíos en temas de ciberseguridad, pese a programas y estrategias relacionadas con el uso responsable al navegar por el ciberespacio. Esta investigación se sustenta en el paradigma comprensivo- interpretativo (sociológico) con un enfoque mixto de preponderancia cualitativa. Se realizó una revisión documental, encuesta a estudiantes y entrevista en profundidad a padres de familia y docentes. Se agruparon los hallazgos en dos categorías; ciberseguridad y educación. Los resultados de la encuesta evidenciaron una hiper- conectividad por parte de los estudiantes; la interacción realizada a través de las redes sociales, especialmente mediante el intercambio de fotos, videos, compartir estados y hacer video llamadas. Los hallazgos de la entrevista expresan que, si bien cada establecimiento educativo es autónomo, no es claro entre padres de familia, cuidadores y docentes una ruta expresamente definida a seguir al momento de evidenciar peligros emergentes al uso evidenciado en redes sociales. También falta mayor corresponsabilidad al identificar ciertos tipos de conductas que atentan contra los estudiantes, dado que algunos padres consideran que es un tema del cual debe encargarse el colegio, mientras que los docentes discurren que es compromiso de los padres. En conclusión, se deja al descubierto, la necesidad de valorar el grado de aceptación, efectividad y alcance de estrategias desarrolladas por colegios y entes privados o gubernamentales, respecto a la sensibilización en temas de ciberseguridad y uso responsable al navegar en internet.

Abstract Background The energy metabolism of drug-resistant tumor cells can provide a survival advantage during therapy, and treatment itself may influence metabolic reprogramming. Petiveria alliacea (Traditional name: Anamu) could inhibit glycolysis and OXPHOX modulating tumor metabolism, making it a potential treatment for tumors with altered metabolism. This clinical study aims to evaluate the safety and efficacy of a standardized Anamu phytomedicine called Esperanza in treating gastric tumors and acute leukemias. Methods This is a prospective, open label, phase I/ randomized, double-blind single-center phase II study designed to evaluate the safety and efficacy of Esperanza extract in patients with metastatic gastrointestinal tumors and acute leukemias. In stage 1, the study will determine the MTD and assess safety. In stage 2, safety at the MTD will be evaluated, and the efficacy of Esperanza extract will be explored in both metastatic gastric tumors and acute leukemias. Quality of life improvement will be the primary outcome in the gastric tumor group, while different efficacy outcomes will be assessed in the acute leukemia group. A placebo group will be used for comparison in the gastric tumor group, and a historical control group will be used in the acute leukemia arm. Discussion This clinical trial aims to evaluate the safety profile of the Esperanza extract in patients with metastatic gastrointestinal tumors and acute leukemias, while exploring its potential efficacy in conjunction with standard treatment for these pathologies. Trial registration This trial was registered in the US National Library of Medicine with identifier NCT05587088. Registered October 19th, 2022.

Este artículo busca problematizar los cimientos intelectuales que sustentan la gobernanza global de la corrupción a través de un método de la narrativa, según el cual las reglas informales o burocracias formales crean marcos de comprensión dentro de los cuales la gente piensa y actúa, para escribir una narrativa que permita argumentar acerca de las influencias y los resultados de la construcción del régimen internacional anticorrupción. Se concluye que, a pesar de que la narrativa hegemónica de la gobernanza neoliberal logró institucionalizarse en los diferentes instrumentos internacionales aprobados, su fase de internalización ha exhibido problemas para asentar su legitimidad. Un enfoque estructural, de configuración en red y que problematice los límites entre lo público/privado y lo legal/ilegal es requerido para repensar la crisis actual por la que atraviesa la norma global anticorrupción.

The decline in Acropora palmata populations in Colombian reefs has been mainly attributed to diseases outbreaks. The population size structure and prevalence of white pox and white band disease were evaluated in six localities of the Colombian Caribbean. Here, we aimed to isolate enteric bacteria and Vibrios from healthy and diseased coral mucus to relate its presence to the health status of Acropora palmata. The isolated bacteria were identified using molecular analyses with the 16S rRNA gene. Larger colonies had the highest percentage of the prevalence of both diseases. The strains that were identified as Vibrio sp. and Bacillus sp. were common in the healthy and diseased mucus of the holobiont. The Exiguobacterium sp. and Cobetia sp. strains isolated from diseased mucus may indicate maintenance and resilience mechanisms in the coral. Enterococcus sp. and other bacteria of the Enterobacteriaceae family were isolated from some localities, suggesting that probably contamination due to poor treatment of domestic wastewater and contributions from river discharges can affect coral health. The spatial heterogeneity of Colombian coral reefs exhibited variability in the bacteria, wherein environmental alterations can trigger signs of disease.

Abstract Background People living with HIV (PLWH) face structural and psychosocial factors that affect health-related quality of life (HRQoL). We aimed to evaluate how syndemic conditions affected HRQoL in PLWH. Methods A cross-sectional survey was conducted among 861 PLWH, to determine whether syndemic conditions (monthly income; sexual satisfaction; depressive symptoms; social role satisfaction; social isolation; cognitive function; nicotine dependence; perception of stigma) have an effect on HRQoL. A linear regression model and measures of Additive Interaction (AI) were used to determine the effects of syndemic conditions on HRQoL, controlling for other risk factors. Results Overall, the most frequently observed were stigma perception (56.9%), poor cognitive function (50.6%) and the perception of social isolation (51.6%). The presence of depressive symptoms was the risk factor most associated with worse Physical Health (PH) (B 3.93, 2.71–5.15) and Mental Health (MH) (B 5.08, 3.81–6.34) in linear regression model. Specifically, an interaction was observed between poor cognitive function and poor satisfaction with social role on worse PH and MH (AI 2.08, 0.14–4.02; AI 2.69, 0.15–5.22, respectively); and low income and perception of stigma (AI 2.98, 0.26–5.71), low income and perception of social isolation (AI 2.79, 0.27–5.32), and low income and poor satisfaction with social role (AI 3.45, 0.99–5.91) on MH. Conclusion These findings provide evidence that syndemic factors impact HRQoL. HIV prevention programs should screen and address co-occurring health problems to improve patient-centered health care and outcomes.

Objectives To perform a budget impact analysis of the HepClink test-and-treat strategy in which community health agents offer hepatitis C virus (HCV) testing, diagnosis and treatment to the Pakistani population living in Catalonia compared with the current practice of the Catalan health system (without targeted screening programmes).Methods We estimated the population of adult Pakistani migrants registered at the primary care centres in Catalonia by means of the Information System for the Development of Research in Primary Care (n=37 972 in 2019, Barcelona health area). This cohort was followed for a time period of 10 years after HCV diagnosis (2019–2028). The statistical significance of the differences observed in the anti-HCV positivity rate between screened and non-screened was confirmed (α=0.05). The budget impact was calculated from the perspective of the Catalan Department of Health. Sensitivity analyses included different levels of participation in HepClink: pessimistic, optimistic and maximum.Results The HepClink scenario screened a higher percentage of individuals (69.8%) compared with the current scenario of HCV care (39.7%). Viraemia was lower in the HepClink scenario compared with the current scenario (1.7% vs 2.5%, respectively). The budget impact of the HepClink scenario was €884 244.42 in 10 years.Conclusions Scaling up the HepClink strategy to the whole Catalan territory infers a high budget impact for the Department of Health and allows increasing the detection of viraemia (+17.8%) among Pakistani migrants ≥18 years. To achieve a sustainable elimination of HCV by improving screening and treatment rates, there is room for improvement at two levels. First, taking advantage of the fact that 68.08% of the Pakistani population had visited their primary care physicians to reinforce targeted screening in primary care. Second, to use HepClink at the community level to reach individuals with reluctance to use healthcare services.

The Covid-19 infection outbreak led to a global epidemic, and although several vaccines have been developed, the appearance of mutations has allowed the virus to evade the immune response. Added to this is the existing risk of the appearance of new emerging viruses. Therefore, it is necessary to explore novel antiviral therapies. Here, we investigate the potential in vitro of plant extracts to modulate cellular stress and inhibit murine hepatitis virus (MHV)-A59 replication. L929 cells were treated with P2Et (Caesalpinia spinosa) and Anamu SC (Petiveria alliacea) plant extracts during infection and virus production, ROS (reactive oxygen species), UPR (unfolded protein response), and autophagy were assessed. P2Et inhibited virus replication and attenuated both ROS production and UPR activation induced during infection. In contrast, the sustained presence of Anamu SC during viral adsorption and replication was required to inhibit viral infection, tending to induce pro-oxidant effects, and increasing UPR gene expression. Notably, the loss of the PERK protein resulted in a slight decrease in virus yield, suggesting a potential involvement of this UPR pathway during replication. Intriguingly, both extracts either maintained or increased the calreticulin surface exposure induced during infection. In conclusion, our findings highlight the development of antiviral natural plant extracts that differentially modulate cellular stress.

Although herbal drugs are often considered safe for consumption, there is increasing evidence that some can generate undesirable health effects. However, polyphenols found in certain plants have been shown to provide a range of benefits for human health. In previous work, a standardized and quantified extract (P2Et) obtained from Caesalpinia spinosa (Dividivi) plant showed promising antioxidant, immunomodulatory, and anti-inflammatory properties in animal models of cancer and COVID-19 patients. The extract has also been subjected to genotoxicity, mutagenicity, and 28-day oral chronic toxicity evaluations, demonstrating a good safety profile. To advance preclinical and clinical development, further acute and chronic toxicity evaluations of the P2Et extract were performed. Acute toxicity tests were performed orally in Wistar rats at a dose of 2000 mg/kg, indicating that the lethal dose 50% (LD50) value exceeded 2000 mg/kg and classifying the P2Et extract as category 5 according to the Globally Harmonized System of Classification (GHS). In this work, chronic toxicity tests were conducted for 180 days on Wistar rats and New Zealand rabbits at a dose of 1000 mg/kg under Good Laboratory Practice (GLP) conditions. No weight loss or alterations in biochemical and hematological parameters associated with treatment were observed in the animals, suggesting the absence of toxicity in the assessed parameters. These results indicate that the P2Et extract is safe for oral administration at doses up to 1000 mg/kg body weight over a six-month period.