Partner or perish: tree microbiomes and climate change.

Understanding the complex relationships between plants, their microbiomes, and environmental changes is crucial for improving growth and survival, especially for long-lived tree species. Trees, like other plants, maintain close associations with a multitude of microorganisms on and within their tissues, forming a 'holobiont'. However, a comprehensive framework for detailed tree-microbiome dynamics, and the implications for climate adaptation, is currently lacking. This review identifies gaps in the existing literature, emphasizing the need for more research to explore the coevolution of the holobiont and the full extent of climate change impact on tree growth and survival. Advancing our knowledge of plant-microbial interactions presents opportunities to enhance tree adaptability and mitigate adverse impacts of climate changes on trees.

[The role of the nurse in the field of public health]. / El rol de la enfermería en el ámbito de la salud pública.

OBJECTIVE: Identify the role of public health nurses and differentiate it from that of community care nurses in the context of Catalonia, through the experiences and perspectives of professionals in the field of public health. METHOD: Descriptive phenomenological qualitative study. Fourteen interviews were conducted with key informants, from the field of public health and community care, selected by i purposive sampling. Content analysis using thematic methodology, creation of categories from the triangulation of results. RESULTS: The professional competencies and functions performed by nursing in the field of public health are analysed. Most of the specific functions were the ones related to "care" and the "global vision" of health. The indeterminacy of functions and roles, related to gender inequality, leads to a low recognition of the profession and a lack of appropriateness of the professional category, reflected in a low presence of nurses in management positions in public health. Although some competencies are shared with the family and community nurse, there are also differences. CONCLUSIONS: This study sheds light on the role of public health nursing, often overlooked. It is urgent to define public health nurses role and functions, in order to avoid inequalities and increase their recognition.

Design of new Mcl-1 inhibitors for cancer using fragments hybridization, molecular docking, and molecular dynamics studies.

Apoptosis is a critical process that regulates cell survival and death and plays an essential role in cancer development. The Bcl-2 protein family, including myeloid leukemia 1 (Mcl-1), is a key regulator of the intrinsic apoptosis pathway, and its overexpression in many human cancers has prompted efforts to develop Mcl-1 inhibitors as potential anticancer agents. In this study, we aimed to design new Mcl-1 inhibitors using various computational techniques. First, we used the Mcl-1 receptor-ligand complex to build an e-pharmacophore hypothesis and screened a library of 567,000 fragments from the Enamine database. We obtained 410 fragments and used them to design 92,384 novel compounds, which we then docked into the Mcl-1 binding cavity using HTVS, SP, and XP docking modes of Glide. To assess their suitability as drug candidates, we conducted MM-GBSA calculations and ADME prediction, leading to the identification of 10 compounds with excellent binding affinity and favorable pharmacokinetic properties. To further investigate the interaction strength, we performed molecular dynamics simulations on the top three Mcl-1 receptor-ligand complexes to study their interaction stability. Overall, our findings suggest that these compounds have promising potential as anticancer agents, pending further experimental validation such as Mcl-1 apoptosis Assay. By combining experimental methods with various in silico approaches, these techniques prove to be invaluable for identifying novel drug candidates with distinct therapeutic applications using fragment-based drug design. This methodology has the potential to expedite the drug discovery process while also reducing its costs.Communicated by Ramaswamy H. Sarma.

Present and future of resistance in Pseudomonas aeruginosa: implications for treatment.

Pseudomonas aeruginosa is a pathogen that has a high propensity to develop antibiotic resistance, and the emergence of multidrug-resistant strains is a major concern for global health. The mortality rate associated with infections caused by this microorganism is significant, especially those caused by multidrug-resistant strains. The antibiotics used to treat these infections include quinolones, aminoglycosides, colistin, and ß-lactams. However, novel combinations of ß-lactams-ß-lactamase inhibitors and cefiderocol offer advantages over other members of their family due to their better activity against certain resistance mechanisms. Selecting the appropriate empiric antibiotic treatment requires consideration of the patient's clinical entity, comorbidities, and risk factors for multidrug-resistant pathogen infections, and local epidemiological data. Optimizing antibiotic pharmacokinetics, controlling the source of infection, and appropriate collection of samples are crucial for successful treatment. In the future, the development of alternative treatments and strategies, such as antimicrobial peptides, new antibiotics, phage therapy, vaccines, and colonization control, holds great promise for the management of P. aeruginosa infections.

Molecular Docking and Molecular Dynamics Studies Reveal the Anticancer Potential of Medicinal-Plant-Derived Lignans as MDM2-P53 Interaction Inhibitors.

The interaction between the tumor suppressor protein p53 and its negative regulator, the MDM2 oncogenic protein, has gained significant attention in cancer drug discovery. In this study, 120 lignans reported from Ferula sinkiangensis and Justicia procumbens were assessed for docking simulations on the active pocket of the MDM2 crystal structure bound to Nutlin-3a. The docking analysis identified nine compounds with higher docking scores than the co-crystallized reference. Subsequent AMDET profiling revealed satisfactory pharmacokinetic and safety parameters for these natural products. Three compounds, namely, justin A, 6-hydroxy justicidin A, and 6'-hydroxy justicidin B, were selected for further investigation due to their strong binding affinities of -7.526 kcal/mol, -7.438 kcal/mol, and -7.240 kcal/mol, respectively, which surpassed the binding affinity of the reference inhibitor Nutlin-3a (-6.830 kcal/mol). To assess the stability and reliability of the binding of the candidate hits, a molecular dynamics simulation was performed over a duration of 100 ns. Remarkably, the thorough analysis demonstrated that all the hits exhibited stable molecular dynamics profiles. Based on their effective binding to MDM2, favorable pharmacokinetic properties, and molecular dynamics behavior, these compounds represent a promising starting point for further refinement. Nevertheless, it is essential to synthesize the suggested compounds and evaluate their activity through in vitro and in vivo experiments.

Modulation of NRF2/KEAP1-Mediated Oxidative Stress for Cancer Treatment by Natural Products Using Pharmacophore-Based Screening, Molecular Docking, and Molecular Dynamics Studies.

Oxidative stress plays a significant role in the development of cancer. Inhibiting the protein-protein interaction (PPI) between Keap1 and Nrf2 offers a promising strategy to activate the Nrf2 antioxidant pathway, which is normally suppressed by the binding of Keap1 to Nrf2. This study aimed to identify natural compounds capable of targeting the kelch domain of KEAP1 using structure-based drug design methods. A pharmacophore model was constructed based on the KEAP1-inhibitor complex, leading to the selection of 6178 compounds that matched the model. Subsequently, docking and MM/GBSA analyses were conducted, resulting in the identification of 10 compounds with superior binding energies compared to the reference compound. From these, three compounds (ZINC000002123788, ZINC000002111341, and ZINC000002125904) were chosen for further investigation. Ligand-residue interaction analysis revealed specific interactions between these compounds and key residues, indicating their stability within the binding site. ADMET analysis confirmed that the selected compounds possessed desirable drug-like properties. Furthermore, molecular dynamics simulations were performed, demonstrating the stability of the ligand-protein complexes over a 100 ns duration. These findings underscore the potential of the selected natural compounds as agents targeting KEAP1 and provide valuable insights for future experimental studies.

Unlocking the potential of approved drugs for the allosteric inhibition of tropomyosin-receptor kinase A using molecular docking and molecular dynamics studies.

Tropomyosin-receptor kinase A (TrkA) is the primary isoform among the tropomyosin-receptor kinases that have been associated with human cancer development, contributing to approximately 7.4% of all cancer cases. TrkA represents an attractive target for cancer treatment; however, currently available TrkA inhibitors face limitations in terms of resistance development and potential toxicity. Hence, the objective of this study was to identify new allosteric-approved inhibitors of TrkA that can overcome these challenges and be employed in cancer therapy. To achieve this goal, a screening of 9,923 drugs from the ChEMBL database was conducted to assess their repurposing potential using molecular docking. The top 49 drug candidates, exhibiting the highest docking scores (-11.569 to -7.962 kcal/mol), underwent MM-GBSA calculations to evaluate their binding energies. Delanzomib and tibalosin, the top two drugs with docking scores of -10.643 and -10.184 kcal/mol, respectively, along with MM-GBSA dG bind values of -67.96 and -50.54 kcal/mol, were subjected to 200 ns molecular dynamic simulations, confirming their stable interactions with TrkA. Based on these findings, we recommend further experimental evaluation of delanzomib and tibalosin to determine their potential as allosteric inhibitors of TrkA. These drugs have the potential to provide more effective and less toxic therapeutic alternatives. The approach employed in this study, which involves repurposing drugs through molecular docking and molecular dynamics, serves as a valuable tool for identifying novel drug candidates with distinct therapeutic uses. This methodology can contribute to reducing the attrition rate and expediting the process of drug discovery.

Cuidados paliativos para personas con enfermedad de Parkinson avanzada. Revisión sistemática / Palliative care for people with advanced Parkinson's disease. A systematic review

Introducción: Los cuidados paliativos hacen referencia al tratamiento dirigido a la identificación precoz e impecable del dolor y otros problemas físicos, psicosociales y espirituales que limitan la calidad de vida de la persona, la familia y sus cuidadores. El objetivo de este artículo es identificar las intervenciones paliativas utilizadas para la valoración y el control de síntomas en personas con enfermedad de Parkinson (EP) avanzada. Materiales y métodos: Se desarrolló una revisión sistémica de la bibliografía aplicando los pasos propuestos por Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). La búsqueda se orientó a partir de una pregunta de revisión estructurada y se incluyeron estudios originales de pacientes con EP avanzada publicados en bases de datos como Medline y Google Scholar entre 2010 a 2021. Resultados: Se revisaron 31 estudios en texto completo y se excluyeron 12 estudios por no alcanzar los criterios de calidad. En total, se incluyeron 19 trabajos en esta revisión sistemática, identificando 10 herramientas clínicas para valorar las necesidades paliativas en EP avanzada, cuatro intervenciones farmacológicas, y tres intervenciones no farmacológicas centradas en disminuir síntomas motores, mejorar la calidad de vida y evitar el estado on/off. Un estudio notificó la derivación del paciente a terapias complementarias y asistidas por dispositivos. Conclusión: Como parte del abordaje paliativo se han descrito un conjunto de herramientas para identificar síntomas y valorar necesidades de atención paliativa. Las intervenciones en la EP avanzada se enfocan en el control de los síntomas motores y no motores para disminuir el impacto de la enfermedad sobre la calidad de vida.(AU)

Introduction: Palliative care refers to treatment aimed at the early and comprehensive identification of pain and other physical, psychosocial and spiritual problems that limit the quality of life of the person, their family and their caregivers. The aim of this article is to identify palliative interventions used for the assessment and control of symptoms in people with advanced Parkinson's disease (PD). Materials and methods: A systematic review of the literature was conducted following the steps proposed by Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The search was guided by a structured review question and included original studies of patients with advanced PD published in databases such as Medline and Google Scholar between 2010 and 2021. Results: Thirty-one full-text studies were reviewed and 12 were excluded due to not meeting quality criteria. A total of 19 papers were included in this systematic review, which identified 10 clinical tools to assess palliative needs in advanced PD, four pharmacological interventions, and three non-pharmacological interventions focused on reducing motor symptoms, improving quality of life and avoiding the on/off state. One study reported the referral of patients to complementary and device-assisted therapies. Conclusion: As part of the palliative approach, a set of tools for identifying symptoms and assessing palliative care needs have been described. Interventions in advanced PD focus on the control of motor and non-motor symptoms so as to reduce the impact of the disease on quality of life.(AU)

Computational Insights into Natural Antischistosomal Metabolites as SmHDAC8 Inhibitors: Molecular Docking, ADMET Profiling, and Molecular Dynamics Simulation.

Schistosomiasis is a neglected tropical disease with a significant socioeconomic impact. It is caused by several species of blood trematodes from the genus Schistosoma, with S. mansoni being the most prevalent. Praziquantel (PZQ) is the only drug available for treatment, but it is vulnerable to drug resistance and ineffective in the juvenile stage. Therefore, identifying new treatments is crucial. SmHDAC8 is a promising therapeutic target, and a new allosteric site was discovered, providing the opportunity for the identification of a new class of inhibitors. In this study, molecular docking was used to screen 13,257 phytochemicals from 80 Saudi medicinal plants for inhibitory activity on the SmHDAC8 allosteric site. Nine compounds with better docking scores than the reference were identified, and four of them (LTS0233470, LTS0020703, LTS0033093, and LTS0028823) exhibited promising results in ADMET analysis and molecular dynamics simulation. These compounds should be further explored experimentally as potential allosteric inhibitors of SmHDAC8.

[Palliative care for people with advanced Parkinson's disease. A systematic review]. / Cuidados paliativos para personas con enfermedad de Parkinson avanzada. Revisión sistemática.

INTRODUCTION: Palliative care refers to treatment aimed at the early and comprehensive identification of pain and other physical, psychosocial and spiritual problems that limit the quality of life of the person, their family and their caregivers. The aim of this article is to identify palliative interventions used for the assessment and control of symptoms in people with advanced Parkinson's disease (PD). MATERIALS AND METHODS: A systematic review of the literature was conducted following the steps proposed by Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The search was guided by a structured review question and included original studies of patients with advanced PD published in databases such as Medline and Google Scholar between 2010 and 2021. RESULTS: Thirty-one full-text studies were reviewed and 12 were excluded due to not meeting quality criteria. A total of 19 papers were included in this systematic review, which identified 10 clinical tools to assess palliative needs in advanced PD, four pharmacological interventions, and three non-pharmacological interventions focused on reducing motor symptoms, improving quality of life and avoiding the on/off state. One study reported the referral of patients to complementary and device-assisted therapies. CONCLUSION: As part of the palliative approach, a set of tools for identifying symptoms and assessing palliative care needs have been described. Interventions in advanced PD focus on the control of motor and non-motor symptoms so as to reduce the impact of the disease on quality of life.

TITLE: Cuidados paliativos para personas con enfermedad de Parkinson avanzada. Revisión sistemática.Introducción. Los cuidados paliativos hacen referencia al tratamiento dirigido a la identificación precoz e impecable del dolor y otros problemas físicos, psicosociales y espirituales que limitan la calidad de vida de la persona, la familia y sus cuidadores. El objetivo de este artículo es identificar las intervenciones paliativas utilizadas para la valoración y el control de síntomas en personas con enfermedad de Parkinson (EP) avanzada. Materiales y métodos. Se desarrolló una revisión sistémica de la bibliografía aplicando los pasos propuestos por Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). La búsqueda se orientó a partir de una pregunta de revisión estructurada y se incluyeron estudios originales de pacientes con EP avanzada publicados en bases de datos como Medline y Google Scholar entre 2010 a 2021. Resultados. Se revisaron 31 estudios en texto completo y se excluyeron 12 estudios por no alcanzar los criterios de calidad. En total, se incluyeron 19 trabajos en esta revisión sistemática, identificando 10 herramientas clínicas para valorar las necesidades paliativas en EP avanzada, cuatro intervenciones farmacológicas, y tres intervenciones no farmacológicas centradas en disminuir síntomas motores, mejorar la calidad de vida y evitar el estado on/off. Un estudio notificó la derivación del paciente a terapias complementarias y asistidas por dispositivos. Conclusión. Como parte del abordaje paliativo se han descrito un conjunto de herramientas para identificar síntomas y valorar necesidades de atención paliativa. Las intervenciones en la EP avanzada se enfocan en el control de los síntomas motores y no motores para disminuir el impacto de la enfermedad sobre la calidad de vida.

El rol de la enfermería en el ámbito de la salud pública / The role of the nurse in the field of public health

Objetivo: Conocer el rol de las enfermeras que trabajan en el campo de la salud pública y la diferencia respecto al rol de atención familiar y comunitaria en el contexto de Cataluña, a través de experiencias y perspectivas de profesionales del ámbito de la salud pública. Método: Estudio cualitativo fenomenológico descriptivo. Realización de 14 entrevistas a informantes clave del campo de la salud pública y del ámbito comunitario, seleccionadas mediante propositivo de máxima variación. Análisis de contenido mediante metodología temática y creación de categorías a partir de la triangulación de resultados. Resultados: Se analizan las competencias profesionales y las funciones que realiza la enfermería en el ámbito de la salud pública. La mayoría de las funciones propias se correspondieron con las funciones relacionadas en «el cuidado» y de los la «visión global» de salud. La indeterminación de las funciones y roles relacionada con la desigualdad de género conlleva un bajo reconocimiento de la profesión y una falta de adecuación de la categoría profesional, reflejados en una escasa presencia de la enfermería en posiciones de gestión en salud pública. Aunque se comparten competencias con la enfermería familiar y comunitaria, se encuentran también diferencias. Conclusiones: Este estudio ha permitido profundizar en el rol de la enfermería de salud pública, poco conocido. Se evidencia la necesidad de definir sus roles y funciones para evitar las desigualdades y aumentar su reconocimiento.(AU)

Objective: Identify the role of public health nurses and differentiate it from that of community care nurses in the context of Catalonia, through the experiences and perspectives of professionals in the field of public health. Method: Descriptive phenomenological qualitative study. Fourteen interviews were conducted with key informants, from the field of public health and community care, selected by i purposive sampling. Content analysis using thematic methodology, creation of categories from the triangulation of results. Results: The professional competencies and functions performed by nursing in the field of public health are analysed. Most of the specific functions were the ones related to “care” and the “global vision” of health. The indeterminacy of functions and roles, related to gender inequality, leads to a low recognition of the profession and a lack of appropriateness of the professional category, reflected in a low presence of nurses in management positions in public health. Although some competencies are shared with the family and community nurse, there are also differences. Conclusions: This study sheds light on the role of public health nursing, often overlooked. It is urgent to define public health nurses role and functions, in order to avoid inequalities and increase their recognition.(AU)

Efficacy and safety of trifluridine/tipiracil in third-line and beyond for the treatment of patients with metastatic colorectal cancer in routine clinical practice: patterns of use and prognostic nomogram.

INTRODUCTION: Trifluridine/tipiracil combination has shown a benefit over placebo in the treatment of patients with chemorefractory metastatic colorectal cancer (mCRC). We evaluated the efficacy and safety of this combination in the real-life setting at eight Galician centers in Spain. PATIENTS AND METHODS: This is a retrospective study of a cohort of patients with mCRC in treatment with trifluridine/tipiracil within usual clinical practice who have been previously treated or are not considered candidates for treatment with available therapies. RESULTS: A total of 160 mCRC patients were included. Our data showed that 11.9% of patients achieved disease control. Median progression-free survival was 2.75 months; at 5.66 months follow-up, median overall survival was 7.94 months. Asthenia and neutropenia (48.1% both) were the most frequent adverse events. Overall survival was lower in patients with ECOG 2, multiple metastatic sites, platelets count 350,000/µl, alkaline phosphatase > 500 IU/l, and carcinoembryonic antigen > 10 ng/ml. CONCLUSION: The results of this study confirm the efficacy and safety of trifluridine/tipiracil in chemorefractory mCRC patients. However, patients in clinical practice differ from patients in clinical trials. Due to this, prognostic factors have special importance to offer the best therapeutic approach.

Effectiveness of proteolytic enzymes to remove gluten residues and feasibility of incorporating them into cleaning products for industrial purposes.

The development of protocols for efficient gluten elimination is one of the most critical aspects of any allergen management strategy in the industry. The suitability of different proteolytic enzymes to be included in a cleaning formulation that allows the effective elimination of gluten residues was studied. Alcalase (ALC), neutrase (NEUT) and flavourzyme (FLAV) were selected from in silico analysis. The presence of 1% (v/v) of linear alkylbenzene sulphonate (LAS), a common anionic detergent, improved the gluten solubility, which may favour its elimination. Chromatographic analysis showed that the three enzymes studied were able to hydrolyse gluten in the presence of LAS. The highest percentage of short peptides (< 5 kDa) was achieved with ALC, what increases the probability of reducing the gluten antigenicity. Besides, in the presence of ALC and detergent LAS have detected the lowest levels of gluten with ELISA kits. So, effective amounts of ALC and LAS were added to a cleaning formulation, where its proteolytic activity was maintained above 90% after 37 days at 4 °C and 25 °C (under dark). Preliminary validation of the effectiveness enzymatic cleaning formulation to hydrolyse gluten was performed in a ready-to-eat/frozen food company, in which previous episodes of cross-contamination with gluten have been detected. The gluten content decreased to values below 0.125 µg/100 cm2 when the cleaning formulation was tested on different surfaces with different cleaning protocols, demonstrating the high suitability of the enzymatic cleaning formulation developed.

Non-valvular intravascular device and endovascular graft-related infection.

In the last few years there has been an increase of implantable cardiac electronic device and vascular graft related infections. This is due in part to a higher complexity of some of these procedures and an increase in patient's comorbidities. Despite wide diagnosis methods availability, early stage diagnosis usually constitutes a challenge as often patients only denote insidious symptoms. In most confirmed cases, removal of the infected device is required to resolve the infection. This is mostly explainable because of bacterial ability to grow as biofilms on biomaterial surfaces, conferring them antimicrobial resistance. If removal is not possible, chronic suppressive antimicrobial therapy could be an option.

Influence of pH on viscoelastic properties of heat-induced gels obtained with a ß-Lactoglobulin fraction isolated from bovine milk whey hydrolysates.

A ß-Lactoglobulin fraction (r-ßLg) was isolated from whey hydrolysates produced with cardosins from Cynara cardunculus. The impact of the hydrolysis process on the r-ßLg structure and the rheological properties of heat-induced gels obtained thereafter were studied at different pH values. Differences were observed between r-ßLg and commercial ß-Lg used as control. Higher values for the fluorescence emission intensity and red shifts of the emission wavelength of r-ßLg suggested changes in its tertiary structure and more solvent-exposed tryptophan residues. Circular dichroism spectra also supported these evidences indicating that hydrolysis yielded an intermediate (non-native) ß-Lg state. The thermal history of r-ßLg through the new adopted conformation improved the microstructure of the gels at acidic pH. So, a new microstructure with better rheological characteristics (higher conformational flexibility and lower rigidity) and greater water holding ability was founded for r-ßLg gel. These results were reflected in the microstructural analysis by scanning electron microscopy.

[Directed therapeutic approach to Staphylococcus aureus infections. Clinical aspects of prescription]. / Aproximación terapéutica dirigida de las infecciones por Staphylococcus aureus. Aspectos clínicos de la prescripción.

Infections caused by Staphylococcus aureus have had classically an important impact in morbidity and mortality in the nosocomial and community scene. The description of methicillin resistance among nosocomial isolates of S. aureus and his widespread diffusion has become methicillin-resistant S. aureus (MRSA) in one of the most common causes of bacterial nosocomial infections. In the last years MRSA strains have also emergence in the community. This together with a progressive increase in resistance to antibiotics used classically has become vancomycin in the treatment of choice in most cases according to clinical guidelines. As a result, a progressive rise in the minimum inhibitory concentration (MIC) to vancomycin has been reported. In this context strains with intermediate susceptibility to vancomycin (MIC 8-4 mg/L) and heteroresistance have been noted. These strains are associated with a higher risk of treatment failure when using vancomycin. Among isolates of S. aureus susceptible to vancomycin there has been described stains with elevated MICs (≥1.5 mg/L). It is controversial if the presence of these strains has an impact on clinical outcome if treatment with vancomycin or ß-lactams is prescribed. The development of new antibiotics with activity against MRSA and exploring synergies offer a promising alternative to treatment with vancomycin.

Structural and thermo-rheological analysis of solutions and gels of a ß-lactoglobulin fraction isolated from bovine whey.

A ß-Lactoglobulin fraction (r-ßLg) was isolated from milk whey hydrolysates produced with cardosins from Cynara cardunculus. The impact of the technological process on the r-ßLg structure and how in turn this determined its heat-induced gelation was investigated. Results were analysed taking pure ß-Lg (p-ßLg) as control sample. The process induced changes in the r-ßLg native conformation causing exposure of hydrophobic groups, lower thermal stability and also, shorter thermal treatments needed to give rise to non-native and aggregated species. At pH 3.2, r-ßLg and p-ßLg solutions exhibited two gelation steps, with the advantage that r-ßLg protein may form stable gels at lower temperature than p-ßLg. At pH 7.2, a specific thermo-viscoelastic stability to 73 °C was found, which corresponded to the gel point in both protein solutions. The difference was that while for p-ßLg solution in sol state δ<45° (solid-like), however for r-ßLg solution δ>45° (fluid-like).

[Recommendations for the use of methotrexate in patients with juvenile idiopathic arthritis]. / Recomendaciones para el uso de metotrexato en pacientes con artritis idiopática juvenil.

OBJECTIVES: To develop a consensus document of recommendations for the use of methotrexate (MTX) in patients with juvenile idiopathic arthritis (JIA). MATERIAL AND METHOD: A group of eleven experts proposed several clinical questions on the use of MTX in patients with JIA. A systematic review was conducted and the evidence and recommendations for each question were extracted. The results were discussed and validated by the experts in a work session to establish the final recommendations. RESULTS: MTX is recommended as the first drug for inducing remission in JIA, and its indication should be made according to the clinical category of the patient. Prior to treatment, it is recommended to perform a complete blood count, including white cells, levels of liver enzymes, serum creatinine, and other analytical parameters according to specific risk factors. Treatment should be initiated with a dose of 10-15 mg/m(2)/week. In cases of uveitis or polyarthritis, an initial dose of 15 mg/m(2)/week should be considered. For a better bioavailability and tolerability, it is preferable to administer MTX parenterally if the dose is ≥15 mg/m(2)/week. It is necessary to periodically perform an analytical monitoring of the patient and to assess possible alterations in liver enzymes to make changes if necessary. Combinations with biological agents may be necessary, as well as the concomitant addition of folic or folinic acid. CONCLUSIONS: This document describes the main recommendations for the appropriate use of MTX in JIA patients, according to scientific evidence and clinical experience.

The Implications of HIV Treatment on the HIV-Malaria Coinfection Dynamics: A Modeling Perspective.

Most hosts harbor multiple pathogens at the same time in disease epidemiology. Multiple pathogens have the potential for interaction resulting in negative impacts on host fitness or alterations in pathogen transmission dynamics. In this paper we develop a mathematical model describing the dynamics of HIV-malaria coinfection. Additionally, we extended our model to examine the role treatment (of malaria and HIV) plays in altering populations' dynamics. Our model consists of 13 interlinked equations which allow us to explore multiple aspects of HIV-malaria transmission and treatment. We perform qualitative analysis of the model that includes positivity and boundedness of solutions. Furthermore, we evaluate the reproductive numbers corresponding to the submodels and investigate the long term behavior of the submodels. We also consider the qualitative dynamics of the full model. Sensitivity analysis is done to determine the impact of some chosen parameters on the dynamics of malaria. Finally, numerical simulations illustrate the potential impact of the treatment scenarios and confirm our analytical results.