Drug-Cannabinoid Interactions in Selected Therapeutics for Symptoms Associated with Epilepsy, Autism Spectrum Disorder, Cancer, Multiple Sclerosis, and Pain.

Clinical practice entails a translation of research that assists in the use of scientific data and therapeutic evidence for the benefit of the patient. This review critically summarizes the potential impact of cannabinoids in conjunction with other drugs when associated with treatments for epilepsy, autism spectrum disorder, cancer, multiple sclerosis, and chronic pain. In these associations, potential drug interactions may occur and alter the predicted clinical results. Therefore, the potential for drug interactions must always be assessed to avoid therapeutic failures and/or increased side effects. Some effects may be additive, synergistic, or antagonistic, but changes in absorption, distribution, metabolism, particularly through cytochrome P450 (CYP) isoenzymes (e.g., CYP2C9 and CYP3A4), and excretion may also occur. For example, the combination of cannabis-derived compounds and the antifungal drug ketoconazole, a CYP3A4 inhibitor, increases the plasma concentration of Δ-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). In contrast, rifampicin, a CYP3A4 inducer, stands out for reducing plasma THC levels by approximately 20-40% and 50% to 60% for CBD. Other CYP3A4 inhibitors and inducers are likely to have a similar effect on plasma concentrations if co-administered. Pharmacokinetic interactions with anticonvulsant medications have also been reported, as have pharmacodynamic interactions between cannabinoids and medications with sympathomimetic effects (e.g., tachycardia, hypertension), central nervous system depressants (e.g., drowsiness, ataxia), and anticholinergics (e.g., tachycardia and somnolence). Although further studies are still pending, there is currently clinical evidence supporting drug interactions with cannabinoids, requiring doctors to evaluate the risk of drug combinations with cannabinoids and vice versa. The tables provided here were designed to facilitate the identification of biorelevant interactions that may compromise therapeutic efficacy and toxicity.

Risk of chronic kidney disease in 260 patients with lupus nephritis-analysis of a nationwide multicentre cohort with up to 35 years of follow-up.

OBJECTIVES: To compare proliferative (PLN) and membranous (MLN) lupus nephritis (LN) regarding clinical and laboratory presentation and long-term outcomes; To investigate predictors of progression to chronic kidney disease (CKD). METHODS: Multicentre observational study, with retrospective analysis of a prospective cohort, using data from the Rheumatic Diseases Portuguese Registry-Reuma.pt. Patients with biopsy-proven PLN, MLN and mixed LN were included. Cox regression survival analysis was used to investigate predictors of CKD. RESULTS: 260 patients were included. Median follow-up was 8 years (IQR 11; minimum 1, maximum 35 years). MLN patients presented with significantly lower serum creatinine (0.70 (IQR 0.20; minimum 0.50, maximum 1.30) mg/dl vs 0.80 (IQR 0.31; minimum 0.26, maximum 2.60) in PLN, p= 0.003). Proteinuria levels did not differ between groups (p= 0.641). Levels of complement were reduced in PLN but nearly normal in MLN patients, and there were fewer patients with positive anti-dsDNA antibodies in the MLN group (p< 0.001). One year after the beginning of treatment, 62% of the patients achieved EULAR/ERA-EDTA complete response, with further 5% achieving partial response. Patients with lower proteinuria at diagnosis were more likely to achieve a complete renal response at one year, however, proteinuria at diagnosis or at one year did not predict long term CKD. Estimated glomerular filtration rate (eGFR) ≤75 mL/min/1.73 m2 at one year was the strongest predictor of progression to CKD (HR 23 [95% CI 8-62], p< 0.001). Other possible predictors included the use of azathioprine for induction of remission, older age at diagnosis and male sex. CONCLUSION: Proteinuria levels did not predict LN histologic class in our cohort. eGFR cutoff of 75 mL/min/1.73 m2 after one year of treatment was strongly predictive of progression to CKD.

An exploratory analysis of PM 2.5 /PM 10 ratio during 2016-2018 in Metropolitan Lima.

Aerosols (PM 2.5 and PM 10 ) represent one of the most critical pollutants due to their negative effects on human health. This research analyzed the relationship of PM and its PM 2.5 /PM 10 ratios with climatic variables in the austral spring (2016-2018) in Metropolitan Lima. Overall, there was an average PM 2.5 /PM 10 ratio of 0.33 with fluctuations from 0.30 to 0.35. However, there have also been high point values that reached ratios greater than one. This situation indicates a moderate condition of contamination by particulate matter with a predominance of coarse aerosols in spring, with an increasing trend over the years. The locations Ate and Villa Maria del Triunfo, especially Ate, presented poor quality conditions. Thursdays showed outstanding pollution peaks by PM 10 , and a decrease is visible on Sundays. On the other hand, the PM 2.5 showed a similar pattern every day, including Sundays. The maximum peaks occurred in the morning and night hours. The increase in anthropogenic emissions associated with the formation of secondary aerosols has been evident, being the case of the location Campo de Marte, the one that had a significant increase in ratios PM 2.5 /PM 10 , which confirms a greater intensity of secondary formations of carbonaceous particles from industrial oil sources, vehicle exhaust, as well as aerosols from metal smelting and biomass burning. There were negative correlations of the ratios with PM 10 , temperature, wind speed, and direction, and positive correlations with PM 2.5 and relative humidity. Contour lines were successfully developed that demonstrated the interaction of climate with PM 2.5 /PM 10 ratios. This will deepen the exploration of emission sources and modeling, which allows for optimizing air quality indices to control emissions and adequately manage air quality in Metropolitan Lima.

Molecular detection and characterization of Blastocystis in herbivore livestock species in Portugal.

Blastocystis is a ubiquitous intestinal protist in humans and animals worldwide. The traditional livestock free-roaming raising system in rural communities increases the risk of infection with contact with a wider range of pathogens transmitted via the faecal-oral route associated with that wildlife-livestock-human interface. However, no studies have been conducted to determine the occurrence and subtype distribution of Blastocystis in livestock in Portugal. Here, we collected 180 faecal samples from herbivore livestock (cattle, goats, horses, and sheep) in different regions of the country to investigate Blastocystis prevalence and subtype diversity using PCR and next-generation amplicon sequencing. Blastocystis was present in 40.6% (73/180; 95% CI: 33.31-48.11) of the samples (goats, 81.0%; sheep, 60.9%; cattle, 32.2%). None of the horse samples were Blastocystis-positive. Eighteen subtypes were detected (ST1-ST3, ST5-ST7, ST10, ST13, ST14, ST21, ST23-ST26, ST30, ST42-ST44). Mixed infections were detected in 97.3% of the Blastocystis-positive samples. Potentially zoonotic subtypes were identified in 75.0%, 96.4%, and 100% of the Blastocystis-positive specimens collected from cattle, sheep, and goats, respectively. These results demonstrate that cattle, sheep, and goats harbour a high diversity of Blastocystis subtypes in the study regions. Importantly, our data provide novel molecular evidence strongly suggesting that some Blastocystis STs/ST subgroups may have differential host specificity.

La tuberculosis en el municipio Marianao: tendencias en dos periodos recientes, 2001­2005 y 2015­2020 / Tuberculosis in the Marianao Municipality: Trends in Two Recent Periods, 2001-2005 and 2015-2020

Introducción: Marianao históricamente ha sido un municipio de La Habana con alta carga de tuberculosis. Una nueva mirada sería importante.

Introduction: Marianao has historically been a municipality of Havana with a high bur-den of tuberculosis. A new look would be important.

Alternativas de procesos para la búsqueda de casos de tuberculosis bajo condiciones económicas limitadas. Cuba 2022-2025 / Process Alternatives for the Tuberculosis Case Finding under Limited Economic Conditions. Cuba 2022-2025

Ejecutar procesos efectivos de búsqueda de casos de tuberculosis es crucial para acele-rar el paso hacia su eliminación. El empeoramiento de las condiciones económicas mun-diales y nacionales no nos permite aplicar extensivamente las tecnologías rápidas mo-leculares idóneas de diagnóstico. Consideramos sensato entonces aplicar algoritmos alternativos que satisfagan las necesidades nacionales presentes hasta que las condi-ciones permitan la cobertura completa de las tecnologías moleculares recomendadas. Sugerimos introducir la radiografía digital para todos los algoritmos, utilizar mejor la microscopía de fluorescencia LED y la óptica convencional ya probadas. En conclusión, es preciso que este enfoque de trabajo, que procura optimizar la efectividad y eficiencia del programa, se introduzca en la práctica cotidiana hasta que lo idóneo sea permisible

Executing effective tuberculosis case-finding processes is crucial to accelerate the path towards elimination of the disease. The worsening of global and national economic conditions do not allow us to extensively apply rapid molecular diagnostic technolo-gies. We consider it sensible and necessary to apply alternative algorithms that meet the current national needs, until conditions allow full coverage of the recommended molecular technologies. We suggest introducing digital X-rays for all algorithms, bet-ter use of LED fluorescence microscopy and conventional optics already appropriate-ly tested. In conclusion, it is necessary that this approach that seeks to optimize the effectiveness and efficiency of the Cuban program be introduced into daily practice until the ideal is permissible

Children with extended oligoarticular and polyarticular juvenile idiopathic arthritis have alterations in B and T follicular cell subsets in peripheral blood and a cytokine profile sustaining B cell activation.

OBJECTIVES: The main goal of this study was to characterise the frequency and phenotype of B, T follicular helper (Tfh) and T follicular regulatory (Tfr) cells in peripheral blood and the cytokine environment present in circulation in children with extended oligoarticular juvenile idiopathic arthritis (extended oligo JIA) and polyarticular JIA (poly JIA) when compared with healthy controls, children with persistent oligoarticular JIA (persistent oligo JIA) and adult JIA patients. METHODS: Blood samples were collected from 105 JIA patients (children and adults) and 50 age-matched healthy individuals. The frequency and phenotype of B, Tfh and Tfr cells were evaluated by flow cytometry. Serum levels of APRIL, BAFF, IL-1ß, IL-2, IL-4, IL-6, IL-10, IL-17A, IL-21, IL-22, IFN-γ, PD-1, PD-L1, sCD40L, CXCL13 and TNF were measured by multiplex bead-based immunoassay and/or ELISA in all groups included. RESULTS: The frequency of B, Tfh and Tfr cells was similar between JIA patients and controls. Children with extended oligo JIA and poly JIA, but not persistent oligo JIA, had significantly lower frequencies of plasmablasts, regulatory T cells and higher levels of Th17-like Tfh cells in circulation when compared with controls. Furthermore, APRIL, BAFF, IL-6 and IL-17A serum levels were significantly higher in paediatric extended oligo JIA and poly JIA patients when compared with controls. These immunological alterations were not found in adult JIA patients in comparison to controls. CONCLUSIONS: Our results suggest a potential role and/or activation profile of B and Th17-like Tfh cells in the pathogenesis of extended oligo JIA and poly JIA, but not persistent oligo JIA.

Desigualdades territoriales de la tuberculosis entre los municipios de La Habana, 2015 y 2016-2020 / Territorial Inequalities of Tuberculosis between the Municipalities of Havana, 2015 and 2016-2020

La Habana notifica el 30% de casos de tuberculosis (TB) en Cuba. Objetivo: valorar las desigualdades territoriales en la ocurrencia de TB en los municipios de La Habana, 2015 y 2016-2020 según algunos determinantes intermedios e individuales. Métodos: estudio ecológico de series temporales sobre las notificaciones de TB en 2015 y 2016-2020. La fuente fue la base de vigilancia del MINSAP. Calculamos la tasa del periodo (TP), la referencia fue la menor, estimamos las diferencias absolutas y relativas, y el Riesgo Atribuible Poblacional Porcentual. Estimamos la TP en menores y mayores de 19 años. Según la TP, propusimos dos escenarios: -reducción 5% anual a todos los municipios, según Hitos de OMS y -reducción discriminada 5% anual a municipios con TP < 9 y 7% los ≥ 9/100.000. Calculamos dos índices de dispersión y proporciones de TB en VIH y reclusos. Categorizamos los municipios según metas renovadas hacia la eliminación. Resultados: el municipio de referencia fue Playa (5,5), la diferencia relativa fue 3,3 veces más en Habana Vieja. Cotorro y Guanabacoa no aportaron casos pediátricos. El segundo escenario tuvo desigualdad moderada. Predominaron los TB-VIH, en Habana Vieja (13,1%). 11/15 municipios categorizaron en control satisfactorio. Conclusiones: las desigualdades en general son moderadas en los municipios Habana, no obstante, las tasas de TB infantil son muy bajas en los territorios, dos de ellos alcanzaron la meta de eliminación. La coinfección TB/VIH concentra las mayores proporciones en algunos municipios. (AU);

Havana notifies 30% of cases of tuberculosis (TB) in Cuba. Objective: to assess the territorial inequalities in the occurrence of TB in the municipalities of Havana, 2015 and 2016-2020 according to some intermediate and individual determinants. Methods: ecological study of time series on TB notifications in 2015 and 2016-2020. The source was the MINSAP surveillance base. We calculated the period rate (TP), the reference was the lowest, we estimated the absolute and relative differences, and the Percentage Population Attributable Risk. We estimate the PT in children under and over 19 years of age. According to the TP, we proposed two scenarios: -5% annual reduction to all municipalities, according to WHO Milestones and -discriminated 5% annual reduction to municipalities with TP < 9 and 7% those ≥ 9/100,000. We calculated two dispersion indices and proportions of TB in HIV and inmates. We categorized the municipalities according to renewed goals towards elimination. Results: the reference municipality was Playa (5.5), the relative difference was 3.3 times more in Habana Vieja. Cotorro and Guanabacoa did not provide pediatric cases. The second scenario had moderate inequality. TB-HIV predominated in Old Havana (13.1%). 11/15 municipalities categorized in satisfactory control. Conclusions: inequalities were generally moderate in the Havana municipalities, however, the rates of childhood TB are very low in the territories, two of them reached the elimination goal. TB/HIV coinfection concentrates the highest proportions in some municipalities. (AU)

Occurrence and molecular characterization of Enterocytozoon bieneusi in wild and domestic animal species in Portugal.

The phylum Microsporidia encompasses a diverse group of obligate, intracellular, and spore-forming organisms able to infect a wide range of animal hosts. Among them, Enterocytozoon bieneusi is the most frequently reported species in humans and animals. Little is known about the presence and epidemiology of E. bieneusi in wildlife. We investigated E. bieneusi occurrence and genetic diversity in wild and domestic mammals, through molecular-detection methods, from different regions across Portugal. A total of 756 samples were collected from 288, 242, and 226 wild carnivores, wild ungulates, and domestic animals, respectively. Overall, eight specimens were E. bieneusi-positive (1.1%, 8/756) obtained from five wild (Iberian lynx, Iberian wolf, red fox, stone marten, and wild boar) and one domestic (sheep) host. Nucleotide sequence analysis identified four genotypes of E. bieneusi, Type IV, Wildboar3, BEB6, and PtEbIX. Three of those genotypes belong to Groups 1 (Type IV and Wildboar3) and 2 (BEB6), which are known to contain genotypes capable of infecting a variety of hosts, including humans, highlighting their public health importance. PtEbIX belongs to the dog-specific Group 11. This study represents the first, largest, and most comprehensive molecular-based epidemiology survey carried out in Portugal in wild and domestic animals to date and the first worldwide identification of E. bieneusi in wolf species. Our study showed that wild carnivores and ungulates may act as reservoirs of zoonotic genotypes of E. bieneusi, establishing their role in maintaining the sylvatic cycle of this parasite while representing a potential source of infection for humans and domestic animals.

The identification of human-pathogenic genotypes of fungi-related Enterocytozoon bieneusi in wild carnivores and ungulates in Portugal suggests cross-species infection events and overlapping of the sylvatic and domestic transmission cycles, demonstrating a potential transmission risk to humans.

Survey of Zoonotic Diarrheagenic Protist and Hepatitis E Virus in Wild Boar (Sus scrofa) of Portugal.

Enteropathogenic parasites and viruses have been frequently reported in swine and can infect a wide range of mammals, including humans. Among the wide variety of parasites infecting swine, diarrhoeagenic protists are among those that cause significant morbidity. Hepatitis E virus (HEV) has also been reported both in domestic pigs and wild boar and is known to have an important public health significance. These agents share the fecal−oral transmission route, but data on their fecal shedding and circulation pathways are still lacking or incomplete. Hence, the aim of the present study was to characterize the presence of microeukaryotes and HEV in the wild boar of Portugal. Wild boar stool samples (n = 144) were obtained during the official hunting seasons (October to February) in 2018/2019, 2019/2020, and 2021/2022 and tested for Cryptosporidium spp., Balantioides coli, Giardia duodenalis, Blastocystis sp., Enterocytozoon bieneusi and HEV by molecular assays, followed by sequencing and phylogenetic analysis. We have detected Cryptosporidium scrofarum (1.4%, 95% CI: 0.2−4.9), B. coli (14.6%, 95% CI: 9.2−21.4), Blastocystis ST5 (29.2%, 95% CI: 21.9−37.2) and HEV genotype 3 (2.8%, 95% CI: 0.7−6.9; subgenotypes 3e and 3m). Co-infections were observed in thirteen animals where two were positive for both HEV and B. coli, one was positive for both C. scrofarum and Blastocystis ST5, and ten were positive for both B. coli and Blastocystis ST5. Giardia duodenalis and E. bieneusi were not detected in the surveyed wild boar population. As far as we know, this is the first report describing protist infections by Cryptosporidium spp., B. coli, and Blastocystis sp., as well as the first identification of the emerging HEV genotype 3m in wild boar of Portugal. The present work shows that potentially zoonotic protozoa and HEV are circulating in wild boar populations in Portugal. Awareness and epidemic-surveillance network implementation measures targeting wild boar are needed to prevent the spread of these pathogenic agents to humans.

Endoparasites of the Iberian wolf (Canis lupus signatus) and mesocarnivores in Central Portugal.

At the end of the nineteenth century, massive population declines were observed in carnivores due to the emergence of infectious diseases. This study aims to investigate, by means of coprological analysis, the prevalence and intensity of the parasites that infect the endangered Iberian wolf Canis lupus signatus and two mesocarnivores (the red fox Vulpes vulpes and the stone marten Martes foina) in Central Portugal. In total, 67.2% of the samples screened were infected; Toxascaris leonina (40.6%) was the parasite with the highest prevalence, followed by Ancylostomatidae and Eimeria spp. (28.1%). Eimeria spp. was found in stone marten with the highest infection rate (37,800 OPG), followed by T. leonina (10,100 EPG) in a red fox sample. Moderate to high levels of parasitic infections were identified in 73.3% of red foxes from the western area. Our results highlight the possibility of cross-infection among these carnivore species and cross-contamination in the wildlife-livestock-human interface.

Modelo general de la determinación social de la salud para la tuberculosis

Introducción : El avance hacia la eliminación de la tuberculosis en Cuba, depende de la justicia social para las personas afectadas y sus familiares, barrio por barrio, área de salud por área de salud y municipio por municipio. Para potenciar las dimensiones de su determinación social será necesario un modelo de eliminación local asentado en su enfoque general. Objetivo : Describir un modelo general con enfoque sistémico de la determinación social en salud, aplicado a la tuberculosis. Métodos : Se realizó un estudio cualitativo basado en una revisión documental de artículos sobre la determinación social, con diseño de un modelo explicativo, simple para su comprensión, con componentes estructurales, intermedios e individuales para ser adaptado en el tema de la tuberculosis. Resultados : El modelo planteado tiene como entrada la voluntad política, dependiente del poder establecido que determina las políticas públicas, interactuando con las dimensiones intermedias como aspectos centrales y con las dimensiones individuales de carácter sociodemográficas, socioculturales y socioeconómicas. Estas a su vez retroalimentan e influyen nuevamente en la Voluntad política y las Políticas públicas, cerrando el ciclo sistémico. Además, se incluye el control interactivo del sistema. Conclusiones : Además de los modelos planteados en la literatura nacional revisada, abundar en su enfoque sistémico contribuye a facilitar la comprensión del monitoreo de la Determinación social de la tuberculosis por parte del personal encargado de dar sostenibilidad del control hacia la eliminación.

Introduction : Progress towards the tuberculosis elimination in Cuba depends on social justice for the people affected and their families, neighborhood by neighborhood, health area by health area and municipality by municipality. To enhance the dimensions of its social determination, a local elimination model based on its general approach will be necessary. Objective: To describe a general model with a systemic approach to Social determination in health, applied to tuberculosis. Methods : A qualitative study based on a documentary review of articles on social determination was carried out, with the design of an explanatory model, simple for its understanding, with structural, intermediate and individual components to be adapted to the topic of tuberculosis. Results : The proposed model has as input the political will, dependent on the established power that determines public policies, interacting with the intermediate dimensions as central aspects and with the individual dimensions of a sociodemographic, sociocultural and socioeconomic nature. These, in turn, feedback and once again influence the political will and Public policies, closing the systemic cycle. In addition, interactive control of the system is included. Conclusions : In addition to the models proposed in the national literature reviewed, abounding in its systemic approach contributes to facilitate the understanding of the monitoring of the Social determination in health in tuberculosis by the personnel in charge of providing sustainability of control towards elimination.

Algunas desigualdades sociodemográficas de la tuberculosis entre las regiones geográficas de Cuba / Some sociodemographic inequalities of tuberculosis among the geographic regions in Cuba

Introducción: El estudio de la ocurrencia de la tuberculosis en los territorios geográficos es importante para guiar a los decisores en las intervenciones diferenciadas. Objetivo: Evaluar las desigualdades en la ocurrencia de tuberculosis y de algunas variables sociodemográficas individuales entre las regiones geográficas cubanas. Métodos: Estudio ecológico de series temporales combinado con un estudio descriptivo sobre el número de casos y las tasas de incidencia de tuberculosis en Occidente, Centro y Oriente. Obtuvimos la información de la base de datos nacional de vigilancia de tuberculosis. Calculamos las tasas de incidencia y sus medias geométricas, la menor fue referencia para calcular las diferencias absolutas y relativas. Estimamos las tendencias de las incidencias regionales y las proporciones de algunas variables individuales. Resultados: La región oriental mostró la menor media geométrica de las tasas (5,2) y fue la referencia: su tendencia resultó descendente con reducción total de 22,6 %. En la incidencia predominaron los hombres de 15-64 años en las tres regiones (63,8 %). Los menores de 15 años estuvieron entre 0,4-1,3 %. La región oriental presentó menos defunciones (25,9 %). La occidental aportó 44,2 % de la tuberculosis pulmonar y 46,3 % del diagnóstico bacteriológico. Conclusiones: La región occidental presentó las desigualdades más importantes y mayor riesgo en la ocurrencia de tuberculosis. Se debe profundizar en el análisis de los determinantes individuales posiblemente relacionados y realizar intervenciones diferenciadas.

Introduction: The study of the occurrence of tuberculosis in the geographic territories is important to guide decision-makers in the differentiated interventions. Objective: To identify inequalities in the occurrence of tuberculosis and evaluate some individual sociodemographic variables among the geographic regions in Cuba. Methods: Ecological time series study combined with a descriptive study on the number of cases and the incidence rate of tuberculosis in the western, central and eastern regions. We gathered data from the national tuberculosis surveillance database. The incidence rate and the geometric means were calculated, the lowest was the reference to calculate absolute and relative differences. We estimated the regional incidence trends and the proportions of some individual variables. Results: The eastern region showed the lowest geometric mean of the rates (5.2) and was the reference. It had a downward trend, with a total reduction of 22.6%. Men aged 15-64 years prevailed in the three regions (63.8%). Those under 15 years of age were between 0.4% and 1.3%. The eastern region had the fewest deaths (25.9%). The western region accounted for 44.2% of pulmonary tuberculosis cases and 46.3% of bacteriological diagnoses. Conclusions: The Western region had the most significant inequalities and a higher risk of tuberculosis. It should be further analyzed the probable relationship among individual determinants and carry out differentiated interventions.

Worldwide Disseminated IncX4 Plasmid Carrying mcr-1 Arrives to Wild Mammal in Portugal.

The mcr-1 gene spread is worldwide recognized as a public health threat at multidrug-resistant infections therapy level. Here, we report for the first time, to the best of our knowledge, the detection of the globally distributed IncX4 plasmid carrying mcr-1 (mcr-1/IncX4) in Escherichia coli isolated from a wild mammal in Portugal and Europe. This plasmid was found in a ST533 E. coli isolate with a multidrug-resistant profile, virulence potential, and possibly phylogenetically related to human isolates. Our work contributes to highlight the importance of antimicrobial resistance (AMR) surveillance in wildlife, an important compartment of the whole ecosystem often overlooked in the fight against AMR. IMPORTANCE Colistin resistance mediated by plasmids is recognized worldwide as an emergency problem connected with the whole ecosystem, since is well described in the interface of the human-animal-environment. The plasmid IncX4 is reported as one of the most prevalent plasmids harboring the gene mcr-1. On an European scale the plasmid IncX4 carrying mcr-1 has been described in humans, the environment, and animals, including wildlife, but only in wild birds. This study shows the first report of the plasmid IncX4 harboring mcr-1 in a wild mammal in Portugal and Europe, identified in a ST533 E. coli commensal that is, curiously, more related to isolates from humans than from livestock. Our findings show that the plasmid IncX4 harboring mcr-1 is well established in a colistin resistance drive embracing the whole ecosystem.

Balantioides coli Fecal Excretion in Hunted Wild Cervids (Cervus elaphus and Dama dama) from Portugal.

Balantioides coli is a zoonotic enteric protozoan parasite of public veterinary health relevance and a concern in animal production and food safety. While wild cervids are recognized reservoirs for several zoonotic pathogens, little is known about the occurrence of B. coli in deer species, especially in Europe. To fill this gap, a total of 130 fecal samples from legally hunted red deer (Cervus elaphus, n = 95) and fallow deer (Dama dama, n = 35) were passively collected during two hunting seasons (October to February; 2018-2019 and 2019-2020) in Portugal. After assessment by PCR assay targeting the complete ITS1-5.8s-rRNA-ITS2 region and the 3' end of the ssu-rRNA gene of the parasite, a prevalence of 4.2% (4/95, 95% CI: 0.2-8.3) in red deer and of 5.7% (2/35, 95% CI: 0.0-13.4) in fallow deer was found. Sequence and phylogenetic analyses allowed the identification of B. coli genetic variants A (in two red deer) and B (in two red deer and two fallow deer). This is the first molecular-based description of B. coli in European deer species, whose population have increased in density and geographical range in recent years. Continued monitoring of wild ungulates as potential vectors of parasitic infection diseases of zoonotic nature is crucial to safeguard public health and food safety.

Statistical modeling approach for PM10 prediction before and during confinement by COVID-19 in South Lima, Perú.

A total of 188,859 meteorological-PM[Formula: see text] data validated before (2019) and during the COVID-19 pandemic (2020) were used. In order to predict PM[Formula: see text] in two districts of South Lima in Peru, hourly, daily, monthly and seasonal variations of the data were analyzed. Principal Component Analysis (PCA) and linear/nonlinear modeling were applied. The results showed the highest annual average PM[Formula: see text] for San Juan de Miraflores (SJM) (PM[Formula: see text]-SJM: 78.7 [Formula: see text]g/m[Formula: see text]) and the lowest in Santiago de Surco (SS) (PM[Formula: see text]-SS: 40.2 [Formula: see text]g/m[Formula: see text]). The PCA showed the influence of relative humidity (RH)-atmospheric pressure (AP)-temperature (T)/dew point (DP)-wind speed (WS)-wind direction (WD) combinations. Cool months with higher humidity and atmospheric instability decreased PM[Formula: see text] values in SJM and warm months increased it, favored by thermal inversion (TI). Dust resuspension, vehicular transport and stationary sources contributed more PM[Formula: see text] at peak times in the morning and evening. The Multiple linear regression (MLR) showed the best correlation (r = 0.6166), followed by the three-dimensional model LogAP-LogWD-LogPM[Formula: see text] (r = 0.5753); the RMSE-MLR (12.92) exceeded that found in the 3D models (RMSE [Formula: see text]) and the NSE-MLR criterion (0.3804) was acceptable. PM[Formula: see text] prediction was modeled using the algorithmic approach in any scenario to optimize urban management decisions in times of pandemic.

Assessment of the outcomes of SARS-CoV-2 infection in children and young people followed at Portuguese pediatric rheumatology clinics.

INTRODUCTION: Coronavirus Disease 2019 (COVID-19) generally appears to have milder clinical symptoms and fewer laboratory abnormalities in children. It remains unknown whether children and young people with inflammatory chronic diseases who acquire SARS-CoV-2 infection have a more severe course, due to either underlying disease or immunosuppressive treatments. OBJECTIVES: To assess the epidemiological features and clinical outcomes of children and young people with inflammatory chronic diseases followed at Pediatric Rheumatology Clinics who were infected with SARS-CoV-2. METHODS: A multicentric prospective observational study was performed. Data on demographic variables, clinical features and treatment were collected between March 2020 and September 2021, using the Rheumatic Diseases Portuguese Register (Reuma.pt) and complemented with data from the hospital clinical records. RESULTS: Thirty-four patients were included, 62% were female, with a median age of 13 [8-16] years and a median time of inflammatory chronic disease of 6 [3-10] years. The most common diagnoses were juvenile idiopathic arthritis (n=22, 64.7%), juvenile dermatomyositis (n=3, 8.8%) and idiopathic uveitis (n=3, 8.8%). Twenty patients were on conventional synthetic disease modifying drugs (csDMARDs) and 10 on biologic DMARDs (bDMARDs). Five patients had an active inflammatory disease at the time of infection (low activity). Seven patients had an asymptomatic infection while 27 patients (79%) had symptoms: cough (n=12), fever (n=11), rhinorrhea (n=10), headache (n=8), malaise (n=8), fatigue (n=7), anosmia (n=5), myalgia (n=5),dysgeusia (n=4), odynophagia (n=4), chest pain (n=2), diarrhea (n=2), arthralgia (n=1), vomiting (n=1) and conjunctivitis (n=1). No patient required hospitalization or directed treatment, and all recovered without sequelae. In 8 patients there was a change in the baseline medication during the infection: suspension of bDMARDs (n=4), reduction of bDMARDs (n=1), suspension of csDMARDs (n=4) and reduction of csDMARDs (n=2). Only in one patient with juvenile dermatomyositis (who discontinued bDMARDs and csDMARDs), the underlying disease worsened. CONCLUSIONS: This is the first study involving children with inflammatory chronic diseases followed at Rheumatology Clinics and SARS-CoV-2 infection in Portugal. In our cohort, mild illness was predominant, which is consistent with the literature. There was no need for hospitalization or specific treatment, and, in most cases, no worsening of the underlying disease was identified.

Methotrexate: Implications of pharmacogenetics in the treatment of patients with Rheumatoid Arthritis.

BACKGROUND: Methotrexate (MTX) is an anti-folate drug with anti-proliferative and anti-inflammatory effects. MTX proved to be the most highly effective, fast-acting disease modifying anti-rheumatic drug (DMARD), being widely used for the treatment of rheumatoid arthritis (RA). This review aims to describe the main genetic variants identified concerning proteins that play a role in methotrexate's kinetics and efficiency profile. METHODS: A literature review was conducted since January of 2000 until December 2020, by searching the PubMed and Embase bibliographic databases, employing the following MeSH terms: methotrexate, pharmacogenetics, pharmacokinetics, and rheumatoid arthritis. The search was limited to articles in English language. Two independent reviewers screened the titles and abstracts followed by a full-text review to assess papers regarding their eligibility. A total of 48 articles matched the research criteria and were analyzed. RESULTS: Reduced folate carrier 1 (RFC1), a constitutively expressed folate transport protein that has high affinity for MTX is responsible, almost exclusively, for the transport of folate and MTX into the cell. The most studied variant of the gene is the 80G>A variant, mapped within exon 2, on chromosome 21. It seems to improve RA responses to MTX, clinical efficacy with long disease remission. ABC transporters are involved in the efflux of MTX from cells. An increased expression and function of these transporters should decrease MTX concentrations in target cells, resulting in lack of therapeutic response. ABCB1 3435 C/T is a high frequency polymorphism, significantly associated with RA good responses, symptom remission and reduced adverse events, due to MTX treatment. Thymidylate synthase (TYMS) is involved in thymidine synthesis. MTX decreases TYMS activity by inhibition and decreasing the access to tetrahydrofolate (THF) cofactors. The most common genetic variant of the TYMS gene consists of a 28 bp tandem repeat, with double and triple number of repeats (2R and 3R). The 3R allele genotype was associated with decreased efficacy and increased toxicity. The 5,10-methylenetetrahydrofolate reductase (MTHFR) enzyme is indirectly inhibited by MTX. The most common SNPs of the MTHFR gene are C677T and A1298C. Both are associated with a decreased efficacy and an increased toxicity of MTX. CONCLUSION: MTX response is affected by many gene variants; the effect of each variant separately is likely to be small. Additionally, gene-gene interaction seems to enhance the potential role of linkage disequilibrium. This shows the emerging need for a better gene characterization and to improve the knowledge about variants distribution according to ethnicity, to explain different responses to MTX at an individual level.