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This study aimed to analyze the prevalence, sociobehavioral factors and clinical-laboratory consequences of late presentation among people living with HIV (PLHIV) in the Brazilian Amazon region. In total, 402 HIV + individuals treated at reference units in Belém city (Pará, Brazil) between 2018 and 2019 were evaluated. Late presentation was defined as a first-collection LTCD4+ count below 350 cells/µL. Sociodemographic, behavioral and clinical data were obtained from questionnaires or medical records. Th1, Th2 and Th17 cytokine profiles were evaluated by flow cytometry. Longitudinal data on viral load, T lymphocytes, and antiretroviral therapy administration were obtained from control and logistic databases. Approximately 52.73% of the participants were late presenters and sought medical care 7-12 + months after their primary HIV diagnosis. Sociobehavioral factors associated with late presentation included illicit drug use for more than 5 years, polyamory, no alcohol consumption, homosexuality, and sexual inactiveness after HIV diagnosis. Clinically, late presentation was associated with coinfection rate; polysymptomatology; high IFN-É£, IL-6 and IL-10 levels; nonresponse to antiretroviral therapy; and virological failure- and tuberculosis coinfection-motivated changes to therapy. In summary, the prevalence of late presentation in Pará in the Brazilian Amazon region is high. Delays in seeking specialized care after a primary HIV diagnosis cause medium/long-term changes in the life expectancy and health of PLHIV.
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OBJECTIVE: The Global Dietary Database (GDD) expanded its previous methods to harmonise and publicly disseminate individual-level dietary data from nutrition surveys worldwide. DESIGN: Analysis of cross-sectional data. SETTING: Global. PARTICIPANTS: General population. METHODS: Comprehensive methods to streamline the harmonisation of primary, individual-level 24-h recall and food record data worldwide were developed. To standardise the varying food descriptions, FoodEx2 was used, a highly detailed food classification and description system developed and adapted for international use by European Food Safety Authority (EFSA). Standardised processes were developed to: identify eligible surveys; contact data owners; screen surveys for inclusion; harmonise data structure, variable definition and unit and food characterisation; perform data checks and publicly disseminate the harmonised datasets. The GDD joined forces with FAO and EFSA, given the shared goal of harmonising individual-level dietary data worldwide. RESULTS: Of 1500 dietary surveys identified, 600 met the eligibility criteria, and 156 were prioritised and contacted; fifty-five surveys were included for harmonisation and, ultimately, fifty two were harmonised. The included surveys were primarily nationally representative (59 %); included high- (39 %), upper-middle (21 %), lower-middle (27 %) and low- (13 %) income countries; usually collected multiple recalls/ records (64 %) and largely captured both sexes, all ages and both rural and urban areas. Surveys from low- and lower-middle v. high- and upper-middle income countries reported fewer nutrients (median 17 v. 30) and rarely included nutrients relevant to diet-related chronic diseases, such as n-3 fatty acids and Na. CONCLUSIONS: Diverse 24-h recalls/records can be harmonised to provide highly granular, standardised data, supporting nutrition programming, research and capacity development worldwide.
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Dieta , Estado Nutricional , Masculino , Femenino , Humanos , Estudios Transversales , Encuestas sobre Dietas , AlimentosRESUMEN
An outbreak of hepatitis A is ongoing in Portugal, with 71 confirmed cases from 7 October 2023 to 24 April 2024. Most cases are male, aged 18-44 years, with many identifying as men who have sex with men (MSM) and reported as suspected sexual transmission. Phylogenetic analysis identified the subgenotype IA, VRD 521-2016 strain, last observed in an MSM-associated multi-country outbreak in 2016 to 2018. We wish to alert colleagues in other countries to investigate potential similar spread.
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Brotes de Enfermedades , Genotipo , Hepatitis A , Homosexualidad Masculina , Filogenia , Humanos , Masculino , Portugal/epidemiología , Hepatitis A/epidemiología , Hepatitis A/transmisión , Homosexualidad Masculina/estadística & datos numéricos , Adulto , Adolescente , Adulto Joven , Virus de la Hepatitis A/genética , Virus de la Hepatitis A/aislamiento & purificación , Virus de la Hepatitis A/clasificación , Persona de Mediana Edad , Conducta Sexual , Femenino , Trazado de ContactoRESUMEN
The cytochrome P450 is a superfamily of hemoproteins mainly present in the liver and are versatile biocatalysts. They participate in the primary metabolism and biosynthesis of various secondary metabolites. Chemical catalysts are utilized to replicate the activities of enzymes. Metalloporphyrins and Salen complexes can contribute to the products' characterization and elucidate biotransformation processes, which are investigated during pre-clinical trials. These catalysts also help discover biologically active compounds and get better yields of products of industrial interest. This review aims to investigate which natural product classes are being investigated by biomimetic chemical models and the functionalities applied in the use of these catalysts. A limited number of studies were observed, with terpenes and alkaloids being the most investigated natural product classes. The research also revealed that Metalloporphyrins are still the most popular in the studies, and the identity and yield of the products obtained depend on the reaction system conditions.
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Productos Biológicos , Sistema Enzimático del Citocromo P-450 , Metaloporfirinas , Productos Biológicos/química , Productos Biológicos/metabolismo , Metaloporfirinas/química , Metaloporfirinas/metabolismo , Catálisis , Sistema Enzimático del Citocromo P-450/metabolismo , Etilenodiaminas/química , Biomimética , Terpenos/química , Terpenos/metabolismo , Materiales Biomiméticos/química , Materiales Biomiméticos/metabolismo , Complejos de Coordinación/químicaRESUMEN
BACKGROUND: An assessment program should be inclusive and ensure that the various components of medical knowledge, clinical skills, and professionalism are assessed. The level and the variation over time in the strength of the correlation between these components of assessment is still a matter of study. Based on the meaningful learning theory and the integrated learning theory, we hypothesize that these components increase their connections during the medical school course. METHODS: This is a retrospective cohort study that analyzed data collected for a 10-year period in one medical school. We included students from the 3rd to 6th year of medical school from 2011 to 2021. Three assessment components were addressed: Knowledge, Clinical Skills, and Professionalism. For data analysis, Pearson correlation coefficients (R) and R2 were calculated to study the correlation between variables and a z-test on Fisher's r-to-z was used to determine the differences between correlation coefficients. RESULTS: 949 medical students were included in the study. The correlation between Clinical Skills and Professionalism showed a medium to strong association (Pearson's R ranging from 0.485 to 0.734), while the correlation between Knowledge and Professionalism was weaker but exhibited a steady evolution with Pearson's R fluctuating between 0.075 and 0.218. The Knowledge and Clinical Skills correlation became statistically significant from 2013 onwards and peaking at Pearson's R of 0.440 for the cohort spanning 2016-2019. We also revealed a strengthening of correlations between Professionalism and Clinical Skills from the beginning to the end of clinical training, but not with the knowledge component. CONCLUSIONS: This analysis contributes to our understanding of the dynamics of correlations of different assessment components within an institution and provides a framework for how they interact and influence each other. TRIAL REGISTRATION: This study was not a clinical trial, but a retrospective observational study, without health care interventions. Nevertheless, we provide herein the number of the study as submitted to the Ethics committee - CEICVS 146/2021.
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Competencia Clínica , Evaluación Educacional , Profesionalismo , Facultades de Medicina , Estudiantes de Medicina , Humanos , Estudios Retrospectivos , Competencia Clínica/normas , Profesionalismo/normas , Educación de Pregrado en Medicina/normas , Femenino , Masculino , Estudios LongitudinalesRESUMEN
This brief report presents the findings of an epidemiological investigation into a large-scale outbreak of norovirus gastroenteritis that occurred in a hotel in Algarve, Portugal, in August 2022. A total of 244 cases were reported, primarily affecting Portuguese families, with the parents aged 40-50 years and the children aged 0-19 years. Reported symptoms included vomiting, nausea, abdominal pain, and diarrhoea. Norovirus genotype GI.3 [P3] was detected in stool samples from eight probable cases, while food samples tested negative for norovirus and common pathogenic bacteria. The investigation data collected suggest that the source of the outbreak was likely in the hotel's common areas, with subsequent person-to-person transmission in other areas. The final report emphasizes the importance of improving outbreak prevention and control measures, including the development of a foodborne outbreak investigation protocol, the establishment of an outbreak response team, and the enhancement of regional laboratory capacity.
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Norovirus , Niño , Humanos , Norovirus/genética , Brotes de Enfermedades , Diarrea , Portugal/epidemiología , VómitosRESUMEN
PURPOSE: This study aims to compare midline lumbar interbody fusion (MIDLIF) and minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) for treatment of patients with severe stenosis and lumbar degenerative spondylolisthesis (DS), focusing on dural tears rates, other complications, clinical and radiological outcomes. METHODS: This cohort study included patients with severe lumbar spinal stenosis (Shizas C or D) and lumbar DS who underwent MIDLIF or MIS-TLIF. Propensity score matching was done and the groups were compared regarding surgery time, length of stay, perioperative complications, clinical results and radiological outcomes, at 1 year of follow-up. RESULTS: The study included initially 80 patients, and 72 patients after matching, 36 in each group. Six patients had dural tears, four in the MIDLIF group and two in the MIS-TLIF group (p = 0.67). General complication rates and reoperations were not significantly different between the groups. Good or excellent clinical was achieved in 75% of the MIDLIF patients and 72% of the MIS-TLIF patients (p = 0.91). Radiological parameters showed small but statistically significant (p < 0.01) improvements after surgery, particularly in segmental lordosis and lumbar lordosis (2.0° and 1.7°), while pelvic tilt and global tilt decreased (1.6° and 2.6°). These findings were similar for both groups. CONCLUSION: Our study confirms that MIDLIF is a safe and reliable minimally invasive alternative for lumbar interbody fusion in DS, even in patients with severe stenosis and previous spine surgery. It seems to offer similar results to MIS-TLIF regarding clinical results, radiological outcomes and complications.
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Lordosis , Fusión Vertebral , Estenosis Espinal , Espondilolistesis , Humanos , Estudios de Cohortes , Vértebras Lumbares/diagnóstico por imagen , Vértebras Lumbares/cirugía , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Estenosis Espinal/diagnóstico por imagen , Estenosis Espinal/cirugía , Constricción Patológica , Espondilolistesis/diagnóstico por imagen , Espondilolistesis/cirugía , Fusión Vertebral/métodos , Resultado del Tratamiento , Estudios RetrospectivosRESUMEN
Arthropods, the largest animal phylum, including insects, spiders and crustaceans, are characterized by their bodies being covered primarily in chitin. Besides being a source of this biopolymer, crustaceans have also attracted attention from biotechnology given their cuticles' remarkable and diverse mechanical properties. The goose barnacle, Pollicipes pollicipes, is a sessile crustacean characterized by their body parts covered with calcified plates and a peduncle attached to a substrate covered with a cuticle. In this work, the composition and structure of these plates and cuticle were characterized. The morphology of the tergum plate revealed a compact homogeneous structure of calcium carbonate, a typical composition among marine invertebrate hard structures. The cuticle consisted of an outer zone covered with scales and an inner homogenous zone, predominantly organic, composed of successive layers parallel to the surface. The scales are similar to the tergum plate and are arranged in parallel and oriented semi-vertically. Structural and biochemical characterization confirmed a bulk composition of É-chitin and suggested the presence of elastin-based proteins and collagen. The mechanical properties of the cuticle showed that the stiffness values are within the range of values described in elastomers and soft crustacean cuticles resulting from molting. The removal of calcified components exposed round holes, detailed the structure of the lamina, and changed the protein properties, increasing the rigidity of the material. This flexible cuticle, predominantly inorganic, can provide bioinspiration for developing biocompatible and mechanically suitable biomaterials for diverse applications, including in tissue engineering approaches.
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Artrópodos , Thoracica , Animales , Thoracica/metabolismo , Quitina/químicaRESUMEN
On 5 April 2022, the United Kingdom reported an increase of cases of severe acute hepatitis of unknown aetiology in children, several needing hospitalisation and some required liver transplant or died. Thereafter, 35 countries reported probable cases, almost half of them in Europe. Facing the alert, on 28 April, Portugal created a multidisciplinary Task Force (TF) for rapid detection of probable cases and response. The experts of the TF came from various disciplines: clinicians, laboratory experts, epidemiologists, public health experts and national and international communication. Moreover, Portugal adopted the European Centre for Disease Prevention and Control (ECDC) and the World Health Organization (WHO) case definition and recommendations. By 31 December 2022, 28 probable cases of severe acute hepatitis of unknown aetiology were reported: 16 male and 17 aged under 2â¯years. Of these cases, 23 were hospitalised but none required liver transplant or died. Adenovirus was detected from nine of 26 tested cases. No association was observed between adenovirus infection and hospital admission after adjusting for age, sex and region in a binomial regression model. The TF in Portugal may have contributed to increase awareness among clinicians, enabling early detection and prompt management of the outbreak.
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Hepatitis , Trasplante de Hígado , Niño , Humanos , Masculino , Anciano , Portugal/epidemiología , Brotes de Enfermedades , Europa (Continente) , Enfermedad AgudaRESUMEN
BACKGROUND: Endolymphatic hydrops (EH) is universal in Ménière´s disease (MD). Given its chronic course, with variable interval before complete clinical picture is installed, it seems relevant to understand the progression of vestibular EH and hemato-perilymphatic barrier disruption in patients with MD and monosymptomatic presentations. METHODS: 239 consecutive patients were referred to us with suspected hydropic ear disease. 50 individuals accepted to participate in this study-final longitudinal sample included 24 patients (7 D1, 7 D2, 10 D3). Control group included ten patients. At recruitment, a clinical and MRI re-evaluation was done (3T, intravenous technique) (MR2) and 2 years after MRI was repeated (MR3). Previous MRI (MRI1) were retrospectively evaluated. Patients were classified as definite (D1), possible (D2) and atypical (D3-monosymptomatic) MD. Control group included non-typical symptoms (C2/C3) and 6 asymptomatic (C1). Vestibular endolymphatic ratio (vER) and grading, presence/absence of cochlear EH, asymmetry of cochlear perilymphatic enhancement, and rate of progression of vER were assessed by two independent neuroradiologists and compared between patient and control groups (index ear). RESULTS: EH was universal and pronounced in D1 and remained stable. vER progression was more variable and higher in some D3 patients (index ear worse) and in D2 (non-index), although this observation was not statistically significant. CONCLUSIONS: Considering that many probable and monosymptomatic presentations progress years later into definite MD and given the bilateral tendency of the disease, these findings may indicate that there is an initial accelerated worsening of EH in initial stages of the disease. These data should be confirmed with controlled and larger sample studies.
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Hidropesía Endolinfática , Enfermedad de Meniere , Humanos , Enfermedad de Meniere/complicaciones , Enfermedad de Meniere/diagnóstico por imagen , Estudios Retrospectivos , Hidropesía Endolinfática/complicaciones , Hidropesía Endolinfática/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Espectroscopía de Resonancia MagnéticaRESUMEN
Collagen is the major structural protein in extracellular matrix present in connective tissues, including skin, being considered a promising material for skin regeneration. Marine organisms have been attracting interest amongst the industry as an alternative collagen source. In the present work, Atlantic codfish skin collagen was analyzed, to evaluate its potential for skincare. The collagen was extracted from two different skin batches (food industry by-product) using acetic acid (ASColl), confirming the method reproducibility since no significant yield differences were observed. The extracts characterization confirmed a profile compatible with type I collagen, without significant differences between batches or with bovine skin collagen (a reference material in biomedicine). Thermal analyses suggested ASColl's native structure loss at 25 °C, and an inferior thermal stability to bovine skin collagen. No cytotoxicity was found for ASColl up to 10 mg/mL in keratinocytes (HaCaT cells). ASColl was used to develop membranes, which revealed smooth surfaces without significative morphological or biodegradability differences between batches. Their water absorption capacity and water contact angle indicated a hydrophilic feature. The metabolic activity and proliferation of HaCaT were improved by the membranes. Hence, ASColl membranes exhibited attractive characteristics to be applied in the biomedical and cosmeceutical field envisaging skincare.
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Gadiformes , Gadus morhua , Animales , Bovinos , Materiales Biocompatibles/farmacología , Materiales Biocompatibles/análisis , Gadus morhua/metabolismo , Reproducibilidad de los Resultados , Piel/metabolismo , Colágeno/química , Gadiformes/metabolismoRESUMEN
Failure of osteosynthesis is a common complication of the nailing of trochanteric fractures which typically occurs through form of cut-out. Tip-Apex distance (TAD), Calcar Tip-Apex distance (CalTAD), and Chang criteria are validated variables to predict failure of cephalomedullary nailing. This is a retrospective study which analyzes treatment of trochanteric fractures from 2018 to 2020 (n = 296) evaluating postoperative radiographs and factors of mechanical failure. Our objective was to assess correlation among these variables and their influence on mechanical failure, either individually or creating a new score. Our results support the CalTAD and Chang's criteria as valid predictors of mechanical failure. Furthermore, they empathize the importance of fracture reduction and proper placement of cervical screw. To our knowledge, this is the first study performing multivariate analysis including these 3 variables.
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Fijación Intramedular de Fracturas , Fracturas de Cadera , Humanos , Estudios Retrospectivos , Clavos Ortopédicos , Fijación Intramedular de Fracturas/métodos , Fracturas de Cadera/diagnóstico por imagen , Fracturas de Cadera/cirugía , Tornillos Óseos , Resultado del TratamientoRESUMEN
We report a case of rickettsiosis caused by Rickettsia monacensis in an immunocompetent 67-year-old man in Portugal who had eschar, erythematous rash, and an attached Ixodes ricinus tick. Seroconversion and eschar biopsy led to confirmed diagnosis by PCR. Physicians should be aware of this rare rickettsiosis, especially in geographic regions with the vector.
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Ixodes , Infecciones por Rickettsia , Rickettsia , Anciano , Animales , Humanos , Ixodes/microbiología , Masculino , Portugal , Rickettsia/genética , Infecciones por Rickettsia/diagnóstico , Infecciones por Rickettsia/tratamiento farmacológico , Infecciones por Rickettsia/microbiologíaRESUMEN
Ménière's disease (MD) is a clinical syndrome characterized by recurrent episodes of spontaneous vertigo, unilateral fluctuating sensorineural hearing loss, tinnitus, and aural fullness. Endolymphatic hydrops is recognized as the pathophysiological substrate of the disease, having been demonstrated in anatomical pathological studies and more recently by magnetic resonance imaging (MRI). The current criteria of the disease, however, remain symptom based and do not include the demonstration of endolymphatic hydrops. The authors review MRI techniques and diagnostic criteria of endolymphatic hydrops and the role of MRI in MD is discussed.
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Hidropesía Endolinfática , Pérdida Auditiva Sensorineural , Enfermedad de Meniere , Acúfeno , Hidropesía Endolinfática/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética , Enfermedad de Meniere/diagnóstico por imagenRESUMEN
AIM: To characterise Bartonella infections in a paediatric population requiring hospital admission and review its treatment. METHODS: Longitudinal observational retrospective data analysis of children and adolescents admitted with Bartonella infection at a paediatric tertiary hospital from 2010 to 2019. RESULTS: We identified 16 cases of bartonellosis, with a mean age of 8.0 ± 4.5 years old, no sex predominance and 14 had contact with cats. Most of the cases occurred in fall and winter. Clinical presentations included osteomyelitis/arthritis (n = 9), hepatosplenic disease (n = 2), lymphadenitis (n = 2), neuroretinitis (n = 2) and encephalitis (n = 1). Clinical diagnosis was confirmed by serology (n = 16) and Bartonella DNA detection in patient's lymph nodes/hepatic lesion (n = 3). Therapeutic approach varied according to the clinical presentation: azithromycin in lymphadenitis, rifampicin plus ciprofloxacin in hepatosplenic disease, rifampicin and doxycycline in neuroretinitis, ceftriaxone in encephalitis and azithromycin, cotrimoxazole or rifampicin plus azithromycin, cefuroxime, ciprofloxacin or doxycycline in osteomyelitis/arthritis. Immunodeficiency was excluded in seven patients. Seven patients' cats were screened by veterinarians and treated when infected (n = 5). CONCLUSIONS: In these clinical presentations, where other infections may be involved, a high index of suspicion is necessary, with emphasis on the epidemiological context. The association of systemic forms with immunodeficiency did not occur in our study. The lack of recommendations for treatment of atypical infection makes the approach of these cases a challenge. Randomised control studies are essential to define the best approach in each case.
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Infecciones por Bartonella , Bartonella henselae , Osteomielitis , Adolescente , Animales , Infecciones por Bartonella/diagnóstico , Infecciones por Bartonella/tratamiento farmacológico , Infecciones por Bartonella/epidemiología , Gatos , Niño , Humanos , Osteomielitis/diagnóstico , Osteomielitis/tratamiento farmacológico , Osteomielitis/epidemiología , Estudios RetrospectivosRESUMEN
Taking into account that the industrial processing of passion fruit generates significant amounts of waste (only the peels represent 51% of the total mass of the fruit), in the present study an economic analysis was conducted to evaluate industrial line viability for pectin extraction from passion fruit peels. Knowing that absolute ethanol (99.50% purity), used in the precipitation and washing steps, has a higher cost, a simulation of extractive distillation was performed using solvents ethylene glycol and glycerol, in the software Aspen Plus v.11, being possible to recover 99.63% of ethanol for both solvents. The results of the economic evaluation showed that the process using ethylene glycol has an advantage, mainly due to its higher profitability (1.13 times higher), lower production cost (94.86% of the price using glycerol), and a lower breakeven point (around 3% smaller). The financial indicators showed profitability and attractiveness for the implementation of this processing line.
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Biotecnología/métodos , Etanol/química , Pectinas/biosíntesis , Biotecnología/economía , Brasil , Simulación por Computador , Glicol de Etileno/química , Tecnología de Alimentos , Glicerol/química , Passiflora , Pectinas/economía , Reproducibilidad de los Resultados , Riesgo , Sensibilidad y Especificidad , Programas Informáticos , Solventes/químicaRESUMEN
The purpose of this study was to investigate pulp mill by-products valorization through activated carbon (AC) production and its application in wastewater treatment. Bio-sludge is a known promising precursor for AC production. The mill's chemical recovery stage generates an effluent (electrostatic precipitator ash leachate - EPAL) with high levels of potassium and sodium, which motivate studies regarding its viability as a chemical source for carbon activation. Bio-sludge and EPAL are problematic by-products and this research line would allow their return to the productive chain, as an adsorbent for the wastewater treatment. Two carbonization heating rates (3.5, 15 °C/min), three activation agents (NaOH, KOH, EPAL) and two activator:bio-sludge ratios (1:1, 2:1) were used for AC production. The best ACs in terms of surface area were those produced at 3.5 °C/min, with KOH or EPAL in 2:1 proportion. ACs produced under these conditions and commercial activated carbon (CAC) were used in adsorption tests with industrial wastewater. For color removal, KOH-activated carbon presented the greatest efficiency (80.45 %), followed by CAC (76.74 %) and EPAL-activated carbon (70.13 %). For COD removal, EPAL-activated carbon presented greater efficiency (53.49 %), followed by CAC (40.84 %) and KOH-activated carbon (36.86 %). Freundlich's model best described the experimental adsorption data. The KOH results were expected to be satisfactory, since KOH is proven to be effective for carbon activation. The EPAL-activated carbon results were remarkable, especially for COD removal, showing that EPAL can be used as an activator and that the by-products have potential for valorization according to the circular economy principles.
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Contaminantes Químicos del Agua , Purificación del Agua , Adsorción , Carbón Orgánico , Aguas del Alcantarillado , Eliminación de Residuos Líquidos , Aguas Residuales , Contaminantes Químicos del Agua/análisisRESUMEN
Hedgehogs (e.g., Erinaceus europaeus, E. roumanicus) are wild mammals that frequently are observed near residential areas. The aim of this study was to investigate ticks and fleas collected from European hedgehogs in Portugal and to evaluate the prevalence of Rickettsia in those ectoparasites. Ticks and fleas were identified by morphological and molecular methods, and molecular detection by PCR and genotypic characterization of Rickettsia spp. was performed targeting ompB, ompA and gltA gene fragments. In total, 1892 ticks and 213 fleas were collected from 33 rescued European hedgehogs captured in seven districts of the north and centre of Portugal. Two tick species were identified - Rhipicephalus sanguineus accounted for 91 % (n = 1719) of the total ticks collected and 9 % (n = 173) were Ixodes hexagonus. All fleas were identified as Archaeopsylla erinacei. Regarding pathogen detection, Rickettsia massiliae DNA was found in 22 of the 212 tested Rh. sanguineus. None of the 48 I. hexagonus tested showed to be positive for rickettsiae. Rickettsia asembonensis DNA was identified in 55 A. erinacei fleas tested (n = 117). These results show that European hedgehogs are exposed to R. massiliae transmitted by ticks and to R. asembonensis via fleas suggesting that these mammals might be involved in the natural transmission cycle of these Rickettsia species. This study is the first report of R. asembonensis in fleas in Portugal.
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Rickettsia , Siphonaptera , Animales , ADN Bacteriano , Erizos , Portugal , Rickettsia/genéticaRESUMEN
The outcomes of patients with metastatic melanoma (MM) have significantly improved after the introduction of BRAF-specific inhibitors. Herein is reported a patient with MM and non-V600-BRAF mutation who responded to iBRAF/iMEK therapy. In July 2014, a 63-year-old man presented with a 4.1mm-thick V600E-BRAF wild type melanoma on the back. Metastases were identified in one sentinel node and two of 11 subsequently excised lymph nodes, with no signs of distant metastatic disease. In September 2017, lung metastasis was observed and pembrolizumab was started. Progressive disease was apparent at cycle 10 and therapy was switched to ipilimumab. After four cycles, an asymmetric response was observed. In November 2017, next generation sequencing genomic profiling disclosed a rare L597K-BRAF mutation and vemurafenib plus cobimetinib therapy was initiated in January 2018. Seven days after treatment start, a remarkable clinical improvement was observed. In April 2018, the patient achieved partial response, which was sustained until October 2018. Cases of patients with non-V600-BRAF mutations responding to iBRAF/iMEK therapy have been reported over the last years. To the best of our knowledge, this is the first case reporting response to combined iBRAF/iMEK therapy in a patient with metastatic melanoma harboring L597K mutation.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Melanoma/tratamiento farmacológico , Melanoma/genética , Proteínas Proto-Oncogénicas B-raf/antagonistas & inhibidores , Proteínas Proto-Oncogénicas B-raf/genética , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/genética , Azetidinas/uso terapéutico , Dorso/patología , Dacarbazina/uso terapéutico , Humanos , Imidazoles/uso terapéutico , Masculino , Melanoma/patología , Persona de Mediana Edad , Mutación , Oximas/uso terapéutico , Piperidinas/uso terapéutico , Piridonas/uso terapéutico , Pirimidinonas/uso terapéutico , Neoplasias Cutáneas/patología , Vemurafenib/uso terapéuticoRESUMEN
BACKGROUND: In recent years, biomedical ontologies have become important for describing existing biological knowledge in the form of knowledge graphs. Data mining approaches that work with knowledge graphs have been proposed, but they are based on vector representations that do not capture the full underlying semantics. An alternative is to use machine learning approaches that explore semantic similarity. However, since ontologies can model multiple perspectives, semantic similarity computations for a given learning task need to be fine-tuned to account for this. Obtaining the best combination of semantic similarity aspects for each learning task is not trivial and typically depends on expert knowledge. RESULTS: We have developed a novel approach, evoKGsim, that applies Genetic Programming over a set of semantic similarity features, each based on a semantic aspect of the data, to obtain the best combination for a given supervised learning task. The approach was evaluated on several benchmark datasets for protein-protein interaction prediction using the Gene Ontology as the knowledge graph to support semantic similarity, and it outperformed competing strategies, including manually selected combinations of semantic aspects emulating expert knowledge. evoKGsim was also able to learn species-agnostic models with different combinations of species for training and testing, effectively addressing the limitations of predicting protein-protein interactions for species with fewer known interactions. CONCLUSIONS: evoKGsim can overcome one of the limitations in knowledge graph-based semantic similarity applications: the need to expertly select which aspects should be taken into account for a given application. Applying this methodology to protein-protein interaction prediction proved successful, paving the way to broader applications.