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Hybrid scaffolds that are based on PLA and PLA/PMMA with 75/25, 50/50, and 25/75 weight ratios and functionalized with 10 wt.% of bioglass nanoparticles (n-BG) were developed using an electrospinning technique with a chloroform/dimethylformamide mixture in a 9:1 ratio for bone tissue engineering applications. Neat PLA and PLA/PMMA hybrid scaffolds were developed successfully through a (CF/DMF) solvent system, obtaining a random fiber deposition that generated a porous structure with pore interconnectivity. However, with the solvent system used, it was not possible to generate fibers in the case of the neat PMMA sample. With the increase in the amount of PMMA in PLA/PMMA ratios, the fiber diameter of hybrid scaffolds decreases, and the defects (beads) in the fiber structure increase; these beads are associated with a nanoparticle agglomeration, that could be related to a low interaction between n-BG and the polymer matrix. The Young's modulus of PLA/PMMA/n-BG decreases by 34 and 80%, indicating more flexible behavior compared to neat PLA. The PLA/PMMA/n-BG scaffolds showed a bioactive property related to the presence of hydroxyapatite crystals in the fiber surface after 28 days of immersion in a Simulated Body Fluids solution (SBF). In addition, the hydrolytic degradation process of PLA/PMMA/n-BG, analyzed after 35 days of immersion in a phosphate-buffered saline solution (PBS), was less than that of the pure PLA. The in vitro analysis using an HBOF-1.19 cell line indicated that the PLA/PMMA/n-BG scaffold showed good cell viability and was able to promote cell proliferation after 7 days. On the other hand, the in vivo biocompatibility evaluated via a subdermal model in BALC male mice corroborated the good behavior of the scaffolds in avoiding the generation of a cytotoxic effect and being able to enhance the healing process, suggesting that the materials are suitable for potential applications in tissue engineering.
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Cerâmica , Nanopartículas , Poliésteres , Polimetil Metacrilato , Engenharia Tecidual , Alicerces Teciduais , Engenharia Tecidual/métodos , Poliésteres/química , Polimetil Metacrilato/química , Alicerces Teciduais/química , Cerâmica/química , Cerâmica/farmacologia , Nanopartículas/química , Animais , Camundongos , Osso e Ossos/efeitos dos fármacos , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Humanos , Linhagem CelularRESUMO
PURPOSE: Assessing competency in surgical procedures is key for instructors to distinguish whether a resident is qualified to perform them on patients. Currently, assessment techniques do not always focus on providing feedback about the order in which the activities need to be performed. In this research, using a Process Mining approach, process-oriented metrics are proposed to assess the training of residents in a Percutaneous Dilatational Tracheostomy (PDT) simulator, identifying the critical points in the execution of the surgical process. MATERIALS AND METHODS: A reference process model of the procedure was defined, and video recordings of student training sessions in the PDT simulator were collected and tagged to generate event logs. Three process-oriented metrics were proposed to assess the performance of the residents in training. RESULTS: Although the students were proficient in classic metrics, they did not reach the optimum in process-oriented metrics. Only in 25% of the stages the optimum was achieved in the last session. In these stages, the four more challenging activities were also identified, which account for 32% of the process-oriented metrics errors. CONCLUSIONS: Process-oriented metrics offer a new perspective on surgical procedures performance, providing a more granular perspective, which enables a more specific and actionable feedback for both students and instructors.
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Competência Clínica , Traqueostomia , Humanos , Dilatação , Retroalimentação , Estudantes , Traqueostomia/educação , Traqueostomia/métodosRESUMO
In this paper, two control laws are proposed and applied in a model for a continuous Microbial Electrochemical Cells system. The used model is based on mass balances describing the behavior of substrate consumption, microbial growth, competition between anodophilic and methanogenic microorganisms for the carbon source in the anode, hydrogen generation, and electrical current production. The main control objective is to improve the electrical current generated and thus the production of bio-hydrogen gas in the reactor, using the dilution rate and the applied potential as individual control input variables. The control laws implemented are nonlinear adaptive type. In order to demonstrate its usefulness, numerical simulation runs involving multiple set-point changes and input perturbations were conducted for each control variable. The results of these simulations show that both control laws were able to respond adequately and efficiently to the disturbances and reach the reference value to which they were subjected. Moreover, it is possible to control both the electrical current produced and the hydrogen produced. Finally, these simulations also show that the highest rate of hydrogen production can be obtained using the applied potential as a control input, but such productivity is only attainable for a short period of time.
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Fontes de Energia Bioelétrica , Purificação da Água , Eletrodos , Eletrólise , HidrogênioRESUMO
Patients who suffer from cancer are at a higher risk of complications when they experience malnutrition. Evidence shows that oral nutritional supplements favor the healing process. The main objective of this study was to evaluate the efficacy of preoperative oral nutritional intervention in oncological patients undergoing surgery. This study assessed retrospectively 55 cancer patients who previously had undergone abdominal surgery and did not have receive pre-surgical nutritional support (control group), and prospectively 30 oncological patients undergoing gastrointestinal surgery and received pre-surgical high-protein nutritional support (experimental group). All patients had to have a NRS 2002 score ≥ 3. Analytical and clinical parameters were analyzed and the NRS 2002 screening test was performed. Post-operative assessments of surgical wound complications were also carried out to determine the impact of nutrition support. Pre-surgical nutritional interventions reduced the incidence and severity of wound complications as well as the length of hospital stays. Only 26.7% of patients in the experimental group had complications compared to 60% of the control group (P = 0.003). We conclude that pre-surgical nutritional interventions of patients undergoing surgery can improve post-surgical patient outcomes of malnourished patients.
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Neoplasias/cirurgia , Apoio Nutricional/métodos , Procedimentos Cirúrgicos Operatórios/efeitos adversos , Ferida Cirúrgica/prevenção & controle , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Nutrição Enteral/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/patologia , Cuidados Pré-Operatórios/métodos , Estudos Retrospectivos , Ferida Cirúrgica/etiologia , Ferida Cirúrgica/patologia , Adulto JovemRESUMO
The aim of this study was to generate practical recommendations to assist rheumatologists and dermatologists in the management of cardiovascular (CV) comorbidities in patients with moderate-to-severe psoriasis (MS-PSO) and psoriatic arthritis (PsA). A two-round Delphi study was conducted. A panel of experts rated their agreement with a set of statements (n = 52) on a nine-point Likert scale (1 = totally disagree; 9 = totally agree). Statements were classified as inappropriate (median 1-3), irrelevant (median 4-6) or appropriate (median 7-9). Consensus was established when at least two-thirds of the panel responded with a score within any one range. A total of 25 experts, 60% rheumatologists and 40% dermatologists, participated in two consultation rounds. There was overall unanimity on the appropriateness of an initial assessment for CV risk factors in all patients with MS-PSO and PsA. Most panelists (88.0%) also supported the evaluation of patients' psychological and physical status. Additionally, most panelists (72.2%) agreed on a novel sequential approach for the management of CV comorbidities. This sequence starts with the assessment of hypertension, diabetes and dyslipidemia along with the identification of depression and anxiety disorders. Once these factors are under control, smoking cessation programs might be initiated. Finally, if patients have not met weight loss goals with lifestyle modifications, they should receive specialized treatment for obesity. This study has drawn up a set of practical recommendations that will facilitate the management of CV comorbidities in patients with MS-PSO and PsA.
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Artrite Psoriásica , Psoríase , Humanos , Artrite Psoriásica/diagnóstico , Artrite Psoriásica/epidemiologia , Artrite Psoriásica/terapia , Psoríase/diagnóstico , Psoríase/epidemiologia , Psoríase/terapia , Comorbidade , Reumatologistas , ObesidadeRESUMO
AIMS: To evaluate in a real-world setting the effectiveness of exenatide once-weekly (ExQW) in patients with T2D and to determine predictors of glycaemic and weight response to this drug at 6 months. METHODS: Observational, retrospective, multicenter study in adult patients with T2D and BMI ≥30 kg/m2 from 4 tertiary Spanish hospitals who started ExQW therapy at least 6 months before the inclusion and had not achieved adequate glycaemic control on oral therapies or other GLP-1 receptor agonists. Glycaemic response was defined as an A1C reduction ≥1.0% and weight response as a weight loss ≥3% 6 months after ExQW. The best predictive models of glycaemic and weight response were estimated by binary logistic regression. RESULTS: One hundred and forty eight patients were included, mean age 58.0 years, A1C 7.7%, weight 105.9 kg and BMI 38.4 kg/m2 . A1C (-1.1%), weight (-3.9 kg), systolic blood pressure (-4.0 mm Hg), diastolic blood pressure (-2.9 mm Hg), LDL-cholesterol (-14.2 mg/dL) and triglycerides (-31.0 mg/dL) significantly decreased 6 months after ExQW. 41.5% of patients had an A1C reduction ≥1.0% and 53.1% lost ≥3% of baseline weight. Glycaemic and weight reductions were sustained in patients completing 1 and 2 years of follow-up. The best predictive model of glycaemic response only included higher A1C levels (OR 3.9), whereas higher BMI (OR 1.1) and prior DPP-4i therapy (OR 3.1) were associated to weight response in the multivariate analysis. CONCLUSIONS: In a real-world setting, ExQW significantly decreased A1C, weight, blood pressure and lipids at 6 months. Our study identified higher baseline A1C as the sole independent predictor of glycaemic response to ExQW and higher BMI and previous DDP4i treatment as predictive factors of meaningful weight response.
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Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Adesão à Medicação , Peptídeos/uso terapêutico , Peçonhas/uso terapêutico , Redução de Peso , Adulto , Idoso , Glicemia/análise , Pressão Sanguínea , Peso Corporal , Doenças Cardiovasculares , Esquema de Medicação , Exenatida , Feminino , Hemoglobinas Glicadas/análise , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
The activation of the highly conserved unfolded protein response (UPR) is prominent in the pathogenesis of the most prevalent neurodegenerative disorders, such as Alzheimer's disease (AD), Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS), which are classically characterized by an accumulation of aggregated or misfolded proteins. This activation is orchestrated by three endoplasmic reticulum (ER) stress sensors: PERK, ATF6 and IRE1. These sensors transduce signals that induce the expression of the UPR gene programme. Here, we first identified an early activator of the UPR and investigated the role of a chronically activated UPR in the pathogenesis of X-linked adrenoleukodystrophy (X-ALD), a neurometabolic disorder that is caused by ABCD1 malfunction; ABCD1 transports very long-chain fatty acids (VLCFA) into peroxisomes. The disease manifests as inflammatory demyelination in the brain or and/or degeneration of corticospinal tracts, thereby resulting in spastic paraplegia, with the accumulation of intracellular VLCFA instead of protein aggregates. Using X-ALD mouse model (Abcd1 - and Abcd1 - /Abcd2 -/- mice) and X-ALD patient's fibroblasts and brain samples, we discovered an early engagement of the UPR. The response was characterized by the activation of the PERK and ATF6 pathways, but not the IRE1 pathway, showing a difference from the models of AD, PD or ALS. Inhibition of PERK leads to the disruption of homeostasis and increased apoptosis during ER stress induced in X-ALD fibroblasts. Redox imbalance appears to be the mechanism that initiates ER stress in X-ALD. Most importantly, we demonstrated that the bile acid tauroursodeoxycholate (TUDCA) abolishes UPR activation, which results in improvement of axonal degeneration and its associated locomotor impairment in Abcd1 - /Abcd2 -/- mice. Altogether, our preclinical data provide evidence for establishing the UPR as a key drug target in the pathogenesis cascade. Our study also highlights the potential role of TUDCA as a treatment for X-ALD and other axonopathies in which similar molecular mediators are implicated.
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Adrenoleucodistrofia/fisiopatologia , Axônios/efeitos dos fármacos , Degeneração Neural/fisiopatologia , Ácido Tauroquenodesoxicólico/farmacologia , Resposta a Proteínas não Dobradas/fisiologia , Animais , Axônios/patologia , Humanos , Camundongos , Camundongos KnockoutRESUMO
X-linked adrenoleukodystrophy is a neurometabolic disorder caused by inactivation of the peroxisomal ABCD1 transporter of very long-chain fatty acids. In mice, ABCD1 loss causes late onset axonal degeneration in the spinal cord in association with locomotor disability resembling the most common phenotype in patients, adrenomyeloneuropathy. Increasing evidence indicates that oxidative stress and bioenergetic failure play major roles in the pathogenesis of X-linked adrenoleukodystrophy. In this study, we aimed to evaluate whether mitochondrial biogenesis is affected in X-linked adrenoleukodystrophy. We demonstrated that Abcd1 null mice show reduced mitochondrial DNA concomitant with downregulation of mitochondrial biogenesis pathway driven by PGC-1α/PPARγ and reduced expression of mitochondrial proteins cytochrome c, NDUFB8 and VDAC. Moreover, we show that the oral administration of pioglitazone, an agonist of PPARγ, restored mitochondrial content and expression of master regulators of biogenesis, neutralized oxidative damage to proteins and DNA, and reversed bioenergetic failure in terms of ATP levels, NAD+/NADH ratios, pyruvate kinase and glutathione reductase activities. Most importantly, the treatment halted locomotor disability and axonal damage in X-linked adrenoleukodystrophy mice. These results lend support to the use of pioglitazone in clinical trials with patients with adrenomyeloneuropathy and reveal novel molecular mechanisms of action of pioglitazone in neurodegeneration. Future studies should address the effects of this anti-diabetic drug on other axonopathies in which oxidative stress and mitochondrial dysfunction are contributing factors.
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Adrenoleucodistrofia/tratamento farmacológico , Axônios/efeitos dos fármacos , Hipoglicemiantes/uso terapêutico , Degeneração Neural/tratamento farmacológico , Tiazolidinedionas/uso terapêutico , Membro 1 da Subfamília D de Transportadores de Cassetes de Ligação de ATP , Transportadores de Cassetes de Ligação de ATP/genética , Adrenoleucodistrofia/genética , Adrenoleucodistrofia/patologia , Animais , Axônios/metabolismo , Axônios/patologia , Modelos Animais de Doenças , Ácidos Graxos/metabolismo , Glutationa Redutase/metabolismo , Humanos , Hipoglicemiantes/farmacologia , Camundongos , Camundongos Knockout , Degeneração Neural/genética , Degeneração Neural/patologia , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Pioglitazona , Tiazolidinedionas/farmacologia , Resultado do TratamentoRESUMO
The cactus moth, Cactoblastis cactorum (Berg) (Lepidoptera: Pyralidae) is native to South America and has been used as a biocontrol agent of Opuntia (Cactaceae) in Australia and South Africa. Its invasion in North America has raised concerns for the native Opuntia in the USA and Mexico. We investigated the reproductive biology and rearing procedures of a host-specific potential biocontrol agent, Apanteles opuntiarum Martínez and Berta (Hymenoptera: Braconidae). Given the gregarious nature of the parasitoid larvae, we studied the morphology of the immature stages and evaluated evidence of polyembryony and superparasitism. We also investigated the effects of host exposure arena and host density on parasitism rates and wasp production. The morphological descriptions provide a basis for comparison with other species. Early larval instars of A. opuntiarum are similar to other microgastrine immature stages. However, the mature larva exhibits placoid sensilla in the epistomal region, a unique character not previously reported. We provide evidence that A. opuntiarum eggs are not polyembryonic; females frequently superparasitize and have an oviposition preference for larvae parasitized 1-2 d previously. Exposing larvae of C. cactorum to wasps while inside the cactus resulted in lower parasitism and fewer offspring from each host than exposing larvae in the arena without the cactus. Parasitism and mortality rates were higher at lower host densities, possibly due to reduced host group defensive behavior. These results suggest that preference for superparasitism, host defensive behavior, and interactions with the cactus may play an important role in per-host wasp production under laboratory conditions.
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BACKGROUND: given the boom in sports in school age, its intensity and the increase in sports in females, we are experiencing a boom in sports injuries characteristic of "adults" in growing patients, the anterior cruciate ligament being an injury with possible serious consequences. METHODS: to show the surgical technique "without bone tunnels" by Micheli-Kocher in anterior cruciate ligament reconstruction in growing patients based on our results in 20 patients. RESULTS: since 2017 we have performed the technique "without bone tunnels" by Micheli-Kocher in 30 patients, 20 of whom have been followed up for more than 2 years. In our study, we have observed a return to previous sports activity in more than 90% of the patients, with only one patient undergoing reoperation due to a new rupture of the plasty. The results on the IKDC scales show an improvement in mean score from 42 points preoperatively to 84 postoperatively and on the Lysholm scale from 48 preoperatively to 94 postoperatively. CONCLUSIONS: the technique "without bone tunnels" by Micheli-Kocher is a technique indicated in patients under 12 years of age and Tanner stage 2 or less. It is a technique of moderate complexity with excellent results in recovery from previous sports activity and knee stability. LEVEL OF EVIDENCE: Level IV (case series).
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INTRODUCTION: The monk parakeet (Myiopsitta monachus) is a widespread invasive species native to southern South America that has become established in many regions of the world. Monk parakeets breed in a large, fully enclosed structure built from twigs, which consist of one to many individual brooding chambers. The species has been considered to be socially and genetically monogamous. However, genetic relatedness of adults to juveniles in the native area was found to be lower than expected for monogamy. To assess the significance of this discrepancy, we examined individual and population genetic patterns of microsatellite loci at two sites in Córdoba province, Argentina. RESULTS: We sampled 154 nestlings and 42 adults in Córdoba, Argentina. Mean value of pairwise relatedness of nestlings within chambers was about 0.40. Contrarily, relatedness of nestlings between chambers was close to zero. We found a considerable degree of variation in nestling pairwise relatedness and parentage within chambers, including chambers with combinations of unrelated, half-sib, and full-sib nestlings. The proportion of sibling relatedness indicated monogamy in 47% and extra pair-paternity in 40% of the chambers. We also found intra-brood parasitism in 3% of the chambers. CONCLUSIONS: Our results indicate that the monk parakeet is sexually polygamous in its native range in Argentina, which is consistent with the observed mean value of relatedness of adults to juveniles of about 0.4. We also confirm the existence of intra-brood parasitism. High density of monk parakeets may favor occurrence of extra-pair paternity and intra-brood parasitism in the native sites.
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Two new species of Tetradiplosis inducing galls on Prosopis caldenia are described from Argentina: Tetradiplosis panghitruz Martínez n. sp. and Tetradiplosis rayen Martínez n. sp. Tetradiplosispanghitruz induces multilocular galls on vegetative stems, whereas T. rayen induces unilocular galls containing multiple larvae on the rachis of the developing inflorescences. The adult male, female, pupa and larva are described and illustrated for both species. A key to the known species of the genus is provided.
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Dípteros/anatomia & histologia , Dípteros/classificação , Tumores de Planta/parasitologia , Prosopis/parasitologia , Animais , Argentina , Dípteros/patogenicidade , Feminino , MasculinoRESUMO
OBJECTIVE: The incidence of COVID-19 infections among health professionals during the sixth wave has suffered an exponential increase, mainly due to the rapid community transmission caused by the Omicron variant. The main objective of the study was to evaluate the time to negativization in COVID-positive health professionals during the sixth wave, according to the PDIA result; and secondarily, to evaluate the possible influence of other factors (previous infection, vaccination, sex, age, job position) on the time to get negative status. METHODS: A descriptive, longitudinal, observational and retrospective study was carried out at Infanta Sofía University Hospital (Madrid, Spain). Made from the registry of the Occupational Risk Prevention Service of suspected or confirmed cases of SARS-COV-2 infection in health professionals, during the period between November 1, 2021 and February 28, 2022. Bivariate comparisons were made using Mann Whitney, Kruskal Wallis or Chi-square test (or exact test) according to variables. Subsequently, logistic regression (explanatory model) was performed. RESULTS: The cumulative incidence of SARS-COV-2 infection in health professionals was 23.07%. The mean time to become negative was 9.94 days. Only the history of previous SARS-COV-2 infection had a statistically significant influence on the time to negativization of PDIA. The variables vaccination, sex and age had no effect on the time to negativization of PDIA. CONCLUSIONS: Professionals with a history of COVID-19 infection present lower times of negativization than those who had not have the disease. The results of our study confirm the immune escape of the vaccine against COVID-19, since more than 95% of those infected had received a complete vaccination schedule.
OBJETIVO: La incidencia de contagios por COVID-19 entre profesionales sanitarios durante la sexta ola, ha sufrido un incremento exponencial motivado principalmente por la rápida trasmisión comunitaria ocasionada por la variante Ómicron. El objetivo principal del estudio fue evaluar el tiempo de negativización en los profesionales sanitarios COVID positivos durante la sexta ola, según resultado de PDIA; y, de forma secundaria, evaluar la posible influencia de otros factores (infección previa, vacunación, sexo, edad, puesto de trabajo) en el tiempo de negativización. METODOS: Se realizó un estudio descriptivo, longitudinal, observacional y retrospectivo en el Hospital Universitario Infanta Sofía (Madrid), a partir del registro del Servicio de Prevención de Riesgos Laborales de casos sospechosos o confirmados de infección por SARS-COV-2 en profesionales sanitarios, durante el periodo comprendido entre el 1 de noviembre de 2021 y el 28 de febrero de 2022. Se hicieron comparaciones bivariadas mediante Mann Whitney, Kruskal Wallis o test de Chi-cuadrado (o test exacto) según variables. Posteriormente se realizó regresión logística (modelo explicativo). RESULTADOS: La incidencia acumulada de infección por SARS-COV-2 en profesionales sanitarios fue del 23,07%. El tiempo medio en negativizar fue de 9,94 días. Únicamente el antecedente de infección previa por SARS-COV-2 influyó de forma estadísticamente significativa en el tiempo de negativización de PDIA. Las variables vacunación, sexo y edad no tuvieron efecto en el tiempo de negativización de PDIA. CONCLUSIONES: Los profesionales con antecedente de infección por COVID-19 presentan tiempos inferiores de negativización que aquellos que no han pasado la enfermedad. Los resultados de nuestro estudio constatan el escape inmunológico de la vacuna frente al COVID-19, pues más del 95% de los infectados habían recibido una pauta de vacunación completa.
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COVID-19 , Humanos , Espanha/epidemiologia , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Estudos Retrospectivos , SARS-CoV-2 , Hospitais Públicos , Atenção à SaúdeRESUMO
In this study, risk estimation based on sampling and subsampling uncertainty was performed for pesticide analysis in homogeneous spice products such as paprika. The results of the subsampling were also used to estimate the minimum weight necessary in subsampling to minimize overall uncertainty. The results show that subsampling has more uncertainty than sampling in the product due to high homogeneity in the manufacturer's batch. On the other hand, results using the Monte Carlo (MC) simulation on the size of the subsample indicate that uncertainty is lower for weights between 20 and 30 g and increases for sample sizes of 100 g. A sample size of 30 g was used for saffron, and the values simulated with the MC method were confirmed.
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Capsicum , Praguicidas , Incerteza , Simulação por Computador , Método de Monte CarloRESUMO
Dithiocarbamate Fungicides (DTFs) are widely analyzed and studied mainly due to the fact that they play an important role in the cultivation of fruits and vegetables. This manuscript aims to display the results of a bibliometric analysis based on the Web of Science© database, performed in the DTF and food research area. A total of 374 publications were examined. The most scientific production was concentrated between 2012 and 2021, showing a decrease of 32% over the last two years. The Journal of Agricultural and Food Chemistry, India, and Sardar Vallabhbhai National Institute of Technology were the most productive journal, country, and institution, respectively. Reference Publication Year Spectroscopy index showed a decrease of 95% in the last last years studied. Finally, current and future trends should focus on keywords such as individual DTF (Mancozeb, Thiram and Maneb), metabolites (Ethylenethiourea, Propilenthiourea) and a change in the analysis methodology: HPLC versus traditional GC.
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Fungicidas Industriais , Fungicidas Industriais/análise , Tiram/análise , Verduras/química , Frutas/química , BibliometriaRESUMO
BACKGROUND: Whole-exome sequencing (WES) and whole-genome sequencing (WGS) have become indispensable tools to solve rare Mendelian genetic conditions. Nevertheless, there is still an urgent need for sensitive, fast algorithms to maximise WES/WGS diagnostic yield in rare disease patients. Most tools devoted to this aim take advantage of patient phenotype information for prioritization of genomic data, although are often limited by incomplete gene-phenotype knowledge stored in biomedical databases and a lack of proper benchmarking on real-world patient cohorts. METHODS: We developed ClinPrior, a novel method for the analysis of WES/WGS data that ranks candidate causal variants based on the patient's standardized phenotypic features (in Human Phenotype Ontology (HPO) terms). The algorithm propagates the data through an interactome network-based prioritization approach. This algorithm was thoroughly benchmarked using a synthetic patient cohort and was subsequently tested on a heterogeneous prospective, real-world series of 135 families affected by hereditary spastic paraplegia (HSP) and/or cerebellar ataxia (CA). RESULTS: ClinPrior successfully identified causative variants achieving a final positive diagnostic yield of 70% in our real-world cohort. This includes 10 novel candidate genes not previously associated with disease, 7 of which were functionally validated within this project. We used the knowledge generated by ClinPrior to create a specific interactome for HSP/CA disorders thus enabling future diagnoses as well as the discovery of novel disease genes. CONCLUSIONS: ClinPrior is an algorithm that uses standardized phenotype information and interactome data to improve clinical genomic diagnosis. It helps in identifying atypical cases and efficiently predicts novel disease-causing genes. This leads to increasing diagnostic yield, shortening of the diagnostic Odysseys and advancing our understanding of human illnesses.
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Algoritmos , Genômica , Humanos , Estudos Prospectivos , Bases de Dados Factuais , Estudos de Associação GenéticaRESUMO
In this work we have assessed the capacity of a linear semiconductor optical amplifier to compensate the fiber and component losses present in a wavelength division multiplexing passive optical network (WDM-PON) evolution from fiber-to-the-building (FTTB) to fiber-to-the-home access. The evaluation measurements confirm that the presence of a semiconductor optical amplifier placed at the entry of a group of optical network units that share the same wavelength channel can raise the loss budget that the link can tolerate in the fiber, compensating for the losses of a passive splitter up to a 1:16 division rate, allowing the upgrade of existing WDM-PON FTTB structures to make the fiber reach the final user's home.
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Parallel phenotypic divergence is the independent differentiation between phenotypes of the same lineage or species occupying ecologically similar environments in different populations. We tested in the Antarctic limpet Nacella concinna the extent of parallel morphological divergence in littoral and sublittoral ecotypes throughout its distribution range. These ecotypes differ in morphological, behavioural and physiological characteristics. We studied the lateral and dorsal outlines of shells and the genetic variation of the mitochondrial gene Cytochrome Oxidase subunit I from both ecotypes in 17 sample sites along more than 2,000 km. The genetic data indicate that both ecotypes belong to a single evolutionary lineage. The magnitude and direction of phenotypic variation differ between ecotypes across sample sites; completely parallel ecotype-pairs (i.e., they diverge in the same magnitude and in the same direction) were detected in 84.85% of lateral and 65.15% in dorsal view comparisons. Besides, specific traits (relative shell height, position of shell apex, and elliptical/pear-shape outline variation) showed high parallelism. We observed weak morphological covariation between the two shape shell views, indicating that distinct evolutionary forces and environmental pressures could be acting on this limpet shell shape. Our results demonstrate there is a strong parallel morphological divergence pattern in N. concinna along its distribution, making this Antarctic species a suitable model for the study of different evolutionary forces shaping the shell evolution of this limpet.
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Ecótipo , Gastrópodes , Animais , Regiões Antárticas , Gastrópodes/genética , FenótipoRESUMO
We describe the case of a 64 years old patient, known for an Enterococcus faecalis endocarditis on a 25 mm Edwards-Carpentier biological aortic valve in 2020, who was re-hospitalized one year later in cardiac surgery for a recurrence of Enterococcus faecalisbacteriemia. During hospitalization, the patient presented a cardiac arrest. The coronarography revealed an acute occlusion of the left coronary artery. The autopsy confirmed an Enterococcus faecalis thrombus on aortic valve and left coronary artery. Although systemic embolism is a common complication of infective endocarditis, septic embolism is an unsual cause of acute coronary syndrome and a very rare cause of cardiac arrest. Our case highlights a rare and potentially fatal complication of infective endocarditis: acute coronary syndrome on septic coronary embolism.