Case report: Equine metacarpophalangeal joint partial and full thickness defects treated with allogenic equine synovial membrane mesenchymal stem/stromal cell combined with umbilical cord mesenchymal stem/stromal cell conditioned medium.

Here, we describe a case of a 5-year-old show-jumping stallion presented with severe lameness, swelling, and pain on palpation of the left metacarpophalangeal joint (MCj). Diagnostic imaging revealed full and partial-thickness articular defects over the lateral condyle of the third metacarpus (MC3) and the dorsolateral aspect of the first phalanx (P1). After the lesion's arthroscopic curettage, the patient was subjected to an innovative regenerative treatment consisting of two intra-articular injections of equine synovial membrane mesenchymal stem/stromal cells (eSM-MSCs) combined with umbilical cord mesenchymal stem/stromal cells conditioned medium (UC-MSC CM), 15 days apart. A 12-week rehabilitation program was accomplished, and lameness, pain, and joint effusion were remarkably reduced; however, magnetic resonance imaging (MRI) and computed tomography (CT) scan presented incomplete healing of the MC3's lesion, prompting a second round of treatment. Subsequently, the horse achieved clinical soundness and returned to a higher level of athletic performance, and imaging exams revealed the absence of lesions at P1, fulfillment of the osteochondral lesion, and cartilage-like tissue formation at MC3's lesion site. The positive outcomes suggest the effectiveness of this combination for treating full and partial cartilage defects in horses. Multipotent mesenchymal stem/stromal cells (MSCs) and their bioactive factors compose a novel therapeutic approach for tissue regeneration and organ function restoration with anti-inflammatory and pro-regenerative impact through paracrine mechanisms.

Biomonitoring of air quality in the Bodoquena microregion, Mato Grosso Do Sul: mutagenic and morphoanatomical alterations in Tradescantia pallida (rose) D.R. Hunt var. purpurea

Abstract The objective of this study was to assess air quality in relation to vehicular traffic flow in cities located at different elevations in the Bodoquena microregion, state of Mato Grosso do Sul, Brazil. To do so, a micronucleus test was carried out using the TRAD-MCN bioassay on young Tradescantia buds collected from February to November 2018 in seven cities of the microregion with different traffic flow intensities. Meteorological parameters were evaluated, and vehicular traffic was counted to determine traffic flow in each city. With data from the Shuttle Radar Topography Mission (SRTM) and processing in Esri ArcGIS® software version 10.5.1, the regions was mapped based on an Elevation Model. Morphoanatomical analyses were performed according to standard methodology. Measurements were taken of thickness, length and width of tissues and structures, including the upper and lower cuticle, upper and lower epidermis, hypodermis and mesophyll. The greatest traffic flow was found in the cities of Bodoquena, Guia Lopes da Laguna, Jardim, and Porto Murtinho, with the period from 5:00 to 6:00 p.m. showing the highest traffic flow. The greatest frequency of mutagenic alterations was found in the city of Guia Lopes da Laguna, although the results did not differ significantly from Bonito, Caracol, and Jardim. Throughout the biomonitoring, the summer and autumn seasons showed the greatest micronuclei frequencies in all evaluated cities. Variations in the tissue/structure thickness was observed across cities and seasons, but with a decrease in thickness during autumn. In general, the tissues/structures were smaller for the cities of Nioaque and Porto Murtinho, while the anatomical and morphological characteristics of leaf length and thickness showed no differences among cities. We found limited correlation between micronuclei frequency and traffic flow, supporting the hypothesis that although mutagenic alterations are observed in T. pallida, in this microregion the changes are numerically lower when compared to other regions of the state. In light of the genotoxic and morphoanatomical factors assessed herein, the Bodoquena microregion appears to be well preserved in terms of air quality, presenting low micronuclei frequency and a limited reduction in tissues and leaf structures, regardless of the season.

Resumo O objetivo deste trabalho foi avaliar a qualidade do ar com base no fluxo veicular das cidades localizadas em diferentes altitudes na microrregião da Bodoquena, no estado de Mato Grosso do Sul, Brasil. Para tal, foi realizado o teste de micronúcleo, por meio do bioensaio TRAD-MCN em botões jovens de Tradescantia coletadas no período entre fevereiro a novembro de 2018 em sete cidades da microrregião da Bodoquena, com diferentes intensidades de fluxo veicular. Foram avaliados os parâmetros meteorológicos, os veículos foram contados para determinar o tráfego de veículos em cada cidade e altitude. A partir da topografia Shuttle Radar (SRTM) e processamento no software Esri ArcGIS® versão 10.5.1 foi possível mapear a área com base no Modelo de Elevação. As análises morfoanatômicos foram realizadas conforme metodologia padrão. As mensurações de espessura, comprimento, largura dos tecidos e estruturas como a cutícula superior, cutícula inferior, face superior e face inferior da epiderme, hipoderme e mesófilo foram avaliadas. O maior fluxo veicular foi encontrado nas cidades de Bodoquena, Guia Lopes da Laguna, Jardim e Porto Murtinho. O horário das 17:00 às 18:00h foi o que apresentou maiores fluxo de veículos. A maior frequência de alterações mutagênicas foi encontrada na cidade de Guia Lopes, não diferindo de Bonito, Caracol e Jardim. Ao longo do biomonitoramento observou-se que as estações de verão e outono foram as que apresentaram maiores frequências de micronúcleo independente da cidade avaliada. Observou-se que a correlação entre a frequência de micronúcleos e o fluxo veicular foi baixa, apoiando a tese de que essa microrregião, embora apresente alterações mutagênicas em T. pallida, as alterações numericamente são pequenas quando comparadas a outras regiões do estado de Mato Grosso do Sul. Observou-se uma variação na espessura dos tecidos/estruturas que é variável entre as diferentes cidades e estações do ano. De forma geral os tecidos/estrutura apresentaram redução na espessura para as cidades de Nioaque e Porto Murtinho quanto aos aspectos anatômicos e morfológicos, sendo que, para o comprimento e espessura foliar não foi observado diferenças entre as cidades. Em relação as estações do ano, observou-se que no outono a espessura dos tecidos/estruturas são menores. Diante dos fatores genotóxicos e morfoanatômicos aqui avaliados, a microrregião da Bodoquena parece estar bem preservada em termos de qualidade do ar, apresentando baixa frequência de micronúcleos e redução limitada de tecidos e estruturas foliares, independentemente da estação do ano.

Peer assessment in medical communication skills training in programmatic assessment: A qualitative study examining faculty and student perceptions.

INTRODUCTION: Current literature recommends assessment of communication skills in medical education combining different settings and multiple observers. There is still a gap in understanding about whether and how peers assessment facilitates learning in communication skills training. METHODS: We designed a qualitative study using focus group interviews and thematic analysis, in a medical course in the Netherlands. We aimed to explore medical students' and teachers' experiences, perceptions, and perspectives about challenges and facilitating factors in PACST (Peer assessment in medical communication skills training). RESULTS: Most of the participants reported that peer feedback was a valuable experience when learning communication skills. The major challenges for the quality and credibility of PACST reported by the participants are the question whether peer feedback is critical enough for learning and the difficulty of actually engaging students in the assessment process. CONCLUSION: Teachers reviewing students' peer assessments may improve the quality and their credibility and the reviewed assessments can best be used for learning purposes. We suggest to pay sufficient attention to teachers' roles in PACST, ensuring a safe and trustworthy environment and additionally helping students to internalize the value of being vulnerable during the evaluation process.

Preclinical assessment of an anti-HTLV-1 heterologous DNA/MVA vaccine protocol expressing a multiepitope HBZ protein.

BACKGROUND: Human T-lymphotropic virus 1 (HTLV-1) is associated with the development of several pathologies and chronic infection in humans. The inefficiency of the available treatments and the challenge in developing a protective vaccine highlight the need to produce effective immunotherapeutic tools. The HTLV-1 basic leucine zipper (bZIP) factor (HBZ) plays an important role in the HTLV-1 persistence, conferring a survival advantage to infected cells by reducing the HTLV-1 proteins expression, allowing infected cells to evade immune surveillance, and enhancing cell proliferation leading to increased proviral load. METHODS: We have generated a recombinant Modified Virus Vaccinia Ankara (MVA-HBZ) and a plasmid DNA (pcDNA3.1(+)-HBZ) expressing a multiepitope protein based on peptides of HBZ to study the immunogenic potential of this viral-derived protein in BALB/c mice model. Mice were immunized in a prime-boost heterologous protocol and their splenocytes (T CD4+ and T CD8+) were immunophenotyped by flow cytometry and the humoral response was evaluated by ELISA using HBZ protein produced in prokaryotic vector as antigen. RESULTS: T CD4+ and T CD8+ lymphocytes cells stimulated by HBZ-peptides (HBZ42-50 and HBZ157-176) showed polyfunctional double positive responses for TNF-α/IFN-γ, and TNF-α/IL-2. Moreover, T CD8+ cells presented a tendency in the activation of effector memory cells producing granzyme B (CD44+High/CD62L-Low), and the activation of Cytotoxic T Lymphocytes (CTLs) and cytotoxic responses in immunized mice were inferred through the production of granzyme B by effector memory T cells and the expression of CD107a by CD8+ T cells. The overall data is consistent with a directive and effector recall response, which may be able to operate actively in the elimination of HTLV-1-infected cells and, consequently, in the reduction of the proviral load. Sera from immunized mice, differently from those of control animals, showed IgG-anti-HBZ production by ELISA. CONCLUSIONS: Our results highlight the potential of the HBZ multiepitope protein expressed from plasmid DNA and a poxviral vector as candidates for therapeutic vaccine.

Temporal and spatial variability in the isotopic composition of sea urchins along Portuguese coast.

Paracentrotus lividus is a sea urchin widely distributed throughout Mediterranean basin and Atlantic coast, highly appreciated for its gonads. It is broadly distributed along the Portuguese coast and its exploitation has potential to grow. Nevertheless, fluctuations on nutritional composition and sensory traits of P. lividus according to each habitat and seasonality are still little understood. Stable isotopes analysis has been recognised as a powerful tool for exploring environmental-ecological-biological processes in aquatic systems. It is also useful to give indications on how to improve available diets for the aquaculture of this species, contributing to a sustainable rearing. Herein, such technique was used to assess temporal and spatial differences in isotopic composition of P. lividus' gonads and intestines and to evaluate its application as a management tool for the identification of the most suitable locations and periods of the year to collect organisms with high quality gonads. Sampling campaigns were carried out between 2019 and 2020 in five rocky shores along the Portuguese coast (Viana do Castelo, Figueira da Foz, Peniche, Sines and Guia). Three rock pools were selected in each shore, and five specimens were collected per pool. The gonadosomatic index (GSI, %) was calculated and carbon and nitrogen elemental and isotopic composition were determined in gonads and intestine using isotope ratio mass spectrometry. Significant spatial and temporal fluctuations were registered among urchins collected along Portuguese coast. Such variations may be associated with latitudinal gradients along the coast and variations of environmental and ecological conditions within each area, especially those affecting algal biomass, on which urchins primarily feed. More research must be pursued to maximise the use of stable isotopes analysis as a management tool for supporting sustainable exploitation of natural stocks or even to contribute to nutritional studies with new diets for sea urchin production that consider the feeding of these animals in the wild.

The geographical distribution and socioeconomic risk factors of COVID-19, tuberculosis and leprosy in Fortaleza, Brazil.

BACKGROUND: Fortaleza (Brazil) is high endemic for coronavirus disease 2019 (COVID-19), tuberculosis (TB) and leprosy. These three diseases share respiratory droplets through coughing or sneezing as the main mode of transmission but differ in incubation time, with COVID-19 having a short and leprosy a long incubation time. Consequently, contacts of a patient are at higher risk of infection and developing these diseases. There might be scope for combined preventive measures, but a better understanding of the geographical distribution and relevant socioeconomic risk factors of the three diseases is needed first. This study aims to describe the geographic distribution of COVID-19, TB and leprosy incidence and to identify common socioeconomic risk factors. METHODS: The total number of new cases of COVID-19, TB and leprosy, as well as socioeconomic and demographic variables, were retrieved from official registers. The geographical distribution of COVID-19, TB and leprosy rates per neighbourhood was visualised in Quantum GIS, and spatial autocorrelation was measured with Moran's I in GeoDa. A spatial regression model was applied to understand the association between COVID-19, TB, leprosy rates, and socioeconomic factors. RESULTS: COVID-19 and TB showed a more homogenous distribution, whereas leprosy is located more in the south and west of Fortaleza. One neighbourhood (Pedras) in the southeast was identified as high endemic for all three diseases. Literacy was a socioeconomic risk factor for all three diseases: a high literacy rate increases the risk of COVID-19, and a low literacy rate (i.e., illiteracy) increases the risk of TB and leprosy. In addition, high income was associated with COVID-19, while low income with TB. CONCLUSIONS: Despite the similar mode of transmission, COVID-19, TB and leprosy show a different distribution of cases in Fortaleza. In addition, associated risk factors are related to wealth in COVID-19 and to poverty in TB and leprosy. These findings may support policymakers in developing (partially combined) primary and secondary prevention considering the efficient use of resources.

Cytotoxicity of isolated compounds from Picrasma crenata (Vell.) Engl. in animal tumor cell (HTC).

The study aim was to evaluate the cytotoxic activity, using the MTT test [3-(4,5-Dimethilthiazol-2-yl)-2,5-diphenil tetrazolium bromide], from the crude extract of Picrasma crenata (Pau Tenente) and its isolated compounds, quassin and parain, in culture of rat liver tumor cells (HTC). The test was carried out exposing the cells for 24, 48 and 72 hours to concentrations of 5, 10, 50, 100, 200, 300, 400, 500 and 1000 µg of crude extract of Pau Tenente/mL of culture medium and 1, 5, 10, 15, 20, 40, 60, 80 and 100 µg of quassin or parain compounds/mL of culture medium. The absorbances averages results obtained showed that the crude extract did not present cytotoxicity for the HTC cells in all the concentrations and evaluated times. For quassin, the concentrations of 80 and 100 µg/mL were cytotoxic, after 72 hours of treatment. For parain, the concentrations of 1, 5, 20, 40, 60, 80 and 100 µg/mL, in 72 hours, were cytotoxic, revealing a new activity for this compound. Thus, the results demonstrate a first indication of the cytotoxic activity of compounds quassin and parain, adding an important social and economic value to them, and may have application in future research and in pharmaceutical industry.

Neuroinflammation Biomarkers in the AT(N) Framework Across the Alzheimer's Disease Continuum.

In the past years, neuroinflammation has been widely investigated in Alzheimer's disease (AD). Evidence from animal, in vivo and post-mortem studies has shown that inflammatory changes are a common feature of the disease, apparently happening in response to amyloid-beta and tau accumulation. Progress in imaging and fluid biomarkers now allows for identifying surrogate markers of neuroinflammation in living individuals, which may offer unprecedented opportunities to better understand AD pathogenesis and progression. In this context, inflammatory mediators and glial proteins (mainly derived from microglial cells and astrocytes) seem to be the most promising biomarkers. Here, we discuss the biological basis of neuroinflammation in AD, revise the proposed neuroinflammation biomarkers, describe what we have learned from anti-inflammatory drug trials, and critically discuss the potential addition of these biomarkers in the AT(N) framework.

How well have CMIP3, CMIP5 and CMIP6 future climate projections portrayed the recently observed warming.

Despite the dire conclusions of the Intergovernmental Panel on Climate Change (IPCC) Assessment Reports in terms of global warming and its impacts on Earth's climate, ecosystems and human society, a skepticism claiming that the projected global warming is alarmist or, at least, overestimated, still persists. Given the years passed since the future climate projections that served as basis for the IPCC 4th, 5th and 6th Assessment Reports were released, it is now possible to answer this fundamental question if the projected global warming has been over or underestimated. This study presents a comparison between CMIP3, CMIP5 and CMIP6 future temperature projections and observations. The results show that the global warming projected by all CMIPs and future climate scenarios here analyzed project a global warming slightly lower than the observed one. The observed warming is closer to the upper level of the projected ones, revealing that CMIPs future climate scenarios with higher GHG emissions appear to be the most realistic ones. These results show that CMIPs future warming projections have been slightly conservative up to 2020, which could suggest a similar cold bias in their warming projections up to the end of the current century. However, given the short future periods here analyzed, inferences about warming at longer timescales cannot be done with confidence, since the models internal variability can play a relevant role on timescales of 20 years and less.

Fano-Feshbach formalism applied to the calculation of autoionization widths through analytic continuation.

A method to calculate the autoionization width from a discretized pseudo-spectrum is proposed. This method relies on an analytic continuation of Green's function within the Fano-Feshbach formalism. The pseudo-spectrum is obtained at the multireference configuration interaction level in a square-integrable basis set, commonly found in quantum chemistry software. Few states around the desired resonance are needed to perform the analytic continuation. This method was applied to atomic (He and Ne) and molecular (HF and benzene) systems, and the results for the autoionization width show good agreement with the available theoretical and experimental values.

In vitro evaluation of the cis-[Ru(phen)2(pPDIp)]2+⁎⁎ complex for antimicrobial photodynamic therapy against Sporothrix brasiliensis and Candida albicans.

BACKGROUND: Photodynamic therapy (PDT) activates a photosensitizer by visible light to generate cytotoxic oxygen species that lead to cell death. With proper illumination, PDT is often used in applications on superficial and sub-surface lesions. Sporotrichosis infection occurs by Sporothrix fungi which causes a skin wound, worsened by Candida albicans infections. This study investigated the photosensitizing efficiency of the Ru(phen)2(pPDIp)(PF6)2 complex, RupPDIp, against S. brasiliensis and C. albicans. MATERIAL AND METHODS: RupPDIp efficiency against these fungi was tested using 450 nm (blue light and 36 J/cm2) and 525 nm (green light, 25.2 J/cm2) at 0.05-20 µM concentrations. To ensure PDT effectiveness, control groups were tested in the absence and in the presence of RupPDIp under light irradiation and in the dark. RESULTS: RupPDIp eliminated both fungi at ≤5.0 µM. Green light showed the best results, eliminating S. brasiliensis and C. albicans colonies at RupPDIp 0.5 µM and 0.05 µM, respectively. CONCLUSION: RupPDIp is a promising photosensitizer in aPDT, eliminating 106 CFU/mL of both fungi at 450 nm and 525 nm, with lower light doses and concentrations when treated with the green light compared to the blue light.

Biomonitoring of air quality in the Bodoquena microregion, Mato Grosso Do Sul: mutagenic and morphoanatomical alterations in Tradescantia pallida (rose) D.R. Hunt var. purpurea.

The objective of this study was to assess air quality in relation to vehicular traffic flow in cities located at different elevations in the Bodoquena microregion, state of Mato Grosso do Sul, Brazil. To do so, a micronucleus test was carried out using the TRAD-MCN bioassay on young Tradescantia buds collected from February to November 2018 in seven cities of the microregion with different traffic flow intensities. Meteorological parameters were evaluated, and vehicular traffic was counted to determine traffic flow in each city. With data from the Shuttle Radar Topography Mission (SRTM) and processing in Esri ArcGIS® software version 10.5.1, the regions was mapped based on an Elevation Model. Morphoanatomical analyses were performed according to standard methodology. Measurements were taken of thickness, length and width of tissues and structures, including the upper and lower cuticle, upper and lower epidermis, hypodermis and mesophyll. The greatest traffic flow was found in the cities of Bodoquena, Guia Lopes da Laguna, Jardim, and Porto Murtinho, with the period from 5:00 to 6:00 p.m. showing the highest traffic flow. The greatest frequency of mutagenic alterations was found in the city of Guia Lopes da Laguna, although the results did not differ significantly from Bonito, Caracol, and Jardim. Throughout the biomonitoring, the summer and autumn seasons showed the greatest micronuclei frequencies in all evaluated cities. Variations in the tissue/structure thickness was observed across cities and seasons, but with a decrease in thickness during autumn. In general, the tissues/structures were smaller for the cities of Nioaque and Porto Murtinho, while the anatomical and morphological characteristics of leaf length and thickness showed no differences among cities. We found limited correlation between micronuclei frequency and traffic flow, supporting the hypothesis that although mutagenic alterations are observed in T. pallida, in this microregion the changes are numerically lower when compared to other regions of the state. In light of the genotoxic and morphoanatomical factors assessed herein, the Bodoquena microregion appears to be well preserved in terms of air quality, presenting low micronuclei frequency and a limited reduction in tissues and leaf structures, regardless of the season.

Electron-molecule collisions with explicit rovibrational resolution at MRCI level and using even tempered basis sets.

A method for calculating the generalized oscillator strengths (GOSs) and differential cross section (DCS) with vibration and rotation resolution is presented. The importance of accounting for the rotational contribution is to be emphasized since it has not previously been considered in GOS calculations. Although largely neglected due to its small effect on various properties, the rotational resolution proved to be fundamental in the study of certain phenomena, such as the interference between rotational states in a molecule. As the general goal of this work is to obtain theoretical values comparable to high resolution experiments, special care was taken on the calculation of the electronic part of the scattering amplitude, particularly in what concerns the choice of the atomic basis set. Accordingly, even-tempered basis sets have proved to lead to good results. The helium atom was taken as a model system for this aspect of the problem. Then, GOS and DCS, for explicit vibrational and rotational transitions, were calculated for hydrogen and nitrogen molecules. For higher accuracy, a non-Franck-Condon approach was used to obtain transitions involving vibrational states. The resultant values have shown good agreement with the available experimental data.