[Visceral Leishmaniasis in an Immunocompetent Patient: A Case Report]. / Leishmaniose Visceral em Doente Imunocompetente: Relato de um Caso.

Leishmaniasis is a parasitic disease transmitted by the bite of female sandflies that occurs in tropical and subtropical climate regions. Visceral leishmaniasis is the most serious manifestation of the disease, leading to a 95% mortality rate after two years of infection if untreated. Visceral leishmaniasis is frequently associated with immunocompromised states, with the human immunodeficiency virus being the most prevalent. Most cases of visceral leishmaniasis are caused by the species Leishmania donovani and Leishmania infantum, the latter being the endemic species in the Mediterranean basin. In Portugal, the number of reported cases of visceral leishmaniasis has decreased in the last few years, with 15 cases reported between 2017 and 2021. The authors present a case of visceral leishmaniasis in an immunocompetent patient who manifested the classic pentad: fever, weight loss, hepatosplenomegaly, pancytopenia and hypergammaglobulinemia. The diagnosis was made by the observation of amastigotes of the Leishmania infantum species in the bone marrow aspirate examination, and the patient was successfully treated with liposomal amphotericin B.

A leishmaniose é uma doença parasitária transmitida através da picada de flebotomíneos fêmea e que ocorre em regiões de clima tropical e subtropical. A leishmaniose visceral é a forma mais grave da doença, com uma mortalidade de 95% aos dois anos de infeção, quando não tratada. A leishmaniose visceral associa-se frequentemente a estados de imunossupressão, sendo a coinfeção com o vírus da imunodeficiência humana o mais prevalente. A maioria dos casos de leishmaniose visceral é causada pelas espécies Leishmania donovani e Leishmania infantum, sendo esta última a espécie endémica na bacia do Mediterrâneo. Em Portugal, o número de casos reportados de leishmaniose visceral tem vindo a diminuir nos últimos anos, sendo que entre 2017 e 2021 foram reportados 15 casos. Os autores apresentam um caso de leishmaniose visceral numa doente imunocompetente, que manifestou a pêntade clássica: febre, perda ponderal, hepatoesplenomegalia, pancitopenia e hipergamaglobulinemia. O diagnóstico foi feito pela observação de amastigotas da espécie Leishmania infantum no exame anatomopatológico da medula óssea e a doente foi tratada com sucesso com anfotericina B lipossómica.

High-Performance Sustainable Electrochromic Devices Based on Carrageenan Solid Polymer Electrolytes with Ionic Liquid.

The development of sustainable functional materials with strong potential to be applied in different areas has been growing and gaining increasing interest to address the environmental impact of current materials and technologies. In this scope, this work reports on sustainable functional materials with electrochromic properties, based on their increasing interest for a variety of applications, including sensing technologies. The materials have been developed based on a natural derived polymer, carrageenan, in which different amounts of the ionic liquid (IL) 1-ethyl-3-methylimidazolium thiocyanate ([EMIM][SCN]) were blended. It is shown that the addition of different amounts of IL to the carrageenan matrix does not affect the properties of the samples in terms of morphology or physicochemical and thermal properties, the most significant difference being the increase of the ionic conductivity with increasing IL content, ranging from 2.3 × 10-11 S·cm-1 for pristine carrageenan to 4.6 × 10-4 S·cm-1 for the samples with 5 and 60 wt % IL content, respectively. A electrochromic device has been developed based on the different IL/carrageenan samples as electrolyte and poly(3,4-ethylenedioxythiophene) polystyrenesulfonate (PEDOT:PSS) as electrodes. Spectroelectrochemistry testing demonstrates functional devices at low voltages between 0.3 and -0.9 V. Among the different samples, the one with 15 wt % IL content presents the best conditions for application, presenting an oxidation time of 6 s, a reduction time of 8 s, and a charge density of 1150 and 1050 µC·cm-2 for oxidation and reduction, respectively. The same sample also presents excellent optical density as a function of load density, presenting an optical switch (Δ%Tx) of 99%. Thus, it is demonstrated that it is possible to develop high efficiency and sustainable electrochromic devices based on natural polymers and ionic liquids.

Nitrogen inputs by irrigation is a missing link in the agricultural nitrogen cycle and related policies in Europe.

Irrigation, one of the 28 agri-environmental indicators defined in the European Common Agricultural Policy, is often neglected in agricultural nitrogen (N) budgets, while it can be a considerable source of N in irrigated agriculture. The annual N input from irrigation water sources (NIrrig) to cropping systems was quantified for Europe for 2000-2010 at a resolution of 10 × 10 km, accounting for crop-specific gross irrigation requirements (GIR) and surface- and groundwater nitrate concentration. GIR were computed for 20 crops, while spatially explicit nitrate concentration in groundwater was derived using a random forest model. We show that although GIR were relatively stable (46-60 km3 yr-1), the Nirrig in Europe increased over the 10-year period (184 to 259 Gg N yr-1), approximately 68 % of which occurred in the Mediterranean region. The main hotspots appeared in areas with both high irrigation requirements and high groundwater nitrate concentration, reaching up to averaged values of 150 kg N ha-1 yr1. These were mainly located in Mediterranean Europe (Greece, Portugal and Spain) and to a lesser extent in Northern Europe (The Netherlands, Sweden and Germany). By not including NIrrig, environmental and agricultural policies are underestimating the real extent of N pollution hotspots in European irrigated systems.

How much can changes in the agro-food system reduce agricultural nitrogen losses to the environment? Example of a temperate-Mediterranean gradient.

Ammonia (NH3) volatilization, nitrous oxide (N2O) emissions, and nitrate (NO3-) leaching from agriculture cause severe environmental hazards. Research studies and mitigation strategies have mostly focused on one of these nitrogen (N) losses at a time, often without an integrated view of the agro-food system. Yet, at the regional scale, N2O, NH3, and NO3- loss patterns reflect the structure of the whole agro-food system. Here, we analyzed at the resolution of NUTS2 administrative European Union (EU) regions, N fluxes through the agro-food systems of a Temperate-Mediterranean gradient (France, Spain, and Portugal) experiencing contrasting climate and soil conditions. We assessed the atmospheric and hydrological N emissions from soils and livestock systems. Expressed per ha agricultural land, NH3 volatilization varied in the range 6.2-44.4 kg N ha-1 yr-1, N2O emission and NO3 leaching 0.3-4.9 kg N ha-1 yr-1 and 5.4-154 kg N ha-1 yr-1 respectively. Overall, lowest N2O emission was found in the Mediterranean regions, where NO3- leaching was greater. NH3 volatilization in both temperate and Mediterranean regions roughly follows the distribution of livestock density. We showed that these losses are also closely correlated with the level of fertilization intensity and agriculture system specialization into either stockless crop farming or intensive livestock farming in each region. Moreover, we explored two possible future scenarios at the 2050 horizon: (1) a scenario based on the prescriptions of the EU-Farm-to-Fork (F2F) strategy, with 25% of organic farming, 10% of land set aside for biodiversity, 20% reduction in N fertilizers, and no diet change; and (2) a hypothetical agro-ecological (AE) scenario with generalized organic farming, reconnection of crop and livestock farming, and a healthier human diet with an increase in the share of vegetal protein to 65% (i.e., the Mediterranean diet). Results showed that the AE scenario, owing to its profound reconfiguration of the entire agro-food system would have the potential for much greater reductions in NH3, N2O, and NO3- emissions, namely, 60-81% reduction, while the F2F scenario would only reach 24-35% reduction of N losses.

Lithium-Ion Battery Solid Electrolytes Based on Poly(vinylidene Fluoride)-Metal Thiocyanate Ionic Liquid Blends.

Solid polymer electrolytes (SPEs) are required to improve battery safety through the elimination of the liquid electrolyte solution in current batteries. This work is focused on the development of a hybrid SPE based on poly(vinylidene fluoride), PVDF, and 1-butyl-3-methylimidazolium cobalt(II) isothiocyanate, [BMIM]2[(SCN)4Co] magnetic ionic liquid (MIL), and its battery cycling behavior at room temperature. The addition of MIL in filler contents up to 40 wt % to the PVDF matrix does not influence the compact morphology of the samples obtained by solvent casting. The polar ß-phase of PVDF increases with increasing MIL content, whereas the degree of crystallinity, thermal degradation temperature, and mechanical properties of the MIL/PVDF blends decrease with increasing MIL content. The ionic conductivity of the MIL/PVDF blends increases both with temperature and MIL content, showing the highest ionic conductivity of 7 × 10-4 mS cm-1 at room temperature for the MIL/PVDF blend with 40 wt % of MIL. The cathodic half-cells prepared with this blend as SPE show good reversibility and excellent cycling behavior at different C-rates, with a discharge capacity of 80 mAh g-1 at a C/10-rate with a Coulombic efficiency of 99%. The developed magnetic SPE, with excellent performance at room temperature, shows potential for the implementation of sustainable lithium-ion batteries, which can be further tuned by the application of an external magnetic field.

Spectroscopic Analysis of Parathyroid and Thyroid Tissues by Ground-State diffuse Reflectance and Laser Induced Luminescence: a Preliminary Report.

Intraoperative discrimination of thyroid and parathyroid tissues is fundamental in thyroid surgery. Recent fluorescence studies have shown stronger NIR emission in parathyroid tissue than in thyroid tissue, presenting a potential avenue for the development of a tool for surgical assistance. However, the fluorophore responsible for this emission has not yet been identified. In this work, spectroscopic analysis was performed to ascertain the origin of the emission peaks in parathyroid tissue. Ground-state diffuse reflectance (GSDR) absorption spectroscopy and laser-induced luminescence (LIL) emission spectroscopy were performed in parathyroid, thyroid, and fatty tissue samples and the resulting spectra were compared with the peaks of known fluorophores to identify the origin of each peak. The spectra of the different tissue types were also compared in order to evaluate the wavelength which presents the highest parathyroid emission relative to the emission of the surrounding tissues, representing the ideal wavelength for parathyroid detection. An emission peak in these conditions was observed for both thyroid and parathyroid tissue at 711 nm, with a higher intensity in parathyroid sample, making it suitable for detection applications. These results show a potential avenue for the development of a system allowing parathyroid detection in a surgical setting.

Development of a groundwater contamination index based on the agricultural hazard and aquifer vulnerability: Application to Portugal.

Reducing nitrate leaching may not result in a significant improvement of groundwater quality. The amount of nitrate reaching groundwater depends not only on the hazard related to agricultural activities but also on-site specific groundwater vulnerability. Using national databases and other compiled datasets, the agricultural hazard was calculated as the ratio of (i) the nitrate leached estimated from the N surplus, and (ii) the water surplus, a proxy of the percolating water below the root zone. By combining the hazard with a multi-parameter groundwater vulnerability, a spatially explicit groundwater contamination risk, developed for mainland Portugal, was computed for 1999 and 2009. Results show an increase from 8,800 to 82,679 ha of the territory rated with a very high contamination risk. The priority areas were successfully screened by the Index, coinciding with the current Vulnerable Zones, although additional hotspots were detected in southern Portugal. Percolation, including both irrigation activity and precipitation, was found to be a key driver for the groundwater contamination risk due to its opposite effects in the hazard and in the vulnerability. Reducing nitrogen leaching may be insufficient to reduce the risk of nitrate contamination if there is a relatively larger reduction in precipitation. This index is particularly useful when applied to contrasting situations of vulnerability and hazard, which require distinct mitigation measures to mitigate groundwater contamination.

Bone Marrow Langerhans Cell Histiocytosis in Association with Kasabach-Merritt Syndrome: The Difficulty of a Differential Diagnosis.

Langerhans cell histiocytosis is a rare haematological disorder with variable clinical findings and a high mortality rate. On the other hand, Kasabach-Merritt syndrome is of rare onset at adult age, requiring the simultaneous presentation of vascular lesion, thrombocytopenia, and consumptive coagulopathy. We present the first reported case of both diseases in a single patient and highlight the difficulties of diagnostic. A 69-year-old woman with immune thrombocytopenic purpura underwent surgery for the removal of giant skin haemangiomas. During post-operative care, intravascular disseminated coagulopathy developed. After weeks of corticosteroids and immunosuppressive therapy with no clinical improvement, pulmonary tuberculosis was diagnosed and appropriate treatment initiated. Despite all the efforts, the patient's clinical condition kept worsening and she eventually died. An autopsy revealed bone marrow Langerhans cell histiocytosis. In this case, the patient's autoimmune background together with tuberculosis and intravascular disseminated coagulopathy masked the presentation and made the diagnosis of a rapidly progressive fatal disease very difficult.

Prospective Comparison of Transient Elastography Using Two Different Devices: Performance of FibroScan and FibroTouch.

PURPOSE: Transient elastography (TE) using FibroScan (FS) has been established to non-invasively assess liver fibrosis and steatosis. The aim of this study was to compare the recently introduced FibroTouch (FT) device with the established FS with respect to liver stiffness and CAP. PATIENTS AND METHODS: Thirty-nine patients with and without liver disease were included. All patients were measured three times with FS (FibroScan 530 compact, Echosens, France) and FT (FibroTouch-FT100, Wuxi Hisky Med, China). For FS, M and XL probe were used according to the manufacturer's specifications. For steatosis, CAP and the comparable FT equivalent UAP (ultrasound attenuation parameter) was determined. Finally, FT and FS were explored in liver tissue-mimicking phantoms. RESULTS: LS between FS and FT correlated well with r=0.91. Root-mean-square (RMS) of the coefficient of variation for LS was better in FS (11.1% vs 27.4%). Bland-Altman analysis showed a 3.1 kPa mean overestimation of LS by FT. In addition, UAP strongly and linearly depended on the BMI following UAP=3.02 × BMI+186. In phantoms, a similar relation was found with UAP (phantom)= 3.78 × BMI + 146 suggesting that UAP is directly calculated from entered BMI instead of assessing shear-wave attenuation. Consequently, RMS-CV was lower for FT (6.0% vs 9.7%). However, if using different BMI, CV-RMS for FT increased to 12.7%. LS of a patient with manifest liver cirrhosis and ascites was 38.8 kPa using the FS-XL probe but almost normal with FT (7.2 kPa). CONCLUSION: Although LS by FT shows good correlation with LS-FS, it has larger variation, continuously overestimates LS and completely fails in ascites. Moreover, FT-UAP seems to be a misleading parameter for steatosis assessment because it is at least in part calculated from mandatory entered patient data. In conclusion, novel LS cut-off values need to be defined for LS-FT and usage of UAP is not recommended.

In-Depth Analysis of the Impact of Different Serum-Free Media on the Production of Clinical Grade Dendritic Cells for Cancer Immunotherapy.

Dendritic cell (DC)-based antitumor vaccines have proven to be a safe approach, but often fail to generate robust results between trials. Translation to the clinic has been hindered in part by the lack of standard operation procedures for vaccines production, namely the definition of optimal culture conditions during ex-vivo DC differentiation. Here we sought to compare the ability of three clinical grade serum-free media, DendriMACS, AIM-V, and X-VIVO 15, alongside with fetal bovine serum-supplemented Roswell Park Memorial Institute Medium (RPMI), to support the differentiation of monocyte-derived DCs (Mo-DCs). Under these different culture conditions, phenotype, cell metabolomic profiles, response to maturation stimuli, cytokines production, allogenic T cell stimulatory capacity, as well as priming of antigen-specific CD8+ T cells and activation of autologous natural killer (NK) cells were analyzed. Immature Mo-DCs differentiated in AIM-V or X-VIVO 15 presented lower levels of CD1c, CD1a, and higher expression of CD11c, when compared to cells obtained with DendriMACS. Upon stimulation, only AIM-V or X-VIVO 15 DCs acquired a full mature phenotype, which supports their enhanced capacity to polarize T helper cell type 1 subset, to prime antigen-specific CD8+ T cells and to activate NK cells. CD8+ T cells and NK cells resulting from co-culture with AIM-V or X-VIVO 15 DCs also showed superior cytolytic activity. 1H nuclear magnetic resonance-based metabolomic analysis revealed that superior DC immunostimulatory capacities correlate with an enhanced catabolism of amino acids and glucose. Overall, our data highlight the impact of critically defining the culture medium used in the production of DCs for clinical application in cancer immunotherapy. Moreover, the manipulation of metabolic state during differentiation could be envisaged as a strategy to enhance desired cell characteristics.

Sarcoidosis and Multiple Myeloma: A Case Report and Literature Review.

The existence of a sarcoidosis-lymphoma syndrome has been previously proposed since the relation between sarcoidosis and an increased risk of lymphoproliferative disorders is well established. Multiple myeloma is a malignant multifocal proliferation of clonal plasma cells within the bone marrow, and its association with sarcoidosis has been rarely described. We present a concurrent diagnosis of sarcoidosis and multiple myeloma and make a brief analysis of the reported cases in the literature. A 65-year-old woman underwent surgery for the excision of a wrist mass that presented 3 years before. Histological analysis showed sarcoid-type epithelioid granulomas without necrosis, establishing soft tissue sarcoidosis. Further evaluation revealed marked interstitial lung parenchyma lesions and large intrathoracic adenopathies. Bronchofibroscopy with transbronchial biopsy confirmed lung sarcoidosis. In addition, blood analysis showed monoclonal IgG kappa gammopathy. A bone marrow biopsy confirmed hypercellularity with 60% plasma cells and plasmocyte infiltration. Thus, the diagnosis of systemic sarcoidosis and multiple myeloma was established simultaneously. In a brief review of the literature, we identified 33 reports of cases with both sarcoidosis and multiple myeloma. We point out the importance of a high level of suspicion for the association of sarcoidosis with malignant haematological diseases such as multiple myeloma.

Subcutaneous delivery of biotherapeutics: challenges at the injection site.

INTRODUCTION: Biotherapeutics are primarily delivered subcutaneously due to better compliance and prolonged rate of absorption compared to other parenteral administration routes. Recent research has allowed for the development of biotherapeutic formulations for subcutaneous delivery that require a lower frequency of administration by increasing drug half-life. Formulations determine shelf-life stability as well as features and transient behaviors that influence stability once implanted in the subcutaneous space. AREAS COVERED: This review provides an overview of the factors affecting subcutaneous absorption with a focus on transient effects at the injection site following administration of biotherapeutics and the subsequent impact on absorption and stability. EXPERT OPINION: Advances have been made in understanding subcutaneous tissue and the complex interplay of factors that regulate its homeostasis. The issue of poor stability after injection has been neglected, and many biotherapeutics are hampered by low bioavailability. With the advent of new in vitro techniques that account for properties of the injection site, stability studies evaluating subcutaneous tissues and impacts on pharmacokinetics of biotherapeutics may be useful in the development of new formulations.

Subcutaneous delivery of monoclonal antibodies: How do we get there?

The convenience of subcutaneous (SC) administration and the increasing interest in monoclonal antibody (mAb)-based therapies for chronic diseases, hint their potential for SC delivery in a near future. In addition, there is a common interest among patients, clinicians and pharmaceutical industry in moving from intravenous to SC administration of mAbs due to benefits of improved patient compliance and reduced costs to the healthcare system. Despite the wide use of this route of administration in diseases like diabetes and rheumatoid arthritis, SC bioavailability of mAbs has been shown to be incomplete and variable in most preclinical and clinical studies. This evidences a gap in the understanding of SC absorption process of mAbs and in their drug development process. Likewise, challenges present in drug formulation, such as high viscosity and aggregation, and the inherent immunogenicity of mAbs have also been hampering the successful translation to clinical settings. This review provides a characterization of the subcutaneously delivered mAbs that have entered the market in the last 10 years as well as a snapshot of the landscape of currently undergoing clinical trials. Moreover, there is an overview of the factors influencing SC absorption of mAbs and the preclinical models in use to study SC pharmacokinetics. Considerations about drug formulation and immunogenicity of mAbs are also explored.

Captura da imagem para cefalometria: comparação da captura de imagem cefalométrica utilizando scanner e máquina fotográfica digital / The capture of cephalometric image

O uso do scanner para a digitalização das imagens é consagrado, devido a sua fidelidade, porém, este método é lento e de alto custo. As máquinas fotográficas digitais passaram por um grande desenvolvimento tecnológico, o que pôde sugerir a sua utilização na captura de imagem para a cefalometria. Este estudo comparou dois métodos de captura indireta de imagem (scanner e máquina fotográfica digital), sendo que, as imagens do scanner foram consideradas como Grupo Controle. Foram utilizadas duas máquinas fotográficas digitais (Mavica FD-91 e DSC-707, ambas da Sony), cada uma com duas regulagens diferentes da lente: grande angular wide (W) e standart (S). Depois da captura das imagens, todas foram traçadas por um programa de cefalometria computadorizada (Radiocef 2000 - Brasil), e tiveram seus resultados comparados com o Grupo Controle. Após a análise estatística dos dados coletados, pode-se concluir que, a utilização da máquina fotográfica digital, substituindo o scanner, é perfeitamente possível, desde que se mantenha a regulagem da lente das máquinas fotográficas digitais no modo standart.

Fixaçäo das fraturas da diáfise da tíbia com as hastes flexíveis de Ender / Fixation of fractures of the tibial shaft with Ender nailing

Quinze fraturas da diáfise tibial foram fixadas com as hastes de Ender, sem o uso de intensificador de imagens, baseando-se na técnica original de Ender. Foi ressaltada a importância do método para a formaçäo do calo externo e a contribuiçäo das fixaçöes elásticas para rápida deambulaçäo e para o menor tempo de consolidaçäo. Viu-se, contudo, que as fraturas com foco aberto demoraram mais para consolidar, em comparaçäo com as de foco fechado