Expression of IL-17RA in Innate Cells of Patients with Common Variable Immunodeficiency (CVID) and its Clinical Implications.

Summary: Background. Common Variable Immunodeficiency (CVID) is a primary immunodeficiency disorder characterized by B-cell dysfunction and immunoglobulin production deficiency. Dysregulation of interleukin-17 (IL-17) and its receptor IL-17RA have been reported in various immune disorders. This study aimed to investigate the expression of IL-17RA in innate immune cells of CVID patients and its correlation with clinical manifestations. Methods. A cross-sectional study included 22 CVID patients and 14 age- and sex-matched healthy controls. IL-17RA expression was assessed in various immune cell subsets using flow cytometry. Demographic and clinical data were collected, and statistical analysis was performed. Results. CVID patients had elevated IL-17RA expression in neutrophils, non-classical monocytes, and dendritic cells compared to healthy controls. Patients with a history of intestinal microbial colonization, particularly with Campylobacter jejuni and Giardia intestinalis, showed significantly higher IL-17RA expression in innate cells. Elevated IL-17RA expression in monocytes and dendritic cells also correlated with higher fecal calprotectin levels in CVID patients, regardless of microbial colonization. Conclusions. The study suggests that despite previous reports of reduced circulating Th17 cells and IL-17 levels in CVID patients, IL-17RA expression in innate cells may be elevated, potentially indicating altered IL-17 signaling. This heightened IL-17RA expression could contribute to a persistent pro-inflammatory state, possibly due to microbial translocation or other inflammatory factors. The association of IL-17RA expression with gastrointestinal microbial colonization and its correlation with fecal calprotectin underscores the complexity of IL-17RA's role in CVID pathophysiology. Further research in larger cohorts could elucidate the implications of IL-17RA expression in both infectious and non-infectious inflammatory aspects of CVID.

Socioeconomic aspects and profile of fishing according to fishers of commercial edible fish in the municipality of Barcelos, middle Negro River, Amazonas, Brazil.

Fishing plays a prominent role in the socioeconomic scope of the Negro River basin and is considered one of the main extractive activities in the region. The objective of this study was to describe the socioeconomic aspects of commercial fishers of edible fish who work in the municipality of Barcelos, in the middle Negro River region, as well as to highlight the scenario of the fishing activity from the point of view of the fishers. The information was collected between January and December 2016 in the municipality of Barcelos, state of Amazonas, via semi-structured questionnaires. Most interviewees were male (71.14%), aged between 18 and 82 years and a mean age of 48 years. With a low level of education, 45.0% had only incomplete elementary education and 15% were illiterate. The fishing tackle most used by fishermen was the gillnet, especially by urban fishermen (70%). Among the fishing sites, the main one was the Demeni River (50%). Commercial fishing for edible fish in Barcelos focused on Characiformes, Perciformes and Siluriformes fish. The main difficulties faced by the activity are related to the seasonality of the level of rivers and local tributaries, as well as the lack of buyers and low selling price of fish, in addition to conflicts over the use of fishing resources. Commercial fishing for edible fish is an activity of great socioeconomic importance for riverside families in the Middle River Negro basin, which needs greater attention from the public authorities. Therefore, it is expected that the information contained in this study can help in the decision-making process for the management of local fisheries resources and contribute to the resumption of growth and sustainability of commercial edible fish fisheries.

Insights into the Release Mechanisms of ITZ:HPMCAS Amorphous Solid Dispersions: The Role of Drug-Rich Colloids.

Understanding the dissolution mechanisms of amorphous solid dispersions (ASDs) and being able to link enhanced drug exposure with process parameters are key when formulating poorly soluble compounds. Thus, in this study, ASDs composed by itraconazole (ITZ) and hydroxypropylmethylcellulose acetate succinate (HPMCAS) were formulated with different polymer grades and drug loads (DLs) and processed by spray drying with different atomization ratios and outlet temperatures. Their in vitro performance and the ability to form drug-rich colloids were then evaluated by a physiologically relevant dissolution method. In gastric media, drug release followed a diffusion-controlled mechanism and drug-rich colloids were not formed since the solubility of the amorphous API at pH 1.6 was not exceeded. After changing to intestinal media, the API followed a polymer dissolution-controlled release, where the polymer rapidly dissolved, promoting the immediate release of API and thus leading to liquid-liquid phase separation (LLPS) and consequent formation of drug-rich colloids. However, the release of API and polymer was not congruent, so API surface enrichment occurred, which limited the further dissolution of the polymer, leading to a drug-controlled release. ASDs formulated with M-grade showed the highest ability to maintain supersaturation and the lowest tendency for AAPS due to its good balance between acetyl and succinoyl groups, and thus strong interactions with both the hydrophobic drug and the aqueous dissolution medium. The ability to form colloids increased for low DL (15%) and high specific surface area due to the high amount of polymer released until the occurrence of API surface enrichment. Even though congruent release was not observed, all ASDs formed drug-rich colloids that were stable in the solution until the end of the dissolution study (4 h), maintaining the same size distribution (ca. 300 nm). Drug-rich colloids can, in vivo, act as a drug reservoir replenishing the drug while it permeates. Designing ASDs that are prone to form colloids can overcome the solubility constraints of Biopharmaceutics Classification System (BCS) II and IV drugs, posing as a reliable formulation strategy.

Are Pesticides Used to Control Thrips Harmonious with Soil-Dwelling Predatory Mite Cosmolaelaps sabelis (Mesostigmata: Laelapidae)?

Edaphic predatory mites could be introduced in pest management programs of pests that live, or spend part of their life cycle, in the soil. Some mesostigmatic mites have been widely used for the management of different species of thrips (Thysanoptera), especially in protected cultivation. The edaphic predator Cosmolaelaps sabelis (Mesostigmata: Laelapidae) was a model species in this study, being exposed to the most applied insecticides for the control of thrips in Brazil. After lethal, sublethal and transgenerational effects were evaluated. The pesticides acephate, acetamiprid + etofenprox, azadirachtin, spinetoram, formetanate hydrochloride, and imidacloprid were classified according to the IOBC/WPRS (International Organization for Biological Control-West Paleartic Regional Section) recommendation, considering the acute toxicity and the effects on adult females' reproduction, in the maternal and first generation. The pesticides acetamiprid + etofenprox and azadirachtin were classified as slightly harmful (Class 2), while spinetoram was classified as moderately harmful (Class 3). Acephate and formetanate hydrochloride were classified as harmful (Class 4). Only imidacloprid didn't cause negative effects on the females. Regarding effects on the first generation, acetamiprid + etofenprox, azadirachtin, and spinetoram caused reduction in the oviposition rates. Therefore, we suggest that complimentary bioassays should be done under semi-field and field conditions using the pesticides that were considered harmful in this study, to assess their effects on this predator in other environments prior to recommending not to use them in integrated programs to manage soil-based pests using chemical and biological tools.

Cauda equina syndrome following combined spinal-epidural anesthesia with levobupivacaine for cesarean section.

Cauda equina syndrome (CES) is a rare but possible complication of neuroaxial anesthesia. Damage to the nerve roots may occur due to compression, inflammation, stretching, direct trauma, spinal ischemia or neurotoxicity, usually with lidocaine or bupivacaine. We describe a case of a 33-year-old patient that underwent an uneventful cesarean section with a combined spinal-epidural technique anesthesia, with levobupivacaine. 48 h after the procedure, she presented diminished muscular strength and abolished osteotendinous reflexes in the left lower limb, limited flexion of the right hallux, urinary retention and saddle anesthesia. Imaging exams excluded hematoma, thickening or compression of the cauda equina nerve roots. CES was suspected and treatment was initiated. 9-month follow up revealed diminished osteotendinous reflexes on the left lower limb and perianal hypoesthesia. Despite being unusual, neurological complications require prompt recognition and management to avoid permanent damage.

Ornamental fishing in the region of Barcelos, Amazonas: socioeconomic description and scenario of activity in the view of piabeiros / A pesca ornamental na região de Barcelos, Amazonas: descrição socieconômica e cenário da atividade na visão dos piabeiros

Abstract The Negro river basin is considered the largest area of extractive of ornamental fish in Brazil. This area has fundamental importance for the populations from the Amazon. The present study aimed to describe socioeconomic profile of ornamental fishermen known as "piabeiros" in the Municipality of Barcelos, as well as the ornamental fishery, fisheries area, target species, environments, fishing techniques, equipment, capture techniques and main difficulties faced by the current activity. This study was carried out in municipality of Barcelos, through semi - structured interviews, with artisanal ornamental fishermen (N= 89). The main families of ornamental fish caught and traded were: Characidae, Lebiasinidae, Gasteropelecidae, Cichilidae, Anostomidae, Loricaridae, Potamotrygonidae and Gymnotidae. The main catchment areas were igarapés, lakes, flooded fields, beaches, river banks and igapó forest. Rapiché was the most used equipment in the fisheries both by the fishermen of the urban areas (43.81%) and rural (41.89%). Most of the fishermen are associated with the colony of fishermen of Barcelos (Z33). The data showed that the dynamics of ornamental fishing have changed in a short time and directly affected fishermen, in addition to the low age renewal with the participation of younger fishermen, threatening the transmission of ecological knowledge to future generations. As a result, the increase of the problems related to the productive chain and absence of public power to the activity, since ornamental fishing has already been treated as one of the main economic activities more important for the local communities and for the State of Amazonas.

Resumo A bacia do rio Negro é considerada a maior área de extrativismo de peixes ornamentais do Brasil. Esta área possui importância fundamental para as populações da Amazônia. O presente estudo objetivou descrever o perfil socioeconômico de pescadores conhecidos como "piabeiros" no município de Barcelos, bem como a pesca ornamental, área de pesca, espécies-alvo, ambientes, técnicas de pesca, equipamentos, técnicas de captura e dificuldades enfrentadas nesta atividade. O estudo foi realizado por meio de entrevistas semi - estruturadas, com pescadores artesanais ornamentais (N= 89). Os dados mostram que as famílias de peixes ornamentais capturados e comercializados foram: Characidae, Lebiasinidae, Gasteropelecidae, Cichilidae, Anostomidae, Loricaridae, Potamotrygonidae e Gymnotidae. As áreas de captura descritas foram igarapés, lagos, alagados, praias, margens de rios e floresta de igapó. O Rapiché foi o equipamento mais utilizado nas pescarias tanto pelos pescadores das áreas urbanas (43,81%) como rurais (41,89%). A maioria dos pescadores está associada à colônia de pescadores de Barcelos (Z33). Os dados coletados mostraram que a dinâmica da pesca ornamental mudou em pouco tempo e afetou diretamente os pescadores. Além da baixa taxa de renovação, com a participação de pescadores mais jovens, ameaçando a transmissão de conhecimento ecológico para as gerações futuras. Como resultado, notamos o aumento dos problemas relacionados à cadeia produtiva e a ausência de poder público na atividade. A pesca ornamental já foi tratada como uma das principais atividades econômicas para as comunidades locais e para o Estado do Amazonas.

Elevated soluble TNFα levels and upregulated TNFα mRNA expression in purified peripheral blood monocyte subsets associated with high-grade hepatocellular carcinoma.

BACKGROUND: Chronic inflammation is involved in the initiation and progression of various cancers, including liver cancer. The current study focuses on the characterization of the peripheral immune response in hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) patients, before and after surgical procedure, in order to assess the effect of tumor resection in the immune system homeostasis and to determine possible prognostic factors associated with high-grade tumors. We developed a whole-blood assay to monitor immune alterations and functional competence of peripheral monocytes in a group of 10 healthy individuals (HG), in 20 HCC patients and 8 CCA patients, by multi-color flow cytometry, qRT-PCR, and ELISA techniques. RESULTS: The qRT-PCR analysis showed an upregulation of TNFα expression by classical and intermediate monocytes purified from HCC patients presenting tumors in grade G3-G4 as compared to G1-G2 HCC patients. Moreover, ELISA assay confirmed elevated serum levels of TNFα in G3-G4 compared to G1-G2 HCC patients. A significant decrease of circulating non-classical monocytes was detected in both CCA and HCC patients before and after surgical procedure. In addition, a functional defect in circulating classical and intermediate monocytes was observed in both groups of cancer patients when compared to the HG, with partial recovery after the surgical intervention. CONCLUSIONS: This integrated analysis permitted the identification of altered functional competence of monocyte subsets in CCA and HCC patients. In addition, our results point to a potential role of TNFα as a prognostic peripheral biomarker in HCC patients, indicating the presence of high-grade tumors that should be further validated.

Enfisema subcutáneo como complicación del uso de una mascarilla laríngea en un niño / Subcutaneous emphysema as a complication of the use of a laryngeal mask in a child

El uso de dispositivos supraglóticos para el manejo de la vía aérea ha aumentado en popularidad, principalmente debido a su alta tasa de éxito y bajas complicaciones. Sin embargo, hay muy poca información disponible sobre las potenciales complicaciones y específicas, con respecto a su uso en niños. Presentamos la primera descripción de un niño que desarrolló enfisema subcutáneo después del uso de una mascarilla laríngea. Creemos que se necesita una mayor conciencia del riesgo de eventos adversos perioperatorios con la inserción de mascarillas laríngeas en la población pediátrica

The use of supraglottic airway devices has been increasing in popularity, mostly due to their high success rate and low complications. However, there is very little information available about the potential and group specific concerns regarding their use in children. We present the first description of a child that developed subcutaneous emphysema after the use of a laryngeal mask. We believe that more awareness to the risk of perioperative adverse events with laryngeal mask insertion in the paediatric population is needed

Subcutaneous emphysema as a complication of the use of a laryngeal mask in a child. / Enfisema subcutáneo como complicación del uso de una mascarilla laríngea en un niño.

The use of supraglottic airway devices has been increasing in popularity, mostly due to their high success rate and low complications. However, there is very little information available about the potential and group specific concerns regarding their use in children. We present the first description of a child that developed subcutaneous emphysema after the use of a laryngeal mask. We believe that more awareness to the risk of perioperative adverse events with laryngeal mask insertion in the paediatric population is needed.

Electrodialytic removal of tungsten and arsenic from secondary mine resources - Deep eutectic solvents enhancement.

Tungsten is a critical raw material for European and U.S. economies. Tungsten mine residues, usually considered an environmental burden due to e.g. arsenic content, are also secondary tungsten resources. The electrodialytic (ED) process and deep eutectic solvents (DES) have been successfully and independently applied for the extraction of metals from different complex environmental matrices. In this study a proof of concept demonstrates that coupling DES in a two-compartment ED set-up enhances the removal and separation of arsenic and tungsten from Panasqueira mine secondary resources. Choline chloride with malonic acid (1:2), and choline chloride with oxalic acid (1:1) were the DES that in batch extracted the average maximum contents of arsenic (16%) and tungsten (9%) from the residues. However, when ED was operated at a current intensity of 100 mA for 4 days, the extraction yields increased 22% for arsenic and 11% for tungsten, comparing to the tests with no current. From the total arsenic and tungsten extracted, 82% and 77% respectively were successfully removed from the matrix compartment, as they electromigrated to the anolyte compartment, from where these elements can be further separated. This achievement potentiates circular economy, as the final treated residue could be incorporated in construction materials production, mitigating current environmental problems in both mining and construction sectors.

Ornamental fishing in the region of Barcelos, Amazonas: socioeconomic description and scenario of activity in the view of "piabeiros".

The Negro river basin is considered the largest area of extractive of ornamental fish in Brazil. This area has fundamental importance for the populations from the Amazon. The present study aimed to describe socioeconomic profile of ornamental fishermen known as "piabeiros" in the Municipality of Barcelos, as well as the ornamental fishery, fisheries area, target species, environments, fishing techniques, equipment, capture techniques and main difficulties faced by the current activity. This study was carried out in municipality of Barcelos, through semi - structured interviews, with artisanal ornamental fishermen (N= 89). The main families of ornamental fish caught and traded were: Characidae, Lebiasinidae, Gasteropelecidae, Cichilidae, Anostomidae, Loricaridae, Potamotrygonidae and Gymnotidae. The main catchment areas were igarapés, lakes, flooded fields, beaches, river banks and igapó forest. Rapiché was the most used equipment in the fisheries both by the fishermen of the urban areas (43.81%) and rural (41.89%). Most of the fishermen are associated with the colony of fishermen of Barcelos (Z33). The data showed that the dynamics of ornamental fishing have changed in a short time and directly affected fishermen, in addition to the low age renewal with the participation of younger fishermen, threatening the transmission of ecological knowledge to future generations. As a result, the increase of the problems related to the productive chain and absence of public power to the activity, since ornamental fishing has already been treated as one of the main economic activities more important for the local communities and for the State of Amazonas.

Functional and Phenotypic Characterization of Tumor-Infiltrating Leukocyte Subsets and Their Contribution to the Pathogenesis of Hepatocellular Carcinoma and Cholangiocarcinoma.

Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) represent the most common primary liver malignancies whose outcome is influenced by the immune response. In the present study, we evaluated the tumor-infiltrating leukocyte (TIL) populations in 21 HCC patients and 8 CCA patients by flow cytometry immediately after the surgical procedure. Moreover, CD4+ T cells, CD8+ T cells, monocytes, and macrophages were purified by cell sorting for further analysis of gene expression by quantitative reverse-transcription polymerase chain reaction. Regarding tumor-infiltrating macrophages, we observed a significantly higher expression of markers associated with M2 phenotype and a higher expression of PD-L1 in patients with HCC in comparison to CCA. In addition, for HCC patients, we found a significant increase in the expression of CD200R in macrophages from tumors that were in grade G3-G4 as compared to tumors in grade G1-G2. Besides, a significantly higher frequency of tumor-infiltrating lymphocytes, CD8+CD56+ T cells, and natural killer cells was detected in HCC biopsies in comparison to CCA. In summary, this study has revealed functional and phenotypic differences in TIL cell subpopulations between CCA and HCC, as well as among different histopathological grades and tumor aggressiveness degrees, and it has provided evidence to better understand the tumor immune microenvironment of CCA and HCC.

Lipoxidation and cancer immunity.

Lipoxidation is a well-known reaction between electrophilic carbonyl species, formed during oxidation of lipids, and specific proteins that, in most cases, causes an alteration in proteins function. This can occur under physiological conditions but, in many cases, it has been associated to pathological process, including cancer. Lipoxidation may have an effect in cancer development through their effects in tumour cells, as well as through the alteration of immune components and the consequent modulation of the immune response. The formation of protein adducts affects different proteins in cancer, triggering different mechanism, such as proliferation, cell differentiation and apoptosis, among others, altering cancer progression. The divergent results obtained documented that the formation of lipoxidation adducts can have either anti-carcinogenic or pro-carcinogenic effects, depending on the cell type affected and the specific adduct formed. Moreover, lipoxidation adducts may alter the immune response, consequently causing either positive or negative alterations in cancer progression. Therefore, in this review, we summarize the effects of lipoxidation adducts in cancer cells and immune components and their consequences in the evolution of different types of cancer.

Author Correction: Osmotic modulation of chromatin impacts on efficiency and kinetics of cell fate modulation.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Osmotic modulation of chromatin impacts on efficiency and kinetics of cell fate modulation.

Chromatin structure is a major regulator of transcription and gene expression. Herein we explore the use of osmotic modulation to modify the chromatin structure and reprogram gene expression. In this study we use the extracellular osmotic pressure as a chromatin structure and transcriptional modulator. Hyposmotic modulation promotes chromatin loosening and induces changes in RNA polymerase II (Pol II) activity. The chromatin decondensation opens space for higher amounts of DNA engaged RNA Pol II. Hyposmotic modulation constitutes an alternative route to manipulate cell fate decisions. This technology was tested in model protocols of induced pluripotency and transdifferentiation in cells growing in suspension and adherent to substrates, CD34+ umbilical-cord-blood (UCB), fibroblasts and B-cells. The efficiency and kinetics of these cell fate modulation processes were improved by transient hyposmotic modulation of the cell environment.

Transaxillary single-port subtotal parathyroidectomy: feasibility study in cadavers.

Objective: to test the minimally invasive technique of single-port transaxillary subtotal parathyroidectomy in non-formalized cadavers to evaluate its viability and reproduction. Method: we performed ten subtotal parathyroidectomies through a transaxillary TriPort access in cadavers. The technique consisted of access through the axillary fossa, creating a subcutaneous tunnel to the anterior cervical region, for handling of the thyroid gland and dissection and resection of the parathyroid glands. Results: all surgeries were successful. The mean time of surgery was 65 minutes (57-79 min), with uncomplicated identification of all anatomical structures. There was no need for complementary incisions in the cervical region. Conclusion: the transaxillary single-port subtotal parathyroidectomy technique was feasible and reproducible, suggesting an alternative for minimally invasive cervical surgery.

Objetivo: testar a técnica minimamente invasiva de paratireoidectomia subtotal transaxilar single-port em cadáveres não formalizados para avaliar sua viabilidade e reprodução. Método: foram realizadas dez paratireoidectomias subtotais por via transaxilar através de acesso por TriPort em cadáveres. A técnica realizada consistiu em acesso pela fossa axilar, criando-se um túnel subcutâneo até a região cervical anterior, para manuseio da glândula tireoide e dissecção e ressecção das paratireoides. Resultados: todas as cirurgias foram realizadas com sucesso. O tempo médio de cirurgia foi 65 minutos (57-79 min), com identificação, sem dificuldades, de todas as estruturas anatômicas. Não houve necessidade de incisões complementares na região cervical. Conclusão: a técnica de paratireoidectomia subtotal transaxilar single-port foi viável e reprodutível, sugerindo uma alternativa para a cirurgia cervical minimamente invasiva.