RAP1-GTPase immunostaining is altered in human precancerous and cancerous cervical lesions.

Aim: This study investigated RAP1 immunostaining variation in different cell types during CC progression.Methods: Paraffin-embedded cervical tissues from 101 patients were categorized into control, pre-neoplastic and neoplastic groups. RAP1 immunolocalization, HPV detection and genotyping were performed. A semiquantitative immunoreactive score was employed to compare labeling intensity, cellular localization, nuclear labeling, percentage and distribution of reactive cells.Results: 73% (72/99) of cervical specimens were HPV+. RAP1 was localized in the nucleus and cytoplasm of all samples. Cytoplasmic RAP1 immunoscore was higher than nuclear score in all CC groups. RAP1 intensity increased with lesion severity. SCC samples exhibited predominantly intense RAP1 immunostaining.Conclusion: RAP1 is an efficient biomarker for detecting invasive CC lesions but has limited utility in distinguishing SCC grades.

[Box: see text].

PCBs contamination in water and Mytilus edulis along the north Portuguese Atlantic Ocean coastline and analysis of potential carcinogenic risk to human health.

Seven seawater polychlorinated biphenyls (PCBs) were measured in water (DAP), suspended particulate matter (SPM), and blue mussels (Mytilus edulis) collected from four beaches in northwest Portugal. PCBs were extracted using solid-phase-extraction, ultrasound-extraction and QuEChERS before GC-MS analysis. The two-year annual average concentrations of PCBs in DAP, SPM and the four-year analysis in mussels were âˆ¼ 4.4 ng/L, ∼15.9 µg/kg, and âˆ¼ 56.0 µg/kg. The results suggest higher concentrations of PCBs in summer for SPM and in spring for mussels, mainly those collected close to the Ave River estuary. The origins of PCBs remain uncertain. Risk assessment shows that PCBs in water are unlikely to harm local biota due to their low thyroid hormone toxicity equivalents (TEQ-TH; ∼1.4E-04 ng/L and âˆ¼ 4.1E-04 µg/kg) and on WHO toxicity equivalents (TEQ-WHO; ∼2.1E-05 ng/L and âˆ¼ 4.9E-05 µg/kg). However, the lifetime carcinogenic risk (LCR) for humans consuming local bivalves is concerning, as it exceeds 1.0E-06.

Maternal mortality in Brazil: an analysis of temporal trends and spatial clustering. / Mortalidade materna no Brasil: análise de tendências temporais e agrupamentos espaciais.

This article aims to analyze spatial and temporal patterns of maternal mortality in Brazil during the period 2010-2020 and identify related socioeconomic indicators. We conducted an ecological study of the maternal mortality ratio (MMR) in Brazil's municipalities using secondary data. Temporal analysis was performed using the joinpoint method. Bayesian statistics, spatial autocorrelation, the Getis Ord Gi* technique and the scan statistic were used to identify spatial clusters, and multiple non-spatial and spatial regression models were used to assess the association between factors and the MMR. There was an increase in the MMR in 2020 and an increase in deaths in the North and Southeast. Clusters were found in Amazonas, Tocantins, Piauí, Maranhão, Bahia and Mato Grosso do Sul. The following indicators were negatively associated with the MMR: cesarean section rate, Municipal Human Development Index, and per capita household income of people who are vulnerable to poverty. The MMR was stable up to 2019, followed by a sharp rise in 2020 coinciding with the onset of the Covid-19 pandemic in the country. It is essential that efforts to reduce maternal mortality in Brazil extend beyond the promotion of improvements in antenatal, childbirth and postpartum care to address the social determinants of the problem.

O objetivo do artigo é analisar o padrão espacial e temporal e identificar indicadores socioeconômicos relacionados à razão de mortalidade materna (RMM) no Brasil de 2010 a 2020. Estudo ecológico que analisou a RMM nos municípios do Brasil, utilizando dados secundários. Para análise temporal, utilizou-se o método joinpoint. Para a identificação de aglomerados espaciais, utilizou-se estatística bayesiana, autocorrelação espacial, a técnica Getis Ord Gi* e a varredura scan. Para a identificação dos fatores associados à RMM, foram adotados modelos múltiplos de regressão não espacial e espacial. Observou-se aumento da RMM de 2019 para 2020. Houve crescimento de óbitos nas regiões Norte e Sudeste. Os clusters foram encontrados no Amazonas, Tocantins, Piauí, Maranhão, Bahia e Mato Grosso do Sul. Estão negativamente relacionados à RMM os seguintes indicadores: taxa de parto cesáreo, índice de desenvolvimento humano municipal e renda domiciliar per capita dos vulneráveis à pobreza. Embora a tendência temporal tenha se mostrado constante até 2019, a RMM apresentou crescimento no ano de início da pandemia de COVID-19 no país. A redução da MM no Brasil vai além da promoção de melhorias na assistência gravídico-puerperal, sendo fundamental focar também nos determinantes sociais do problema.

Effect of proton pump inhibitors on susceptibility and melanogenesis of Sporothrix species.

Introduction. Sporotrichosis is a subcutaneous infection caused by dimorphic Sporothrix species embedded in the clinical clade. Fungi have virulence factors, such as biofilm and melanin production, which contribute to their survival and are related to the increase in the number of cases of therapeutic failure, making it necessary to search for new options.Gap statement. Proton pump inhibitors (PPIs) have already been shown to inhibit the growth and melanogenesis of other fungi.Aim. Therefore, this study aimed to evaluate the effect of the PPIs omeprazole (OMP), rabeprazole (RBP), esomeprazole, pantoprazole and lansoprazole on the susceptibility and melanogenesis of Sporothrix species, and their interactions with itraconazole, terbinafine and amphotericin B.Methodology. The antifungal activity of PPIs was evaluated using the microdilution method, and the combination of PPIs with itraconazole, terbinafine and amphotericin B was assessed using the checkerboard method. The assessment of melanogenesis inhibition was assessed using grey scale.Results. The OMP and RBP showed significant MIC results ranging from 32 to 256 µg ml-1 and 32 to 128 µg ml-1, respectively. Biofilms were sensitive, with a significant reduction (P<0.05) in metabolic activity of 52% for OMP and 50% for RBP at a concentration of 512 µg ml-1 and of biomass by 53% for OMP and 51% for RBP at concentrations of 512 µg ml-1. As for the inhibition of melanogenesis, only OMP showed inhibition, with a 54% reduction.Conclusion. It concludes that the PPIs OMP and RBP have antifungal activity in vitro against planktonic cells and biofilms of Sporothrix species and that, in addition, OMP can inhibit the melanization process in Sporothrix species.

Recent advances in Emulsan production, purification, and application: Exploring bioemulsifiers unique potentials.

Bioemulsifiers are compounds produced by microorganisms that reduce the interfacial forces between hydrophobic substances and water. Due to their potential in the pharmaceutical and food industries and their efficiency in oil spill remediation, they have been the subject of study in the scientific community while being safe, biodegradable, and sustainable compared to synthetic options. These biomolecules have high molecular weight and polymeric structures, distinguishing them from traditional biosurfactants. Emulsan, a bioemulsifier exopolysaccharide, is produced by Acinetobacter strains and is highly efficient in forming stable emulsions. Its low toxicity and high potential as an emulsifying agent promote its application in pharmaceutical and food industries as a drug-delivery vehicle and emulsion stabilizer. Due to the high environmental impact of oil spills, bioemulsifiers have great potential for environmental applications, such as bioremediation. This unique feature gives them a distinct mechanism of action in forming emulsions, resulting in minimal environmental impact. A better understanding of these aspects can improve the use of bioemulsifiers and environmental remediation in various industries. This review will discuss the production and characterization of Emulsan, focusing on recent advancements in cultivation conditions, purification techniques, compound identification, and ecotoxicity.

Antiphospholipid Syndrome and Patent Foramen Ovale: A Case Report and Literature Review.

Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by arterial, venous, or microvascular thrombosis, pregnancy morbidity, or non-thrombotic manifestations in patients with persistent antiphospholipid antibodies (aPL). Catastrophic APS is a rare and severe form of APS that is defined by the presence of multiple vascular occlusive events. When a patent foramen ovale (PFO) is present, paradoxical embolization can occur, simultaneously leading to arterial and venous thrombosis. We present a complex clinical case of a patient who presented with multiple arterial and venous thrombotic events with positive aPL. The suspicion of catastrophic APS was removed when a PFO was found in a transesophageal echocardiogram, justifying paradoxical embolization. This emphasizes the importance of searching for PFO in patients with APS presenting with simultaneous venous and arterial thrombosis for management and prognosis purposes.

Reframing the clinical phenotype and management of cryptococcal meningitis.

Cryptococcal meningitis is an important global health problem, resulting from infection with the yeast Cryptococcus, especially Cryptococcus neoformans and Cryptococcus gattii, which cause a spectrum of disease ranging from pulmonary and skin lesions to life-threatening central nervous system involvement. The diagnosis and management of cryptococcal meningitis have substantially changed in recent years. Cryptococcal meningitis often occurs in people living with advanced HIV infection, though in high-income countries with robust HIV detection and treatment programmes, it increasingly occurs in other groups, notably solid-organ transplant recipients, other immunosuppressed patients and even immunocompetent hosts. This review outlines the clinical presentation, management and prognosis of cryptococcal meningitis, including its salient differences in people living with HIV compared with HIV-negative patients. We discuss the importance of managing raised intracranial pressure and highlight the advantages of improved multidisciplinary team working involving neurologists, infectious disease specialists and neurosurgeons.

Diel and seasonal mixing patterns and water quality dynamics in a multipurpose tropical semiarid reservoir.

Eutrophication has become a recurrent concern in reservoirs worldwide. This problem is intensified in tropical semiarid regions, where the reservoirs have high seasonal and annual variability of water level and volume. Therefore, an extensive understanding of the diel variation of water quality key-parameters can help improve management of such reservoirs. This study focuses on Castanhão reservoir with the largest multipurpose dam in the Brazilian semiarid. Its main water uses are irrigation, fish farming, and human supply. The reservoir faced a decline in water quality due to a prolonged drought period. While previous research has predominantly emphasized the seasonal dynamics of thermal and chemical stratification, our investigation provides diel assessments of multiple water quality parameters, including nutrient concentrations and phytoplankton abundance. Our primary objective is to compare seasonal and diel variations in stratification and nutrient distribution within the reservoir. Key findings reveal a diel cycle of thermal stratification, primarily during dry season, driven by higher wind speeds. This is corroborated by a significant negative correlation between wind speed and the relative water column stability index. In contrast, during the rainy season, the reservoir experiences continuous thermal stratification due to inflowing water being warmer than the reservoir's water temperature. Notably, a significant negative correlation between total phosphorus and chlorophyll-a, along with a two-fold increase of this nutrient throughout the day during the rainy season, underscores the influence of the phytoplankton community dynamics on the diel nutrient variation. Chemical stratification of dissolved oxygen occurred during dry and rainy seasons, indicating that even during the dry season, where there is no significant inflow, the internal nutrient loading can also significantly impact the water quality of a reservoir. This study advances the understanding of diel water quality dynamics in tropical semiarid reservoirs, shedding light on both climatic and anthropogenic influences on water resources.

The use of green protic ionic liquids in the crystallization of isoniazid: Evaluation of physicochemical and biological properties of drug.

This study evaluated the synthesis of protic ionic liquids (PILs), 2-hydroxy ethylammonium formate (2-HEAF) and 2-hydroxy ethylammonium acetate (2-HEAA), and their applicability in the crystallization process of the active pharmaceutical ingredient isoniazid (INH) as anti-solvent. Isoniazid is an antibiotic used in the treatment of tuberculosis infections, being used as a first-line chemotherapeutic agent against Mycobacterium tuberculosis. Futhermore, this investigation was conducted in order to evaluate how these PILs can influence the habit, solubility, stability, and therapeutic efficiency of the obtained isoniazid crystals. The 2-HEAF and 2-HEAA PILs were easily formed in reactions between ethanolamine and carboxylic acids (formic or acetic acid), and they have no toxicity against Artemia salina. The PILs were able to crystallize isoniazid, influencing the crystal habit and size. The greatest variations in the hydrogen signals of the NH2 and NH groups of the amine and low variations in the chemical shifts of the hydrogens of the cation of the ethanolamine group from 2-HEAA and 2-HEAF indicate that PILs establish possibly weak interactions with INH. The obtained crystals were amorphous and showed higher solubility in water than standard INH. Moreover, these crystals showed therapeutic efficiency inantimycobacterial activity to inhibit the growth of Mycobacterium tuberculosis. The INH:2-HEAF only degraded 5.1 % (w/w), however, INH:2-HEAA degraded 32.8 % (w/w) after 60 days in an accelerated atmosphere. Then, the 2-HEAA and 2-HEAF were able to crystallize isoniazid, being a new application for these PILs. The used PILs also influenced the characteristics of isoniazid crystals.

Immune recovery and the role of recent thymic emigrated T lymphocytes after pediatric hematopoietic stem cell transplantation.

BACKGROUND AIMS: Adequate re-establishment of thymopoiesis is critical for long-term immune reconstitution after hematopoietic cell transplantation (HCT), potentially impacting patient survival rates. This study aimed to evaluate immune reconstitution in pediatric HCT recipients by quantifying recent thymic emigrants (RTEs), specifically CD3+CD31+CD45RA+ cells. METHODS: We conducted a retrospective analysis of 186 pediatric patients transplanted between 2013 and 2020, undergoing their first allogeneic HCT, who were alive in the first 100 days after transplantation with immune recovery evaluation at three time points: day 100, day 180 and day 360 after HCT. We analyzed the distribution of peripheral blood subsets of T, B and natural killer lymphocytes and assessed the impact of underlying disease, HCT type, stem cell source, recipient age, conditioning regimen, graft-versus-host disease (GVHD) occurrence and cytomegalovirus (CMV) reactivation on immune recovery. RESULTS: At day 100, patients under 10 years exhibited higher RTE CD4+ and CD8+CD31+CD45RA+ counts compared with older patients (5.3 versus 2.2 cells/µL, P = 0.022 and 48 versus 72.8 cells/µL, P = 0.049, respectively). Patients with haploidentical HCT had lower RTE CD4+ counts compared with those with unrelated or related donors (2.4 versus 4.4 versus 7.9 cells/µL, P = 0.024). Administration of rabbit anti-thymocyte globulin negatively impacted RTE CD4+ production (median, 6.5 versus 2.4 cells/µL, P = 0.007). At day 180, the presence of GVHD had a negative influence on RTE production (11.7 versus 56.8 cells/µL, P < 0.001), particularly higher-grade acute GVHD (without, 56.8 cells/µL, grade 1-2, 28.1 cells/µL, grade 3-4, 6.0 cells/µL, P < 0.001). Patients with CMV reactivation had higher CD8+CD31+CD45RA+ compared with those without reactivation (median, 204.6 versus 100.2 cells/µL, P = 0.022). At day 360, no variables significantly affected RTE recovery. Overall survival at 5-year follow-up was 87.7%, with a median of 1170 days (range, 122-3316). Multivariate analysis showed that age >10 years (P = 0.038), negative CMV donor serology (P = 0.0029) and acute GVHD (P = 0.0026) had a negative impact on survival. CONCLUSIONS: This study highlights variations in RTE production based on patient age, donor type and immunosuppression regimen employed.

Bioemulsifier production by Acinetobacter venetianus AMO1502: Potential for bioremediation and environmentally friendly applications.

At the best conditions of the bioprocess (30 °C, pH 7.0, 3.0 g/L NaCl) were obtained 0.66 g/L cell concentration, 3.3 g/L of bioemulsifier, which showed high emulsifying activity (53 % ± 2), reducing the surface tension of the water in 47.2 % (38 mN/m). The polymeric structure of the purified bioemulsifier comprised a carbohydrate backbone composed of hexose-based amino sugars with a monomeric mass of 1099 Da, structurally similar to emulsan. A. venetianus bioemulsifier is non-phytotoxic (GI% > 80 %) against Ocimum basilicum and Brassica oleracea and non-cytotoxic (LC50 5794 mg/L) against Artemia salina, being safe local organisms in comparison to other less eco-friendly synthetic emulsifiers. This bioemulsifier effectively dispersed spilled oil in vitro (C22-C33), reducing oil mass by 12 % (w/w) and dispersing oil in a displacement area of 75 cm2 (23.8 % of the spilled area). Thus, the isolated A. venetianus AMO1502 produced a bioemulsifier potentially applicable for environmentally friendly oil spill remediation.

O papel da escola e da Educação Física no controle do sobrepeso e obesidade juvenil na perspectiva de professores atuantes no ensino superior / The role of schools and Physical Education in the control of overweight and juvenile obesity from the perspective of teachers working in higher education / El papel de las escuelas y la Educación Física en el control del sobrepeso y la obesidad juvenil desde la perspectiva de docentes que trabajan en la educación superior

O presente artigo apresenta os resultados de uma pesquisa quantitativa com viés exploratório descritivo, cujo objetivo foi analisar a percepção de 22 professores de Educação Física (18 homens e 04 mulheres), atuantes no magistério superior, sobre o papel da escola e da Educação Física no controle do sobrepeso e obesidade juvenil. Foi utilizada versão adaptada do Perceptions of Youth Obesity and Physical Education Questionnaire. A análise dos dados deu-se a partir das seguintes categorias: percepção da obesidade juvenil, papel da escola e papel da Educação Física permitiu inferir que os professores percebem a escola como um espaço potencial para a promoção de ações, como a oferta de disciplinas curriculares voltadas ao controle do peso corporal. Contudo, tanto a escola, quanto o professor e sua práxis nas aulas de Educação Física não devem restringir as intervenções de forma circunscrita ao tratamento e controle da obesidade juvenil (AU).

This article presents the results of a quantitative research with a descriptive exploratory bias, whose objective was to analyze the perception of 22 Physical Education teachers (18 men and 04 women), working in higher education, about the role of school and Physical Education in controlling overweight and juveni-le obesity. An adapted version of the Perceptions of Youth Obesity and Physical Education Questionnaire was used. The analysis of the data from the categories called perception of youth obesity, role of the school and role of Physical Education allowed inferring that teachers perceive the school as a potential space for the promotion of actions, such as the offer of curricular disciplines aimed at controlling the body weight. However, both the school and the teacher and their practice in Physical Education classes should not limit interventions to the treatment and control of juvenile obesity (AU).

Este artículo presenta los resultados de una investigación cuantitativa con sesgo exploratorio descriptivo, cuyo objetivo fue analizar la percepción de 22 profesores de Educación Física (18 hombres y 04 mujeres), que actúan en la enseñanza superior, sobre el papel de la escuela y la Educación Física en el control so-brepeso y obesidad juvenil. Se utilizó una versión adaptada del Cuestionario de Percepciones de Obesidad Juvenil y Educación Física. El análisis de los datos de las categorías denominadas per-cepción de la obesidad juvenil, rol de la escuela y rol de la Educación Física permitió inferir que los docentes perciben la escuela como un espacio potencial para la promoción de acciones, como la ofer-ta de disciplinas curriculares dirigidas al control el peso corporal. Sin embargo, tanto la escuela como el docente y su práctica en las clases de Educación Física no deben limitar las intervenciones al tratamiento y control de la obesidad juvenil (AU).

O papel da escola e da Educação Física no controle do sobrepeso e obesidade juvenil na perspectiva de professores atuantes no ensino superior / The role of schools and Physical Education in the control of overweight and juvenile obesity from the perspective of teachers working in higher education / El papel de las escuelas y la Educación Física en el control del sobrepeso y la obesidad juvenil desde la perspectiva de docentes que trabajan en la educación superior

O presente artigo apresenta os resultados de uma pes-quisa quantitativa com viés exploratório descritivo, cujo objetivo foi analisar a percepção de 22 professores de Educação Física (18 homens e 04 mulheres), atuantes no magistério superior, sobre o papel da escola e da Educação Física no controle do sobrepeso e obesidade juvenil. Foi utilizada versão adaptada do Perceptions of Youth Obesity and Physical Education Questionnaire. A análise dos dados deu-se a partir das seguintes categorias: percepção da obe-sidade juvenil, papel da escola e papel da Educação Física permi-tiu inferir que os professores percebema escola como um espaço potencial para a promoção de ações, como a oferta de disciplinas curriculares voltadas ao controle do peso corporal. Contudo, tanto a escola, quanto o professor e sua práxis nas aulas de Educação Física não devem restringir as intervenções de forma circunscrita ao tratamento e controle da obesidade juvenil.

This article presents the results of a quantitative re-search with a descriptive exploratory bias, whose objective was to analyze the perception of 22 Physical Education teachers (18 men and 04 women), working in higher education, about the role of school and Physical Education in controlling overweight and juveni-le obesity. An adapted version of the Perceptions of Youth Obesity and Physical Education Questionnaire was used. The analysis of the data from the categories called perception of youth obesity, role of the school and role of Physical Education allowed inferring that teachers perceive the school as a potential space for the pro-motion of actions, such as the offer of curricular disciplines aimed at controlling the body weight. However, both the school and the teacher and their practice in Physical Education classes should not limit interventions to the treatment and control of juvenile obesity.

Este artículo presenta los resultados de una investiga-ción cuantitativa con sesgo exploratorio descriptivo, cuyo objetivo fue analizar la percepción de 22 profesores de Educación Física (18 hombres y 04 mujeres), que actúan en la enseñanza superior, sobre el papel de la escuela y la Educación Física en el control so-brepeso y obesidad juvenil. Se utilizó una versión adaptada del Cuestionario de Percepciones de Obesidad Juvenil y Educación Física. El análisis de los datos de las categorías denominadas per-cepción de la obesidad juvenil, rol de la escuela y rol de la Educación Física permitió inferir que los docentes perciben la escuela como un espacio potencial para la promoción de acciones, como la ofer-ta de disciplinas curriculares dirigidas al control el peso corporal. Sin embargo, tanto la escuela como el docente y su práctica en las clases de Educación Física no deben limitar las intervenciones al tratamiento y control de la obesidad juvenil.

The cytosolic hyperoxidation-sensitive and -robust Leishmania peroxiredoxins cPRX1 and cPRX2 are both dispensable for parasite infectivity.

Typical two-cysteine peroxiredoxins (2-Cys-PRXs) are H2O2-metabolizing enzymes whose activity relies on two cysteine residues. Protists of the family Trypanosomatidae invariably express one cytosolic 2-Cys-PRX (cPRX1). However, the Leishmaniinae sub-family features an additional isoform (cPRX2), almost identical to cPRX1, except for the lack of an elongated C-terminus with a Tyr-Phe (YF) motif. Previously, cytosolic PRXs were considered vital components of the trypanosomatid antioxidant machinery. Here, we shed new light on the properties, functions and relevance of cPRXs from the human pathogen Leishmania infantum. We show first that LicPRX1 is sensitive to inactivation by hyperoxidation, mirroring other YF-containing PRXs participating in redox signaling. Using genetic fusion constructs with roGFP2, we establish that LicPRX1 and LicPRX2 can act as sensors for H2O2 and oxidize protein thiols with implications for signal transduction. Third, we show that while disrupting the LicPRX-encoding genes increases susceptibility of L. infantum promastigotes to external H2O2in vitro, both enzymes are dispensable for the parasites to endure the macrophage respiratory burst, differentiate into amastigotes and initiate in vivo infections. This study introduces a novel perspective on the functions of trypanosomatid cPRXs, exposing their dual roles as both peroxidases and redox sensors. Furthermore, the discovery that Leishmania can adapt to the absence of both enzymes has significant implications for our understanding of Leishmania infections and their treatment. Importantly, it questions the conventional notion that the oxidative response of macrophages during phagocytosis is a major barrier to infection and the suitability of cPRXs as drug targets for leishmaniasis.

A Proof-of-Concept for a Hypolipidemic Brown Trout Model.

The impacts of hypolipidemic pharmaceuticals on fish lipid metabolism remain unexplored. However, data points to similar effects and mechanisms of action between fish and humans. Therefore, fish may be a strong model for screening hypolipidemic drug candidates and water pollution by lipid-modulating agents. This study aimed to test a new hypolipidemic model assay with juvenile brown trout using atorvastatin (ATV)-a hypolipidemic chemical. We selected 17α-ethinylestradiol (EE2), known to cause hyperlipidemia in fish, to ensure model functionality. Fish received intramuscular injections of 4 µL/g for two weeks under the following experimental conditions: control-C (0.7% NaCl), solvent control-SC (0.7% NaCl, 0.9% ethanol, 0.1% dimethyl sulfoxide), ATV (0.3 µg/g), EE2 (2 µg/g), and a mixture of both compounds-MIX (0.3 µg/g ATV and 2 µg/g EE2). Endpoints included blood lipid biochemistry, hepatic lipid droplet quantification, and liver mRNA expression of lipid-related target genes (related to lipogenesis, lipid transport, and ß-oxidation pathways). ATV lowered blood total cholesterol, high-density lipoproteins (HDL), and low-density lipoproteins (LDL) levels, whilst triglycerides and very-low-density lipoproteins (VLDL) were highest under EE2. Hepatic lipid droplet deposition significantly increased in the ATV, EE2, and MIX groups. ATV and MIX caused a significant downregulation of the peroxisome proliferator-activated receptor γ (pparγ) and acetyl Co-A oxidase 3 (acox3). EE2 upregulated acyl-CoA long-chain synthetase 1 (acsl1) and downregulated both fatty acid binding protein 1 (fabp1) and acetyl Co-A oxidase 1-3I (acox1-3I). ATV caused hypolipidemic effects in juvenile brown trout and could even counteract EE2-stimulated hyperlipidemia, reinforcing the potential of fish hypo- and hyperlipidemic models.

Anthraquinones against Cryptococcus neoformans sensu stricto: antifungal interaction, biofilm inhibition and pathogenicity in the Caenorhabditis elegans model.

Introduction. Cryptococcal biofilms have been associated with persistent infections and antifungal resistance. Therefore, strategies, such as the association of natural compounds and antifungal drugs, have been applied for the prevention of biofilm growth. Moreover, the Caenorhabditis elegans pathogenicity model has been used to investigate the capacity to inhibit the pathogenicity of Cryptococcus neoformans sensu stricto.Hypothesis. Anthraquinones and antifungals are associated with preventing C. neoformans sensu stricto biofilm formation and disrupting these communities. Antraquinones reduced the C. neoformans sensu stricto pathogenicity in the C. elegans model.Aim. This study aimed to evaluate the in vitro interaction between aloe emodin, barbaloin or chrysophanol and itraconazole or amphotericin B against growing and mature biofilms of C. neoformans sensu stricto.Methodology. Compounds and antifungal drugs were added during biofilm formation or after 72 h of growth. Then, the metabolic activity was evaluated by the MTT reduction assay, the biomass by crystal-violet staining and the biofilm morphology by confocal laser scanning microscopy. C. neoformans sensu stricto's pathogenicity was investigated using the nematode C. elegans. Finally, pathogenicity inhibition by aloe emodin, barbarloin and chrysophanol was investigated using this model.Results. Anthraquinone-antifungal combinations affected the development of biofilms with a reduction of over 60 % in metabolic activity and above 50 % in biomass. Aloe emodin and barbaloin increased the anti-biofilm activity of antifungal drugs. Chrysophanol potentiated the effect of itraconazole against C. neoformans sensu stricto biofilms. The C. elegans mortality rate reached 76.7 % after the worms were exposed to C. neoformans sensu stricto for 96 h. Aloe emodin, barbaloin and chrysophanol reduced the C. elegans pathogenicity with mortality rates of 61.12 %, 65 % and 53.34 %, respectively, after the worms were exposed for 96 h to C. neoformans sensu stricto and these compounds at same time.Conclusion. These results highlight the potential activity of anthraquinones to increase the effectiveness of antifungal drugs against cryptococcal biofilms.

Nephrectomy with Autotransplantation-A Key Treasure.

Background: Nephrectomy with autotransplantation (NAT) has been performed as an alternative treatment for complex renovascular lesions, intricate ureteral strictures and nephron-sparing surgery in complex renal tumors. Methods: A retrospective observational study was conducted including patients who underwent a NAT from January 2010 to September 2023. Data collected included surgery indications, surgical technique, complications according to Clavien-Dindo classification and mean hospital stay. Descriptive and inferential statistical analysis was performed using IBM® SPSS® Statistics version 28.0.1.0. Results: A total of 34 consecutive patients underwent 38 NATs at our institution. Surgery indications were complex renovascular conditions in 35 cases (92.1%), of which 24 had renal artery aneurysms, and ureteral injuries in 3 cases (7.9%). Thirty-four kidneys (89.5%) were retrieved through a laparoscopic approach. No significant difference was observed between post- and pre-operative creatinine levels (0.81 vs. 0.72, p = 0.303). Early high-grade complications developed in 12 procedures (31.6%). Median cold ischemia time was significantly longer in patients who developed complications (163.0 vs. 115.0, p = 0.010). The median hospital stay was 10 days (8-13). The median follow-up was 51.5 months. Conclusions: NAT emerges as a successful therapeutic strategy for a highly select group of patients dealing with intricate ureteral lesions and kidney vascular abnormalities, demonstrating positive outcomes that endure in the long term.

Transperitoneal vs. Retroperitoneal Approach in Laparoscopic Partial Nephrectomy for Posterior Renal Tumors: A Retrospective, Multi-Center, Comparative Study.

Purpose: The aim of our study is to compare the perioperative, functional, and oncological outcomes of laparoscopic transperitoneal partial nephrectomy (LTPN) and laparoscopic retroperitoneal partial nephrectomy (LRPN) for posterior cT1 renal tumors. Methods: We retrospectively collected data on all patients who consecutively underwent LTPN and LRPN for posterior cT1 renal tumors in three different centers from January 2015 to January 2023. Patients with a single, unilateral, cT1 renal mass, located in the posterior renal surface were included. Patients' data regarding perioperative, functional, and oncological outcomes were collected from medical records and statistically analyzed and compared. Results: A total of 128 patients was obtained, with 53 patients in the LPTN group and 75 patients in the LRPN group. Baseline characteristics were similar. Warm ischemia time (WIT) (18.8 vs. 22.6 min, p = 0.002) and immediate postoperative eGFR drop (-6.1 vs. -13.0 mL/min/1.73 m2, p = 0.047) were significantly lower in the LPTN group. Estimated blood loss (EBL) (100 vs. 150 mL, p = 0.043) was significantly lower in the LRPN group. All other perioperative and functional outcomes and complications were similar between the groups. The positive surgical margin (PSM) rate was lower in the LRPN group, although without statistical significance (7.2% vs. 13.5%, p = 0.258). Surgical success defined by Trifecta (WIT ≤ 25 min, no PSM, and no major postoperative complication) was similar between both approaches. Conclusions: LTPN has significantly shorter WIT and a significantly smaller drop in immediate eGFR when compared to LRPN for posterior renal tumors. On the other hand, LRPN has significantly less EBL than LTPN. LRPN demonstrated fewer PSMs than LTPN, albeit without statistical significance. In terms of overall surgical success, as defined by Trifecta, both approaches achieved similar results.

Hydrogels based on lignin extracted from cashew apple bagasse and its application in antimicrobial wound dressings.

Hydrogels are versatile materials with a three-dimensional network structure that can retain water and release bioactive compounds. They have found applications in various fields, including agriculture, biomaterial synthesis, and pharmaceuticals. Incorporating natural antimicrobial compounds into hydrogels is a promising approach to developing non-toxic biomedical materials, particularly for wound healing dressings. It was evaluated the extraction and use of cashew apple bagasse lignin (CAB-Lig) due to its healing, anti-inflammatory, and antimicrobial properties for producing a hydrogel-based bandage. The extraction process involved acid and alkali treatments followed by precipitation. The antimicrobial potential of CAB-Lig was evaluated at different concentrations for formulating hydrogels. Hydrogels containing 0.1 % and 3 % lignin showed high swelling and liquid retention abilities. The 3 % lignin hydrogel exhibited effectiveness against Escherichia coli and Staphylococcus aureus. Incorporating CAB-Lig into the hydrogel structure improved its mechanical properties, making it more suitable for application as a bandage. Moreover, the extracted lignin showed low toxicity, indicating its safe use. A bandage was formulated by combining the CAB-Lig-based hydrogel with polyester, which possessed antimicrobial properties and demonstrated biocompatibility (L929 and HaCat cells). The results confirmed the potential of CAB-Lig for synthesizing hydrogels and dressings with antimicrobial properties, offering a sustainable solution for utilizing lignocellulosic biomass.

SNUPN deficiency causes a recessive muscular dystrophy due to RNA mis-splicing and ECM dysregulation.

SNURPORTIN-1, encoded by SNUPN, plays a central role in the nuclear import of spliceosomal small nuclear ribonucleoproteins. However, its physiological function remains unexplored. In this study, we investigate 18 children from 15 unrelated families who present with atypical muscular dystrophy and neurological defects. Nine hypomorphic SNUPN biallelic variants, predominantly clustered in the last coding exon, are ascertained to segregate with the disease. We demonstrate that mutant SPN1 failed to oligomerize leading to cytoplasmic aggregation in patients' primary fibroblasts and CRISPR/Cas9-mediated mutant cell lines. Additionally, mutant nuclei exhibit defective spliceosomal maturation and breakdown of Cajal bodies. Transcriptome analyses reveal splicing and mRNA expression dysregulation, particularly in sarcolemmal components, causing disruption of cytoskeletal organization in mutant cells and patient muscle tissues. Our findings establish SNUPN deficiency as the genetic etiology of a previously unrecognized subtype of muscular dystrophy and provide robust evidence of the role of SPN1 for muscle homeostasis.