Antifungal drug penetration in soft tissue abscesses: a comparative analysis.

BACKGROUND: Invasive fungal infections (IFIs) are severe and difficult-to-treat infections affecting immunocompromised patients. Antifungal drug penetration at the site of infection is critical for outcome and may be difficult to achieve. Data about antifungal drug distribution in infected human tissues under real circumstances of IFI are scarce. METHODS: Multiple samples were obtained from soft tissue abscesses of a lung transplant patient with Candida albicans invasive candidiasis who underwent recurrent procedures of drainage, while receiving different consecutive courses of antifungal therapy [itraconazole (ITC), fluconazole, caspofungin]. Antifungal drug concentrations were measured simultaneously at the site of infection (surrounding inflammatory tissue and fluid content of the abscess) and in plasma for calculation of the tissue/plasma ratio (R). The concentration within the infected tissue was interpreted as appropriate if it was equal or superior to the MIC of the causal pathogen. RESULTS: A total of 30 tissue samples were collected for measurements of ITC (n = 12), fluconazole (n = 17) and caspofungin (n = 1). Variable concentrations were observed in the surrounding tissue of the lesions with median R of 2.79 (range 0.51-15.9) for ITC and 0.94 (0.21-1.37) for fluconazole. Concentrations ranges within the fluid content of the abscesses were 0.39-1.83 for ITC, 0.66-1.02 for fluconazole and 0.23 (single value) for caspofungin. The pharmacodynamic target (tissue concentration ≥ MIC) was achieved in all samples for all three antifungal drugs. CONCLUSIONS: This unique dataset of antifungal drug penetration in infected human soft tissue abscesses suggests that ITC, fluconazole and caspofungin could achieve appropriate concentrations in soft tissue abscesses.

Prediction and biological analysis of yeast VDAC1 phosphorylation.

The mitochondrial outer membrane protein porin 1 (Por1), the yeast orthologue of mammalian voltage-dependent anion channel (VDAC), is the major permeability pathway for the flux of metabolites and ions between cytosol and mitochondria. In yeast, several Por1 phosphorylation sites have been identified. Protein phosphorylation is a major modification regulating a variety of biological activities, but the potential biological roles of Por1 phosphorylation remains unaddressed. In this work, we analysed 10 experimentally observed phosphorylation sites in yeast Por1 using bioinformatics tools. Two of the residues, T100 and S133, predicted to reduce and increase pore permeability, respectively, were validated using biological assays. In accordance, Por1T100D reduced mitochondrial respiration, while Por1S133E phosphomimetic mutant increased it. Por1T100A expression also improved respiratory growth, while Por1S133A caused defects in all growth conditions tested, notably in fermenting media. In conclusion, we found phosphorylation has the potential to modulate Por1, causing a marked effect on mitochondrial function. It can also impact on cell morphology and growth both in respiratory and, unpredictably, also in fermenting conditions, expanding our knowledge on the role of Por1 in cell physiology.

Sit4 Genetically Interacts with Vps27 to Regulate Mitochondrial Function and Lifespan in Saccharomyces cerevisiae.

The Sit4 protein phosphatase plays a key role in orchestrating various cellular processes essential for maintaining cell viability during aging. We have previously shown that SIT4 deletion promotes vacuolar acidification, mitochondrial derepression, and oxidative stress resistance, increasing yeast chronological lifespan. In this study, we performed a proteomic analysis of isolated vacuoles and yeast genetic interaction analysis to unravel how Sit4 influences vacuolar and mitochondrial function. By employing high-resolution mass spectrometry, we show that sit4Δ vacuolar membranes were enriched in Vps27 and Hse1, two proteins that are part of the endosomal sorting complex required for transport-0. In addition, SIT4 exhibited a negative genetic interaction with VPS27, as sit4∆vps27∆ double mutants had a shortened lifespan compared to sit4∆ and vps27∆ single mutants. Our results also show that Vps27 did not increase sit4∆ lifespan by improving protein trafficking or vacuolar sorting pathways. However, Vps27 was critical for iron homeostasis and mitochondrial function in sit4∆ cells, as sit4∆vps27∆ double mutants exhibited high iron levels and impaired mitochondrial respiration. These findings show, for the first time, cross-talk between Sit4 and Vps27, providing new insights into the mechanisms governing chronological lifespan.

Fabrication of CNT-N@Manganese Oxide Hybrid Nanomaterials through a Versatile One-Pot Eco-Friendly Route toward Engineered Textile Supercapacitors.

The expansion of the Internet of Things market and the proliferation of wearable technologies have generated a significant demand for textile-based energy storage systems. This work reports the engineered design of hybrid electrode nanomaterials of N-doped carbon nanotubes (CNT-N) functionalized with two types of manganese oxides (MOs)-birnessite (MnO2) and hausmannite (Mn3O4)-and their application in solid-state textile-based hybrid supercapacitors (SCs). A versatile citric acid-mediated eco-friendly one-pot aqueous precipitation process is proposed for the fabrication of the hybrids. Remarkably, different types of MOs were obtained by simply changing the reaction temperature from room temperature to 100 °C, without any post-thermal treatment. Asymmetric textile SCs were developed using cotton fabrics coated with CNT-N and the hybrids as textile electrodes, and poly(vinyl) alcohol/orthophosphoric acid as the solid-gel electrolyte. The asymmetric devices presented enhanced energy storage performance relative to the symmetric device based on CNT-N and excellent cycling stability (>96%) after 8000 charge/discharge cycles owing to synergistic effects between CNT-N and the MOs, which endowed nonfaradaic and pseudocapacitive features to the SCs. The asymmetric SC based on CNT-N@MnO2 featured 47% higher energy density and comparable power density to the symmetric CNT-N-based device (8.70 W h cm-2 at 309.01 µW cm-2 vs. 5.93 W h cm-2 at 346.58 µW cm-2). The engineered hybrid CNT-N@MO nanomaterials and the eco-friendly citric acid-assisted one-pot precipitation route open promising prospects not only for energy storage, but also for (photo)(electro)catalysis, wastewater treatment, and (bio)sensing.

Voltammetric immunosensor based on oxidized carbon nanotubes/MnFe2O4 hybrid nanoplatform for amplified detection of celery (Apium graveolens).

Celery is a food allergen that must be included in the ingredient list of commercial food products in the European Union. This is a challenge for the food industry because of potential cross-contamination and undeclared ingredients because of their low concentrations. So, the food industry requires expedited high-performance analytical methods. The development, validation and application of a magnetic nanomaterial-based voltammetric immunosensor is reported to quantify a major celery allergen (Api g 1), achieving a low limit of detection (32 pg·mL-1, in a 40-µL sample). The applicability of the biosensor was evaluated by analysing twenty food products and the lowest Api g 1 content (1.1 ± 0.9 mg·kg-1) was quantified in a cooked sample. The selectivity of the method and the interference of similar fresh products (e.g., parsley, basil) were evaluated. This portable and easy-to-use biosensor can be a fit-for-purpose solution to tackle a major problem for the food industry.

Flexible Magnetocaloric Fiber Mats for Room-Temperature Energy Applications.

Currently, magnetocaloric refrigeration technologies are emerging as ecofriendly and more energy-efficient alternatives to conventional expansion-compression systems. However, major challenges remain. A particular concern is the mechanical properties of magnetocaloric materials, namely, their fatigue under cycling and difficulty in processing and shaping. Nevertheless, in the past few years, using multistimuli thermodynamic cycles with multicaloric refrigerants has led to higher heat-pumping efficiencies. To address simultaneously the challenges and develop a multicaloric material, in this work, we have prepared magnetocaloric-based flexible composite mats composed of micrometric electroactive (EA) polyvinylidene fluoride (PVDF) fibers with embedded magnetocaloric/strictive La(Fe,Si)13 particles by the simple and cost-effective electrospinning technique. The composite's structural characterization, using X-ray diffraction (XRD) analysis, Fourier transform infrared (FTIR) spectroscopy, and measurements of the local-scale piezoresponse, revealed a cubic NaZn13-type structure of the La(Fe,Si)13 phase and the formation of the dominant polar ß-phase of the PVDF polymer. The PVDF-La(Fe,Si)13 composite showed an enhancement of the longitudinal piezoelectric coefficient (effective d33) (-11.01 pm/V) compared with the single PVDF fiber matrix (-9.36 pm/V). The main magnetic properties of La(Fe,Si)13 powder were retained in the PVDF-La(Fe,Si)13 composite, including its giant magnetocaloric effect. By retaining the unique magnetic properties of La(Fe,Si)13 embedded in the electroactive piezoelectric polymer fiber mats, we have designed a flexible, easily shapeable, and multifunctional composite enabling its potential application in multicaloric heat-pumping devices and other sensing and actuating devices.

Impactos Psicossociais e na Qualidade de Vida do Tratamento Oncológico em Crianças e Adolescentes / Psychosocial and Quality-of-Life Impacts of Cancer Treatment in Children and Adolescents / Impactos Psicosociales y en la Calidad de Vida del Tratamiento del Cáncer en Niños y Adolescentes

Introdução: Tão importante quanto o diagnóstico e o tratamento do câncer pediátrico são os cuidados relacionados ao impacto psicossocial, educacional e emocional. Objetivo: Avaliar em crianças e adolescentes com diagnóstico de câncer os impactos psicossociais, de qualidade de vida e da presença de acompanhante durante os procedimentos. Método: Estudo transversal, descritivo, com pacientes de 8 a 18 anos e diagnóstico de neoplasia maligna. Os pacientes responderam aos questionários: PedsQL 4.0 Qualidade de Vida (8 a 12 anos), PedsQL 3.0 Módulo de Câncer (8 a 12 anos), PedsQL 4.0 Qualidade de Vida (13 a 18 anos), PedsQL 3.0 Módulo de Câncer (13 a 18 anos) e outro sobre acompanhantes elaborado pelos autores. Resultados: Foram incluídos 25 pacientes pediátricos oncológicos que se sentiam mais felizes na presença de um acompanhante e menos ansiosos durante os procedimentos. Foi percebido grande impacto na qualidade de vida. No questionário Qualidade de Vida, não houve diferença significativa (p=0,627) entre os grupos de pacientes com 8 a 12 anos e 13 a 18 anos, porém o grupo com 8 a 12 anos teve impacto significativamente maior no questionário Módulo de Câncer (p=0,0094). Conclusão: O impacto psicossocial e na qualidade de vida é razoavelmente grande em pacientes pediátricos oncológicos. Além disso, os mais jovens parecem sofrer um impacto psicossocial maior. Os pacientes se dizem mais felizes com a presença de acompanhante, e mais ansiosos na sua ausência.

Introduction: As important as the diagnosis and treatment of pediatric cancer are the care related to psychosocial, educational, and emotional impact. Objective: To evaluate in children and adolescents diagnosed with cancer the psychosocial and quality-of-life impacts and the presence of a companion during the procedures. Method: Cross-sectional descriptive study of patients aged 8 to 18 years of age diagnosed with malignant neoplasms. Patients responded the questionnaires PedsQL 4.0 Quality of Life (8 to 12 years), PedsQL 3.0 Cancer Module (8 to 12 years), PedsQL 4.0 Quality of Life (13 to 18 years), PedsQL 3.0 Cancer Module (13 to 18 years) and another about companions created by the authors. Results: There were 25 pediatric oncology patients included who felt happier in the presence of a companion, and less anxious during the procedures. A great impact on quality of life was perceived. In the Quality-of-Life questionnaire, no significant difference (p=0.627) between the groups of patients aged 8 to 12 years and 13 to 18 years were found, but the group aged 8 to 12 years had a significantly higher impact on the Cancer Module questionnaire (p= 0.0094). Conclusion: The impact on quality of life and psychosocial is fairly large in pediatric oncology patients. The youngest appear to suffer great psychosocial impact. Patients claim they are happier in the presence of a companion, and more anxious in its absence

Introducción: Tan importante como el diagnóstico y tratamiento del cáncer pediátrico, son los cuidados sobre el impacto psicosocial, educativo y emocional. Objetivo: Evaluar en niños y adolescentes diagnosticados de cáncer el impacto psicosocial y en la calidad de vida y la presencia de un acompañante durante los procedimientos. Método: Estudio transversal descriptivo de pacientes de 8 a 18 años con diagnóstico de neoplasia maligna. Los pacientes respondieron a los cuestionarios: PedsQL 4.0 Calidad de Vida (8 a 12 años), PedsQL 3.0 Módulo de Cáncer (8 a 12 años), PedsQL 4.0 Calidad de Vida (13 a 18 años), PedsQL 3.0 Módulo de Cáncer (13 a 18 años) y otro sobre cuidadores elaborado por los autores. Resultados: Se incluyeron 25 pacientes de oncología pediátrica que se sentían más felices con la presencia de un acompañante y menos ansiosos al realizar procedimientos. Se percibió un gran impacto en la calidad de vida. En el cuestionario de Calidad de Vida, no hubo diferencia significativa (p=0,627) entre los grupos de pacientes de 8 a 12 años y de 13 a 18 años, pero el grupo de 8 a 12 años tuvo un impacto significativamente mayor en el cuestionario del Módulo de Cáncer (p=0,0094). Conclusión: El impacto en la calidad de vida y psicosocial es razonablemente grande en los pacientes oncológicos pediátricos. Los de menor edad parecen sufrir un mayor impacto psicosocial. Los pacientes dicen sentirse más felices con la presencia de un acompañante, y más ansiosos en su ausencia.

Saúde LGBTQIA+: análise na educação médica / LGBTQIA+ health: analysis in medical education

O trabalho insere-se nas áreas temáticas da atenção à saúde da população LGBTQIA+ e da formação dos profissionais de saúde focada nesta área. Tem por objetivo analisar o conhecimento específico dos estudantes de medicina do Paraná, Brasil, no atendimento à saúde da população LGBTQIA+ e realizar levantamento do nível de conhecimento referido pelos estudantes acerca da atenção à saúde da população LGBTQIA+. Foram entrevistados 240 acadêmicos de medicina de 11 instituições de ensino médico do Estado do Paraná, por intermédio de questionário eletrônico disponibilizado via redes sociais, e analisadas as porcentagens das respostas. A maior parte (68,4%) "discordam totalmente" ou "discordam" que receberam formação específica na área de atendimento à saúde da população LGBTQIA+. Há pouca familiaridade dos estudantes com a terminologia existente dentro desse universo. Em conclusão, percebe-se a necessidade de adequação da educação médica no que concerne às especificidades da saúde da população LGBTQIA+

The work is part of the thematic areas of health care for the LGBTQIA+ population and the training of health professionals focused on this area. It aims to analyze the specific knowledge of medical students in Paraná, Brazil, in the health care of the LGBTQIA+ population and to carry out a survey of the level of knowledge reported by the students about the health care of the LGBTQIA+ population. A total of 240 medical students from 11 medical education institutions in the State of Paraná were interviewed, using an electronic questionnaire made available via social networks, and the percentages of responses were analyzed. Most (68.4%) "strongly disagree" or "disagree" that they received specific training in the area of health care for the LGBTQIA+ population. There is little familiarity of students with the terminology existing within this universe. In conclusion, there is a need to adapt medical education with regard to the health specifics of the LGBTQIA+ population

Distrofa miotónica congénita en una Unidad de Cuidados Intensivos Neonatales: serie de casos / Congenital myotonic dystrophy in a Neonatal Intensive Care Unit: case series

La distrofia miotónica de Steinert es una enfermedad multisistémica, autosómica dominante, con un amplio espectro de gravedad y manifestaciones clínicas. La forma más grave es aquella que se manifesta en el periodo neonatal, llamada distrofa miotónica congénita. Se destaca la hipotonía global al nacer y el compromiso de la función respiratoria. Las complicaciones son frecuentes, principalmente, retraso del desarrollo psicomotor, del crecimiento pondoestatural, difcultades alimentarias y constipación. Se asocia a un mal pronóstico, con una mortalidad global de hasta un 50% de los niños gravemente afectados. Presentamos cinco casos de distrofa miotónica congénita con el objetivo de describir manifestaciones clínicas, métodos diagnósticos, tratamiento y pronóstico. Los datos existentes en la literatura sobre el desarrollo psicomotor, complicaciones y pronóstico de los supervivientes con distrofa miotónica congénita son pocos. En nuestra serie de casos, las limitaciones psicomotoras presentadas son signifcativas.

Steinert myotonic dystrophy is a multisystemic disease, autosomal dominant, with a wide spectrum of severity and clinical manifestations. The most severe form is one that manifests in the neonatal period, called congenital myotonic dystrophy. This condition is distinguished by overall hypotonia at birth and respiratory function compromise. Complications are frequent, mainly psychomotor development delay, growth failure, food diffculties and constipation. It is associated with a poor prognosis, with an overall mortality of up to 50% of severely affected children. We present fve patients with congenital myotonic dystrophy in order to describe clinical manifestations, diagnosis, treatment and prognosis. Existing data in the literature on psychomotor development, complications and prognosis of survivors withcongenital myotonic dystrophy are scarce. In our case studies, we have found signifcant chronic psychomotor limitations.