Protective effects of amphetamine and methylphenidate against dopaminergic neurotoxicants in SH-SY5Y cells.

Full treatment of the second most common neurodegenerative disorder, Parkinson's disease (PD), is still considered an unmet need. As the psychostimulants, amphetamine (AMPH) and methylphenidate (MPH), were shown to be neuroprotective against stroke and other neuronal injury diseases, this study aimed to evaluate their neuroprotective potential against two dopaminergic neurotoxicants, 6-hydroxydopamine (6-OHDA) and paraquat (PQ), in differentiated human dopaminergic SH-SY5Y cells. Neither cytotoxicity nor mitochondrial membrane potential changes were seen following a 24-hour exposure to either therapeutic concentration of AMPH or MPH (0.001-10 µM). On the other hand, a 24-hour exposure to 6-OHDA (31.25-500 µM) or PQ (100-5000 µM) induced concentration-dependent mitochondrial dysfunction, assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, and lysosomal damage, evaluated by the neutral red uptake assay. The lethal concentrations 25 and 50 retrieved from the concentration-toxicity curves in the MTT assay were 99.9 µM and 133.6 µM for 6-OHDA, or 422 µM and 585.8 µM for PQ. Both toxicants caused mitochondrial membrane potential depolarization, but only 6-OHDA increased reactive oxygen species (ROS). Most importantly, PQ-induced toxicity was partially prevented by 1 µM of AMPH or MPH. Nonetheless, neither AMPH nor MPH could prevent 6-OHDA toxicity in this experimental model. According to these findings, AMPH and MPH may provide some neuroprotection against PQ-induced neurotoxicity, but further investigation is required to determine the exact mechanism underlying this protection.

First occurrence of feline sporotrichosis in a metropolitan area of Central-West Brazil.

Sporotrichosis is a neglected mycosis that affects human and animal hosts, including domestic cats. In Brazil, its most frequently diagnosed etiological agent is Sporothrix brasiliensis. Zoonotic transmission of S. brasiliensis occurs via direct contact between an infected cat and a susceptible human host. Notification of confirmed cases of feline sporotrichosis is not mandatory in Brazil. The metropolitan area of Goiania city can be considered a silent area for the occurrence of feline sporotrichosis. In this context, voluntary reporting of feline sporotrichosis cases is recommended for all healthcare professionals. This study aimed to report the first occurrence of S. brasiliensis in a cat from the metropolitan area of Goiania city. Cytopathology, mycology, thermal dimorphism and calmodulin gene amplification tests were performed. The mycological and molecular biological diagnoses corresponded to S. brasiliensis. The etiological agent of zoonotic sporotrichosis was detected in the metropolitan area of Goiania city, and therefore there is a risk of the emergence of new cases of cats infected with S. brasiliensis and the occurrence of zoonotic transmission of this fungus.

Staphylococcus aureus nasal colonization and susceptibility profile to antimicrobials in hemodialysis patients using a protocol of seven collections.

BACKGROUND: Patients colonized with Staphylococcus aureus in their nasal passages have a higher risk of acquiring infection, especially if they are immunocompromised or have comorbidities such as chronic renal failure undergoing hemodialysis (HD). OBJECTIVE: This study aimed to report the prevalence of nasal carriage of S. aureus among HD patients utilizing a seven-week sampling protocol and to assess the susceptibility of these isolates to various antimicrobial agents. METHODS: Over seven consecutive weeks, nasal swab samples were collected from 47 HD patients, resulting in a total of 329 samples. The microorganisms were identified using biochemical methods and subjected to antimicrobial susceptibility testing via disk diffusion and microdilution techniques. RESULTS: Out of all the patients analyzed, 25 individuals (53.19%) were found to be colonized by S. aureus, with 21 of them displaying intermittent colonization. Additionally, 38% showed positive results for S. aureus in only the 6th or 7th week of sampling. Within the 58 isolates, 17.2% (n=10) exhibited methicillin (oxacillin)-resistance and 25.86% (n=15) displayed elevated vancomycin MIC values (2 µg/ml). Based on the results, daptomycin and gentamicin were found to be effective treatment options. However, 31% of the isolates (n=18) exhibited a MIC of 1 µg/ml for daptomycin. CONCLUSION: Over half of the patients were colonized by S. aureus, but mostly on an intermittent basis. The identification of oxacillin resistance and high vancomycin and daptomycin MICs serve as warnings for possible future complications in managing bacteremia caused by S. aureus in these patients.

Safety and efficacy of salvage endoscopic submucosal dissection for Barrett's neoplasia recurrence after radiofrequency ablation.

BACKGROUND AND STUDY AIMS: This study evaluated the safety and efficacy of salvage endoscopic submucosal dissection for Barrett's neoplasia recurrence after radiofrequency ablation. PATIENTS AND METHODS: Data from patients at sixteen centers were collected for a multicentric retrospective study. Patients who underwent at least one RFA treatment for Barrett's esophagus and thereafter underwent further esophageal ESD for neoplasia recurrence were included. RESULTS: Data from 56 patients treated by salvage ESD performed between April 2014 and November 2022 were collected. Immediate complications included one muscular tear (1.8%) treated with stent (Agree classification: grade IIIa), two patients had transmural perforations (4%) and five patients had muscular tears (9%) treated with clips and without clinical impact and not considered as adverse event. Seven patients (12.5%) developed strictures, treated by balloon dilation (grade IIIa). Histological analysis showed 36 adenocarcinomas, 17 high-grade dysplasia, and 3 low-grade dysplasia. En-bloc and R0 resection rates were 89% and 66%, respectively. Resections were curative in thirty-three patients (59%), non-curative in 22 patients (39%), including 11 "local risk" (19.5%) and 11 "high risk" resections (19.5%). At the end of follow-up with a median time of 14 [0-75] months after salvage ESD eventually associated with further endoscopic treatment (RFA, argon plasma coagulation, endoscopic mucosal resection, ESD), neoplasia remission ratio was 37/53 (70%) and the median remission time was 13 [1-75] months. CONCLUSION: In expert hands, salvage ESD is a safe and effective treatment for recurrence of Barrett's neoplasia after RFA treatment.

Application of BactTiter-Glo ATP bioluminescence assay for Mycobacterium tuberculosis detection.

BACKGROUND: Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), remains a global health threat, necessitating faster and more accessible diagnostic methods. This study investigates critical parameters in the application of a commercial ATP bioluminescence assay for the detection of MTB. METHOD: Our objective was to optimize the ATP bioluminescence protocol using BacTiter-Glo™ for MTB, investigating the impact of varying volumes of MTB suspension and reagent on assay sensitivity, evaluating ATP extraction methods, establishing calibration curves, and elucidating strain-specific responses to antimicrobial agents. RESULTS: ATP extraction methods showed no significant improvement over controls. Calibration curves revealed a linear correlation between relative light units (RLU) and colony-forming units (CFU/mL), establishing low detection limits. Antimicrobial testing demonstrated strain-specific responses aligning with susceptibility and resistance patterns. CONCLUSION: Our findings contribute to refining ATP bioluminescence protocols for enhanced MTB detection and susceptibility testing. Further refinements and validation efforts are warranted, holding promise for more efficient diagnostic platforms in the future.

Endoscopic Submucosal Dissection Is Safe and Effective for Lesions Located at the Anorectal Junction: Analysis from Two Referral European Centers.

Introduction: Endoscopic submucosal dissection (ESD) is a well-established resection technique for colorectal superficial tumors, but its role in the treatment of anorectal junction (ARJ) lesions still remains to be determined. With this study, we aimed to evaluate the feasibility, safety, and efficacy of ESD for the resection of ARJ lesions, in comparison to more proximal rectal lesions. Methods: We performed a retrospective analysis of prospectively collected data concerning all consecutive rectal ESD procedures performed in two European centers, from 2015 to 2021. Results: A total of two hundred and fifty-two rectal lesions were included. Sixty (24%) were ARJ lesions, and the remaining 192 (76%) were located proximally. Technical success was achieved in 248 procedures (98%), and its rate was similar in both locations (p = 0.246). Most of the lesions presented high-grade dysplasia/Tis adenocarcinoma (54%); 36 (15%) had submucosal adenocarcinoma, including 20 superficial (sm1) and 16 deeply invasive (>SM1) T1 cancers. We found no differences between ARJ and rectal lesions in regard to en bloc resection rate (100% vs. 96%, p = 0.204), R0 resection rate (76% vs. 75%, p = 0.531), curative resection rate (70% vs. 70%, p = 0.920), procedures' median duration (120 min vs. 90 min, p = 0.072), ESD velocity (14 vs. 12 mm2/min, p = 0.415), histopathology result (p = 0.053), and the need for surgery due to a non-curative ESD (5% vs. 3%, p = 0.739). Also, there was no statistically significant difference that concerns delayed bleeding (7% vs. 8%, p = 0.709), perforation (0% vs. 5%, p = 0.075), or the need for readmission (2% vs. 2%, p = 0.939). Nevertheless, anorectal stenosis (5% vs. 0%, p = 0.003) and anorectal pain (9% vs. 1%, p = 0.002) were significantly more frequent in ARJ lesions. Conclusion: ESD is a safe and efficient resection technique for the treatment of rectal lesions located in the ARJ.

Introdução: A dissecção endoscópica da submucosa (ESD) é uma técnica endoscópica com demonstrada eficácia nas lesões neoplásicas superficiais colorectais. No entanto, a evidência da sua eficácia nas lesões localizadas na junção ano-rectal é escassa. O nosso objectivo foi avaliar a segurança e eficácia da ESD nas lesões da junção anorectal (menos de 2 cm da linha pectínea), em comparação com as lesões mais proximais do recto. Métodos: Análise retrospectiva de registos colhidos prospectivamente de dois centros europeus de referência, entre 2015 e 2021. Resultados: Foram incluídas 252 lesões. Sessenta (24%) localizavam-se na junção ano-rectal, e as restantes 192 noutro local do recto. O sucesso técnico foi de 98% (n = 248) e foi semelhante nas 2 localizações (p = 0.246). A maioria das lesões eram displasias de alto grau/Tis (54%); 36 (15%) tinham adenocarcinoma submucoso, tendo 20 invasão submucosa superficial (sm1) e 16 invasão profunda (>SM1). Não foram encontradas diferenças entre as duas localizações relativamente às taxas de ressecção em bloco (100% vs. 96%, p = 0.204), R0 (76% vs. 75%, p = 0.531), ou curativa (70% vs. 70%, p = 0.920), duração da ESD (mediana 120 min vs. 90 min, p = 0.072), velocidade da ESD (14 vs. 12 mm2/min, p = 0.415) ou resultado histológico (p = 0.053), assim como na necessidade de cirurgia por ESD não curativa (5% vs. 3%, p = 0.739). Além disso, as taxas de hemorragia tardia (7% vs. 8%, p = 0.709), perfuração (0% vs. 5%, p = 0.075) e necessidade de internamento por complicações (2% vs. 2%, p = 0.939) não revelaram diferenças estatisticamente significativas. A estenose ano-rectal (5% vs. 0%, p = 0.003) e a dor ano-rectal (9% vs. 1%, p = 0.002) foram mais frequentes nas lesões da junção ano-rectal. Conclusão: A ESD é uma técnica segura e eficaz no tratamento das lesões do recto localizadas na junção ano-rectal.

Comparative In Vitro Study of the Cytotoxic Effects of Doxorubicin's Main Metabolites on Cardiac AC16 Cells Versus the Parent Drug.

Doxorubicin (DOX; also known as adriamycin) serves as a crucial antineoplastic agent in cancer treatment; however, its clinical utility is hampered by its' intrinsic cardiotoxicity. Although most DOX biotransformation occurs in the liver, a comprehensive understanding of the impact of DOX biotransformation and its' metabolites on its induced cardiotoxicity remains to be fully elucidated. This study aimed to explore the role of biotransformation and DOX's main metabolites in its induced cardiotoxicity in human differentiated cardiac AC16 cells. A key discovery from our study is that modulating metabolism had minimal effects on DOX-induced cytotoxicity: even so, metyrapone (a non-specific inhibitor of cytochrome P450) increased DOX-induced cytotoxicity at 2 µM, while diallyl sulphide (a CYP2E1 inhibitor) decreased the 1 µM DOX-triggered cytotoxicity. Then, the toxicity of the main DOX metabolites, doxorubicinol [(DOXol, 0.5 to 10 µM), doxorubicinone (DOXone, 1 to 10 µM), and 7-deoxydoxorubicinone (7-DeoxyDOX, 1 to 10 µM)] was compared to DOX (0.5 to 10 µM) following a 48-h exposure. All metabolites evaluated, DOXol, DOXone, and 7-DeoxyDOX caused mitochondrial dysfunction in differentiated AC16 cells, but only at 2 µM. In contrast, DOX elicited comparable cytotoxicity, but at half the concentration. Similarly, all metabolites, except 7-DeoxyDOX impacted on lysosomal ability to uptake neutral red. Therefore, the present study showed that the modulation of DOX metabolism demonstrated minimal impact on its cytotoxicity, with the main metabolites exhibiting lower toxicity to AC16 cardiac cells compared to DOX. In conclusion, our findings suggest that metabolism may not be a pivotal factor in mediating DOX's cardiotoxic effects.

betAS: intuitive analysis and visualization of differential alternative splicing using beta distributions.

Next-generation RNA sequencing allows alternative splicing (AS) quantification with unprecedented resolution, with the relative inclusion of an alternative sequence in transcripts being commonly quantified by the proportion of reads supporting it as percent spliced-in (PSI). However, PSI values do not incorporate information about precision, proportional to the respective AS events' read coverage. Beta distributions are suitable to quantify inclusion levels of alternative sequences, using reads supporting their inclusion and exclusion as surrogates for the two distribution shape parameters. Each such beta distribution has the PSI as its mean value and is narrower when the read coverage is higher, facilitating the interpretability of its precision when plotted. We herein introduce a computational pipeline, based on beta distributions accurately modeling PSI values and their precision, to quantitatively and visually compare AS between groups of samples. Our methodology includes a differential splicing significance metric that compromises the magnitude of intergroup differences, the estimation uncertainty in individual samples, and the intragroup variability, being therefore suitable for multiple-group comparisons. To make our approach accessible and clear to both noncomputational and computational biologists, we developed betAS, an interactive web app and user-friendly R package for visual and intuitive differential splicing analysis from read count data.

Phenolic-rich extracts from toasted white and tannin sorghum flours have distinct profiles influencing their antioxidant, antiproliferative, anti-adhesive, anti-invasive, and antimalarial activities.

Sorghum is a gluten-free cereal commonly used in foods, and its consumption has been associated with the prevention of human chronic conditions such as obesity and cancer, due to the presence of dietary fiber and phenolic compounds. This study aimed to evaluate, for the first time, the antiproliferative, antioxidant, anti-adhesion, anti-invasion, and antimalarial activities of phenolic extracts from toasted white and tannin sorghum flours to understand how different phenolic profiles contribute to sorghum biological activities. Water and 70 % ethanol/water (v/v), eco-friendly solvents, were used to obtain the phenolic extracts of toasted sorghum flours, and their phenolic profile was analyzed by UPLC-MSE. One hundred forty-five (145) phenolic compounds were identified, with 23 compounds common to all extracts. The solvent type affected the phenolic composition, with aqueous extract of both white sorghum (WSA) and tannin sorghum (TSA) containing mainly phenolic acids. White sorghum (WSE) and tannin sorghum (TSE) ethanolic extracts exhibited a higher abundance of flavonoids. WSE demonstrated the lowest IC50 on EA.hy926 (IC50 = 46.6 µg/mL) and A549 cancer cells (IC50 = 33.1 µg/mL), while TSE showed the lowest IC50 (IC50 = 70.8 µg/mL) on HCT-8 cells (human colon carcinoma). Aqueous extracts also demonstrated interesting results, similar to TSE, showing selectivity for cancer cells at higher IC50 concentrations. All sorghum extracts also reduced the adhesion and invasion of HCT-8 cells, suggesting antimetastatic potential. WSE, rich in phenolic acids and flavonoids, exhibited greater toxicity to both the W2 (chloroquine-resistant) and 3D7 (chloroquine-sensitive) strains of Plasmodium falciparum (IC50 = 8 µg GAE/mL and 22.9 µg GAE/mL, respectively). These findings underscore the potential health benefits of toasted sorghum flours, suggesting diverse applications in the food industry as a functional ingredient or even as an antioxidant supplement. Moreover, it is suggested that, besides the phenolic concentration, the phenolic profile is important to understand the health benefits of sorghum flours.

The Role of Nrf2 and Inflammation on the Dissimilar Cardiotoxicity of Doxorubicin in Two-Time Points: a Cardio-Oncology In Vivo Study Through Time.

Doxorubicin (DOX) is a topoisomerase II inhibitor used in cancer therapy. Despite its efficacy, DOX causes serious adverse effects, such as short- and long-term cardiotoxicity. This work aimed to assess the short- and long-term cardiotoxicity of DOX and the role of inflammation and antioxidant defenses on that cardiotoxicity in a mice model. Adult CD-1 male mice received a cumulative dose of 9.0 mg/kg of DOX (2 biweekly intraperitoneal injections (ip), for 3 weeks). One week (1W) or 5 months (5M) after the last DOX administration, the heart was collected. One week after DOX, a significant increase in p62, tumor necrosis factor receptor (TNFR) 2, glutathione peroxidase 1, catalase, inducible nitric oxide synthase (iNOS) cardiac expression, and a trend towards an increase in interleukin (IL)-6, TNFR1, and B-cell lymphoma 2 associated X (Bax) expression was observed. Moreover, DOX induced a decrease on nuclear factor erythroid-2 related factor 2 (Nrf2) cardiac expression. In both 1W and 5M, DOX led to a high density of infiltrating M1 macrophages, but only the 1W-DOX group had a significantly higher number of nuclear factor κB (NF-κB) p65 immunopositive cells. As late effects (5M), an increase in Nrf2, myeloperoxidase, IL-33, tumor necrosis factor-α (TNF-α), superoxide dismutase 2 (SOD2) expression, and a trend towards increased catalase expression were observed. Moreover, B-cell lymphoma 2 (Bcl-2), cyclooxygenase-2 (COX-2), and carbonylated proteins expression decreased, and a trend towards decreased p38 mitogen-activated protein kinase (MAPK) expression were seen. Our study demonstrated that DOX induces adverse outcome pathways related to inflammation and oxidative stress, although activating different time-dependent response mechanisms.

Adherence to the EAT-Lancet diet and its relation with food insecurity and income in a Brazilian population-based sample. / Adesão à dieta EAT-Lancet e sua relação com insegurança alimentar e renda em uma amostra de base populacional brasileira.

This study aimed to investigate the relation of adherence to the planetary diet with food and nutrition security status and per capita household income in a study with a representative sample of the Brazilian population. Among the data from the 2017-2018 Brazilian Household Budgets Survey (POF), the inequality indicators selected for the analysis were data on per capita household income and food and nutrition security. We also considered data on the individual food consumption of 46,164 Brazilians aged ≥ 10 years, obtained through 24-hour dietary recalls, in the National Food Survey, conducted with the POF 2017-2018. The Planetary Health Diet Index (PHDI) was used to measure adherence to the planetary diet. Sociodemographic data were expressed as frequency (%), with analysis of the mean and 95% confidence interval (95%CI) of the PHDI score. The relation of food and nutrition security and income with the PHDI score was tested in multiple linear regression models. The calculations were performed in the Stata software, adopting a 5% significance. Lower PHDI means were observed among food insecure individuals, male, < 20 years old, mixed-race and indigenous, with income < 0.5 minimum wage, residing in rural areas and in the North and Northeast regions. In the multiple linear regression, food insecurity was inversely related to PHDI score (ꞵ = -0.56; 95%CI: -1.06; -0.06), with the lowest scores associated with severe food insecurity (ß = -1.31; 95%CI: -2.19; -0.55). Income categories were not independently associated to PHDI score (p-trend = 0.900). Therefore, food insecurity has been shown to negatively affect Brazilians' adherence to the planetary diet.

O objetivo deste estudo foi investigar a relação entre a adesão à dieta planetária com a situação de segurança alimentar e nutricional e renda familiar per capita, utilizando amostra representativa da população brasileira. Entre os dados da Pesquisa de Orçamentos Familiares (POF) de 2017-2018, os indicadores de desigualdade selecionados para a análise foram as informações sobre renda familiar per capita e segurança alimentar e nutricional. Também foram considerados dados de consumo alimentar individual de 46.164 brasileiros com idade ≥ 10 anos, obtidos por meio de recordatórios alimentares de 24 horas, no Inquérito Nacional de Alimentação, conduzido junto à POF 2017-2018. O Índice de Dieta Planetária (PHDI) foi empregado para mensurar a adesão à dieta planetária. Dados sociodemográficos foram expressos como frequência (%), com análise da média e intervalo de 95% de confiança (IC95%) do escore do PHDI. A relação entre segurança alimentar e nutricional e renda com o escore do PHDI foi testada em modelos de regressão linear múltipla. Os cálculos foram executados no software Stata, adotando uma significância de 5%. Menores médias do PHDI foram observadas entre indivíduos em insegurança alimentar, do sexo masculino, < 20 anos, pardos e indígenas, com renda < 0,5 salário mínimo, domiciliados na zona rural e das regiões Norte e Nordeste. Na regressão linear múltipla, a insegurança alimentar foi inversamente relacionada ao escore do PHDI (ꞵ = -0,56; IC95%: -1,06; -0,06), sendo as menores pontuações associadas à insegurança alimentar grave (ß = -1,31; IC95%: -2,19; -0,55). As categorias de renda não foram independentemente associadas com o escore PHDI (p de tendência = 0,900). Portanto, a insegurança alimentar demonstrou afetar negativamente a adesão dos brasileiros à dieta planetária.

El objetivo de este estudio fue investigar la relación entre la adherencia a la dieta planetaria con la situación de seguridad alimentaria y nutricional y el ingreso familiar per cápita en un estudio con una muestra representativa de la población brasileña. Entre los datos de la Encuesta de Presupuestos Familiares (POF) 2017-2018, los indicadores de desigualdad seleccionados para el análisis fueron la información sobre el ingreso familiar per cápita y la seguridad alimentaria y nutricional. También se utilizaron los datos de consumo alimentario individual de 46.164 brasileños ≥ 10 años, obtenidos mediante registros de alimentos de 24 horas, en la Encuesta Nacional Alimentaria, realizada con POF 2017-2018. Se utilizó el Índice de Dieta Planetaria (PHDI) para medir la adherencia a la dieta planetaria. Los datos sociodemográficos se expresaron como frecuencia (%), con análisis de la media e intervalo de 95% de confianza (IC95%) de la puntuación del PHDI. La relación entre el seguridad alimentaria y nutricional y los ingresos con la puntuación del PHDI se probó en modelos de regresión lineal múltiple. Los cálculos se realizaron en el software Stata, con el nivel de significación del 5%. Se observaron medias más bajas del PHDI entre individuos con inseguridad alimentaria, hombres, < 20 años, pardos e indígenas, con ingresos < 0,5 salario mínimo, residentes en zonas rurales y en las regiones Norte y Nordeste de Brasil. En la regresión lineal múltiple, la inseguridad alimentaria se relacionó inversamente con la puntuación del PHDI (ꞵ = -0,56; IC95%: -1,06; -0,06), y las puntuaciones más bajas estaban asociadas con la inseguridad alimentaria grave (ß = -1,31; IC95%: -2,19; -0,55). Las categorías de ingresos no se asociaron de forma independiente con la puntuación PHDI (p de tendencia = 0,900). Por lo tanto, la inseguridad alimentaria afecta negativamente la adherencia de los brasileños a la dieta planetaria.

Role of short germination and milling on physical properties, amino acid and metabolomic profiles of high amylose rice fractions.

Short germination is a process that can improve bioactive compounds in rice. This work aimed investigate the physical properties, phenolic compounds (PC), antioxidant activity and amino acids composition of husk + bran, brown and milled rice with high amylose content after short germination (16 h). α-amylase activity (Falling Number, FN) and enthalpy (ΔH) were unchanged (p < 0.05). RVA curve profiles were similar, even though after short germination and milling. Globally, metabolomics analysis identified 117 PC, in which 111 (bound), 104 (free) and 21 revealed in both extracts. p-Coumaric, trans-ferulic and ferulic acids were the most abundant PC revealed in all fractions. The portion husk + bran showed the highest level of total antioxidant activity (709.90 µmol TE) in both free and bound fractions. In terms of total amino acids, there was no statistical difference (p < 0.05) among non-germinated and germinated samples, contrary to free amino acids content. Glutamic acid (Glu) presented the highest values combining short germination and milling (1725-1900 mg/100 g) consequently, leads to higher value of GABA (12.21 mg/100 g). The combination of short germination and milling demonstrated a good strategy to improve the nutritional quality of rice, unless the thermal and pasting properties have been altered, contribute to potential health benefits on human nutrition.

ATG9A regulates the dissociation of recycling endosomes from microtubules to form liquid influenza A virus inclusions.

It is now established that many viruses that threaten public health establish condensates via phase transitions to complete their lifecycles, and knowledge on such processes may offer new strategies for antiviral therapy. In the case of influenza A virus (IAV), liquid condensates known as viral inclusions, concentrate the 8 distinct viral ribonucleoproteins (vRNPs) that form IAV genome and are viewed as sites dedicated to the assembly of the 8-partite genomic complex. Despite not being delimited by host membranes, IAV liquid inclusions accumulate host membranes inside as a result of vRNP binding to the recycling endocytic marker Rab11a, a driver of the biogenesis of these structures. We lack molecular understanding on how Rab11a-recycling endosomes condensate specifically near the endoplasmic reticulum (ER) exit sites upon IAV infection. We show here that liquid viral inclusions interact with the ER to fuse, divide, and slide. We uncover that, contrary to previous indications, the reported reduction in recycling endocytic activity is a regulated process rather than a competition for cellular resources involving a novel role for the host factor ATG9A. In infection, ATG9A mediates the removal of Rab11a-recycling endosomes carrying vRNPs from microtubules. We observe that the recycling endocytic usage of microtubules is rescued when ATG9A is depleted, which prevents condensation of Rab11a endosomes near the ER. The failure to produce viral inclusions accumulates vRNPs in the cytosol and reduces genome assembly and the release of infectious virions. We propose that the ER supports the dynamics of liquid IAV inclusions, with ATG9A facilitating their formation. This work advances our understanding on how epidemic and pandemic influenza genomes are formed. It also reveals the plasticity of recycling endosomes to undergo condensation in response to infection, disclosing new roles for ATG9A beyond its classical involvement in autophagy.

A 3D-printed pedal fixator for connecting different pedal-operated tools reduces the number of mistakes during endoscopic submucosal dissection.

Background and study aims What distinguishes endoscopic submucosal dissection (ESD) from endoscopic mucosal resection is the need for three foot pedals to activate the electrosurgical unit, flushing and knife injection. The lack of connection between the various pedals of different shapes and brands leads to numerous pedals displacements and potential mistakes. The aim of this study was to evaluate an Innovative PEdal FIXator (IPEFIX) to reduce pedal mistakes during ESD. Methods This was a prospective, multicenter, randomized study. Consecutive ESD procedures were randomly assigned to two groups: a control group with the three pedals free and the IPEFIX group in which the three pedals were linked by IPEFIX. The main outcome evaluated was the number of foot mistakes (wrong pedal, foot push beside the pedal). Results A total of 107 ESDs were performed by eight experts in five centers. The median number of mistakes per hour of ESD procedure was 0/h in the IPEFIX group and 1.9/h in the control group ( P <0.001). The mean number of times to look down to control the position of the pedals was 2.2/h the IPEFIX group and 7.7/h in the control group ( P <0.001). Mean replacements of the pedals were 0./h in the IPEFIX group and 1.7/h in the control group ( P <0.001). Similar results were obtained in trainees in simulated ESD on animal models. Conclusions IPEFIX is a simple device to connect different pedals during endoscopic procedures. It helps to reduce the numbers of foot mistakes during ESD and improves operator comfort.

Impact of early-onset fetal growth restriction on the neurodevelopmental outcome of very preterm infants at 24 months: a retrospective cohort study.

BACKGROUND: The association between fetal growth restriction (FGR) and childhood neurodevelopmental delay is unclear and the evidence available to the present date shows conflicting results. Our aim was to analyse the impact of early-onset FGR on the neurodevelopmental outcome at 24 months of corrected age in very preterm infants. METHODS: Retrospective cohort study of very preterm infants (≤ 32 weeks' gestation) admitted to a neonatal intensive care unit between 1 January 2013-31 December 2019. The control group comprised appropriate for gestational age (AGA) newborns. Griffiths III Mental Development Scale was performed at 24 months of corrected age. RESULTS: 132 infants were included: 44 FGR and 88 AGA. Mean Global Development Quotient (GDQ) was lower for FGR infants (p = 0.004) even after adjusting for maternal and perinatal factors (ßadjusted -16.703; p = 0.009). The average scores for the neurodevelopmental domains were highest for personal-social-emotional skills (107.02 ± 16.34), followed by eye/hand coordination (105.61 ± 14.20) and foundation of learning skills (102.23 ± 13.74) and were lowest for gross motor (97.90 ± 11.88) and language/communication skills (96.39 ± 18.88). FGR had a significant negative impact on all domains except for gross motor skills. After adjustment, FGR continued to have a significant adverse impact on language/communication (ßadjusted -21.924; p = 0.013), eye/hand coordination (ßadjusted -15.446; p = 0.015) and foundation of learning skills (ßadjusted -15.211; p = 0.013). CONCLUSIONS: In very preterm infants, FGR was associated with a significantly increased risk of poor neurodevelopmental outcome at 24 months of corrected age compared to age-matched AGA infants.

Percepções de mulheres com câncer de mama acerca dos tratamentos / Perceptions of women with breast cancer regarding treatments

O objetivo deste estudo foi compreender a percepção das mulheres com câncer de mama acerca dos tratamentos. Trata-se de um estudo qualitativo, descritivo, transversal, no qual participaram 40 mulheres em quimioterapia para tratamento do câncer mamário em um hospital especializado em oncologia. O instrumento utilizado para coleta de dados foi uma entrevista semiestruturada. Os dados foram analisados mediante Análise de Conteúdo de Bardin e categorizados conforme o Modelo de Crenças em Saúde. Originaram-se quatro categorias: "Suscetibilidade percebida: câncer e COVID-19", "Percepção da gravidade em face do impacto dos tratamentos", "Desafios e barreiras nos tratamentos" e "Benefícios percebidos no tratamento do câncer". Conclui-se que existem diferentes fatores que ressoam na percepção que a mulher tem sobre os tratamentos e que geram repercussões na forma de enfrentá-los. O conhecimento desses fatores pelos profissionais de saúde pode auxiliar na assistência às mulheres para melhor enfrentamento da doença.

The objective of this study was to understand the perception of women with breast cancer about treatments. This is a qualitative, descriptive, cross-sectional study, involving 40 women undergoing chemotherapy for the treatment of breast cancer in a hospital specialized in oncology. The instrument used for data collection was a semi-structured interview. Data was analyzed using Bardin's Content Analysis and categorized according to the Health Belief Model. Four categories emerged: "Perceived susceptibility: cancer and COVID-19", "Perception of severity in view of treatments impact", "Challenges and barriers in treatments" and "Perceived benefits in cancer treatment". It is concluded that there are different factors that resonate in women's perception of treatments and that generate repercussions in the way of facing them. Knowledge of these factors by healthcare professionals can help in providing better assistance to women in facing the disease.

The role of inflammation and antioxidant defenses in the cardiotoxicity of doxorubicin in elderly CD-1 male mice.

Doxorubicin (DOX) is a potent chemotherapeutic agent used against several cancer types. However, due to its cardiotoxic adverse effects, the use of this drug may be also life-threatening. Although most cancer patients are elderly, they are poorly represented and evaluated in pre-clinical and clinical studies. Considering this, the present work aims to evaluate inflammation and oxidative stress as the main mechanisms of DOX-induced cardiotoxicity, in an innovative approach using an experimental model constituted of elderly animals treated with a clinically relevant human cumulative dose of DOX. Elderly (18-20 months) CD-1 male mice received biweekly DOX administrations, for 3 weeks, to reach a cumulative dose of 9.0 mg/kg. One week (1W) or two months (2 M) after the last DOX administration, the heart was collected to determine both drug's short and longer cardiac adverse effects. The obtained results showed that DOX causes cardiac histological damage and fibrosis at both time points. In the 1W-DOX group, the number of nuclear factor kappa B (NF-κB) p65 immunopositive cells increased and a trend toward increased NF-κB p65 expression was seen. An increase of inducible nitric oxide synthase (iNOS) and interleukin (IL)-33 and a trend toward increased IL-6 and B-cell lymphoma-2-associated X (Bax) expression were seen after DOX. In the same group, a decrease in IL-1ß, p62, and microtubule-associated protein 1A/1B-light chain 3 (LC3)-I, p38 mitogen-activated protein kinase (MAPK) expression was observed. Contrariwise, the animals sacrificed 2 M after DOX showed a significant increase in glutathione peroxidase 1 and Bax expression with persistent cardiac damage and fibrosis, while carbonylated proteins, erythroid-2-related factor 2 (Nrf2), NF-κB p65, myeloperoxidase, LC3-I, and LC3-II expression decreased. In conclusion, our study demonstrated that in an elderly mouse population, DOX induces cardiac inflammation, autophagy, and apoptosis in the heart in the short term. When kept for a longer period, oxidative-stress-linked pathways remained altered, as well as autophagy markers and tissue damage after DOX treatment, emphasizing the need for continuous post-treatment cardiac monitoring.

Dental consensus on HSCT - Part II: dental Care during HSCT

ABSTRACT During the state of immune vulnerability in hematopoietic stem cell transplantation (HSCT), the patient has an increased risk of developing a vast number of complications, including severe problems in the oral cavity. These situations require professional oral care to act in the diagnosis and treatment of these conditions, as well as to develop prevention protocols to minimize patient's complications. Oral mucositis, opportunistic infections, bleeding, specific microbiota, taste, and salivary alterations are complications that can occur during HSCT and interfere with various aspects, such as pain control, oral intake, nutrition, bacteremia and sepsis, days of hospitalization and morbidity. Several guidelines have been published to address the role of professional oral care during the HSCT, we describe a consensus regarding these recommendations.

Marsupial position on life-history continua and the potential contribution of life-history traits to population growth.

Previous studies have suggested that mammal life history varies along the fast-slow continuum and that, in eutherians, this continuum is linked to variation in the potential contribution of survival and reproduction to population growth rate (λ). Fast eutherians mature early, have large litters and short lifespans, and exhibit high potential contribution of age at first reproduction and fertility to λ, while slow eutherians show high potential contribution of survival to λ. However, marsupials have typically been overlooked in comparative tests of mammalian life-history evolution. Here, we tested whether the eutherian life-history pattern extends to marsupials, and show that marsupial life-history trade-offs are organized along two major axes: (i) the reproductive output and dispersion axis, and (ii) the fast-slow continuum, with an additional association between adult survival and body mass. Life-history traits that potentially drive changes in λ are similar in eutherians and marsupials with slow life histories, but differ in fast marsupials; age at first reproduction is the most important trait contributing to λ and fertility contributes little. Marsupials have slower life histories than eutherians, and differences between these clades may derive from their contrasting reproductive modes; marsupials have slower development, growth and metabolism than eutherians of equivalent size.