Cloud point method applied to the extraction and preconcentration of thiabendazole pesticide from whole grape juice samples and amperometric detection by HPLC.

A cloud point method was developed and applied for the first time to extract and preconcentrate thiabendazole (TBZ) from commercial whole grape juice samples, with determination by high performance liquid chromatography coupled to electrochemical detection (HPLC/EC), using a cathodically pretreated boron-doped diamond electrode (BDD). The best conditions for extraction and preconcentration of TBZ by cloud point extraction (CPE) were performed at pH 6.0, by adding 1 mL of the surfactant Tergitol TMN-6 at 10% (mass-to-mass ratio), without heating (at 27 °C) and ultrasonic stirring time of (20 kHz) for 60 min. The HPLC/EC determination was duly validated in a C8 column, in mobile phase with a 69 : 31 ratio (V/V) of phosphate buffer (pH 7.0):ACN, at a flow rate of 1.2 mL min-1 and electrochemical detection with BDD electrode by applying 1.40 V × Ag/AgCl (3.0 mol L-1). Under these conditions, the procedure showed a preconcentration factor (FC) of 21.7, and limits of detection (LOD) and quantification (LOQ) of 6.64 × 10-9 mol L-1 (or 1.33 µg L-1) and 1.66 × 10-8 mol L-1 (or 3.34 µg L-1), respectively. The method provided a percent recovery of 81% to 98%, with a coefficient of variation between 3% and 15%.

Optimizing Screw Speed and Barrel Temperature for Textural and Nutritional Improvement of Soy-Based High-Moisture Extrudates.

Soy remains the legume protein of excellence for plant-based meat alternatives due to its fiber-forming potential. In this study, protein-rich powders from soy protein isolate (SPI), concentrate (SPC), and their mixture (SPM) were thoroughly characterized for their proximate composition, nutritional quality, and physicochemical properties to understand their structuring behavior during high-moisture extrusion. SPI presented higher degrees of protein denaturation and aggregation, least gelation concentration and lower essential amino acid contents. Thus, an SPI:SPC combination (1:9 ratio, 70% protein) was extruded at three different screw speeds (300, 350, and 400 rpm) and two temperature profiles (120 and 140 °C maximum temperature). The effects of the processing parameters on the extrudates were evaluated for their appearance (fibrousness), texture (TPA, cutting force, and anisotropy), color, protein structure (FTIR), and trypsin inhibitors. Higher temperatures resulted in softer and darker extrudates, with increased visual and instrumental anisotropy. Increasing screw speeds led to softer and lighter extrudates, without a clear fibrousness effect. ß-sheet structures decreased and intermolecular aggregates (A1) increased after extrusion, especially at 140 °C, together with the formation of intramolecular aggregates (A2). Extrusion also significantly decreased the amount of trypsin inhibitors (>90%). This study demonstrates that extrusion parameters need to be carefully selected to achieve meat analogs with optimal textural and nutritional characteristics.

The familial amyotrophic lateral sclerosis-associated A4V SOD1 mutant is not able to regulate aerobic glycolysis.

Under certain stress conditions, astrocytes operate in aerobic glycolysis, a process controlled by pyruvate dehydrogenase (PDH) inhibition through its E1 α subunit (Pda1) phosphorylation. This supplies lactate to neurons, which save glucose to obtain NADPH to, among other roles, counteract reactive oxygen species. A failure in this metabolic cooperation causes severe damage to neurons. In this work, using humanized Saccharomyces cerevisiae cells in which its endogenous Cu/Zn Superoxide Dismutase (SOD1) was replaced by human ortholog, we investigated the role of human SOD1 (hSOD1) in aerobic glycolysis regulation and its implications to amyotrophic lateral sclerosis (ALS), a neurodegenerative disease. Yeast cells ferment glucose even in the presence of oxygen and switch to respiratory metabolism after glucose exhaustion. However, like cells of SOD1-knockout strain, cells expressing A4V mutant of hSOD1 growing on glucose showed a respiratory phenotype, i.e., low glucose and high oxygen consumptions and low intracellular oxidation levels in response to peroxide stress, contrary to cells expressing wild-type (WT) SOD1 (yeast or human). The A4V mutation in hSOD1 is linked to ALS. In contrast to WT SOD1 strains, PDH activity of both sod1Δ and A4V hSOD1 cells did not change in response to a metabolic shift toward oxidative metabolism, which was associated to lower Pda1 phosphorylation levels under growth on glucose. Taken together, our results suggest that A4V mutant cannot regulate aerobic glycolysis via Pda1 phosphorylation the same way WT hSOD1, which might be linked to problems observed in the motor neurons of ALS patients with the SOD1 A4V mutation.

Epidemiology of the SARS-CoV-2 Omicron Variant Emergence in the Southeast Brazilian Population.

The aim of this study was to describe epidemiological characteristics and perform SARS-CoV-2 genomic surveillance in the southeastern region of São Paulo State. During the first months of 2022, we compared weekly SARS-CoV-2 infection prevalence considering age, Ct value, and variants' lineages. An increase in the number of SARS-CoV-2-positive cases until the fourth epidemiological week of 2022 was observed. From the fourth epidemiological week onwards, the number of tests for SARS-CoV-2 diagnosis began to decrease, but the number of positive samples for SARS-CoV-2 remained high, reaching its most expressive level with a rate of 60% of infected individual cases. In this period, we observed a progressive increase in SARS-CoV-2 infection within the 0-10 age group throughout the epidemiological weeks, from 2.8% in the first epidemiological week to 9.2% in the eighth epidemiological week of 2022. We further observed significantly higher Ct values within younger patient samples compared to other older age groups. According to lineage assignment, SARS-CoV-2 (BA.1) was the most prevalent (74.5%) in the younger group, followed by BA.1.1 (23%), BA.2 (1.7%), and Delta (1%). Phylogenetic analysis showed that BA.2 sequences clustered together, indicating sustained transmission of this Omicron VOC sub-lineage by that time. Our results suggest the initial dissemination steps of the Omicron's sub-linage BA.2 into the younger group, due to specific genomic features of the detected sequences. These data provide interesting results related to the spread, emergence, and evolution of the Omicron variant in the southeast Brazilian population.

Dynamic clade transitions and the influence of vaccine rollout on the spatiotemporal circulation of SARS-CoV-2 variants in São Paulo, Brazil.

Since 2021, the emergence of variants of concern (VOC) has led Brazil to experience record numbers of in COVID-19 cases and deaths. The expanded spread of the SARS-CoV-2 combined with a low vaccination rate has contributed to the emergence of new mutations that may enhance viral fitness, leading to the persistence of the disease. Due to limitations in the real-time genomic monitoring of new variants in some Brazilian states, we aimed to investigate whether genomic surveillance, coupled with epidemiological data and SARS-CoV-2 variants spatiotemporal spread in a smaller region, can reflect the pandemic progression at a national level. Our findings revealed three SARS-CoV-2 variant replacements from 2021 to early 2022, corresponding to the introduction and increase in the frequency of Gamma, Delta, and Omicron variants, as indicated by peaks of the Effective Reproductive Number (Reff). These distinct clade replacements triggered two waves of COVID-19 cases, influenced by the increasing vaccine uptake over time. Our results indicated that the effectiveness of vaccination in preventing new cases during the Delta and Omicron circulations was six and eleven times higher, respectively, than during the period when Gamma was predominant, and it was highly efficient in reducing the number of deaths. Furthermore, we demonstrated that genomic monitoring at a local level can reflect the national trends in the spread and evolution of SARS-CoV-2.

Gamma-delta T cells suppress microbial metabolites that activate striatal neurons and induce repetitive/compulsive behavior in mice.

Intestinal γδ T cells play an important role in shaping the gut microbiota, which is critical not only for maintaining intestinal homeostasis but also for controlling brain function and behavior. Here, we found that mice deficient for γδ T cells (γδ-/-) developed an abnormal pattern of repetitive/compulsive (R/C) behavior, which was dependent on the gut microbiota. Colonization of WT mice with γδ-/- microbiota induced R/C behavior whereas colonization of γδ-/- mice with WT microbiota abolished the R/C behavior. Moreover, γδ-/- mice had elevated levels of the microbial metabolite 3-phenylpropanoic acid in their cecum, which is a precursor to hippurate (HIP), a metabolite we found to be elevated in the CSF. HIP reaches the striatum and activates dopamine type 1 (D1R)-expressing neurons, leading to R/C behavior. Altogether, these data suggest that intestinal γδ T cells shape the gut microbiota and their metabolites and prevent dysfunctions of the striatum associated with behavior modulation.

Photobiomodulation Therapy to Treat Snakebites Caused by Bothrops atrox: A Randomized Clinical Trial.

Importance: Bothrops venom acts almost immediately at the bite site and causes tissue damage. Objective: To investigate the feasibility and explore the safety and efficacy of low-level laser therapy (LLLT) in reducing the local manifestations of B atrox envenomations. Design, Setting, and Participants: This was a double-blind randomized clinical trial conducted at Fundação de Medicina Tropical Doutor Heitor Vieira Dourado, in Manaus, Brazil. A total of 60 adult participants were included from November 2020 to March 2022, with 30 in each group. Baseline characteristics on admission were similarly distributed between groups. Data analysis was performed from August to December 2022. Intervention: The intervention group received LLLT combined with regular antivenom treatment. The laser used was a gallium arsenide laser with 4 infrared laser emitters and 4 red laser emitters, 4 J/cm2 for 40 seconds at each application point. Main Outcomes and Measures: Feasibility was assessed by eligibility, recruitment, and retention rates; protocol fidelity; and patients' acceptability. The primary efficacy outcome of this study was myolysis estimated by the value of creatine kinase (U/L) on the third day of follow-up. Secondary efficacy outcomes were (1) pain intensity, (2) circumference measurement ratio, (3) extent of edema, (4) difference between the bite site temperature and that of the contralateral limb, (5) need for the use of analgesics, (6) frequency of secondary infections, and (7) necrosis. These outcomes were measured 48 hours after admission. Disability assessment was carried out from 4 to 6 months after patients' discharge. P values for outcomes were adjusted with Bonferroni correction. Results: A total of 60 patients (mean [SD] age, 43.2 [15.3] years; 8 female individuals [13%] and 52 male individuals [87%]) were included. The study was feasible, and patient retention and acceptability were high. Creatine kinase was significantly lower in the LLLT group (mean [SD], 163.7 [160.0] U/L) 48 hours after admission in relation to the comparator (412.4 [441.3] U/L) (P = .03). Mean (SD) pain intensity (2.9 [2.7] vs 5.0 [2.4]; P = .004), circumference measurement ratio (6.6% [6.6%] vs 17.1% [11.6%]; P < .001), and edema extent (25.8 [15.0] vs 40.1 [22.7] cm; P = .002) were significantly lower in the LLLT group in relation to the comparator. No difference was observed between the groups regarding the mean difference between the bite site temperature and the contralateral limb. Secondary infections, necrosis, disability outcomes, and the frequency of need for analgesics were similar in both groups. No adverse event was observed. Conclusions and Relevance: The data from this randomized clinical trial suggest that the use of LLLT was feasible and safe in a hospital setting and effective in reducing muscle damage and the local inflammatory process caused by B atrox envenomations. Trial Registration: Brazilian Registry of Clinical Trials Identifier: RBR-4qw4vf.

Conhecimento, Atitude e Prática de Gestantes Sobre Incontinência Urinária: Estudo Observacional / Knowledge, Attitude, and Practice of Pregnant Women About Urinary Incontinence: Observational Study / Conocimiento, Actitud y Práctica De Gestantes Sobre la Incontinencia Urinaria: Estudio Observacional

Objetivo:avaliar o conhecimento, a atitude e a prática (CAP) de gestantes sobre incontinência urinária (IU), identificar a prevalência de IU durante a gestação, avaliar seu impacto na qualidade de vida (QV) e identificar os fatores associados ao CAP inadequados em relação à IU. Metodologia: Estudo observacional realizado de maio a novembro de 2019 na cidade de Fortaleza, Ceará. Utilizaram-se dois instrumentos para coleta de dados: um para avaliação sociodemográfica, obstétrica e de perdas urinárias e outro para avaliação do CAP sobre IU. Resultados: Participaram 237 gestantes. A prevalência de IU foi de 49,3% e observou-se baixo impacto na QV. A maioria apresentou conhecimento (89,6%) e prática inadequados tanto para prevenir (89,2%) quanto para tratar (78,8%) a IU. Identificaram-se baixos percentuais de acerto relacionados ao conhecimento sobre fatores de risco (46,8%), prevenção (43,8%) e tratamento da IU (42,8%). Apesar disso, a atitude foi considerada adequada para a maioria das mulheres (98,5%). Ausência de orientação sobre o preparo do períneo para o parto durante o pré-natal (p = 0,019), baixa escolaridade (p < 0,001), casos mais leves de IU (p = 0,027) e gestação de alto risco (p = 0,004) associaram-se a prática inadequada. Conclusão: o conhecimento sobre causas, prevenção e tratamento da IU é insuficiente e interfere no manejo dessa condição.perineum for childbirth during prenatal care (p = 0.019), low education (p < 0.001), milder cases of UI (p = 0.027) and high-risk pregnancy (p = 0.004) were associated with inappropriate practice. Conclusions: knowledge about the causes, prevention and treatment of UI is insufficient and interferes with the management of this condition.

Objectives:To assess the knowledge, attitude and practice (KAP) of pregnant women about urinary incontinence (UI), identify the prevalence of UI, assess its impact on quality of life (QoL) and identify factors associated with inadequate KAP in relation to UI. Methodology: Observational study carried out from May to November 2019 in the city of Fortaleza, Ceará, Brazil. Two instruments were used for data collection: one for sociodemographic, obstetric and urinary loss assessment and another for KAP assessment on UI. Results: 237 pregnant women participated. The prevalence of UI was 49.3% and a low impact on QoL was observed. Most had knowledge (89.6%) and inadequate practice both to prevent (89.2%) and to treat (78.8%). Low percentages of correct answers were identified related to knowledge about risk factors (46.8%), prevention (43.8%) and treatment of UI (42.8%). Despite this, the attitude was considered adequate for most women (98.5%). Absence of guidance on preparation of the perineum for childbirth during prenatal care (p = 0.019), low education (p < 0.001), milder cases of UI (p = 0.027) and high-risk pregnancy (p = 0.004) were associated with inappropriate practice. Conclusions: knowledge about the causes, prevention and treatment of UI is insufficient and interferes with the management of this condition.

Objetivos:evaluar el conocimiento, la actitud y la práctica (CAP) de las gestantes sobre la incontinencia urinaria (IU), identificar la prevalencia de la IU, evaluar su impacto en la calidad de vida (CV) e identificar los factores asociados a una PAC inadecuada en relación con la IU. Metodología: estudio observacional realizado de mayo a noviembre de 2019 en la ciudad de Fortaleza/CE. Se utilizaron dos instrumentos para la recolección de datos: uno para la evaluación sociodemográfica, obstétrica y de pérdidas urinarias y otro para la evaluación del CAP en la IU. Resultados: Participaron 237 gestantes. La prevalencia de IU fue del 49,3% y se observó un bajo impacto en la CV. La mayoría tenía conocimiento (89,6%) y práctica inadecuada tanto para prevenir (89,2%) como para tratar (78,8%). Se identificaron bajos porcentajes de aciertos relacionados con el conocimiento sobre factores de riesgo (46,8%), prevención (43,8%) y tratamiento de la IU (42,8%). A pesar de ello, la actitud fue considerada adecuada por la mayoría de las mujeres (98,5%). La ausencia de orientación sobre la preparación del perineo para el parto durante el control prenatal (p = 0,019), la baja escolaridad (p < 0,001), los casos más leves de IU (p = 0,027) y el embarazo de alto riesgo (p = 0,004) se asociaron con una atención inadecuada. práctica. Conclusión: el conocimiento sobre las causas, la prevención y el tratamiento de la IU es insuficiente e interfiere con el manejo de esta condición.

Utilização das boas práticas no parto e experiência e satisfação materna / Using good delivery practices and maternal experience and satisfaction

Objetivo: Descrever a utilização das boas práticas de atenção ao parto e nascimento e o grau de satisfação e experiência de puérperas com o parto. Métodos: Estudo transversal, realizado no período de julho de 2017 a janeiro de 2018, em uma maternidade de referência em Fortaleza, Ceará. Para coleta de dados utilizou-se o Questionário de Experiência e Satisfação com o Parto e questionário para avaliação dos dados sociodemográficos e obstétricos. Os dados foram analisados no softwareStatistical Package for the Social Science. O estudo foi aprovado pelo Comitê de Ética em Pesquisa. Resultados: Participaram 237 puérperas com média de idade de 26 anos. 168 (70,9%) mulheres estiveram bastante satisfeitas com a estrutura da instituição, 119 (50,2%) com os cuidados profissionais prestados e 160 (67,5%) com o trabalho de parto e parto. Dentre os fatores que estiveram associados à experiência positiva com o parto, destaca-se a realização do contato pele a pele, o estímulo ao aleitamento materno e a utilização dos métodos não farmacológicos de alívio da dor. Conclusão: Para uma experiência mais positiva de parto, ressalta-se a importância de abordagens mais humanizadas que incentivem práticas como contato pele a pele e início precoce do aleitamento materno, além de garantir que profissionais de saúde forneçam cuidados holísticos. Descritores: Satisfação do Paciente; Enfermagem Obstétrica; Trabalho de Parto; PartoNormal; PartoHumanizado.

Objective:To describe the use of good practices in delivery and childbirth care and the satisfaction levels and experiences of puerperal women with their deliveries.Methods:A cross-sectional study conducted from July 2017 to January 2018 in a reference maternity hospital from Fortaleza, Ceará. The Childbirth Experience and Satisfaction Questionnaire and another one to assess the sociodemographic and obstetric data were used for data collection. The data were analyzed in the Statistical Package for the Social Science. The study was approved by the Research Ethics Committee. Results:The participants were 237 puerperal women with a mean age of 26 years old. 168 (70.9%) women were quite satisfied with the institution's structure, 119 (50.2%) with the professional care provided, and 160 (67.5%) with labor and delivery. Among the factors that were associated with positive experiences with delivery, the most important are skin-to-skin contact, stimulating breastfeeding, and using non-pharmacological pain relief methods. Conclusion: For a more positive experience with delivery, it is worth emphasizing the importance of more humanized approaches that encourage practices such as skin-to-skin contact and early breastfeeding initiation, as well as ensuring that health professionals provide holistic care. Descriptors:Patient Satisfaction; Obstetric Nursing; Labor. Normal Delivery; Humanized Delivery.

Epidemiological and Genomic Analysis of Asymptomatic SARS-CoV-2 Infections during the Delta and Omicron Epidemic Waves in São Paulo City, Brazil.

We examined the asymptomatic rates of SARS-CoV-2 infection during the Delta and Omicron waves in the city of São Paulo. Nasopharyngeal swabs were collected at strategic points of the city (open-air markets, bus terminals, airports) for SARS-CoV-2 RNA testing. Applying the questionnaire, the symptomatic individuals were excluded, and only asymptomatic cases were analyzed. During the Delta wave, a total of 4315 samples were collected, whereas 2372 samples were collected during the first Omicron wave. The incidence of the asymptomatic SARS-CoV-2 infection was 0.6% during the Delta wave and 0.8% during the Omicron wave. No statistical differences were found in the threshold amplification cycle. However, there was a statistical difference observed in the sublineage distribution between asymptomatic and symptomatic individuals. Our study determined the incidence of asymptomatic infection by monitoring individuals who remained symptom-free, thereby providing a reliable evaluation of asymptomatic SARS-CoV-2 carriage. Our findings reveal a relatively low proportion of asymptomatic cases, which could be attributed to our rigorous monitoring protocol for the presence of clinical symptoms. Investigating asymptomatic infection rates is crucial to develop and implement effective disease control strategies.

Unveiling the role of osteosarcoma-derived secretome in premetastatic lung remodelling.

BACKGROUND: Lung metastasis is the most adverse clinical factor and remains the leading cause of osteosarcoma-related death. Deciphering the mechanisms driving metastatic spread is crucial for finding open therapeutic windows for successful organ-specific interventions that may halt or prevent lung metastasis. METHODS: We employed a mouse premetastatic lung-based multi-omics integrative approach combined with clinical features to uncover the specific changes that precede lung metastasis formation and identify novel molecular targets and biomarker of clinical utility that enable the design of novel therapeutic strategies. RESULTS: We found that osteosarcoma-bearing mice or those preconditioned with the osteosarcoma cell secretome harbour profound lung structural alterations with airway damage, inflammation, neutrophil infiltration, and extracellular matrix remodelling with increased deposition of fibronectin and collagens by resident stromal activated fibroblasts, favouring the adhesion of disseminated tumour cells. Systemic-induced microenvironmental changes, supported by transcriptomic and histological data, promoted and accelerated lung metastasis formation. Comparative proteome profiling of the cell secretome and mouse plasma identified a large number of proteins involved in extracellular-matrix organization, cell-matrix adhesion, neutrophil degranulation, and cytokine-mediated signalling, consistent with the observed lung microenvironmental changes. Moreover, we identified EFEMP1, an extracellular matrix glycoprotein exclusively secreted by metastatic cells, in the plasma of mice bearing a primary tumour and in biopsy specimens from osteosarcoma patients with poorer overall survival. Depletion of EFEMP1 from the secretome prevents the formation of lung metastasis. CONCLUSIONS: Integration of our data uncovers neutrophil infiltration and the functional contribution of stromal-activated fibroblasts in ECM remodelling for tumour cell attachment as early pro-metastatic events, which may hold therapeutic potential in preventing or slowing the metastatic spread. Moreover, we identified EFEMP1, a secreted glycoprotein, as a metastatic driver and a potential candidate prognostic biomarker for lung metastasis in osteosarcoma patients. Osteosarcoma-derived secreted factors systemically reprogrammed the lung microenvironment and fostered a growth-permissive niche for incoming disseminated cells to survive and outgrow into overt metastasis. Daily administration of osteosarcoma cell secretome mimics the systemic release of tumour-secreted factors of a growing tumour in mice during PMN formation; Transcriptomic and histological analysis of premetastatic lungs revealed inflammatory-induced stromal fibroblast activation, neutrophil infiltration, and ECM remodelling as early onset pro-metastatic events; Proteome profiling identified EFEMP1, an extracellular secreted glycoprotein, as a potential predictive biomarker for lung metastasis and poor prognosis in osteosarcoma patients. Osteosarcoma patients with EFEMP1 expressing biopsies have a poorer overall survival.

O efeito da polarização política na crença em notícias falsas / The effect of political polarization on belief in fake news

A polarização política pode ser entendida como o afastamento severo de grupos com pensamentos e sentimentos opostos aos do seu grupo político. No cenário brasileiro, a polarização está presente em diversos contextos, principalmente no contexto político e pode ser capaz de influenciar o endosso de notícias falsas. Buscando entender as fake news em um contexto de polarização política, o presente artigo buscou avaliar a relação entre a polarização política e a crença em notícias falsas, tanto de esquerda quanto de direita. Para tanto, 211 participantes responderam um questionário contendo quatro instrumentos distintos: termômetro de sentimentos; avaliação de notícias; posicionamento político; e suscetibilidade às notícias falsas. Os resultados indicaram que os indivíduos tendem a acreditar em notícias falsas do seu próprio grupo político, embora participantes de direita apresentem uma maior tendência de endossar fake news em comparação com participantes de esquerda. De maneira geral, verificou-se que a polarização política afeta o endosso de fake news. Implicações para compreensão e combate às fake news são discutidas.

Political polarization can be understood as the strong alienation of groups with thoughts and feelings opposite to those of their political group. In the Brazilian scenario, polarization is present in different contexts, especially in the political context and can influence the endorsement of fake news. Seeking to understand fake news in the context of political polarization, the present article sought to evaluate the relationship between political polarization and belief in fake news, both on the left and on the right. To this end, 211 participants completed a questionnaire that included four different instruments: mood thermometer; news rating; political positioning; and susceptibility to fake news. The results indicate that individuals tend to believe fake news from their own political group, although participants from the right-wing participants are more likely to endorse fake news than participants to left-wing participants. Overall, political polarization was found to affect the endorsement of fake news. Implications for understanding and combating fake news are discussed.

Glycation modulates superoxide dismutase 1 aggregation and toxicity in models of sporadic amyotrophic lateral sclerosis.

Different SOD1 proteoforms are implicated## in both familial and sporadic cases of Amyotrophic Lateral Sclerosis (ALS), an aging-associated disease that affects motor neurons. SOD1 is crucial to neuronal metabolism and health, regulating the oxidative stress response and the shift between oxidative-fermentative metabolism, which is important for astrocyte-neuron metabolic cooperation. Neurons have a limited capacity to metabolize methylglyoxal (MGO), a potentially toxic side product of glycolysis. MGO is highly reactive and can readily posttranslationally modify proteins, in a reaction known as glycation, impacting their normal biology. Here, we aimed to investigate the effect of glycation on the aggregation and toxicity of human SOD1WT (hSOD1WT). Cells with deficiency in MGO metabolism showed increased levels of hSOD1WT inclusions, displaying also reduced hSOD1WT activity and viability. Strikingly, we also found that the presence of hSOD1WT in stress granules increased upon MGO treatment. The treatment of recombinant hSOD1WT with MGO resulted in the formation of SDS-stable oligomers, specially trimers, and thioflavin-T positive aggregates, which can promote cell toxicity and TDP-43 pathology. Together, our results suggest that glycation may play a still underappreciated role on hSOD1WT and TDP-43 pathologies in sporadic ALS, which could open novel perspectives for therapeutic intervention.

Innate Immune Cells in the Tumor Microenvironment of Liver Metastasis from Colorectal Cancer: Contribution to a Comprehensive Therapy.

Colorectal cancer (CRC) is the third most prevalent type of cancer, and liver metastasis is the most common site of metastatic development. In the tumor microenvironment (TME), various innate immune cells are known to influence cancer progression and metastasis occurrence. CD274 (PD-L1) and CD206 (MRC1) are proteins that have been associated with poor prognosis and disease progression. We conducted a study on tumoral and non-tumoral biopsies from 47 patients with CRC liver metastasis, using flow cytometry to phenotypically characterize innate immune cells. Our findings showed an increase in the expression of CD274 on classical, intermediate, and non-classical monocytes when comparing tumor with non-tumor samples. Furthermore, tumor samples with a desmoplastic growth pattern exhibited a significantly decreased percentage of CD274- and CD206-positive cells in all monocyte populations compared to non-desmoplastic samples. We found a correlation between a lower expression of CD206 or CD274 on classical, intermediate, and non-classical monocytes and increased disease-free survival, which points to a better prognosis for these patients. In conclusion, our study has identified potential new targets and biomarkers that could be incorporated into a personalized medicine approach to enhance the outcome for colorectal cancer patients.

Self-Renewal and Pluripotency in Osteosarcoma Stem Cells' Chemoresistance: Notch, Hedgehog, and Wnt/ß-Catenin Interplay with Embryonic Markers.

Osteosarcoma is a highly malignant bone tumor derived from mesenchymal cells that contains self-renewing cancer stem cells (CSCs), which are responsible for tumor progression and chemotherapy resistance. Understanding the signaling pathways that regulate CSC self-renewal and survival is crucial for developing effective therapies. The Notch, Hedgehog, and Wnt/ß-Catenin developmental pathways, which are essential for self-renewal and differentiation of normal stem cells, have been identified as important regulators of osteosarcoma CSCs and also in the resistance to anticancer therapies. Targeting these pathways and their interactions with embryonic markers and the tumor microenvironment may be a promising therapeutic strategy to overcome chemoresistance and improve the prognosis for osteosarcoma patients. This review focuses on the role of Notch, Hedgehog, and Wnt/ß-Catenin signaling in regulating CSC self-renewal, pluripotency, and chemoresistance, and their potential as targets for anti-cancer therapies. We also discuss the relevance of embryonic markers, including SOX-2, Oct-4, NANOG, and KLF4, in osteosarcoma CSCs and their association with the aforementioned signaling pathways in overcoming drug resistance.

Striatal dopamine D2-like receptors availability in obesity and its modulation by bariatric surgery: a systematic review and meta-analysis.

There is significant evidence linking a 'reward deficiency syndrome' (RDS), comprising decreased availability of striatal dopamine D2-like receptors (DD2lR) and addiction-like behaviors underlying substance use disorders and obesity. Regarding obesity, a systematic review of the literature with a meta-analysis of such data is lacking. Following a systematic review of the literature, we performed random-effects meta-analyses to determine group differences in case-control studies comparing DD2lR between individuals with obesity and non-obese controls and prospective studies of pre- to post-bariatric surgery DD2lR changes. Cohen's d was used to measure effect size. Additionally, we explored factors potentially associated with group differences in DD2lR availability, such as obesity severity, using univariate meta-regression. In a meta-analysis including positron emission tomography (PET) and single-photon emission computed tomography (SPECT) studies, striatal DD2lR availability did not significantly differ between obesity and controls. However, in studies comprising patients with class III obesity or higher, group differences were significant, favoring lower DD2lR availability in the obesity group. This effect of obesity severity was corroborated by meta-regressions showing inverse associations between the body mass index (BMI) of the obesity group and DD2lR availability. Post-bariatric changes in DD2lR availability were not found, although a limited number of studies were included in this meta-analysis. These results support lower DD2lR in higher classes of obesity which is a more targeted population to explore unanswered questions regarding the RDS.

Retrospective Insights of the COVID-19 Epidemic in the Major Latin American City, São Paulo, Southeastern Brazil.

São Paulo is the financial center of Brazil, with a population of over 12 million, that receives travelers from all over the world for business and tourism. It was the first city in Brazil to report a case of COVID-19 that rapidly spread across the city despite the implementation of the restriction measures. Despite many reports, much is still unknown regarding the genomic diversity and transmission dynamics of this virus in the city of São Paulo. Thus, in this study, we provide a retrospective overview of the COVID-19 epidemic in São Paulo City, Southeastern, Brazil, by generating a total of 9995 near-complete genome sequences from all the city's different macro-regions (North, West, Central, East, South, and Southeast). Our analysis revealed that multiple independent introduction events of different variants (mainly Gamma, Delta, and Omicron) occurred throughout time. Additionally, our estimates of viral movement within the different macro-regions further suggested that the East and the Southeast regions were the largest contributors to the Gamma and Delta viral exchanges to other regions. Meanwhile, the North region had a higher contribution to the dispersion of the Omicron variant. Together, our results reinforce the importance of increasing SARS-CoV-2 genomic monitoring within the city and the country to track the real-time evolution of the virus and to detect earlier any eventual emergency of new variants of concern that could undermine the fight against COVID-19 in Brazil and worldwide.

Profile of the leprosy endemic in the district of Murrupula, Nampula, Mozambique: A population-based study.

BACKGROUND: Leprosy is a neglected chronic infection caused by Mycobacterium leprae, that is curable. The magnitude of the disease and severity of the debilitation it causes renders leprosy a public health problem. This study aimed to analyze the endemic profile of leprosy in the Murrupula district and evaluate the socioeconomic, clinical, and serological profiles of leprosy contacts. METHODS: A cross-sectional study of patients with leprosy diagnosed between 2013 and 2017 and their household and community contacts was conducted in Murrupula District, Nampula Province, Mozambique. Interviews, simplified dermatoneurological examinations, Mycobacterium leprae flow (ML Flow) tests, and Mitsuda tests were performed. RESULTS: Most of the leprosy cases were multibacillary. The patients had some degree of physical disability. ML Flow positivity was more common in household contacts of the patients diagnosed with leprosy and in community individuals who spontaneously presented for testing. In total, 17 patients were diagnosed with leprosy. CONCLUSIONS: This study revealed an active chain of transmission, hidden prevalence, and operational deficiencies in leprosy surveillance and care. The results suggest that the implementation of a public health policy for leprosy prevention and control in Nampula Province is necessary. In future, the possibility of expanding the policy to the entire country should be considered.

The Candida glabrata Parent Strain Trap: How Phenotypic Diversity Affects Metabolic Fitness and Host Interactions.

Reference strains improve reproducibility by standardizing observations and methodology, which has ultimately led to important insights into fungal pathogenesis. However, recent investigations have highlighted significant genotypic and phenotypic heterogeneity across isolates that influence genetic circuitry and virulence within a species. Candida glabrata is the second leading cause of candidiasis, a life-threatening infection, and undergoes extensive karyotype and phenotypic changes in response to stress. Much of the work conducted on this pathogen has focused on two sequenced strains, CBS138 (ATCC 2001) and BG2. Few studies have compared these strains in detail, but key differences include mating type and altered patterns of expression of EPA adhesins. In fact, most C. glabrata isolates and BG2 are MATa, while CBS138 is MATα. However, it is not known if other phenotypic differences between these strains play a role in our understanding of C. glabrata pathogenesis. Thus, we set out to characterize metabolic, cell wall, and host-interaction attributes for CBS138 and BG2. We found that BG2 utilized a broader range of nitrogen sources and had reduced cell wall size and carbohydrate exposure than CBS138, which we hypothesized results in differences in innate immune interactions and virulence. We observed that, although both strains were phagocytosed to a similar extent, BG2 replicated to higher numbers in macrophages and was more virulent during Galleria mellonella infection than CBS138 in a dose-dependent manner. Interestingly, deletion of SNF3, a major nutrient sensor, did not affect virulence in G. mellonella for BG2, but significantly enhanced larval killing in the CBS138 background compared to the parent strain. Understanding these fundamental differences in metabolism and host interactions will allow more robust conclusions to be drawn in future studies of C. glabrata pathogenesis. IMPORTANCE Reference strains provide essential insights into the mechanisms underlying virulence in fungal pathogens. However, recent studies in Candida albicans and other species have revealed significant genotypic and phenotypic diversity within clinical isolates that are challenging paradigms regarding key virulence factors and their regulation. Candida glabrata is the second leading cause of candidiasis, and many studies use BG2 or CBS138 for their investigations. Therefore, we aimed to characterize important virulence-related phenotypes for both strains that might alter conclusions about C. glabrata pathogenesis. Our study provides context for metabolic and cell wall changes and how these may influence host interaction phenotypes. Understanding these differences is necessary to support robust conclusions about how virulence factors may function in these and other very different strain backgrounds.

A traveling SARS-CoV-2 laboratory as part of a pandemic response among vulnerable Brazilian populations.

BACKGROUND: Brazil has been dramatically hit by the SARS-CoV-2 pandemic and is a world leader in COVID-19 morbidity and mortality. Additionally, the largest country of Latin America has been a continuous source of SARS-CoV-2 variants and shows extraordinary variability of the pandemic strains probably related to the country´s outstanding position as a Latin American economical and transportation hub. Not all regions of the country show sufficient infrastructure for SARS-CoV-2 diagnosis and genotyping which can negatively impact the pandemic response. METHODS: Due to this reason and to disburden the diagnostic system of the inner São Paulo State, the Butantan Institute established the Mobile Laboratory (in Portuguese: LabMovel) for SARS-CoV-2 testing which started a trip of the most important "hotspots" of the most populous Brazilian region. The LabMovel initiated in two important cities of the State: Aparecida do Norte (an important religious center) and the Baixada Santista region which incorporates the port of Santos, the busiest in Latin America. The LabMovel was fully equipped with an automatized system for SARS-CoV-2 diagnosis and sequencing/genotyping. It also integrated the laboratory systems for patient records and results divulgation including in the Federal Brazilian Healthcare System. RESULTS: Currently,16,678 samples were tested, among them 1,217 from Aparecida and 4,564 from Baixada Santista. We tracked the delta introductio in the tested regions with its high diversification. The established mobile SARS-CoV-2 laboratory had a major impact on the Public Health System of the included cities including timely delivery of the results to the healthcare agents and the Federal Healthcare system, evaluation of the vaccination status of the positive individuals in the background of exponential vaccination process in Brazil and scientific and technological divulgation of the fieldwork to the most vulnerable populations. CONCLUSIONS: The SARS-CoV-2 pandemic has demonstrated worldwide the importance of science to fight against this viral agent and the LabMovel shows that it is possible to integrate researchers, clinicians, healthcare workers and patients to take rapid actions that can in fact mitigate this and other epidemiological situations.