Novel indices reveal that pollinator exposure to pesticides varies across biological compartments and crop surroundings.

Declines in insect pollinators have been linked to a range of causative factors such as disease, loss of habitats, the quality and availability of food, and exposure to pesticides. Here, we analysed an extensive dataset generated from pesticide screening of foraging insects, pollen-nectar stores/beebread, pollen and ingested nectar across three species of bees collected at 128 European sites set in two types of crop. In this paper, we aimed to (i) derive a new index to summarise key aspects of complex pesticide exposure data and (ii) understand the links between pesticide exposures depicted by the different matrices, bee species and apple orchards versus oilseed rape crops. We found that summary indices were highly correlated with the number of pesticides detected in the related matrix but not with which pesticides were present. Matrices collected from apple orchards generally contained a higher number of pesticides (7.6 pesticides per site) than matrices from sites collected from oilseed rape crops (3.5 pesticides), with fungicides being highly represented in apple crops. A greater number of pesticides were found in pollen-nectar stores/beebread and pollen matrices compared with nectar and bee body matrices. Our results show that for a complete assessment of pollinator pesticide exposure, it is necessary to consider several different exposure routes and multiple species of bees across different agricultural systems.

First Transcriptome Analysis of Hepatoblastoma in Brazil: Unraveling the Pivotal Role of Noncoding RNAs and Metabolic Pathways.

Hepatoblastoma stands as the most prevalent liver cancer in the pediatric population. Characterized by a low mutational burden, chromosomal and epigenetic alterations are key drivers of its tumorigenesis. Transcriptome analysis is a powerful tool for unraveling the molecular intricacies of hepatoblastoma, shedding light on the effects of genetic and epigenetic changes on gene expression. In this study conducted in Brazilian patients, an in-depth whole transcriptome analysis was performed on 14 primary hepatoblastomas, compared to control liver tissues. The analysis unveiled 1,492 differentially expressed genes (1,031 upregulated and 461 downregulated), including 920 protein-coding genes (62%). Upregulated biological processes were linked to cell differentiation, signaling, morphogenesis, and development, involving known hepatoblastoma-associated genes (DLK1, MEG3, HDAC2, TET1, HMGA2, DKK1, DKK4), alongside with novel findings (GYNG4, CDH3, and TNFRSF19). Downregulated processes predominantly centered around oxidation and metabolism, affecting amines, nicotinamides, and lipids, featuring novel discoveries like the repression of SYT7, TTC36, THRSP, CCND1, GCK and CAMK2B. Two genes, which displayed a concordant pattern of DNA methylation alteration in their promoter regions and dysregulation in the transcriptome, were further validated by RT-qPCR: the upregulated TNFRSF19, a key gene in the embryonic development, and the repressed THRSP, connected to lipid metabolism. Furthermore, based on protein-protein interaction analysis, we identified genes holding central positions in the network, such as HDAC2, CCND1, GCK, and CAMK2B, among others, that emerged as prime candidates warranting functional validation in future studies. Notably, a significant dysregulation of non-coding RNAs (ncRNAs), predominantly upregulated transcripts, was observed, with 42% of the top 50 highly expressed genes being ncRNAs. An integrative miRNA-mRNA analysis revealed crucial biological processes associated with metabolism, oxidation reactions of lipids and carbohydrates, and methylation-dependent chromatin silencing. In particular, four upregulated miRNAs (miR-186, miR-214, miR-377, and miR-494) played a pivotal role in the network, potentially targeting multiple protein-coding transcripts, including CCND1 and CAMK2B. In summary, our transcriptome analysis highlighted disrupted embryonic development as well as metabolic pathways, particularly those involving lipids, emphasizing the emerging role of ncRNAs as epigenetic regulators in hepatoblastomas. These findings provide insights into the complexity of the hepatoblastoma transcriptome and identify potential targets for future therapeutic interventions.

[Cost-effectiveness analysis of a vaccine for Helicobacter pylori in southern Europe]. / Análisis coste-efectividad de una vacuna para Helicobacter pylori en el sur de Europa.

OBJECTIVE: There is sufficient evidence on the feasibility of a vaccine to prevent Helicobacter pylori infection. Modeling studies in low prevalence environments report a very probable long-term cost-effectiveness. The objective of this study was to quantify its efficiency in a local context. METHODS: The evolution of a cohort of newborns was simulated through a compartmental model representing a series of clinical situations regarding H. pylori infection and related diseases. The model was run under the assumption of both vaccination in the first year of life and no intervention. The time horizon was set as equivalent to the life expectancy and the perspective of the health system was taken into account. RESULTS: Vaccination against H. pylori would cost an average of €2,168/person more than no intervention. This would yield an average additional 0.32 quality-adjusted life years gained (QALY), which would entail an incremental cost-effectiveness ratio (ICER) of €7,196/QALY. For a willingness to pay of €24,506/QALY, 99.96% of the simulations were cost-effective at eighty-four years old. This threshold was crossed thirty years after vaccination. The variables that carried the most weight in explaining the variability of the ICER were, in this order, vaccine effectiveness, the incidence of infection in young children, and the price of the vaccine. Vaccination would cease to be cost-effective with a price greater than €3,634/dose or with effective population coverage less than 11%. CONCLUSIONS: When implemented in an environment with the epidemiological and economic characteristics of Southern Europe, a prophylactic vaccination against H. pylori would be cost-effective in the long run.

OBJECTIVE: Existen pruebas de la factibilidad de una vacuna para prevenir la infección por Helicobacter pylori. Modelizaciones en entornos de baja prevalencia informan de una muy probable coste-efectividad a largo plazo. El objetivo de este estudio fue cuantificar su eficiencia en un contexto local. METHODS: Se simuló la evolución de una cohorte de nacidos a través de un modelo compartimental representativo de varios estados clínicos en relación a la infección por H. pylori. Se ejecutó dicho modelo bajo las premisas de vacunación en el periodo de lactante y de no intervención. El horizonte temporal fue equivalente a la esperanza de vida y se tuvo en cuenta la perspectiva del sistema de salud. RESULTS: La vacunación frente a H. pylori costaría de media 2.168 €/persona más que la no intervención. Con ello se obtendrían 0,32 años de vida ganados ajustados por calidad (AVAC), lo que implicaría una razón de coste-efectividad incremental (RCEI) media de 7.196 €/AVAC. Para una disposición a pagar de 24.506 €/AVAC, el 99,96% de las simulaciones resultaron coste-efectivas al alcanzar el horizonte temporal y se cruzó dicho umbral a partir de los treinta años de la vacunación. Las variables que más peso tuvieron para explicar la variabilidad de la RCEI fueron, en este orden, la efectividad vacunal, la incidencia de la infección en la primera infancia y el precio de la vacuna. La vacunación dejaría de ser coste-efectiva con un precio mayor de 3.634€/vial o con una cobertura poblacional efectiva menor del 11%. CONCLUSIONS: Una vacunación frente a la infección por H. pylori administrada en la infancia sería coste-efectiva a largo plazo en un entorno con las características epidemiológicas y económicas del sur de Europa.

Insulin in combination with pioglitazone prevents advanced cachexia in 256-Walker tumor-bearing rats: effect is greater than treatment alone and is associated with improved insulin sensitivity.

BACKGROUND: Insulin (INS) resistance and hypoinsulinemia commonly observed in cancer-carrying, can contribute to cachexia. However, the effects of INS and INS sensitizers, such as pioglitazone (PIO), particularly when used in combination therapy, on cancer cachexia have not been evaluated sufficiently. We investigated the effects of INS and PIO, at various doses, either isolated or combined, on cachexia in Walker-256 tumor-bearing rats (TB rats). METHODS: INS or INS + PIO were administered in TB rats, for 6 or 12 days, starting from the day of tumor cells inoculation. RESULTS: INS at 18 or 27 U/kg (12-days treatment), but not 9 U/kg, reduced fat loss and slightly prevented weight loss. However, INS 18 U/kg + PIO 5, 10, 20, or 40 mg/kg (6 or 12-day treatment) reduced fat loss and markedly prevented weight loss but did not affect muscle wasting. While TB rats lost weight (37.9% in 12 days), TB rats treated with INS 18 U/kg + PIO 5 mg/kg showed pronounced weight gain (73.7%), which was greater than the sum (synergism) of the weight gains promoted by isolated treatments with INS 18 U/kg (14.7%) or PIO 5 mg/kg (13.1%). The beneficial effect of the INS 18 U/kg + PIO 5 mg/kg on weight loss was associated with improved INS sensitivity, as indicated by the higher blood glucose clearance constant (kITT), decreased levels of free fatty acids and triacylglycerols (INS resistance-inducing factors) in the blood, and increased expression of p-Akt (INS signaling pathway protein) in adipose tissue. CONCLUSIONS: The combined treatment with INS 18 U/kg + PIO 5 mg/kg was more effective in preventing advanced cachexia in TB rats than each treatment alone, emerging as the best approach, considering the lower dosage and higher efficacy. This combination completely preserved adipose mass and markedly reduced weight loss through a synergistic mechanism linked to improved insulin sensitivity. These findings provide new insights into the importance of drug combinations in effectively combating fat loss in advanced cachexia.

Prevalence and clinical implications of germline pathogenic variants in cancer predisposing genes in young patients across sarcoma subtypes.

BACKGROUND: Sarcomas are a rare and diverse group of cancers occurring mainly in young individuals for which an underlying germline genetic cause remains unclear in most cases. METHODS: Germline DNA from 177 children, adolescents and young adults with soft tissue or bone sarcomas was tested using multigene panels with 113 or 126 cancer predisposing genes (CPGs) to describe the prevalence of germline pathogenic/likely pathogenic variants (GPVs). Subsequent testing of a subset of tumours for loss of heterozygosity (LOH) evaluation was performed to investigate the clinical and molecular significance of these variants. RESULTS: GPVs were detected in 21.5% (38/177) of the patients (15.8% in children and 21.6% in adolescents and young adults), with dominant CPGs being altered in 15.2% overall. These variants were found in genes previously associated with the risk of developing sarcomas (TP53, RB1, NF1, EXT1/2) but also in genes where that risk is still emerging/limited (ERCC2, TSC2 and BRCA2) or unknown (PALB2, RAD50, FANCM and others). The detection rates of GPVs varied from 0% to 33% across sarcoma subtypes and GPV carriers were more likely to present more than one primary tumour than non-carriers (21.1%×6.5%; p=0.012). Loss of the wild-type allele was detected in 48% of tumours from GPV carriers, mostly in genes definitively associated with sarcoma risk. CONCLUSION: Our findings reveal that a high proportion of young patients with sarcomas presented a GPV in a CPG, underscoring the urgency of establishing appropriate genetic screening strategies for these individuals and their families.

Microencapsulated antioxidant stevia fraction fortifies whey protein and enhances its antidiabetic activity.

Whey protein was fortified with a microencapsulated fraction of Stevia rebaudiana, in the proportion 1:4 (w/w), with maltodextrin from the elite variety of Stevia UEM-13, rich in antioxidant compounds, and evaluated its antioxidant and antidiabetic potential in vitro. The fraction in ethyl acetate, the microencapsulated fraction, the whey protein obtained by membrane and a commercial whey protein were characterized and were also investigated solubility, microencapsulation efficiency and stability and digestion in vitro. In addition, these products and two formulations of the icroencapsulated fraction with the obtained whey protein were tested for their potential to inhibit the α-amylase and α-glucosidase enzyme (antidiabetic activity). The microencapsulated fraction (0.5%) and the supplement fortified with the 20% fraction microencapsulated showed inhibitory potential for the enzyme. As for the α-glucosidase enzyme, all products tested showed inhibition, with the formulation with 1.6% microencapsulated fraction added to whey protein being significantly higher. The microencapsulated fraction showed better solubility and stability, including in vitro digestion analysis, and showed antioxidant and antidiabetic capacity. A sensory evaluation was performed with panelists who regularly consume whey protein supplements and products with stevia and the supplement formulation with 1.6 g microencapsulated stevia per 100 g of whey protein have good sensory acceptance.

Assessment of SARS-CoV-2 neutralizing antibody titers in breastmilk from convalescent and vaccinated mothers.

Breastmilk contains antibodies that could protect breastfed infants from infections. In this work, we examined if antibodies in breastmilk could neutralize SARS-CoV-2 in 84 breastmilk samples from women that were either vaccinated (Comirnaty, mRNA-1273, or ChAdOx1), infected with SARS-CoV-2, or both infected and vaccinated. The neutralization capacity of these sera was tested using pseudotyped vesicular stomatitis virus carrying either the Wuhan-Hu-1, Delta, or BA.1 Omicron spike proteins. We found that natural infection resulted in higher neutralizing titers and that neutralization correlated positively with levels of immunoglobulin A in breastmilk. In addition, significant differences in the capacity to produce neutralizing antibodies were observed between both mRNA-based vaccines and the adenovirus-vectored ChAdOx1 COVID-19 vaccine. Overall, our results indicate that breastmilk from naturally infected women or those vaccinated with mRNA-based vaccines contains SARS-CoV-2 neutralizing antibodies that could potentially provide protection to breastfed infants from infection.

Efficacy, Convenience, Safety and Durability of DTG-Based Antiretroviral Therapies: Evidence from a Prospective Study by the Italian MaSTER Cohort.

Background: Dolutegravir (DTG) is recommended by international guidelines as a main component of an optimal initial regimen of cART (combination antiretroviral treatment) in people living with HIV (PLWH) and in case of switching for failure or optimization strategies. However, studies on the performance of DTG-containing regimens and indications for switching therapies in the long term are sparse. The purpose of this study was to evaluate prospectively the performance of DTG-based regimens, using the metrics of "efficacy", "safety", "convenience" and ''durability'', among a nationally representative cohort of PLWH in Italy. Methods: We selected all PLWH in four centers of the MaSTER cohort who initiated a DTG-based regimen either when naïve or following a regimen switch between 11 July 2018 and 2 July 2021. Participants were followed until the outcomes were recorded or until the end of the study on 4 August 2022, whichever occurred first. Interruption was reported even when a participant switched to another DTG-containing regimen. Survival regression models were fitted to evaluate associations between therapy performance and age, sex, nationality, risk of HIV transmission, HIV RNA suppression status, CD4+ T-cell count, year of HIV diagnosis, cART status (naïve or experienced), cART backbone and viral hepatitis coinfection. Results: There were 371 participants in our cohort who initiated a DTG-based cART regimen in the time frame of the study. The population was predominantly male (75.2%), of Italian nationality (83.3%), with a history of cART use (80.9%), and the majority initiated a DTG-based regimen following a switch strategy in 2019 (80.1%). Median age was 53 years (interquartile range (IQR): 45-58). Prior cART regimen was based mostly on a combination of NRTI drugs plus a PI-boosted drug (34.2%), followed by a combination of NRTIs plus an NNRTI (23.5%). Concerning the NRTI backbone, the majority comprised 3TC plus ABC (34.5%), followed by 3TC alone (28.6%). The most reported transmission risk factor was heterosexual intercourse (44.2%). Total interruptions of the first DTG-based regimen were registered in 58 (15.6%) participants. The most frequent reason for interruption was due to cART simplification strategies, which accounted for 52%. Only 1 death was reported during the study period. The median time of total follow-up was 556 days (IQR: 316.5-722.5). Risk factors for poor performance of DTG-containing-regimens were found to be: a backbone regimen containing tenofovir, being cART naïve, having detectable HIV RNA at baseline, FIB-4 score above 3.25 and having a cancer diagnosis. By contrast, protective factors were found to be: higher CD4+ T-cell counts and higher CD4/CD8 ratio at baseline. Conclusion: DTG-based regimens were used mainly as a switching therapy in our cohort of PLWH who had undetectable HIV RNA and a good immune status. In this type of population, the durability of DTG-based regimens was maintained in 84.4% of participants with a modest incidence of interruptions mostly due to cART simplification strategies. The results of this prospective real-life study confirm the apparent low risk of changing DTG-containing regimens due to virological failure. They may also help physicians to identify people with increased risk of interruption for different reasons, suggesting targeted medical interventions.

Safety and efficacy of a new supplementation protocol in patients with cystic fibrosis and vitamin D deficiency.

OBJECTIVES: Based on the European and American Cystic Fibrosis (CF) consensus recommendations, an increase in vitamin D (VD) supplementation in patients with CF and insufficient or defficient levels was proposed. The objective of our study was to determine the safety and efficacy of this new protocol. MATERIAL AND METHODS: Multicentre nonrandomized uncontrolled experimental study. Patients with insufficient levels (<30 ng/mL) received increasing doses of VD (between 800 and 10 000 IU/day). Patients were followed up for 12 months, during which their vitamin and nutritional status, pulmonary function and calcium and phosphate metabolism were assessed. STATISTICAL ANALYSIS: t test for paired data and multivariate logistic regression analysis. RESULTS: Thirty patients aged 1-39 years (median, 9.1) completed the follow-up. Two patients were dropped from the study on account of 25-OH VD levels greater than 100 ng/mL at 3 months without clinical or laboratory signs of hypercalcaemia. At 12 months, we observed an increase of 7.6 ng/mL (95% CI, 4.6-10 ng/mL) in the mean 25-OH VD level and an improvement in vitamin status: 37% achieved levels of 30 ng/mL or greater, 50% levels between 20 and 30 ng/mL and 13% remained with levels of less than 20 ng/mL. We found no association between improved VD levels and pulmonary function. CONCLUSIONS: The proposed protocol achieved an increase in serum VD levels and a decrease in the percentage of patients with VD insufficiency, although it was still far from reaching the percentages of sufficiency recommended for this entity.

Greenhouse Gas (GHG) Emissions from Honey Production: Two-Year Survey in Italian Beekeeping Farms.

The objective of this study was to quantify the climate change (CC) impact of the honey supply chain in different beekeeping systems and farms, over two consecutive years. The CC impact category is quantified as kg CO2 equivalent and it evaluates the GHG emissions, mainly CO2, N2O, and CH4. The results ranged from 0.44 to 3.18 (p = 0.039) kg CO2e/kg honey with higher values in 2021 than 2020. The main contributors to climate change of the honey supply chain are represented by transport and supplemental feeding inputs. The beekeeping system (migratory or stationary) influenced CC: the contribution to CC for stationary farms was estimated at 0.58 kg CO2e/kg honey and 2.48 for migratory ones (p < 0.001). Given the close connection between honey yield and LCA results due to the unit of measurement of impact, i.e., kg of honey produced, an index was developed (wildflower honey climate index) as a simple benchmark tool for prediction of honey yield in the survey context. Using the data from the present study, we found that the index is positively related to honey yield (r = 0.504; p < 0.05) but negatively related to supplemental feeding (r = -0.918; p < 0.01) and overall carbon footprint (r = -0.657; p < 0.05). Further studies are needed to better explain the effects of weather on honey production, as well as environmental impact.

Safety and Efficacy of Outpatient Treatments for COVID-19: Real-Life Data from a Regionwide Cohort of High-Risk Patients in Tuscany, Italy (the FEDERATE Cohort).

Early COVID-19 treatments can prevent progression to severe disease. However, real-life data are still limited, and studies are warranted to monitor the efficacy and tolerability of these drugs. We retrospectively enrolled outpatients receiving early treatment for COVID-19 in 11 infectious diseases units in the Tuscany region of Italy between 1 January and 31 March 2022, when Omicron sublineages BA.1 and BA.2 were circulating. Eligible COVID-19 patients were treated with sotrovimab (SOT), remdesivir (RMD), nirmatrelvir/ritonavir (NRM/r), or molnupiravir (MOL). We gathered demographic and clinical features, 28-day outcomes (hospitalization or death), and drugs tolerability. A total of 781 patients (median age 69.9, 66% boosted for SARS-CoV-2) met the inclusion criteria, of whom 314 were treated with SOT (40.2%), 205 with MOL (26.3%), 142 with RMD (18.2%), and 120 with NRM/r (15.4%). Overall, 28-day hospitalization and death occurred in 18/781 (2.3%) and 3/781 (0.3%), respectively. Multivariable Cox regression showed that patients receiving SOT had a reduced risk of meeting the composite outcome (28-day hospitalization and/or death) in comparison to the RMD cohort, while no significant differences were evidenced for the MOL and NRM/r groups in comparison to the RMD group. Other predictors of negative outcomes included cancer, chronic kidney disease, and a time between symptoms onset and treatment administration > 3 days. All treatments showed good safety and tolerability, with only eight patients (1%) whose treatment was interrupted due to intolerance. In the first Italian multicenter study presenting real-life data on COVID-19 early treatments, all regimens demonstrated good safety and efficacy. SOT showed a reduced risk of progression versus RMD. No significant differences of outcome were observed in preventing 28-day hospitalization and death among patients treated with RMD, MOL, and NRM/r.

Distinct breast milk microbiota, cytokine, and adipokine profiles are associated with infant growth at 12 months: an in vitro host-microbe interaction mechanistic approach.

Breast milk (BM) is important for adequate infant development, and it contains bioactive compounds, such as bacteria, cytokines and some adipokines which play a role in infant microbial, metabolic, and immunological maturation. However, little is known about its impact on growth and development in early life. The objective of this study was to evaluate the impact of milk microbiota, cytokine, and adipokine profiles on the risk of overweight at 12 months of life to find the possible mechanisms of host-microbe interactions. In this study, BM samples from 100 healthy women collected during 15 d after birth were included. BM microbiota was analysed by 16S rRNA gene sequencing, and cytokine and adipokine levels were measured by the Luminex approach. In addition, infant weight and length were recorded during the first 12 months and z-scores were obtained according to the WHO databases. Infants were classified as risk of overweight (ROW) and no-risk of overweight (NOROW) based on their body mass index z-score (BMIZ) and infant weight-for-length z-score (WLZ) at 12 months. In order to study host-microbe interactions, epithelial intestinal and mammary cell lines were exposed to milk microbes to assess the host response by interleukin (IL)-6 production as a potential inflammatory marker. BM was dominated by Staphylococcus and Streptococcus genera, and the most abundant cytokines were IL-6 and IL-18. Leptin levels were positively correlated with the pregestational body mass index (BMI). Higher relative abundance of the Streptococcus genus was associated with higher IL-10 and higher relative abundance of the Bifidobacterium genus was associated with lower IL-6 concentrations in milk. Infant WLZ at 12 months could be partially predicted by Streptococcus genus proportions and IL-10 and IL-18 levels in BM. BM microbiota significantly induced cytokine responses in mammary epithelial cells. Higher levels of IL-6 production were observed in mammary cells exposed to BM microbiota from mothers with ROW offspring compared to mothers with NOROW offspring. In conclusion, BM microbiota is related to the cytokine profile. IL-10 and IL-18 levels and the abundance of the Streptococcus genus could affect early infant development. Further research is needed to clarify the specific impact of BM microbiota and cytokines on infant growth and the risk of overweight.

O fortalecimento do patriarcado e a desvalorização do trabalho de cuidado no capitalismo / The strengthenin of patriarchy and the devaluation of care work in capitalism

Resumo: Este artigo busca compreender como os processos de colonização europeia e de acumulação primitiva do capital estão relacionados à destinação de atividades de cuidado para as mulheres, e a simultânea invisibilidade e desvalorização dessas experiências femininas. À luz de autoras feministas, são discutidos como a expansão do capitalismo e a colonização desencadearam o fortalecimento do patriarcado e a potencialização da divisão sexual do trabalho.

Abstract: This article seeks to understand how the processes of European colonization and primitive capital accumulation are related to the allocation of care activities for women and the simultaneous invisibility and devaluation of these female experiences. In the light of feminist authors, it is discussed how the expansion of capitalism and colonization triggered the strengthening of patriarchy and the potentiation of the sexual division of labor.

Perfil Socioeconômico de Pessoas com Câncer de Laringe e Cavidade Oral em Tratamento no Instituto Nacional de Câncer / Socioeconomic Profile of People with Cancer of the Larynx and Oral Cavity Being Treated at National Cancer Institute / Perfil Socioeconómico de las Personas con Cáncer de Laringe y Cavidad Oral en Tratamiento en el Instituto Nacional de Cáncer

Introdução: O câncer é um dos principais problemas de saúde pública do mundo. O câncer de cabeça e pescoço apresenta como principais fatores de risco o tabagismo, o etilismo, entre outros fatores associados ao modelo econômico vigente, explicitando a associação entre desigualdades socioeconômicas e incidência/mortalidade. Objetivo: Conhecer o perfil socioeconômico das pessoas com câncer de laringe e cavidade oral, matriculadas na clínica de cabeça e pescoço do HCI/INCA no período de fevereiro a julho de 2017. Método: O caminho metodológico empregado se divide em dois eixos: revisão de literatura narrativa e definição conceitual de terminologias utilizadas na pesquisa; e questionário aplicado com pessoas adoecidas. Trata-se de uma pesquisa exploratória que visa levantar elementos qualitativos para a construção do perfil socioeconômico. Resultados: Os resultados apresentam o perfil socioeconômico, demonstram a magnitude das condições socioeconômicas e como estas podem impactar no processo de tratamento oncológico. Conclusão: Tais questões são desafiadoras para o trabalho em equipes de saúde, que, diante de situações complexas, precisam desenvolver a interlocução entre diferentes saberes para subsidiar decisões compartilhadas.

Introduction: Cancer is one of the main public health problems in the world. The main risk factors for head and neck cancer are smoking, alcoholism, and others associated with the current economic model, explaining the association between socioeconomic inequalities and incidence/mortality. Objective: To know the socioeconomic profile of people with cancer of the larynx and oral cavity, enrolled in the head and neck clinic at HCI/INCA from February to July 2017. Method: The methodological path used is divided into two axes: the narrative literature review and conceptual definition of terminologies used in the research and the questionnaire applied with sick people. This is an exploratory investigation that aims to raise qualitative elements for the construction of the socioeconomic profile. Results: The results describe the socioeconomic profile, demonstrate the magnitude of socioeconomic conditions and how these can impact the oncology treatment process. Conclusion: These issues are challenging for the work of health teams that, when faced with complex situations, need to develop the dialogue between different types of expertise to support shared decisions.

Introducción: El cáncer es uno de los principales problemas de salud pública en el mundo. El cáncer de cabeza y cuello presenta como principales factores de riesgo el tabaquismo, alcoholismo, entre otros asociados al modelo económico actual, explicando la asociación entre desigualdades socioeconómicas e incidencia/mortalidad. Objetivo: Conocer el perfil socioeconómico de las personas con cáncer de laringe y cavidad oral, inscritas en la clínica de cabeza y cuello del HCI/INCA de febrero a julio de 2017. Método: La ruta metodológica utilizada se divide en dos ejes: la revisión bibliográfica narrativa y definición conceptual de terminologías utilizadas en la investigación y el cuestionario aplicado a las personas enfermas. Se trata de una investigación exploratoria que pretende levantar elementos cualitativos para la construcción del perfil socioeconómico. Resultados: Los resultados presentan el perfil socioeconómico, demuestran la magnitud de las condiciones socioeconómicas y cómo estas pueden impactar en el proceso de tratamiento del cáncer. Conclusión: Tales cuestiones son desafiantes para el trabajo de los equipos de salud que frente a cuestiones complejas necesitan desarrollar la interlocución entre diferentes conocimientos para subvencionar las decisiones compartidas

High-Resolution Magic-Angle-Spinning NMR in Revealing Hepatoblastoma Hallmarks.

Cancer is one of the leading causes of death in children and adolescents worldwide; among the types of liver cancer, hepatoblastoma (HBL) is the most common in childhood. Although it affects only two to three individuals in a million, it is mostly asymptomatic at diagnosis, so by the time it is detected it has already advanced. There are specific recommendations regarding HBL treatment, and ongoing studies to stratify the risks of HBL, understand the pathology, and predict prognostics and survival rates. Although magnetic resonance imaging spectroscopy is frequently used in diagnostics of HBL, high-resolution magic-angle-spinning (HR-MAS) NMR spectroscopy of HBL tissues is scarce. Using this technique, we studied the alterations among tissue metabolites of ex vivo samples from (a) HBL and non-cancer liver tissues (NCL), (b) HBL and adjacent non-tumor samples, and (c) two regions of the same HBL samples, one more centralized and the other at the edge of the tumor. It was possible to identify metabolites in HBL, then metabolites from the HBL center and the border samples, and link them to altered metabolisms in tumor tissues, highlighting their potential as biochemical markers. Metabolites closely related to liver metabolisms such as some phospholipids, triacylglycerides, fatty acids, glucose, and amino acids showed differences between the tissues.

Intra-specific variation in sensitivity of Bombus terrestris and Osmia bicornis to three pesticides.

There is growing evidence that pesticides may be among the causes of worldwide bee declines, which has resulted in repeated calls for their increased scrutiny in regulatory assessments. One recurring concern is that the current frameworks may be biased towards assessing risks to the honey bee. This paradigm requires extrapolating toxicity information across bee species. Most research effort has therefore focused on quantifying differences in sensitivity across species. However, our understanding of how responses to pesticides may vary within a species is still very poor. Here we take the first steps towards filling this knowledge gap by comparing acute, lethal hazards in sexes and castes of the eusocial bee Bombus terrestris and in sexes of the solitary bee Osmia bicornis after oral and contact exposure to the pesticides sulfoxaflor, Amistar (azoxystrobin) and glyphosate. We show that sensitivity towards pesticides varies significantly both within and across species. Bee weight was a meaningful predictor of pesticide susceptibility. However, weight could not fully explain the observed differences, which suggests the existence of unexplored mechanisms regulating pesticide sensitivity across bee sexes and castes. Our data show that intra-specific responses are an overlooked yet important aspect of the risk assessment of pesticides in bees.

Sensitivity profile of blood culture isolates in a clinical analysis laboratory, Fortaleza, CE / Perfil de sensibilidade de isolados de hemocultura em um laboratório de análises clínicas, Fortaleza, CE / Perfil de sensibilidad de hemocultivos aislados en un laboratorio de análisis clínicos, Fortaleza, CE

Background and objectives: bacteremia is defined from the presence of bacteria in the bloodstream. Its clinical importance is associated with the high morbidity and mortality rate in the world. In severe cases, it can culminate in sepsis, with a constant increase in cases in Brazil. Therefore, this study aims to assess the main bacterial isolates in blood cultures and a possible change in their sensitivity profiles in a clinical analysis laboratory in Fortaleza, Ceará. Methods: an epidemiological, descriptive, retrospective study was carried out, with a quantitative approach of positive blood cultures, seeking to assess the main isolated microorganisms and their sensitivity profiles. The data used were obtained from the laboratory system through the EpiCenter→ software, from January 2019 to December 2020. Statistical analysis was performed using the Graphpad 7.0 software. Results: 840 microorganisms were identified from blood cultures, and the main ones were E. coli, K. pneumoniae, P. aeruginosa, S. epidermidis, S. aureus and S. haemolyticus. Some isolates show a change in the sensitivity profile, such as K. pneumoniae and P. aeruginosa, showing an increase in sensitivity to carbapenems and cephalosporins, while S. epidermidis showed a decrease in sensitivity to minocycline in the comparison between years 2019 and 2020.Conclusion: clinical isolates from blood cultures showed a change in the sensitivity profile between 2019 and 2020, taking into account that, for K. pneumoniae, P. aeruginosa, this change resulted in an increase in sensitivity, with an increase in resistance in S. epidermidis isolates.(AU)

Justificativa e objetivos: bacteremia é definida a partir da presença de bactérias na corrente sanguínea. Sua importância clínica está associada à alta taxa de morbidade e mortalidade no mundo. Nos casos graves, pode culminar em sepse, com constante aumento dos casos no Brasil. Portanto, o presente estudo tem como objetivo avaliar os principais isolados bacterianos em hemoculturas e uma possível alteração nos seus perfis de sensibilidade em um laboratório de análises clínicas de Fortaleza, Ceará. Métodos: foi realizado um estudo epidemiológico, descritivo, retrospectivo, com abordagem quantitativa de hemoculturas positivas, buscando avaliar os principais microrganismos isolados e seus perfis de sensibilidades. Os dados utilizados foram obtidos a partir do sistema laboratorial através do software EpiCenter→, referente ao período de janeiro de 2019 a dezembro de 2020. A análise estatística foi realizada pelo software Graphpad 7.0. Resultados: foram identificados 840 microrganismos a partir das hemoculturas, sendo os principais E. coli, K. pneumoniae, P. aeruginosa, S. epidermidis, S. aureus e S. haemolyticus. Alguns isolados apresentam uma alteração no perfil de sensibilidade, como K. pneumoniae e P. aeruginosa, apresentando um aumento na sensibilidade frente aos carbapenêmicos e as cefalosporinas, enquanto o S. epidermidis apresentou uma diminuição na sensibilidade frente à minociclina na comparação entre os anos de 2019 e 2020. Conclusão: os isolados clínicos de hemocultura apresentaram uma alteração no perfil de sensibilidade entre 2019 e 2020, levando em consideração que, para K. pneumoniae e P. aeruginosa, essa alteração resultou no aumento na sensibilidade, com aumento na resistência nos isolados de S. epidermidis.(AU)

Justificación y objetivos: la bacteriemia se define por la presencia de bacterias en el torrente sanguíneo. Su importancia clínica está asociada con la alta tasa de morbimortalidad en el mundo. En casos severos, puede culminar en sepsis, con un aumento constante de casos en Brasil. Por tanto, este estudio tiene como objetivo evaluar los principales aislados bacterianos en hemocultivos y un posible cambio en sus perfiles de sensibilidad en un laboratorio de análisis clínicos en Fortaleza, Ceará. Métodos: se realizó un estudio epidemiológico, descriptivo, retrospectivo, con abordaje cuantitativo de hemocultivos positivos, buscando evaluar los principales microorganismos aislados y sus perfiles de sensibilidad. Los datos utilizados se obtuvieron del sistema de laboratorio a través del software EpiCenter→, para el período de enero de 2019 a diciembre de 2020. El análisis estadístico se realizó mediante el software Graphpad 7.0. Resultados: se identificaron 840 microorganismos a partir de hemocultivos, siendo los principales E. coli, K. pneumoniae, P. aeruginosa, S. epidermidis, S. aureus y S. haemolyticus. Algunos aislados muestran un cambio en el perfil de sensibilidad, como K.pneumoniae y P. aeruginosa, mostrando un aumento en la sensibilidad a los carbapenémicos y cefalosporinas, mientras que S. epidermidis mostró una disminución en la sensibilidad a la minociclina, en la comparación entre los años de 2019 y 2020. Conclusiones: los aislados clínicos de hemocultivos mostraron un cambio en el perfil de sensibilidad entre 2019 y 2020, teniendo en cuenta que para K. pneumoniae, P. aeruginosa, este cambio resultó en un aumento de la sensibilidad, con un aumento de la resistencia en los aislados de S. epidermidis

Unraveling the Genetic Architecture of Hepatoblastoma Risk: Birth Defects and Increased Burden of Germline Damaging Variants in Gastrointestinal/Renal Cancer Predisposition and DNA Repair Genes.

The ultrarare hepatoblastoma (HB) is the most common pediatric liver cancer. HB risk is related to a few rare syndromes, and the molecular bases remain elusive for most cases. We investigated the burden of rare damaging germline variants in 30 Brazilian patients with HB and the presence of additional clinical signs. A high frequency of prematurity (20%) and birth defects (37%), especially craniofacial (17%, including craniosynostosis) and kidney (7%) anomalies, was observed. Putative pathogenic or likely pathogenic monoallelic germline variants mapped to 10 cancer predisposition genes (CPGs: APC, CHEK2, DROSHA, ERCC5, FAH, MSH2, MUTYH, RPS19, TGFBR2 and VHL) were detected in 33% of the patients, only 40% of them with a family history of cancer. These findings showed a predominance of CPGs with a known link to gastrointestinal/colorectal and renal cancer risk. A remarkable feature was an enrichment of rare damaging variants affecting different classes of DNA repair genes, particularly those known as Fanconi anemia genes. Moreover, several potentially deleterious variants mapped to genes impacting liver functions were disclosed. To our knowledge, this is the largest assessment of rare germline variants in HB patients to date, contributing to elucidate the genetic architecture of HB risk.