Factors associated with concurrent alcohol, tobacco and illicit drug use: 2019 National School-Based Health Survey. / Fatores associados ao policonsumo de álcool, tabaco e drogas ilícitas: Pesquisa Nacional de Saúde do Escolar 2019.

The aim of this study was to analyze the factors associated with concurrent alcohol, tobacco and illicit drug use among Brazilian schoolchildren aged 13-17. We conducted a cross-sectional study using data from the 2019 National School-Based Health Survey. The outcome was use of the three substances during the last 30 days. Hierarchical multiple logistic regression was carried out with independent variables grouped into four blocks: sociodemographic characteristics; family context; behavioral aspects; and stressors. Variables with p<0.05 were retained in the final model. The prevalence of concurrent substance use was 3.3%. Being male, living in the Midwest, South and Southeast, skipping school without parent permission, parents not knowing what their children do in their free time, having parents who smoke, having experienced physical aggression from parents, feeling that life is not worth living, trying drinking and illicit drugs before the age of 13, and having friends who drink alcohol, smoke and use drugs in their presence remained associated with the outcome in the final model. The findings reveal high prevalence of concurrent alcohol, cigarette and illicit drug use among adolescents and that poly use is associated with sociodemographic, family, and behavioral factors and stressors.

Objetivou-se analisar os fatores associados ao policonsumo de álcool, tabaco e drogas ilícitas, entre adolescentes escolares brasileiros de 13 a 17 anos. Estudo transversal, com dados da Pesquisa Nacional de Saúde do Escolar (2019). A variável desfecho foi o relato de consumo das três substâncias nos últimos 30 dias. As variáveis independentes foram agrupadas em quatro blocos: características sociodemográficas; contexto familiar; situações estressoras; aspectos comportamentais. Foi realizada análise de regressão logística múltipla hierarquizada, permanecendo no modelo final as variáveis com p<0,05. A prevalência de policonsumo em adolescentes escolares foi 3,3%. No modelo final, sexo masculino, morar na região Centro-Oeste, Sul e Sudeste, faltar a escola sem permissão, pais não saberem o que fazem no tempo livre, ter pais fumantes, sofrer agressão física pelos pais, sentir que a vida não vale a pena ser vivida, experimentar bebida alcoólica e drogas ilícitas antes dos 13 anos, ter amigos que bebem bebida alcoólica, fumam e usam drogas na sua presença permaneceram associados ao desfecho. Os dados mostram alta prevalência de policonsumo de três substâncias entre adolescentes e sua associação a fatores sociodemográficos, familiares, comportamentais e a eventos estressantes.

Potential effects of the discharge of wastewater treatment plant (WWTP) effluents in benthic communities: evidence from three distinct WWTP systems.

Wastewater treatment plant (WWTP) effluents can be sources of environmental contamination. In this study, we aimed to understand whether effluents of three different WWTPs may have ecological effects in riverine recipient ecosystems. To achieve this, we assessed benthic phytobenthos and macroinvertebrate communities at three different locations relative to the effluent discharge: immediately upstream, immediately downstream and 500-m downstream the effluent discharge. Two approaches were employed: the ecological status classification as defined in the Water Framework Directive (WFD) based on biological indicators; constrained multivariate analysis to disentangle the environmental drivers (physicochemical variables and contaminants, namely metals, polycyclic aromatic hydrocarbons, pharmaceuticals, and personal care products) of ecological changes across the study sites. The results showed inconsistencies between the WFD approach and the multivariate approach, as well as between the responses of macroinvertebrates and diatoms. The WWTP effluents impacted benthic communities in a single case: macroinvertebrates were negatively affected by one of the WWTP effluents, likely by the transported pharmaceuticals (other stressors are essentially homogeneous among sites). Given the findings and the scarcity of consistent evidence on ecological impacts that WWTP effluents may have in recipient ecosystems, further research is needed towards more sustainable regulation and linked environmental protection measures.

Inhibition of protein translational machinery in triple-negative breast cancer as a promising therapeutic strategy.

Y-box binding protein-1 (YB-1) is a proto-oncogenic protein associated with protein translation regulation. It plays a crucial role in the development and progression of triple-negative breast cancer (TNBC). In this study, we describe a promising approach to inhibit YB-1 using SU056, a small-molecule inhibitor. SU056 physically interacts with YB-1 and reduces its expression, which helps to restrain the progression of TNBC. Proteome profiling analysis indicates that the inhibition of YB-1 by SU056 can alter the proteins that regulate protein translation, an essential process for cancer cell growth. Preclinical studies on human cells, mice, and patient-derived xenograft tumor models show the effectiveness of SU056. Moreover, toxicological studies have shown that SU056 treatment and dosing are well tolerated without any adverse effects. Overall, our study provides a strong foundation for the further development of SU056 as a potential treatment option for patients with TNBC by targeting YB-1.

Contextual and individual factors associated with traumatic dental injuries in deprived 12-year-old schoolchildren: A cohort study.

AIM: Traumatic dental injuries (TDIs) among children and adolescents have been acknowledged as of public health concern worldwide. The aim of the study was to assess the relationship between contextual and individual characteristics and TDIs in 12-year-old schoolchildren. MATERIALS AND METHODS: A cohort study was conducted with 355 schoolchildren living in deprived communities in the city of Manaus, Brazil. Contextual factors (place of residence and socio-economic indicators) and individual characteristics, including sex, family income, parents/guardians years of schooling, overjet and open bite (Dental Aesthetic Index), self-esteem (Rosenberg Self-Esteem Scale), sense of coherence (Sense of Coherence Scale), oral health beliefs, social support (Social Support Appraisals) were assessed at baseline. TDIs were measured at baseline and at 2-year follow-up using the O'Brien Index. Data were analysed through confirmatory factor analysis and structural equation modeling. RESULTS: The baseline prevalence of TDIs was 17.6% and the incidence of TDIs at 2-year follow-up was 26.8%. Better psychosocial status had a direct protective effect on the incidence of TDIs (ß = -.184). Better contextual characteristics (ß = -.135) and greater overjet (ß = -.203) were directly associated with poor psychosocial status. Higher schooling of parents/guardians directly predicted better psychosocial status (ß = .154). Psychosocial status mediated the relationship of greater overjet (ß = .036), contextual factors (ß = .024) and parental/guardian schooling (ß = -.027) with TDIs. CONCLUSIONS: Contextual factors and individual characteristics predicted TDIs. Psychosocial status was a relevant individual attribute in the causal network of TDIs, due to the direct effect on the incidence of TDIs as well as a mediator on the influence of contextual factors, overjet and parents/guardians schooling on the incidence of TDIs.

Influence of sex on the timing of coronary angiography and the prescription of antiplatelet therapy in patients with nonST-segment elevation myocardial infarction. / Impacto del sexo en los tiempos de cateterismo y en el uso de pretratamiento antiagregante plaquetario en pacientes con síndrome coronario agudo sin elevación del segmento ST (SCASEST).

OBJECTIVES: To assess differences in the clinical management of nonST-segment elevation myocardial infarction (NSTEMI), including in-hospital events, according to biological sex. MATERIAL AND METHODS: Prospective observational multicenter study of patients diagnosed with NSTEMI and atherosclerosis who underwent coronary angiography. RESULTS: We enrolled 1020 patients in April and May 2022; 240 (23.5%) were women. Women were older than men on average (72.6 vs 66.5 years, P .001), and more women were frail (17.1% vs 5.6%, P .001). No difference was observed in pretreatment with any P2Y12 inhibitor (prescribed in 68.8% of women vs 70.2% of men, P = .67); however, more women than men were prescribed clopidogrel (56% vs 44%, P = .009). Women prescribed clopidogrel were more often under the age of 75 years and not frail. Coronary angiography was performed within 24 hours less corooften in women (29.8% vs 36.9%, P = .03) even when high risk was recognized. Frailty was independently associated with deferring coronary angiography in the adjusted analysis; biological sex by itself was not related. The frequency and type of revascularization were the same in both sexes, and there were no differences in in-hospital cardiovascular events. CONCLUSION: Women were more often prescribed less potent antithrombotic therapy than men. Frailty, but not sex, correlated independently with deferral of coronary angiography. However, we detected no differences in the frequency of coronary revascularization or in-hospital events according to sex.

OBJETIVO: Evaluar las diferencias en el manejo clínico y eventos intrahospitalarios en una cohorte de pacientes con síndrome coronario agudo sin elevación del segmento ST (SCASEST) en función del sexo. METODO: Estudio observacional, prospectivo y multicéntrico que incluyó pacientes consecutivos con diagnóstico de SCASEST sometidos a coronariografía con enfermedad ateroesclerótica responsable. RESULTADOS: Entre abril y mayo de 2022 se incluyeron 1.020 pacientes; de ellos, 240 eran mujeres (23,5%). En comparación con los hombres, las mujeres fueron mayores (72,6 años vs 66,5 años; p 0,001) y más frágiles (17,1% vs 5,6%; p 0,001). No hubo diferencias en el pretratamiento con un inhibidor del receptor P2Y12 (68,8% vs 70,2%, p = 0,67), aunque las mujeres recibieron más pretratamiento con clopidogrel (56% vs 44%, p = 0,009), principalmente aquellas de edad 75 años y sin fragilidad. En las mujeres se realizaron menos coronariografías precoces (# 24 h) (29,8% vs 36,9%; p = 0,03) a pesar de presentar la misma indicación (criterios de alto riesgo). En el análisis ajustado, la fragilidad, pero no el sexo, se asoció de forma independiente con la realización de una coronariografía diferida. La tasa y el tipo de revascularización fue igual en ambos sexos, y no hubo diferencias en los eventos cardiovasculares intrahospitalarios. CONCLUSIONES: Las mujeres recibieron con mayor frecuencia un tratamiento antitrombótico menos potente. La fragilidad y no el sexo se asoció con la realización de coronariografía diferida. Sin embargo, no hubo diferencias en la tasa de revascularización coronaria ni en los eventos intrahospitalarios en función del sexo.

Validation of the Equidyn protocol for evaluation of dynamic balance in older adults through a smartphone application.

BACKGROUND: Different tasks and proxy measurements have been employed to evaluate dynamic balance in older individuals. However, due to inherent limitations, results from most evaluations could hardly be taken as valid measurements of dynamic balance. RESEARCH QUESTION: Is the Equidyn smartphone application-based protocol valid and sensitive for assessment of dynamic balance in older adults? METHODS: Dynamic balance was evaluated in 52 physically active individuals, age range 60-80 years (M = 69.36). The dynamic tasks were one-leg sway either in the mediolateral (ML) or anteroposterior (AP) direction while supported on the contralateral leg, and cyclic sit-to-stand with a narrow support base. These tasks were performed under standardized movement amplitude and rhythm. Outcomes were correlated with unipedal quiet standing. A smartphone was attached to the trunk backside, and a custom-made application (Equidyn) was employed to provide guidance throughout evaluation, timed beeps to pace the movements, and three-dimensional trunk acceleration measurement for balance evaluation. RESULTS: Our data showed (a) that both ML and AP leg sway tasks were sensitive to aging and to direction of leg sway movements; (b) referenced to quiet unipedal stance, moderate/strong correlations for the ML/AP leg sway tasks and moderate correlations for the sit-to-stand task; and (c) moderate/strong correlations between the ML and AP leg sway tasks, and moderate correlations between the sit-to-stand and the two unipedal dynamic tasks in the ML acceleration direction. SIGNIFICANCE: The current results support the conclusion that the Equidyn protocol is a sensitive and valid tool to evaluate dynamic balance in healthy older individuals. The protocol tasks standardized in amplitude and rhythm favor their reproducibility and trunk acceleration data interpretation. As the whole assessment is made through a smartphone application, this dynamic balance evaluation could be made in a low-cost simple way both in the laboratory and clinical settings.

AZGP1 deficiency promotes angiogenesis in prostate cancer.

BACKGROUND: Loss of AZGP1 expression is a biomarker associated with progression to castration resistance, development of metastasis, and poor disease-specific survival in prostate cancer. However, high expression of AZGP1 cells in prostate cancer has been reported to increase proliferation and invasion. The exact role of AZGP1 in prostate cancer progression remains elusive. METHOD: AZGP1 knockout and overexpressing prostate cancer cells were generated using a lentiviral system. The effects of AZGP1 under- or over-expression in prostate cancer cells were evaluated by in vitro cell proliferation, migration, and invasion assays. Heterozygous AZGP1± mice were obtained from European Mouse Mutant Archive (EMMA), and prostate tissues from homozygous knockout male mice were collected at 2, 6 and 10 months for histological analysis. In vivo xenografts generated from AZGP1 under- or over-expressing prostate cancer cells were used to determine the role of AZGP1 in prostate cancer tumor growth, and subsequent proteomics analysis was conducted to elucidate the mechanisms of AZGP1 action in prostate cancer progression. AZGP1 expression and microvessel density were measured in human prostate cancer samples on a tissue microarray of 215 independent patient samples. RESULT: Neither the knockout nor overexpression of AZGP1 exhibited significant effects on prostate cancer cell proliferation, clonal growth, migration, or invasion in vitro. The prostates of AZGP1-/- mice initially appeared to have grossly normal morphology; however, we observed fibrosis in the periglandular stroma and higher blood vessel density in the mouse prostate by 6 months. In PC3 and DU145 mouse xenografts, over-expression of AZGP1 did not affect tumor growth. Instead, these tumors displayed decreased microvessel density compared to xenografts derived from PC3 and DU145 control cells, suggesting that AZGP1 functions to inhibit angiogenesis in prostate cancer. Proteomics profiling further indicated that, compared to control xenografts, AZGP1 overexpressing PC3 xenografts are enriched with angiogenesis pathway proteins, including YWHAZ, EPHA2, SERPINE1, and PDCD6, MMP9, GPX1, HSPB1, COL18A1, RNH1, and ANXA1. In vitro functional studies show that AZGP1 inhibits human umbilical vein endothelial cell proliferation, migration, tubular formation and branching. Additionally, tumor microarray analysis shows that AZGP1 expression is negatively correlated with blood vessel density in human prostate cancer tissues. CONCLUSION: AZGP1 is a negative regulator of angiogenesis, such that loss of AZGP1 promotes angiogenesis in prostate cancer. AZGP1 likely exerts heterotypical effects on cells in the tumor microenvironment, such as stromal and endothelial cells. This study sheds light on the anti-angiogenic characteristics of AZGP1 in the prostate and provides a rationale to target AZGP1 to inhibit prostate cancer progression.

Fetal Programming Influence on Microbiome Diversity and Ruminal and Cecal Epithelium in Beef Cattle.

We explored the influence of maternal nutritional strategies on the development of the rumen and cecum in offspring. Additionally, we investigated the potential repercussions of prenatal nutrition on the rumen and fecal microbiota composition, utilizing metagenomic 16S techniques, to understand the effects of fetal programming (FP) in Nellore cattle. A total of 63 bulls submitted to different prenatal nutrition strategies, namely, non-programming (NP), partial programming (PP), and complete programming (CP), were evaluated. The rumen epithelium was methodically evaluated based on the presence of rumenitis and structural irregularities. The assessment of cecum lesions was conducted post-evisceration, whereby all thoroughly cleaned ceca were methodically evaluated. Samples from 15 animals of rumen fluid at slaughter and feces during the finishing phase were collected, respectively. All DNA extraction were carried out using the Macherey Nagel NucleoSpin Tissue®, and 16S sequencing was conducted using the V4 primers on the MiSeq platform. Within the ruminal ecosystem, an estimated range of 90 to 130 distinct amplicon sequence variants was discerned, as distributed across 45,000 to 70,000 sequencing reads. Our metagenomic exploration unveils microbial communities that distinctly mirror gastrointestinal tract microenvironments and dietary influences. In sum, this comprehensive study advances our comprehension of FP, highlighting the interplay of maternal nutrition, gastrointestinal development, and microbial communities, contributing significantly to the fields of animal science.

Assessment of the components of fluid balance in patients with septic shock: a prospective observational study.

BACKGROUND: The optimal amount for initial fluid resuscitation is still controversial in sepsis and the contribution of non-resuscitation fluids in fluid balance is unclear. We aimed to investigate the main components of fluid intake and fluid balance in both survivors and non-survivor patients with septic shock within the first 72 hours. METHODS: In this prospective observational study in two intensive care units, we recorded all fluids administered intravenously, orally, or enterally, and losses during specific time intervals from vasopressor initiation: T1 (up to 24 hours), T2 (24 to 48 hours) and T3 (48 to 72 hours). Logistic regression and a mathematical model assessed the association with mortality and the influence of severity of illness. RESULTS: We included 139 patients. The main components of fluid intake varied across different time intervals, with resuscitation and non-resuscitation fluids such as antimicrobials and maintenance fluids being significant contributors in T1 and nutritional therapy in T2/T3. A positive fluid balance both in T1 and T2 was associated with mortality (p = 0.049; p = 0.003), while nutritional support in T2 was associated with lower mortality (p = 0.040). The association with mortality was not explained by severity of illness scores. CONCLUSIONS: Non-resuscitation fluids are major contributors to a positive fluid balance within the first 48 hours of resuscitation. A positive fluid balance in the first 24 and 48 hours seems to independently increase the risk of death, while higher amount of nutrition seems protective. This data might inform fluid stewardship strategies aiming to improve outcomes and minimize complications in sepsis.

In vitro susceptibility to fosfomycin in clinical and environmental extended-spectrum beta-lactamase producing and/or ciprofloxacin-non-susceptible Escherichia coli isolates.

Extended-spectrum beta-lactamase producing and ciprofloxacin-non-susceptible Escherichia coli are clinical and environmental issues. We evaluated the susceptibility profile of fosfomycin in non-susceptible E. coli isolated from urine and the environment. We measured the activity of fosfomycin against 319 and 36 E. coli strains from urine and environmental isolates, respectively, collected from rivers. Fosfomycin resistance profiles were investigated using the minimal inhibitory concentration (MIC), according to the Clinical and Laboratory Standards Institute (CLSI) and the European Committee for Antimicrobial Susceptibility Testing (EUCAST) guidelines. Antibiotic susceptibility testing revealed that 5% and 6.6% of urine samples were non-susceptible to fosfomycin according to CLSI and EUCAST guidelines, respectively. The fosfomycin MIC50/90 was 0.5/4 mg/L. Of the 36 E. coli isolates from river water, 11.1% and 13,8% were non-susceptible to fosfomycin according to CLSI and EUCAST, respectively (range ≤0.25 ≥512 mg/L). All the isolates with MIC ≥512 mg/L for fosfomycin showed the fosA3 gene. Fosfomycin resistance was more frequent in the environment than in clinical samples.

From Anxiety to Hardiness: The Role of Self-Efficacy in Spanish CCU Nurses in the COVID-19 Pandemic.

Background and Objectives: Evidence shows that throughout the COVID-19 pandemic, nurses suffered from emotional symptoms, yet in spite of this, few studies within "positive psychology" have analyzed the emergence/promotion of positive traits, such as hardiness. In this context, the present study aimed to test a model regarding the mediating role of self-efficacy between anxiety experienced at the beginning of the COVID-19 pandemic and hardiness assessed six months later among nurses in critical care units (CCU) in Spain. Materials and Methods: An observational, descriptive, prospective longitudinal study with two data collection periods: (1) from the 1 to the 21 June 2020 (final phase of the state of alarm declared in Spain on 14 March) in which socio-demographic and occupational variables, anxiety (Depression, Anxiety and Stress Scale, DASS-21), self-efficacy (General Self-Efficacy Scale, GSES) and basal resilience (Resilience Scale-14, RS-14) were assessed, and (2) a follow-up 6 months later (January-March 2021) in which hardiness (Occupational Hardiness Questionnaire, OHQ) was evaluated. To analyze the data, multivariate regressions were performed using the PROCESS macro (simple mediation, model 4). Results: A total of 131 Spanish nurses from CCUs, with a mean age of 40.54 years (88.5% women) participated in the study. Moderate and severe levels of anxiety were observed in 19.1% of the sample. Significant and positive correlations were observed between self-efficacy, hardiness and resilience (all p < 0.001). Significant negative correlations were observed between anxiety and self-efficacy (p < 0.001), hardiness (p = 0.027) and resilience (p = 0.005). The indirect effect of anxiety on hardiness through self-efficacy was significant (Effect (SE) = -0.275 (0.100); LLCI = -0.487, ULCI = -0.097), contributing to 28% of the variance, including resilience (p = 0.015), age (p = 0.784), gender (p = 0.294) and years of experience (p = 0.652) as covariates. A total mediation was observed (non-significant anxiety-hardiness direct effect; Effect (SE) = -0.053 (0.215), t = 0.248, p = 0.804, LLCI = -0.372, ULCI = 0.479). Conclusions: The results suggest that in Spanish CCU nurses, anxiety experienced at the beginning of the COVID-19 pandemic may contribute to the development of hardiness through positive resources such as self-efficacy.

Comprehensive Development of a Cellulose Acetate and Soy Protein-Based Scaffold for Nerve Regeneration.

BACKGROUND: The elaboration of biocompatible nerve guide conduits (NGCs) has been studied in recent years as a treatment for total nerve rupture lesions (axonotmesis). Different natural polymers have been used in these studies, including cellulose associated with soy protein. The purpose of this report was to describe manufacturing NGCs suitable for nerve regeneration using the method of dip coating and evaporation of solvent with cellulose acetate (CA) functionalized with soy protein acid hydrolysate (SPAH). METHODS: The manufacturing method and bacterial control precautions for the CA/SPAH NGCs were described. The structure of the NGCs was analyzed under a scanning electron microscope (SEM); porosity was analyzed with a degassing method using a porosimeter. Schwann cell (SCL 4.1/F7) biocompatibility of cell-seeded nerve guide conduits was evaluated with the MTT assay. RESULTS: The method employed allowed an easy elaboration and customization of NGCs, free of bacteria, with pores in the internal surface, and the uniform wall thickness allowed manipulation, which showed flexibility; additionally, the sample was suturable. The NGCs showed initial biocompatibility with Schwann cells, revealing cells adhered to the NGC structure after 5 days. CONCLUSIONS: The fabricated CA/SPAH NGCs showed adequate features to be used for peripheral nerve regeneration studies. Future reports are necessary to discuss the ideal concentration of CA and SPAH and the mechanical and physicochemical properties of this biomaterial.

Utilization of dental services by children with autism spectrum conditions: The role of primary health care.

AIM: Children with autism spectrum conditions (ASC) face many barriers to access dental health services, despite having a greater need for care. The aim of the study was to evaluate the use of dental health services by children with ASC and the individual factors related to the demand for primary care services. METHODS: A cross-sectional study was carried out with 100 caregivers of children with ASC aged 6-12 years in a city in Brazil. After the descriptive analysis, logistic regression analyses were carried out to estimate the odds ratio and 95% confidence intervals. RESULTS: The caregivers reported that 25% of the children had never been to the dentist and 57% had an appointment over the past 12 months. Seeking primary care for dental treatment and frequent toothbrushing were positively associated with both outcomes and participating in oral health preventive activities decreased the chance of never having been to the dentist. Having male caregivers and activity limitations due to autism decreased the chance of having been to the dentist over the past year. CONCLUSION: The findings suggest that reorganizing care of children with ASC can contribute to reducing access barriers to dental health services.

Formulation and optimization of pH-sensitive nanocrystals for improved oral delivery.

The challenge of low water solubility in pharmaceutical science profoundly impacts drug absorption and therapeutic effectiveness. Nanocrystals (NC), consisting of drug molecules and stabilizing agents, offer a promising solution to enhance solubility and control release rates. In the pharmaceutical industry, top-down techniques are favored for their flexibility and cost-effectiveness. However, increased solubility can lead to premature drug dissolution in the stomach, which is problematic due to the acidic pH or enzymes. Researchers are exploring encapsulating agents that facilitate drug release at customized pH levels as a valuable strategy to address this. This study employed wet milling and spray drying techniques to create encapsulated NC for delivering the drug to the intestinal tract using the model drug ivermectin (IVM). Nanosuspensions (NS) were efficiently produced within 2 h using NanoDisp®, with a particle size of 198.4 ± 0.6 nm and a low polydispersity index (PDI) of 0.184, ensuring uniformity. Stability tests over 100 days at 4 °C and 25 °C demonstrated practical viability, with no precipitation or significant changes observed. Cytotoxicity evaluations indicated less harm to Caco-2 cells compared to the pure drug. Furthermore, the solubility of the NC increased by 47-fold in water and 4.8-fold in simulated intestinal fluid compared to the pure active compound. Finally, dissolution tests showed less than 10% release in acidic conditions and significant improvement in simulated intestinal conditions, promising enhanced drug solubility and bioavailability. This addresses a long-standing pharmaceutical challenge in a cost-effective and scalable manner.

p53 stabilisation potentiates [177Lu]Lu-DOTATATE treatment in neuroblastoma xenografts.

PURPOSE: Molecular radiotherapy is a treatment modality that is highly suitable for targeting micrometastases and [177Lu]Lu-DOTATATE is currently being explored as a potential novel treatment option for high-risk neuroblastoma. p53 is a key player in the proapoptotic signalling in response to radiation-induced DNA damage and is therefore a potential target for radiosensitisation. METHODS: This study investigated the use of the p53 stabilising peptide VIP116 and [177Lu]Lu-DOTATATE, either alone or in combination, for treatment of neuroblastoma tumour xenografts in mice. Initially, the uptake of [177Lu]Lu-DOTATATE in the tumours was confirmed, and the efficacy of VIP116 as a monotherapy was evaluated. Subsequently, mice with neuroblastoma tumour xenografts were treated with placebo, VIP116, [177Lu]Lu-DOTATATE or a combination of both agents. RESULTS: The results demonstrated that monotherapy with either VIP116 or [177Lu]Lu-DOTATATE significantly prolonged median survival compared to the placebo group (90 and 96.5 days vs. 50.5 days, respectively). Notably, the combination treatment further improved median survival to over 120 days. Furthermore, the combination group exhibited the highest percentage of complete remission, corresponding to a twofold increase compared to the placebo group. Importantly, none of the treatments induced significant nephrotoxicity. Additionally, the therapies affected various molecular targets involved in critical processes such as apoptosis, hypoxia and angiogenesis. CONCLUSION: In conclusion, the combination of VIP116 and [177Lu]Lu-DOTATATE presents a promising novel treatment approach for neuroblastoma. These findings hold potential to advance research efforts towards a potential cure for this vulnerable patient population.

The association between malocclusion and health-related quality of life in adolescents: A mediation analysis.

This study investigated the role of oral health-related functional limitations and social well-being, self-perceived health, psychosocial factors, and social support in mediating the impact of malocclusion on health-related quality of life (HRQoL). A school-based 6-month cohort study was conducted with 376 12-year-old deprived adolescents. Measures at baseline included malocclusion (DAI score), dental caries, sociodemographic characteristics, psychosocial traits (self-esteem, sense of coherence, oral health beliefs), and social support. The oral health-related functional limitations and symptoms (social well-being) domains of the CPQ11-14 , self-perceived health, and HRQoL (Kiddo-KINDL) were evaluated at the 6-month follow-up. Associations between observed and latent variables (social support, psychosocial factors, and HRQoL) were evaluated using structural equation modelling, according to the Wilson and Cleary theoretical model. Malocclusion was indirectly associated with worse HRQoL, mediated by functional limitations, social well-being, and self-perceived health. Better psychosocial status was directly associated with better HRQoL, and higher social support was indirectly associated with better HRQoL via psychosocial factors. Dental caries experience, female sex, and lower family income were indirectly associated with worse HRQoL. The impact of malocclusion on HRQoL was mediated by oral health-related functional limitations, social well-being, and self-perceived health. Sociodemographic and psychosocial factors, and social support also impacted HRQoL.

In vitro susceptibility to fosfomycin in clinical and environmental extended-spectrum beta-lactamase producing and/or ciprofloxacin-non-susceptible Escherichia coli isolates

ABSTRACT Extended-spectrum beta-lactamase producing and ciprofloxacin-non-susceptible Escherichia coli are clinical and environmental issues. We evaluated the susceptibility profile of fosfomycin in non-susceptible E. coli isolated from urine and the environment. We measured the activity of fosfomycin against 319 and 36 E. coli strains from urine and environmental isolates, respectively, collected from rivers. Fosfomycin resistance profiles were investigated using the minimal inhibitory concentration (MIC), according to the Clinical and Laboratory Standards Institute (CLSI) and the European Committee for Antimicrobial Susceptibility Testing (EUCAST) guidelines. Antibiotic susceptibility testing revealed that 5% and 6.6% of urine samples were non-susceptible to fosfomycin according to CLSI and EUCAST guidelines, respectively. The fosfomycin MIC50/90 was 0.5/4 mg/L. Of the 36 E. coli isolates from river water, 11.1% and 13,8% were non-susceptible to fosfomycin according to CLSI and EUCAST, respectively (range ≤0.25 ≥512 mg/L). All the isolates with MIC ≥512 mg/L for fosfomycin showed the fosA3 gene. Fosfomycin resistance was more frequent in the environment than in clinical samples.

Uso dos serviços de saúde por pessoas idosas em áreas rurais e urbanas do Brasil / Health services utilization by older adults in rural and urban areas of Brazil

Resumo Objetivo Avaliar o uso dos serviços de saúde por pessoas idosas residentes em áreas urbanas e rurais do Brasil. Método Estudo transversal que analisou dados da Pesquisa Nacional de Saúde 2019, referentes aos moradores idosos (≥60 anos) selecionados nos domicílios, totalizando 22.728 entrevistas (3.300 em área rural e 19.426 em área urbana). Foram estimadas para as áreas rurais e urbanas as prevalências de cadastro na Estratégia Saúde da Família, intervalo de tempo da última consulta médica e odontológica, procura do serviço nas últimas duas semanas, última aferição da pressão arterial e da glicemia e avaliados os fatores associados à utilização dos serviços de saúde médicos e odontológicos nos últimos 12 meses. Resultados A autopercepção da saúde como 'muito boa' ou 'boa' foi maior na área urbana (47,32%), assim como a proporção de pessoas idosas que relataram consulta médica e odontológica nos últimos 12 meses (90,54%). Evidenciou-se menor frequência do acompanhamento da aferição de pressão arterial (81,30%) e da glicemia (45,83%) em áreas rurais. As pessoas idosas que possuem baixa escolaridade, residem em áreas rurais, na região Norte são as que possuem menor chance de utilização dos serviços. Conclusão A população idosa residente em área rural apresenta piores condições de saúde em relação à população residente em área urbana.

Abstract Objective To assess health services utilization by older adults in urban and rural areas of Brazil. Method A cross-sectional study was conducted analyzing data from the 2019 National Health Survey on older adults (≥60 years) selected from households based on 22,728 interviews (3,300 in rural and 19,426 in urban areas). For rural and urban areas, the prevalence of Family Health Strategy enrolment, time since last medical and dental visit, service use in past 2 weeks, and last blood pressure and blood glucose measurements were estimated. Also, the factors associated with medical and dental health services utilization in the past 12 months were explored. Results Self-rated health of "Very good" or "Good" was greater in urban areas (47.32%), as was the proportion of older adults reporting a medical or dental visit within the last 12 months (90.54%). Rates of blood pressure (81.30%) and glucose (45.83%) monitoring were lower in rural areas. Older individuals that had low education, resided in rural areas, and the North region, had a lower likelihood of using health services Conclusion The older population living in rural areas had poorer health status compared with the urban population.

History of exposure to copper influences transgenerational gene expression responses in Daphnia magna.

The establishment of transgenerational effects following chemical exposure is a powerful phenomenon, capable of modulating ecosystem health beyond exposure periods. This study assessed the transgenerational effects occurring due to copper exposure in the invertebrate D. magna at the transcriptional level, while evaluating the role of exposure history on such responses. Thus, daphnids acclimated for several generations in a copper vs. clean medium were then exposed for one generation (F0) to this metal, and monitored for the following non-exposed generations (F1, F2 and F3). Organisms differing in exposure histories showed remarkably different transcriptional profiles at the F0, with naïve organisms being more profoundly affected. These trends were confirmed for F3 treatments, which presented different transcriptional patterns for genes involved in detoxification, oxidative stress, DNA damage repair, circadian clock functioning and epigenetic regulation. Furthermore, regardless of exposure history, a great number of histone modifier genes were always found transcriptionally altered, thus suggesting the involvement of histone modifications in the response of Daphnia to metal exposure. Lastly, remarkably distinct transgenerational transcriptional responses were found between naïve and non-naïve organisms, thereby highlighting the influence of exposure history on gene expression and confirming the capacity of metals to determine transgenerational transcriptional effects across non-exposed generations.

Casos, óbitos e letalidade por COVID-19: análise de dados sociais e assistenciais do Nordeste brasileiro / Cases, deaths and lethality due to COVID-19: analysis of social and assistance data from the Brazilian Northeast

Objetivo: Analisar o impacto da cobertura da Atenção Primária à Saúde, Índice de Desenvolvimento Humano e Bolsa Família na ocorrência de casos, óbitos e letalidade por COVID-19 no Nordeste brasileiro. Método: Estudo descritivo, de caráter transversal, com dados extraídos das plataformas estaduais da COVID-19, Sistema de Informação em Saúde para Atenção Básica e Instituto de Pesquisa Econômica Aplicada. Foram utilizados testes de correlação de Spearman e Kruskal-Wallis. Resultados: Verificou-se que foram notificados 483.793 casos confirmados de COVID-19 e 19.307 óbitos por esse agravo no Nordeste brasileiro. Com relação à ocorrência da COVID-19, o Estado do Ceará apresentou maior taxa de casos (1200,83/100.000 habitantes). Observou-se que quanto maior cobertura da ESF maior identificação da ocorrência de casos confirmados (r=0,855 e p-valor=0,002) e óbitos (r=0,818 e p-valor=0,004) por COVID-19. Conclusão: A Estratégia Saúde da Família é um modelo organizativo da Atenção Primária à Saúde potente para enfrentamento da pandemia, a partir da prevenção, rastreamento entre grupos mais vulneráveis, identificação e notificação dos casos e óbitos por COVID-19. Descritores: Atenção Primária à Saúde; Cobertura de Serviços de Saúde; Indicadores de Desenvolvimento; Infecções por Coronavírus; Programas Sociais.

Objective:To analyze the impact of the coverage of Primary Health Care, Human Development Index and Bolsa Família on the occurrence of cases, deaths and lethality due to COVID-19 in the Brazilian Northeast. Method:Descriptive, cross-sectional study, with data extracted from the state platforms for COVID-19, the Health Information System for Primary Care and the Institute for Applied Economic Research. Spearman and Kruskal-Wallis correlation tests were used. Results:It was found that 483,793 confirmed cases of COVID-19 and 19,307 deaths from this condition were reported in the Brazilian Northeast. Regarding the occurrence of COVID-19, the State of Ceará had the highest rate of cases (1200.83/100,000 inhabitants). It was observed that the greater the coverage of FHS, the greater the number of confirmed cases (r=0.855 and p-value=0.002) and deaths (r=0.818 and p-value=0.004) due to COVID-19. Conclusion:The Family Health Strategy is an organizational model of Primary Health Care powerful to cope with the pandemic, based on prevention, tracking among the most vulnerable groups, identification and notification of cases and deaths due to COVID-19. Descriptors: Primary Health Care; Health Services Coverage; Development Indicators; Coronavirus Infections; Social Programs