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.

In vitro and in vivo activities of a trithiolato-diRuthenium complex conjugated with sulfadoxine against the apicomplexan parasite Toxoplasma gondii.

Organometallic compounds, including Ruthenium complexes, have been widely developed as anti-cancer chemotherapeutics, but have also attracted much interest as potential anti-parasitic drugs. Recently hybrid drugs composed of organometallic Ruthenium moieties that were complexed to different antimicrobial agents were synthesized. One of these compounds, a trithiolato-diRuthenium complex (RU) conjugated to sulfadoxine (SDX), inhibited proliferation of Toxoplasma gondii tachyzoites grown in human foreskin fibroblast (HFF) monolayers with an IC50 < 150 nM, while SDX and the non-modified RU complex applied either individually or as an equimolar mixture were much less potent. In addition, conjugation of SDX to RU lead to decreased HFF cytotoxicity. RU-SDX did not impair the in vitro proliferation of murine splenocytes at concentrations ranging from 0.1 to 0.5 µM but had an impact at 2 µM, and induced zebrafish embryotoxicity at 20 µM, but not at 2 or 0.2 µM. RU-SDX acted parasitostatic but not parasiticidal, and induced transient ultrastructural changes in the mitochondrial matrix of tachyzoites early during treatment. While other compounds that target the mitochondrion such as the uncouplers FCCP and CCCP and another trithiolato-Ruthenium complex conjugated to adenine affected the mitochondrial membrane potential, no such effect was detected for RU-SDX. Evaluation of the in vivo efficacy of RU-SDX in a murine T. gondii oocyst infection model comprised of non-pregnant outbred CD1 mice showed no effects on the cerebral parasite burden, but reduced parasite load in the eyes and in heart tissue.

Current and novel approaches in yeast cell death research.

The study of cell death mechanisms in fungi, particularly yeasts, has gained substantial interest in recent decades driven by the potential for biotechnological advancements and therapeutic interventions. Examples include the development of robust yeast strains for industrial fermentations and high-value compound production, novel food preservation strategies against spoilage yeasts, and the identification of targets for treating fungal infections in the clinic. In this review, we discuss a wide range of methods to characterize cellular alterations associated with yeast cell death, noting the advantages and limitations. We describe assays to monitor reversible events versus those that mark a commitment to cell death (point-of-no-return), as these distinctions are important to decipher the underlying regulatory mechanisms. Several well-known challenges remain, including the varied susceptibilities to death within a cell population and the delineation of detailed cell death mechanisms. The identification and characterization of morphologically distinct subsets of dying yeast cells within dynamic yeast populations provides opportunities to reveal novel vulnerabilities and survival mechanisms. Elucidating the intricacies of yeast regulated cell death (yRCD) will contribute to the advancement of scientific knowledge and foster breakthrough discoveries with broad-ranging implications.

Working towards the development of vaccines and chemotherapeutics against neosporosis-With all of its ups and downs-Looking ahead.

Neospora caninum is an apicomplexan and obligatory intracellular parasite, which is the leading cause of reproductive failure in cattle and affects other farm and domestic animals, but also induces neuromuscular disease in dogs of all ages. In cattle, neosporosis is an important health problem, and has a considerable economic impact. To date there is no protective vaccine or chemotherapeutic treatment on the market. Immuno-prophylaxis has long been considered as the best control measure. Proteins involved in host cell interaction and invasion, as well as antigens mediating inflammatory responses have been the most frequently assessed vaccine targets. However, despite considerable efforts no effective vaccine has been introduced to the market to date. The development of effective compounds to limit the effects of vertical transmission of N. caninum tachyzoites has emerged as an alternative or addition to vaccination, provided suitable targets and safe and efficacious drugs can be identified. Additionally, the combination of both treatment strategies might be interesting to further increase protectivity against N. caninum infections and to decrease the duration of treatment and the risk of potential drug resistance. Well-established and standardized animal infection models are key factors for the evaluation of promising vaccine and compound candidates. The vast majority of experimental animal experiments concerning neosporosis have been performed in mice, although in recent years the numbers of experimental studies in cattle and sheep have increased. In this review, we discuss the recent findings concerning the progress in drug and vaccine development against N. caninum infections in mice and ruminants.

Elements of fatherhood involved in the gestational period: a scoping review.

OBJECTIVE: To identify in the literature and summarize the elements and characteristics of fatherhood involved during pregnancy. METHOD: Scoping review that used PRISMA-ScR guide to report this review. Searches were carried out in PubMed, CINAHL, PsycInfo, LILACS and Scopus. Google search engines and public health agency websites assisted in searches of gray literature and Rayyan in screening studies. RESULTS: A total of 406 articles were identified, of which 16 made up the final sample. Five elements make up an involved fatherhood: feeling like a father, being a provider and protector, being a partner and participant in pregnancy, participating in prenatal appointments and feeling prepared to take care of a baby. CONCLUSION: Fathers want to be involved in prenatal care, but feel excluded from this process. Public policies that encourage paternal involvement and healthcare professional training to better welcome and promote paternal involvement are of paramount importance.

Hypertensive disorders during pregnancy as a major cause of preterm birth and adverse perinatal outcomes: findings from a Brazilian National Survey.

OBJECTIVE: This study aimed to evaluate the prevalence of hypertensive disorders during pregnancy among Brazilian women with preterm births and to compare the epidemiological characteristics and perinatal outcomes among preterm births of women with and without hypertension. METHODS: This was a secondary cross-sectional analysis of the Brazilian Multicenter Study on Preterm Birth. During the study period, all women with preterm births were included and further split into two groups according to the occurrence of any hypertensive disorder during pregnancy. Prevalence ratios were calculated for each variable. Maternal characteristics, prenatal care, and gestational and perinatal outcomes were compared between the two groups using χ2 and t-tests. RESULTS: A total of 4,150 women with preterm births were included, and 1,169 (28.2%) were identified as having hypertensive disorders. Advanced maternal age (prevalence ratio (PR) 2.49) and obesity (PR= 2.64) were more common in the hypertensive group. The gestational outcomes were worse in women with hypertension. Early preterm births were also more frequent in women with hypertension. CONCLUSION: Hypertensive disorders of pregnancy were frequent among women with preterm births, and provider-initiated preterm births were the leading causes of premature births in this group. The factors significantly associated with hypertensive disorders among women with preterm births were obesity, excessive weight gain, and higher maternal age.

The fungicide cymoxanil impairs respiration in Saccharomyces cerevisiae via cytochrome c oxidase inhibition.

Cymoxanil (CYM) is a widely used synthetic acetamide fungicide, but its biochemical mode of action remains elusive. Since CYM inhibits cell growth, biomass production, and respiration in Saccharomyces cerevisiae, we used this model to characterize the effect of CYM on mitochondria. We found it inhibits oxygen consumption in both whole cells and isolated mitochondria, specifically inhibiting cytochrome c oxidase (CcO) activity during oxidative phosphorylation. Based on molecular docking, we propose that CYM blocks the interaction of cytochrome c with CcO, hampering electron transfer and inhibiting CcO catalytic activity. Although other targets cannot be excluded, our data offer valuable insights into the mode of action of CYM that will be instrumental in driving informed management of the use of this fungicide.

Mitochondrial Haplogroups and Weight Gain After Initiating ART in Patients with HIV.

We studied the association of mitochondrial DNA (mtDNA) haplogroups with weight and body mass index (BMI) gain at 96 weeks in 1,019 treatment-naïve persons with HIV (PWH) who initiated first-line antiretroviral therapy (ART) since 2014. The mean increase in weight and BMI over the study period was 2.90 Kg and 0.98 Kg/m2, respectively. We found a significant adjusted association between the major UK mtDNA haplogroup and lower weight and BMI increase at 96 weeks after ART initiation. Our findings reveal a potential role for mitochondrial genetics in the complex phenomenon of weight gain after initial ART in PWH.

Needs and preferences regarding a mobile application to support diabetic foot self-care.

OBJECTIVE: To identify the needs and preferences of individuals with type 2 diabetes regarding the functionalities and characteristics for a mobile application to support foot self-care. METHOD: Qualitative research with 16 individuals diagnosed with type 2 diabetes recruited during clinical care at a university hospital in Porto, Portugal. Data were collected through semi-structured interviews between March and June 2022 and analyzed using inductive content analysis. RESULTS: Three categories and nine subcategories were identified. Categories included informational needs, essential functionalities for foot health self-care, and user-relevant experience. The preference for objective, limited data input, flexible, and customizable applications was an important factor influencing technology engagement. CONCLUSION: The research highlighted a preference for customizable and flexible applications, aiding nurses in creating solutions that transform care delivery and enhance the quality of life for individuals living with diabetes.

Plasma metabolomic profile is near-normal in people with HIV on long-term suppressive antiretroviral therapy.

Background: Combination antiretroviral therapy (ART) has transformed human immunodeficiency virus (HIV) infection in people with HIV (PWH). However, a chronic state of immune activation and inflammation is maintained despite achieving HIV suppression and satisfactory immunological recovery. We aimed to determine whether the plasma metabolomic profile of PWH on long-term suppressive ART and immunologically recovered approximates the normality by comparison with healthy controls with similar age and gender. Methods: We carried out a cross-sectional study in 17 PWH on long-term ART (HIV-RNA <50 copies/mL, CD4+ ≥500 cells/mm3, and CD4+/CD8+ ≥1) and 19 healthy controls with similar age and gender. Metabolomics analysis was performed by gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS). The statistical association analysis was performed by principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), and Generalized Linear Models (GLM) with a gamma distribution (log-link). Significance levels (p-value) were corrected for multiple testing (q-value). Results: PCA and PLS-DA analyses found no relevant differences between groups. Adjusted GLM showed 14 significant features (q-value<0.20), of which only three could be identified: lysophosphatidylcholine (LysoPC) (22:6) (q-value=0.148), lysophosphatidylethanolamine (LysoPE) (22:6) (q-value=0.050) and hydroperoxy-octadecatrienoic acid (HpOTrE)/dihydroperoxy-octadecatrienoic acid (DiHOTrE)/epoxy-octadecadienoic acid (EpODE) (q-value=0.136). These significant identified metabolites were directly correlated to plasma inflammatory biomarkers in PWH and negatively correlated in healthy controls. Conclusion: PWH on long-term ART have a metabolomic profile that is almost normal compared to healthy controls. Nevertheless, residual metabolic alterations linked to inflammatory biomarkers persist, which could favor the development of age-related comorbidities among this population.

Extracellular vesicles in nanomedicine and regenerative medicine: A review over the last decade.

Small extracellular vesicles (sEVs) are known to be secreted by a vast majority of cells. These sEVs, specifically exosomes, induce specific cell-to-cell interactions and can activate signaling pathways in recipient cells through fusion or interaction. These nanovesicles possess several desirable properties, making them ideal for regenerative medicine and nanomedicine applications. These properties include exceptional stability, biocompatibility, wide biodistribution, and minimal immunogenicity. However, the practical utilization of sEVs, particularly in clinical settings and at a large scale, is hindered by the expensive procedures required for their isolation, limited circulation lifetime, and suboptimal targeting capacity. Despite these challenges, sEVs have demonstrated a remarkable ability to accommodate various cargoes and have found extensive applications in the biomedical sciences. To overcome the limitations of sEVs and broaden their potential applications, researchers should strive to deepen their understanding of current isolation, loading, and characterization techniques. Additionally, acquiring fundamental knowledge about sEVs origins and employing state-of-the-art methodologies in nanomedicine and regenerative medicine can expand the sEVs research scope. This review provides a comprehensive overview of state-of-the-art exosome-based strategies in diverse nanomedicine domains, encompassing cancer therapy, immunotherapy, and biomarker applications. Furthermore, we emphasize the immense potential of exosomes in regenerative medicine.

Epidemiological Profile of Human Papillomavirus in a Healthcare Center in Portugal: Implications for Public Health Policies.

Introduction Human papillomavirus (HPV) infection, a prevalent sexually transmitted disease, affects the majority of sexually active individuals at least once in their lifetime. Cervical cancer stands as a significant contributor to mortality among women. Cervical cancer screening (CCS) and HPV vaccination are recent, with few studies about their impact on the prevalence of HPV types. The emergence of novel predominant pathogen strains can be driven by vaccine-induced pathogen strain replacement, thereby enhancing and altering selection. Objective The aim of the study was to characterize the high-risk (HR) HPV infection in two Portuguese primary care units (PCUs). Materials and methods In this observational, cross-sectional, and descriptive study, we included women aged 25-64 years and registered in two PCUs, who were screened by SiiMA Rastreios (population-based screening management application), and were HR-HPV positive, between August 2015 and May 2018. The results of cervical cancer screening (CCS) can be accessed through the SiiMA Rastreios information system. For data treatment, we used MS Excel (Microsoft Corporation, Redmond, Washington, USA), IBM SPSS Statistics for Windows, Version 20 (Released 2011; IBM Corp., Armonk, New York, USA), and non-parametric tests. Results In our study, we included 4,614 women aged between 25 and 64 years old. CCS was performed on 24.47%, of whom 39.95% were tested for HR-HPV. The infection rate was 18.85%, and all 14 types of infection were identified. The most common HPV type was 31, followed by 16 and 68. We found HPV other than 16/18 in 84.43%. We found coinfections in 34.1%, with no statistically significant difference by age group. In the 25-34 age group, the incidence of infection was 33.7% vs. 17.54% in the 35-54 age group and 4.55% in the 55-64 age group. HPV16 was the most common infection in the 25-34 age group. In nulliparous women, the most common was HPV31. The relationship between smoking habits and HR-HPV infection was statistically significant, but economic insufficiency was not. Conclusion The infection incidence in this study was slightly higher than in the 2011 national study. Statistically, the infection rate was significantly higher in the younger age groups. The most frequent type varied from the national and international study results. This may be due to regional differences in HPV infection, changes in the pattern of incidence, or the effect of vaccination. The HPV pattern may be changing, so the scientific community must keep updated to develop increasingly efficient screening and vaccination programs.

Anaphylactic Shock After Cervical Conization Hemostasis With a Packing Soaked in Monsel's Solution.

Anaphylactic shock is a life-threatening medical emergency, and its successful approach depends on early recognition and treatment. We present a case report of a 54-year-old female, with the American Society of Anesthesiology (ASA) Physical Status Classification III, admitted for cervical conization. She presented with known allergies to paracetamol, diclofenac, and nimesulide, and a history of nickel contact dermatitis, with no reports of complicated anesthesia. During conization, adrenaline was infiltrated in the cervix, and hemostasis was performed with packing soaked in Monsel's solution. The immediate postoperative period in the post-anesthesia care unit was uneventful, and no drugs were administered during this period. Three hours after discharge to the ward, the patient had progressive dyspnea with desaturation and maculopapular exanthema. Anesthesia medical emergency was activated. Upon arrival of the emergency team, the patient presented: marked edema of the lips and tongue, respiratory distress, SpO2 82% (under non-rebreathing high concentration oxygen mask), audible vesicular murmur but diminished in all lung fields (without bronchospasm), blood pressure of 60/40 mmHg, increased capillary refill time (4-5 seconds), Glasgow Coma Scale score of 14, as well as generalized maculopapular exanthema and eyelid edema. Gas analysis revealed the following: pH 7.36, pO2 150, pCO2 33, HCO3 22, and lactate 2.2 mmol/L. Anaphylactic shock was immediately diagnosed without an identified causative agent. Intramuscular adrenaline (0.5mg), endovenous hydrocortisone (200 mg), clemastine (2 mg), and profuse fluid therapy were administered. There was an initial slight improvement followed by subsequent worsening. Additional administration of 0.5 mg intramuscular adrenaline and endovenous methylprednisolone (125 mg) provided similar results. Considering that no other drugs were administered in the ward, the emergency team and the attending gynecologist assumed an association between nickel allergy and the chemical composition of Monsel's solute. Thus, it was decided to remove the packing soaked in Monsel's solute from the vaginal cavity and wash it with saline solution. After removing the packing and further administration of 0.5 mg intramuscular adrenaline, there was progressive improvement in the blood pressure and SpO2. Tryptase samples collected one hour later were increased (23.9 ug/L; normal: <11.4 ug/L). The patient was shifted to the intensive care unit for surveillance, from which she was discharged after 2 days, with scheduled immunoallergology consultation, which is waiting. This case highlights the importance of causative agent identification as a key point for anaphylactic shock resolution, as well as a multidisciplinary discussion among professionals.

Do Men and Women Differ in Hematological Adaptations to 24 Weeks of Crossfit® Training?

Regular exercise can modulate the immune system functioning through changes in the number and function of leukocytes as well as in red blood cells and other typical blood markers. High intensity exercise promotes increases in cytotoxic activity, phagocytic capacity, chemotaxis and cell apoptosis. The aim of the study was to compare the chronic effects of a 24-week training program using CrossFit® methodology on hematological variables of men vs. women. Twenty-nine CrossFit® athletes (35.3 ± 10.4 years, 175.0 ± 9.2 cm, 79.5 ± 16.4 kg) participated in the study. The blood count, the lipid profile and glucose markers were measured every two months during the study period. The erythrocyte count and hemoglobin concentrations increased in months 4 and 6 in men and women, respectively. Hematocrit levels increased in men in months 2, 4 and 6, while in women only in month 6. Red cell distribution width increased in men in month 6 when compared to the value in month 2. Segmented neutrophils increased in men in month 6 and eosinophil levels increased in women in month 6. Differences between the two sexes were observed in monocytes levels at baseline, as well as in months 2, 4 and 6. Cross-Fit® training increased red cell count indicators in both sexes, which may be related to increased erythropoiesis. Some white blood cell counts were altered and these differed between sexes. The number of lymphocytes remained stable throughout the experiment.

Vitiligo-like Lesions as a Predictor of Response to Immunotherapy in Non-Small Cell Lung Cancer: Comprehensive Review and Case Series from a University Center.

The reference to vitiligo-like lesions (VLLs) induced by immune checkpoint inhibitors (ICIs) as a valuable predictive marker of treatment success of immunotherapy with ICIs in melanoma has been mentioned in the literature. Its role in non-small cell lung cancer (NSCLC)-treated patients remains a poorly recognized phenomenon with uncertain significance regarding its predictive value. A retrospective, observational, single-center report was performed, with descriptive analysis of clinicopathological and treatment characteristics of patients with stage IV NSCLC who developed ICI-induced VLL between January 2018 and December 2022, contextualized in a comprehensive review of the literature and reported cases regarding this phenomenon. During the first 5 years' experience of ICI use in stage IV NSCLC treatment, three cases of ICI-induced VLLs were diagnosed. In line with the previous reports, two of the three presented cases exhibited treatment response and favorable prognosis. The recognition and understanding of the pathophysiological processes underlying ICI-induced VLLs may represent a promising opportunity to identify a predictive marker of tumor response to ICIs, with impact in treatment selection and patient management. It also may contribute to the recognition of new patterns of molecular expression that could lead to improvements in therapeutic development.

In Vitro Characterization of Reversine-Treated Gingival Fibroblasts and Their Safety Evaluation after In Vivo Transplantation.

Reversine is a purine derivative that has been investigated with regard to its biological effects, such as its anticancer properties and, mostly, its ability to induce the dedifferentiation of adult cells, increasing their plasticity. The obtained dedifferentiated cells have a high potential for use in regenerative procedures, such as regenerative dentistry (RD). Instead of replacing the lost or damaged oral tissues with synthetic materials, RD uses stem cells combined with matrices and an appropriate microenvironment to achieve tissue regeneration. However, the currently available stem cell sources present limitations, thus restricting the potential of RD. Based on this problem, new sources of stem cells are fundamental. This work aims to characterize mouse gingival fibroblasts (GFs) after dedifferentiation with reversine. Different administration protocols were tested, and the cells obtained were evaluated regarding their cell metabolism, protein and DNA contents, cell cycle changes, morphology, cell death, genotoxicity, and acquisition of stem cell characteristics. Additionally, their teratoma potential was evaluated after in vivo transplantation. Reversine caused toxicity at higher concentrations, with decreased cell metabolic activity and protein content. The cells obtained displayed polyploidy, a cycle arrest in the G2/M phase, and showed an enlarged size. Additionally, apoptosis and genotoxicity were found at higher reversine concentrations. A subpopulation of the GFs possessed stem properties, as supported by the increased expression of CD90, CD105, and TERT, the existence of a CD106+ population, and their trilineage differentiation capacity. The dedifferentiated cells did not induce teratoma formation. The extensive characterization performed shows that significant functional, morphological, and genetic changes occur during the dedifferentiation process. The dedifferentiated cells have some stem-like characteristics, which are of interest for RD.