Navigating Neurotoxicity and Safety Assessment of Nanocarriers for Brain Delivery: Evaluation Models and Insights.

Nanomedicine, an area which uses nanomaterials for theragnostic purposes, is advancing rapidly, particularly in the detection and treatment of neurodegenerative diseases. The design of nanocarriers can be optimized to enhance drug bioavailability and targeting to specific organs, improving therapeutic outcomes. However, clinical translation hinges on biocompatibility and safety. Nanocarriers can cross the blood-brain barrier (BBB), potentially causing neurotoxic effects through mechanisms such as oxidative stress, DNA damage, and neuroinflammation. Concerns about their accumulation and persistence in the brain make it imperative to carry out a nanotoxicological risk assessment. Generally, this involves identifying exposure sources and routes, characterizing physicochemical properties, and conducting cytotoxicity assays both in vitro and in vivo. The lack of a specialized regulatory framework creates substantial gaps, making it challenging to translate findings across development stages. Additionally, there is a pressing need for innovative testing methods due to constraints on animal use and the demand for high-throughput screening. This review examines the mechanisms of nanocarrier-induced neurotoxicity and the challenges in risk assessment, highlighting the impact of physicochemical properties and the advantages and limitations of current neurotoxicity evaluation models. Future perspectives are also discussed. Additional guidance is crucial to improve the safety of nanomaterials and reduce associated uncertainty. STATEMENT OF SIGNIFICANCE: Nanocarriers show tremendous potential for theragnostic purposes in neurological diseases, enhancing drug targeting to the brain, and improving biodistribution and pharmacokinetics. However, their neurotoxicity is still a major field to be explored, with only 5% of nanotechnology-related publications addressing this matter. This review focuses on the issue of neurotoxicity and safety assessment of nanocarriers for brain delivery. Neurotoxicity-relevant exposure sources, routes and molecular mechanisms, along with the impact of the physicochemical properties of nanomaterials, are comprehensively described. Moreover, the different experimental models used for neurotoxicity evaluation are explored at length, including their main advantages and limitations. To conclude, we discuss current challenges and future perspectives for a better understanding of risk assessment of nanocarriers for neurobiomedical applications.

Description of vaccination coverage and hesitancy obtained by epidemiological survey of children born in 2017-2018, in Belo Horizonte and Sete Lagoas, Minas Gerais, Brazil.

OBJECTIVE: To describe vaccination coverage and hesitation for the basic children's schedule in Belo Horizonte and Sete Lagoas, Minas Gerais state, Brazil. METHODS: Population-based epidemiological surveys performed from 2020 to 2022, which estimated vaccine coverage by type of immunobiological product and full schedule (valid and ministered doses), according to socioeconomic strata; and reasons for vaccination hesitancy. RESULTS: Overall coverage with valid doses and vaccination hesitancy for at least one vaccine were, respectively, 50.2% (95%CI 44.1;56.2) and 1.6% (95%CI 0.9;2.7), in Belo Horizonte (n = 1,866), and 64.9% (95%CI 56.9;72.1) and 1.0% (95%CI 0.3;2.8), in Sete Lagoas (n = 451), with differences between socioeconomic strata. Fear of severe reactions was the main reason for vaccination hesitancy. CONCLUSION: Coverage was identified as being below recommended levels for most vaccines. Disinformation should be combated in order to avoid vaccination hesitancy. There is a pressing need to recover coverages, considering public health service access and socioeconomic disparities. MAIN RESULTS: Vaccination coverage of children up to 4 years old was 50.2% in Belo Horizonte, and 64.9% in Sete Lagoas. Fear of severe reactions and believing that vaccination against eradicated diseases is unnecessary were the main reasons for vaccination hesitancy. IMPLICATIONS FOR SERVICES: Recovery of high vaccination coverage among children, considering public health service access conditions and socioeconomic inequities. Acting on reasons for hesitancy that can assist in targeting actions. PERSPECTIVES: The multifactorial context of vaccination hesitancy demands the development of health education strategies to raise awareness about child immunization.

Impact of the improvement of living conditions on tuberculosis mortality in Brazil: an ecological study.

BACKGROUND: The risk of death due to tuberculosis (TB) in Brazil is high and strongly related to living conditions (LC). However, epidemiological studies investigating changes in LC and their impact on TB are lacking. OBJECTIVES: To evaluate the impact of LC on TB mortality in Brazil. DESIGN AND SETTING: This ecological study, using panel data on spatial and temporal aggregates, was conducted in 1,614 municipalities between 2002 and 2015. METHODS: Data were collected from the Mortality Information System and the Brazilian Institute of Geography and Statistics. The proxy variable used for LC was the Urban Health Index (UHI). Negative binomial regression models were used to estimate the effect of the UHI on TB mortality rate. Attributable risk (AR) was used as an impact measure. RESULTS: From 2002 to 2015, TB mortality rate decreased by 23.5%, and LC improved. The continuous model analysis resulted in an RR = 0.89 (95%CI = 0.82-0.96), so the AR was -12.3%. The categorized model showed an effect of 0.92 (95%CI = 0.83-0.95) in municipalities with intermediate LC and of 0.83 (95%CI = 0.82-0.91) in those with low LC, representing an AR for TB mortality of -8.7% and -20.5%, respectively. CONCLUSIONS: Improved LC impacted TB mortality, even when adjusted for other determinants. This impact was greater in the strata of low-LC municipalities.

Real-World Healthcare Resource Use Associated with Recurrent or Metastatic Head and Neck Cancer Patients Care in Portugal-TRACE Study.

Recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) is a challenging disease, requiring personalized management by a multidisciplinary team. The aim of this retrospective multicentric study was to characterize real-world healthcare resource use and patient care for R/M HNSCC in Portugal during the first year after diagnosis. A total of 377 patients ineligible for curative treatment were included, mostly male (92.8%), aged 50-69 years (74.5%), with heavy alcohol (72.7%) or smoking habits (89.3%). Oropharynx (33.2%) and oral cavity (28.7%) were primary tumor locations, with lung metastases being the most common (61.4%). Eligible patients for systemic treatment with palliative intent (80.6%) received up to four treatment lines, with varied regimens. Platinum-based combination chemotherapy dominated first-line treatment (>70%), while single-agent chemotherapy and anti-PD1 immunotherapy were prevalent in later lines. Treatment approaches were uniform across disease stages and primary tumor locations but varied geographically. Treated patients received more multidisciplinary support than those who were ineligible. This study provides the first Portuguese real-world description of R/M HNSCC patient characteristics, treatment patterns, and supportive care during the year after diagnosis, highlighting population heterogeneity and aiming to improve patient management.

Use of Marsupialization as a Definitive Treatment for Large-sized Dentigerous Cysts in a Patient with Mucopolysaccharidosis Type I.

The correct diagnosis is fundamental for the appropriate treatment to be employed in a particular pathology. The best treatment is not the one that solves only local problems, fragmenting the patient, and therefore, it is necessary to integrate the entire systemic condition of the individual before initiating any local treatment. This context inevitably requires dentistry to participate in a multidisciplinary approach, where the role of the dentist is expanded in concepts that encompass ethics, human dignity, and professional valorization. This article describes a clinical case of a patient with mucopolysaccharidosis type I, whose treatment of cystic lesions present in the mandible was exclusively performed through marsupialisation. The objective of this study is to demonstrate, within the complexity of this rare syndrome, the difficulties of diagnosis and the need for evaluation of the patient beyond the limits of the oral cavity, as well as to report two cases of large dentigerous cysts, surgically treated conservatively through marsupialisation, without the need for re-approach for enucleation and without recurrences over a 20-year period.

Cultural Adaptation and Validation of the Ambulatory Self-Confidence Questionnaire (ASCQ), Portuguese (European) Version.

In a world where physical activity and social participation are fundamental pillars of a full and healthy life, confidence in walking has emerged as a fundamental aspect to assess, especially for older adults. Therefore, the purpose of this study was to develop a Portuguese (European) version of the Ambulatory Self-Confidence Questionnaire (ASCQ) that was both linguistically and psychometrically adapted. To do so, a translation method was used, followed by an assessment of its validity and reliability. The Portuguese version was completed by 173 older adults. To assess reliability, Cronbach's alpha and intraclass correlation coefficients (ICCs) were used. For sociodemographic and clinical characterization, as well as questionnaire scoring, descriptive statistical analysis was used. Pearson's correlation (r), Student's t-test, and one-way ANOVA were used to analyze criterion and construction validity. The Portuguese interactions with ASCQ were effectively translated and adjusted, revealing exceptional internal consistency and test-retest reliability, as reflected in Cronbach's alpha and ICC values of 0.95. No floor effect was observed; however, a ceiling effect was identified (3.5%). The criterion and construct validity were verified as all the correlations established were statistically significant. The adaptation of the ASCQ to Portuguese culture is adequate, making it valid for use within the Portuguese population.

[Survival rate of laryngeal cancer patients treated in Brazil's Unified Health System - SUS, 2002-2010]. / Sobrevida por câncer de laringe em pacientes tratados no Sistema Único de Saúde - SUS, 2002-2010.

The scope of this article was to analyze the five-year survival rate among patients with laryngeal cancer treated in the Unified Health System in Brazil and its regions between January 2002 and June 2010. There is still scarce information in Brazil regarding the scale and survival rate of laryngeal cancer patients, which makes it difficult to adopt specific strategies for the control of the condition in the country. A retrospective cohort study based on the National Oncology Database was conducted, and the survival probability rate for laryngeal cancer according to age, sex and Brazilian regions/states was estimated using the Kaplan-Meier method. The log-rank test was used to assess the differences observed, considering a 5% significance level. Survival in Brazil was estimated at 50.8% (95%CI: 49.9%-51.8%), being lower among male patients (49.1%; 95%CI: 48.10%-50.16%); between 50 and 60 years of age (48.4%; 95%CI: 46.7%-50.0%); for residents of the Northern region (45.5%; 95%CI: 39.5%-51.3%). The regional variation in the survival rate for laryngeal cancer in Brazil reveals disparities between Brazilian regions/states that may be linked to inequality of access to diagnosis and/or treatment.

O objetivo do artigo foi analisar a sobrevida de cinco anos em pacientes com câncer de laringe tratados no Sistema Único de Saúde no Brasil e regiões entre janeiro de 2002 e junho de 2010. São escassas as informações relativas à magnitude e sobrevida do câncer de laringe no país, o que dificulta a adoção de estratégias específicas para seu controle. Foi realizado um estudo de coorte retrospectiva a partir da Base Nacional em Oncologia. Estimou-se a probabilidade de sobrevida para o câncer de laringe segundo faixa etária, sexo e regiões/estados brasileiros por meio do método de Kaplan-Meier. O teste de log-rank foi aplicado para avaliar as diferenças na sobrevida, considerando-se o nível de significância de 5%. A sobrevida no Brasil foi estimada em 50,8% (IC95%: 49,9-51,8), sendo menor em pacientes do sexo masculino (49,1%; IC95%: 48,10-50,16); com idade entre 50 e 60 anos (48,4%; IC95%: 46,7-50,0); e para moradores da região Norte (45,5%; IC95%: 39,5-51,3). A variação na sobrevida para o câncer de laringe em relação aos estados e às regiões do país aponta disparidades que podem estar relacionadas à desigualdade de acesso ao diagnóstico e/ou tratamento.

Association of Malocclusion with Temporomandibular Disorders: A Cross-Sectional Study.

Background/Objectives: Temporomandibular disorders (TMD) encompass a range of musculoskeletal and neuromuscular conditions affecting the temporomandibular joint (TMJ) and associated structures. This cross-sectional study, conducted in a Portuguese TMD department, aimed to assess the relationship between malocclusion and TMD severity. Methods: Data on demographic variables, TMD clinical symptoms, and malocclusion classes were collected using the EUROTMJ database. The Chi-square test (χ2) identified associations, with their intensity measured by Cramér's V (φc). Results: The study included 1170 patients (932 females and 238 males), with a mean age of 41.73 ± 16.80 years. Most patients exhibited Angle Class I malocclusion (85.5%), followed by Angle Class II (13.5%) and Angle Class III (1.1%). Class II malocclusion was associated with increased TMD severity (p < 0.001), higher myalgia levels (p = 0.002), more frequent disc displacement without reduction (p = 0.002) and lower maximum mouth opening values (Class II: 38.13 ± 7.78 mm, Class I: 39.93 ± 8.67 mm). Significant associations were also found between malocclusion type and arthralgia (p = 0.021), mouth-opening limitation (p = 0.016), and TMJ crepitus (p = 0.017). In cases of malocclusion, the presence of oral signs of bruxism explained the degree of myalgia, disc displacement, and severity (p = 0.003; p = 0.048; p = 0.045). Conclusions: This study highlights that (1) the most common type of dental malocclusion in TMD patients was Class I; (2) Class II malocclusion was associated with increased TMD severity and oral signs of bruxism; and (3) Class III was rarely observed in TMD consultation. The findings suggest that bruxism behavior in cases of malocclusion may be significant in TMD.

Racial inequalities in child vaccination and barriers to vaccination in Brazil among live births in 2017 and 2018: an analysis of a retrospective cohort of the first two years of life.

OBJECTIVE: To describe timely vaccination completion and obstacles in the first 24 months of life in Brazil, examining associations with maternal race/skin color. METHODS: Study participants were 37,801 children born in 2017 and 2018 included in the National Immunization Coverage Survey. We calculated prevalence and 95% confidence intervals for timely vaccine completeness and obstacles at 5, 12 and 24 months of life, according to maternal race/skin color. Associations were analyzed using logistic regression. RESULTS: 7.2% (95%CI 6.3;8.2) of mothers faced difficulties in taking their children to be vaccinated, and 23.4% (95%CI 21.7;25.1) were not vaccinated when taken. These proportions were 75% (95%CI 1.25;2.45) and 97% (95%CI 1.57;2.48) higher, respectively, among Black mothers. At least one vaccination was delayed among 49.9% (95%CI 47.8;51.9) and 61.1% (95%CI 59.2;63.0) of children by 5 and 12 months, respectively. These rates were higher among Black/mixed race mothers. CONCLUSION: There are racial inequalities in both the obstacles faced and in vaccination rates in Brazil. MAIN RESULTS: Marked racial inequalities were found in the obstacles to vaccination of children under 24 months in Brazil and to timely vaccination at 5 months and in the first year of life. IMPLICATIONS FOR SERVICES: Racial inequalities in the occurrence of vaccination shortcomings in health services, in the objective restrictions faced by families in taking their children to vaccination centers and in incomplete vaccination in a timely manner need to be addressed by the Brazilian National Health System. PERSPECTIVES: Equal public policies to address barriers to vaccination and qualification of health services need to be implemented. Studies need to deepen understanding of the structural determinants that lead to racial disparities.

Unusual Anastomosis between Branches of the Ulnar Nerve (Kaplan Type Anastomotic Variant) - Case Report.

The Kaplan anastomosis is a rare communication originally described between the superficial and dorsal branches of the ulnar nerve, distal to the ulnar tunnel, and in strict relation with the pisiform bone. It reveals, by its particular location, a formation of high clinical-surgical expressiveness. In this paper, we describe a Kaplan-type communication from a left upper limb with an unusual loop conformation between branches of the ulnar nerve in the pisiform bone.

Chronic Kidney Disease Study in Diabetic Patients: Insights From Primary Care Units in Northern Portugal.

Introduction Diabetes mellitus (DM) remains a primary cause of morbidity and mortality, leading to complications such as blindness, kidney failure, and lower limb amputations. Early detection of kidney damage, indicated by microalbuminuria (MA), is crucial for managing DM. Given the impact of these conditions, evaluating the prevalence of chronic kidney disease (CKD) in diabetic populations within primary healthcare is essential. Methodology This was a cross-sectional and observational study. Adults diagnosed with DM type 1 or 2, from five primary care units (PCUs) located in the North of Portugal, were included in this study. Descriptive and correlational statistics were performed using IBM SPSS Statistics for Windows, Version 28.0 (IBM Corp., Armonk, NY). Statistical significance was set to P < 0,05. Logistic regression models were created to identify the factors associated with CKD and DM. Results A sample of 357 diabetic patients was obtained, with 166 (46.5%) females. Of the sample, 250 (70.1%) were aged 65 or older, and the median known duration of DM was 9.36 years. Excess weight or obesity accounted for 79.8%, with a median body mass index of 28.73 kg/m2 and hypertension in 284 (79.6%). An estimated glomerular filtration rate (eGFR) less than 60 mL/min was present in 89 (24.9%) and an MA of 30 mg/dL or higher was present in 68 (19.0%). In total, 130 (36.4%) individuals exhibited eGFR and MA consistent with CKD. Among these, 25 (78.1%) had other identifiable causes of CKD besides DM, hypertension, overweight, or obesity. Binary logistic regression models were constructed to find a relationship between CKD with eGFR < 60 mL/min and MA. A statistically significant association was found between CKD with eGFR < 60 mL/minute and age (odds ratio [OR] = 1.150; P < 0.001), kidney stones (OR = 5.112; P = 0.003), absence of excess weight or obesity (OR = 0.267; P < 0.001). The use of GLP1 agonists showed statistical significance as a predictor (OR = 4.653; P = 0.042) of the presence of MA. Discussion The study investigates the impact of DM and its complications in the surveyed population. While most patients had controlled DM (284, 76.2%), prolonged disease duration correlated with poorer glycemic control, underscoring the need for more effective management strategies in advanced disease stages. Notably, a third of individuals with DM had CKD, with significant implications for therapeutic interventions and heightened risks of renal failure and cardiovascular morbidity. MA was a crucial marker for endothelial injury, with prevalence influenced by DM duration and medication type. However, in many cases, correct identification of CKD was lacking, suggesting under-recognition of renal deterioration in DM. While the study offers valuable insights, its limited sample size and geographic scope warrant cautious interpretation, emphasizing the need for broader, context-specific research to inform comprehensive healthcare strategies. Conclusions In conclusion, this study highlights the significant burden of CKD among diabetic patients, emphasizing the need for proactive screening, personalized management, and accurate diagnosis. Despite limitations, it underscores the importance of early detection and tailored interventions, advocating for improved diabetes care to mitigate renal complications on a broader scale.

Transcultural adaptation of the Adaptive Behavior Assessment System (ABAS-3).

This study describes the cross-cultural adaptation to Brazilian Portuguese of the Adaptive Behavior Assessment System (ABAS-3), which assesses 11 skills areas within three major adaptive domains: the conceptual, social, and practical. The translation was performed by two independent translators, which was followed by the synthesis of the translations by two experts and then an analysis of the synthesis by 33 specialists from the areas of health and education (three per subscale) who were experts in the domains evaluated by ABAS-3. Of the 1121 items of the five ABAS-3 forms, 82 (7.31%) needed revision. There was good agreement between the specialists in respect of most items, with only minor adjustments being required. There was good evidence of content validity and the adequacy of the adaptation in respect of the conceptual, idiomatic, and semantic aspects of the items of the instrument. This initial process of cross-cultural adaptation was necessary because adaptive behavior is strongly influenced by environmental factors such as socioeconomic status and culture.

A novel NKp80-based strategy for universal identification of normal, reactive and tumor/clonal natural killer-cells in blood.

Purpose: Natural killer (NK) cells are traditionally identified by flow cytometry using a combination of markers (CD16/CD56/CD3), because a specific NK-cell marker is still missing. Here we investigated the utility of CD314, CD335 and NKp80, compared to CD16/CD56/CD3, for more robust identification of NK-cells in human blood, for diagnostic purposes. Methods: A total of 156 peripheral blood (PB) samples collected from healthy donors (HD) and patients with diseases frequently associated with loss/downregulation of classical NK-cell markers were immunophenotyped following EuroFlow protocols, aimed at comparing the staining profile of total blood NK-cells for CD314, CD335 and NKp80, and the performance of distinct marker combinations for their accurate identification. Results: NKp80 showed a superior performance (vs. CD314 and CD335) for the identification of NK-cells in HD blood. Besides, NKp80 improved the conventional CD16/CD56/CD3-based strategy to identify PB NK-cells in HD and reactive processes, particularly when combined with CD16 for further accurate NK-cell-subsetting. Although NKp80+CD16 improved the identification of clonal/tumor NK-cells, particularly among CD56- cases (53%), aberrant downregulation of NKp80 was observed in 25% of patients, in whom CD56 was useful as a complementary NK-cell marker. As NKp80 is also expressed on T-cells, we noted increased numbers of NKp80+ cytotoxic T-cells at the more advanced maturation stages, mostly in adults. Conclusion: Here we propose a new robust approach for the identification of PB NK-cells, based on the combination of NKp80 plus CD16. However, in chronic lymphoproliferative disorders of NK-cells, addition of CD56 is recommended to identify clonal NK-cells, due to their frequent aberrant NKp80- phenotype.

Bovine Alphaherpesvirus 1, Bovine Alphaherpesvirus 5 and Bubaline Alphaherpesvirus 1 in Palatine Tonsils from Water Buffaloes in Northern Brazil and Possible Links with the Origin of Bovine Alphaherpesvirus Type 5.

Herpesviruses are significant pathogens of ruminants. In water buffaloes (Bubalus bubalis), however, herpesviruses have not been thoroughly studied. Although bubaline alphaherpesvirus 1 (BuAHV1) and bovine alphaherpesvirus 1 (BoAHV1) have already been recovered from water buffaloes, to date, no reports on the occurrence of bovine alphaherpesvirus 5 (BoAHV5) in these animals have been published. Therefore, the aim of this study was to search for BuAHV1, BoAHV1, and BoAHV5 in palatine tonsils of apparently healthy water buffaloes from the Pará state, Northern Brazil. Tissue samples of tonsils (n = 293) were screened by a nested PCR (nPCR) targeting a region of UL44 (gC coding gene), followed by sequencing, to detect and differentiate between the viral types. Viral genome segments were detected in 18 out of 293 (6.1%) of the palatine tonsil samples. Two animals carried genomes of BoAHV1 only, eleven animals carried BoAHV5 genomes only, and four animals carried BuAHV1 only. Another animal had both BoAHV1 and BoAHV5 genomes in its tonsils. No infectious virus could be recovered from any of the samples. The BuAHV1 sequences identified here were more closely related to BuAHV1 genomes identified in India. Phylogenetic analyses suggested a closer relationship between the recovered BoAHV5 and BuAHV1 genomes. Therefore, evidence is provided here to confirm that not only BoAHV1 and BuAHV1, but also BoAHV5, can infect water buffaloes. This report highlights (i) the first detection of BoAHV5 in water buffaloes and (ii) the occurrence of coinfections with BoAHV1 and BoAHV5 in that species. Such findings and the similarity of BoAHV5 to Indian herpesvirus genomes suggest that the origin of type 5 may be linked to recombinations between bovine and bubaline herpesviruses within bubalines, since the scenario for generation of recombinants in buffaloes is potentially present.

The virome of bubaline (Bubalus bubalis) tonsils reveals an unreported bubaline polyomavirus.

Water buffalo (Bubalus bubalis) farming is increasing in many regions of the world due to the species' ability to thrive in environments where bovine cattle would struggle. Despite water buffaloes being known for their resistance to diseases, there is a lack of data about the diversity of the microbiome of the species. In this study, we examined the virome diversity in palatine tonsils collected from animals from the island of Marajó, northern Pará state, Brazil, which harbors the largest bubaline flock in the country. Tonsil fragments from 60 clinically healthy bubalines were randomly selected from a sample of 293 animals. The samples were purified, extracted, and randomly amplified with phi29 DNA polymerase. After amplification, the products were purified and sequenced. Circular DNA viruses were predominant in the tonsils' virome. Sequences of genome segments representative of members of the genera Alphapolyomavirus (including a previously unreported bubaline polyomavirus genome) and Gemycircularvirus were identified, along with other not yet classified circular virus genomes. As the animals were clinically healthy at the time of sampling, such viruses likely constitute part of the normal tonsillar virome of water buffaloes inhabiting the Ilha do Marajó biome.

Hog1 acts in a Mec1-independent manner to counteract oxidative stress following telomerase inactivation in Saccharomyces cerevisiae.

Replicative senescence is triggered when telomeres reach critically short length and activate permanent DNA damage checkpoint-dependent cell cycle arrest. Mitochondrial dysfunction and increase in oxidative stress are both features of replicative senescence in mammalian cells. However, how reactive oxygen species levels are controlled during senescence is elusive. Here, we show that reactive oxygen species levels increase in the telomerase-negative cells of Saccharomyces cerevisiae during replicative senescence, and that this coincides with the activation of Hog1, a mammalian p38 MAPK ortholog. Hog1 counteracts increased ROS levels during replicative senescence. While Hog1 deletion accelerates replicative senescence, we found this could stem from a reduced cell viability prior to telomerase inactivation. ROS levels also increase upon telomerase inactivation when Mec1, the yeast ortholog of ATR, is mutated, suggesting that oxidative stress is not simply a consequence of DNA damage checkpoint activation in budding yeast. We speculate that oxidative stress is a conserved hallmark of telomerase-negative eukaryote cells, and that its sources and consequences can be dissected in S. cerevisiae.

Maternal and perinatal health indicators in Brazil over a decade: assessing the impact of the COVID-19 pandemic and SARS-CoV-2 vaccination through interrupted time series analysis.

Background: Few studies have evaluated the effects of the Coronavirus disease 2019 (COVID-19) pandemic, caused by the SARS-CoV-2 virus, on maternal and perinatal health at a populational level. We investigated maternal and perinatal health indicators in Brazil, focusing on the effects of the COVID-19 pandemic, and SARS-CoV-2 vaccination campaign for pregnant women. Methods: Utilizing interrupted time series analysis (January 2013-December 2022), we examined Maternal Mortality Ratio, Perinatal Mortality Rate, Preterm Birth Rate, Cesarean Section Rate, and other five indicators. Interruptions occurred at the pandemic's onset (March 2020) and pregnant women's vaccination (July 2021). Results were expressed as percent changes on time series' level and slope. Findings: The COVID-19 onset led to immediate spikes in Maternal Mortality Ratio (33.37%) and Perinatal Mortality Rate (3.20%) (p < 0.05). From March 2020 to December 2022, Cesarean Section and Preterm Birth Rates exhibited upward trends, growing monthly at 0.13% and 0.23%, respectively (p < 0.05). Post start of SARS-CoV-2 vaccination (July 2021), Maternal Mortality Ratio (-34.10%) and Cesarean Section Rate (-1.87%) promptly declined (p < 0.05). Subsequently, we observed a monthly decrease of Maternal Mortality Ratio (-9.43%) and increase of Cesarean Section Rate (0.25%) (p < 0.05), while Perinatal Mortality Rate and Preterm Birth Rate showed a stationary pattern. Interpretation: The pandemic worsened all analyzed health indicators. Despite improvements in Maternal Mortality Ratio, following the SARS-CoV-2 vaccination campaign for pregnant women, the other indicators continued to sustain altered patterns from the pre-pandemic period. Funding: No funding.