Prevalence and Risk Factors for Dysphonia in Preschoolers at Five Years Old in a Capital City in the Northeast of Brazil.

GOALS: Identifying the prevalence and risk factors of childhood dysphonia in children turning 5 years old; and assess the link with the interactional, behavioral, sociodemographic, economic, and biological indicators METHOD: Analytical, transversal, nested within a birth cohort 5 years after its creation. Original cohort biologic data were recovered from the previous database. The current demographic and personal data were acquired from the official health institutions where the individuals were found. We managed to find 371 preschoolers, both sexes, enrolled in 141 public and private schools. Face-to-face interviews were performed with mothers regarding maternal and child health and biological, sociodemographic, economic, interactional-affective, and behavioral indicators. Speech therapists used the Consensus of Auditory-Perceptual Evaluation of Voice authorized for Portuguese for the perceptual-auditory judgment of children's voices. Bivariate and multivariate analyzes of the data were performed. A significance level of 5% (P < 0.05) was considered in all analyses. RESULTS: The prevalence of mild-moderate general dysphonia occurred in 26.4% of the preschoolers assessed with tense, rough, and breathy voice quality; low pitch; strong loudness and laryngeal resonance. There was a contrast between preschoolers with dysphonia, calm temperament, and family income of up to three minimum wages and those without these characteristics. We also have noted that a greater chance of dysphonia occurred in preschoolers with a calm temperament, family income of up to three minimum wages, nocturnal bruxism up to 3 years old and who did not use a pacifier. CONCLUSION: There was a high prevalence of dysphonia at 5 years old. Biological indicators have an impact on voice, while interactional, behavioral, sociodemographic, and economic indicators have a higher impact. There is a great need for investments in prevention, promotion, and vocal treatment to minimize negative socio-educational impacts and provide higher quality of life for children at greater risk for dysphonia.

Live, Attenuated, Tetravalent Butantan-Dengue Vaccine in Children and Adults.

BACKGROUND: Butantan-Dengue Vaccine (Butantan-DV) is an investigational, single-dose, live, attenuated, tetravalent vaccine against dengue disease, but data on its overall efficacy are needed. METHODS: In an ongoing phase 3, double-blind trial in Brazil, we randomly assigned participants to receive Butantan-DV or placebo, with stratification according to age (2 to 6 years, 7 to 17 years, and 18 to 59 years); 5 years of follow-up is planned. The objectives of the trial were to evaluate overall vaccine efficacy against symptomatic, virologically confirmed dengue of any serotype occurring more than 28 days after vaccination (the primary efficacy end point), regardless of serostatus at baseline, and to describe safety up to day 21 (the primary safety end point). Here, vaccine efficacy was assessed on the basis of 2 years of follow-up for each participant, and safety as solicited vaccine-related adverse events reported up to day 21 after injection. Key secondary objectives were to assess vaccine efficacy among participants according to dengue serostatus at baseline and according to the dengue viral serotype; efficacy according to age was also assessed. RESULTS: Over a 3-year enrollment period, 16,235 participants received either Butantan-DV (10,259 participants) or placebo (5976 participants). The overall 2-year vaccine efficacy was 79.6% (95% confidence interval [CI], 70.0 to 86.3) - 73.6% (95% CI, 57.6 to 83.7) among participants with no evidence of previous dengue exposure and 89.2% (95% CI, 77.6 to 95.6) among those with a history of exposure. Vaccine efficacy was 80.1% (95% CI, 66.0 to 88.4) among participants 2 to 6 years of age, 77.8% (95% CI, 55.6 to 89.6) among those 7 to 17 years of age, and 90.0% (95% CI, 68.2 to 97.5) among those 18 to 59 years of age. Efficacy against DENV-1 was 89.5% (95% CI, 78.7 to 95.0) and against DENV-2 was 69.6% (95% CI, 50.8 to 81.5). DENV-3 and DENV-4 were not detected during the follow-up period. Solicited systemic vaccine- or placebo-related adverse events within 21 days after injection were more common with Butantan-DV than with placebo (58.3% of participants, vs. 45.6%). CONCLUSIONS: A single dose of Butantan-DV prevented symptomatic DENV-1 and DENV-2, regardless of dengue serostatus at baseline, through 2 years of follow-up. (Funded by Instituto Butantan and others; DEN-03-IB ClinicalTrials.gov number, NCT02406729, and WHO ICTRP number, U1111-1168-8679.).

Growth and Nutritional Biomarkers in Brazilian Infants with Cow's Milk Allergy at Diagnosis and 18-Month Follow-Up: A Prospective Cohort Study.

Purpose: This study aimed to describe the growth, body protein status, and micronutrient biomarkers of Brazilian infants with cow's milk allergy (CMPA) at baseline and at 18 months of follow-up in comparison with their healthy peers. Methods: Thirty infants with CMPA younger than six months of age were included in this longitudinal study, and their nutritional status was compared with that of 24 non-allergic age-matched children. Anthropometric measurements were used to assess growth, and blood and urine samples were analyzed for protein and micronutrient status. Mixed linear models adjusted for birth weight, socioeconomic status, infant feeding at baseline, weight-for-age, C-reactive protein, serum albumin, micronutrient dietary supplementation, and salt consumption were employed to evaluate the evolution of nutritional parameters throughout the follow-up period. Results: Overall, the mean age of the children at enrolment was 2.9 (standard deviation 1.7) months, and 29 children (53.7%) were male. Infants with CMPA showed a higher prevalence of functional iron depletion (transferrin saturation <20) (p=0.027), lower serum ferritin (p=0.009), and lower urinary iodine (p=0.034) levels than non-allergic children at baseline. Patients with CMPA showed a higher increment in weight-for-age and length-for-age over time than those in the control group (p<0.01). Mixed linear analyses showed a significantly lower increase in serum vitamin B12 (s-B12) (p=0.001) and urinary iodine (p<0.001) concentrations over time compared to the control group. Conclusion: Infants with CMPA on a cow's milk elimination diet had a higher weight and length at 18 months of follow-up but showed signs of inadequate iron, iodine, and B-12 vitamin status.

The Use of Nanocarriers to Enhance the Anti-neuroinflammatory Potential of Dietary Flavonoids in Animal Models of Neurodegenerative Diseases: A Systematic Review.

BACKGROUND: Neurodegenerative diseases (NDs) have become a common and growing cause of mortality and morbidity worldwide, especially in older adults. The natural flavonoids found in fruits and vegetables have been shown to have therapeutic effects against many diseases, including NDs; however, in general, flavonoids have limited bioavailability to the target cells. One promising strategy to increase bioavailability is to entrap them in nanocarriers. OBJECTIVE: This article aims to review the potential role of nanocarriers in enhancing the anti-neuroinflammatory efficacy of flavonoids in experimentally induced ND. METHODS: A literature search was conducted in the scientific databases using the keywords "neurodegenerative", "anti-neuroinflammatory", "dietary flavonoids," "nanoparticles", and "therapeutic mechanisms". RESULTS: A total of 289 articles were initially identified, of which 45 articles reported on flavonoids. After completion of the selection process, five articles that met the criteria of the review were selected for analysis. Preclinical studies identified in this review showed that nanoencapsulated flavonoids attenuated cognitive impairment and seizure, improved behavioral patterns, and reduced levels of astrocytes. Importantly, they exhibited strong antioxidant properties, increasing the levels of antioxidant enzymes and reducing oxidative stress (OS) biomarkers. Moreover, nanocarrier-complexed flavonoids decreased the levels of the pro-inflammatory cytokines, interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α), by inhibiting nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and nod-like receptor protein 3 inflammasome activation (NLRP3). They also had remarkable effects on important ND-related neurotransmitters, improved cognitive function via cholinergic neurotransmission, and increased prefrontal cortical and hippocampal norepinephrine (NE) and 5-hydroxytryptamine (5-HT). CONCLUSION: Nanoencapsulated flavonoids should, therefore, be considered a novel therapeutic approach for the treatment of NDs.

Pediatric Dysphonia and the Access to Voice Therapy: A Study in Speech Therapy Services Available in a Capital City in the Northeast of Brazil.

OBJECTIVES: Defining the laryngeal and vocal alterations in the pediatric group studied in private speech therapy facilities; and estimating the time period between the problem being identified by the parents and the access to the proper provided services. METHODS: A cross-sectional analytical observational research with data collected from medical records by the speech therapist of each private facility. A written form was prepared and sent to the speech therapists of the 40 existing facilities. We received 124 of them from the pediatric group being assisted in 15 of the facilities. The form included questions about gender, age, vocal complaints; general degree of dysphonia; otorhinolaryngological diagnosis of vocal fold alterations; the age that the problem was identified by the parents and the beginning of speech therapy. The larynx was examined by videonasopharyngolaryngoscopy, and voice quality by auditory-perceptual assessment. RESULTS: The time period between the identification of the participant's dysphonia by the parents and the start of speech therapy was considered long (3.5years). The group showed variance in the proportion of nodule and cyst between genders. The highest prevalence of nodules occurred in boys; and the cyst in girls. Moderate general dysphonia occurred between 4 and 17years old, average age of 7years and 7months, with greater distribution between 5 and 10years of age. CONCLUSIONS: The average time delay until the start of speech therapy was 3.5years, more frequently in the 5-10years group and due to nodules in boys and cysts in girls.

Impact of the Koala Project on clinical outcomes of preterm infants in two maternity hospitals.

OBJECTIVE: To describe the impact of the Koala project (Actively Controlling Target Oxygen) on clinical outcomes in patients born with less than 36 weeks of gestation, in two maternity hospitals, comparing before and after the strategy implementation. METHODS: This is an intervention study with 100 preterm infants with gestational age ≤36 weeks, who used oxygen in two maternity hospitals between January 2020 and August 2021. One of the hospitals was a private institution and the other was philanthropic. The goal for the target oxygen saturation with this project was 91-95%. Comparisons between the two stages (before and after the implementation of the project) were made evaluating the outcomes of retinopathy of prematurity, bronchopulmonary dysplasia, necrotizing enterocolitis, and deaths. The continuous variables were described using mean, median, standard deviation and interquartile interval. The significance level adopted was 5% and the software used was R Core Team 2021 (version 4.1.0). RESULTS: After oxygen control use according to the Koala protocol, there was a significant reduction in the cases of retinopathy of prematurity (p<0.001) and bronchopulmonary dysplasia (p<0.001). There were no deaths in the second stage, and there was a non-significant increase in the absolute number of necrotizing enterocolitis cases. CONCLUSIONS: The Koala project seems to be an effective and feasible strategy to reduce adverse situations in the management of premature children, but research with a greater sample is needed.

National Vaccine Coverage Survey 2020: methods and operational aspects.

OBJECTIVE: The national vaccination coverage survey on full vaccination at 12 and 24 months of age was carried out to investigate drops in coverage as of 2016. METHODS: A sample of 37,836 live births from the 2017 or 2018 cohorts living in capital cities, the Federal District, and 12 inner cities with 100 thousand inhabitants were followed for the first 24 months through vaccine record cards. Census tracts stratified according to socioeconomic levels had the same number of children included in each stratum. Coverage for each vaccine, full vaccination at 12 and 24 months and number of doses administered, valid and timely, were calculated. Family, maternal and child factors associated with coverage were surveyed. The reasons for not vaccinating analyzed were: medical contraindications, access difficulties, problems with the program, and vaccine hesitancy. RESULTS: Preliminary results showed that less than 1% of children were not vaccinated, full coverage was less than 75% at all capitals and the Federal District, vaccines requiring more than one dose progressively lost coverage, and there were inequalities among socioeconomic strata, favorable to the highest level in some cities and to the lowest in others. CONCLUSION: There was an actual reduction in full vaccination in all capitals and the Federal District for children born in 2017 and 2018, showing a deteriorating implementation of the National Immunization Program from 2017 to 2019. The survey did not measure the impacts of the COVID-19 pandemic, which may have further reduced vaccination coverage.

Multitargeted molecular docking and dynamics simulation studies of flavonoids and volatile components from the peel of Citrus sinensis L. (Osbeck) against specific tumor protein markers.

Citrus sinensis (L.) Osbeck (Rutaceae), commonly known as the sweet orange, is a popular and widely consumed fruit with several medicinal properties. The present study aimed to perform the in silico screening of 18 flavonoids and eight volatile components from the peel of C. sinensis against apoptotic and inflammatory proteins, metalloprotease, and tumor suppressor markers. Flavonoids obtained higher probabilities than volatile components against selected anti-cancer drug targets. Hence, the data from the binding energies against the essential apoptotic and cell proliferation proteins substantiate that they may be promising compounds in developing effective candidates to block cell growth, proliferation, and induced cell death by activating the apoptotic pathway. Further, the binding stability of the selected targets and the corresponding molecules were analyzed by 100 ns molecular dynamics (MD) simulations. Chlorogenic acid has the most binding affinity against the important anti-cancer targets iNOS, MMP-9, and p53. The congruent binding mode to different drug targets focused on cancer shown by chlorogenic acid suggests that it may be a compound with significant therapeutic potential. Moreover, the binding energy predictions indicated that the compound had stable electrostatic and van der Waal energies. Thus, our data reinforce the medicinal importance of flavonoids from C. sinensis and expand the need for more studies, seeking to optimize results and amplify the impacts of further in vitro and in vivo studies. Communicated by Ramaswamy H. Sarma.

Health functions and related molecular mechanisms of Miconia genus: A systematic review.

The Miconia genus is traditionally used in folk medicine in Brazil and other tropical American countries and is represented by 282 species in this region. It is a multifaceted genus of medicinal plants widely used to treat rheumatoid arthritis (RA), pain, inflammatory diseases, and many more therapeutic applications. In the present study, we systematically identify and discuss the literature on in vivo and in vitro studies focusing on the therapeutic potentials and related molecular mechanisms of the Miconia genus. The review also assessed phytochemicals and their pharmacological properties and considered safety concerns related to the genus. Literature searches to identify studies on the Miconia genus were carried out through four main electronic databases, namely PubMed, Embase, Scopus, and Web of Science limited to Medical Subjects Headings (MeSH) and Descriptores en Ciencias de la Salud (DCS) (Health Sciences Descriptors) to identify studies published up to December 2022. The relevant information about the genus was gathered using the keywords 'Miconia', 'biological activities', 'therapeutic mechanisms', 'animal model, 'cell-line model', 'antinociceptive', 'hyperalgesia', 'anti-inflammatory', and 'inflammation'. The therapeutic potentials and mechanisms of action of 14 species from genus Miconia were examined in 18 in vitro studies and included their anti-inflammatory, anticancer, analgesic, antibacterial, cytotoxic, mutagenic, antioxidant, anti-leishmanial, antinociceptive, schistosomicidal, and anti-osteoarthritis potentials, and in eight in vivo studies, assessing their analgesic, antioxidant, antinociceptive, and anti-osteoarthritis activities. Some of the main related molecular mechanisms identified are the modulation of cytokines such as IL-1ß, IL-6, and TNF-α, as well as the inhibition of inflammatory mediators and prostaglandin synthesis. The limited number of studies showed that commonly available species from the genus Miconia are safe for consumption. Miconia albicans Sw.Triana and Miconia rubiginosa (Bonpl.) DC was the most frequently used species and showed significant efficacy and potential for developing safe drugs to treat pain and inflammation.

Impact of the Koala Project on clinical outcomes of preterm infants in two maternity hospitals / Impacto do Projeto Coala nos resultados clínicos de pacientes prematuros em duas maternidades

ABSTRACT Objective: To describe the impact of the Koala project (Actively Controlling Target Oxygen) on clinical outcomes in patients born with less than 36 weeks of gestation, in two maternity hospitals, comparing before and after the strategy implementation. Methods: This is an intervention study with 100 preterm infants with gestational age ≤36 weeks, who used oxygen in two maternity hospitals between January 2020 and August 2021. One of the hospitals was a private institution and the other was philanthropic. The goal for the target oxygen saturation with this project was 91-95%. Comparisons between the two stages (before and after the implementation of the project) were made evaluating the outcomes of retinopathy of prematurity, bronchopulmonary dysplasia, necrotizing enterocolitis, and deaths. The continuous variables were described using mean, median, standard deviation and interquartile interval. The significance level adopted was 5% and the software used was R Core Team 2021 (version 4.1.0). Results: After oxygen control use according to the Koala protocol, there was a significant reduction in the cases of retinopathy of prematurity (p<0.001) and bronchopulmonary dysplasia (p<0.001). There were no deaths in the second stage, and there was a non-significant increase in the absolute number of necrotizing enterocolitis cases. Conclusions: The Koala project seems to be an effective and feasible strategy to reduce adverse situations in the management of premature children, but research with a greater sample is needed.

RESUMO Objetivo: Descrever o impacto do projeto Coala (Controle Ativo de Oxigênio Alvo) nos desfechos clínicos em pacientes nascidos com menos de 36 semanas de gestação, em duas maternidades, comparando antes e depois da implementação da estratégia. Métodos: Trata-se de um estudo de intervenção com cem prematuros vivos, com idade gestacional ≤36 semanas, que utilizaram oxigênio em duas maternidades entre janeiro de 2020 e agosto de 2021. A meta para a saturação de oxigênio alvo com este projeto foi de 91-95%. Comparações entre as duas etapas (antes e depois da implantação do projeto) foram feitas avaliando os desfechos de retinopatia da prematuridade, displasia broncopulmonar, enterocolite necrosante e óbitos. As variáveis contínuas foram descritas por meio de média, mediana, desvio padrão e intervalo interquartil. O nível de significância adotado foi de 5% e o software empregado foi o R Core Team 2021 (versão 4.1.0). Resultados: Observou-se que, após o uso de controle de oxigênio segundo o protocolo Coala, houve redução significativa nos casos de retinopatia da prematuridade (p<0,001) e displasia broncopulmonar (p<0,001). Não houve óbitos na segunda etapa e houve aumento não significativo no número absoluto de casos de enterocolite necrosante. Conclusões: O projeto Coala parece ser uma estratégia eficaz e viável para reduzir situações adversas no manejo de crianças prematuras, mas pesquisas com amostras maiores são necessárias.

Anti-inflammatory natural products modulate interleukins and their related signaling markers in inflammatory bowel disease: A systematic review.

This review aims to identify in vivo studies investigating the potential of plant substances and their natural molecules in managing inflammatory bowel disease (IBD). Specifically, the objective is to examine the impact of these substances on interleukins and other key inflammatory signaling markers. Relevant articles published up to December 2022 were identified through a search of the PubMed, Scopus, Web of Science, and Embase databases. The search used keywords including "inflammatory bowel disease", "medicinal plants", "natural molecules", "anti-inflammatory", and "ulcerative colitis", and identified 1,878 potentially relevant articles, of which 89 were included in this review after completion of the selection process. This study provides preclinical data on natural products (NPs) that can potentially treat IBD, including ulcerative colitis. The main actions of these NPs relate to their effects on nuclear factor kappa B (NF-κB), the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway, the regulation of T helper 17/regulatory T cells balance, and oxidative stress. The ability of these NPs to inhibit intestinal inflammation appears to be dependent on lowering levels of the pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1ß, and IL-17, via the Jun N-terminal kinase (JNK)1, NF-κß-p65, and STAT3 pathways. In addition, NPs were shown to reduce oxidative stress and the severity of ulcerative colitis, as well as increase the activity of antioxidant enzymes. These actions suggest that NPs represent a promising treatment for IBD, and potentially have greater efficacy and safety than current treatments.

Spatial clusters, social determinants of health and risk of COVID-19 mortality in Brazilian children and adolescents: A nationwide population-based ecological study.

Background: Data regarding the geographical distribution of cases and risk factors for COVID-19 death in children and adolescents are scarce. We describe the spatial distribution of COVID-19 cases and deaths in paediatric population and their association with social determinants of health in Brazil. Methods: This is a population-based ecological study with a spatial analysis of all cases and deaths due to COVID-19 in Brazil among children and adolescents aged 0-19 years from March 2020 to October 2021. The units of analysis were the 5570 municipalities. Data on COVID-19 cases and deaths, social vulnerability, health inequities, and health system capacity were obtained from publicly available databases. Municipalities were stratified from low to very high COVID-19 incidence and mortality using K-means clustering procedures, and spatial clusters and relative risks were estimated using spatial statistics with Poisson probability models. The relationship between COVID-19 estimates and social determinants of health was explored by using multivariate Beta regression techniques. Findings: A total of 33,991 COVID-19 cases and 2424 deaths among children and adolescents aged 0-19 years were recorded from March 2020 to October 2021. There was a spatial dependence for the crude mortality coefficient per 100,000 population in the paediatric population aged 0-19 years (I Moran 0·10; P < 0·001). Forty municipalities had higher mortality rates, of which 20 were in states from the Northeast region. Seven spatial clusters were identified for COVID-19 mortality, with four clusters in the Northeast region and three in the North region. Municipalities with higher social inequality and vulnerability had higher COVID-19 mortality in the paediatric population. Interpretation: The main clusters of risk for mortality among children and adolescents were identified in municipalities in the North and Northeast regions, which are the regions with the worst socioeconomic indicators and greatest health disparities in the country. Our findings confirmed the higher burden of COVID-19 for Brazilian paediatric population in municipalities with higher social inequality and vulnerability and worse socioeconomic indicators. To reduce the burden of COVID-19 on children, mass immunisation is necessary. Funding: None.

Cochlear implant complications in a low-income area of Brazil.

OBJECTIVE: The primary objective was to analyze and report on the complications that occurred in the cochlear implant surgeries performed at a large philanthropic teaching hospital located in a low-income area of Brazil. METHODS: A historical cohort study that analyzed surgical records of 432 patients of all age groups and both genders who received unilateral cochlear implant in a tertiary referral center that serves only Brazil's Public Health Care System patients, from February 2009 to December 2017. RESULTS: A total of 67 (15.5%) complications occurred in the cochlear implant surgeries, with 21 (5.4%) major complications. Minor complications occurred in 50 (12%) cases. The most frequent major complication was receiver-stimulator displacement (four cases). There were three cases of hardware failure. Only one case of meningitis and one case of facial nerve paralysis (grade VI in House-Brackmann scale) were found. Six patients needed to be explanted due to a major complication. The relative risk of major complications in the population aged 60 years and older was 4.41 (1.53-12.72; 95% confidence interval [CI]). CONCLUSIONS: Elderly patients suffered more complications than younger patients. receiver-stimulator displacement and dizziness were the most frequent complications (major and minor, respectively). The overall complication rates were comparable to those in the literature. Age as an isolated risk factor for complications in cochlear implant surgery is a path to be explored in future observations.

Cochlear implant complications in a low-income area of Brazil

SUMMARY OBJECTIVE: The primary objective was to analyze and report on the complications that occurred in the cochlear implant surgeries performed at a large philanthropic teaching hospital located in a low-income area of Brazil. METHODS: A historical cohort study that analyzed surgical records of 432 patients of all age groups and both genders who received unilateral cochlear implant in a tertiary referral center that serves only Brazil's Public Health Care System patients, from February 2009 to December 2017. RESULTS: A total of 67 (15.5%) complications occurred in the cochlear implant surgeries, with 21 (5.4%) major complications. Minor complications occurred in 50 (12%) cases. The most frequent major complication was receiver-stimulator displacement (four cases). There were three cases of hardware failure. Only one case of meningitis and one case of facial nerve paralysis (grade VI in House-Brackmann scale) were found. Six patients needed to be explanted due to a major complication. The relative risk of major complications in the population aged 60 years and older was 4.41 (1.53-12.72; 95% confidence interval [CI]). CONCLUSIONS: Elderly patients suffered more complications than younger patients. receiver-stimulator displacement and dizziness were the most frequent complications (major and minor, respectively). The overall complication rates were comparable to those in the literature. Age as an isolated risk factor for complications in cochlear implant surgery is a path to be explored in future observations.

Natural products modulating interleukins and other inflammatory mediators in tumor-bearing animals: A systematic review.

BACKGROUND: Cancer is a group of diseases characterized by abnormal cell growth and proliferation. Natural products are a potentially important source for bioactive phytochemicals in the management of cancer, which regulate a broad range of biological events via the modulation of interleukins (ILs), pro- and anti-inflammatory modulators, and other cancer hallmark-mediated signaling pathways. PURPOSE: To systematically review the literature to identify in vivo studies investigating the anticancer properties of medicinal plants and natural molecules as modulators of ILs and their related pro- and anti-inflammatory signaling markers in tumor-bearing animals. METHODS: Articles published in English were searched, without any constraint in respect of countries. The electronic databases PubMed, Embase, Scopus, and Web of Science were used for the literature search for studies published between January 2010 and January 2022. The search terms used included medicinal plants, anticancer, antineoplasic agent, ILs, cytokine, and their combinations. A manual search to detect any articles not found in the databases was also made. The identified studies were then critically reviewed and relevant data were extracted and summarized. RESULTS: Natural products were found to modulate ILs, including IL-1ß, IL-2, IL-4, IL-6, IL-8, IL-18, IL-23, and IL-12, and interferon gamma; increase tissue inhibitor metalloprotease; decrease vascular endothelial growth factor, tumor necrosis factor alpha, granulocyte macrophage colony-stimulating factor, and nuclear factor kappa B; augment immunity by increasing the major histocompatibility complexes II and CD4+, cluster of differentiation 8 + T cell and class II trans-activator expression; and heighten the action of antioxidant enzymes, which are involved in the detoxification of free radicals and reactive oxygen species. CONCLUSION: Natural products discussed in this review show great potential to regulate ILs and weaken associated pro- and anti-inflammatory signaling markers in tumor-bearing animals. Flavonoids, polyphenols, polysaccharides, alkaloids and tannins are important phytochemicals in the modulation of ILs, especially pro-inflammatory ones. However, in terms of future research, the importance of clinical trials to investigate their beneficial properties should be warranted.

Clinical characteristics and risk factors for maternal deaths due to COVID-19 in Brazil: a nationwide population-based cohort study.

BACKGROUND: Monitoring the characteristics and associated factors for death among pregnant and postpartum women with coronavirus disease 19 (COVID-19) is necessary. We investigated the clinical characteristics and risk factors associated with maternal deaths in a nationwide cohort of Brazil. METHODS: This was a population-based cohort of all pregnant and postpartum women hospitalised with COVID-19 notified to the Sistema de Informação de Vigilância Epidemiológica da Gripe of Brazil (SIVEP-Gripe), from February 2020 to September 2021. The primary outcome was time to in-hospital death, with risk factors analysed with univariable and multivariable Cox proportional hazards regression models. RESULTS: Cumulative observation time was 248 821 person-days from hospital admission to the end of follow-up for 15 105 individuals. There were 1858 deaths (12.3%) for a maternal mortality rate of 7.5 (95% CI 7.1-7.8) per 1000 patients-days. The cumulative mortality increased over time. Black/Brown ethnicity had a higher risk of death than women self-identifying as White. Women in the North, Northeast, Central-West and Southeast regions had higher risk of death than women in the South region. The characteristics independently associated with death were a postpartum status on admission [adjusted hazard ratio, HR 1.4 (95% confidence interval, CI 1.2-1.6)], pre-existing clinical conditions [adjusted HRs 1.2 (95%CI 1.1-1.3) for one and 1.3 (95%CI 1.1-1.5) for two comorbidities], hypoxaemia on admission [adjusted HR 1.2 (95%CI 1.1-1.4)] and requiring non-invasive [adjusted HR 2.6 (95%CI 2.1-3.3)] or invasive ventilatory support [adjusted HR 7.1 (95%CI 5.6-9.2)]. CONCLUSION: In Brazil, the in-hospital maternal mortality rate due to COVID-19 is high and the risk of death increases with the length of hospitalisation. Socio-demographic and biological factors are associated with an increased risk of maternal death. The presence of respiratory signs and symptoms should be considered early markers of disease severity and an adequate management is necessary. Our findings reinforce the need for vaccination of pregnant and postpartum women against COVID-19.

Effects of the COVID-19 pandemic on routine pediatric vaccination in Brazil.

BACKGROUND: COVID-19 pandemic has disrupted health services, including vaccination demand. We describe the impact of the COVID-19 pandemic on routine pediatric vaccination in Brazil. METHODS: We conducted a retrospective analysis of all vaccine doses provided to children aged 0-6 years from January 2019 to December 2020. We obtained data stratified by age group (0 to 2 years and >2 to 6 years) and Brazilian region. Difference-in-difference (DiD) analyses were performed to compare vaccine uptake in the pre-pandemic (January-February), stay-at-home (March-June), and reopening (July-December) periods. RESULTS: The number of vaccine doses administered declined in the stay-at-home period. For children aged 0 to 2 years, the highest reductions were recorded in the North (-25.3%), Northeast (-16.8%) and Central-West (-10.2%) regions. For children aged >2 to 6 years, the highest decline was observed in the North (DiD = -27.2%) and South (DiD = -14.0%) regions. The number of vaccine doses administered in the reopening period has slightly increased in all regions. CONCLUSIONS: Vaccination decreased during the COVID-19 pandemic. Although the number of doses recovered in part during the reopening phase, additional strategies, such as increased public awareness and vaccination booster campaigns are required.