Bioavailability of a novel sustained-release pellet formulation of 5-flucytosine in healthy-fed participants for use in patients with cryptococcal meningitis.

Cryptococcal meningoencephalitis (CM) is an opportunistic fungal infection and a major cause of death among people living with human immunodeficiency virus in sub-Saharan Africa. 5-flucytosine (5-FC) is a unique, brain-permeable antifungal agent used to reduce mortality from CM and to prevent disease in individuals carrying cryptococcal antigen. 5-FC has a short plasma half-life, requiring 6-hourly oral dosing with an immediate-release (IR) formulation, a significant challenge in hospital and outpatient settings, risking a lack of compliance. We recently reported the relative bioavailability in fasting conditions of a sustained release (SR) oral pellet formulation of 5-FC. In this phase I study, we assessed the safety and pharmacokinetic profiles of the new 5-FC SR formulation in a single dose (2 × 3000 mg), relative to 5-FC IR tablets (Ancotil®; 1500 mg b.i.d.) in healthy participants in fed conditions. This randomized, two-period crossover study was conducted in South Africa to confirm the dose of the identified 5-FC SR formulation for a twice-daily 5-FC regimen in patients. Thirty-six healthy participants were included. All treatments were well tolerated and no serious adverse event was reported. Cmax and AUC(0-t) for the SR formulation (49.2 ± 10.49 µg/mL and 640.4 ± 126.4 h.µg/mL, respectively) were significantly higher than for the IR formulation (36.8 ± 7.61 µg/mL and 456.6 ± 72.8 h.µg/mL, respectively). A physiological based pharmacokinetic model (PBPK) predicted that under fasting conditions, 6000 mg SR pellets would show a good overlap with the IR product (3000 mg b.i.d), thus 6000 mg SR 5-FC b.i.d. in fasting conditions is recommended.

Paving the way for affordable and equitable liposomal amphotericin B access worldwide.

Amphotericin B has long been crucial for treating many serious infectious diseases, such as invasive fungal infections and visceral leishmaniasis, particularly for patients who are immunocompromised, including those with advanced HIV infection. The conventional amphotericin B deoxycholate formulation has largely been replaced in high-income countries with liposomal amphotericin B (LAmB), which has many advantages, including lower rates of adverse events, such as nephrotoxicity and anaemia. Despite an evident need for LAmB in low-income and middle-income countries, where mortality from invasive fungal infections is still substantial, many low-income and middle-income countries still often use the amphotericin B deoxycholate formulation because of a small number of generic formulations and the high price of the originator LAmB. The pricing of LAmB is also highly variable between countries. Overcoming supply barriers through the availability of additional quality-assured, generic formulations of LAmB at accessible prices would substantially facilitate equitable access and have a substantial effect on mortality attributable to deadly fungal infections.

Correction: Facing the escalating burden of dengue: Challenges and perspectives.

[This corrects the article DOI: 10.1371/journal.pgph.0002598.].

Climate change, malaria and neglected tropical diseases: a scoping review.

To explore the effects of climate change on malaria and 20 neglected tropical diseases (NTDs), and potential effect amelioration through mitigation and adaptation, we searched for papers published from January 2010 to October 2023. We descriptively synthesised extracted data. We analysed numbers of papers meeting our inclusion criteria by country and national disease burden, healthcare access and quality index (HAQI), as well as by climate vulnerability score. From 42 693 retrieved records, 1543 full-text papers were assessed. Of 511 papers meeting the inclusion criteria, 185 studied malaria, 181 dengue and chikungunya and 53 leishmaniasis; other NTDs were relatively understudied. Mitigation was considered in 174 papers (34%) and adaption strategies in 24 (5%). Amplitude and direction of effects of climate change on malaria and NTDs are likely to vary by disease and location, be non-linear and evolve over time. Available analyses do not allow confident prediction of the overall global impact of climate change on these diseases. For dengue and chikungunya and the group of non-vector-borne NTDs, the literature privileged consideration of current low-burden countries with a high HAQI. No leishmaniasis papers considered outcomes in East Africa. Comprehensive, collaborative and standardised modelling efforts are needed to better understand how climate change will directly and indirectly affect malaria and NTDs.

Population pharmacokinetics of ravidasvir in adults with chronic hepatitis C virus infection and impact of antiretroviral treatment.

Ravidasvir (RDV) is a novel NS5A inhibitor that exhibits potent pan-genotypic inhibition of hepatitis C virus (HCV) replication. Sofosbuvir (SOF) plus RDV was demonstrated to be efficacious and safe in adults with active HCV infection, including those living with HIV (LWHIV), in the STORM-C-1 trial. We assessed the population pharmacokinetics (PK) of RDV in a sub-study nested within STORM-C-1 conducted in Thailand and Malaysia. SOF (400 mg) plus RDV (200 mg) was administered orally once daily for 12 weeks to adults with chronic HCV infection, but without cirrhosis and for 24 weeks to those with compensated cirrhosis. Intensive and sparse PK samples were collected at 4, 8, and 12 weeks after treatment initiation. Population PK parameters of RDV and the impact of covariates were evaluated using nonlinear mixed-effects modeling. Five hundred ninety-four participants were included, 235 (40%) had compensated cirrhosis, and 189 (32%) were LWHIV. RDV plasma concentrations were best described by a two-compartment model with first-order elimination. Oral clearance (CL/F) and volume of distribution (Vd/F) parameters were allometrically scaled on fat-free mass. Concomitant antiretroviral treatment (ART) increased RDV CL/F by 30%-60%, with efavirenz-based ART having the largest impact. Females had 16% lower RDV CL/F than males, and higher albumin levels reduced RDV central volume of distribution. While several covariates impact RDV CL/F and Vd/F, the effect on RDV exposures was not clinically relevant based on the efficacy data reported in this diverse Asian adult population. There were no meaningful drug-drug interactions in adults LWHIV on ART.

A scoping literature review of global dengue age-stratified seroprevalence data: estimating dengue force of infection in endemic countries.

BACKGROUND: Dengue poses a significant burden worldwide, and a more comprehensive understanding of the heterogeneity in the intensity of dengue transmission within endemic countries is necessary to evaluate the potential impact of public health interventions. METHODS: This scoping literature review aimed to update a previous study of dengue transmission intensity by collating global age-stratified dengue seroprevalence data published in the Medline, Embase and Web of Science databases from 2014 to 2023. These data were then utilised to calibrate catalytic models and estimate the force of infection (FOI), which is the yearly per-capita risk of infection for a typical susceptible individual. FINDINGS: We found a total of 66 new publications containing 219 age-stratified seroprevalence datasets across 30 endemic countries. Together with the previously available average FOI estimates, there are now more than 250 dengue average FOI estimates obtained from seroprevalence studies from across the world. INTERPRETATION: The results show large heterogeneities in average dengue FOI both across and within countries. These new estimates can be used to inform ongoing modelling efforts to improve our understanding of the drivers of the heterogeneity in dengue transmission globally, which in turn can help inform the optimal implementation of public health interventions. FUNDING: UK Medical Research Council, Wellcome Trust, Community Jameel, Drugs for Neglected Disease initiative (DNDi) funded by the French Development Agency, Médecins Sans Frontières International; Swiss Agency for Development and Cooperation and UK aid.

Bioavailability of three novel oral, sustained-release pellets, relative to an immediate-release tablet containing 500 mg flucytosine: A randomized, open-label, crossover study in healthy volunteers.

The opportunistic fungal infection cryptococcal meningoencephalitis is a major cause of death among people living with HIV in sub-Saharan Africa. We report pharmacokinetic (PK) and safety data from a randomized, four-period crossover phase I trial of three sustained-release (SR) oral pellet formulations of 5-flucytosine conducted in South Africa. These formulations were developed to require less frequent administration, to provide a convenient alternative to the current immediate release (IR) formulation, A. Formulations B, C, and D were designed to release 5-flucytosine as a percentage of the nominal dose in vitro. We assessed their safety and PK profiles in a single dose (1 × 3000 mg at 0 h), relative to commercial IR tablets (Ancotil 500 mg tablets; 3 × 500 mg at 0 h and 3 × 500 mg at 6 h) in healthy, fasted participants. Forty-two healthy participants were included. All treatments were well-tolerated. The primary PK parameters, maximum observed plasma concentration (Cmax ) and area under the concentration-time profiles, were significantly lower for the SR formulations than for the IR tablets, and the geometric mean ratios fell outside the conventional bioequivalence limits. The median maximum time to Cmax was delayed for the SR pellets. Physiologically-based PK modeling indicated a twice-daily 6400 mg dose of SR formulation D in fasted condition would be optimal for further clinical development. This regimen is predicted to result in a rapid steady-state plasma exposure with effective and safe trough plasma concentration and Cmax values, within the therapeutic boundaries relative to plasma exposure after four times per day administration of IR tablets (PACTR202201760181404).

Efficacy and safety of fexinidazole for treatment of chronic indeterminate Chagas disease (FEXI-12): a multicentre, randomised, double-blind, phase 2 trial.

BACKGROUND: More than six million people worldwide, particularly in vulnerable communities in Latin America, are infected with Trypanosoma cruzi, the causative agent of Chagas disease. Only a small portion have access to diagnosis and treatment. Both drugs used to treat this chronic, neglected infection, benznidazole and nifurtimox, were developed more than 50 years ago, and adverse drug reactions during treatment pose a major barrier, causing 20% of patients to discontinue therapy. Fexinidazole proved efficacious in an earlier, interrupted clinical trial, but the doses evaluated were not well tolerated. The present study evaluated fexinidazole at lower doses and for shorter treatment durations. METHODS: In this randomised, double-blind, phase 2 trial, we included adult patients (18-60 years old) with confirmed T cruzi infection by serology and PCR and without signs of organ involvement. We evaluated three regimens of fexinidazole-600 mg once daily for 10 days (6·0 g total dose), 1200 mg daily for 3 days (3·6 g), and 600 mg daily for 3 days followed by 1200 mg daily for 4 days (6·6 g)-and compared them with a historical placebo control group (n=47). The primary endpoint was sustained negative results by PCR at end of treatment and on each visit up to four months of follow-up. This study is registered with ClinicalTrials.gov, NCT03587766, and EudraCT, 2016-004905-15. FINDINGS: Between Oct 16, 2017, and Aug 7, 2018, we enrolled 45 patients (n=15 for each group), of whom 43 completed the study. Eight (19%) of 43 fexinidazole-treated patients reached the primary endpoint, compared with six (13%) of 46 in the historical control group. Mean parasite load decreased sharply following treatment but rebounded beginning 10 weeks after treatment. Five participants had seven grade 3 adverse events: carpal tunnel, sciatica, device infection, pneumonia, staphylococcal infection, and joint and device dislocation. Two participants discontinued treatment due to adverse events unrelated to fexinidazole. INTERPRETATION: The fexinidazole regimens in this study had an acceptable safety profile but did not prove effective against T cruzi infection. Development of fexinidazole monotherapy for treating T cruzi infection has been stopped. FUNDING: The Drugs for Neglected Diseases initiative.

[A global core outcome measurement set for snakebite clinical trials]. / Définition d'un jeu universel de critères de décision de base pour les essais cliniques sur les morsures de serpent.

Background: Snakebite clinical trials have often used heterogeneous outcome measures and there is an urgent need for standardisation. Method: A globally representative group of key stakeholders came together to reach consensus on a globally relevant set of core outcome measurements. Outcome domains and outcome measurement instruments were identified through searching the literature and a systematic review of snakebite clinical trials. Outcome domains were shortlisted by use of a questionnaire and consensus was reached among stakeholders and the patient group through facilitated discussions and voting. Results: Five universal core outcome measures should be included in all future snakebite clinical trials: mortality, WHO disability assessment scale, patient-specific functional scale, acute allergic reaction by Brown criteria, and serum sickness by formal criteria. Additional syndrome-specific core outcome measures should be used depending on the biting species. Conclusion: This core outcome measurement set provides global standardisation, supports the priorities of patients and clinicians, enables meta-analysis, and is appropriate for use in low-income and middle-income settings.

Facing the escalating burden of dengue: Challenges and perspectives.

Dengue is the most rapidly emerging mosquito-borne infection and, due to climate change and unplanned urbanization, it is predicted that the global burden of dengue will rise further as the infection spreads to new geographical locations. Dengue-endemic countries are often unable to cope with such increases, with health care facilities becoming overwhelmed during each dengue season. Furthermore, although dengue has been predominantly a childhood illness in the past, it currently mostly affects adults in many countries, with higher incidence of severe disease and mortality rates in pregnant women and in those with comorbidities. As there is currently no specific treatment for dengue and no early biomarker to identify those who will progress to develop vascular leakage, all individuals with dengue are closely monitored in case they need fluid management. Furthermore, diagnosing patients with acute dengue is challenging due to the similarity of clinical symptoms during early illness and poor sensitivity and specificity of point-of-care diagnostic tests. Novel vector control methods, such as the release of Wolbachia-infected mosquitoes, have shown promising results by reducing vector density and dengue incidence in clinical trial settings. A new dengue vaccine, TAK-003, had an efficacy of 61.2% against virologically confirmed dengue, 84.1% efficacy against hospitalizations and a 70% efficacy against development of dengue haemorrhagic fever (DHF) at 54 months. While vaccines and mosquito control methods are welcome, they alone are unlikely to fully reduce the burden of dengue, and a treatment for dengue is therefore essential. Several novel antiviral drugs are currently being evaluated along with drugs that inhibit host mediators, such as mast cell products. Although viral proteins such as NS1 contribute to the vascular leak observed in severe dengue, the host immune response to the viral infection also plays a significant role in progression to severe disease. There is an urgent need to discover safe and effective treatments for dengue to prevent disease progression.

A simulation-based method to inform serosurvey design for estimating the force of infection using existing blood samples.

The extent to which dengue virus has been circulating globally and especially in Africa is largely unknown. Testing available blood samples from previous cross-sectional serological surveys offers a convenient strategy to investigate past dengue infections, as such serosurveys provide the ideal data to reconstruct the age-dependent immunity profile of the population and to estimate the average per-capita annual risk of infection: the force of infection (FOI), which is a fundamental measure of transmission intensity. In this study, we present a novel methodological approach to inform the size and age distribution of blood samples to test when samples are acquired from previous surveys. The method was used to inform SERODEN, a dengue seroprevalence survey which is currently being conducted in Ghana among other countries utilizing samples previously collected for a SARS-CoV-2 serosurvey. The method described in this paper can be employed to determine sample sizes and testing strategies for different diseases and transmission settings.

Deep Learning in the Recognition of Activities of Daily Living Using Smartwatch Data.

The recognition of human activities (HAR) using wearable device data, such as smartwatches, has gained significant attention in the field of computer science due to its potential to provide insights into individuals' daily activities. This article aims to conduct a comparative study of deep learning techniques for recognizing activities of daily living (ADL). A mapping of HAR techniques was performed, and three techniques were selected for evaluation, along with a dataset. Experiments were conducted using the selected techniques to assess their performance in ADL recognition, employing standardized evaluation metrics, such as accuracy, precision, recall, and F1-score. Among the evaluated techniques, the DeepConvLSTM architecture, consisting of recurrent convolutional layers and a single LSTM layer, achieved the most promising results. These findings suggest that software applications utilizing this architecture can assist smartwatch users in understanding their movement routines more quickly and accurately.

Population pharmacokinetics of benznidazole in neonates, infants and children using a new pediatric formulation.

BACKGROUND: There is a major need for information on pharmacokinetics (PK) of benznidazole (BNZ) in children with Chagas disease (CD). We conducted a multicentre population PK, safety and efficacy study in children, infants and neonates with CD treated with BNZ (formulated in 100 mg tablets or 12.5 mg dispersible tablets, developed by the pharmaceutical company LAFEPE, in a collaboration with DNDi). METHODS: 81 children 0-12 years old were enrolled at 5 pediatric centers in Argentina. Diagnosis of T. cruzi infection was confirmed by direct microscopic examination, or at least two positive conventional serological tests. Subject enrolment was stratified by age: newborns to 2 years (minimum of 10 newborns) and >2-12 years. BNZ 7.5 mg/kg/d was administered in two daily doses for 60 days. Five blood samples per child were obtained at random times within pre-defined time windows at Day 0 at 2-5 h post-dose; during steady state, one sample at Day 7 and at Day 30; and two samples at 12-24 h after final BNZ dose at Day 60. The primary efficacy endpoint was parasitological clearance by qualitative PCR at the end of treatment. RESULTS: Forty-one (51%) patients were under 2 years of age (including 14 newborns <1 month of age). Median age at enrolment was 22 months (mean: 43.2; interquartile range (IQR) 7-72 months). The median measured BNZ Cmax was 8.32 mg/L (IQR 5.95-11.8; range 1.79-19.38). Median observed BNZ Cmin (trough) concentration was 2 mg/L (IQR 1.25-3.77; range 0.14-7.08). Overall median simulated Css was 6.3 mg/L (IQR 4.7-8.5 mg/L). CL/F increased quickly during the first month of postnatal life and reached adult levels after approximately 10 years of age. Negative qPCR was observed at the end of treatment in all 76 patients who completed the treatment. Five patients discontinued treatment (3 due to AEs and 2 due to lack of compliance). CONCLUSION: We observed lower BNZ plasma concentrations in infants and children than those previously reported in adults treated with comparable mg/kg doses. Despite these lower concentrations, pediatric treatment was well tolerated and universally effective, with a high response rate and infrequent, mild AEs. TRIAL REGISTRATION: Registered in clinicaltrials.gov #NCT01549236.

Biosorption of bioactive compounds in bacterial nanocellulose: Mechanisms and physical-chemical properties.

Bacterial cellulose (BC) is a biomaterial produced by Gluconacetobacter xylinus, with wide applicability in different areas, such as biomedical, pharmaceutical, and food. BC production is usually carried out in a medium containing phenolic compounds (PC), such as teas, however, the purification process leads to the loss of such bioactive. Thus, the innovation of this research consists of the reincorporation of PC after the purification of the BC matrices through the biosorption process. In this context, the effects of the biosorption process in BC were evaluated to maximize the incorporation of phenolic compounds from a ternary mixture of hibiscus (Hibiscus sabdariffa), white tea (Camellia sinensis), and grape pomace (Vitis labrusca). The biosorbed membrane (BC-Bio) showed a great concentration of total phenolic compounds (TPC = 64.89 mg L-1) and high antioxidant capacity through different assays (FRAP: 130.7 mg L-1, DPPH: 83.4 mg L-1, ABTS: 158.6 mg L-1, TBARS: 234.2 mg L-1). The physical tests also indicated that the biosorbed membrane presented high water absorption capacity, thermal stability, low permeability to water vapor and improved mechanical properties compared to BC-control. These results indicated that the biosorption of phenolic compounds in BC efficiently increases bioactive content and improves physical membrane characteristics. Also, PC release in a buffered solution suggests that BC-Bio can be used as a polyphenol delivery system. Therefore, BC-Bio is a polymer with wide application in different industrial segments.

Cone-beam computed tomography texture analysis can help differentiate odontogenic and non-odontogenic maxillary sinusitis.

Purpose: This study aimed to assess texture analysis (TA) of cone-beam computed tomography (CBCT) images as a quantitative tool for the differential diagnosis of odontogenic and non-odontogenic maxillary sinusitis (OS and NOS, respectively). Materials and Methods: CBCT images of 40 patients diagnosed with OS (N=20) and NOS (N=20) were evaluated. The gray level co-occurrence (GLCM) matrix parameters, and gray level run length matrix texture (GLRLM) parameters were extracted using manually placed regions of interest on lesion images. Seven texture parameters were calculated using GLCM and 4 parameters using GLRLM. The Mann-Whitney test was used for comparisons between the groups, and the Levene test was performed to confirm the homogeneity of variance (α=5%). Results: The results showed statistically significant differences (P<0.05) between the OS and NOS patients regarding 3 TA parameters. NOS patients presented higher values for contrast, while OS patients presented higher values for correlation and inverse difference moment. Greater textural homogeneity was observed in the OS patients than in the NOS patients, with statistically significant differences in standard deviations between the groups for correlation, sum of squares, sum of entropy, and entropy. Conclusion: TA enabled quantitative differentiation between OS and NOS on CBCT images by using the parameters of contrast, correlation, and inverse difference moment.

A global core outcome measurement set for snakebite clinical trials.

Snakebite clinical trials have often used heterogeneous outcome measures and there is an urgent need for standardisation. A globally representative group of key stakeholders came together to reach consensus on a globally relevant set of core outcome measurements. Outcome domains and outcome measurement instruments were identified through searching the literature and a systematic review of snakebite clinical trials. Outcome domains were shortlisted by use of a questionnaire and consensus was reached among stakeholders and the patient group through facilitated discussions and voting. Five universal core outcome measures should be included in all future snakebite clinical trials-mortality, WHO disability assessment scale, patient-specific functional scale, acute allergic reaction by Brown criteria, and serum sickness by formal criteria. Additional syndrome-specific core outcome measures should be used depending on the biting species. This core outcome measurement set provides global standardisation, supports the priorities of patients and clinicians, enables meta-analysis, and is appropriate for use in low-income and middle-income settings.

A Phase 2, Randomized, Multicenter, Placebo-Controlled, Proof-of-Concept Trial of Oral Fexinidazole in Adults With Chronic Indeterminate Chagas Disease.

BACKGROUND: Chagas disease (CD) has significant global health impact, but safe, effective treatments remain elusive. The nitroimidazole fexinidazole is a potential treatment. METHODS: This double-blind, randomized, placebo-controlled, dose-finding, proof-of-concept study was conducted in Bolivia. Adults with serologically confirmed chronic indeterminate CD and positive PCR were randomly assigned to 1 of 6 fexinidazole regimens (1200 or 1800 mg/day for 2, 4, or 8 weeks) or placebo. Target recruitment was 20 patients/arm. The primary endpoint was sustained parasitological clearance by serial negative qPCR from end of treatment (EOT) until 6 months follow-up in the intention-to-treat (ITT) population. Follow-up was extended to 12 months. RESULTS: Enrollment was interrupted after 4/47 patients presented with transient asymptomatic grade 3 and 4 neutropenia. Treatment of ongoing patients was stopped in all patients administered >2 weeks. A total of 40 patients received treatment with fexinidazole from 3 days to 8 weeks. Delayed-onset neutropenia (n = 8) and increased liver enzymes (n = 8) were found in fexinidazole patients vs none in the placebo arm. In the ITT analysis, sustained parasitological clearance from EOT to 12 months follow-up varied between 66.7% (1200 mg-2 week) and 100.0% (1800 mg-2 week). Rapid, sustained clearance of parasitemia was observed in all treated patients with available data, but not in any patients in the placebo group, at 12 months (P = .0056). Further exploratory exposure-response analysis suggested low dosages of fexinidazole may be safe and effective. CONCLUSIONS: Further evaluation is needed to establish fexinidazole's minimum effective dosage and risk-benefit relationship. Results suggest potential for effective treatment regimens <10 days. CLINICAL TRIALS REGISTRATION: NCT02498782.

O impacto de maus-tratos na saúde mental de crianças e adolescentes: revisão integrativa de literatura / The impact of maltreatment on the mental health of children and adolescents: an integrative literature review / El impacto del maltrato en la salud mental de niños y adolescentes: una revisión bibliográfica integradora

Os maus-tratos na infância e na adolescência consistem em abusos psicoló- gicos, físicos e sexuais, além de negligência dos cuidadores, gerando prejuízos psicoló- gicos nesses indivíduos. O objetivo do estudo foi analisar na literatura nacional e interna- cional o impacto dos maus-tratos na saúde mental de crianças e adolescentes. Trata-se de uma revisão integrativa da literatura realizada entre agosto e outubro de 2020, na Biblio- teca Virtual em Saúde (BVS), por meio da questão norteadora: "Quais são os estudos originais nacionais e internacionais que abordam o impacto de maus-tratos na saúde men- tal de crianças e adolescentes?". Foram incluídos artigos em inglês, disponíveis na ínte- gra, e correspondentes aos últimos três anos. Excluíram-se documentos que não apresen- tavam pertinência no estudo conduzido. Foram eleitos dezesseis artigos para análise, que foram divididos em quatro categorias:"I: Associação direta entre maus-tratos e problemas de saúde mental por crianças e adolescentes", a qual evidenciou prejuízos psicológicos como depressão e distúrbios do sono; "II: Fatores de proteção para a saúde mental de crianças e adolescentes vítimas de maus-tratos", que indicou atividades extracurriculares e ambiente familiar acolhedor como fatores de melhor prognóstico diante dos abusos; "III: Relação entre culpabilização da vítima de maus-tratos pela sociedade e sua saúde mental", a qual apresentou consequências negativas da cultura de culpabilização da ví- tima; e "IV: Influência da experiência pregressa de maus-tratos em cuidadores como fator preditor de perpetuação de abusos", que identificou a reprodução de estruturas familiares abusivas. Observa-se que os maus-tratos são uma problemática de saúde pública, o que afirma a necessidade de consolidação de políticas públicas no âmbito, a fim de garantir maior proteção a crianças e adolescentes.

Maltreatments in childhood and adolescence consists of psychological, physical and sexual absuses, in addition to negligence by caregivers, generating psycho- logical disturbs in these individuals. The objective of the study was to analyze in the national and international literature the impact of maltreatments in the mental health of children and adolescents. This is na integrative literature review conducted between Au- gust and October 2020, at the Biblioteca Virtual em Saúde (BVS), through the guiding question: "What are the original national and international studies that address the impact of maltreatments in the mental health of children and adolescents?". Articles in English, fully available, and corresponding to the last three years were included. Documents which were not relevant in the study conducted were excluded. Sixteen articles were chosen for analysis, which were divided into four categories: "I: Direct association between abuse and mental health problems by children and adolescents", which showed psychological damage such as depression and sleep disordes; "II: Protection factors for the mental health of children and adolescents who were victims of abuse", that indicated extracurricular activities and welcoming family environment as factors of better prognosis in the face of abuse; "III: Relationship between culpabilization of the victim of abuse by society and its mental health", which presented negative consequences of the culture of culpabilization of the victim; and "IV: Influence of the previous experience of maltreatment in caregivers as a predictor of perpetuation of abuse", that identified the reproduction of abusive family structures. It is observed that maltreatment is a public health problem, which affirms the need to consolidate public policies in the scope, in order to ensure greater protection for children and adolescents.

Los malos tratos en la infancia y adolescencia consisten en ausencias psico- lógicas, físicas y sexuales, además de negligencia por parte de los cuidadores, generando disturbios psico-lógicos en estos individuos. El objetivo del estudio fue analizar en la literatura nacional e internacional el impacto de los malos tratos en la salud mental de niños y adolescentes. Trata-se de uma revisão integrativa da literatura realizada entre ago- sto e outubro de 2020, na Biblioteca Virtual em Saúde (BVS), através da pergunta orien- tadora: "¿Cuáles son los estudios originales nacionales e internacionales que abordan el impacto de los malos tratos en la salud mental de niños y adolescentes?". Se incluyeron artículos en inglés, totalmente disponibles y correspondientes a los últimos tres años. Se excluyeron los documentos que no eran relevantes para el estudio realizado. Se eligieron 16 artículos para el análisis, que se dividieron en cuatro categorías: "I: Asociación directa entre maltrato y problemas de salud mental de niños y adolescentes", que mostraba daños psicológicos como depresión y trastornos del sueño; "II: Factores de protección para la salud mental de niños y adolescentes víctimas de maltrato", que indicaba las actividades extraescolares y el ambiente familiar acogedor como factores de mejor pronóstico ante el maltrato; "III: Relación entre la culpabilización de la víctima de maltrato por parte de la sociedad y su salud mental", que presentó las consecuencias negativas de la cultura de culpabilización de la víctima; y "IV: Influencia de la experiencia previa de maltrato en los cuidadores como predictor de perpetuación del maltrato", que identificó la reproduc- ción de estructuras familiares abusivas. Se observa que el maltrato es un problema de salud pública, lo que afirma la necesidad de consolidar políticas públicas en el ámbito, a fin de garantizar una mayor protección a los niños y adolescentes.

Aquisição de alimentos em domicílios brasileiros com e sem crianças / Food pourchase in brazilian households with and without child

-A construção dos hábitos alimentares infantis pode ser influenciada pela disponibilidade dos alimentos presentes nos domicílios. Não se sabe o quanto os pais modificam seu padrão de compra de alimentos para mais saudáveis quando há crianças em casa. Esta informação é importante para avaliar a percepção dos pais sobre a influência do ambiente domiciliar na formação de hábitos alimentares saudáveis em seus filhos. A renda familiar é uma variável que pode ter efeito na modificação dos hábitos alimentares dos pais, uma vez que reflete os recursos financeiros disponíveis para compra de alimentos. Investigar a aquisição de alimentos no Brasil em dois períodos com dez anos de diferença possibilita avaliar o efeito macroeconômico do engajamento dos pais na alimentação de seus filhos, uma vez que o país experimentou momentos econômicos distintos na última década. A fim de comparar a aquisição de alimentos saudáveis e não saudáveis em domicílios com e sem crianças no Brasil este estudo utilizou os dados da Pesquisa de Orçamentos Familiares (POF) conduzidos pelo IBGE, no Brasil, em seus inquéritos de 2008-2009 e 2017-2018. Os domicílios foram classificados em: i) presença ou não de crianças de um a cinco anos de idade e ii) maiores de cinco anos até dez anos de idade. Foram considerados todos os domicílios que compunham as amostras: 55.970 (POF 2007-2008) e 69.660 (POF 2017-2018), sem distinção por macrorregião ou zona urbana e rural, assim representando todo o território brasileiro. Os grupos de alimentos utilizados foram constituídos a partir das adaptações de agregados estipulados pela POF nas duas edições do inquérito. Foram estimadas as médias per capita em quilogramas da aquisição (Kg) de frutas, vegetais, refrigerantes e biscoitos num período de 7 dias consecutivos (uma semana). As diferenças das médias per capita da aquisição (Kg) dos alimentos entre domicílios com e sem criança foram estimadas por modelos de regressão de duas partes, combinando um modelo de regressão logística e um modelo linear generalizado de distribuição gama para valores positivos de aquisição, em função da distribuição assimétrica e inflada de zeros para compra de alguns itens alimentares. As análises foram estratificadas por quartos de renda domiciliar per capita, com ajustes pelo sexo e idade do morador de referência do domicílio, número de bebês, adolescentes, adultos e idosos vivendo no domicílio, e gasto mensal com alimentação. A comparação entre as médias de aquisição de alimentos entre os domicílios com e sem crianças foi dada pela intersecção dos intervalos de confiança de 95% e levou-se em consideração o peso amostral e o desenho complexo das POF. A média de aquisição de frutas em 2008-2009 foi maior nos domicílios com crianças das duas faixas etárias nos domicílios mais pobres. Em 2017-2018, a média de aquisição de frutas foi maior entre os domicílios com crianças de cinco a dez anos de idade pertencentes aos estratos socioeconômicos mais ricos. A compra de vegetais diferiu para menos em domicílios com crianças de 5-10 anos nos dois períodos. Houve uma maior média de aquisição per capita de biscoitos nos domicílios com crianças de todas as classes de rendimentos, em ambos os períodos avaliados.

The construction of children's eating habits can be influenced by the availability of food at the home. It's not known how much parents change their pattern of food purchase when there are children at household. That information is important in order to assess parents' perception of the home environment influence in the construction of healthy eating habits at their children. It's possible that family income have an effect on parents' eating habits, once reflects the financial resources available to food purchase. Investigating the food purchase in Brazil in two periods with ten years of diference leads to assess the macroeconomic effect of parental engagement in children's eating habits, since the country has experienced different moments in the last decade. In order to compare the food disponibility in households with and without children, this study utilized data from the Household Budget Surveys (POF) conducted by the Brazilian Institute of Geography and Statistics (IBGE), in Brazil, surveys 2008-2009 and 2017- 2018. The households were categorized into: i) presence or not of children aged between one and five years old and ii) children aged five and ten years old. The sample considered was 55,970 (POF 2007-2008) and 69,660 (POF 2017-2018). The food groups used were constituted from the recommendations of aggregates previously stipulated by the POF in the two editions of the survey. The means per capita were calculated in kilograms of purchase (Kg) of fruits, vegetables, soft drinks and cookies, over a period of 7 consecutive days (one week). Diferences in of food means per capita purchase (Kg) between households with and without children were estimated by using two-part regression models, that combines a logistic regression model and a generalized linear model with gamma distribution for positive values ​​of purchase, in function of the asymmetric and zero-inflated distribution for purchase of some food items. The analyzes were stratified by income quartiles per capita. With adjustments for sex and age of the household's main resident, number of babies, adolescents, adults and elderlys living in the household, and monthly expenditure on food purchase. The comparison between the means of food purchase between households with and without children was given by the intersection of the 95% confidence intervals, considering the weight sample. The means per capita purchase (Kg) of fruit in 2008-2009 was higher in households with children of both age groups in the poorest households. In 2017-2018, the average purchase of fruit was higher among households with children between five and ten years of age belonging to the elevates socioeconomic stratas. The purchase of vegetables were less in households with children aged 5-10 years in both periods. There was a higher purchase of cookies in households with children of all income classes, in both periods.

Dependência, ciclo do capital e limites do fundo público no Brasil / Dependency, capital cycle and limits of the public fund in Brazil

Resumo: Este artigo visa identificar a participação e os limites do fundo público no ciclo do capital da economia dependente brasileira. Para isso, aborda as implicações do intercâmbio desigual, da transferência de valor e da superexploração da força de trabalho para a composição e direcionamento do fundo público no Brasil, utilizando-se da coleta e análise de dados acerca do sistema tributário brasileiro.

Abstract: This article aims to identify the participation and limits of the public fund in the capital cycle of the Brazilian dependent economy. To this end, it addresses the implications of unequal exchange, value transfer and overexploitation of the labor force for the composition and direction of public fund in Brazil, using the analysis of data about the Brazilian tax system.