A nanochitosan-D-galactose formulation increases the accumulation of primaquine in the liver.

Primaquine is the mainstream antimalarial drug to prevent Plasmodium vivax relapses. However, this drug can induce hemolysis in patients with glucose-6-phosphate dehydrogenase deficiency. Nanostructure formulations of primaquine loaded with D-galactose were used as a strategy to target the drug to the liver and decrease the hemolytic risks. Nanoemulsion (NE-Pq) and nanochitosan (NQ-Pq) formulations of primaquine diphosphate containing D-galactose were prepared and characterized by their physicochemistry properties. Pharmacokinetic and biodistribution studies were conducted using Swiss Webster mice. A single dose of 10 mg/kg of each nanoformulation or free primaquine solution was administered by gavage to the animals, which were killed at 0.5, 1, 2, 4, 8, and 24 hours. Blood samples and tissues were collected, processed, and analyzed by high-performance liquid chromatography. The nanoformulation showed sizes around 200 nm (NE-Pq) and 400 nm (NQ-Pq) and physicochemical stability for over 30 days. Free primaquine solution achieved higher primaquine Cmax in the liver than NE-Pq or NQ-Pq at 0.5 hours. However, the half-life and mean residence time (MRT) of primaquine in the liver were three times higher with the NQ-Pq formulation than with free primaquine, and the volume distribution was four times higher. Conversely, primaquine's half-life, MRT, and volume distribution in the plasma were lower for NQ-Pq than for free primaquine. NE-Pq, on the other hand, accumulated more in the lungs but not in the liver. Galactose-coated primaquine nanochitosan formulation showed increased drug targeting to the liver compared to free primaquine and may represent a promising strategy for a more efficient and safer radical cure for vivax malaria.

Mortality due to cervical and breast cancer in health regions of Brazil: impact of public policies on cancer care.

OBJECTIVE: This analysis assessed the association between regional income, screening coverage for cervical and breast cancer, and temporal trends in mortality from these cancers in different Brazilian health regions. STUDY DESIGN: Spatiotemporal ecological study across 450 health regions of Brazil. METHODS: Data from 2010 Demographic Census were used to assess income. Variations in income distribution within health regions were measured using the Gini index. Data on screening coverage were obtained from the Ambulatory Information System (SIA/SUS). Mortality was assessed from the Global Burden of Disease Study 2019 data. The average annual percentage change (AAPC) in cervical and breast cancer mortality rates, 2010-2018, was calculated by health regions. Results were presented in regional maps. The associations between income, screening coverage and mortality changes were estimated by bivariate spatial correlation. RESULTS: Health regions located in the South and Southeast regions of Brazil had the greatest percentages of screening coverage and highest per capita incomes with the lowest Gini index values. From 2010 to 2018, mortality rates for cervical cancer were highest in the North and Northeast health regions. Breast cancer mortality rates were highest in the South and Southeast health regions. The AAPC in breast and cervical cancer mortality had a negative association with per capita income and screening coverage, and a positive association with the Gini index. CONCLUSIONS: There are large regional variations in income, screening coverage, and mortality rates for women with breast and cervical cancer. These inequities could be mitigated by policies to address income disparities and improved access to screening.

Glomerulocystic kidney in two red piranhas Pygocentrus nattereri.

Glomerulocystic kidney (GCK) is defined by a dilatation of the Bowman's space (greater than 2 times the normal size) of more than 5% of all glomeruli. Although GCK has been occasionally documented in dogs, cats, and humans with renal failure, in fish, reports of spontaneous GCK are rare. For the present study, 2 captive adult red piranhas Pygocentrus nattereri from a closed population were submitted for post-mortem examination. Clinical history included lethargy, inappetence, dyspnea, and altered buoyancy. Macroscopically, the fish displayed coelomic distension and ascites. The kidneys were markedly enlarged and dark yellow. Histologically, Bowman's space was noticeably dilated, occasionally with atrophic glomerular tufts. Degeneration and necrosis of the tubular epithelium, infiltration, and nephrocalcinosis were also present. To the authors' knowledge, this present study is the first report of spontaneously occurring GCK in red piranhas and freshwater fish in general. Despite being rare, GCK is a condition with the potential to impair the health of fish and mammals, and further studies are needed to shed new light on this condition.

Allergic emergencies in the prehospital setting: a 5 year retrospective study.

Summary: Background. Patients with severe allergic conditions often request support from the prehospital emergency services given the rapid, unexpected and potentially life-threatening nature of the reactions, such as anaphylaxis. Studies regarding prehospital incidents for allergic conditions are scarce. This study aimed to characterize prehospitalar medical requesting assistance due to suspected hypersensitivity reactions (HSR). Methods. Retrospective study of allergic-related requesting assistances between 2017-2022 of a Portuguese emergency dispatch centre - Emergency and Resuscitation Medical Vehicle (VMER), in Coimbra University Hospital. Demographic and clinical variables were analysed, including clinical manifestations, anaphylaxis severity grading, therapeutic interventions, and post-incident allergic work-up. Regarding anaphylactic events, three diagnosis timings were compared: on-site, hospital emergency department and Investigator-diagnosis based on data reviewed. Results. Out of 12689 VMER requesting assistances, 210 (1.7%) were classified as suspected HSR reactions. After on-site medical evaluation, 127 (60.5%) cases maintained the HSR classification (median age 53 years; 56% males) and the main diagnoses included HSR to Hymenoptera venom (29.9%), food allergy (29.1%), and pharmaceutical drugs (25.5%). Anaphylaxis was assumed on-site in 44 (34.7%) cases, in the hospital emergency department in 53 cases (41.7%) and by investigators in 76 (59.8%) cases. Regarding management, epinephrine was administered on-site in 50 cases (39.4%). Conclusions. The main reason for prehospital requesting assistance was HSR to Hymenoptera venom. A high proportion of incidents met the criteria for anaphylaxis and despite the inherent difficulties of the prehospital setting, many of the on-site diagnoses agreed with the criteria. Regarding management, epinephrine was underused in this setting. Referral to specialized consultation is crucial for the management of prehospital incidents.

Key elements in hypersensitivity reactions to chemotherapy: experience with rapid drug desensitization in gynaecological cancer in a Tertiary Hospital.

Summary: Rapid drug desensitization (RDD) is a procedure performed when no alternative drug is considered equally effective. The aim of our study is to describe the experience with RDD to cytostatics in patients being treated for gynaecological cancer in a tertiary hospital, over a period of 5 years. In this paper, we review 22 cases and 107 episodes of RDD; 86.3% of patients had advanced disease and the mortality rate at the time of data collection was 50.0%. RDD was performed on 81.8% patients for platinum, 13.6% for taxanes, and 4.5% for anthracyclines. The reintroduction of antineoplastic drugs in all patients with a previous history of immediate hypersensitivity reaction demonstrated the safety and efficacy of this procedure. There was serious complication (anaphylaxis) in only one case.

Venous anomalies in hypoplastic posterior fossa: unsolved questions.

INTRODUCTION: Anomalous intracranial venous anatomy is described in patients with syndromic craniosynostosis and is of significant importance when it comes to surgical morbidity. However, it is still controversial its origin, type of circulation in each syndrome, how it behaves over time, when it can be interrupted and wether it needs to be studied. The purpose of this paper is to discuss these issues by reviewing the literature. METHODS: A literature search was performed using the PubMed database with a focus on papers including detailed descriptions of the venous outflow in complex and syndromic craniosynostosis. Search details used were the following: ("veins"[MeSH Terms] OR "veins"[All Fields] OR "venous"[All Fields]) AND ("abnormalities"[Subheading] OR "abnormalities"[All Fields] OR "anomalies"[All Fields]) AND syndromic[All Fields] AND ("craniosynostoses" [MeSH Terms] OR "craniosynostoses"[All Fields] OR "craniosynostosis"[All Fields]). Studies that exposed details of venous anomalies found in syndromic or complex craniosynostosis were selected. RESULTS: Of a total of 211 articles found, 11 were selected for this review. Of these, 5 were case reports, 5 retrospective studies, and only 1 prospective study. From the 6 series of cases presented, 5 discussed the relationship between jugular foramen stenosis (JFS) and collateral venous drainage. The authors discuss data from the literature for each leading question presented: 1-collateral circulation: is it an intrinsic trouble, a consequence of stenosis of the cranial base foramina or related to raised intracranial pressure (ICP)?; 2-what venous anomalies should we search for, and what is the best exam to study them?; 3-collateral circulation changes with time?; 4-can neurosurgeons interrupt the collateral circulation?; 5-should we study all complex types of craniosynostosis? CONCLUSION: The importance of the study of the venous outflow in patients with complex craniosynostosis is evident in the literature. The real relationship between intracranial hypertension, hypoplastic skull base foramen, Chiari I malformation, hydrocephalus, and venous collateral circulation remains unknown. Prospective studies focusing on molecular biology analysis will possibly solve all of these leading questions.

Socioeconomic inequalities and temporomandibular joint disorders in adolescents: contributions from a Maranhão cohort.

AIM: To assess the prevalence of temporomandibular disorder (TMD) in adolescents and estimate possible associations with poverty. BASIC RESEARCH DESIGN: A cross-sectional study nested within a prospective birth cohort study conducted in São Luís, Maranhão, Brazil. PARTICIPANTS: 2,412 adolescents aged 18-19 years. MATERIAL AND METHODS: The presence of TMD, classified according to the Fonseca Anamnestic Index, was used as the outcome. The following explanatory variables were assessed: gender, household head, paved/asphalted street, piped water, and socioeconomic background, based on the Brazilian Association of Market Research criteria and the poverty income ratio (PIR). Logistic regression analysis was performed with the estimation of odds ratios (OR) and 95% confidence intervals. RESULTS: TMD was common (51.4%) and was associated with poverty, as it was more frequent among adolescents from social classes D-E (OR=2.60; 95% CI: 1.48-4.55) and C (OR=1.82; 95% CI: 1.12-2.99) compared to A/B, and among poor adolescents using the PIR (OR=1.50; 95% CI: 1.02-2.33). CONCLUSIONS: The prevalence of TMD in socioeconomically disadvantaged adolescents in São Luís is high, and these data allow the early identification of at-risk groups. We recommend carrying out other population-based studies, using diagnostic strategies with greater accuracy.

Risk clusters of COVID-19 transmission in northeastern Brazil: prospective space-time modelling.

This study aimed to analyse the trend and spatial-temporal clusters of risk of transmission of COVID-19 in northeastern Brazil. We conducted an ecological study using spatial and temporal trend analysis. All confirmed cases of COVID-19 in the Northeast region of Brazil were included, from 7 March to 22 May 2020. We used the segmented log-linear regression model to assess time trends, and the local empirical Bayesian estimator, the global and local Moran indexes for spatial analysis. The prospective space-time scan statistic was performed using the Poisson probability distribution model. There were 113 951 confirmed cases of COVID-19. The average incidence rate was 199.73 cases/100 000 inhabitants. We observed an increasing trend in the incidence rate in all states. Spatial autocorrelation was reported in metropolitan areas, and 178 municipalities were considered a priority, especially in the states of Ceará and Maranhão. We identified 11 spatiotemporal clusters of COVID-19 cases; the primary cluster included 70 municipalities from Ceará state. COVID-19 epidemic is increasing rapidly throughout the Northeast region of Brazil, with dispersion towards countryside. It was identified high risk clusters for COVID-19, especially in the coastal side.

COVID-19 mortality in an area of northeast Brazil: epidemiological characteristics and prospective spatiotemporal modelling.

This study aimed to analyse the spatial-temporal distribution of COVID-19 mortality in Sergipe, Northeast, Brazil. It was an ecological study utilising spatiotemporal analysis techniques that included all deaths confirmed by COVID-19 in Sergipe, from 2 April to 14 June 2020. Mortality rates were calculated per 100 000 inhabitants and the temporal trends were analysed using a segmented log-linear model. For spatial analysis, the Kernel estimator was used and the crude mortality rates were smoothed by the empirical Bayesian method. The space-time prospective scan statistics applied the Poisson's probability distribution model. There were 391 COVID-19 registered deaths, with the majority among ⩾60 years old (62%) and males (53%). The most prevalent comorbidities were hypertension (40%), diabetes (31%) and cardiovascular disease (15%). An increasing mortality trend across the state was observed, with a higher increase in the countryside. An active spatiotemporal cluster of mortality comprising the metropolitan area and neighbouring cities was identified. The trend of COVID-19 mortality in Sergipe was increasing and the spatial distribution of deaths was heterogeneous with progression towards the countryside. Therefore, the use of spatial analysis techniques may contribute to surveillance and control of COVID-19 pandemic.