''Inserting the etonorgestrel implant into the thigh: A case report''.

Etonorgestrel implant is inserted on the inner surface of the non-dominant medial upper arm in women, over the triceps area. However, this case report aims to describe an alternative insertion site for etonorgestrel implant - the medial side of the thigh - in nephropathic patients with arteriovenous fistulas undergoing hemodialysis.

Grade-4/5 motor activity log-Brazil for post-stroke individuals with a severely impaired upper limb: a validity, reliability and measurement error study.

PURPOSE: This study examined the clinimetrics of the Brazilian-Portuguese translation of the Grade-4/5 Motor Activity Log (MAL 4/5), which assesses everyday use of the more affected upper-limb (UL) in stroke survivors with moderate/severe or severe motor impairment. MATERIALS AND METHODS: The translated MAL 4/5 was administered to 47 stroke survivors with moderate/severe or severe UL motor impairment. Accelerometers were worn on participants' wrists for five days on average prior to the first assessment. Test-retest and inter-rater reliabilities were assessed using the intraclass correlation coefficient (ICC), internal consistency using Cronbach's α, and construct validity was tested with correlations with the accelerometry. The measurement error (SEM) and the minimal detectable change (MDC) were calculated. RESULTS: MAL4/5-Brazil's test-retest reliability (AOU: ICC = 0.84; QOU: ICC = 0.90), inter-rater reliability (AOU: ICC = 0.83; QOU: ICC = 0.91), internal consistency (Cronbach's α = 0.91 and 0.95 for AOU and QOU scales, respectively), the SEM and MDC were 0.3 and 0.8 points for the AOU subscale and 0.2 and 0.5 points for the QOU subscale, respectively. The construct validity (AOU scale: r = 0.67; QOU scale: r = 0.76) was high. CONCLUSION: Grade-4/5 Motor Activity Log-Brazil is a reliable and valid instrument for assessing the more-affected UL use of stroke patients with moderate/severe or severe UL motor impairments.

Reliability and concurrent validity of the Grade-4/5 MAL-Brazil were established in adults with hemiparesis moderate/severe or severe upper extremity post Stroke.The minimum detectable change for the Grade-4/5 MAL-Brazil was 0.8 points for the Amount of Use scale and 0.5 points for the Quality of Use scale.Data from the accelerometry supports the construct validity of this instrument.The assessment can now be used clinically and for research in adults with impairment upper extremity moderate/severe or severe post Stroke.

Standard practices in cardiac monitoring: training needs of intensive care unit nurses.

BACKGROUND: Enforcing practice standards for cardiac monitoring in intensive care units (ICUs) has been shown to reduce misdiagnoses and inappropriate interventions. Continuous professional development (CPD) programs are committed to aligning clinical practices with recommended standards. The crucial initial phase in CPD development involves assessing the training needs of the targeted population. OBJECTIVE: To assess the training needs of ICU nurses in cardiac monitoring. The overarching goal was to formulate a focused Continuous Professional Development (CPD) program geared towards implementing standard practices in cardiac monitoring. METHODS: This study employed a generic qualitative approach with a descriptive design, utilizing interviews and focus groups from July to September 2018. Involving 16 ICU nurses. Content analysis was employed, encompassing transcription, fluctuant and iterative reading, unitization, categorization, coding, description, and interpretation. RESULTS: All nurses recognized cardiac monitoring's importance in the ICU but reported barriers to its effective implementation which were related to factors that could addressed by a CPD as insufficient knowledge and skills. Training needs were identified in both clinical and technical aspects, with recommendations for practical and theoretical activities and e-learning strategies. Barriers related to organizational aspects (equipment and communication within the healthcare team) were also mentioned. CONCLUSION: ICU nurses presented clear and specific training needs related to cardiac monitoring as knowledge, skills, and competencies. Other organizational aspects were also reported as barriers. Addressing these learning needs through targeted CPD aligned with organizational initiatives can contribute to enhancing the quality of cardiac monitoring practices in ICUs.

Five-year Contraceptive Use of 52-mg Levonorgestrel Releasing Intrauterine System in Young Women, Menstrual Patterns, and New Contraceptive Choice.

OBJECTIVE: To evaluate the continuation rates of the 52-mg levonorgestrel-releasing intrauterine system (LNG-IUS) during the first 5 years of use, reasons for its discontinuation, bleeding patterns, and new contraceptive choice after the 5th year, in adolescents and young women. METHODS: The present study was a 5-year prospective cohort conducted in a Family Planning Service of a tertiary hospital in Brazil. We selected 100 healthy women between 15 and 24 years old who used 52-mg LNG-IUS for contraception. The clinical follow-up of these women took place from June 2017 to December 2022. The study evaluated the continuation rates of the method, reasons for its discontinuation, bleeding patterns, and new contraceptive choice after the 5th year. Continuous data were reported as mean ± standard deviation (SD) and range (minimum-maximum). Categorical variables were described as percentages. RESULTS: The continuation rates of LNG-IUS were 89.1% (82/92), 82.9% (72/87), 75.3% (64/85), 70.5% (60/85), and 64.2% (54/84) in the 1st, 2nd, 3rd, 4th, and 5th years of use, respectively. The main reason for discontinuation was acne (11/30). Amenorrhea rates were 50, 54.1, 39, 35.7, and 51.8% at 12, 24, 36, 48, and 60 months, respectively. All patients who completed the study and needed contraception after the 5th year opted for long-acting contraceptive methods (LARC). CONCLUSION: The LNG-IUS showed high continuation rates in adolescents and young women in the first 5 years of use. Most patients who completed the study chose a LARC method after the 5th year.

OBJETIVO: Avaliar as taxas de continuação do sistema intrauterino liberador de levonorgestrel (SIU-LNG) 52 mg durante os primeiros 5 anos de uso, razões de sua descontinuação, padrões de sangramento e nova escolha contraceptiva após o 5° ano, em adolescentes e mulheres jovens. MéTODOS: O estudo foi uma coorte prospectiva de 5 anos realizada em um Serviço de Planejamento Familiar de um hospital terciário no Brasil. Selecionamos 100 mulheres saudáveis entre 15 e 24 anos que usaram o SIU-LNG 52 mg para contracepção. O acompanhamento clínico dessas mulheres ocorreu de junho de 2017 a dezembro de 2022. O estudo avaliou as taxas de continuação do método, razões de sua descontinuação, padrões de sangramento e nova escolha contraceptiva após o 5° ano. Os dados contínuos foram relatados como média ± DP e intervalo (mínimo-máximo). As variáveis categóricas foram descritas como porcentagens. RESULTADOS: As taxas de continuação do SIU-LNG foram 89,1% (82/92), 82,9% (72/87), 75,3% (64/85), 70,5% (60/85) e 64,2% (54/84) no 1°, 2°, 3°, 4° e 5° anos de uso, respectivamente. O principal motivo de descontinuação foi a acne (11/30). As taxas de amenorreia foram de 50, 54,1, 39, 35,7 e 51,8% aos 12, 24, 36, 48 e 60 meses, respectivamente. Todas as pacientes que completaram o estudo e necessitaram de contracepção após o 5° ano optaram por métodos contraceptivos de longa duração (LARC). CONCLUSãO: O SIU-LNG apresentou altas taxas de continuação em adolescentes e mulheres jovens nos primeiros 5 anos de uso. A maioria das pacientes que completou o estudo escolheu um método LARC após o 5° ano.

Dengue virus serotype 2 genotype III evolution during the 2019 outbreak in Mato Grosso, Midwestern Brazil.

DENV-2 was the main responsible for a 70% increase in dengue incidence in Brazil during 2019. That year, our metagenomic study by Illumina NextSeq on serum samples from acute febrile patients (n = 92) with suspected arbovirus infection, sampled in 22 cities of the state of Mato Grosso (MT), in the middle west of Brazil, revealed eight complete genomes and two near-complete sequences of DENV-2 genotype III, one Human parvovirus B19 genotype I (5,391 nt) and one Coxsackievirus A6 lineage D (4,514 nt). These DENV-2 sequences share the aminoacidic identities of BR4 lineage on E protein domains I, II and III, and were included in a clade with sequences of the same lineage circulating in the southeast of Brazil in the same year. Nevertheless, 11/34 non-synonymous mutations are unique to three strains inthis study, distributed in the E (n = 6), NS3 (n = 2) and NS5 (n = 3) proteins. Other 14 aa changes on C (n = 1), E (n = 3), NS1 (n = 2), NS2A (n = 1) and NS5 (n = 7) were first reported in a genotype III lineage, having been already reported only in other DENV-2 genotypes. All 10 sequences have mutations in the NS5 protein (14 different aa changes). Nine E protein aa changes found in two sequences, six of which are unique, are in the ectodomain; where the E:M272T change is on the hinge of the E protein at domain II, in a region critical for the anchoring to the host cell receptor. The NS5:G81R mutation, in the methyltransferase domain, was found in one strain of this study. Altogether, these data points to an important evolution of DENV-2 genotype III lineage BR4 during this outbreak in 2019 in MT. Genomic surveillance is essential to detect virus etiology and evolution, possibly related to immune evasion and viral fitness changes leading to future novel outbreaks.

Increased interregional virus exchange and nucleotide diversity outline the expansion of chikungunya virus in Brazil.

The emergence and reemergence of mosquito-borne diseases in Brazil such as yellow fever, zika, chikungunya, and dengue have had serious impacts on public health. Concerns have been raised due to the rapid dissemination of the chikungunya virus across the country since its first detection in 2014 in Northeast Brazil. In this work, we carried out on-site training activities in genomic surveillance in partnership with the National Network of Public Health Laboratories that have led to the generation of 422 chikungunya virus genomes from 12 Brazilian states over the past two years (2021-2022), a period that has seen more than 312 thousand chikungunya fever cases reported in the country. These genomes increased the amount of available data and allowed a more comprehensive characterization of the dispersal dynamics of the chikungunya virus East-Central-South-African lineage in Brazil. Tree branching patterns revealed the emergence and expansion of two distinct subclades. Phylogeographic analysis indicated that the northeast region has been the leading hub of virus spread towards other regions. Increased frequency of C > T transitions among the new genomes suggested that host restriction factors from the immune system such as ADAR and AID/APOBEC deaminases might be driving the genetic diversity of the chikungunya virus in Brazil.

Increased interregional virus exchange and nucleotide diversity outline the expansion of the chikungunya virus ECSA lineage in Brazil.

The emergence and reemergence of mosquito-borne diseases in Brazil such as Yellow Fever, Zika, Chikungunya, and Dengue have had serious impacts on public health. Concerns have been raised due to the rapid dissemination of the chikungunya virus (CHIKV) across the country since its first detection in 2014 in Northeast Brazil. Faced with this scenario, on-site training activities in genomic surveillance carried out in partnership with the National Network of Public Health Laboratories have led to the generation of 422 CHIKV genomes from 12 Brazilian states over the past two years (2021-2022), a period that has seen more than 312 thousand chikungunya fever cases reported in the country. These new genomes increased the amount of available data and allowed a more comprehensive characterization of the dispersion dynamics of the CHIKV East-Central-South-African (ECSA) lineage in Brazil. Tree branching patterns revealed the emergence and expansion of two distinct subclades. Phylogeographic analysis indicated that the northeast region has been the leading hub of virus spread towards other regions. Increased frequency of C>T transitions among the new genomes suggested that host restriction factors from the immune system such as ADAR and AID/APOBEC deaminases might be driving CHIKV ECSA lineage genetic diversity in Brazil.

A Multiplex Nanopore Sequencing Approach for the Detection of Multiple Arboviral Species.

The emergence and continued geographic expansion of arboviruses and the growing number of infected people have highlighted the need to develop and improve multiplex methods for rapid and specific detection of pathogens. Sequencing technologies are promising tools that can help in the laboratory diagnosis of conditions that share common symptoms, such as pathologies caused by emerging arboviruses. In this study, we integrated nanopore sequencing and the advantages of reverse transcription polymerase chain reaction (RT-PCR) to develop a multiplex RT-PCR protocol for the detection of Chikungunya virus (CHIKV) and several orthoflaviviruses (such as dengue (Orthoflavivirus dengue), Zika (Orthoflavivirus zikaense), yellow fever (Orthoflavivirus flavi), and West Nile (Orthoflavivirus nilense) viruses) in a single reaction, which provides data for sequence-based differentiation of arbovirus lineages.

Hepatitis B vaccination coverage and serological status among health care workers exposed to occupational biological hazards.

Introduction: Health care workers are often exposed to hepatitis B infection during the course of their professional roles. Objectives: To analyze the hepatitis B vaccination coverage and the presence of antibodies against hepatitis B among health care professionals who were exposed to contaminated biological material at a hospital complex. Methods: This descriptive, retrospective, and quantitative study is based on the analysis of accident notification form data (n = 2,466) from a hospital complex covering the period between 2011 and 2020. Results: Among the affected individuals, women (69.5%), medical residents (35.7%), and nursing staff (25.5%) accounted for the highest proportion of hazards. Regarding vaccination status, 98% of the health care professionals reported being fully immunized, and antibodies were detected in 90.9% of the participants. Percutaneous exposure (76.4%) was the most prevalent type of hazard, with blood being the most commonly involved material (79.4%). Conclusions: The findings show that despite the risks of Hepatitis B contamination associated with the incidents, the professionals were protected due to the high vaccination coverage and evidence of immunity.

Introdução: Os trabalhadores da saúde estão constantemente expostos ao vírus da hepatite B durante a atividade laboral. Objetivos: Analisar a cobertura vacinal contra a hepatite B e a presença do anticorpo contra o antígeno de superfície da hepatite B (anti-HBs) entre profissionais e estudantes da área da saúde que sofreram acidente com material biológico em um complexo hospitalar universitário. Métodos: Tratou-se de um estudo descritivo, retrospectivo e quantitativo, baseado na análise dos dados das fichas de notificação (n = 2.466) dos acidentes ocorridos no período de 2011 a 2020. Resultados: As mulheres (69,5%), os residentes de medicina (35,7%) e os técnicos e auxiliares de enfermagem (25,5%) foram os que mais se acidentaram. Quanto ao estado vacinal dos trabalhadores de saúde para hepatite B, 98% declararam ter o esquema vacinal completo, e a presença de anti-HBs reagente foi detectada em 90,9%. Quanto às características dos acidentes, houve prevalência de exposição percutânea (76,4%), e sangue foi o material orgânico mais comumente envolvido (79,4%). Conclusões: Os achados demonstram que, apesar do risco de contaminação para o vírus da hepatite B associado a acidentes no ambiente de trabalho, os profissionais estavam protegidos devido à elevada cobertura vacinal e à imunidade comprovada.

Citrus aurantium L. and synephrine improve brown adipose tissue function in adolescent mice programmed by early postnatal overfeeding.

Introduction and aims: Obesity is a multifactorial condition with high health risk, associated with important chronic disorders such as diabetes, dyslipidemia, and cardiovascular dysfunction. Citrus aurantium L. (C. aurantium) is a medicinal plant, and its active component, synephrine, a ß-3 adrenergic agonist, can be used for weight loss. We investigated the effects of C. aurantium and synephrine in obese adolescent mice programmed by early postnatal overfeeding. Methods: Three days after birth, male Swiss mice were divided into a small litter (SL) group (3 pups) and a normal litter (NL) group (9 pups). At 30 days old, SL and NL mice were treated with C. aurantium standardized to 6% synephrine, C. aurantium with 30% synephrine, isolated synephrine, or vehicle for 19 days. Results: The SL group had a higher body weight than the NL group. Heart rate and blood pressure were not elevated. The SL group had hyperleptinemia and central obesity that were normalized by C. aurantium and synephrine. In brown adipose tissue, the SL group showed a higher lipid droplet sectional area, less nuclei, a reduction in thermogenesis markers related to thermogenesis (UCP-1, PRDM16, PGC-1α and PPARg), and mitochondrial disfunction. C. aurantium and synephrine treatment normalized these parameters. Conclusion: Our data indicates that the treatment with C. aurantium and synephrine could be a promising alternative for the control of some obesity dysfunction, such as improvement of brown adipose tissue dysfunction and leptinemia.

Genomic epidemiology reveals the impact of national and international restrictions measures on the SARS-CoV-2 epidemic in Brazil.

Brazil has experienced some of the highest numbers of COVID-19 cases and deaths globally and from May 2021 made Latin America a pandemic epicenter. Although SARS-CoV-2 established sustained transmission in Brazil early in the pandemic, important gaps remain in our understanding of virus transmission dynamics at the national scale. Here, we describe the genomic epidemiology of SARS-CoV-2 using near-full genomes sampled from 27 Brazilian states and a bordering country - Paraguay. We show that the early stage of the pandemic in Brazil was characterised by the co-circulation of multiple viral lineages, linked to multiple importations predominantly from Europe, and subsequently characterized by large local transmission clusters. As the epidemic progressed under an absence of effective restriction measures, there was a local emergence and onward international spread of Variants of Concern (VOC) and Variants Under Monitoring (VUM), including Gamma (P.1) and Zeta (P.2). In addition, we provide a preliminary genomic overview of the epidemic in Paraguay, showing evidence of importation from Brazil. These data reinforce the usefulness and need for the implementation of widespread genomic surveillance in South America as a toolkit for pandemic monitoring that provides a means to follow the real-time spread of emerging SARS-CoV-2 variants with possible implications for public health and immunization strategies.

Consumption of food groups and associated factors among children aged 6 to 23 months.

OBJECTIVE: To assess the consumption of food groups among children aged 6 to 23 months in day care centers and at home and its associated factors. METHODS: This is a population-based cross-sectional study conducted with children from nursery schools in Guaratuba, Paraná. Parents answered a socioeconomic and demographic questionnaire. Food consumption was assessed by directly weighing the meals offered at the day care center. At home, parents filled an estimated food record. The reported foods were classified into seven food groups. Minimum dietary diversity was calculated by the proportion of children who consumed foods from four or more groups. Data were analyzed by simple and multiple logistic regression, presented as odds ratios. RESULTS: A total of 213 children participated in this study. The average number of food groups consumed was 4.2±1.0 at home and 4.2±1.2 in day care centers. At the day care center, all children consumed grains, roots, and tubers, while at home, this rate was 99.1%. The egg group was the least consumed both at day care (6.6%) and at home (2.8%). At home, more than 60% of children consumed sweets and sugar-sweetened beverages. Children aged 12 to 23 months were more likely to consume milk and dairy products, as well as flesh foods. Higher income was associated with the consumption of legumes, and older maternal age with the consumption of fruits and vegetables. CONCLUSIONS: At home, children had a predominantly dairy-based diet and a high intake of ultra-processed foods. In day care centers, the consumption of healthy foods was higher, indicating the need for families to participate in the formation of healthy eating habits.

Late effects of early weaning on food preference and the dopaminergic and endocannabinoid systems in male and female rats.

Early weaning (EW) is associated with obesity later in life. Here, using an EW model in rats, we investigated changes in feeding behavior and the dopaminergic and endocannabinoid systems (ECS) in the adult offspring. Lactating Wistar rats were divided into two groups: EW, dams were wrapped with a bandage to interrupt suckling during the last 3 days of breastfeeding; CONT; dams fed the pups throughout the period without hindrances. EW animals were compared with CONT animals of the same sex. At PN175, male and female offspring of both groups could freely self-select between high-fat and high-sugar diets (food challenge test). EW males preferred the high-fat diet at 30 min and more of the high-sugar diet after 12 h compared to CONT males. EW females did not show differences in their preference for the palatable diets compared to CONT females. Total intake of standard diet from PN30-PN180 was higher in both male and female EW animals, indicating hyperphagia. At PN180, EW males showed lower type 2 dopamine receptor (D2r) in the nucleus accumbens (NAc) and dorsal striatum, while EW females had lower tyrosine hydroxylase in the ventral tegmental area and NAc, D1r in the NAc, and D2r in the prefrontal cortex. In the lateral hypothalamus, EW males had lower fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase, whereas EW females showed lower N-arachidonoyl-phosphatidylethanolamine phospholipase-D and increased FAAH. Early weaning altered both the dopaminergic and ECS parameters at adulthood, contributing to the eating behavior changes of the progeny in a sex-dependent manner.

Humoral response to spike S1 and S2 and nucleocapsid proteins on microarray after SARS-CoV-2 infection.

Many aspects of the humoral immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), such as its role in protection after natural infection, are still unclear. We evaluated IgA and IgG response to spike subunits 1 and 2 (S1 and S2) and Nucleocapsid proteins of SARS-COV-2 in serum samples of 109 volunteers with viral RNA detected or seroconversion with different clinical evolution (asymptomatic, mild, moderate, and severe coronavirus disease 2019), using the ViraChip® Test Kit. We observed that the quantification of antibodies to all antigens had a positive correlation to disease severity, which was strongly associated with the presence of comorbidities. Seroreversion was not uncommon even during the short (median of 77 days) observation, occurring in 15% of mild-asymptomatic cases at a median of 55 days for IgG and 46 days for IgA. The time to reach the maximal antibody response did not differ significantly among recovered and deceased volunteers. Our study illustrated the dynamic of anti-S1, anti-N, and anti-S2 IgA and IgG antibodies, and suggests that high production of IgG and IgA does not guarantee protection to disease severity and that functional responses that have been studied by other groups, such as antibody avidity, need further attention.

Inhibition of receptor-binding domain-ACE2 interaction after two doses of Sinovac's CoronaVac or AstraZeneca/Oxford's AZD1222 SARS-CoV-2 vaccines.

Practical laboratory proxies that correlate to vaccine efficacy may facilitate trials, identify nonresponders, and inform about boosting strategies. Among clinical and laboratory markers, assays that evaluate antibodies that inhibit receptor-binding domain (RBD) ligation to angiotensin-converting enzyme-2 receptor (receptor-binding inhibition [RBI]) may provide a surrogate for viral neutralization assays. We evaluated RBI before and after a median of 34 days (interquartile range [IQR]: 33-40) of the second dose of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Sinovac's CoronaVac (CN) or AstraZeneca/Oxford's AZD1222 (AZ) vaccines in 166 individuals. Both vaccines elicited high inhibitory titers in most subjects, 95% (158/166), with signal inhibition above 30% and 89% (127/143) with more than fourfold increase from prevaccination titers, but titers tend to decrease over time. Both postvaccination inhibitory titers (95%, IQR 85%-97% for AZ vs. 79%, IQR 60%-96% for CN, p = 0.004) and pre/post-titer increase (AZ 76%, IQR 51%-86% for AZ vs. 47%, IQR 24%-67% for CN, p < 0.0001) were higher among AZ vaccinees. Previous serological reactivity due to natural infection was associated with high prevaccination signal inhibition titers. The study documents a robust antibody response capable of interfering with RBD-angiotensin-converting enzyme binding. Evaluation of SARS-CoV-2 infection incidence in these populations is necessary to assess its association to protection and its duration.

Humanization of care for adult ICU patients: a scoping review protocol.

OBJECTIVE: The objective of this review is to review and map data from studies on the humanization of care in intensive care units based on a conceptual framework. INTRODUCTION: The critical context of adult patients in intensive care units directs the focus on clinical medical interventions, drawing attention away from the humanization of care. Rethinking intensive care is imperative and the humanization of care is an absolute priority. Literature on this topic is scattered under umbrella terms such as "patient-centered care" or specific terms referring to target interventions. A scoping review based on a conceptual framework will map the literature on humanization in intensive care units. INCLUSION CRITERIA: The review will consider studies on the humanization of care, or on one of the seven components of the conceptual framework (communication, visiting hours, patients' and health care professionals' well-being, family involvement and satisfaction, post-intensive care unit syndrome, and physical environment) focusing on adult patients in intensive care units. Studies on co-existing states or end-of-life care will be excluded. METHODS: A search of Embase, PubMed, and CINAHL will be conducted to identify relevant studies in English or French on the humanization of care, holistic care, or person-centered care in an adult intensive-care environment. The time period covered will be January 1, 2010 to the present. An iterative team approach will be used to screen and select studies and extract data. Data will be charted according to study design, distribution in time, cultural context, concepts, use of theoretical models, and intervention. The results will be summarized and reported, identifying the implications for policy, practice, and research.

Neonatal nicotine exposure changes insulin status in fat depots: sex-related differences.

Nicotine is the main psychoactive substance present in cigarette smoke that is transferred to the baby by breast milk. In rats, maternal nicotine exposure during breastfeeding induces obesogenesis and hormone dysfunctions in adult male offspring. As glucocorticoid (GC), insulin, and vitamin D change both adipogenesis and lipogenesis processes, we assessed parameters related to metabolism and action of these hormones in visceral and subcutaneous adipose tissues (VAT and SAT) of adult male and female rats in a model of neonatal nicotine exposure. At postnatal (PN) day 2, dams were kept with six pups (three per sex) and divided into nicotine and control groups for implantation of osmotic minipumps that released 6 mg/kg nicotine or saline, respectively. At PN180, fat mass, hormone levels, and protein contents of biomarkers of the GC activation and receptor (11beta-hydroxysteroid dehydrogenase type 1 and glucocorticoid receptor alpha), insulin signaling pathway [insulin receptor beta (IRß), phosphorylated insulin receptor substrate 1, insulin receptor substrate 1 (IRS1), phosphorylated serine/threonine kinase (pAKT), serine/threonine kinase, glucose transporter type 4 (GLUT4)], and vitamin D activation and receptor (1α-hydroxylase and vitamin D receptor) were evaluated. While nicotine-exposed males showed increased fat mass, hypercorticosteronemia, hyperinsulinemia, and higher 25-hydroxyvitamin D, these alterations were not observed in nicotine-exposed females. Nicotine-exposed males only showed lower IRS1 in VAT, while the females had hyperglycemia, higher pAKT in VAT, while lower IRß, IRS1, and GLUT4 in SAT. Parameters related to metabolism and action of GC and vitamin D were unaltered in both sexes. We evidence that exposure exclusively to nicotine during breastfeeding affects the hormone status and fat depots of the adult progeny in a sex-dependent manner.

Anti-Inflammatory Potential of the Oleoresin from the Amazonian Tree Copaifera reticulata with an Unusual Chemical Composition in Rats.

Copaifera reticulata Ducke is a popularly known species known as copaíba that is widely spread throughout the Amazon region. The tree yields an oleoresin which is extensively used in local traditional medicine mainly as an anti-inflammatory and antinociceptive agent. The aim of the present study was to assess the anti-inflammatory potential of this oleoresin obtained from a national forest in the central Amazon which presented an unusual chemical composition. The chemical composition of volatile compounds of oleoresin was analyzed by gas chromatography-mass spectrometry. The acute toxicity assay was performed with a single dose of 2000 mg/kg. The anti-inflammatory potential was evaluated by carrageenan-induced paw edema and air pouch assays using four different C. reticulata oleoresin concentrations (10, 100, and 400 mg/kg). The exudate was evaluated for nitrite concentration through the colorimetric method and for TNF-α, IL-1ß, and PGE2 by ELISA. C. reticulata oleoresin collected in the Amazonian summer contained six major sesquiterpene compounds (ß-bisabolene, cis-eudesma-6,11-diene, trans-α-bergamotene, ß-selinene, α-selinene, and ß-elemene) and was nontoxic at a dose of 2000 mg/kg, showing low acute toxicity. Different from oleoresin obtained from other sites of the Brazilian Amazon, the major volatile compound found was ß-Bisabolene with 25.15%. This ß-Bisabolene-rich oleoresin reduced the formation of paw edema induced by carrageenan and reduced the global number of cells in the air pouch assay, as well as exudate volume and nitrite, TNF-α, IL-1ß, and prostaglandin E2 levels (p < 0.05). C. reticulata oleoresin with a high ß-Bisabolene concentration showed anti-inflammatory activity, reducing vascular permeability and consequently edema formation, and thus reducing cell migration and the production of inflammatory cytokine, confirming its traditional use by local Amazonian communities.

DC-SIGN Mediates the Interaction Between Neutrophils and Leishmania amazonensis-Infected Dendritic Cells to Promote DC Maturation and Parasite Elimination.

Background: Leishmaniasis is a neglected arthropod-borne disease that affects millions of people worldwide. Successful Leishmania infections require the mitigation of immune cell functions leading to parasite survival and proliferation. A large body of evidence highlights the involvement of neutrophils (PMNs) and dendritic cells (DCs) in the establishment of immunological responses against these parasites. However, few studies, contemplate to what extent these cells interact synergistically to constrain Leishmania infection. Objective: We sought to investigate how PMNs and infected DCs interact in an in vitro model of Leishmania amazonensis infection. Material and Methods: Briefly, human PMNs and DCs were purified from the peripheral blood of healthy donors. Next, PMNs were activated with fibronectin and subsequently co-cultured with L. amazonensis-infected DCs. Results: We observed that L. amazonensis-infected DC exhibited lower rates of infection when co-cultivated with either resting or activated PMNs. Surprisingly, we found that the release of neutrophil enzymes was not involved in Leishmania killing. Next, we showed that the interaction between PMNs and infected-DCs was intermediated by DC-SIGN, further suggesting that parasite elimination occurs in a contact-dependent manner. Furthermore, we also observed that TNFα and ROS production was dependent on DC-SIGN-mediated contact, as well as parasite elimination is dependent on TNFα production in the co-culture. Finally, we observed that direct contact between PMNs and DCs are required to restore the expression of DC maturation molecules during L. amazonensis infection. Conclusion: Our findings suggest that the engagement of direct contact between PMNs and L. amazonensis-infected DC via DC-SIGN is required for the production of inflammatory mediators with subsequent parasite elimination and DC maturation.

Use of naproxen versus intracervical block for pain control during the 52-mg levonorgestrel-releasing intrauterine system insertion in young women: a multivariate analysis of a randomized controlled trial.

BACKGROUND: To compare the effectiveness of 550 mg naproxen sodium versus 6 mL 2%-lidocaine intracervical block in pain lowering at the 52-mg levonorgestrel-releasing intrauterine system (LNG-IUS) placement in young women. METHODS: In this randomized controlled trial, 100 women aged 15-24 years were block-randomized to receive either 6 mL 2%-lidocaine intracervical block 5 min before the LNG-IUS insertion or 550 mg naproxen 30 min before the procedure. Forty-nine women received 550 mg naproxen and 51 received intracervical block. The primary outcome was pain at LNG-IUS insertion. Secondary outcomes were ease of insertion, insertion failures, and correct IUS positioning. Neither participants nor doctors were blinded. Pain at insertion was assessed by using a Visual Analog Scale (VAS). RESULTS: Women randomized to lidocaine intracervical block presented lower mean pain score at insertion, when compared to women who received naproxen (5.4 vs. 7.3, respectively; p < 0.001). Parous women had a 90.1% lower chance of experiencing severe pain (p = 0.004). There was a 49.8% reduction in the chance of severe pain for every 1-cm increase in the hysterometry (p = 0.002). The only complication observed during insertion was vasovagal-like reactions (7%). The insertion was performed without difficulty in 82% of the women. Participants in the intracervical block group presented higher proportion of malpositioned IUS on transvaginal ultrasound examination compared to women in naproxen group. Nevertheless, all the malpositioned IUS were inserted by resident physicians. CONCLUSION: Lidocaine intracervical block was found to be more effective than naproxen in reducing LNG-IUS insertion pain. TRIAL REGISTRATION NUMBER: RBR-68mmbp, Brazilian Registry of Clinical Trials, Retrospectively registered (August 4, 2020), URL of trial registry record: https://ensaiosclinicos.gov.br/rg/RBR-68mmbp/ .