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Due to the limitations of Chagas disease therapy, microalgae can be promising in the search of new trypanocidal compounds, since these organisms produce bioactive compounds with large pharmaceutical applications, including antiparasitic effects. In this work, trypanocidal activity of aqueous extract of Tetradesmus obliquus and, for the first time, aqueous extract of Chlorella vulgaris, were evaluated against trypomastigote forms of Trypanosoma cruzi . In addition, cytotoxic activity in Vero cells was evaluated. Our results showed that C. vulgaris and T. obliquus present trypanocidal activity (IC 50 = 32.9 µg ml -1 and 36.4 µg ml -1 , respectively), however, C. vulgaris did not present cytotoxic effects in Vero cells (CC 50 > 600 µg ml -1 ) and displayed a higher selectivity against trypomastigotes forms of T. cruzi (SI > 18). Thus, microalgae extracts, such as aqueous extract of C. vulgaris , are promising potential candidates for the development of natural antichagasic drugs.

Trypanosoma cruzi is a parasite with a high capacity to adapt to the host. Animal models have already demonstrated that the tropism of this parasite occurs not only in cardiac/digestive tissues but also in adipose tissue (AT). That said, the consequences ofT. cruziinfection for AT and the implications of treatment with Benzonidazole in this tissue are under discussion. Here, we tested the hypothesis that T. cruzi infection in adipose tissue upon treatment with Benzonidazole (Bz) and the interaction of mononuclear immune cells (PBMC) influences the relative expression of ACAT1, FASN, and PNPLA2 genes. Thus, stem cells derived from adipose tissue (ADSC) after adipogenic differentiation were indirectly cultivated with PBMC after infection with the T. cruzi Y strain and treatment with Bz. We use the TcSAT-IAM system and RT-qPCR to evaluate the parasite load and the relative quantification (ΔCt) of the ACAT1, FASN, and PNPLA2 genes. Our results demonstrate that treatment with Bz did not reduce adipocyte infection in the presence (p-value: 0.5796) or absence (p-value: 0.1854) of cultivation with PBMC. In addition, even though there is no statistical difference when compared to the control group (AT), T. cruzi induces the FASN expression (Rq: 14.00). However, treatment with Bz in AT suggests the increases of PNPLA2 expression levels (Rq: 12.58), even in the absence of T. cruzi infection. During indirect cultivation with PBMC, T. cruzi smooths the expression of PNPLA2 (Rq: 0.824) and instigates the expression of ACAT1 (Rq: 1.632) and FASN (Rq: 1.394). Furthermore, the treatment with Bz during infection induces PNPLA2 expression (Rq: 1.871), maintaining FASN expression levels (Rq: 1.334). Given this, our results indicate that treatment with Benzonidazole did not decrease T. cruzi infection in adipose tissue. However, treating the adipocyte cells with Bz during the interaction with PBMC cells influences the lipid pathways scenario, inducing lipolytic metabolism through the expression of PNPLA2., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Enhancing the design of family planning interventions is crucial for promoting gender equality and improving maternal and child health outcomes. We identified, critically appraised, and synthesized policies and strategies from five selected countries that successfully increased family planning coverage., Methods: We conducted a policy analysis through a scoping review and document search, focusing on documents published from 1950 to 2023 that examined or assessed policies aimed at enhancing family planning coverage in Brazil, Ecuador, Egypt, Ethiopia, and Rwanda. A search was conducted through PubMed, SCOPUS, and Web of Science. Government documents and conference proceedings were also critically analyzed. National health surveys were analyzed to estimate time trends in demand for family planning satisfied by modern methods (mDFPS) at the national level and by wealth. Changes in the method mix were also assessed. The findings of the studies were presented in a narrative synthesis., Findings: We selected 231 studies, in which 196 policies were identified. All countries started to endorse family planning in the 1960s, with the number of identified policies ranging between 21 in Ecuador and 52 in Ethiopia. Most of the policies exclusively targeted women and were related to supplying contraceptives and enhancing the quality of the services. Little focus was found on monitoring and evaluation of the policies implemented., Conclusion: Among the five selected countries, a multitude of actions were happening simultaneously, each with its own vigor and enthusiasm. Our findings highlight that these five countries were successful in increasing family planning coverage by implementing broader multi-sectoral policies and considering the diverse needs of the population, as well as the specific contextual factors at play. Successful policies require a nuanced consideration of how these policies align with each culture's framework, recognizing that both sociocultural norms and the impact of past public policies shape the current state of family planning., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Hellwig, Moreira, Silveira, Vieira, Rios-Quituizaca, Masabanda, Serucaca, Rudasingwa, Nyandwi, Mulu, Rashad and Barros.)

Vocal production learning ("vocal learning") is a convergently evolved trait in vertebrates. To identify brain genomic elements associated with mammalian vocal learning, we integrated genomic, anatomical, and neurophysiological data from the Egyptian fruit bat ( Rousettus aegyptiacus ) with analyses of the genomes of 215 placental mammals. First, we identified a set of proteins evolving more slowly in vocal learners. Then, we discovered a vocal motor cortical region in the Egyptian fruit bat, an emergent vocal learner, and leveraged that knowledge to identify active cis-regulatory elements in the motor cortex of vocal learners. Machine learning methods applied to motor cortex open chromatin revealed 50 enhancers robustly associated with vocal learning whose activity tended to be lower in vocal learners. Our research implicates convergent losses of motor cortex regulatory elements in mammalian vocal learning evolution.

Background/introduction: Adipose tissue (AT) has been highlighted as a promising reservoir of infection for viruses, bacteria and parasites. Among them is Trypanosoma cruzi , which causes Chagas disease. The recommended treatment for the disease in Brazil is Benznidazole (BZ). However, its efficacy may vary according to the stage of the disease, geographical origin, age, immune background of the host and sensitivity of the strains to the drug. In this context, AT may act as an ally for the parasite survival and persistence in the host and a barrier for BZ action. Therefore, we investigated the immunomodulation of T. cruzi-infected human AT in the presence of peripheral blood mononuclear cells (PBMC) where BZ treatment was added., Methods: We performed indirect cultivation between T. cruzi-infected adipocytes, PBMC and the addition of BZ. After 72h of treatment, the supernatant was collected for cytokine, chemokine and adipokine assay. Infected adipocytes were removed to quantify T. cruzi DNA, and PBMC were removed for immunophenotyping., Results: Our findings showed elevated secretion of interleukin (IL)-6, IL-2 and monocyte chemoattractant protein-1 (MCP-1/CCL2) in the AT+PBMC condition compared to the other controls. In contrast, there was a decrease in tumor necrosis factor (TNF) and IL-8/CXCL-8 in the groups with AT. We also found high adipsin secretion in PBMC+AT+T compared to the treated condition (PBMC+AT+T+BZ). Likewise, the expression of CD80+ and HLA-DR+ in CD14+ cells decreased in the presence of T. cruzi., Discussion: Thus, our findings indicate that AT promotes up-regulation of inflammatory products such as IL-6, IL-2, and MCP-1/CCL2. However, adipogenic inducers may have triggered the downregulation of TNF and IL-8/CXCL8 through the peroxisome proliferator agonist gamma (PPAR-g) or receptor expression. On the other hand, the administration of BZ only managed to reduce inflammation in the microenvironment by decreasing adipsin in the infected culture conditions. Therefore, given the findings, we can see that AT is an ally of the parasite in evading the host's immune response and the pharmacological action of BZ., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Moreira, Silva, Costa-Oliveira, Silva-Júnior, Oliveira, Torres, Barros, Rabello and de Lorena.)

Introduction: Permanent liquor diversion is associated with a high risk of failure and often requires re-intervention. The ventriculo-gallbladder shunt (VGS) has been recognized as a last-resort alternative for treating hydrocephalus when the peritoneum or other distal sites are no longer suitable for receiving shunts. This article aims to report a case from a neurosurgery referral service in Brazil and review the literature on this issue., Methods: A systematic literature review was conducted in accordance with the PRISMA statement. The PubMed, Embase, and Web of Science databases were searched for data screening and extraction. The reported case was conducted with ethical approval from the neurosurgical hospital's ethics committee., Results: G.B.S, male, 43 years old, no comorbidities, who has been dealing with a 12-year history of hydrocephalus, with post-surgical chronic fungal meningitis. Two years ago, he underwent a ventriculoatrial shunt (VAS) placement due to multiple ventriculoperitoneal shunt (VPS) failures. Endocarditis was suspected, and the VAS was removed. As an alternative, VGS was implanted 6 months ago, and since then, there has been no need for a new system review. The gallbladder has an absorptive capacity of 1500 cc of liquid daily, which is more than the normal daily production of cerebrospinal fluid (CSF). Therefore, it is a good alternative when the ventriculoperitoneal shunt is not feasible due to postsurgical peritoneal adhesions or when there are contraindications for ventriculoatrial shunts., Conclusion: VGS is an alternative for patients who cannot undergo the most common surgical interventions, such as VPS., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Studies involving the immune response in Chagas disease suggest an imbalance in the immune response of symptomatic patients, with an inflammatory profile dominating in Chagas heart disease, mainly by tumour necrosis factor (TNF). TNF is considered a key cytokine in immunopathology in chronic carriers in several processes during the immune response. Our work aimed to evaluate regulatory (interleukin [IL]-4 and IL-10) and inflammatory (TNF, interferon-gamma [IFN-γ], IL-2 and IL-6) cytokines in peripheral blood mononuclear cells culture supernatants. of affected patients with undetermined clinical forms-IND (n = 13) mild heart form-CARD1 (n = 13) and severe cardiac form-CARD2 (n = 16), treated in vitro with two TNF blockers, Adalimumab (ADA) and Etanercept (ETA) alone or in association with Benznidazole (BZ). The results indicate that ADA was more competent in blocking TNF (compared to ETA) in all groups but with much lower levels in the CARD2 group. ETA statistically decreased TNF levels only in the CARD2 group. IFN-γ increased in the CARD2 group after treatment with ETA relative to ADA. IL-4 had its levels decreased when treated by both drugs. IL-2 was detected in cells from CARD2 carriers compared to the NEG group after treatment with both drugs. The association with BZ decreased levels of IL-2/TNF and increased IL-4. These data reinforce the participation of TNF in severe Chagas heart disease and bring perspectives on using these blockers in the immunological treatment of Chagas disease since the use of BZ is extremely limited in these patients., (© 2024 John Wiley & Sons Ltd.)

Geographic barriers are frequently invoked to explain genetic structuring across the landscape. However, inferences on the spatial and temporal origins of population variation have been largely limited to evolutionary neutral models, ignoring the potential role of natural selection and intrinsic genomic processes known as genomic architecture in producing heterogeneity in differentiation across the genome. To test how variation in genomic characteristics (e.g. recombination rate) impacts our ability to reconstruct general patterns of differentiation between species that cooccur across geographic barriers, we sequenced the whole genomes of multiple bird populations that are distributed across rivers in southeastern Amazonia. We found that phylogenetic relationships within species and demographic parameters varied across the genome in predictable ways. Genetic diversity was positively associated with recombination rate and negatively associated with species tree support. Gene flow was less pervasive in genomic regions of low recombination, making these windows more likely to retain patterns of population structuring that matched the species tree. We further found that approximately a third of the genome showed evidence of selective sweeps and linked selection, skewing genome-wide estimates of effective population sizes and gene flow between populations toward lower values. In sum, we showed that the effects of intrinsic genomic characteristics and selection can be disentangled from neutral processes to elucidate spatial patterns of population differentiation., Competing Interests: Conflict of Interest None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for Molecular Biology and Evolution.)

Cerebrospinal fluid (CSF) is a clear, transparent fluid derived from blood plasma that protects the brain and spinal cord against mechanical shock, provides buoyancy, clears metabolic waste and transports extracellular components to remote sites in the brain. Given its contact with the brain and the spinal cord, CSF is the most informative biofluid for studies of the central nervous system (CNS). In addition to other components, CSF contains extracellular vesicles (EVs) that carry bioactive cargoes (e.g., lipids, nucleic acids, proteins), and that can have biological functions within and beyond the CNS. Thus, CSF EVs likely serve as both mediators of and contributors to communication in the CNS. Accordingly, their potential as biomarkers for CNS diseases has stimulated much excitement for and attention to CSF EV research. However, studies on CSF EVs present unique challenges relative to EV studies in other biofluids, including the invasive nature of CSF collection, limited CSF volumes and the low numbers of EVs in CSF as compared to plasma. Here, the objectives of the International Society for Extracellular Vesicles CSF Task Force are to promote the reproducibility of CSF EV studies by providing current reporting and best practices, and recommendations and reporting guidelines, for CSF EV studies. To accomplish this, we created and distributed a world-wide survey to ISEV members to assess methods considered 'best practices' for CSF EVs, then performed a detailed literature review for CSF EV publications that was used to curate methods and resources. Based on responses to the survey and curated information from publications, the CSF Task Force herein provides recommendations and reporting guidelines to promote the reproducibility of CSF EV studies in seven domains: (i) CSF Collection, Processing, and Storage; (ii) CSF EV Separation/Concentration; (iii) CSF EV Size and Number Measurements; (iv) CSF EV Protein Studies; (v) CSF EV RNA Studies; (vi) CSF EV Omics Studies and (vii) CSF EV Functional Studies., (© 2023 The Authors. Journal of Extracellular Vesicles published by Wiley Periodicals LLC on behalf of International Society for Extracellular Vesicles.)

Objective: To investigate how tibial long axis (TLA) shift affects the postoperative tibial plateau angle (TPA) in four cranial closing wedge ostectomy (CCWO) techniques., Study Design: In silico study., Sample Population: A total of 15 client-owned dogs., Methods: Computed tomography (CT) scans of 15 client-owned dogs were reviewed using an open-source 3D computer graphics editor. Each computer-generated 3D tibia model underwent a CCWO, with cranial cortex alignment, in 10° increments up to 70° using each of the four previously described techniques. The TLA shift, TPA and mechanical tibial length (mTL) were calculated, using trigonometry, for each model. Equations for predicting final TPA were generated with linear regression., Results: A total of 433 3D computer generated tibial models were analyzed. With each technique, the TPA varied in a linear fashion within the studied range of wedge angles. The TLA shift and tibial shortening magnitude varied between the four different CCWO techniques, with maximum mTL reduction of ranging from 7.5% to 40.9%. All predicted TPAs using the generated equations were within the target range of 4-6°., Conclusion: A linear relationship between ostectomy wedge angle and TPA correction was observed in this study, which allowed for generation of accurate corrective equations., Clinical Significance: These results allow extrapolation of the wedge angle required to reach a postoperative TPA of 5°, by considering the TLA shift. The use of the generated corrective equations may thus increase CCWO planning precision., (© 2023 The Authors. Veterinary Surgery published by Wiley Periodicals LLC on behalf of American College of Veterinary Surgeons.)

Background: Trypanosoma cruzi, which causes Chagas disease (CD), is a versatile haemoparasite that uses several strategies to evade the host's immune response, including adipose tissue (AT), used as a reservoir of infection. As it is an effective barrier to parasite evasion, the effectiveness of the drug recommended for treating CD, Benznidazole (BZ), may be questionable., Objective: To this end, we evaluated the parasite load and immunomodulation caused by BZ treatment in the culture of adipocytes differentiated from human adipose tissue-derived stem cells (ADSC) infected with T. cruzi., Methods: The ADSC were subjected to adipogenic differentiation. We then carried out four cultures in which we infected the differentiated AT with trypomastigote forms of the Y strain of T. cruzi and treated them with BZ. After the incubation, the infected AT was subjected to quantitative polymerase chain reaction (qPCR) to quantify the parasite load and transmission electron microscopy (TEM) to verify the infection. The supernatant was collected to measure cytokines, chemokines, and adipokines., Findings: We found elevated secretion of IL-6, CXCL-10/IP-10, CCL2/MCP-1, CCL5/RANTES, and leptin in infected fat cells. However, treatment with BZ promoted a decrease in IL-6., Main Conclusion: Therefore, we believe that BZ has a beneficial role as it reduces inflammation in infected fat cells.

American trypanosomiasis, or Chagas disease, is caused by the protozoan parasite Trypanosoma cruzi and is characterized by the presence of cardiac or gastrointestinal symptoms in a large number of patients during the chronic phase of the disease. Although the origin of the symptoms is not clear, several mechanisms have been described involving factors related to T. cruzi and the host immune response. In this sense, the extracellular vesicles (EVs) secreted by the parasite and the immune complexes (ICs) formed after their recognition by host IgGs (EVs-IgGs) may play an important role in the immune response during infection. The aim of the present work is to elucidate the modulation of the immune response exerted by EVs and the ICs they form by analyzing the variation in the subpopulations of small and large peritoneal macrophages after intraperitoneal inoculation in mice and to evaluate the role of the sialylation of the host IgGs in this immunomodulation. Both macrophage subpopulations were purified and subjected to cytokine expression analysis by RT-qPCR. The results showed an increase in the small peritoneal macrophage subpopulation after intraperitoneal injection of parasite EVs, but a greater increase in this subpopulation was observed when sialylated and non-sialylated ICs were injected, which was similar to inoculation with the trypomastigote stage of the parasite. The cytokine expression results showed the ability of both subpopulations to express inflammatory and non-inflammatory cytokines. These results suggest the role of free EVs in the acute phase of the disease and the possible role of immune complexes in the immune response in the chronic phase of the disease, when the levels of antibodies against the parasite allow the formation of immune complexes. The differential expression of interleukins showed after the inoculation of immune complexes formed with sialylated and non-sialylated IgGs and the interleukins expression induced by EVs, demonstrates that the IgG glycosilation is involved in the type of immune response that dominates in each of the phases of the Chagas disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Cornet-Gomez, Moreira, Gomez-Samblás and Osuna.)

Convergent local adaptation offers a glimpse into the role of constraint and stochasticity in adaptive evolution, in particular the extent to which similar genetic mechanisms drive adaptation to common selective forces. Here, we investigated the genomics of local adaptation in two nonsister woodpeckers that are codistributed across an entire continent and exhibit remarkably convergent patterns of geographic variation. We sequenced the genomes of 140 individuals of Downy ( Dryobates pubescens ) and Hairy ( Dryobates villosus ) woodpeckers and used a suite of genomic approaches to identify loci under selection. We showed evidence that convergent genes have been targeted by selection in response to shared environmental pressures, such as temperature and precipitation. Among candidates, we found multiple genes putatively linked to key phenotypic adaptations to climate, including differences in body size (e.g., IGFPB ) and plumage (e.g., MREG ). These results are consistent with genetic constraints limiting the pathways of adaptation to broad climatic gradients, even after genetic backgrounds diverge.

Zoonomia is the largest comparative genomics resource for mammals produced to date. By aligning genomes for 240 species, we identify bases that, when mutated, are likely to affect fitness and alter disease risk. At least 332 million bases (~10.7%) in the human genome are unusually conserved across species (evolutionarily constrained) relative to neutrally evolving repeats, and 4552 ultraconserved elements are nearly perfectly conserved. Of 101 million significantly constrained single bases, 80% are outside protein-coding exons and half have no functional annotations in the Encyclopedia of DNA Elements (ENCODE) resource. Changes in genes and regulatory elements are associated with exceptional mammalian traits, such as hibernation, that could inform therapeutic development. Earth's vast and imperiled biodiversity offers distinctive power for identifying genetic variants that affect genome function and organismal phenotypes.

Chagas disease (CD), caused by the protozoan Trypanosoma cruzi (T. cruzi), affects millions of people worldwide. Polymerase Chain Reaction (PCR) and real-time quantitative PCR (qPCR) have been used as tools to monitor parasitic levels in the bloodstream of individuals exposed to infection, thus enabling the monitoring of relapses and the effectiveness of therapy, for example. The aim of this study was to evaluate the TcSAT-IAM system, developed by our research group, on samples from patients with suspected Chagas disease infection. Initially, primer systems were developed for the detection of the nuclear DNA (SAT-DNA) from T. cruzi (TcSAT-IAM). The Cruzi system, predicted in the literature, and TcSAT-IAM were then evaluated in relation to their analytical sensitivity, specificity and efficiency. Afterwards, the applicability of the qPCR technique using both systems (separately) for the diagnosis of acute CD was evaluated in samples from 77 individuals exposed to the outbreak that occurred in Pernambuco-Brazil, relating the results obtained to those of the classical diagnostic methods recommended for this stage of the infection. TcSAT-IAM and Cruzi had a detection limit of 1 fg of target DNA (0,003 parasites). Thirty-eight cases were recorded, 28 by laboratory criteria and 10 by clinical and epidemiological criteria. Blood samples from 77 subjects were submitted to qPCR by both systems, reaching an agreement of 89.61% between them. After analyzes between systems and diagnostic criteria, the TcSAT-IAM showed sensitivity and specificity of 52.36% (CI 37.26-67.52) and 92.31% (CI 79.68-97.35), respectively, accuracy of 72.73% and moderate agreement. The TcSAT-IAM showed an accuracy of 72.58% and 75% in relation to parasitological and serological tests (IgM anti-T. cruzi), respectively. Therefore, quantitative PCR should be incorporated into the diagnosis of suspected acute cases of Chagas disease., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

The influence of genetic drift on population dynamics during Pleistocene glacial cycles is well understood, but the role of selection in shaping patterns of genomic variation during these events is less explored. We resequenced whole genomes to investigate how demography and natural selection interact to generate the genomic landscapes of Downy and Hairy Woodpecker, species codistributed in previously glaciated North America. First, we explored the spatial and temporal patterns of genomic diversity produced by neutral evolution. Next, we tested (i) whether levels of nucleotide diversity along the genome are correlated with intrinsic genomic properties, such as recombination rate and gene density, and (ii) whether different demographic trajectories impacted the efficacy of selection. Our results revealed cycles of bottleneck and expansion, and genetic structure associated with glacial refugia. Nucleotide diversity varied widely along the genome, but this variation was highly correlated between the species, suggesting the presence of conserved genomic features. In both taxa, nucleotide diversity was positively correlated with recombination rate and negatively correlated with gene density, suggesting that linked selection played a role in reducing diversity. Despite strong fluctuations in effective population size, the maintenance of relatively large populations during glaciations may have facilitated selection. Under these conditions, we found evidence that the individual demographic trajectory of populations modulated linked selection, with purifying selection being more efficient in removing deleterious alleles in large populations. These results highlight that while genome-wide variation reflects the expected signature of demographic change during climatic perturbations, the interaction of multiple processes produces a predictable and highly heterogeneous genomic landscape., (© 2023 John Wiley & Sons Ltd.)

Background: Despite international efforts to improve reproductive health indicators, little attention is paid to the contributions of contextual factors to modern contraceptive coverage, especially in the Latin America and the Caribbean (LAC) region. This study aimed to identify the association between country-level Gender Inequality and Health Expenditure with demand for family planning satisfied by modern contraceptive methods (DFPSm) in Latin American sexually active women., Methods: Our analyses included data from the most recent (post-2010) Demographic and Health Survey or Multiple Indicator Cluster Survey from 14 LAC countries. Descriptive analyses and multilevel logistic regressions were performed. Six individual-level factors were included. The effect of the country-level factors Gender Inequality Index (GII) and Current Health Expenditure on DFPSm was investigated., Findings: DFPSm ranged from 41.8% (95% CI: 40.2-43.5) in Haiti to 85.6% (95% CI: 84.9-86.3) in Colombia, with an overall median coverage of 77.8%. A direct association between the odds of DFPSm and woman's education, wealth index, and the number of children was identified. Women from countries in the highest GII tertile were less likely (OR: 0.32, 95% CI: 0.13-0.76) to have DFPSm than those living in countries in the lowest tertile., Interpretation: Understanding the contribution of country-level factors to modern contraception may allow macro-level actions focused on the population's reproductive needs. In this sense, country-level gender inequalities play an important role, as well as individual factors such as wealth and education., Funding: Bill and Melinda Gates Foundation and Associação Brasileira de Saúde Coletiva (ABRASCO)., Competing Interests: The authors declare no conflict of interest. RGPL, who is a staff member of the Pan American Health Organization, hold sole responsibility for the views expressed in their texts, which may not necessarily reflect the opinion or policy of the Pan American Health Organization., (© 2023 The Author(s).)

Soluble TNF receptors (sTNFR1 and sTNFR2) are natural endogenous inhibitors of TNF and are elevated in inflammatory, autoimmune, and chronic degenerative diseases. In Chagas disease, pleiotropic cytokine TNF is considered key in immunopathology. Thus, we aimed to evaluate the levels of TNF, sTNFR1, and sTNFR2 in the serum of patients with chronic Chagas disease. TNF and its soluble receptors were quantified using Cytometric Bead Array in the serum of 132 patients, of which 51 had the indeterminate form (IND), 39 the mild cardiac form (CARD 1), 42 the severe cardiac form (CARD 2), and 20 non-infected individuals (NI). The results indicate that the soluble receptors may regulate TNF in Chagas disease, as their leves were higher in T. cruzi-infected individuals when compared to non-infected individuals. We found a moderate negative correlation between sTNFR1 and TNF in individuals with the IND form, suggesting a relationship with non-progression to more severe forms, such as heart disease. sTNFR1 and sTNFR2 were increased in all clinical forms, but with a moderate positive correlation in more severe patients (r = 0.50 and p = 0.0005). TNF levels showed no statistical differences in the groups of patients. These findings suggest the importance of the endogenous balance of the levels of soluble TNF receptors in the protection and balance in patients with chronic Chagas disease, besides revealing the immunological complexity in chronic T. cruzi-infected individuals., (Copyright © 2021. Published by Elsevier GmbH.)

Monitoring trends of contraceptive use and identifying the groups with less coverage are needed to guide public policies and make them more efficient. But, in Brazil, recent data about these aspects are limited. This study aimed to investigate the prevalence of contraceptive use and its inequalities during adolescence and early adulthood. Data from the 1993 Pelotas birth cohort, Rio Grande do Sul State, Brazil, were used. At 15, 18 and 22 years, respectively, 335, 1,458 and 1,711 women reported having started their sexual lives and were included in analysis. Prevalence and 95% confidence intervals were obtained to describe the most used contraceptive methods. Inequalities in modern contraceptive use were evaluated according to wealth index, scholastic backwardness and ethnicity. In all follow-ups, more than 80% of women used at least one modern method. The use of barrier methods decreased with age; at 22 this prevalence was 36.3%. Such use concomitant with other modern methods was lower than 50% in all follow-ups. We observed inequalities in the use of modern contraceptive methods, mainly in barrier methods used with other modern methods. These findings may contribute and improve the public policies in family planning.

Schizophrenia and autism spectrum disorders (ASD) are psychiatric neurodevelopmental disorders that cause high levels of functional disabilities. Also, the currently available therapies for these disorders are limited. Therefore, the search for treatments that could be beneficial for the altered course of the neurodevelopment associated with these disorders is paramount. Preclinical and clinical evidence points to cannabidiol (CBD) as a promising strategy. In this review, we discuss clinical and preclinical studies on schizophrenia and ASD investigating the behavioral, molecular, and functional effects of chronic treatment with CBD (and with cannabidivarin for ASD) during neurodevelopment. In summary, the results point to CBD's beneficial potential for the progression of these disorders supporting further investigations to strengthen its use., Competing Interests: JC is a member of the International Advisory Board of the Australian Centre for Cannabinoid Clinical and Research Excellence (ACRE), National Health and Medical Research Council (NHMRC). JC and JH have received travel support to attend scientific meetings and personal consultation fees from BSPG-Pharm. JC, JH, and AZ are coinventors of the patent “Fluorinated CBD compounds, compositions and uses thereof. Pub. No.: WO/2014/108899. International Application No.: PCT/IL2014/050023,” Def. US number Reg. 62193296; July 29, 2015; INPI on August 19, 2015 (BR1120150164927; Mechoulam R, Zuardi AW, Kapczinski F, Hallak JEC, Guimarâes FS, Crippa JAS, Breuer A). Universidade de São Paulo (USP) has licensed this patent to Phytecs Pharm (USP Resolution No. 15.1.130002.1.1) and has an agreement with Prati-Donaduzzi to “develop a pharmaceutical product containing synthetic CBD and prove its safety and therapeutic efficacy in the treatment of epilepsy, schizophrenia, Parkinson’s disease, and anxiety disorders.” JC, JH, and AZ are coinventors of the patent “Cannabinoid-containing oral pharmaceutical composition, method for preparing and using same,” INPI on September 16, 2016 (BR 112018005423-2). The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Loss, Teodoro, Rodrigues, Moreira, Peres, Zuardi, Crippa, Hallak and Abílio.)

Although the treatment of chronic Chagas disease (CCD) patients with Benznidazole (Bz) is still controversial, its use may prevent or delay the progression of the disease to the most severe forms. One of the main factors that can influence the effectiveness of the treatment is the possible cooperation between drug effect and the host immune response. Herein, we evaluated the immune response of peripheral blood mononuclear cells (PBMCs) infected with Trypanosoma cruzi and submitted to Bz treatment. Blood samples of CCD patients (n = 7) and non-infected individuals (n = 6) were drawn to obtain PBMCs. After cell culture, the supernatants were harvested and stored, and the cell analyzed by flow cytometer. The results showed that Bz positively regulated the molecular process of cell activation (CD80) and antigen presentation (HLA-DR), increased phagocytosis receptor and macrophage activation (CD64), and did not induce an exacerbated immune response. In conclusion, these results highlight the relevance of using Bz that, despite not being a true hero, it is also not a villain, as it presents a wide range of pharmacological/immunological response interactions, important for the immune balance in the clinical progression of CCD., (Copyright © 2020 Elsevier GmbH. All rights reserved.)

Objective: To estimate prevalence and factors associated with intimate partner psychological violence against women in a rural area in the state of Rio Grande do Sul, in 2017., Methods: This was a cross-sectional population-based study with women aged 18-49 years old and who had had an intimate partner in their lifetime. Questions from the World Health Organization Violence Against Women Study were administered. Poisson regression was used to estimate prevalence ratios (PR) and 95% confidence intervals (95%CI)., Results: 971 women participated. Prevalence of lifetime psychological violence was 17.2% (95%CI 14.9;19.7). Those diagnosed with depression (PR=2.23 - 95%CI 1.70;2.91) and who had consumed alcohol in the last week were more likely to refer lifetime psychological violence (PR=1.53 - 95%CI 1.07;2.17). Single women were more likely to experience psychological violence than married women (PR=1.86 - 95%CI 1.32;2.63)., Conclusion: Psychological violence against woman in rural areas was related to mental health and alcohol use.

Objective: To characterize the access and use of health services considered reference among the older rural population from a municipality in southern Brazil, whose rural area has full coverage of the Family Health Strategy (FHS), investigating factors associated with the choice of the Basic Family Health Unit (BFHU) as reference., Methods: This is a cross-sectional study conducted in 2017 with systematic sampling of rural households in the municipality of Rio Grande (RS) using a standardized in-house questionnaire. We performed descriptive analyses of sociodemographic profile, type of reference service chosen, and reasons for choosing/using the prime-choice service and the nearest BFHU. Poisson regression was used to investigate factors associated with the type of reference service chosen., Results: Among the 1,030 older adults who participated in the study, 61.4% considered the BFHU a prime choice/reference service mostly due to its proximity (82.6%); the others sought other places due to a greater ease (34.6%) and resoluteness (52.6%). Almost ⅔ of the respondents sought care at the BFHU during the last year, and the reasons differed among those who considered the unit as reference (chronic disease) and those who sought another place (procedures). We also found that the lower the age, income, education, and household-unit distance, the greater the likelihood of the older adult considering the nearest BFHU as reference service., Conclusions: The FHS has reached the vulnerable older rural population, approaching an equitable public health system. However, further evaluations are necessary to verify the quality and adequacy of care, given that social structure, enabling factors (such as economic condition), and possible beliefs regarding health still establish the standards for choosing a service.

Objectives: To assess time trends in unplanned pregnancy, stratified by sociodemographic status, reproductive history, and inequalities in family income and women's skin color, in Pelotas, Brazil., Methods: Data from mothers of participants of the 1993 (N = 5264), 2004 (N = 4243), and 2015 (N = 4268) Pelotas birth cohorts were analyzed. Unplanned pregnancy was investigated in the perinatal period, with tests to assess changes over time among different sociodemographic and reproductive history subgroups and inequalities as a function of family income and skin color., Results: The prevalence of unplanned pregnancy was 62.7% (3299/ 5264), 65.9% (2794/ 4243), and 52.2% (2226/ 4268) in the 1993, 2004, and 2015 cohorts, respectively. Black or brown women and women of lower socioeconomic status had a higher prevalence of unplanned pregnancy in all cohorts. The overall rate of unplanned pregnancy decreased over time in most subgroups. Inequality as a function of family income and skin color increased during the time frame of assessment., Conclusions: The prevalence of unplanned pregnancies decreased in the period analyzed, but it is still unjustifiably high. Efforts aimed at reducing unplanned pregnancy are vital and will require special attention to the most vulnerable groups.

Objective: This study aimed to assess the validity of a portable anthropometer against the gold standard among 2-year-old infants from the 2015 Pelotas (Brazil) Birth Cohort., Design: Birth cohort study., Setting: A fixed Harpenden® infant anthropometer was considered as the gold standard for measuring infant length due to its greater precision and stability. The portable SANNY® (model ES2000) anthropometer was the instrument to be validated. The acceptable mean difference in length between the anthropometers was 0·5 cm. In order to compare length estimates, the interviewers carried out two length measures for each of the anthropometers (fixed and portable) and for each child. The mean of the two lengths was calculated for each anthropometer, and their difference was calculated., Participants: A subsample of 252 24-month-old members of the 2015 Pelotas (Brazil) birth cohort study., Results: Children's mean age was 23·5 months. According to Bland-Altman plot, there were no differences in overall lengths between the portable and the fixed anthropometers, or in lengths according to sex. There was a high overall concordance between the length estimates of the fixed and portable anthropometers (ρ = 0·94; 95 % CI 0·92, 0·95)., Conclusions: The portable anthropometer proved to be accurate to measure the length of 24-month-old infants, being applicable to studies using the same standardised protocol used in the present study.

Trypanosoma cruzi causes the lethal Chagas disease, which is endemic in Latin America. Flowers of Moringa oleifera (Moringaceae) express a trypsin inhibitor (MoFTI) whose toxicity to T. cruzi trypomastigotes was previously reported. Here, we studied the effects of MoFTI on the viability of human peripheral blood mononuclear cells (PBMCs) as well as on the production of cytokines and nitric oxide (NO) by T. cruzi -infected PBMCs. Incubation with MoFTI (trypsin inhibitory activity: 62 U/mg) led to lysis of trypomastigotes (LC 50 of 43.5 µg/mL) but did not affect the viability of PBMCs when tested at concentrations up to 500 µg/mL. A selectivity index > 11.48 was determined. When T. cruzi -infected PBMCs were treated with MoFTI (43.5 or 87.0 µg/mL), the release of the pro-inflammatory cytokine TNF-α and INF-γ, as well as of NO, was stimulated. The release of the anti-inflammatory cytokine IL-10 also increased. In conclusion, the toxicity to T. cruzi and the production of IL-10 by infected PBMCs treated with MoFTI suggest that this molecule may be able to control parasitemia while regulating the inflammation, preventing the progress of Chagas disease. The data reported here stimulate future investigations concerning the in vivo effects of MoFTI on immune response in Chagas disease.

Spatial patterns of intraspecific variation are shaped by geographical distance among populations, historical changes in gene flow and interactions with local environments. Although these factors are not mutually exclusive and operate on both genomic and phenotypic variation, it is unclear how they affect these two axes of variation. We address this question by exploring the predictors of genomic and phenotypic divergence in Icterus gularis, a broadly distributed Middle American bird that exhibits marked geographical variation in body size across its range. We combined a comprehensive single nucleotide polymorphism and phenotypic data set to test whether genome-wide genetic and phenotypic differentiation are best explained by (i) isolation by distance, (ii) isolation by history or (iii) isolation by environment. We find that the pronounced genetic and phenotypic variation in I. gularis are only partially correlated and differ regarding spatial predictors. Whereas genomic variation is largely explained by historical barriers to gene flow, phenotypic diversity can be best predicted by contemporary environmental heterogeneity. Our genomic analyses reveal strong phylogeographical structure coinciding with the Chivela Pass at the Isthmus of Tehuantepec that was formed during the Pleistocene, when populations were isolated in north-south refugia. In contrast, we found a strong association between body size and environmental variables, such as temperature and precipitation. The relationship between body size and local climate is consistent with a pattern produced by either natural selection or environmental plasticity. Overall, these results provide empirical evidence for why phenotypic and genomic data are often in conflict in taxonomic and phylogeographical studies., (© 2020 John Wiley & Sons Ltd.)

Background: Nonuse of contraceptive methods by women in need of contraception may impact their sexual and reproductive health. The aim of this study was to describe the reasons for nonuse of contraception among women with demand for contraception not satisfied in low and middle-income countries (considering both overall countries and various subgroups of women)., Methods: We used the latest Demographic and Health Survey data from 47 countries. A descriptive analysis of the reasons for nonuse of contraceptive methods was performed among sexually active women with demand for contraception not satisfied. The prevalence of each reported reason was also evaluated according to marital status, woman's age and schooling, area of residence, wealth index, and parity. Wealth-related absolute inequality for each reason was also evaluated using the Slope Index of Inequality. A pro-rich inequality pattern means that the reason is more prevalent among the richest women while a pro-poor means the reason is more common among the poorest ones., Results: On average, 40.9% of women in need of contraception were not using any contraceptive methods to avoid pregnancy. Overall, the most prevalent reasons for nonuse of contraceptives were "health concerns" and "infrequent sex," but the prevalence of each reason varied substantially across countries. Nonuse due to "opposition from others" was higher among married than unmarried women; in turn, the prevalence of nonuse due to "lack of access" or "lack of knowledge" was about two times higher in rural areas than in urban areas. Women with less schooling more often reported nonuse due to "lack of access." Pro-rich inequality was detected for reasons "health concerns," "infrequent sex," and "method-related", while the reasons "other opposed," "fatalistic," "lack of access," and "lack of knowledge" were linked to patterns of pro-poor inequality., Conclusions: Family planning promotion policies must take into account the different reasons for the nonuse of contraceptive methods identified in each country as well as the contextual differences regarding women of reproductive age (such as social norms and barriers that prevent women from accessing and using contraceptives).

Objective: To investigate the influence of maternal depression on child health-care services utilization., Methodology: Data from The Pelotas 2004 Birth Cohort collected at birth and at 12- and 24-month follow-ups were used. Four outcomes occurring in the second year of life were investigated: number of well-baby visits, number of medical appointments, number of visits to emergency rooms, and number of hospitalizations. The main exposure was maternal depression symptoms at 12-month post-partum as assessed by the Edinburgh Postpartum Depression Scale (EPDS). Adjusted prevalence ratios (PR) with 95% confidence intervals (95% CI) were calculated by Poisson regression., Results: The prevalence of mothers with depressive symptoms was 27.6% (95% CI: 26.2-29.0%). These mothers showed a 10% lower probability of taking their children to well-baby visits (0.90; 0.85-0.95; p = 0.001); 16% higher probability to seek medical consultations (1.16; 1.09-1.25, p = 0.001); and they sought emergency services for their children more often (1.30; 1.17-1.45, p < 0.001) as compared to mothers who did not present depressive symptoms. Although the PR for hospitalizations was 26% higher for children from mothers with depressive symptoms, the association did not achieve statistical significance (1.26; 0.98-1.63; p = 0.072)., Conclusion: Children from mothers with depressive symptoms attend fewer number of preventive consultations. In contrast, they are taken to medical and emergency care more often, suggesting that these children are given healthcare when they are at more advanced stages of their illnesses., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Laboratory reports on adipose tissue suggest that fat grafting to the breast may pose an oncologic risk. One possible reason for this is the theoretic chronic inflammation due to adipokynes released by grafted white adipose tissue (WAT)., Objectives: The aim of this study was to analyze inflammatory activity in lipofilled breast through the use of proinflammatory markers., Methods: Fifty-four paired-breasts of female rats were divided into 4 groups: control, sham, and breasts grafted with either autologous subcutaneous (SC) WAT or autologous omentum (OM). The WAT was prepared through centrifugation, and the grafting was performed with the use of 0.9-mm blunt-tip cannula. The rats were killed 8 weeks postoperatively, and their breasts were harvested for immunohistochemical staining for CD68-expressing macrophages, gene expression (real-time PCR) for monocyte chemoattractant protein 1 (MCP-1), F4/80, Cox-2, and IL-6., Results: The weights of the rats that underwent a procedure differed from those of the unmanipulated control group (P < 0.01). The macrophage counts of CD68 differed only between breasts lipofilled with OM and control (P < 0.01). MCP-1, F4/80, and Cox-2 were similarly expressed among the groups (P = 0.422, P = 0.143, and P = 0.209, respectively). The expression of IL-6 differed between breast samples grafted with SC and OM WAT (P = 0.015), but not between samples of control and OM (P = 0.752), and control and SC (P = 0.056)., Conclusions: No inflammation activity was identified in the microenvironment of lipofilled breasts, indicating that chronic inflammation does not seem to be triggered by the breast lipofilling procedure., (© 2018 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com.)

Objectives: This work evaluated the antibacterial activity, cytotoxicity and immunomodulatory effect on human peripheral blood mononuclear cells (PBMCs) promoted by aqueous extract from Conocarpus erectus leaves (AELCe)., Methods: The extract was characterized by thin layer chromatography and ultraperformance liquid chromatography coupled to mass spectrometry (UPLC-MS). Cytotoxicity of AELCe (6.25-50 μg/ml) was investigated using annexin V and propidium iodide. Cytokine and nitric oxide levels in PBMCs culture supernatants exposed or not to AELCe (12.5 μg/ml) were determined, and antibacterial activity was evaluated by disc diffusion and broth microdilution methods., Key Findings: AELCe contained 3',4'-OH flavonoids, phenylpropanoglycosides, saponins, polymeric proanthocyanidins and hydrolysable tannins. Moreover, 10 other compounds were identified through UPLC-MS technique. AELCe did not affect lymphocyte viability at 6.25 and 12.5 μg/ml. IL-2, IL-10, TNF-α, IFN-γ and nitric oxide was produced in higher levels by cells treated with AELCe. Proliferation and activation of CD8 + T lymphocytes were also stimulated. AELCe showed bacteriostatic activity against clinical and antibiotic-resistant strains of Staphylococcus aureus (MIC between 250 and 1000 μg/ml)., Conclusions: AELCe showed a moderate bacteriostatic activity and promoted an immunomodulatory status through higher production of Th1 cytokines, nitric oxide release and T CD8 + lymphocytes stimulation., (© 2018 Royal Pharmaceutical Society.)

Aims: A new L-asparaginase produced by Streptomyces ansochromogenes UFPEDA 3420 actinobacteria was used in this study against human lymphocyte cultures to evaluate the immunological profile induced by this enzyme., Methods and Results: Cultures of lymphocytes were stimulated with S. ansochromogenes L-asparaginase, and cytotoxicity, cell viability, cell stimulation and cytokine production were analysed. This new S. ansochromogenes L-asparaginase induced activation and proliferation of the TCD8 + lymphocyte subset and produced higher TNF-α, IFN-γ, IL-2 and IL-10 levels in a 24-h assay., Conclusion: Streptomyces ansochromogenes L-asparaginase is a promising molecule to be used in in vivo models and to deepen preclinical tests against acute lymphoblast leukaemia., Significance and Impact of Study: L-asparaginase is an indispensable component of the chemotherapeutic treatment of acute lymphoblast leukaemia (ALL) and acute myeloid leukaemia (AML). Currently, drugs such as Asparaginase ® , Kidrolase ® , and Elspar ® and Erwinase ® are efficient against leukemic disease, but promote immunosuppression and other side effects in human organisms. Our purified S. ansochromogenes L-asparaginase showed promissory results inducing, in vitro, higher immunostimulation in human PBMC, especially in T CD8 + lymphocyte subsets., (© 2017 The Society for Applied Microbiology.)

The aim of this study is to identify the prevalence of pregnancy and abortion experience, along with associated factors among street children, adolescents and youths in Porto Alegre and Rio Grande, RS, Brazil. The sampling method in this cross-sectional study was Respondent-Driven Sampling (RDS), innovative in research about hidden populations. Interviews were conducted with 307 subjects, aged 10 to 21 years. In multivariate analysis, Poisson regression with a robust error variance was used. Most of this sample were males, with no contact with school and family. Almost half of the participants had been on the street for five years or more, spending more than 15 hours per day on the streets. The prevalence of pregnancy experience was 29.3%, independently associated with being a girl, having 10 sexual partners or more in the last year, having a fixed sexual partner in the last year, and being older. The prevalence of abortion experience was 10.4%, independently associated with not living with the family, having more than two pregnancies, and being younger. The high prevalence of pregnancy and abortion experience highlights the need for the development of better sexual and reproductive health policies focused on this population.

A cross-sectional study was conducted to measure the prevalence of condom use in the last sexual intercourse and associated factors among university students. Undergraduate students from a public university aged 18 and over of the Rio Grande (RS) campuses were eligible. A systematic single-stage sampling was used, based on class lists and self-administered questionnaire. Descriptive, bivariate and multivariable analyses were employed, with Poisson regression for the latter two. Most of the 1,215 university students included in the analysis were aged 20 to 29 (65.6%) and 69.3% began their sexual life before the age of 18. The prevalence of condom use in the last intercourse was 41.5% (95%CI: 38.7-44.3). Male gender, lower age group, condom use at first sexual intercourse, older age of onset of sexual activity, not having a partner and casual partner in the last sexual intercourse increased the likelihood of condom use.

In this study, we report the purification and characterization of a multifunctional lectin (MvFL) from Microgramma vacciniifolia fronds as well as its immunomodulatory properties on human peripheral blood mononuclear cells (PBMCs). MvFL (pI 4.51; 54kDa) is a glycoprotein able to inhibit trypsin activity and that has sequence similarities (32% coverage) with a plant RNA-binding protein. Hemagglutinating activity of MvFL was not altered by heating at 100°C for 30min, but was reduced in alkaline pH (8.0 and 9.0). Fluorimetric analyses showed that this lectin did not undergo marked conformational changes when heated. However, the MvFL conformation changed depending on the pH. MvFL at 6.25-25μg/mL was not cytotoxic to lymphocytes present among PBMCs. The PBMCs incubated for 24h with the lectin (12.5μg/mL) showed increased TNF-α, IFN-γ, IL-6, IL-10, and nitric oxide production. MvFL also stimulated T lymphocytes from PBMCs to differentiate into CD8 + cells. The activation (indicated by CD28 expression) of these cells was also stimulated. In conclusion, MvFL is a heat-stable and multifunctional protein, with both lectin and trypsin inhibitor activities, and capable of inducing predominantly a Th1 response in human PBMCs as well as activation and differentiation of T lymphocytes., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Alpinia purpurata is an ornamental crop known as a source of bioactive molecules. This is the first study to report isolation of a lectin (carbohydrate-binding protein) from A. purpurata inflorescences (ApuL). The immunomodulatory potential of ApuL was evaluated by investigating its effects on the production of cytokines and release of nitric oxide by human peripheral blood mononuclear cells (PBMCs). In addition, the differentiation and activation of lymphocytes treated with ApuL was evaluated by immunophenotyping assays. ApuL is an acidic and oligomeric protein with native molecular mass of 34kDa. The hemagglutinating activity (HA) of ApuL was inhibited by the glycoproteins fetuin and ovalbumin, was resistant to heating at 100°C and stimulated in the presence of calcium and magnesium ions. ApuL showed highest HA at pH 7.5 but failed to agglutinate erythrocytes at pH 8.0 and 9.0. ApuL induced the release of cytokines belonging to Th1 (IFN-γ, TNF-α, and IL-6) and Th17 (IL-17A) profiles as well as of nitric oxide, stimulating a pro-inflammatory environment. Moreover, ApuL also stimulated the production of IL-10, an anti-inflammatory cytokine with regulatory role. Incubation with lectin resulted in differentiation and activation of both T CD8 + and CD4 + subsets of lymphocytes, as evident from the expression of the CD28 costimulatory molecule. In conclusion, A. purpurata inflorescence is a source of an immunomodulatory lectin with potential immunoregulatory application, thereby adding biotechnological value to this ornamental crop., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Background: The results of experimental studies indicate that grafting of autologous adipose tissue may induce tumorigenesis at the recipient site, but clinical results do not support a carcinogenic effect of fat grafting to the breast., Objectives: The authors assessed cancer risk following transplantation of autologous fat into murine mammary tissue., Methods: In this animal study, mammary tissues from 54 breasts of 9 female rats were either grafted with autologous subcutaneous fat, grafted with autologous omental fat, or unmanipulated. Tissues were harvested and processed for histologic and immunohistochemical analyses, and the mRNA expression levels of specific genes were determined., Results: No atypia or changes in lobular structures were observed in lipofilled breasts compared with controls. The numbers of ductal cell layers and terminal ductal units were similar for lipofilled and control breasts. Macrophage concentrations also were similar for the 3 groups. The localization and magnitude of plasminogen activator inhibitor 1 were similar for lipofilled and unmanipulated breast tissue. The percentages of cells expressing Ki67 or estrogen receptor (ER) and the ER/Ki67 balance were similar for the 3 groups. Gene expression was not altered in lipofilled breasts, compared with controls., Conclusions: No theoretical risk of cancer was detected in the microenvironment of the lipofilled rat breast., (© 2016 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com)

Hemicelluloses are a vast group of complex, non-cellulosic heteropolysaccharides that are classified according to the principal monosaccharides present in its structure. Xylan is the most abundant hemicellulose found in lignocellulosic biomass. In the current trend of a more effective utilization of lignocellulosic biomass and developments of environmentally friendly industrial processes, increasing research activities have been directed to a practical application of the xylan component of plants and plant residues as biopolymer resources. A variety of enzymes, including main- and side-chain acting enzymes, are responsible for xylan breakdown. Xylanase is a main-chain enzyme that randomly cleaves the β-1,4 linkages between the xylopyranosyl residues in xylan backbone. This enzyme presents varying folds, mechanisms of action, substrate specificities, hydrolytic activities, and physicochemical characteristics. This review pays particular attention to different aspects of the mechanisms of action of xylan-degrading enzymes and their contribution to improve the production of bioproducts from plant biomass. Furthermore, the influence of phenolic compounds on xylanase activity is also discussed.

Eugenia dysenterica DC. (Myrtaceae) is a perennial tree producing edible fruits and ornamental flowers of potential value widely distributed in Brazilian "Cerrados" (savannas), but available genetic resources and potential for future breeding programs must be evaluated. Here we evaluated the reproductive system and pollen-mediated gene flow in one generation of Eugenia dysenterica germplasm collection of Agronomy School, Federal University of Goiás (in Goiânia city, Central Brazil). We collected leaves from all adults from the germplasm collection (682 plants) and seeds (542) from 23 mother-trees. Genotypes were obtained for seven microsatellite loci. Genetic diversity was high and did not significantly differ between adults (H e = 0.777) and progeny arrays (H e = 0.617). Our results showed that E. dysenterica has an allogamous mating system in the germplasm collection (t m = 0.957), but with high and significant biparental inbreeding (t m - t s = 0.109). Because sibs are very close to each other, mating between closely related individuals is likely. Paternity correlation was also relatively high, indicating a 11.9 % probability that a randomly chosen pair of outcrossed progeny from the same array are full sibs. The maximum pollen dispersal distance (224 m), estimated using assignment test, corresponded to the boundaries of the orchard. We were able to assign the paternity to only 64 % of the 349 seeds analyzed, indicating potential pollen immigration to the germplasm collection. The variance effective population size estimated for one maternal family in the germplasm collection (N ev = 3.42) is very close to the theoretical maximum value for half-sibs (Nev = 4.0). Because E. dysenterica has a long life cycle and generation time, the maintenance of an effective population size of at least 100 in the germplasm collection is suggested, which can be achieved by maintaining a seed-trees number around 30 individuals.

Hydrogen is a promising alternative for the increased global energy demand since it has high energy density and is a clean fuel. The aim of this work was to evaluate the photo-fermentation by Rhodobacter capsulatus, using the dark fermentation effluent as substrate. Different systems were tested by changing the type of sugar in the dark fermentation, investigating the influence of supplementing DFE with sugar and adding alternate and periodically lactose and glucose throughout the process. The supplementation of the DFE with sugar resulted in higher H2 productivity and the replacement of the sugars repeatedly during the photo-fermentation process was important to maintain the cell culture active. By controlling the residual amount of sugar, bacteria inhibition was avoided; lactic acid, that was toxic to the biomass, was consumed and the metabolic route of butyric acid production was predominant. Under optimum conditions, the H2 productivity reached 208.40mmolH2/Ld in 52h., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Two endo-β-1,4-xylanases named XylT1 and XylT2, previously purified from Aspergillus terreus, were structurally investigated by fluorescence quenching and characterized with respect to their binding properties with phenolic compounds. Neutral and charged quenchers had access to both enzymes in neutral and alkaline pHs. The greatest access was noted for the negative quencher, possibly due to positive amino acid residues in the vicinity of tryptophan. These tryptophan environments may partially explain the conformational differences and lower binding constants of phenolic compounds for XylT2 than XylT1Phenolic compounds had lower binding constants for XylT2 than XylT1. These results show that xylanases present structural and functional differences, despite belonging to similar families. XylT1 and XylT2 were also evaluated for their ability to hydrolyze cellulose pulp in different stages of bleaching. Both enzymes promoted hydrolysis of cellulose pulps, which was confirmed by the release of total reducing sugars, pentoses and chromophoric material. Analysis of released xylooligosaccharides demonstrated a preferential release of xylobiose. None of xylanases released glucose, showing that they do not hydrolyze the cellulose present in the pulp, making both enzymes excellent choices for bio-bleaching applications., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

The liver regeneration is an important clinical issue after major hepatectomies. Unfortunately, many organs (including the liver) exhibit age-related impairments regarding their regenerative capacity. Recent studies found that low-power laser irradiation (LPLI) has a stimulatory effect on the liver regeneration process. However, its effects in elderly remain unknown. Thus, this study aimed to investigate the main molecular mechanisms involved in liver regeneration of partially hepatectomized elderly rats exposed to LPLI. The effects of 15 min of LPLI (wavelength of 632.8 nm; fluence of 0.97 J/cm(2); total energy delivered of 3.6 J) were evaluated in hepatectomized elderly Wistar male rats. Afterwards, through immunoblotting approaches, the protein expression and phosphorylation levels of hepatocyte growth factor (HGF), Met, Akt and Erk 1/2 signaling pathways as well as the proliferating cell nuclear antigen (PCNA) were investigated. It was observed that LPLI was not able to improve liver regeneration in elderly rats as evidenced by the lack of improvement of HGF and PCNA protein expression or phosphorylation levels of Met, Akt and Erk 1/2 in the remnant livers. In sum, this study demonstrated that the main molecular pathway, i.e. HGF/Met → Akt and Erk 1/2 → PCNA, involved in the hepatic regeneration process was not improved by LPLI in elderly hepatectomized rats, which in turn rules out LPLI as an adjuvant therapy, as observed in this protocol of liver regeneration evaluation (i.e. at 48 h after 70 % resection), in elderly.

Background: Although its unclear oncological risk, which led to more than 20 years of prohibition of its use, fat grafting to the breast is widely used nowadays even for aesthetic purposes. Thus, we proposed an experimental model in rats to analyze the inflammatory activity, cellular proliferation and levels of Plasminogen Activator Inhibitor (PAI-1) in grafted fat, and in native fat exposed to high-energy diet in order to study the oncological potential of fat tissue., Methods: Samples of grafted fat of rats on regular-energy diet were compared with paired samples of native fat from the same rat on regular-energy diet and on high-energy diet in a different time. Analysis involved microscopic comparisons using hematoxylin-eosin staining, immunohistochemistry with anti-CD68-labelled macrophages, and gene expression of Ki-67 and PAI-1., Results: Hematoxylin-eosin staining analyses did not find any atypical cellular infiltration or unusual tissue types in the samples of grafted fat. The inflammatory status, assessed through immunohistochemical identification of CD68-labelled macrophages, was similar among samples of native fat and grafted fat of rat on regular-energy diet and of native fat of rats on high-energy diet. Real-time PCR revealed that high-energy diet, but not fat grafting, leads to proliferative status on adipose tissue (overexpression of ki-67, p = 0.046) and raised its PAI-1 levels, p < 0.001., Conclusion: While the native adipose tissue overexpressed PAI-1 and KI67 when exposed to high-energy diet, the grafted fat by itself was unable to induce cellular proliferation, chronic inflammatory activity and/or elevation of PAI-1 levels.

A simple, easy, and safe procedure aiming to improve liver regeneration could be of great clinical benefit in critical situations such as major hepatectomy, trauma, or hemorrhage. Low-power laser irradiation (LPLI) has come into a wide range of use in clinical practice by inducing regeneration in healthy and injured tissues. However, the effect of LPLI on the process of liver regeneration, especially those related to the molecular mechanisms, is not fully understood. Thus, the aim of the present study was to investigate the main molecular mechanisms involved in liver regeneration of partially hepatectomized rats exposed to LPLI. We used Wistar male rats, which had their remaining liver irradiated or not with LPLI (wavelength of 632.8 nm and fluence of 65 mW/cm(2)) for 15 min after a 70% hepatectomy. We subsequently investigated hepatocyte growth factor (HGF), Met, Akt, and Erk 1/2 signaling pathways through protein expression and phosphorylation analyses along with cell proliferation (proliferating cell nuclear antigen (PCNA) and Ki-67) using immunoblotting and histological studies. Our results show that LPLI can improve liver regeneration as shown by increased HGF protein expression and the phosphorylation levels of Met, Akt, and Erk 1/2 accompanied by higher levels of the PCNA and Ki-67 protein in the remnant livers. In summary, our results suggest that LPLI may play a clinical role as a simple, fast, and easy-to-perform strategy in order to enhance the liver regenerative capacity of a small liver remnant after hepatectomy.

Sugarcane bagasse was used as an inexpensive alternative carbon source for production of β-xylanases from Aspergillus terreus. The induction profile showed that the xylanase activity was detected from the 6th day of cultivation period. Two low molecular weight enzymes, named Xyl T1 and Xyl T2 were purified to apparent homogeneity by ultrafiltration, gel filtration and ion exchange chromatographies and presented molecular masses of 24.3and 23.60 kDa, as determined by SDS-PAGE, respectively. Xyl T1 showed highest activity at 50 °C and pH 6.0, while Xyl T2 was most active at 45 °C and pH 5.0. Mass spectrometry analysis of trypsin digested Xyl T1 and Xyl T2 showed two different fingerprinting spectra, indicating that they are distinct enzymes. Both enzymes were specific for xylan as substrate. Xyl T1 was inhibited in greater or lesser degree by phenolic compounds, while Xyl T2 was very resistant to the inhibitory effect of all phenolic compounds tested. The apparent km values of Xyl T2, using birchwood xylan as substrate, decreased in the presence of six phenolic compounds. Both enzymes were inhibited by N-bromosuccinimide and Hg(2+) and activated by Mn(2+). Incubation of Xyl T1 and Xyl T2 with L-cysteine increased their half-lives up to 14 and 24 h at 50 °C, respectively. Atomic force microscopy showed a bimodal size distribution of globular particles for both enzymes, indicating that Xyl T1 is larger than Xyl T2., (Copyright © 2013 Elsevier Inc. All rights reserved.)

We describe the isolation and characterization of ten microsatellite loci from the red-winged tinamou (Rhynchotus rufescens) and also evaluated the cross-amplification of these loci and other ten loci previously developed for the great tinamou (Tinamus major) in other tinamous. Genetic variability was assessed using 24 individuals. Six loci were polymorphic with moderate to high number of alleles per locus (2-12 alleles) and showed expected heterozygosity (HE) ranging from 0.267 to 0.860. All loci conformed to the Hardy-Weinberg expectation and linkage disequilibrium was not significant for any pair of loci. This battery of polymorphic loci showed high paternity exclusion probability (0.986) and low genetic identity probability (4.95 × 10(-5)), proving to be helpful for parentage tests and population analyses in the red-winged tinamou. The cross-amplification was moderate where of the 160 locus/taxon combinations, 46 (28.75%) successfully amplified.

Holocellulose structures from agro-industrial residues rely on main and side chain attacking enzymes with different specificities for complete hydrolysis. Combinations of crude enzymatic extracts from different fungal species, including Aspergillus terreus, Aspergillus oryzae, Aspergillus niger and Trichoderma longibrachiatum, were applied to sugar cane bagasse, banana stem and dirty cotton residue to investigate the hydrolysis of holocellulose structures. A. terreus and A. oryzae were the best producers of FPase and xylanase activities. A combination of A. terreus and A. oryzae extracts in a 50% proportion provided optimal hydrolysis of dirty cotton residue and banana stem. For the hydrolysis of sugar cane bagasse, the best results were obtained with samples only containing A. terreus crude extract.