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João Marcelo Barreto Silva,1,2 Paulo Henrique De Souza Bermejo,3 Marina Figueiredo Moreira,3 David Nadler Prata,1 Daniela Mascarenhas de Queiroz Trevisan,1 Otávio Augusto dos Santos2 1Program in Governance and Digital Transformation, Federal University of Tocantins, Palmas, TO, Brazil; 2Department of Assistance Regulation and Control, Ministry of Health, Brasília, DF, Brazil; 3Administration Department, Faculty of Economics, Administration, Accounting and Public Policy Management of University of Brasília, Brasília, DF, BrazilCorrespondence: João Marcelo Barreto Silva, Department of Assistance Regulation and Control, Ministry of Health, St. de Adm. Federal Sul Q1-G, Sala 147B, Brasília, DF, 70058-900, Brasil, Email joao.marcelo@saude.gov.brBackground: Analyzing patients’ nonattendance at medical appointments helps address an issue impacting the management and sustainability of health systems globally, providing valuable insights for healthcare managers. This study aims to identify factors at both patient and health system levels that contribute to understanding missed appointments.Methods: The analysis was conducted using data from secondary care consultations within the Brazilian Unified Health System between April 2018 and March 2020. Primary care includes general medical consultations, while secondary care involves specialized services provided by doctors with advanced expertise. We examined demographic factors (age, sex, race/color, socioeconomic level) and health system practices (waiting time, hospitalization, distance to service, medical specialty, and severity of clinical condition) to assess their impact on patient attendance. A weighted analysis and receiver operating characteristic (ROC) analysis were applied to determine the relative risk of nonattendance.Findings: Of 5,003,159 consultations, 435,523 (8.7%) were missed. Nonattendance was highest among patients facing long distances to the service (13.3%, [RRR] 1.227), younger age (16– 30 years: 11.8%, [RRR] 1.041), and waiting times (> 30: 10.9%, [RRR] 1.738). Socially vulnerable patients were more likely to miss appointments (9.6%, [RRR] 1.055) compared to less vulnerable groups (8.6%). Practice-level factors had a slightly greater impact on nonattendance (ROC: 0.621) than patient-level factors (ROC: 0.5674). The overall predictive model achieved a C statistic of 0.6228, resulting in a fair predictive ability. However, the model showed only modest prediction of no-shows, indicating the need for more detailed data to improve accuracy. Gauging which group suffers the highest risk of nonattendance was a secondary goal of this analysis.Interpretation: Young, socially vulnerable patients with long commutes and extended waiting times are at higher risk of nonattendance. Effective management of these risk factors and targeted preventive actions are essential to reduce absenteeism and improve health system efficiency.Keywords: absenteeism, health policy, medical appointment, health management

Background: Endometriosis, characterized by the presence of endometrial-like tissue outside the uterus, results in chronic pelvic pain. However, lesion characteristics alone cannot fully explain the complexity of endometriosis-related pain. Pain catastrophizing, a cognitive process that influences pain perception, has traditionally been studied through cross-sectional or two-wave designs, which struggle to capture its dynamic interplay with endometriosis pain. To address these gaps, our study explores the bidirectional relationship between pain catastrophizing and pain outcomes-including intensity, frequency, and flares-over a detailed four-week period, an aggregated 30-day timeframe, and across sensory and affective dimensions., Methods: A Latent Growth Curve Model assessed the relationship between pain catastrophizing, initial pain levels, and endometriosis pain trajectories over four weeks. Additionally, four mediator models explored how baseline pain catastrophizing affects various pain aspects, including sensory and affective dimensions, and its subsequent influence on pain catastrophizing., Results: Results indicate that high levels of pain catastrophizing significantly escalate endometriosis pain over four weeks, affecting average pain intensity, episode frequency, and flares over 30 days. Pain catastrophizing also adversely impacts sensory and affective dimensions. These elements partially mediate baseline pain catastrophizing's effect on week five levels, revealing a bidirectional relationship. Notably, while the affective dimension amplifies subsequent pain catastrophizing, the sensory dimension exerts a contrasting negative influence., Conclusion: The study highlights the bidirectional influence between pain catastrophizing and several aspects of endometriosis-related pain. Sensory and affective dimensions play distinct roles, with implications for personalized interventions. Limitations and clinical relevance are discussed., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The enzyme arginine kinase (AK), EC 2.7.3.3, catalyzes the reversible phosphorylation of arginine with adenosine triphosphate, forming phosphoarginine, which acts as an energy reservoir due to its high-energy phosphate content that can be rapidly transferred to ADP for ATP renewal. It has been proposed that AK should be associated with some ATP biosynthesis mechanisms, such as glycolysis and oxidative phosphorylation. Arginine kinase is an analogue of creatine kinase found in vertebrates. A literature survey has recovered the physicochemical and structural characteristics of AK. This enzyme is widely distributed in invertebrates such as protozoa, bacteria, porifera, cnidaria, mollusca, and arthropods. Arginine kinase may be involved in the response to abiotic and biotic stresses, being up regulated in several organisms and controlling energy homeostasis during environmental changes. Additionally, phosphoarginine plays a role in providing energy for the transport of protozoa, the beating of cilia, and flagellar movement, processes that demand continuous energy. Arginine kinase is also associated with allergies to shellfish and arthropods, such as shrimp, oysters, and cockroaches. Phenolic compounds such as resveratrol, which decrease AK activity by 50 % in Trypanosoma cruzi, inhibit the growth of the epimastigote and trypomastigote forms, making them a significant target for the development of medications for Chagas Disease treatment., Competing Interests: 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., (© 2024 The Authors. Published by Elsevier B.V.)

Temperature is a determining factor for the viral cycle. In this study, we investigate the effect of different temperatures on the cycles of two important arboviruses-Zika (ZIKV) and Chikungunya (CHIKV)-in Vero (mammalian) and C6/36 (mosquito) cells. We compare genome quantification to infectivity at 28 °C and 37 °C in both cell types. Virus-cell interaction was also examined by transmission electron microscopy, allowing the observation of phenomena such as virus-surfing and giant forms for CHIKV, as well as the the scarcity of ZIKV in C6/36 cells compared to its cycle in mammalian cells.

Endometriosis-related pain is supposedly mainly responsible for generating psychological stress and deteriorating the quality of life. However, the interaction between these factors has not been investigated, considering its multidimensional nature and through the path of effects of psychosocial approaches. The present study aims to investigate the effect of a brief mindfulness-based intervention (bMBI) on pain dimensions and its mediator role on psychological stress and QoL-Vitality improvement. A secondary analysis of a pilot randomized controlled trial using a series of parallel and serial mediators was carried out. The results showed that bMBI improves the sensory (B = -6.09 [-9.81, -2.52], β = -0.42) and affective (B = -3.40 [-5.02, -1.80], β = -0.47) pain. The bMBI effect on psychological stress reduction was mediated by these changes in sensory (B = -2.81 [-6.06, -0.41], β = -0.21) and affective (B = -1.97 [-5.07, -0.17], β = -0.15) pain. Serial sensory pain and psychological stress reduction (B = 2.27 [0.11, 5.81], β = -0.09) mediated the bMBI effect on quality of life vitality. Meditation training promotes additional improvement in affective and sensory pain characteristics through which psychological stress is reduced. The sensory pain dimension must be positively impacted in combination with psychological stress for the bMBI improves women's vitality. Adding a psychosocial intervention like meditation training to the standard treatment plan may be required for some women to achieve the needed changes to restore well-being., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Endometriosis is a gynecological disease that involves a broad biopsychosocial compromise with the potential to create a negative vicious cycle. Despite the complexity of factors influencing women's improvement, most interventions investigated target just the peripheral nociceptive sources of endometriosis-related pain. An alternative is intervening in self-regulation, which can potentially influence multiple domains of the illness experience. The present study examines the effect of a brief Mindfulness-Based Intervention (bMBI) on attention and autonomic nervous system regulation in women with endometriosis-related pain. Also, explore the interaction between these self-regulation domains and the affective pain dimension. An exploratory analysis of the secondary outcomes of a pilot randomized controlled trial was performed. The vagally-mediated Heart Rate Variability (vmHRV) at rest, cognitive stress, and recovery was employed to measure autonomic regulation. The Flanker and Stroop tasks were used to estimate the attention domains. Results showed that bMBI (n = 26) significantly improved Flanker accuracy and Flanker and Stroop reaction time compared to the control group (n = 28). bMBI significantly increased vmHRV at rest and recovery after cognitive stress. Attention mediated the bMBI effect on affective pain improvement. Results suggest that bMBI improves self-regulation domains with the potential to develop a broad biopsychosocial benefit in the endometriosis context. PERSPECTIVE: This article demonstrates the positive impact of a brief Mindfulness-Based Intervention on attention and parasympathetic regulation in women suffering from endometriosis-related pain. This mindfulness-induced self-regulation improvement can benefit affective pain and potentially multiple psychophysiological processes relevant to endometriosis., (Copyright © 2023 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.)

Brazil is a continental country with significant socioeconomic and ethnic inequalities. It is important to understand how these differences are reflected in health care, especially during the COVID-19 pandemic. We investigated the potential impacts of the reduced number Transcranial Doppler Ultrasound (TCD) tests performed in Brazil during the COVID-19 pandemic, and its reflections according to region and race/color for patients with Sickle Cell Disease (SCD). This study performed data queries from the Brazilian Ministry of Health, literature research, and quantitative analysis using descriptive statistical analysis. We found evidence for a decrease in the number of TCD tests performed during the pandemic (-83 %) relative to the same non-pandemic period, and disparities in tests given in five regions in Brazil. Our data show, that in absolute numbers, most people with SCD are brown, but the highest prevalence of cases was among blacks. We also found evidence for racial discrimination when performing TCD test, which leads us to believe that the Brazilian Unified Health System (SUS) may be susceptible to racism when treating this disease. The implications of these findings serve as a warning to other countries with high indices of mixed ancestry in formulating health care policies for patients with SCD., Competing Interests: 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., (© 2023 The Authors.)

Background: There is poor knowledge about the therapeutic mechanisms of the conservative interventions for endometriosis. We hypothesized that the effects of a brief mindfulness-based intervention (bMBI) on pelvic pain intensity (PPI), pain unpleasantness (PU) and quality of life mental health (QoL-MH) are mediated by direct and indirect paths of changes in pain catastrophizing (PC), positive affect (PA) and negative affect (NA)., Methods: A secondary analysis of a pilot randomized controlled trial of women with endometriosis, assigned to standard medical treatment (n = 32) and standard medical treatment plus bMBI (n = 31). We tested a series of parallel and serial mediators (PC, PA and NA) of the relationship between bMBI and outcomes (PPI, PU and QoL-MH)., Results: The bMBI group demonstrated improvement in PA (Cohen's f 2  = 0.12 [0.01, 0.36]), decreases in NA (Cohen's f 2  = 0.06 [0.00, 0.24]) and PC (Cohen's f 2  = 0.16 [0.02, 0.42]). The PC reduction mediated the effect of the bMBI on PPI and PU directly; however, the PC effect through PA increase mediated the PU marginally but not PPI changes. bMBI effect on Qol-MH was mediated directly by PA and NA. The PC improved Qol-MH through PA increase and Pain decrease but not via NA., Conclusions: Our findings showed that bMBI impacts pain through changes in pain-related cognitive-affective factors. bMBI can improve QoL-MH by multiple pathways, including but not limited to pain reduction, highlighting the independent potential of improvement in affect to restore mental health in endometriosis., Significance: Brief mindfulness-based intervention improves endometriosis pain through pain-related cognitive-affective factors and quality of life mental health via pain and affect changes unrelated to pain., (© 2023 European Pain Federation - EFIC ®.)

Dengue virus is an important circulating arbovirus in Brazil responsible for high morbidity and mortality worldwide, representing a huge economic and social burden, in addition to affecting public health. In this study, the biological activity, toxicity, and antiviral activity against dengue virus type 2 (DENV-2) of tizoxanide (TIZ) was evaluated in Vero cell culture. TIZ has a broad spectrum of action in inhibiting different pathogens, including bacteria, protozoa, and viruses. Cells were infected for 1 h with DENV-2 and then treated for 24 h with different concentrations of the drug. The quantification of viral production indicated the antiviral activity of TIZ. The protein profiles in infected Vero cells treated and not treated with TIZ were analyzed using the label-free quantitative proteomic approach. TIZ was able to inhibit virus replication mainly intracellularly after DENV-2 penetration and before the complete replication of the viral genome. Additionally, the study of the protein profile of infected not-treated and infected-treated Vero cells showed that TIZ interferes with cellular processes such as intracellular trafficking and vesicle-mediated transport and post-translational modifications when added after infection. Our results also point to the activation of immune response genes that would eventually lead to a decrease of DENV-2 production. TIZ is a promising therapeutic molecule for the treatment of DENV-2 infections.

Zika virus (ZIKV) is a positive-sense single-stranded RNA flavivirus and is mainly transmitted by Aedes mosquitoes. This arbovirus has had a significant impact on health in recent years by causing malformations, such as microcephaly in babies and Guillain-Barré syndrome in adults. Some evidence indicates that ZIKV can be sexually transmitted and may persist in the male reproductive tract for an extended period in humans. Knockout and vasectomized mice have been used as models to reveal ZIKV infection in the male reproductive tract as a virus source. ZIKV presence in male and female mosquito reproductive tracts and eggs point to venereal and vertical/transovarian transmission, again demonstrating that the reproductive tract can be involved in the spread of ZIKV. Moreover, eggs protected by eggshells have the potential to be a ZIKV reservoir. Given the +-lack of vaccines and therapies for Zika fever and the underestimated prevalence rate, an understanding of ZIKV infection and its spread from the reproductive tract, which is protected from the immune system and potentially active for virus transmission, is imperative. We must also develop cheaper, more efficient techniques for virological surveillance inside vectors and humans, control vectors with ecofriendly insecticides, and promote condom use to avoid ZIKV contamination during sexual intercourse, as recommended by the World Health Organization.

This work studied the influence of hydrogel's physical properties (geometry and hierarchical roughness) on the in vitro sorption/release profiles of molecules. To achieve this goal, chitosan (CS) solutions were cast in 3D-printed (3DP) molds presenting intricate shapes (cubic and half-spherical with/without macro surface roughness) and further immersed in alkaline solutions of NaOH and NaCl. The resulting physically crosslinked hydrogels were mechanically stable in aqueous environments and successfully presented the shapes and geometries imparted by the 3DP molds. Sorption and release profiles were evaluated using methyl orange (MO) and paracetamol (PMOL) as model molecules, respectively. Results revealed that distinct MO sorption/PMOL release profiles were obtained according to the sample's shape and presence/absence of hierarchical roughness. MO sorption capacity of CS samples presented both dependencies of hierarchical surface and geometry parameters. Hence, cubic samples without a hierarchical surface presented the highest (up to 1.2 × greater) dye removal capacity. Moreover, PMOL release measurements were more dependent on the surface area of hydrogels, where semi-spherical samples with hierarchical roughness presented the fastest (~1.13 × faster) drug delivery profiles. This work demonstrates that indirect 3DP (via fused filament fabrication (FFF) technology) could be a simple strategy to obtain hydrogels with distinct sorption/release profiles.

Objective: This study investigates the spatial differences in the occurrence of COVID-19 in Brazilian Tropical Zone and its relationship with climatic, demographic, and economic factors based on data from February 2020 to May 2021., Methods: A Linear Regression Model with the GDP per capita, demographic density and climatic factors from 5.534 Brazilian cities with (sub)tropical climate was designed and used to explain the spread of COVID-19 in Brazil., Main Results: The model shows evidence that economic, demographic and climate factors maintain a relationship with the variation in the number of cases of COVID-19. The Köppen climate classification defines climatic regions by rainfall and temperature. Some studies have shown an association between temperature and humidity and the survival of SARS-CoV-2. In this cohort study, Brazilian cities located in tropical regions without a dry season (monthly rainfall > 60 mm) showed a greater prevalence than in cities located in tropical regions with a dry season (some monthly rainfall < 60 mm)., Conclusion: Empirical evidence shows that the Brazil's tropical-climate cities differ in the number (contamination rate) of COVID-19 cases, mainly because of humidity. This study aims to alert the research community and public policy-makers to the trade-off between temperature and humidity for the stability of SARS-COV-2, and the implications for the spread of the virus in tropical climate zones., Competing Interests: 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., (© 2022 The Authors.)

Background: Women with endometriosis suffer from frequent symptoms despite multiple treatments in tertiary care. Although there is a need for a biopsychosocial perspective on endometriosis treatment, few conservative treatments have been investigated. We aimed to investigate the effects of a brief Mindfulness-Based Intervention (bMBI) in women with deep endometriosis who remain symptomatic despite undergoing conventional medical treatment., Methods: A randomized controlled trial was performed with two groups: a standard medical treatment plus bMBI program and only standard medical treatment as a control. A total of 63 eligible participants were randomized to bMBI and control groups. The primary outcome was endometriosis-related pain, and secondary outcomes were quality of life and stress perception post-treatment. Analyses were carried out using multiple regression models., Results: The results show that bMBI significantly improved pain unpleasantness (Cohen's f 2  = 0.67, NNT = 3.2), pelvic pain (Cohen's f 2  = 0.16, NNT = 5.3) and dyschezia (Cohen's f 2  = 0.23, NNT = 2.9) immediately post-treatment and decreased all endometriosis-related pain (Cohen's f 2 ranging from 0.20 to 0.60 and NNT ranging from 5 to -9) after the follow-up. We found an extensive positive effect of bMBI on the mental health dimension in the two time point measures (Cohen's f 2  = 0.34 and 0.25, NNT = 3.5 and 2.3) and vitality (Cohen's f 2  = 0.22, NNT = 2.1) after the follow-up., Conclusions: Our study suggests that bMBI is useful for managing endometriosis-related pain and restoring women's psychological well-being., Significance: Brief Mindfulness-Based Intervention (bMBI) improved endometriosis-related pain and mental health compared to standard medical care. The present findings contribute to the applicability of MBI in visceral pain patients., (© 2022 European Pain Federation - EFIC®.)

Background: Zika fever has been a global health security threat, especially in the tropical and subtropical regions where most of the cases occur. The disease is caused by Zika virus (ZIKV), which belongs to the family Flaviviridae, genus Flavivirus. The virus is transmitted by Aedes mosquitoes, mostly by Aedes aegypti, during its blood meal. In this study we present a descriptive analysis, by transmission electron microscopy (TEM), of ZIKV infection in A. aegypti elected tissues at the 3rd day of infection. ZIKV vertical transmission experiments by oral infection were conducted to explore an offspring of natural infection., Results: Gut and ovary tissues harbored a higher number of viral particles. The ZIKV genome was also detected, by RT-qPCR technique, in the organism of orally infected female mosquitoes and in their eggs laid., Conclusions: The data obtained suggest that the ovary is an organ susceptible to be infected with ZIKV and that virus can be transmitted from mother to a fraction of the progeny., (© 2021. The Author(s).)

In November 2020, Brazil ranked third in the number of cases of coronavirus disease 2019 (COVID-19) and second in the number of deaths due to the disease. We carried out a descriptive study of deaths, mortality rate, years of potential life lost (YPLL) and excess mortality due to COVID-19, based on SARS-CoV-2 records in SIVEP-Gripe (Ministry of Health of Brazil) from 16 February 2020, to 1 January 2021. In this period, there were 98,025 deaths from COVID-19 in Brazil. Men accounted for 60.5% of the estimated 1.2 million YPLLs. High YPLL averages showed prematurity of deaths. The population aged 45-64 years (both sexes) represented more than 50% of all YPLLs. Risk factors were present in 69.5% of deaths, with heart disease, diabetes and obesity representing the most prevalent comorbidities in both sexes. Indigenous people had the lowest number of deaths and the highest average YPLL. However, in indigenous people, pregnant women and mothers had an average YPLL of over 35 years. The excess mortality for Brazil was estimated at 122,914 deaths (9.2%). The results show that the social impacts of YPLL due to COVID-19 are different depending on gender, race and risk factors. YPLL and excess mortality can be used to guide the prioritization of health interventions, such as prioritization of vaccination, lockdowns, or distribution of facial masks for the most vulnerable populations.

The world is facing the coronavirus pandemic (COVID-19), which began in China. By August 18, 2020, the United States, Brazil, and India were the most affected countries. Health infrastructure and socioeconomic vulnerabilities may be affecting the response capacities of these countries. We compared official indicators to identify which vulnerabilities better determined the exposure risk to COVID-19 in both the most and least affected countries. To achieve this purpose, we collected indicators from the Infectious Disease Vulnerability Index (IDVI), the World Health Organization (WHO), the World Bank, and the Brazilian Geography and Statistics Institute (IBGE). All indicators were normalized to facilitate comparisons. Speed, incidence, and population were used to identify the groups of countries with the highest and lowest risks of infection. Countries' response capacities were determined based on socioeconomic, political, and health infrastructure conditions. Vulnerabilities were identified based on the indicator sensitivity. The highest-risk group included the U.S., Brazil, and India, whereas the lowest-risk group (with the largest population by continent) consisted of China, New Zealand, and Germany. The high-sensitivity cluster had 18 indicators (50% extra IDVI), such as merchandise trade, immunization, public services, maternal mortality, life expectancy at birth, hospital beds, GINI index, adolescent fertility, governance, political stability, transparency/corruption, industry, and water supply. The greatest vulnerability of the highest-risk group was related first to economic factors (merchandise trade), followed by public health (immunization), highlighting global dependence on Chinese trade, such as protective materials, equipment, and diagnostic tests. However, domestic political factors had more indicators, beginning with high sensitivity and followed by healthcare and economic conditions, which signified a lesser capacity to guide, coordinate, and supply the population with protective measures, such as social distancing., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Ergonomic risks are a major health hazard for teachers, causing musculoskeletal pain and decreasing both their quality of life and the quality of the education offered to students., Objectives: To evaluate musculoskeletal pain and ergonomic risk factors in the workplace of teachers at the São Bento do Sul Campus of the Instituto Federal Catarinense., Methods: Twenty-five teachers completed sociodemographic and ergonomic risk questionnaires, as well as the Nordic Musculoskeletal Questionnaire. The furniture and equipment at their workstations were also evaluated using a checklist., Results: Seventy two percent of teachers were male, and the mean age of the sample was 37.08±7.14 years. In response to the questionnaires, 72% of participants reported little knowledge of ergonomics and 68% said they did not apply these principles in their daily life. The main ergonomic risks to which teachers were exposed were prolonged sitting and standing, sharp corners on desks, use of laptop touchpads and inadequate monitor height. All teachers reported pain in the past 12 months, with the most frequently affected areas being the low back (60%), neck (56%) and shoulders (48%)., Conclusions: These findings highlight the importance of ergonomic adaptations and changes in the work habits of teachers in order to improve their health and quality of life, while also allowing them to deliver higher-quality education to their students.

The adult females of Aedes aegypti mosquitoes are facultative hematophagous insects but they are unable to feed on blood right after pupae emergence. The maturation process that takes place during the first post-emergence days, hereafter named hematophagic and gonotrophic capacitation, comprises a set of molecular and physiological changes that prepare the females for the first gonotrophic cycle. Notwithstanding, the molecular bases underlying mosquito hematophagic and gonotrophic capacitation remain obscure. Here, we investigated the molecular and biochemical changes in adult Ae. aegypti along the first four days post-emergence, prior to a blood meal. We performed a RNA-Seq analysis of the head and body, comparing male and female gene expression time courses. A total of 811 and 203 genes were differentially expressed, respectively in the body and head, and both body parts showed early, mid, and late female-specific expression profiles. Female-specific up-regulation of genes involved in muscle development and the oxidative phosphorylation pathway were remarkable features observed in the head. Functional assessment of mitochondrial oxygen consumption in heads showed a gradual increase in respiratory capacity and ATP-linked respiration as a consequence of induced mitochondrial biogenesis and content over time. This pattern strongly suggests that boosting oxidative phosphorylation in heads is a required step towards blood sucking habit. Several salivary gland genes, proteases, and genes involved in DNA replication and repair, ribosome biogenesis, and juvenile hormone signaling were up-regulated specifically in the female body, which may reflect the gonotrophic capacitation. This comprehensive description of molecular and biochemical mechanisms of the hematophagic and gonotrophic capacitation in mosquitoes unravels potentially new targets for vector control., Competing Interests: The authors have declared that no competing interests exist. Author Mario Alberto C da Silva-Neto, was unable to confirm their authorship contributions. On their behalf, the corresponding author has reported their contributions to the best of their knowledge.

Odorant-binding proteins (OBPs) are small soluble proteins whose biological function is believed to be facilitating olfaction by assisting the transport of volatile chemicals in both vertebrate and insect sensory organs, where they are secreted. Their capability to interact with a broad range of hydrophobic compounds combined with interesting features such as being small, stable, and easy to produce and modify, makes them suitable targets for applied research in various industrial segments, including textile, cosmetic, pesticide, and pharmaceutical, as well as for military, environmental, health, and security field applications. In addition to reviewing already established biotechnological applications of OBPs, this paper also discusses their potential use in prospecting of new technologies. The development of new products for insect population management is currently the most prevailing use for OBPs, followed by biosensor technology, an area that has recently seen a significant increase in studies evaluating their incorporation into sensing devices. Finally, less typical approaches include applications in anchorage systems and analytical tools. KEY POINTS: • Odorant-binding proteins (OBPs) present desired characteristics for applied research. • OBPs are mainly used for developing new products for insect population control. • Incorporation of OBPs into chemosensory devices is a growing area of study. • Less conventional uses for OBPs include anchorage systems and analytical purposes. Graphical Abstract.

Background: We performed an in-depth analysis of the ABC gene family in Aedes aegypti (Diptera: Culicidae), which is an important vector species of arthropod-borne viral infections such as chikungunya, dengue, and Zika. Despite its importance, previous studies of the Arthropod ABC family have not focused on this species. Reports of insecticide resistance among pests and vectors indicate that some of these ATP-dependent efflux pumps are involved in compound traffic and multidrug resistance phenotypes., Results: We identified 53 classic complete ABC proteins annotated in the A. aegypti genome. A phylogenetic analysis of Aedes aegypti ABC proteins was carried out to assign the novel proteins to the ABC subfamilies. We also determined 9 full-length sequences of DNA repair (MutS, RAD50) and structural maintenance of chromosome (SMC) proteins that contain the ABC signature., Conclusions: After inclusion of the putative ABC proteins into the evolutionary tree of the gene family, we classified A. aegypti ABC proteins into the established subfamilies (A to H), but the phylogenetic positioning of MutS, RAD50 and SMC proteins among ABC subfamilies-as well as the highly supported grouping of RAD50 and SMC-prompted us to name a new J subfamily of A. aegypti ABC proteins.

Background: Accurate knowledge of the prevalence and profile of sickness absenteeism enables direct analysis of work environments and the health-disease process., Objective: To establish the prevalence and profile of sick leaves granted to Oswaldo Cruz Foundation (FIOCRUZ) employees from 2012 through 2016., Method: Cross-sectional study with analysis of variables sex, age range, age at onset of sick leave, job position, FIOCRUZ unit, leave type, ICD code, leave duration, number of leave extensions, and outcomes; p=0.05 and 95% confidence interval were considered in all the analyses., Results: Work accidents accounted for 2.30% of sick leaves; the absenteeism rate was 2.89%. Musculoskeletal diseases (21.2%), mental and behavioral disorders (13.1%) and consequences of external causes (11.3%) were the main reasons for sick leave. Mental and behavioral disorders exhibited the longest median leave duration (30 days). The odds of requiring a sick leave were highest among women (OR=4.08), employees with technical positions (OR=2.86), aged 25 to 34 years old (OR=2.68) or allocated to production units (OR=176.30) and hospitals (OR=34.05)., Conclusions: We corroborate the relevance of accurate knowledge of aspects related to absenteeism for the planning of strategies to promote the functional capacity of workers, and reduce its consequences on the health-work-disease relationship.

Zika virus infection and dengue and chikungunya fevers are emerging viral diseases that have become public health threats. Their aetiologic agents are transmitted by the bite of genus Aedes mosquitoes. Without effective therapies or vaccines, vector control is the main strategy for preventing the spread of these diseases. Increased insecticide resistance calls for biorational actions focused on control of the target vector population. The chitin required for larval survival structures is a good target for biorational control. Chitin synthases A and B (CHS) are enzymes in the chitin synthesis pathway. Double-stranded RNA (dsRNA)-mediated gene silencing (RNAi) achieves specific knockdown of target proteins. Our goal in this work, a new proposed RNAi-based bioinsecticide, was developed as a potential strategy for mosquito population control. DsRNA molecules that target five different regions in the CHSA and B transcript sequences were produced in vitro and in vivo through expression in E. coli HT115 and tested by direct addition to larval breeding water. Mature and immature larvae treated with dsRNA targeting CHS catalytic sites showed significantly decreased viability associated with a reduction in CHS transcript levels. The few larval and adult survivors displayed an altered morphology and chitin content. In association with diflubenzuron, this bioinsecticide exhibited insecticidal adjuvant properties.

Rhodnius prolixus is one of the most important vectors of Chagas disease in Central and South America for which repellents and attractants are sorely needed. Repellents like DEET, picaridin, and IR3535 are widely used as the first line of defense against mosquitoes and other vectors, but they are ineffective against R. prolixus. Our initial goal was to identify in R. prolixus genome odorant receptors sensitive to putative sex pheromones. We compared gene expression of 21 ORs in the R. prolixus genome, identified 4 ORs enriched in male (compared with female) antennae. Attempts to de-orphanize these ORs using the Xenopus oocyte recording system showed that none of them responded to putative sex pheromone constituents. One of the them, RproOR80, was sensitive to 4 compounds in our panel of 109 odorants, namely, 2-heptanone, γ-octalactone, acetophenone, and 4-methylcychohexanol. Interestingly, these compounds, particularly 4-methylcyclohexanol, showed strong repellency activity as indicated not only by a significant decrease in residence time close to a host, but also by a remarkable reduction in blood intake. 4-Methylcyclohexanol-elicited repellency activity was abolished in RNAi-treated insects. In summary, our search for pheromone receptors led to the discovery of repellents for R. prolixus., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Olfactory proteins mediate a wide range of essential behaviors for insect survival. Odorant binding proteins (OBPs) are small soluble olfactory proteins involved in the transport of odor molecules (=odorants) through the sensillum lymph to odorant receptors, which are housed on the dendritic membrane of olfactory sensory neurons also known as olfactory receptor neurons. Thus, a better understanding of the role(s) of OBPs from Rhodnius prolixus , one of the main vectors of Chagas disease, may ultimately lead to new strategies for vector management. Here we aimed at functionally characterize OBPs from R. prolixus . Genes of interest were selected using conventional bioinformatics approaches and subsequent quantification by qPCR. We screened and estimated expression in different tissues of 17 OBPs from R. prolixus adults. These analyses showed that 11 OBPs were expressed in all tissues, whereas six OBP genes were specific to antennae. Two OBP genes, RproOBP6 and RproOBP13 , were expressed in both male and female antennae thus suggesting that they might be involved in the recognition of semiochemicals mediating behaviors common to both sexes, such host finding (for a blood meal). Transcripts for RproOBP17 and RproOBP21 were enriched in female antennae and possibly involved in the detection of oviposition attractants or other semiochemicals mediating female-specific behaviors. By contrast, RproOBP26 and RproOBP27 might be involved in the reception of sex pheromones given that their transcripts were highly expressed in male antennae. To test this hypothesis, we silenced RproOBP27 using RNAi and examined the sexual behavior of the phenotype. Indeed, adult males treated with dsOBP27 spent significantly less time close to females as compared to controls. Additionally, docking analysis suggested that RproOBP27 binds to putative sex pheromones. We therefore concluded that RproOBP27 might be a pheromone-binding protein.

Dengue virus (DENV), an arbovirus transmitted by mosquitoes, has become a major threat to American human life, reaching approximately 23 million cases from 1980 to 2017. Brazil is among the countries most affected by this terrible viral disease, with 13.6 million cases. DENV has four different serotypes, DENV1-4, which show a broad clinical spectrum. Dengue creates a staggering epidemiological and economic burden for endemic countries. Without a specific therapy and with a commercial vaccine that presents some problems relative to its full effectiveness, initiatives to improve vector control strategies, early disease diagnostics and the development of vaccines and antiviral drugs are priorities. In this study, we present the probable origins of dengue in America and the trajectories of its spread. Overall, dengue diagnostics are costly, making the monitoring of dengue epidemiology more difficult and affecting physicians' therapeutic decisions regarding dengue patients, especially in developing countries. This review also highlights some recent and important findings regarding dengue in Brazil and the Americas. We also summarize the existing DENV polymerase chain reaction (PCR) diagnostic tests to provide an improved reference since these tests are useful and accurate at discriminating DENV from other flaviviruses that co-circulate in the Americas. Additionally, these DENV PCR assays ensure virus serotyping, enabling epidemiologic monitoring.

Reception of odorants is essential in insects' life since the chemical signals in the environment (=semiochemicals) convey information about availability of hosts for a blood meal, mates for reproduction, sites for oviposition and other relevant information for fitness in the environment. Once they reach the antennae, these semiochemicals bind to odorant-binding proteins and are transported through the sensillar lymph until reach the odorant receptors. Such perireceptor events, particularly the interactions with transport proteins, are the liaison between the external environment and the entire neuroethological system and, therefore, a potential target to disrupt insect chemical communication. In this study, a proteomic profile of female and male antennae of Rhodnius prolixus, a vector of Chagas disease, was obtained in an attempt to unravel the entire repertoire of olfactory proteins involved in perireceptor events. Using shotgun proteomics and two-dimensional gel electrophoresis approaches followed by nano liquid chromatography coupled with tandem LTQ Velos Orbitrap mass spectrometry, we have identified 581 unique proteins. Putative olfactory proteins, including 17 odorant binding proteins, 6 chemosensory proteins, 2 odorant receptors, 3 transient receptor channels and 1 gustatory receptor were identified. Proteins involved in general cellular functions such as generation of precursor metabolites, energy generation and catabolism were expressed at high levels. Additionally, proteins that take part in signal transduction, ion binding, and stress response, kinase and oxidoreductase activity were frequent in antennae from both sexes. This proteome strategy unraveled for the first time the complex nature of perireceptor and other olfactory events that occur in R. prolixus antennae, including evidence for phosphorylation of odorant-binding and chemosensory proteins. These findings not only increase our understanding of the olfactory process in triatomine species, but also identify potential molecular targets to be explored for population control of such insect vectors., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Detection of chemical signals from the environment through olfaction is an indispensable mechanism for maintaining an insect's life, evoking critical behavioral responses. Among several proteins involved in the olfactory perception process, the odorant binding protein (OBP) has been shown to be essential for a normally functioning olfactory system. This paper discusses the role of OBPs in insect chemoreception. Here, structural aspects, mechanisms of action and binding affinity of such proteins are reviewed, as well as their promising application as molecular targets for the development of new strategies for insect population management and other technological purposes., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

A question is raised about an increased risk of severe infection from the use of biological drugs in patients with rheumatoid arthritis. This systematic review of observational studies aimed at assessing the risk of severe infection associated with the use of anakinra, rituximab, and abatacept in patients with rheumatoid arthritis. The following databases were searched: PubMed, Science Direct, Scopus, Web of Knowledge, Scirus, Cochrane, Exerpta Medica Database, Scielo, and Lilacs up to July 2010. Severe infections were defined as those life-threatening ones in need of the use of parenteral antibiotics or of hospitalization. Longitudinal observational studies were selected without language restriction, involving adult patients diagnosed with rheumatoid arthritis and who used anakinra, rituximab, or abatacept. In four studies related to anakinra, 129 (5.1%) severe infections were related in 2896 patients, of which three died. With respect to rituximab, two studies reported 72 (5.9%) severe infections in 1224 patients, of which two died. Abatacept was evaluated in only one study in which 25 (2.4%) severe infections were reported in 1046 patients. The main site of infection for these three drugs was the respiratory tract. One possible explanation for the high frequency of severe infections associated with anakinra may be the longer follow-up time in the selected studies. The high frequency of severe infections associated with rituximab could be credited to the less strict inclusion criteria for the patients studied. Therefore, infection monitoring should be cautious in patients with rheumatoid arthritis in use of these three drugs., (Copyright © 2016. Published by Elsevier Editora Ltda.)

Aedes aegypti females ingest sugar or blood to obtain the nutrients needed to maintain cellular homeostasis. During human blood ingestion, female mosquitoes may transmit different viruses such as dengue, yellow fever and, more recently, zika and chikungunya. Here, we report changes in protein expression in the heads of adult female Ae. aegypti mosquitoes in response to the ingestion of blood or sugar. Proteins extracted from the heads of Ae. aegypti fed exclusively on blood (BF) or sugar (SF) were trypsin hydrolyzed (off-gel) and analyzed by the reverse-phase nano-liquid chromatography coupled with hybrid mass spectrometry. A total of 1139 proteins were identified in female heads, representing 7.4% of the predicted proteins in Ae. aegypti genome (total = 15 419 active genes). Gene ontology annotation and categories showed that, in this insect, the head was rich in proteins involved in the metabolic process, proton transport, organelle, macromolecular complex, structural molecule activity, antioxidant activity, and catalytic activity. Our report is the first indicating that many of the annotated genes are translated into functional proteins in heads of adult female Ae. aegypti. Interestingly, we identified 8.7 times more exclusively expressed proteins involved in signal transduction, replication-transcription-translation (5.5 x), and transport (2.9 x) activity in BF than in SF groups. This paper discusses the protein profile of Ae. aegypti female heads and its implications for blood ingestion and carbohydrate intake., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Rheumatoid arthritis (RA) and periodontitis (PD) are chronic inflammatory disorders that cause bone loss. PD tends to be more prevalent and severe in RA patients. Previous experimental studies demonstrated that RA triggers alveolar bone loss similarly to PD. The aim of this study was to investigate if arthritis-induced alveolar bone loss is associated with modification in the oral microbiota. Checkerboard DNA-DNA hybridization was employed to analyze forty oral bacterial species in 3 groups of C57BL/6 mice: control (n = 12; without any challenge); Y4 (n = 8; received oral inoculation of Aggregatibacter Actinomycetemcomitans strain FDC Y4) and AIA group (n = 12; chronic antigen-induced arthritis). The results showed that AIA and Y4 group exhibited similar patterns of bone loss. The AIA group exhibited higher counts of most bacterial species analyzed with predominance of Gram-negative species similarly to infection-induced PD. Prevotella nigrescens and Treponema denticola were detected only in the Y4 group whereas Campylobacter showae, Streptococcus mitis and Streptococcus oralis were only found in the AIA group. Counts of Parvimonas micra, Selenomonas Noxia and Veillonella parvula were greater in the AIA group whereas Actinomyces viscosus and Neisseira mucosa were in large proportion in Y4 group. In conclusion, AIA is associated with changes in the composition of the oral microbiota, which might account for the alveolar bone loss observed in AIA mice., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Chitin is an essential component of the peritrophic matrix (PM), which is a structure that lines the insect's gut and protects against mechanical damage and pathogens. Rhodnius prolixus (Hemiptera: Reduviidae) does not have a PM, but it has an analogous structure, the perimicrovillar membrane (PMM); chitin has not been described in this structure. Here, we show that chitin is present in the R. prolixus midgut using several techniques. The FTIR spectrum of the KOH-resistant putative chitin-material extracted from the midgut bolus showed peaks characteristic of the chitin molecule at 3500, 1675 and 1085 cm(1). Both the midgut bolus material and the standard chitin NMR spectra showed a peak at 1.88 ppm, which is certainly due to methyl protons in the acetamide a group. The percentages of radioactive N-acetylglucosamine (CPM) incorporated were 2 and 4% for the entire intestine and bolus, respectively. The KOH-resistant putative chitin-material was also extracted and purified from the N-acetylglucosamine radioactive bolus, and the radioactivity was estimated through liquid scintillation. The intestinal CHS cDNA translated sequence was the same as previously described for the R. prolixus cuticle and ovaries. Phenotypic alterations were observed in the midgut of females with a silenced CHS gene after a blood meal, such as retarded blood meal digestion; the presence of fresh blood that remained red nine days after the blood meal; and reduced trachea and hemozoin content compared with the control. Wheat germ agglutinin (a specific probe that detects chitin) labeling proximal to the intestine (crop and midgut) was much lower in females with a silenced CHS gene, especially in the midgut region, where almost no fluorescence signal was detected compared with the control groups. Midguts from females with a CHS gene silenced by dsRNA-CHS and control midguts pre-treated with chitinase showed that the chitin-derived fluorescence signal decreased in the region around the epithelium, the region facing the midgut and projections towards the intestinal lumen when evaluated microscopically. The relative reduction in CHS transcripts by approximately 80% using an RNAi assay supports the phenotypical alterations in the midgut observed using fluorescence microscopy assays. These data show that chitin is present in the R. prolixus midgut epithelium and in its surface projections facing the lumen. The CHS gene expression and the presence of chitin in the R. prolixus midgut may suggest a target for controlling Chagas disease vectors and addressing this public health problem., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Olfaction is one of the main sensory modalities that allow insects to interpret their environment. Several proteins, including odorant-binding proteins (OBPs) and odorant receptors (ORs), are involved in this process. Odorant receptors are ion channels formed by a binding unit OR and an odorant receptor co-receptor (Orco). The main goal of this study was to characterize the Orco gene of Rhodnius prolixus (RproOrco) and to infer its biological functions using gene silencing. The full-length RproOrco gene sequence was downloaded from VectorBase. This gene has 7 introns and is located in the genome SuperContig GL563069: 1,017,713-1,023,165. RproOrco encodes a protein of 473 amino acids, with predicted 7 transmembrane domains, and is highly expressed in the antennae during all R. prolixus developmental stages. The RNAi technique effectively silenced RproOrco, reducing the gene's expression by approximately 73%. Interestingly, the effect of gene silencing persisted for more than 100 days, indicating a prolonged effect of dsRNA that was maintained even after molting. The phenotypic effects of silencing involved the following: (1) loss of the ability to find a vertebrate host in a timely manner, (2) decreased ingested blood volume, (3) delayed and decreased molt rate, (4) increased mortality rate, and (5) decreased egg laying. Our data strongly suggest that dsOrco disrupts R. prolixus host-finding behavior, which is further reflected in the blood ingestion, molting, mortality, and egg laying data. This study clearly demonstrates that Orco is an excellent target for controlling triatomine populations. Thus, the data presented here open new possibilities for the control of vector-borne diseases., (Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: To investigate the effect of Lithothamnium sp (LTT) supplement, a calcium-rich alga widely used for mineral reposition, on strain-induced (orthodontic tooth movement [OTM]) and infection-induced bone resorption (periodontal disease [PD]) in mice., Materials and Methods: Mice were divided into two bone resorption models: one with an orthodontic appliance and the other with PD induced by the oral inoculation of Aggregatibacter actinomycetencomitans (Aa). Both groups were fed a regular diet (vehicle), LTT-rich diet (LTT), or calcium-rich diet (CaCO3). Alveolar bone resorption (ABR), the number of osteoclasts, and the levels of tumor necrosis factor α (TNF-α), calcium, and vitamin D3 were evaluated., Results: The number of osteoclasts was reduced in LTT and CaCO3 mice, which led to diminished OTM and infection-induced alveolar bone loss. In addition, LTT- and calcium-treated groups also presented decreased levels of TNF-α in periodontal tissues and increased levels of calcium in serum., Conclusions: These results indicate that the LTT supplement influences ABR, probably due to its calcium content, by affecting osteoclast function and local inflammatory response, thus modulating OTM and PD.

In a previous study, we found that the embryonic cuticle of Rhodnius prolixus is a chitin-based structure that helps the first instar nymph to hatch from the chorion. Here, we investigated how the reduction of transcripts induced by CHS dsRNA injection affects R. prolixus embryogenesis and eclosion. Deposition of chitin in the embryonic cuticle begins later at embryogenesis, around day 8, and ends approximately at day 15, when the insects are ready for eclosion. In R. prolixus, chitin deposition follows pari passu with the synthesis of the chitin synthase mRNA, indicating a regulation at the transcriptional level. The reduction of the chitin synthase gene transcripts by the injection of CHS dRNA prevented chitin deposition during embryonic cuticle formation, being lethal to hatching nymphs, which end up dying while stuck in the chorionic border trying to leave the chorion. The successful eclosion rates were reduced by 60% in animals treated with CHS dsRNA when compared to animals injected with a control (dsRNA no related gene or water). We found that the harmful effects on oviposition and eclosion are possibly due to changes in the structure of the embryonic cuticle, as observed by directly comparing the morphology of control and chitin-deficient embryonic cuticles under the transmission electron microscope. The lack of chitin and changes in its morphological characteristics appears to alter the embryonic cuticle physiology and functionality. Additionally, we observed that the effects of CHS dRNA treatment on R. prolixus females lasted up to 3 egg-laying cycles (∼100 days), pointing to R. prolixus as a useful model for developmental studies., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

In this study, we provided the demonstration of the presence of a single CHS gene in the Rhodnius prolixus (a blood-sucking insect) genome that is expressed in adults (integument and ovary) and in the integument of nymphs during development. This CHS gene appears to be essential for epidermal integrity and egg formation in R. prolixus. Because injection of CHS dsRNA was effective in reducing CHS transcript levels, phenotypic alterations in the normal course of ecdysis occurred. In addition, two phenotypes with severe cuticle deformations were observed, which were associated with loss of mobility and lifetime. The CHS dsRNA treatment in adult females affected oogenesis, reducing the size of the ovary and presenting a greater number of atresic oocytes and a smaller number of chorionated oocytes compared with the control. The overall effect was reduced oviposition. The injection of CHS dsRNA modified the natural course of egg development, producing deformed eggs that were dark in color and unable to hatch, distinct from the viable eggs laid by control females. The ovaries, which were examined under fluorescence microscopy using a probe for chitin detection, showed a reduced deposition on pre-vitellogenic and vitellogenic oocytes compared with control. Taken together, these data suggest that the CHS gene is fundamentally important for ecdysis, oogenesis and egg hatching in R. prolixus and also demonstrated that the CHS gene is a good target for controlling Chagas disease vectors., (Published by Elsevier Ltd.)

The embryonic cuticle (EC) of Rhodnius prolixus envelopes the entire body of the embryo during hatching and provides physical protection, allowing the embryo to pass through a narrow chorionic border. Most of the knowledge about the EC of insects is derived from studies on ultrastructure and secretion processes during embryonic development, and little is known about the molecular composition of this structure. We performed a comprehensive molecular characterization of the major components extracted from the EC of R. prolixus, and we discuss the role of the different molecules that were identified during the eclosion process. The results showed that, similar to the post-embryonic cuticles of insects, the EC of R. prolixus is primarily composed of carbohydrates (57%), lipids (19%), and proteins (8%). Considering only the carbohydrates, chitin is by far the major component (approximately 70%), and it is found primarily along the body of the EC. It is scarce or absent in its prolongations, which are composed of glycosaminoglycans. In addition to chitin, we also identified amino (15%), neutral (12%) and acidic (3%) carbohydrates in the EC of R. prolixus. In addition carbohydrates, we also identified neutral lipids (64.12%) and phospholipids (35.88%). Proteomic analysis detected 68 proteins (55 were identified and 13 are hypothetical proteins) using the sequences in the R. prolixus genome (http://www.vectorbase.org). Among these proteins, 8 out of 15 are associated with cuticle metabolism. These proteins are unequivocally cuticle proteins, and they have been described in other insects. Approximately 35% of the total proteins identified were classified as having a structural function. Chitin-binding protein, amino peptidase, amino acid oxidase, oxidoreductase, catalase and peroxidase are all proteins associated with cuticle metabolism. Proteins known to be cuticle constituents may be related to the function of the EC in assisting the insect during eclosion. To our knowledge, this is the first study to describe the global molecular composition of an EC in insects., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

This study aimed to analyse the effect of growth during a summer break on biomechanical profile of talented swimmers. Twenty-five young swimmers (12 boys and 13 girls) undertook several anthropometric and biomechanical tests at the end of the 2011-2012 season (pre-test) and 10 weeks later at the beginning of the 2012-2013 season (post-test). Height, arm span, hand surface area, and foot surface area were collected as anthropometric parameters, while stroke frequency, stroke length, stroke index, propelling efficiency, active drag, and active drag coefficient were considered as biomechanical variables. The mean swimming velocity during an all-out 25 m front crawl effort was used as the performance outcome. After the 10-week break, the swimmers were taller with an increased arm span, hand, and foot areas. Increases in stroke length, stroke index, propelling efficiency, and performance were also observed. Conversely, the stroke frequency, active drag, and drag coefficient remained unchanged. When controlling the effect of growth, no significant variation was determined on the biomechanical variables. The performance presented high associations with biomechanical and anthropometric parameters at pre-test and post-test, respectively. The results show that young talented swimmers still present biomechanical improvements after a 10-week break, which are mainly explained by their normal growth.

Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophic factor family. Outside the nervous system, BDNF has been shown to be expressed in various nonneural tissues, such as periodontal ligament, dental pulp, and odontoblasts. Although a role for BDNF in periodontal regeneration has been suggested, a function for BDNF in periodontal disease has not yet been studied. The aim of this study was to analyze the BDNF levels in periodontal tissues of patients with chronic periodontitis (CP) and periodontally healthy controls (HC). All subjects were genotyped for the rs4923463 and rs6265 BDNF polymorphisms. Periodontal tissues were collected for ELISA, myeloperoxidase (MPO), and microscopic analysis from 28 CP patients and 29 HC subjects. BDNF levels were increased in CP patients compared to HC subjects. A negative correlation was observed when analyzing concentration of BDNF and IL-10 in inflamed periodontium. No differences in frequencies of BDNF genotypes between CP and HC subjects were observed. However, BDNF genotype GG was associated with increased levels of BDNF, TNF-α, and CXCL10 in CP patients. In conclusion, BDNF seems to be associated with periodontal disease process, but the specific role of BDNF still needs to be clarified.

Re-emergence of vector-borne diseases such as dengue and yellow fever, which are both transmitted by the Aedes aegypti mosquito, has been correlated with insecticide resistance. P-glycoproteins (P-gps) are ATP-dependent efflux pumps that are involved in the transport of substrates across membranes. Some of these proteins have been implicated in multidrug resistance (MDR). In this study, we identified a putative P-glycoprotein in the Ae. aegypti database based on its significantly high identity with Anopheles gambiae, Culex quinquefasciatus, Drosophila melanogaster and human P-gps. The basal ATPase activity of ATP-binding cassette transporters in larvae was significantly increased in the presence of MDR modulators (verapamil and quinidine). An eightfold increase in Ae. aegypti P-gp (AaegP-gp) gene expression was detected in temephos-treated larvae as determined by quantitative PCR. To analyse the potential role of AaegP-gp in insecticide efflux, a temephos larvicide assay was performed in the presence of verapamil. The results showed an increase of 24% in temephos toxicity, which is in agreement with the efflux reversing effect. RNA interference (RNAi)-mediated silencing of the AaegP-gp gene caused a significant increase in temephos toxicity (57%). In conclusion, we have demonstrated for the first time in insects that insecticide-induced P-gp expression can be involved in the modulation of insecticide efflux., (© 2013 Royal Entomological Society.)

Periodontal disease (PD) is a chronic inflammatory and alveolar bone destructive disease triggered by oral biofilm-producing microorganisms, such as Aggregatibacter actinomycetemcomitans. The levels of the phospholipid platelet-activating factor (PAF) in the saliva, gingival crevicular fluid, and periodontal tissues are significantly increased during inflammatory conditions, such as PD, but the exact mechanism that links PAF to alveolar bone resorption is not well understood. In the current study, alveolar bone resorption was induced by experimental PD through the oral inoculation of A. actinomycetemcomitans in wild-type (WT) and PAF receptor knockout (Pafr(-/-)) mice. In vitro experiments using A. actinomycetemcomitans lipopolysaccharide (LPS)-stimulated RAW 264.7 cells treated with a PAF receptor antagonist (UK74505) were also performed. The expression of lyso-PAF acetyltransferase in periodontal tissues was significantly increased 3 h after A. actinomycetemcomitans LPS injection in mice. WT and Pafr(-/-) mice that were subjected to oral inoculation of A. actinomycetemcomitans presented neutrophil accumulation and increased levels of CXCL-1 and tumor necrosis factor alpha (TNF-α) in periodontal tissues. However, Pafr(-/-) mice presented less alveolar bone loss than WT mice. The in vitro blockade of the PAF receptor impaired the resorptive activity of A. actinomycetemcomitans LPS-activated osteoclasts. In conclusion, this study shows for the first time that the blockade of PAF receptor may contribute to the progression of PD triggered by A. actinomycetemcomitans by directly affecting the differentiation and activity of osteoclasts.

Aim: This study aimed to investigate whether chronic antigen-induced arthritis (AIA) influences infection-induced periodontitis (PD) in mice and whether PD modifies the clinical course of AIA. The contribution of anti-TNF-α therapy was also evaluated., Materials and Methods: The PD was induced in C57BL/6 mice by oral infection with Aggregatibacter actinomycetemcomitans. AIA was induced after infection. Anti-TNF-α and chlorhexidine therapies were used to investigate the role of TNF-α and oral infection on PD and AIA interaction. Maxillae, knee joints, lymph nodes and serum samples were used for histomorphometric, immunoenzymatic and/or real time-PCR analyses., Results: Antigen-induced arthritis exacerbated alveolar bone loss triggered by PD infection. In contrast, PD did not influence AIA in the evaluated time-points. PD exacerbation was associated with enhanced production of IFN-γ in maxillae and expression of the Th1 transcription factor tBET in submandibular lymph nodes. Increased serum levels of IL-6 and C-reactive protein were also detected. Anti-TNF-α and antiseptic therapies prevented the development and exacerbation of infectious-PD. Anti-TNF-α therapy also resulted in reduced expression of IFN-γ, TNF-α and IL-17 in maxillae., Conclusions: Altogether, the current results indicate that the exacerbation of infection-induced PD by arthritis is associated with an alteration in lymphocyte polarization pattern and increased systemic immunoreactivity. This process was ameliorated by anti-TNF-α and antiseptic therapies., (© 2012 John Wiley & Sons A/S.)

Periodontal disease (PD) is a chronic inflammatory and alveolar bone destructive disease triggered by microorganisms from the oral biofilm. Oral inoculation of mice with the periodontopathogen Aggregatibacter actinomycetemcomitans (Aa) induces marked alveolar bone loss and local production of inflammatory mediators, including Macrophage Migration Inhibitory Factor (MIF). The role of MIF for alveolar bone resorption during PD is not known. In the present study, experimental PD was induced in BALB/c wild-type mice (WT) and MIF knockout mice (MIF⁻/⁻) through oral inoculation of Aa. Despite enhanced number of bacteria, MIF⁻/⁻ mice had reduced infiltration of TRAP-positive cells and reduced alveolar bone loss. This was associated with decreased neutrophil accumulation and increased levels of IL-10 in periodontal tissues. TNF-α production was similar in both groups. In vitro, LPS from Aa enhanced osteoclastic activity in a MIF-dependent manner. In conclusion, MIF has role in controlling bacterial growth in the context of PD but contributes more significantly to the progression of bone loss during PD by directly affecting differentiation and activity of osteoclasts., (Copyright © 2011 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.)

Objective: Interleukin-17 (IL-17) is a cytokine that induces neutrophil recruitment and the release of inflammatory mediators in several inflammatory conditions; nevertheless, the involvement of IL-17 gene polymorphisms in chronic periodontitis (CP) has not been addressed yet. Our aim was to evaluate the association between periodontal status and the polymorphisms IL-17A G197A and IL-17F C7488T in subjects with CP along with their impact on levels of inflammatory mediators., Material and Methods: Genomic DNA was obtained from 30 CP patients and 30 healthy controls (HCs). IL-17A G197A and IL-17F C7488T polymorphisms were determined using PCR-RFLP. Serum and periodontal tissues were collected and processed for ELISA, myeloperoxidase (MPO), and/or microscopic analysis., Results: The frequencies of genotypes in the CP group were significantly different from those of HC. Odds ratio indicated that increased risks for CP were associated with the -197A allele, not with the -7488T allele. In addition, the -197A allele was correlated with worse clinical parameters, higher MPO activity, and increased expression of inflammatory mediators (IL-17A and IL-8) than the other genotypes., Conclusions: These results indicate that the IL-17A -197A allele is associated with increased risk for CP, likely because this genotype relates to the enhanced inflammation in periodontal tissues.

Rheumatoid arthritis (RA) and periodontal disease (PD) are prevalent chronic inflammatory disorders that affect bone structures. Individuals with RA are more likely to experience PD, but how disease in joints could induce PD remains unknown. This study aimed to experimentally mimic clinical parameters of RA-induced PD and to provide mechanistic findings to explain this association. Chronic Ag-induced arthritis (AIA) was triggered by injection of methylated BSA in the knee joint of immunized mice. Anti-TNF-α was used to assess the role of this cytokine. Intra-articular challenge induced infiltration of cells, synovial hyperplasia, bone resorption, proteoglycan loss, and increased expression of cytokines exclusively in challenged joints. Simultaneously, AIA resulted in severe alveolar bone loss, migration of osteoclasts, and release of proinflammatory cytokines in maxillae. Anti-TNF-α therapy prevented the development of both AIA and PD. AIA did not modify bacterial counts in the oral cavity. PD, but not AIA, induced by injection of Ag in immunized mice was decreased by local treatment with antiseptic, which decreased the oral microbiota. AIA was associated with an increase in serum C-reactive protein levels and the expression of the transcription factors RORγ and Foxp3 in cervical lymph nodes. There were higher titers of anti-collagen I IgG, and splenocytes were more responsive to collagen I in AIA mice. In conclusion, AIA-induced PD was dependent on TNF-α and the oral microbiota. Moreover, PD was associated with changes in expression of lymphocyte transcription factors, presence of anti-collagen Abs, and increased reactivity to autoantigens.

Periapical lesions are inflammatory conditions of tooth periapical tissues, triggered by dental pulp infection and characterized by exudation of immune cells to the affected tissues and production of inflammatory mediators such as cytokines. The inflammatory periapical reaction is mainly driven by Th1, Th2, and Th17 responses, and such polarization may modulate progression of the disease and expression of bone proresorptive cytokines. IL-12 is a potent inducer of IFN-γ production, which stimulates Th1 effector cells. Many evidences have shown a positive correlation between the bone resorptive cytokine IL-1β and the production of IL-12 and IFN-γ. Furthermore, IL-12 may have a potential role in the release of bone resorptive mediators and blockade of Th2 cytokines, affecting the progression of periapical bone loss. Nevertheless, IL-12 and IFN-γ have also been described as suppressors of osteoclast differentiation and activation, favoring bone maintenance. This paper focuses on the controversial roles of IL-12 in periapical lesions.

A nonphotochemical laser-induced phase transition was studied in a supercooled 4;{'}-n -pentyl-4-cyanobiphenyl (5CB, also referred to as PCB and K15) liquid crystal, using linearly polarized 45 ps light pulses at a wavelength of 532 nm. The laser induced nucleation from the metastable supercooled isotropic phase to the nematic phase during slow cooling (0.001 degrees C/min) and high light intensity (3.9 MW/cm{2}) . The resulting nematic director tended to be aligned along the direction of the plane of polarization of the light. At the intensities used, there is no observable laser-induced realignment of the director once the sample is in the nematic phase, nor any permanent laser-induced ordering when the sample is illuminated only in the stable isotropic phase during slow cooling. These experimental results are consistent with a mechanism based on optical Kerr alignment.