Reproductive toxicity of maternal exposure to di(2-ethylhexyl)phthalate and butyl paraben (alone or in association) on both male and female Wistar offspring.

Parabens and phthalates are commonly found as contaminants in human fluids and are able to provoke reproductive toxicity, being considered endocrine disruptors. To evaluate the effects of phthalate and paraben, alone or in combination, on reproductive development of the offspring, female pregnant Wistar rats were allocated in six experimental groups: Three control groups (gavage [CG], subcutaneous [CS], and gavage + subcutaneous) received corn oil as vehicle, and the remaining groups were exposed to di(2-ethylhexyl)phthalate (DEHP) (500 mg/kg, gavage), butyl paraben (BP) (100 mg/kg, subcutaneously), or MIX (DEHP + BP), from Gestational Day 12 until Postnatal Day (PND) 21. The following parameters were assessed on the offspring: anogenital distance and weight at PND 1, nipple counting at PND 13, puberty onset, estrous cycle, weights of reproductive and detoxifying organs, histological evaluation of reproductive organs, and sperm evaluations (counts, morphology, and motility). Female pups from MIX group presented reduced body weight at PND 1, lower AGD, and decreased endometrium thickness. Male animals showed decreased body weight at PND 1 and lower number of Sertoli cells on DEHP and MIX groups, MIX group revealed increase of abnormal seminiferous tubules, DEHP animals presented delayed preputial separation and higher percentage of immotile sperms, and BP males presented diminished number of Leydig cells. In conclusion, the male offspring was more susceptible to DEHP toxicity; even when mixed to paraben, the main negative effects observed seem to be due to antiandrogenic phthalate action. On the other hand, DEHP seems to be necessary to improve the effects of BP on reducing estrogen-dependent and increasing androgen-dependent events.

Context-dependent operation of neural circuits underlies a navigation behavior in Caenorhabditis elegans.

The nervous system evaluates environmental cues and adjusts motor output to ensure navigation toward a preferred environment. The nematode Caenorhabditis elegans navigates in the thermal environment and migrates toward its cultivation temperature by moving up or down thermal gradients depending not only on absolute temperature but on relative difference between current and previously experienced cultivation temperature. Although previous studies showed that such thermal context-dependent opposing migration is mediated by bias in frequency and direction of reorientation behavior, the complete neural pathways-from sensory to motor neurons-and their circuit logics underlying the opposing behavioral bias remain elusive. By conducting comprehensive cell ablation, high-resolution behavioral analyses, and computational modeling, we identified multiple neural pathways regulating behavioral components important for thermotaxis, and demonstrate that distinct sets of neurons are required for opposing bias of even single behavioral components. Furthermore, our imaging analyses show that the context-dependent operation is evident in sensory neurons, very early in the neural pathway, and manifested by bidirectional responses of a first-layer interneuron AIB under different thermal contexts. Our results suggest that the contextual differences are encoded among sensory neurons and a first-layer interneuron, processed among different downstream neurons, and lead to the flexible execution of context-dependent behavior.

Synapsin Is Required for Dense Core Vesicle Capture and cAMP-Dependent Neuropeptide Release.

Release of neuropeptides from dense core vesicles (DCVs) is essential for neuromodulation. Compared with the release of small neurotransmitters, much less is known about the mechanisms and proteins contributing to neuropeptide release. By optogenetics, behavioral analysis, electrophysiology, electron microscopy, and live imaging, we show that synapsin SNN-1 is required for cAMP-dependent neuropeptide release in Caenorhabditis elegans hermaphrodite cholinergic motor neurons. In synapsin mutants, behaviors induced by the photoactivated adenylyl cyclase bPAC, which we previously showed to depend on ACh and neuropeptides (Steuer Costa et al., 2017), are altered as in animals with reduced cAMP. Synapsin mutants have slight alterations in synaptic vesicle (SV) distribution; however, a defect in SV mobilization was apparent after channelrhodopsin-based photostimulation. DCVs were largely affected in snn-1 mutants: DCVs were ∼30% reduced in synaptic terminals, and their contents not released following bPAC stimulation. Imaging axonal DCV trafficking, also in genome-engineered mutants in the serine-9 protein kinase A phosphorylation site, showed that synapsin captures DCVs at synapses, making them available for release. SNN-1 colocalized with immobile, captured DCVs. In synapsin deletion mutants, DCVs were more mobile and less likely to be caught at release sites, and in nonphosphorylatable SNN-1B(S9A) mutants, DCVs traffic less and accumulate, likely by enhanced SNN-1 dependent tethering. Our work establishes synapsin as a key mediator of neuropeptide release.SIGNIFICANCE STATEMENT Little is known about mechanisms that regulate how neuropeptide-containing dense core vesicles (DCVs) traffic along the axon, how neuropeptide release is orchestrated, and where it occurs. We found that one of the longest known synaptic proteins, required for the regulation of synaptic vesicles and their storage in nerve terminals, synapsin, is also essential for neuropeptide release. By electrophysiology, imaging, and electron microscopy in Caenorhabditis elegans, we show that synapsin regulates this process by tethering the DCVs to the cytoskeleton in axonal regions where neuropeptides are to be released. Without synapsin, DCVs cannot be captured at the release sites and, consequently, cannot fuse with the membrane, and neuropeptides are not released. We suggest that synapsin fulfills this role also in vertebrates, including humans.

Rhodopsin-based voltage imaging tools for use in muscles and neurons of Caenorhabditis elegans.

Genetically encoded voltage indicators (GEVIs) based on microbial rhodopsins utilize the voltage-sensitive fluorescence of all-trans retinal (ATR), while in electrochromic FRET (eFRET) sensors, donor fluorescence drops when the rhodopsin acts as depolarization-sensitive acceptor. In recent years, such tools have become widely used in mammalian cells but are less commonly used in invertebrate systems, mostly due to low fluorescence yields. We systematically assessed Arch(D95N), Archon, QuasAr, and the eFRET sensors MacQ-mCitrine and QuasAr-mOrange, in the nematode Caenorhabditis elegans ATR-bearing rhodopsins reported on voltage changes in body wall muscles (BWMs), in the pharynx, the feeding organ [where Arch(D95N) showed approximately 128% ΔF/F increase per 100 mV], and in neurons, integrating circuit activity. ATR fluorescence is very dim, yet, using the retinal analog dimethylaminoretinal, it was boosted 250-fold. eFRET sensors provided sensitivities of 45 to 78% ΔF/F per 100 mV, induced by BWM action potentials, and in pharyngeal muscle, measured in simultaneous optical and sharp electrode recordings, MacQ-mCitrine showed approximately 20% ΔF/F per 100 mV. All sensors reported differences in muscle depolarization induced by a voltage-gated Ca2+-channel mutant. Optogenetically evoked de- or hyperpolarization of motor neurons increased or eliminated action potential activity and caused a rise or drop in BWM sensor fluorescence. Finally, we analyzed voltage dynamics across the entire pharynx, showing uniform depolarization but compartmentalized repolarization of anterior and posterior parts. Our work establishes all-optical, noninvasive electrophysiology in live, intact C. elegans.

In vivo synaptic recovery following optogenetic hyperstimulation.

Local recycling of synaptic vesicles (SVs) allows neurons to sustain transmitter release. Extreme activity (e.g., during seizure) may exhaust synaptic transmission and, in vitro, induces bulk endocytosis to recover SV membrane and proteins; how this occurs in animals is unknown. Following optogenetic hyperstimulation of Caenorhabditis elegans motoneurons, we analyzed synaptic recovery by time-resolved behavioral, electrophysiological, and ultrastructural assays. Recovery of docked SVs and of evoked-release amplitudes (indicating readily-releasable pool refilling) occurred within ∼8-20 s (τ = 9.2 s and τ = 11.9 s), whereas locomotion recovered only after ∼60 s (τ = 20 s). During ∼11-s stimulation, 50- to 200-nm noncoated vesicles ("100nm vesicles") formed, which disappeared ∼8 s poststimulation, likely representing endocytic intermediates from which SVs may regenerate. In endophilin, synaptojanin, and dynamin mutants, affecting endocytosis and vesicle scission, resolving 100nm vesicles was delayed (>20 s). In dynamin mutants, 100nm vesicles were abundant and persistent, sometimes continuous with the plasma membrane; incomplete budding of smaller vesicles from 100nm vesicles further implicates dynamin in regenerating SVs from bulk-endocytosed vesicles. Synaptic recovery after exhaustive activity is slow, and different time scales of recovery at ultrastructural, physiological, and behavioral levels indicate multiple contributing processes. Similar processes may jointly account for slow recovery from acute seizures also in higher animals.

Caenorhabditis elegans nicotinic acetylcholine receptors are required for nociception.

Polymodal nociceptors sense and integrate information on injurious mechanical, thermal, and chemical stimuli. Chemical signals either activate nociceptors or modulate their responses to other stimuli. One chemical known to activate or modulate responses of nociceptors is acetylcholine (ACh). Across evolution nociceptors express subunits of the nicotinic acetylcholine receptor (nAChR) family, a family of ACh-gated ion channels. The roles of ACh and nAChRs in nociceptor function are, however, poorly understood. Caenorhabditis elegans polymodal nociceptors, PVD, express nAChR subunits on their sensory arbor. Here we show that mutations reducing ACh synthesis and mutations in nAChR subunits lead to defects in PVD function and morphology. A likely cause for these defects is a reduction in cytosolic calcium measured in ACh and nAChR mutants. Indeed, overexpression of a calcium pump in PVD mimics defects in PVD function and morphology found in nAChR mutants. Our results demonstrate, for the first time, a central role for nAChRs and ACh in nociceptor function and suggest that calcium permeating via nAChRs facilitates activity of several signaling pathways within this neuron.

Pre-Exposure Prophylaxis to Prevent Hematophagous Bat-Mediated Rabies Outbreaks in Remote Amazon Communities: Lessons from a Pilot for Public Health Policy.

In 2018, an outbreak of human rabies caused by the hematophagous bat Desmodus rotundus hit the Brazilian Amazon Basin community of Melgaço, Brazil, resulting in the death of 10 people, 9 of them children. The incidence of rabies has been on the rise among populations in conditions of vulnerability in this ecosystem due to human expansion into sylvatic environments and limited access to public health services. To address this issue, in September 2019, a collaborative effort from national, local, and international institutions promoted and executed a pilot for pre-exposure prophylaxis of a population in high-risk areas for hematophagous bat-mediated rabies. This measure is usually only implemented in response to outbreaks. The pilot was conducted in Portel, in a nearby location to the previous outbreak, with the use of fluvial transportation, and 2987 individuals in 411 dwellings were successfully vaccinated. It established a methodology for pre-exposure prophylaxis for populations in conditions of vulnerability, identifying logistics and costs, as well as characterizing the target riverine population regarding risk factors associated with bites by hematophagous bats. This approach offers a proactive measure to prevent future outbreaks and provides valuable insights into how to address the issue of rabies in remote and difficult-to-reach areas.

Photoactivated Adenylyl Cyclases as Optogenetic Modulators of Neuronal Activity.

In the past 15 years, optogenetic methods became invaluable tools in neurobiological research but also in general cell biology. Most prominently, optogenetic methods utilize microbial rhodopsins to elicit neuronal de- or hyperpolarization. However, other optogenetic tools have emerged that allow influencing neuronal function by different approaches. In this chapter we describe the use of photoactivated adenylyl cyclases (PACs) as modulators of neuronal activity. Using Caenorhabditis elegans as a model organism, this chapter shows how to measure the effect of PAC photoactivation by behavioral assays in different tissues (neurons and muscles), as well as their significance to neurobiology. Further, this chapter describes in vitro cyclic nucleoside-3',5'-monophosphate measurements (cNMP) to characterize new PACs in C. elegans.

A Protocol for the Diagnosis of Autism Spectrum Disorder Structured in Machine Learning and Verbal Decision Analysis.

Autism Spectrum Disorder is a mental disorder that afflicts millions of people worldwide. It is estimated that one in 160 children has traces of autism, with five times the higher prevalence in boys. The protocols for detecting symptoms are diverse. However, the following are among the most used: the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5), of the American Psychiatric Association; the Revised Autistic Diagnostic Observation Schedule (ADOS-R); the Autistic Diagnostic Interview (ADI); and the International Classification of Diseases, 10th edition (ICD-10), published by the World Health Organization (WHO) and adopted in Brazil by the Unified Health System (SUS). The application of machine learning models helps make the diagnostic process of Autism Spectrum Disorder more precise, reducing, in many cases, the number of criteria necessary for evaluation, denoting a form of attribute engineering (feature engineering) efficiency. This work proposes a hybrid approach based on machine learning algorithms' composition to discover knowledge and concepts associated with the multicriteria method of decision support based on Verbal Decision Analysis to refine the results. Therefore, the study has the general objective of evaluating how the mentioned hybrid methodology proposal can make the protocol derived from ICD-10 more efficient, providing agility to diagnosing Autism Spectrum Disorder by observing a minor symptom. The study database covers thousands of cases of people who, once diagnosed, obtained government assistance in Brazil.

Epidermal Growth Factor Signaling Promotes Sleep through a Combined Series and Parallel Neural Circuit.

Sleep requires sleep-active neurons that depolarize to inhibit wake circuits. Sleep-active neurons are under the control of homeostatic mechanisms that determine sleep need. However, little is known about the molecular and circuit mechanisms that translate sleep need into the depolarization of sleep-active neurons. During many stages and conditions in C. elegans, sleep requires a sleep-active neuron called RIS. Here, we defined the transcriptome of RIS and discovered that genes of the epidermal growth factor receptor (EGFR) signaling pathway are expressed in RIS. Because of cellular stress, EGFR directly activates RIS. Activation of EGFR signaling in the ALA neuron has previously been suggested to promote sleep independently of RIS. Unexpectedly, we found that ALA activation promotes RIS depolarization. Our results suggest that ALA is a drowsiness neuron with two separable functions: (1) it inhibits specific behaviors, such as feeding, independently of RIS, (2) and it activates RIS. Whereas ALA plays a strong role in surviving cellular stress, surprisingly, RIS does not. In summary, EGFR signaling can depolarize RIS by an indirect mechanism through activation of the ALA neuron that acts upstream of the sleep-active RIS neuron and through a direct mechanism using EGFR signaling in RIS. ALA-dependent drowsiness, rather than RIS-dependent sleep bouts, appears to be important for increasing survival after cellular stress, suggesting that different types of behavioral inhibition play different roles in restoring health. VIDEO ABSTRACT.

A GABAergic and peptidergic sleep neuron as a locomotion stop neuron with compartmentalized Ca2+ dynamics.

Animals must slow or halt locomotion to integrate sensory inputs or to change direction. In Caenorhabditis elegans, the GABAergic and peptidergic neuron RIS mediates developmentally timed quiescence. Here, we show RIS functions additionally as a locomotion stop neuron. RIS optogenetic stimulation caused acute and persistent inhibition of locomotion and pharyngeal pumping, phenotypes requiring FLP-11 neuropeptides and GABA. RIS photoactivation allows the animal to maintain its body posture by sustaining muscle tone, yet inactivating motor neuron oscillatory activity. During locomotion, RIS axonal Ca2+ signals revealed functional compartmentalization: Activity in the nerve ring process correlated with locomotion stop, while activity in a branch correlated with induced reversals. GABA was required to induce, and FLP-11 neuropeptides were required to sustain locomotion stop. RIS attenuates neuronal activity and inhibits movement, possibly enabling sensory integration and decision making, and exemplifies dual use of one cell across development in a compact nervous system.

Using a Robust and Sensitive GFP-Based cGMP Sensor for Real-Time Imaging in Intact Caenorhabditis elegans.

cGMP plays a role in sensory signaling and plasticity by regulating ion channels, phosphodiesterases, and kinases. Studies that primarily used genetic and biochemical tools suggest that cGMP is spatiotemporally regulated in multiple sensory modalities. FRET- and GFP-based cGMP sensors were developed to visualize cGMP in primary cell culture and Caenorhabditis elegans to corroborate these findings. While a FRET-based sensor has been used in an intact animal to visualize cGMP, the requirement of a multiple emission system limits its ability to be used on its own as well as with other fluorophores. Here, we demonstrate that a C. elegans codon-optimized version of the cpEGFP-based cGMP sensor FlincG3 can be used to visualize rapidly changing cGMP levels in living, behaving C. elegans We coexpressed FlincG3 with the blue-light-activated guanylyl cyclases BeCyclOp and bPGC in body wall muscles, and found that the rate of change in FlincG3 fluorescence correlated with the rate of cGMP production by each cyclase. Furthermore, we show that FlincG3 responds to cultivation temperature, NaCl concentration changes, and sodium dodecyl sulfate in the sensory neurons AFD, ASEL/R, and PHB, respectively. Intriguingly, FlincG3 fluorescence in ASEL and ASER decreased in response to a NaCl concentration upstep and downstep, respectively, which is opposite in sign to the coexpressed calcium sensor jRGECO1a and previously published calcium recordings. These results illustrate that FlincG3 can be used to report rapidly changing cGMP levels in an intact animal, and that the reporter can potentially reveal unexpected spatiotemporal landscapes of cGMP in response to stimuli.

Combinatorial optimization models for finding genetic signatures from gene expression datasets.

The aim of this chapter is to present combinatorial optimization models and techniques for the analysis of microarray datasets. The chapter illustrates the application of a novel objective function that guides the search for high-quality solutions for sequential ordering of expression profiles. The approach is unsupervised and a metaheuristic method (a memetic algorithm) is used to provide high-quality solutions. For the problem of selecting discriminative groups of genes, we used a supervised method that has provided good results in a variety of datasets. This chapter illustrates the application of these models in an Alzheimer's disease microarray dataset.

Functionally asymmetric motor neurons contribute to coordinating locomotion of Caenorhabditis elegans.

Locomotion circuits developed in simple animals, and circuit motifs further evolved in higher animals. To understand locomotion circuit motifs, they must be characterized in many models. The nematode Caenorhabditis elegans possesses one of the best-studied circuits for undulatory movement. Yet, for 1/6th of the cholinergic motor neurons (MNs), the AS MNs, functional information is unavailable. Ventral nerve cord (VNC) MNs coordinate undulations, in small circuits of complementary neurons innervating opposing muscles. AS MNs differ, as they innervate muscles and other MNs asymmetrically, without complementary partners. We characterized AS MNs by optogenetic, behavioral and imaging analyses. They generate asymmetric muscle activation, enabling navigation, and contribute to coordination of dorso-ventral undulation as well as anterio-posterior bending wave propagation. AS MN activity correlated with forward and backward locomotion, and they functionally connect to premotor interneurons (PINs) for both locomotion regimes. Electrical feedback from AS MNs via gap junctions may affect only backward PINs.

Food Sensation Modulates Locomotion by Dopamine and Neuropeptide Signaling in a Distributed Neuronal Network.

Finding food and remaining at a food source are crucial survival strategies. We show how neural circuits and signaling molecules regulate these food-related behaviors in Caenorhabditis elegans. In the absence of food, AVK interneurons release FLP-1 neuropeptides that inhibit motorneurons to regulate body posture and velocity, thereby promoting dispersal. Conversely, AVK photoinhibition promoted dwelling behavior. We identified FLP-1 receptors required for these effects in distinct motoneurons. The DVA interneuron antagonizes signaling from AVK by releasing cholecystokinin-like neuropeptides that potentiate cholinergic neurons, in response to dopaminergic neurons that sense food. Dopamine also acts directly on AVK via an inhibitory dopamine receptor. Both AVK and DVA couple to head motoneurons by electrical and chemical synapses to orchestrate either dispersal or dwelling behavior, thus integrating environmental and proprioceptive signals. Dopaminergic regulation of food-related behavior, via similar neuropeptides, may be conserved in mammals.

Data on sand fly fauna (Diptera, Psychodidae, Phlebotominae) in Itatiaia National Park, Rio de Janeiro State, Brazil.

The sand fly fauna in Itatiaia National Park, Rio de Janeiro, Brazil, was investigated in different habitats ranging from sylvatic areas to those altered by human activity related to ecotourism, specifically identifying species that have been suggested as potential leishmaniasis vectors. Sand flies were captured from June 2002 to March 2004, using CDC light traps and Shannon traps. A total of 1,256 sand fly specimens were captured, from species belonging to genera Lutzomyia and Brumptomyia: Brumptomyia guimaraesi, B. troglodytes, Lutzomyia (Lutzomyia) amarali, L. lanei, L. migonei, L. sallesi, L. edwardsi, L. tupynambai, L. (Pintomyia) pessoai, L. (P.) bianchigalatie, L. rupicola, L. (Psathyromyia) shannoni, L. pascalei, L. (Psychodopygus) matosi, L. (P.) davisi, L. (P.) hirsuta hirsuta, L. (P.) ayrozai, L. peresi, L. monticola, and L. misionensis. Worthy of special attention were four species that are considered potential vectors for cutaneous leishmaniasis in Brazil: L. ayrozai, L. hirsuta hirsuta, L. migonei, and L. davisi, representing 19.19% of the specimens captured in this study.

Fast cAMP Modulation of Neurotransmission via Neuropeptide Signals and Vesicle Loading.

Cyclic AMP (cAMP) signaling augments synaptic transmission, but because many targets of cAMP and protein kinase A (PKA) may be involved, mechanisms underlying this pathway remain unclear. To probe this mechanism, we used optogenetic stimulation of cAMP signaling by Beggiatoa-photoactivated adenylyl cyclase (bPAC) in Caenorhabditis elegans motor neurons. Behavioral, electron microscopy (EM), and electrophysiology analyses revealed cAMP effects on both the rate and on quantal size of transmitter release and led to the identification of a neuropeptidergic pathway affecting quantal size. cAMP enhanced synaptic vesicle (SV) fusion by increasing mobilization and docking/priming. cAMP further evoked dense core vesicle (DCV) release of neuropeptides, in contrast to channelrhodopsin (ChR2) stimulation. cAMP-evoked DCV release required UNC-31/Ca2+-dependent activator protein for secretion (CAPS). Thus, DCVs accumulated in unc-31 mutant synapses. bPAC-induced neuropeptide signaling acts presynaptically to enhance vAChT-dependent SV loading with acetylcholine, thus causing increased miniature postsynaptic current amplitudes (mPSCs) and significantly enlarged SVs.

Avaliação do interesse das mulheres assistidas pelo centro de atenção à mulher de Rio do Sul em cirurgias estéticas íntimas / Evaluation of the interest of women assisted by the Centro de Atenção à Mulher (CAM) of Rio do Sul in intimate aesthetic surgeries

Introdução: O termo cirurgia genital feminina engloba várias técnicas com o objetivo de melhorar a área vulvar feminina estética e funcionalmente. Sentimentos de sofrimento emocional são comuns nas mulheres que buscam tais cirurgias, impactando significativamente em sua autoestima, sexualidade, higiene e funcionalidade vulvar. O objetivo é avaliar Avaliar o interesse das mulheres assistidas em um Centro de Atenção à Mulher em cirurgias íntimas. Métodos: Estudo observacional transversal ocorrido no Centro de Atenção à Mulher (CAM) de Rio do Sul-SC. Para coleta dos dados, foi utilizado um questionário semiestruturado elaborado pelos autores. Os dados foram tratados e agrupados no programa Microsoft Excel e realizadas as análises descritivas dos dados utilizando o programa Statistical Package for the Social Sciences (SPSS). Resultados: Os achados indicaram que houve um grande interesse geral na realização de cirurgias de estética íntima. Das 100 mulheres entrevistadas, 32 apresentavam interesse em realizar algum tipo de cirurgia de estética íntima. Conclusão: Devido à importância dada à estética íntima na interferência física, psicossocial, sexual e cotidiana, com importante impacto na qualidade de vida dessas pessoas, é imperativo que recursos adequados sejam alocados para maior fornecimento de tais procedimentos no Sistema Único de Saúde para a população do Brasil.

Introduction: The term female genital surgery encompasses several techniques to improve the female vulvar area, both aesthetically and functionally. Feelings of emotional distress are common in women who seek such surgeries, significantly impacting their self-esteem, sexuality, hygiene and vulvar functionality. The objective is to To evaluate the interest of women assisted in a Women Care Center in intimate surgery. Methods: Observational study carried out at the Women Care Center (CAM) in Rio do Sul-SC. For data collection, a semi-structured questionnaire developed by the authors was used. Data were processed and grouped in Microsoft Excel, and descriptive data analysis was performed using the Statistical Package for Social Sciences (SPSS) program. Results: The findings indicated a great general interest in performing intimate aesthetic surgeries. Of the 100 women interviewed, 32 were interested in performing some intimate aesthetic surgery. Conclusion: Due to the importance given to intimate cosmetics in physical, psychosocial, sexual and everyday interference, with a major impact on the quality of life of these people, adequate resources must be allocated to a greater supply of such procedures in the Unified Health System for the population of Brazil.

Infecções sexualmente transmissíveis na população residente no projeto de assentamento rural Nova Amazônia, Brasil / Sexually transmitted infections in the population living in the rural settlement project Nova Amazonia, Brazil

O adoecimento pode revelar impactos e consequências das desigualdades sociais, econômicas e culturais. Avaliar a soroprevalência da infecção pelo HIV, Hepatites B e C e Sífilis e o comportamento sexual dos moradores do Projeto de Assentamento Nova Amazônia (PANA). Trata-se de estudo observacional, transversal, descritivo, quantitativo e qualitativo, envolvendo 246 moradores do PANA, realizado entre novembro de 2019 e setembro de 2020. Foi aplicado um questionário e realizados testes rápidos para HIV 1 e 2, Sífilis e Hepatites B e C. Foi possível observar a prevalência de 4,1% para infecções sexualmente transmissíveis, estando associada estatisticamente com ser do gênero masculino (p = 0,04), ter mais de 40 anos (p = 0,003) e ter se relacionado com mais de 10 parceiros sexuais ao longo da vida (p = 0,03). Devido à identificação de condutas sexuais de risco, como baixíssima adesão ao uso do preservativo, faz-se necessária a realização de diagnóstico precoce e monitoramento de novos casos.

The illness can reveals impacts and consequences of social, economic and cultural inequalities. To evaluate the seroprevalence of HIV infection, Hepatitis B and C and Syphilis and sexual behavior of residents of the Nova Amazônia Settlement Project (PANA). Observational, cross-sectional, descriptive, quantitative and qualitative study, involving 246 residents of PANA, carried out between November 2019 and September 2020. A questionnaire was applied and rapid tests were performed for HIV 1 and 2, Syphilis and Hepatitis B and C. A prevalence of 4.1% for sexually transmitted diseases was observed, statistically associated with being male (p = 0.04), being over 40 years old (p = 0.003) and having been related with more than 10 sexual partners throughout life (p = 0.03). Due to the identification of risky sexual behaviors, such as very low adherence to condom use, it is necessary to perform an early diagnosis and monitor new cases.

Arrhythmogenic effects of mutated L-type Ca 2+-channels on an optogenetically paced muscular pump in Caenorhabditis elegans.

Cardiac arrhythmias are often associated with mutations in ion channels or other proteins. To enable drug development for distinct arrhythmias, model systems are required that allow implementing patient-specific mutations. We assessed a muscular pump in Caenorhabditis elegans. The pharynx utilizes homologues of most of the ion channels, pumps and transporters defining human cardiac physiology. To yield precise rhythmicity, we optically paced the pharynx using channelrhodopsin-2. We assessed pharynx pumping by extracellular recordings (electropharyngeograms--EPGs), and by a novel video-microscopy based method we developed, which allows analyzing multiple animals simultaneously. Mutations in the L-type VGCC (voltage-gated Ca(2+)-channel) EGL-19 caused prolonged pump duration, as found for analogous mutations in the Cav1.2 channel, associated with long QT syndrome. egl-19 mutations affected ability to pump at high frequency and induced arrhythmicity. The pharyngeal neurons did not influence these effects. We tested whether drugs could ameliorate arrhythmia in the optogenetically paced pharynx. The dihydropyridine analog Nemadipine A prolonged pump duration in wild type, and reduced or prolonged pump duration of distinct egl-19 alleles, thus indicating allele-specific effects. In sum, our model may allow screening of drug candidates affecting specific VGCCs mutations, and permit to better understand the effects of distinct mutations on a macroscopic level.