Transmissão vertical do HIV na rede de saúde: reflexões bioéticas sobre gênero e cuidado a partir de um caso emblemático / Vertical transmission of HIV in the health network: bioethics reflections on gender and care based on an emblematic case

Resumo Num cenário epidêmico ainda preocupante, a prevenção da Transmissão Vertical (TV) do HIV impõe problemas complexos, devido as vulnerabilidades individual, social e moral das mulheres vivendo com o vírus, somadas às fragilidades da rede de saúde. A partir de um caso emblemático, este estudo buscou compreender os desafios bioéticos do cuidado para a prevenção da TV do HIV no âmbito do Comitê de Porto Alegre/RS. Os eixos analíticos desenvolvidos refletem sobre como a produção do cuidado se articula, por um lado, com discursos e práticas relacionais pautadas no gênero e interseccionadas por raça e classe social e, por outro, com vulnerabilidades programáticas das políticas de saúde. Vislumbrou-se um processo de extrema estigmatização, em que as poucas ofertas para as mulheres cisgênero se dirigiam à regulação reprodutiva e perpetuavam dinâmicas de violência estrutural. Discute-se caminhos para a construção de um cuidado que incorpore a perspectiva decolonial e busque produzir equidade e justiça social ao reconhecer as trajetórias das mulheres.

Abstract In a still worrying epidemic scenario, the prevention of Vertical Transmission (VT) of HIV poses complex problems, due to the individual, social, and moral vulnerabilities of women living with the virus, in addition to the weaknesses of the health network. Based on an emblematic case, this study sought to understand the bioethical challenges of HIV VT prevention in the scope of the Porto Alegre/RS Committee. The analytical categories developed reflect on how the production of care is articulated, on the one hand, with relational discourses and practices based on gender and intersected by race and social class and, on the other, with programmatic vulnerabilities of health policies. A process of extreme stigmatization was revealed, in which the few offers for cisgender women were aimed toward reproductive regulation and perpetuated dynamics of structural violence. We discuss ways of building care that incorporates a decolonial perspective and seeks to produce equity and social justice by recognizing women's trajectories.

Epidemiological profile and genetic resistance of Neisseria gonorrhoeae infection in women in a poor region of São Paulo, Brazil.

BACKGROUND AND AIM: Gonorrhea is a bacterial infection in the urogenital tract, transmitted by sexual or perinatal contact, caused by Neisseria gonorrhoeae, a gram-negative diplococcus. The present study evaluates the frequency of N. gonorrhoeae in women treated at Hospital Wladimir Arruda in poor area of São Paulo and also verifies the presence of genetic resistance against three antimicrobials of different classes: Tetracycline, Azithromycin and Ciprofloxacin. METHODS: This is an observational and descriptive study with a quantitative approach. Samples were collected at Hospital Escola Wladimir Arruda. The volunteers are women from 16 to 65 years of age. Sociodemographic, gynecological, sexual and health data are collected through a questionnaire, their symptoms/clinical manifestation were requested by the medical records, and then the participant is referred for collection of samples of cervical vaginal smear. The samples were screened for N. gonorrhoeae (dcmH gene) and tested for resistance genes to Tetracycline, Azithromycin and Ciprofloxacin through PCR. RESULTS: In the total of 127 samples analyzed by Real-Time PCR, 23 were positive and correspond to a general prevalence of a gonococcal infection in the studied population of 17% (CI:95%), and the participants were married (43.4%), had active sexual life (56.5%) and did not use any type of condom during sexual intercourse (52.1%). The resistance to the tetM ribosomal gene was found in 14 samples, prevalence of 60% (CI= 95%). CONCLUSIONS: We have described a concerning frequency of N. gonorrhoeae infection in females attended in an outcare patient. Also, most of the strains detected presented resistance to one or more antimicrobials.

Astrocyte structural heterogeneity in the mouse hippocampus.

Astrocytes are integral components of brain circuits, where they sense, process, and respond to surrounding activity, maintaining homeostasis and regulating synaptic transmission, the sum of which results in behavior modulation. These interactions are possible due to their complex morphology, composed of a tree-like structure of processes to cover defined territories ramifying in a mesh-like system of fine leaflets unresolved by conventional optic microscopy. While recent reports devoted more attention to leaflets and their dynamic interactions with synapses, our knowledge about the tree-like "backbone" structure in physiological conditions is incomplete. Recent transcriptomic studies described astrocyte molecular diversity, suggesting structural heterogeneity in regions such as the hippocampus, which is crucial for cognitive and emotional behaviors. In this study, we carried out the structural analysis of astrocytes across the hippocampal subfields of Cornu Ammonis area 1 (CA1) and dentate gyrus in the dorsoventral axis. We found that astrocytes display heterogeneity across the hippocampal subfields, which is conserved along the dorsoventral axis. We further found that astrocytes appear to contribute in an exocytosis-dependent manner to a signaling loop that maintains the backbone structure. These findings reveal astrocyte heterogeneity in the hippocampus, which appears to follow layer-specific cues and depend on the neuro-glial environment.

Circulating Dopamine Is Regulated by Dietary Glucose and Controls Glucagon-like 1 Peptide Action in White Adipose Tissue.

Dopamine directly acts in the liver and white adipose tissue (WAT) to regulate insulin signaling, glucose uptake, and catabolic activity. Given that dopamine is secreted by the gut and regulates insulin secretion in the pancreas, we aimed to determine its regulation by nutritional cues and its role in regulating glucagon-like peptide 1 (GLP-1) action in WAT. Solutions with different nutrients were administered to Wistar rats and postprandial dopamine levels showed elevations following a mixed meal and glucose intake. In high-fat diet-fed diabetic Goto-Kakizaki rats, sleeve gastrectomy upregulated dopaminergic machinery, showing the role of the gut in dopamine signaling in WAT. Bromocriptine treatment in the same model increased GLP-1R in WAT, showing the role of dopamine in regulating GLP-1R. By contrast, treatment with the GLP-1 receptor agonist Liraglutide had no impact on dopamine receptors. GLP-1 and dopamine crosstalk was shown in rat WAT explants, since dopamine upregulated GLP-1-induced AMPK activity in mesenteric WAT in the presence of the D2R and D3R inhibitor Domperidone. In human WAT, dopamine receptor 1 (D1DR) and GLP-1R expression were correlated. Our results point out a dietary and gut regulation of plasma dopamine, acting in the WAT to regulate GLP-1 action. Together with the known dopamine action in the pancreas, such results may identify new therapeutic opportunities to improve metabolic control in metabolic disorders.

Peripheral Dopamine Directly Acts on Insulin-Sensitive Tissues to Regulate Insulin Signaling and Metabolic Function.

Dopamine is a key regulator of glucose metabolism in the central nervous system. However, dopamine is also present in the periphery and may have direct effects on insulin-sensitive tissues. Dopamine receptor 2 (D2R) agonist bromocriptine is a FDA-approved drug for type 2 diabetes. Herein, we explored the role of peripheral dopamine and its receptors in regulating glucose uptake and metabolism on insulin-sensitive tissues. Peripheral dopamine effect in [3H]2-deoxyglucose uptake in insulin-sensitive tissues was tested in vivo in rats. Direct effects on [3H]2-deoxyglucose uptake, insulin receptor phosphorylation, and regulation of metabolic function were tested ex vivo in the liver, soleus muscle, and white and brown adipose tissues. Bromocriptine and the antagonists domperidone, D2R antagonist, and haloperidol, antagonist of both dopamine receptor 1 (D1R) and D2R, were used to disclose dopamine receptors' involvement. Peripheral dopamine increases glucose uptake in vivo. Ex vivo, only dopamine increased glucose uptake in the soleus, while bromocriptine increased it in the liver; the effects were reverted by haloperidol and domperidone, respectively. In adipose tissue, domperidone reverted dopamine- and bromocriptine-mediated potentiation of insulin-induced glucose uptake, but in turn increased the insulin receptor, Akt, AMPK, HSL, ACC, and ACL, phosphorylation. In the soleus muscle, AMPK-phosphorylation increased with bromocriptine and dopamine whose effects were suppressed by domperidone and haloperidol. In conclusion, peripheral dopamine stimulates glucose uptake with its receptors being differentially involved in glucose uptake in insulin-sensitive tissues. Dopamine also has a role in lipid metabolism in white adipose tissue. Altogether, these results suggest that peripheral modulation of the dopaminergic system should be further evaluated as a putative therapeutic approach for metabolic disorders.

Ações dos Tribunais de Contas no enfrentamento dos efeitos do coronavírus / Acciones de los Tribunales de Cuentas para enfrentar los efectos del coronavirus / Actions by the Courts of Accounts to minimize effects of coronavirus

Resumo Este estudo visa evidenciar os esforços empreendidos pelos Tribunais de Contas (TCs) brasileiros no período de pandemia do coronavírus a fim de colaborar com seus jurisdicionados, seus servidores e a sociedade para o enfrentamento de seus efeitos. Realizou-se pesquisa descritiva, com abordagem qualitativa, por meio de análise das legislações emitidas pelos TCs, para avaliação das ações tomadas por eles. Entre os achados, destacam-se as ações de âmbito interno e pedagógicas empreendidas na forma de medidas destinadas ao público externo (como a limitação no atendimento presencial), à suspensão de eventos coletivos, de reuniões presenciais e viagens, à adoção de teletrabalho, ao contingenciamento de despesas, cursos à distância etc. Entre as ações processuais, destacam-se as suspensões de Sessões Plenárias ou das Câmaras, dos prazos processuais e da remessa das prestações de contas. Por fim, no tocante às ações orientativas e de monitoramento empreendidas pelos TCs, constatou-se que foi elaborada uma série de diretrizes e recomendações em relação às práticas adotadas pelos órgãos de controle externo de modo colaborativo aos demais poderes, de modo orientar os gastos públicos, a aquisição e a contratação de serviços com dispensa de licitação, entre outros riscos. Conclui-se que o conjunto de medidas implementadas pelos TCs demonstra mudança no status tradicional de controle posterior das contas públicas, que enseja uma atuação punitiva para um controle prévio e concomitante, por meio de recomendações, fiscalizações e monitoramento, quando o gestor ainda dispõe de instrumentos para corrigir eventuais erros e evitar o desperdício e a má aplicação do recurso público.

Resumen Este estudio tiene como objetivo evidenciar los esfuerzos realizados por los Tribunales de Cuentas (TC) brasileños en el período de la pandemia de coronavirus para colaborar con sus jurisdiccionales, funcionarios y la sociedad para enfrentar sus efectos. Se realizó una investigación descriptiva con enfoque cualitativo mediante el análisis de la legislación emitida por los TC para evaluar las acciones tomadas por los estos. Entre los resultados, se destacan las acciones administrativas y pedagógicas emprendidas en forma de medidas dirigidas al público externo, como la limitación en el servicio presencial, la suspensión de eventos colectivos, de reuniones presenciales y viajes; la adopción del teletrabajo, la restricción de gastos, y cursos de aprendizaje a distancia. Entre las acciones procesales están las suspensiones de sesiones plenarias o cámaras, de plazos procesales y de envío de las prestaciones de cuentas. Finalmente, con respecto a las acciones de orientación y supervisión emprendidas por los TC, se constató la elaboración de una serie de directrices y recomendaciones con relación a las prácticas adoptadas por los organismos de control externo de manera colaborativa con los otros poderes, a los efectos de orientar el gasto público, la adquisición y contratación de servicios sin licitación, entre otros riesgos. Se concluye que el conjunto de medidas implementadas por los TC muestra un cambio en el estatus tradicional: del control posterior de las cuentas públicas ‒ que da lugar a acciones punitivas ‒ hacia el control previo y concomitante, a través de recomendaciones, inspecciones y monitoreo, cuando el administrador tiene los instrumentos para corregir eventuales errores y evitar el desperdicio y la mala utilización de los recursos públicos.

Abstract This study aims to highlight the efforts made by the Brazilian Courts of Accounts (CAs) during the COVID-19 pandemic to collaborate with its jurisdictional authorities, civil servants, and society to face its effects. Descriptive and qualitative research was carried out, analyzing the legislation issued by the CAs to evaluate their actions. Among the findings, it was observed that the CAs took administrative and pedagogical measures to protect the public, such as the suspension or restriction of face-to-face service. Also, the courts suspended collective events, face-to-face meetings, and travel, adopted telework, limited expenditures and distance learning courses. Among the procedural measures, Plenary Sessions or Chambers, procedural deadlines, and remittance of accounts were suspended. Finally, the activities of guidance and monitoring were conducted under a series of guidelines and recommendations created collaboratively with other agencies and branches of government, guiding public spending, the acquisition and contracting of services with no bidding requirements, among other procedures. It is concluded that the set of measures implemented by the CAs shows a change in the traditional status of subsequent control of public accounts - which gives rise to punitive action - for prior and concurrent control, with recommendations, inspections, and monitoring, when the manager still has instruments to amend errors and avoid waste and misapplication of public resources.

The Attentional Drift Diffusion Model of Simple Perceptual Decision-Making.

Perceptual decisions requiring the comparison of spatially distributed stimuli that are fixated sequentially might be influenced by fluctuations in visual attention. We used two psychophysical tasks with human subjects to investigate the extent to which visual attention influences simple perceptual choices, and to test the extent to which the attentional Drift Diffusion Model (aDDM) provides a good computational description of how attention affects the underlying decision processes. We find evidence for sizable attentional choice biases and that the aDDM provides a reasonable quantitative description of the relationship between fluctuations in visual attention, choices and reaction times. We also find that exogenous manipulations of attention induce choice biases consistent with the predictions of the model.

Astrocytic signaling supports hippocampal-prefrontal theta synchronization and cognitive function.

Astrocytes interact with neurons at the cellular level through modulation of synaptic formation, maturation, and function, but the impact of such interaction into behavior remains unclear. Here, we studied the dominant negative SNARE (dnSNARE) mouse model to dissect the role of astrocyte-derived signaling in corticolimbic circuits, with implications for cognitive processing. We found that the blockade of gliotransmitter release in astrocytes triggers a critical desynchronization of neural theta oscillations between dorsal hippocampus and prefrontal cortex. Moreover, we found a strong cognitive impairment in tasks depending on this network. Importantly, the supplementation with d-serine completely restores hippocampal-prefrontal theta synchronization and rescues the spatial memory and long-term memory of dnSNARE mice. We provide here novel evidence of long distance network modulation by astrocytes, with direct implications to cognitive function.

Employing an open-source tool to assess astrocyte tridimensional structure.

Astrocytes display important features that allow them to maintain a close dialog with neurons, ultimately impacting brain function. The complex morphological structure of astrocytes is crucial to the role of astrocytes in brain networks. Therefore, assessing morphologic features of astrocytes will help provide insights into their physiological relevance in healthy and pathological conditions. Currently available tools that allow the tridimensional reconstruction of astrocytes present a number of disadvantages, including the need for advanced computational skills and powerful hardware, and are either time-consuming or costly. In this study, we optimized and validated the FIJI-ImageJ, Simple Neurite Tracer (SNT) plugin, an open-source software that aids in the reconstruction of GFAP-stained structure of astrocytes. We describe (1) the loading of confocal microscopy Z-stacks, (2) the selection criteria, (3) the reconstruction process, and (4) the post-reconstruction analysis of morphological features (process length, number, thickness, and arbor complexity). SNT allows the quantification of astrocyte morphometric parameters in a simple, efficient, and semi-automated manner. While SNT is simple to learn, and does not require advanced computational skills, it provides reproducible results, in different brain regions or pathophysiological states.

'Smelling' the cerebrospinal fluid: olfactory signaling molecules are expressed in and mediate chemosensory signaling from the choroid plexus.

The olfactory-type signaling machinery has been known to be involved not only in odorant detection but also in other tissues with unsuspected sensory roles. As a barrier, the choroid plexus (CP) is an active participant in the monitoring of the cerebrospinal fluid (CSF), promptly responding to alterations in its composition. We hypothesized that olfactory signaling could be active in CP, contributing to the surveillance of the CSF composition. We determined the mRNA and protein expression of the major components of the olfactory transduction pathway in the rat CP, including odorant receptors, the olfactory G-protein (Gαolf), adenylate cyclase 3 and cyclic nucleotide-gated channel 2. The functionality of the transduction pathway and the intracellular mechanisms involved were analyzed by DC field potential recording electrophysiological analysis, in an ex vivo CP-brain setup, using polyamines as stimuli and blockers of the downstream signaling pathways. Concentration-dependent responses were obtained for the polyamines studied (cadaverine, putrescine, spermine and spermidine), all known to be present in the CSF. Transfection of a CP epithelial cell line with siRNA against Gαolf effectively knocked down protein expression and reduced the CP cells' response to spermine. Thus, the key components of the olfactory chemosensory apparatus are present and are functional in murine CP, and polyamines seem to trigger both the cAMP and the phospholipase C-inositol 1,4,5-trisphosphate pathways. Olfactory-like chemosensory signaling may be an essential component of the CP chemical surveillance apparatus to detect alterations in the CSF composition, and to elicit responses to modulate and maintain brain homeostasis.

Taraxerol 4-Methoxybenzoate, an in vitro Inhibitor of Photosynthesis Isolated from Pavonia multiflora A. St-Hil. (Malvaceae).

A phytochemical study of Pavonia multiflora A. St-Hil. (Malvaceae) led to the isolation through chromatographic techniques of 10 secondary metabolites: vanillic acid (1), ferulic acid (2), p-hydroxybenzoic acid (3), p-coumaric acid (4), loliolide (5), vomifoliol (6), 4,5-dihydroblumenol A (7), 3-oxo-α-ionol (9), blumenol C (10), and taraxerol 4-methoxybenzoate (8), the latter being a novel metabolite. Their structures were identified by (1) H- and (13) C-NMR, using one- and two-dimensional techniques, and X-ray crystallography. In this work, we report the effect of compounds 5 and 8 on several photosynthetic activities in an attempt to search for new compounds as potential herbicide agents that affect photosynthesis. Both compounds inhibited the electron flow from H2 O to methyl viologen; therefore, they act as Hill reaction inhibitors. Using polarographic techniques and studies of the fluorescence of chlorophyll a, the interaction sites of these compounds were located at photosystem II.

Scaling-laws of human broadcast communication enable distinction between human, corporate and robot Twitter users.

Human behaviour is highly individual by nature, yet statistical structures are emerging which seem to govern the actions of human beings collectively. Here we search for universal statistical laws dictating the timing of human actions in communication decisions. We focus on the distribution of the time interval between messages in human broadcast communication, as documented in Twitter, and study a collection of over 160,000 tweets for three user categories: personal (controlled by one person), managed (typically PR agency controlled) and bot-controlled (automated system). To test our hypothesis, we investigate whether it is possible to differentiate between user types based on tweet timing behaviour, independently of the content in messages. For this purpose, we developed a system to process a large amount of tweets for reality mining and implemented two simple probabilistic inference algorithms: 1. a naive Bayes classifier, which distinguishes between two and three account categories with classification performance of 84.6% and 75.8%, respectively and 2. a prediction algorithm to estimate the time of a user's next tweet with an R(2) ≈ 0.7. Our results show that we can reliably distinguish between the three user categories as well as predict the distribution of a user's inter-message time with reasonable accuracy. More importantly, we identify a characteristic power-law decrease in the tail of inter-message time distribution by human users which is different from that obtained for managed and automated accounts. This result is evidence of a universal law that permeates the timing of human decisions in broadcast communication and extends the findings of several previous studies of peer-to-peer communication.

Familial hyperparathyroidism: surgical outcome after 30 years of follow-up in three families with germline HRPT2 mutations.

BACKGROUND: Familial forms of hyperparathyroidism are responsible for approximately 10% of the cases of primary hyperparathyroidism, and their management is different from the sporadic forms. Our objective was to study the gene sequence and expression of HRPT2 and clinical outcome regarding recurrence or persistence rates in three Brazilian kindreds with familial hyperparathyroidism after up to 30 years of follow-up. METHODS: Clinical and biochemical data, direct sequencing of germline DNA of the HRPT2 gene, and analysis of parafibromin expression (HRPT2 gene product) using RT-PCR and immunohistochemistry of resected parathyroid neoplasms were performed. RESULTS: Affected members of kindred A were found to carry a novel, germline, nonsense mutation in exon 1 (c.96G>A; W32X) of HRPT2. Six of seven patients who have undergone less than total parathyroidectomy recurred after up to 30 years of follow-up. An unrelated affected patient from kindred B had a germline mutation in exon 7 (c.686delGAGT), and the disease recurred with several pulmonary metastases after 5 years follow-up. The affected member of kindred C also had a previously described mutation in exon 7 (c.679delAG) and the disease recurred after 10 years of follow-up. All parathyroid neoplasms from these families had diffuse loss of expression by immunohistochemistry. CONCLUSIONS: An unacceptable recurrence/persistence rate (80%) associated with increasingly difficult re-operations and risk of parathyroid carcinoma in the setting of germline mutations of HRPT2 gene with familial hyperparathyroidism suggest that a more aggressive operative approach should be undertaken in these patients. Parafibromin immunohistochemistry may serve as a cost-effective screen for HRPT2-related aggressive parathyroid disease.

HRPT2 gene alterations in ossifying fibroma of the jaws.

Ossifying fibroma (OF) is a benign neoplasm related to bone characterized by a progressive enlargement of the affected jaw. Recently, the candidate tumor suppressor gene HRPT2 was identified and alterations in this gene were related with the Hyperparathyroidism-jaw tumor syndrome that is characterized by parathyroid adenoma or carcinoma, fibro-osseous lesions (mainly OF) of the jaws, and renal lesions. The purpose of the present study was to evaluate the HRPT2 gene in OF. Tumour and blood samples were obtained from 3 patients with OF and one with juvenile ossifying fibroma (JOF). The results demonstrated three novel mutations in two out of three genotyped OF's. Interestingly, one of these patients showed a germ-line mutation after blood analysis. RT-PCR amplification was performed to analyze HRPT2 mRNA expression and only wild-type HRPT2 transcript was found in all tumours. Investigation of the parafibromin protein by immunohistochemistry showed a similar pattern of immunolocalization with strong nuclear and cytoplasmic staining in all cases. In conclusion, the present study shows for the first time mutations of HRPT2 gene in OF and suggests that OF may arise due to haploinsufficiency of the HRPT2 gene.