Corticostriatal Suppression of Appetitive Pavlovian Conditioned Responding.

The capacity to suppress learned responses is essential for animals to adapt in dynamic environments. Extinction is a process by which animals learn to suppress conditioned responding when an expected outcome is omitted. The infralimbic (IL) cortex to nucleus accumbens shell (NAcS) neural circuit is implicated in suppressing conditioned responding after extinction, especially in the context of operant cocaine-seeking behavior. However, the role of the IL-to-NAcS neural circuit in the extinction of responding to appetitive Pavlovian cues is unknown, and the psychological mechanisms involved in response suppression following extinction are unclear. We trained male Long Evans rats to associate a 10 s auditory conditioned stimulus (CS; 14 trials per session) with a sucrose unconditioned stimulus (US; 0.2 ml per CS) in a specific context, and then following extinction in a different context, precipitated a renewal of CS responding by presenting the CS alone in the original Pavlovian conditioning context. Unilateral, optogenetic stimulation of the IL-to-NAcS circuit selectively during CS trials suppressed renewal. In a separate experiment, IL-to-NAcS stimulation suppressed CS responding regardless of prior extinction and impaired extinction retrieval. Finally, IL-to-NAcS stimulation during the CS did not suppress the acquisition of Pavlovian conditioning but was required for the subsequent expression of CS responding. These results are consistent with multiple studies showing that the IL-to-NAcS neural circuit is involved in the suppression of operant cocaine-seeking, extending these findings to appetitive Pavlovian cues. The suppression of appetitive Pavlovian responding following IL-to-NAcS circuit stimulation, however, does not appear to be an extinction-dependent process.SIGNIFICANCE STATEMENT Extinction is a form of inhibitory learning through which animals learn to suppress conditioned responding in the face of nonreinforcement. We investigated the role of the IL cortex inputs to the NAcS in the extinction of responding to appetitive Pavlovian cues and the psychological mechanisms involved in response suppression following extinction. Using in vivo optogenetics, we found that stimulating the IL-to-NAcS neural circuit suppressed context-induced renewal of conditioned responding after extinction. In a separate experiment, stimulating the IL-to-NAcS circuit suppressed conditioned responding in an extinction-independent manner. These findings can be used by future research aimed at understanding how corticostriatal circuits contribute to behavioral flexibility and mental disorders that involve the suppression of learned behaviors.

Context-induced renewal of passive but not active coping behaviours in the shock-probe defensive burying task.

Renewal is the return of extinguished responding after removal from the extinction context. Renewal has been extensively studied using classical aversive conditioning procedures that measure a passive freezing response to an aversive conditioned stimulus. However, coping responses to aversive stimuli are complex and can be reflected in passive and active behaviours. Using the shock-probe defensive burying task, we investigated whether different coping responses are susceptible to renewal. During conditioning, male, Long-Evans rats were placed into a specific context (Context A) where an electrified shock-probe delivered a 3 mA shock upon contact. During extinction, the shock-probe was unarmed in either the same (Context A) or a different context (Context B). Renewal of conditioned responses was assessed in the conditioning context (ABA) or in a novel context (ABC or AAB). Renewal of passive coping responses, indicated by an increased latency and a decreased duration of shock-probe contacts, was observed in all groups. However, renewal of passive coping, measured by increased time spent on the side of the chamber opposite the shock-probe, was only found in the ABA group. Renewal of active coping responses linked to defensive burying was not observed in any group. The present findings highlight the presence of multiple psychological processes underlying even basic forms of aversive conditioning and demonstrate the importance of assessing a broader set of behaviours to tease apart these different underlying mechanisms. The current findings suggest that passive coping responses may be more reliable indicators for assessing renewal than active coping behaviours associated with defensive burying.

Leprosy and tuberculosis control scenario of the national program for the improvement of access and quality of primary care in Brazil.

BACKGROUND: In Brazil, despite advances in public health policies aimed at eliminating and controlling infectious and parasitic diseases, the incidence of neglected diseases is still high. The epidemiological scenario in Brazil of diseases such as tuberculosis and leprosy evidences a public policy agenda that has not been resolute in terms of control, nor in terms of elimination. OBJECTIVE: To analyze the actions of diagnosis and treatment of leprosy and tuberculosis in the context of primary health care. METHODS: In this ecological study, data from the third cycle of the Program for the Improvement of Access and Quality of Primary Care were extracted from electronic address of the Primary Health Care Secretariat of Brazil in the area of Actions, Programs and Strategies. A total of 37,350 primary health care teams were that answered the questionnaire were eligible, with variables extracted from leprosy and tuberculosis control actions. The municipalities were grouped according to the characteristic of the Brazilian municipality. The partition chi-square and the Residuals Test were used to assess whether there was a difference in the proportion of tuberculosis and leprosy actions between types of municipalities. Statistics were carried out using Minitab 20 and Bioestat 5.3. RESULTS: Regarding the leprosy treatment location, there is a higher proportion of people referred to be treated at the reference in adjacent rural (p = 0.0097) and urban (p < 0.0001) municipalities; monitoring of people with leprosy referred to the service network (p. = 0.0057) in remote rural areas. Lower proportion of teams requesting bacilloscopy in remote rural areas (p = 0.0019). Rural areas have a higher proportion of teams that diagnose new cases (p = 0.0004). Regarding the actions of diagnosis and treatment of tuberculosis. There is a higher proportion of teams that carry out consultations at the unit itself in rural areas when compared to adjacent intermediaries (p = 0.0099) and urban (p < 0.0001); who requested sputum smear microscopy in adjacent intermediaries (p = 0.0021); X-ray in adjacent intermediaries (p < 0.0001) and urban (p < 0.0001); collection of the first sputum sample in urban (p < 0.0001) and adjacent rural areas (p < 0.0001); directly observed treatment (p < 0.0001) in adjacent rural municipalities. CONCLUSION: There are inequalities in the diagnosis and treatment of leprosy and tuberculosis among the types of municipalities.

Safety and Preliminary Efficacy of a Novel Host-Modulatory Therapy for Reducing Gingival Inflammation.

Background: Periodontal disease is among the sixth most common inflammatory diseases worldwide with high risk to promote complications from other inflammatory diseases including diabetes, cardiovascular disease and Alzheimer's Disease. Failure of active resolution of inflammation pathways is implicated in pathogenesis of periodontal diseases, including gingivitis. Lipoxin A4 (LXA4), a member of the specialized pro-resolving lipid mediators (SPMs) that drive resolution of inflammation via GPC-receptor mediated pathways, offered therapeutic advantages in preclinical models of periodontitis. Methods: We conducted a randomized, placebo-controlled, parallel-group Phase 1 clinical trial to determine the safety and preliminary efficacy of an LXA4 analog in patients with gingival inflammation. One hundred twenty-seven (127) individuals were randomized to daily use of an oral rinse containing a LXA4 mimetic, methyl ester-benzo-lipoxin A4 (BLXA4), placebo rinse or a no-rinse control group for 28 days. Treatment emergent adverse events (TEAEs) were assessed for safety, the primary outcome. Secondary outcomes included the change in the level of gingival inflammation and periodontal pocket depth (PD). Serum SPMs were monitored using targeted lipid mediator lipidomics to assess potential systemic impact of BLXA4. Results: The frequency of TEAEs was similar in BLXA4 and placebo-treated groups with no study-related SAEs. Once-daily rinsing with BLXA4 for 28-days resulted in a greater decrease in gingival inflammation compared to placebo rinse and no-rinse control groups (mean change: 0.26 GI unit vs 0.21 and 0.17, respectively). PD reduction was also greater with BLXA4 oral rinse compared to placebo and no-rinse groups (mean reduction: 1.23 mm vs. 0.71 mm and 0.46 mm, respectively). Topical application of BLXA4 increased serum levels of SPMs. Conclusion: Treatment with BLXA4 reduces local inflammation, and increases abundance of pro-resolution molecules systemically, which may dampen inflammation that can mediate progression and course of inflammatory diseases beyond periodontitis. Clinical Trial Registration: ClinicalTrials.gov, identifier (NCT02342691).

Use of amnion-derived cellular cytokine solution for the treatment of gingivitis: A 2-week safety, dose-ranging, proof-of-principle randomized trial.

BACKGROUND: A 6-week Phase I clinical trial was performed to primarily evaluate the safety and secondarily determine the preliminary efficacy of a novel biological solution, ST266, comprised of a mixture of cytokines, growth factors, nucleic acids, and lipids secreted by cultured amnion-derived multipotent progenitor cells on gingival inflammation. METHODS: Fifty-four adults with gingivitis/periodontitis were randomly assigned to 1X ST266 or diluted 0.3X ST266 or saline topically applied on facial/lingual gingiva (20 µL/tooth). Safety was assessed through oral soft/hard tissue exam, adverse events, and routine laboratory tests. Efficacy was assessed by modified gingival index (MGI), bleeding on probing, plaque index, probing depth (PD), and clinical attachment level (CAL). Assessments were performed on day 0, 8, 12, and 42. ST266 and saline applied daily starting at day 0 through day 12 except weekend days. Plasma was analyzed for safety and proinflammatory cytokines, interleukin (IL)-1ß, IL-6, tumor necrosis factor-alpha, and interferon gamma. Gingival crevicular fluid (GCF) was analyzed for the same cytokines. Subgingival plaque was primarily analyzed by checkerboard DNA-DNA hybridization. Comparisons with saline were modeled through a generalized estimating equations method adjusting for baseline. RESULTS: No safety concern was found related to ST266. Statistically significant reduction in MGI was noted at day 42 by 1X ST266 compared with saline (P = 0.044). PD and CAL were reduced by both doses of ST266 at day 42 (P <0.01) and by 1X ST266 at day 12 (P <0.05). GCF IL-1ß and IL-6 levels were reduced by both doses of ST266 at day 12 (P <0.05, P <0.01, respectively). IL-6 was also significantly reduced in plasma of both ST266 groups (P <0.05). Significant reductions in red complex bacteria were detected in both ST266 doses. CONCLUSIONS: In this "first in human oral cavity" study, topical ST266 was safe and effective in reducing gingival inflammation in 6 weeks. Longitudinal studies with large sample sizes are warranted to assess the therapeutic value of this novel host modulatory compound in the treatment of periodontal diseases.

Práticas de Enfermagem na Coordenação do Cuidado na Atenção Primária à Saúde / Nursing Practices In Coordination Care In Primary Health Care / Prácticas de Enfermería Coordinación Del Cuidado En La Atención Primaria da Salud

Objetivo: analisar as características das equipes e as práticas associadas ao acompanhamento e coordenação do cuidado no Pará e compreender como ocorre essa prática executada pelo enfermeiro como membro da equipe na Atenção Primária à Saúde. Métodos: estudo de métodos mistos. Os participantes foram enfermeiros da atenção básica do Pará. A coleta ocorreu entre novembro de 2019 a agosto de 2021, através de um formulário eletrônico e entrevista. A análise integrativa dos dados foi feita pela conexão dos métodos qualitativos e quantitativos. Resultados: A proporção de enfermeiros que acompanha e coordena os usuários que estão em uso de outros serviços foi de 50% (90/180). Houve associação significativa (p <0,05) entre o acompanhamento e coordenação do cuidado e o tipo de equipe, carga horária de trabalho, regulação das demandas locais na perspectiva da rede, articulação com profissionais de saúde de outros níveis de atenção, trabalhos com profissionais de outras formações e a condução da clínica ampliada/ matriciamento. As categorias temáticas "relação da Atenção Primária à Saúde com a rede de atenção" e "práticas de coordenação e continuidade do cuidado horizontal e vertical" apresentaram convergência com os dados quantitativos e a categoria temática "Práticas de coordenação do cuidado sob a forma do trabalho em equipe" converge com os dados quantitativos, mas divergem no apoio matricial. Conclusão: Os enfermeiros realizam o acompanhamento e coordenação do cuidado, porém enfrentam dificuldades que resultam em sobrecarga e realização de atribuições que não são da categoria profissional. (AU)

Objective: to analyze the characteristics of the teams and the practices associated with the monitoring and coordination of care in Pará and to understand how this practice is carried out by the nurse as a member of the team in Primary Health Care. Methods: study of mixed methods. The participants were primary care nurses in Pará. The collection took place between November 2019 and August 2021, through an electronic form and interview. The integrative data analysis was performed by connecting qualitative and quantitative methods. Results: The proportion of nurses who monitor and coordinate users who are using other services was 50% (90/180). There was a significant association (p <0.05) between monitoring and coordination of care and the type of team, workload, regulation of local demands from the perspective of the network, articulation with health professionals from other levels of care, work with professionals from other backgrounds and conducting the expanded clinic/matrix support. The thematic categories "relationship between Primary Health Care and the care network" and "practices of coordination and continuity of horizontal and vertical care" showed convergence with the quantitative data and the thematic category "Practices of coordination of care in the form of work in a team" converges with the quantitative data, but differs in matrix support. Conclusion: Nurses carry out monitoring and coordination of care, but they face difficulties that result in overload and carrying out tasks that are not of the professional category. (AU)

Objetivo: analizar las características de los equipos y las prácticas asociadas al seguimiento y coordinación del cuidado en Pará y comprender cómo esa práctica es realizada por el enfermero como miembro del equipo en la Atención Primaria de Salud. Métodos: estudio de métodos mixtos. Los participantes eran enfermeros de atención primaria de Pará. La recolección se realizó entre noviembre de 2019 y agosto de 2021, a través de formulario electrónico y entrevista. El análisis integrador de datos se realizó conectando métodos cualitativos y cuantitativos. Resultados: La proporción de enfermeros que acompañan y coordinan usuarios que utilizan otros servicios fue del 50% (90/180). Hubo asociación significativa (p<0,05) entre el seguimiento y coordinación de la atención y el tipo de equipo, carga de trabajo, regulación de las demandas locales desde la perspectiva de la red, articulación con profesionales de salud de otros niveles de atención, trabajo con profesionales de otros antecedentes y dirigiendo el apoyo clínico/matriz ampliado. Las categorías temáticas "relación entre la Atención Primaria de Salud y la red de atención" y "prácticas de coordinación y continuidad del cuidado horizontal y vertical" mostraron convergencia con los datos cuantitativos y la categoría temática "Prácticas de coordinación del cuidado en la forma de trabajo en un team" converge con los datos cuantitativos, pero difiere en el soporte de la matriz. Conclusión: Los enfermeros realizan seguimiento y coordinación de los cuidados, pero enfrentan dificultades que resultan en sobrecarga y realización de tareas que no son de categoría profesional. (AU)

Speech therapy assistance to the transgender population: an experience report / Atendimento fonoaudiológico à população transgênera: um relato de experiência

An incompatible voice with one's own identity is a theme frequently pointed out by the transgender population in speech therapy sessions. Speech therapy is a technique that allows the adjustment of the speaker's voice within a range of possibilities. The speech-language pathologist's role is to provide training, guidance, and counseling to this population, taking into account the specificities of each individual. In light of this, this study aims to report the experience of undergraduate students and speech-language professionals in providing care to the transgender population in a communication laboratory. Initially, key concepts, such as the differences between sex, gender, gender identity, and sexual orientation, are presented. Topics addressed include the violence suffered by the transgender population, the pursuit of vocal adaptation, the creation and development of the communication clinic, the support and assistance provided by professionals to the transgender population and their families, as well as the procedures adopted by the clinic. Among the conclusions, it is highlighted that speech therapy has demonstrated the importance of individual-centered care, legitimizing the guarantee of promoting the users' health. Furthermore, the importance of the speech-language professional in the vocal and communicative improvement of this population, which is often stigmatized, is emphasized (AU).

Voz incompatível com a própria identidade é um tema frequentemente apontado pela população transgênera em atendimentos fonoaudiológicos. A fonoterapia é uma técnica que permite a adequação da voz do falante, dentro de um campo de possibilidades. Ao fonoaudiólogo cabe o treinamento, a orientação e o aconselhamento dessa população, levando em conta as especificidades de cada indivíduo. Diante disso, este estudo tem como objetivo relatar a experiência de estudantes de graduação e profissionais de Fonoaudiologia no atendimento voltado à população transgênera em um laboratório de comunicação. Inicialmente são apresentados conceitos-chave, tais como as diferenças entre sexo, gênero, identidade de gênero, e orientação sexual. São abordados temas como a violência sofrida pela população trans, a busca pela adequação vocal, a criação e o desenvolvimento do ambulatório de comunicação, o acolhimento e o suporte prestado pelos profissionais à população trans e a seus familiares, além dos procedimentos adotados pelo ambulatório. Dentre as conclusões, destaca-se que a assistência fonoaudiológica tem mostrado a importância do cuidado centrado no indivíduo, legitimando a garantia da promoção de saúde dos usuários. Ademais, é destacada a importância do profissional de fonoaudiologia no aprimoramento vocal e comunicativo dessa população que é frequentemente estigmatizada (AU).

Clinical-pathological alterations, serological and molecular diagnosis in dogs with suspected leptospirosis / Alterações clínico-patológicas, diagnóstico sorológico e molecular em cães com suspeita de leptospirose

Leptospirosis is a globally important zoonosis that causes death in humans and animals, especially unvaccinated dogs. Dogs are infected through contact with urine or water contaminated by pathogenic spirochaete bacteria of the genus Leptospira. This study aimed to assess the performance of two diagnostic tests in characterizing dogs with leptospirosis and associate it with the main clinical-pathological alterations in dogs with suspected infection. From September 2019 to September 2020, 24 dogs with suspected canine leptospirosis were treated at the Veterinary Hospital of the Federal University of Uberlândia (UFU). Complementary tests such as a complete blood count (CBC) and serum creatinine, ALT (alanine transaminase) and ALP (alkaline phosphatase) levels were prescribed. In order to confirm the leptospirosis diagnosis, serum and molecular tests were performed using the microscopic agglutination test (MAT) and real-time quantitative polymerase chain reaction (qPCR). Of the 24 suspected cases of canine leptospirosis, six (25%) were positive in the MAT and three (12.5%) in the qPCR, with one (4.17%) returning positive results in both diagnostic tests. Positive results were obtained for 8/24 (33.3%) for combined MAT + qPCR. The predominant reactive serogroups were Icterohaemorrhagiae (33.33%) and Djasiman (33.33%), followed by Ballum (16.60%). The sensitivity and specificity of the qPCR in relation to the gold standard test (MAT) were 16.7 and 88.9%, respectively. Changes were observed in serum levels of creatinine, urea and ALP in the group that tested positive (MAT/qPCR); however, only urea and ALP levels were high in the negative group. Comparison of biochemical parameters in the positive (MAT/qPCR) and negative groups showed no statistically significant difference between the elements assessed (p>0.05). It was concluded that in order to diagnose acute canine leptospirosis, veterinarians should combine the clinical-pathological findings with paired sample MAT and qPCR urine test results.(AU)

A leptospirose é uma zoonose de importância mundial que causa mortes tanto em humanos, como em animais, especialmente em cães não vacinados. A infecção em cães ocorre pelo contato com urina ou água contaminada pela bactéria espiroqueta patogênica do gênero Leptospira. Objetivou-se avaliar dois testes diagnósticos na caracterização de cães com leptospirose, e associar com as principais alterações clínicos-patológicas de cães suspeitos. Foram atendidos no Hospital Veterinário da Universidade Federal de Uberlândia no período de setembro de 2019 a setembro de 2020, 24 cães com suspeita clínica de leptospirose canina. Exames complementares como hemograma completo, dosagens séricas de creatinina, ureia, ALT (alanina aminotransferase), FA (fosfatase alcalina) foram solicitados. Para o diagnóstico confirmatório de leptospirose foi realizado teste sorológico pelo teste de aglutinação microscópica (MAT) e também teste molecular pela reação em cadeia da polimerase em tempo real (qPCR). Dos 24 casos de cães suspeitos de leptospirose, seis (25%) foram positivos no MAT, e três (12,5%) no qPCR, sendo 1 (um) (4,17%) positivo nos dois testes diagnósticos avaliados. Quando se associou MAT + qPCR a positividade foi para 8/24 (33,3%). Os sorogrupos reativos predominantes foram Icterohaemorrhagiae (33,33%) e Djasiman (33,33%), seguido de Ballum (16,60%). A sensibilidade e especificidade da qPCR em relação teste padrão ouro (MAT) foi 16,7 % e 88,9%, respectivamente. Houve alterações nos níveis séricos de creatinina, ureia e FA no grupo positivo aos testes diagnósticos (MAT/qPCR), porém somente ureia e FA apresentaram valores elevados no grupo negativo. Quando se comparou os parâmetros bioquímicos no grupo positivo aos testes diagnósticos (MAT/qPCR), e negativo, não se observou nenhuma diferença estatística significativa entre os elementos avaliados (p>0,05). Conclui-se para o diagnóstico de leptospirose canina aguda, o médico veterinário deve associar os achados clínicos-patológicos aos resultados do MAT de forma pareada e o qPCR de urina.(AU)