Characterisation of the novel HLA-A*02:1140 allele, first identified in a Brazilian individual.

The novel HLA-A*02:1140 allele, first described in a potential bone marrow donor from Brazil.

Characterisation of the novel HLA-C*15:274 allele using short and long-read sequencing technologies.

The novel HLA-C*15:274 allele, first described in a potential bone marrow donor from Brazil.

Phenotypical characterization of exteroceptive sensation and pain symptoms on diabetic patients.

BACKGROUD: Diabetic neuropathy (DN) is one of the most common complications of diabetes, affecting about half of individuals with the disease. Among the various symptoms of DN, the development of chronic pain stands out and manifests as exacerbated responses to sensorial stimuli. The conventional clinical treatments used for general neuropathy and associated painful symptoms, still brings uncomplete and unsatisfactory pain relief. Patients with neuropathic pain syndromes are heterogeneous. They present with a variety of sensory symptoms and pain qualities which difficult the correct diagnosis of sensory comorbidities and consequently, the appropriate chronic pain management. AIMS: Herein, we aimed to demonstrate the existence of different sensory profiles on diabetic patients by investigating epidemiological and clinical data on the symptomatology of a group of patients with DN. METHODS: This is a longitudinal and observational study, with a sample of 57 volunteers diagnosed with diabetes from outpatient day clinic of Hospital Universitário of the University of São Paulo-Brazil. After being invited and signed the Informed Consent Form (ICF), patients were submitted to clinical evaluation and filled out pain and quality of life questionnaires. They also performed quantitative sensory test (QST) and underwent skin biopsy for correlation with cutaneous neuropathology. RESULTS: Data demonstrate that 70% of the studied sample presented some type of pain, manifesting in a neuropathic or nociceptive way, what has a negative impact on the life of patients with DM. We also demonstrated a positive association between pain and anxiety and depression, in addition to pain catastrophic thoughts. Three distinct profiles were identified in the sample, separated according to the symptoms of pain: (i) subjects without pain; (ii) with mild or moderate pain; (iii) subjects with severe pain. We also identified through skin biopsy that diabetic patients presented advanced sensory impairment, as a consequence of the degeneration of the myelinated and unmyelinated peripheral fibers. This study characterized the painful symptoms and exteroceptive sensation profile in these diabetic patients, associated to a considerable level of sensory degeneration, indicating, and reinforcing the importance of the long-term clinical monitoring of individuals diagnosed with DM, regarding their symptom profiles and exteroceptive sensitivity.

Performance of self-etching adhesives on caries-affected primary dentin treated with glutaraldehyde or silver diamine fluoride.

OBJECTIVES: to evaluate the quality and stability of adhesive interfaces established by self-etching adhesives on caries-affected primary dentin (CAD) treated with glutaraldehyde (GA) or silver diamine fluoride (SDF). METHODS: 42 primary molars were exposed to a microbiological caries-inducing protocol and divided into 6 groups according to the adhesive system (Clearfil SE - CL or FL Bond II - FL) and pretreatment (water, GA or SDF) applied on CAD. One tooth from each group was analyzed for surface modification using infrared spectroscopy. Crowns were restored with resin composite (n = 36) and cut into beams and slices. The beams were subjected to microtensile testing, Raman spectroscopy and SEM after 24 h and 6 months of storage. The slices were analyzed using Micro-Raman spectroscopy to determine the diffusion zone thickness (DZ) in each period. Data were analyzed by ANOVA and Tukey or Kruskal-Wallis and Dunn tests (α = 0.05%). RESULTS: SDF reduced the immediate bond strength for both adhesives. The control groups showed a decrease in BS after 6 months in artificial saliva. GA increased immediate DZ for FL, while SDF had the opposite effect on CL. GA decreased the DZ for FL at 6 months. There was a predominance of adhesive failures with areas of cohesive dentin fractures within control groups. SIGNIFICANCE: Modifications caused by dentin surface treatments may directly affect the performance of adhesive systems and the quality and stability of adhesive restorations.

Effect of photobiomodulation on neuropathic pain of diabetic origin: a narrative review of the literature.

To update the literature on the effectiveness of photobiomodulation (PBM) therapy in relieving pain in patients with diabetic peripheral neuropathy (DPN) compared to the effects of post-intervention, control/placebo groups, and other therapies. Search on the following databases: PORTAL PERIODICOS CAPES, PUBMED, GOOGLE ACADEMIC/SCHOLAR, SCOPUS, SCIELO, CENTRAL, and MEDLINE. Manual search: 1) manually capture the references of relevant articles originally selected to be included in the eligible studies. Two independent researchers performed the screening and selection of studies, methods assessment, and data extraction with unblinded authors and impressions. Subsequently, the full text of the originally selected studies was screened. The screening form registered the criteria for excluding literature from the full-text screening. The screening resulted in a total of 1692 citations. Out of these, 1402 citations were examined for titles and abstracts, followed by the removal of duplicated studies; therefore, 68 articles remained for full-text evaluation. 54 articles were excluded after full-text screening. Fourteen articles met the selection criteria, hence being selected and included in this narrative review. PBM showed to be a promising modality in relieving painful symptoms in DPN, especially when implemented in combination with other therapies, by improving the quality of life of diabetic patients.

Design, Synthesis and Phenotypic Profiling of Simplified Gedatolisib Analogues.

Targeted antitumour therapy has revolutionized the treatment of several types of tumours. Among the validated targets, phosphatidylinositol-3 kinase (PI3K) deserves to be highlighted. Several PI3K inhibitors have been developed for the treatment of cancer, including gedatolisib (4). This inhibitor was elected as a prototype and molecular modifications were planned to design a new series of simplified gedatolisib analogues (5a-f). The analogues were synthesised, and the comparative cytotoxic activity profile was studied in phenotypic models employing solid and nonadherent tumour cell lines. Compound 5f (LASSBio-2252) stood out as the most promising of the series, showing good aqueous solubility (42.38 µM (pH = 7.4); 39.33 µM (pH = 5.8)), good partition coefficient (cLogP = 2.96), cytotoxic activity on human leukemia cell lines (CCRF-CEM, K562 and MOLT-4) and an excellent metabolic stability profile in rat liver microsomes (t1/2 = 462 min; Clapp = 0.058 mL/min/g). The ability of 5f to exert its cytotoxic effect through modulation of the PI3K pathway was demonstrated by flow cytometry analysis in a comparative manner to gedatolisib.

Evasão acadêmica no curso de Odontologia de uma instituição pública e ações voltadas para mitigar o abandono discente / Evasión académica en la carrera de Odontología en una institución pública y acciones encaminadas a mitigar la deserción estudiantil / Academic evasion in the Dentistry course of a public institution and actions to mitigate student dropout

O estudo investigou aspectos da evasão e avaliou a satisfação de calouros no curso de Odontologia de uma instituição de ensino superior pública, além de relatar intervenções de combate ao abandono acadêmico desenvolvidas neste período. Trata-se de um estudo com uma fase observacional, transversal, descritiva, quanti-qualitativa, com aplicação de questionários; e outra intervencionista, com atividades voltadas ao combate à evasão. Foram entrevistados 74 alunos, matriculados no primeiro ano do curso, com idade entre 15 e 30 anos. Os dados foram expressos em frequências absoluta e percentual e analisados pelos testes exato de Fisher ou qui-quadrado de Pearson (p ≤0,05). Variáveis com associação significativa foram submetidas ao modelo de regressão logística multinomial (RLM). Observou-se que o grau de insatisfação com o curso foi maior entre os alunos com menor faixa etária (entre 15 e 20 anos) e menor renda familiar (até 2 salários mínimos). Além disso, cerca de 66% dos possíveis desistentes ainda não haviam vivenciado nenhum tipo de experiência prática odontológica, enquanto 69% dos que pretendem completar o curso já passaram por algum contato com vivências clínicas. A RLM revelou que a Odontologia não ser a primeira opção aumenta em 7,96 vezes a probabilidade de desistência do curso, independente do semestre. Observou-se, ainda, redução nos índices de evasão a medida em que intervenções (cerimônia do jaleco, visita clínica guiada e apadrinhamento de alunos calouros) foram realizadas. Conclui-se que asações implementadas para o combate de evasão no curso de Odontologia impactaram positivamente nos índices de abandono do curso nos semestres analisados (AU).

El estudio investigó aspectos de la evasión y evaluó la satisfacción de los estudiantes de primer año de la carrera de Odontología de una institución de enseñanza superior pública, además de relatar las intervenciones para combatir la deserción académica desarrolladas en ese período. Se trata de un estudio con fase observacional, transversal, descriptivo, cuantitativo y cualitativo, con aplicación de cuestionarios; y otra intervencionista, con actividades encaminadas a combatir la evasión. Fueron entrevistados 74 estudiantes, matriculados en el primer año de la carrera, con edades entre 15 y 30 años. Los datos se expresaron como frecuencias absolutas y porcentuales y se analizaron mediante la prueba exacta de Fisher o la prueba de chi-cuadrado de Pearson (p ≤0,05). Las variables con asociación significativa fueron sometidas al modelo de regresión logística multinomial (RLM). Se observóque el grado de insatisfacción con el curso fue mayor entre los estudiantes de menor franja etaria (entre 15 y 20 años) y menor renta familiar (hasta 2 salarios mínimos). Además, alrededor del 66% de los posibles desertores aún no habían tenido ningún tipo de experiencia práctica en odontología, mientras que el 69% de los que pretendían completar el curso ya habían tenido algúncontacto con experiencias clínicas. El RLM reveló que el hecho de no ser Odontología la primera opción aumenta en 7,96 veces la probabilidad de deserción de la carrera, independientemente del semestre. También hubo una reducción en las tasas de deserción a medida que se realizaron intervenciones (ceremonia de bata de laboratorio, visita clínica guiada y patrocinio de estudiantes de primer año). Se concluye que las acciones implementadas para combatir la deserción en la carrera de Odontología incidieron positivamente en las tasas de deserción de la carrera en los semestres analizados (AU).

The study investigated aspects of evasion and evaluated the satisfaction of freshmen in the Dentistry course at a public higher education institution, in addition to reporting interventions to combat academic dropout developed during this period. This is astudy with an observational, cross-sectional, descriptive, quantitative and qualitative phase, with the application of questionnaires; and another interventionist, with activities aimed at combating evasion. 74 students were interviewed, enrolled in the first year of the course, aged between 15 and 30 years old. Data were expressed as absolute and percentage frequencies and analyzed using Fisher's exact test or Pearson's chi-square test (p ≤0.05). Variables with significant association were submitted to the multinomial logistic regression model (RLM). It was observed that the degree of dissatisfaction with the course was higher among students with a lower age group (between 15 and 20 years old) and lower family income (up to 2 minimum wages). In addition, around 66% of possible dropouts had not yet had any kind of practical dental experience, while 69% of those intending to complete the course had already had some contact with clinical experiences. The RLM revealed that Dentistry not being the first option increases the probability of dropping out of the course by 7.96 times, regardless of the semester. There was also a reduction in dropout rates as interventions were carried out (lab coat ceremony, guided clinical visit and sponsorship of freshman students)were performed. It is concluded that the actions implemented to combat dropout in the Dentistry course had a positive impact on the dropout rates of the course in the analyzed semesters (AU).

Time perception and pain: Can a temporal illusion reduce the intensity of pain?

It is commonly known-and previous studies have indicated-that time appears to last longer during unpleasant situations. This study examined whether a reciprocal statement can be made-that is, whether changes in the perception of time can influence our judgment (or rating) of a negative event. We used a temporal illusion method (Pomares et al. Pain 152, 230-234, 2011) to induce distortions in the perception of time. Two stimuli were presented for a constant time: a full clock, which stayed on the screen until its clock hand completed a full rotation (360°); and a short clock, in which the clock hand moved just three-quarters of the way (270°), thus suggesting a reduced interval duration. However, both stimuli were shown for the same amount of time. We specifically investigated (a) whether we could induce a temporal illusion with this simple visual manipulation, and (b) whether this illusion could change participants' ratings of a painful stimulus. In Experiment I (n = 22), to answer (a) above, participants were asked to reproduce the duration in which the different clocks were presented. In Experiment II (n = 30), a painful thermal stimulation was applied on participants' hands while the clocks were shown. Participants were asked to rate the perceived intensity of their pain, and to reproduce its duration. Results showed that, for both experiments, participants reproduced a longer interval after watching the full clock compared with the short clock, confirming that the clock manipulation was able to induce a temporal illusion. Furthermore, the second experiment showed that participants rated the thermal stimuli as less painful when delivered with the short clock than with the full clock. These findings suggest that temporal distortions can modulate the experience of pain.

Psychopharmacology of smoking cessation medications: focus on patients with mental health disorders.

The adverse effects of smoking cessation in individuals with mental health disorders have been a point of concern, and progress in the development of treatment has been slow. The primary first-line treatments for smoking cessation are Nicotine Replacement Therapy, Bupropion, Varenicline, and behavioural support. Nortriptyline and Clonidine are second-line treatments used when the first-line treatments are not effective or are contraindicated. Smoking cessation medications have been shown to be effective in reducing nicotine cravings and withdrawal symptoms and promoting smoking cessation among patients living with mental disorders. However, these medications may have implications for patients' mental health and need to be monitored closely. The efficacy and side effects of these medications may vary depending on the patient's psychiatric condition, medication regimen, substance use, or medical comorbidities. The purpose of this review is to synthesise the pharmacokinetics, pharmacodynamics, therapeutic effects, adverse effects, and pharmacological interactions of first- and second-line smoking cessation drugs, with an emphasis on patients suffering from mental illnesses. Careful consideration of the risks and benefits of using smoking cessation medications is necessary, and treatment plans must be tailored to individual patients' needs. Monitoring symptoms and medication regimens is essential to ensure optimal treatment outcomes.

Efeito da intervenção motora domiciliar centrada na família para a funcionalidade de indivíduos com Duchenne / Effect of family-centered home motor intervention on the functioning of individuals with Duchenne

RESUMO O objetivo foi investigar o impacto de um Programa de Intervenção Motora Domiciliar (PIMD), com a abordagem centrada na família, na funcionalidade de indivíduos com Distrofia Muscular de Duchenne (DMD). Foi realizado uma série de casos, entre novembro de 2020 a junho de 2021 e aplicado a função motora grossa dos membros superiores e inferiores antes e após o PIMD, durante 16 sessões. Permaneceram seis crianças entre 12-13 (±2,90) anos de idade; 9,14 (±0,90) anos para perda de deambulação e 6,38 (±1,06) anos para idade de diagnóstico. A Medida da Função Motora inicial foi 47,8 (±20,13) e final, 56 (±20,53); na Escala de Vignos, inicial foi 7 (±1,73) e final, 6,4 (±1,95); na Escala de Brooke, inicial foi 2,0 (±1,30) e final, 2,2 (±1,22); na Performance of the Upper Limb, inicial foi 28,29 (±11,94) e final, 35 (±13,28). Na criança deambuladora, a média do escore de North Star Ambulatory Assessment (NSAA) total inicial foi 25 e final, 27. Portanto, o PIMD pode ser uma alternativa para prolongar a funcionalidade do curso clínico da DMD, em períodos sem intervenção presencial. A telerreabilitação é uma estratégia promissora, entretanto, é necessário treinamento da equipe de cuidados à saúde e o envolvimento dos pais.

ABSTRACT The objective was to investigate the impact of a Home Motor Intervention Program (PIMD), with a family-centered approach, on the functionality of individuals with Duchenne Muscular Dystrophy (DMD). A series of cases was carried out between November 2020 and June 2021 and applied to the gross motor function of the upper and lower limbs before and after PIMD, during 16 sessions. Six children between 12-13 (±2.90) years of age remained; 9.14 (±0.90) years for loss of ambulation and 6.38 (±1.06) years for age at diagnosis. The initial Motor Function Measure was 47.8 (±20.13) and final, 56 (±20.53); on the Vignos Scale, initial was 7 (±1.73) and final, 6.4 (±1.95); on the Brooke Scale, initial was 2.0 (±1.30) and final, 2.2 (±1.22); in the Performance of the Upper Limb, initial was 28.29 (±11.94) and final, 35 (±13.28). In the ambulatory child, the initial total North Star Ambulatory Assessment (NSAA) mean score was 25 and the final score was 27. Therefore, PIMD can be an alternative to prolong the functionality of the clinical course of DMD, in periods without face-to-face intervention. Telerehabilitation is a promising strategy, however, training of the health care team and parental involvement is required.

Effects of specific hypnotic suggestions on mechanical and thermal sensitivity of healthy volunteers: randomized and double-blind study / Efeito de sugestões hipnóticas específicas sobre a nocicepção mecânica e térmica em voluntários saudáveis: estudo randomizado e duplo-cego

ABSTRACT BACKGROUND AND OBJECTIVES: Hypnotic suggestions for hypoalgesia or analgesia are efficient for relieving different pain conditions, presenting few or no side effects. However, little is known about its direct effect on the modulation of peripheral nociception. The goal of this study was to evaluate the mechanical and thermal response after specific hypnotic suggestions in healthy volunteers. METHODS: This is a randomized double-blinded controlled trial that aimed to evaluate both mechanical and thermal nociception after specific hypnotic suggestions in healthy volunteers. For this, twenty-seven participants were enrolled, according to the following eligibility criteria: age between 18-65 years and absence of pain complaints or psychological disorders. After signed Free Informed Consent Term (FICT) the participants were divided by a computer-generated randomization in three groups: sham group (no induction of hypnosis), hypnosis-induced pain group and hypnosis-induced analgesia group. Susceptibility to hypnosis was assessed through the Waterloo-Stanford Group C (WSGC) scale of hypnotic susceptibility and outcomes included evaluation of questionnaires (Hospital Anxiety and Depression Scale and Short Form Brief Pain Inventory) as well as the examination of mechanical and thermal nociception through the Quantitative Sensory Testing (QST), a tool widely used to investigate somatosensory sensitivity by assessing functions of small A-δ and C nerve sensory fibers, before and after specific hypnotic suggestion for pain and analgesia made by a qualified hypnotherapist. RESULTS: Data demonstrated that specific hypnotic suggestions induced significant changes in mechanical and thermal sensitivity. The pain group revealed an increase in mechanical hyperalgesia and allodynia, while the analgesia group increased pain thresholds to thermal stimulations, being conditioned to withstand temperature changes after hypnosis, demonstrating a modulatory effect for both pain and analgesia sensations in healthy volunteers. CONCLUSION: The evidence presented in this study supports the use of the hypnosis technique as an auxiliary tool in clinical practice. HIGHLIGHTS Specific hypnotic suggestions can modulate peripheral nociception in healthy subjects. Data show a modulatory effect for both pain and analgesia sensations. Hypnosis can be considered a feasible technique for the clinical pain management.

RESUMO JUSTIFICATIVA E OBJETIVOS: Sugestões hipnóticas de hipoalgesia ou analgesia são eficientes para aliviar diferentes quadros álgicos, apresentando poucos ou nenhum efeito colateral. No entanto, pouco se sabe sobre seu efeito direto na modulação da nocicepção periférica. O objetivo deste estudo foi avaliar a resposta mecânica e térmica após sugestões hipnóticas específicas em voluntários saudáveis. MÉTODOS: Este é um estudo randomizado e duplo-cego que visou avaliar a nocicepção mecânica e térmica após sugestões hipnóticas específicas em voluntários saudáveis. Para isso, vinte e sete participantes foram selecionados, de acordo com os seguintes critérios de elegibilidade: idade entre 18 e 65 anos e ausência de distúrbios psicológicos e de queixas de dor. Após a assinatura do Termo de Consentimento Livre e Esclarecido (TCLE), os participantes foram divididos por randomização gerada por computador em três grupos: grupo sham (sem indução de hipnose), grupo dor induzida por hipnose e grupo analgesia induzida por hipnose. A suscetibilidade à hipnose foi avaliada através da escala Waterloo-Stanford Group C (WSGC) de suscetibilidade hipnótica e os resultados incluíram a avaliação de questionários (Escala Hospitalar de Ansiedade e Depressão e Inventário Breve de Dor), bem como o exame de nocicepção mecânica e térmica através do Teste Sensorial Quantitativo (QST), uma ferramenta amplamente utilizada para investigar a sensibilidade somatossensorial por meio da avaliação das funções das fibras sensoriais finas dos nervos A-δ e C, antes e após sugestão hipnótica específica para dor e analgesia aplicada por um hipnoterapeuta qualificado. RESULTADOS: Os dados mostraram que as sugestões hipnóticas específicas induziram mudanças significativas na sensibilidade mecânica e térmica dos indivíduos. O grupo dor revelou aumento da hiperalgesia mecânica e da alodinia, enquanto o grupo analgesia aumentou os limiares de dor por estímulos térmicos, sendo condicionado a suportar mudanças de temperatura após a hipnose, demonstrando efeito modulador tanto para as sensações de dor quanto de analgesia em voluntários saudáveis. CONCLUSÃO: As evidências apresentadas neste estudo sustentam o uso da técnica de hipnose como ferramenta auxiliar na prática clínica. DESTAQUES Sugestões hipnóticas específicas podem modular a nocicepção periférica em sujeitos saudáveis. Os dados mostram um efeito modulador tanto para as sensações de dor quanto de analgesia. A hipnose pode ser considerada uma técnica viável para o manejo clínico da dor.

Pre-clinical evaluation of LASSBio-1491: From in vitro pharmacokinetic study to in vivo leishmanicidal activity.

Leishmaniasis is a public health issue. It is among the top five parasitic illnesses worldwide and is one of the most neglected diseases. The current treatment disease includes limitations of toxicity, variable efficacy, high costs and inconvenient doses and treatment schedules. LASSBio-1736 was described as antileishmanial drug-candidate to cutaneous leishmaniasis, displaying plasma stability and with no preliminary signals of hepatic or renal toxicity. In this paper, we described the in vitro pharmacokinetic study of LASSBio-1491 (a less lipophilic isostere of LASSBio-1736) and it is in vitro and in vivo leishmanicidal activities. Our results demonstrated that LASSBio-1491 has high permeability, satisfactory aqueous solubility, long plasma and microsomal half-lives and low in vitro systemic clearance, suggesting a pharmacokinetic profile suitable for its use in a single daily dose. The antileishmanial effect of LASSBio-1491 was confirmed in vitro and in vivo. It exhibited no cytotoxic effect to mammalian cells and displayed good in -vivo effect against BALB/c mice infected with Leishmania major LV39 substrain, being 3 times more efficient than glucantime.

Annotation and functional characterization of long noncoding RNAs deregulated in pancreatic adenocarcinoma.

PURPOSE: Transcriptome analysis of pancreatic ductal adenocarcinoma (PDAC) has been useful to identify gene expression changes that sustain malignant phenotypes. Yet, most studies examined only tumor tissues and focused on protein-coding genes, leaving long non-coding RNAs (lncRNAs) largely underexplored. METHODS: We generated total RNA-Seq data from patient-matched tumor and nonmalignant pancreatic tissues and implemented a computational pipeline to survey known and novel lncRNAs. siRNA-mediated knockdown in tumor cell lines was performed to assess the contribution of PDAC-associated lncRNAs to malignant phenotypes. Gene co-expression network and functional enrichment analyses were used to assign deregulated lncRNAs to biological processes and molecular pathways. RESULTS: We detected 9,032 GENCODE lncRNAs as well as 523 unannotated lncRNAs, including transcripts significantly associated with patient outcome. Aberrant expression of a subset of novel and known lncRNAs was confirmed in patient samples and cell lines. siRNA-mediated knockdown of a subset of these lncRNAs (LINC01559, LINC01133, CCAT1, LINC00920 and UCA1) reduced cell proliferation, migration and invasion. Gene co-expression network analysis associated PDAC-deregulated lncRNAs with diverse biological processes, such as cell adhesion, protein glycosylation and DNA repair. Furthermore, UCA1 knockdown was shown to specifically deregulate co-expressed genes involved in DNA repair and to negatively impact DNA repair following damage induced by ionizing radiation. CONCLUSIONS: Our study expands the repertoire of lncRNAs deregulated in PDAC, thereby revealing novel candidate biomarkers for patient risk stratification. It also provides a roadmap for functional assays aimed to characterize novel mechanisms of action of lncRNAs in pancreatic cancer, which could be explored for therapeutic development.

Structural analysis of TrkA mutations in patients with congenital insensitivity to pain reveals PLCγ as an analgesic drug target.

Chronic pain is a major health issue, and the search for new analgesics has become increasingly important because of the addictive properties and unwanted side effects of opioids. To explore potentially new drug targets, we investigated mutations in the NTRK1 gene found in individuals with congenital insensitivity to pain with anhidrosis (CIPA). NTRK1 encodes tropomyosin receptor kinase A (TrkA), the receptor for nerve growth factor (NGF) and that contributes to nociception. Molecular modeling and biochemical analysis identified mutations that decreased the interaction between TrkA and one of its substrates and signaling effectors, phospholipase Cγ (PLCγ). We developed a cell-permeable phosphopeptide derived from TrkA (TAT-pQYP) that bound the Src homology domain 2 (SH2) of PLCγ. In HEK-293T cells, TAT-pQYP inhibited the binding of heterologously expressed TrkA to PLCγ and decreased NGF-induced, TrkA-mediated PLCγ activation and signaling. In mice, intraplantar administration of TAT-pQYP decreased mechanical sensitivity in an inflammatory pain model, suggesting that targeting this interaction may be analgesic. The findings demonstrate a strategy to identify new targets for pain relief by analyzing the signaling pathways that are perturbed in CIPA.

Significados e ações inferidos por enfermeiras para a minimização do erro de medicamentos em pediatria / Meanings and actions inferred by nurses for minimizing medication errors in pediatrics*

RESUMO Objetivo compreender os significados e as ações inferidos por enfermeiras para a minimização do erro na administração de medicamentos em pediatria. Métodos estudo de natureza qualitativa ancorado no Interacionismo Simbólico. Realizou-se a coleta de dados mediante entrevista semiestruturada com 11 enfermeiras, que atribuíram os significados e suas ações para a redução do erro de medicamentos em Pediatria. A análise do conteúdo foi composta por pré-análise, exploração, tratamento e interpretação dos dados. Resultados emergiram três categorias: Ações individuais (planejamento, atenção, comunicação e aplicação do checklist na utilização dos "certos"); Interações multiprofissionais e organizacionais (trabalho em equipe, sistema automatizado, dimensionamento de pessoal, dupla verificação na conferência das medicações, articulação profissional, ações organizacionais, políticas institucionais e comunicação) e Estratégias na educação continuada (treinamentos e capacitações). Conclusão aspectos técnicos, dinâmica de trabalho, necessidade de atualização, atitudes relacionadas às ações individuais, interações multiprofissionais, organizacionais e educação continuada foram significados e ações inferidos por enfermeiras para a minimização do erro na administração de medicamentos em Pediatria. Contribuições para a prática: faz-se necessário que o tema administração de medicamentos seja ponto contínuo dos programas de educação permanente nos serviços de saúde com vistas a garantir a minimização dos erros e assim promover maior segurança aos usuários.

ABSTRACT Objective to understand the meanings and actions inferred by nurses to minimize the error in the administration of medications in pediatrics. Methods a qualitative study anchored in Symbolic Interactionism. Data were collected through semi-structured interviews with 11 nurses, who attributed the meanings and their actions to reduce medication errors in Pediatrics. The content analysis was composed of pre-analysis, exploration, treatment and interpretation of data. Results three categories emerged: Individual actions (planning, attention, communication and application of the checklist in the use of the "right ones"); Multi-professional and organizational interactions (teamwork, automated system, staff dimensioning, double-checking in checking medications, professional articulation, organizational actions, institutional policies and communication) and Continuing education strategies (training and capacity building). Conclusion technical aspects, work dynamics, need for updating, attitudes related to individual actions, multi-professional interactions, organizational and continuing education were meanings and actions inferred by nurses for the minimization of the error in medication administration in Pediatrics. Contributions to practice: it is necessary that the topic of medication administration be a continuous point in the permanent education programs in the health services in order to guarantee the minimization of errors and thus promote greater safety for users.

A formação de futuros professores no Programa Escola Integrada (PEI)

O presente artigo trata dos resultados parciais da pesquisa "Educação Básica e Família: reproduções e invenções no Programa Escola Integrada (PEI) de Belo Horizonte" que objetiva investigar as relações estabelecidas entre estudantes, professores, escolas e família. O PEI é um programa de formação docente implantado e mantido pela Prefeitura Municipal de Belo Horizonte, com base na ampliação da jornada escolar, do qual fazem parte estudantes universitários de diferentes licenciaturas. A metodologia utilizada para abranger a complexidade dessas relações é a pesquisa-intervenção e as ideias de Deleuze e Guattari seu marco teórico. A partir do grupo de estudos feitos em conjunto com os estudantes e os professores supervisores do programa e de entrevistas, analisamos o processo deformação docente, mapeando as linhas duras, flexíveis e de fuga do rizoma PEI. Concluímos que a formação docente é uma experimentação na qual a invenção é necessária resistir à precarização da educação.

The main strategies adopted by the Toronto government in the COVID-19 pandemic: epidemiology / Las principales estrategias adoptadas por el gobierno de Toronto en la pandemia de COVID-19: estudio de epidemiología

ABSTRACT Objetive To analyze the epidemiological data and the main government measures adopted against the COVID-19 pandemic. Methods Epidemiologic study built with data from the integrated Public Health Information System (iPHIS) and the official Government of Canada website in a time frame from January to July 2020. Results Toronto presents the first case of COVID 19 on January 23rd and until July 1st, 2020, it records a number of 14 468 cases, 12.574 recovered cases, 1.100 deaths and 171 institutional outbreaks. About 53,04% of the cases were female, aged 40-59 years (29,81%), followed by 20-39 years (28,37%). Contagion forms were analyzed: 56,40% had close contact with a case, 24,23% in the community, 10,30% in health services, 5,58% while traveling and 3,49% in institutions. Economic and financial actions, travel measures, support for Canadians abroad, public education, research and technology were developed. Conclusion The COVID-19 is a serious threat to public health around the world. Canada has a strong history of pandemic planning and has worked together with public health for its developed actions to become adaptable based on evolution, outbreak containment and prevention of further spread.

RESUMEN Objetivo Analizar los datos epidemiológicos y las principales medidas gubernamentales adoptadas contra la pandemia de COVID-19. Métodos Estudio epidemiológico construido con datos del Sistema de Información de Salud Pública integrado (iPHIS) y el sitio web oficial del Gobierno de Canadá en un período de tiempo de enero a julio de 2020. Resultados Toronto presentó el primer caso de COVID-19 el 23 de enero y hasta el 1 de julio de 2020 registró 14 468 casos; 12 574 casos recuperados, 1 100 muertes y 171 brotes institucionales. Aproximadamente el 53,04% de los casos fueron de mujeres entre los 40 y 59 años (29,81%), seguidas de las de 20 a 39 años (28,37%). Se analizaron formas de contagio: 56,40% tuvo contacto cercano con un caso, 24,23% en la comunidad; 10,30%, en servicios de salud; 5,58%, en viajes, y 3,49% en instituciones. Se desarrollaron acciones económicas y financieras, medidas de viaje, apoyo a los canadienses en el exterior, educación pública, investigación y tecnología. Conclusión El COVID-19 es una grave amenaza para la salud pública en todo el mundo. Canadá tiene una sólida historia de planificación para pandemias y ha trabajado junto con la salud pública para que sus acciones desarrolladas se vuelvan adaptables en función de la evolución, la contención de brotes y la prevención de una mayor propagación.

Pain in Covid Era.

The COVID19 pandemic has impacted the lives and health of persons worldwide and although majority of COVID19 patients present with respiratory symptoms, pain emerges as an important feature of COVID19 infection. About 15-20% of patients progress to a severe condition that requires hospitalization. Although the disease was initially reported as a respiratory syndrome, other systems such as cardiovascular, renal, and nervous systems may be affected in the acute stages, increasing the need for continuous support to treat multiple sequelae caused by the disease. Due to the severity of the disease, damages found after discharge should also be considered. Providing multidisciplinary interventions promoting physical and psychological recovery in the first stages of hospitalization can minimize these damages. Cognitive, physical and psychological dysfunction reported by COVID19 patients after discharge can have profound effects on quality of life. Pain is usually part of this dysfunction, but it is still poorly understood how it affects survivors of COVID19 infections. There is limited information about the clinical characteristics, treatment and outcome of maintenance of pain in COVID19 patients. The purpose of this narrative review is to provide an overview of the implications of COVID19 on acute and chronic pain states.

Electrical stimulation of the posterior insula induces mechanical analgesia in a rodent model of neuropathic pain by modulating GABAergic signaling and activity in the pain circuitry.

The insula has emerged as a critical target for electrical stimulation since it influences pathological pain states. We investigated the effects of repetitive electrical stimulation of the insular cortex (ESI) on mechanical nociception, and general locomotor activity in rats subjected to chronic constriction injury (CCI) of the sciatic nerve. We also studied neuroplastic changes in central pain areas and the involvement of GABAergic signaling on ESI effects. CCI rats had electrodes implanted in the left agranular posterior insular cortex (pIC), and mechanical sensitivity was evaluated before and after one or five daily consecutive ESIs (15 min each, 60 Hz, 210 µs, 1 V). Five ESIs (repetitive ESI) induced sustained mechanical antinociception from the first to the last behavioral assessment without interfering with locomotor activity. A marked increase in Fos immunoreactivity in pIC and a decrease in the anterior and mid-cingulate cortex, periaqueductal gray and hippocampus were noticed after five ESIs. The intrathecal administration of the GABAA receptor antagonist bicuculline methiodide reversed the stimulation-induced antinociception after five ESIs. ESI increased GAD65 levels in pIC but did not interfere with GABA, glutamate or glycine levels. No changes in GFAP immunoreactivity were found in this work. Altogether, the results indicate the efficacy of repetitive ESI for the treatment of experimental neuropathic pain and suggest a potential influence of pIC in regulating pain pathways partially through modulating GABAergic signaling.

Electrical stimulation of the posterior insula induces mechanical analgesia in a rodent model of neuropathic pain by modulating GABAergic signaling and activity in the pain circuitry

The insula has emerged as a critical target for electrical stimulation since it influences pathological pain states. We investigated the effects of repetitive electrical stimulation of the insular cortex (ESI) on mechanical nociception, and general locomotor activity in rats subjected to chronic constriction injury (CCI) of the sciatic nerve. We also studied neuroplastic changes in central pain areas and the involvement of GABAergic signaling on ESI effects. CCI rats had electrodes implanted in the left agranular posterior insular cortex (pIC), and mechanical sensitivity was evaluated before and after one or five daily consecutive ESIs (15 min each, 60 Hz, 210 μs, 1 V). Five ESIs (repetitive ESI) induced sustained mechanical antinociception from the first to the last behavioral assessment without interfering with locomotor activity. A marked increase in Fos immunoreactivity in pIC and a decrease in the anterior and mid-cingulate cortex, periaqueductal gray and hippocampus were noticed after five ESIs. The intrathecal administration of the GABAA receptor antagonist bicuculline methiodide reversed the stimulation-induced antinociception after five ESIs. ESI increased GAD65 levels in pIC but did not interfere with GABA, glutamate or glycine levels. No changes in GFAP immunoreactivity were found in this work. Altogether, the results indicate the efficacy of repetitive ESI for the treatment of experimental neuropathic pain and suggest a potential influence of pIC in regulating pain pathways partially through modulating GABAergic signaling.