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CONTEXT: SARS-CoV-2, responsible for COVID-19, has led to over 500 million infections and more than 6 million deaths globally. There have been limited effective treatments available. The study aims to find a drug that can prevent the virus from entering host cells by targeting specific sites on the virus's spike protein. METHOD: We examined 13,397 compounds from the Malaria Box library against two specific sites on the spike protein: the receptor-binding domain (RBD) and a predicted cryptic pocket. Using virtual screening, molecular docking, molecular dynamics, and MMPBSA techniques, they evaluated the stability of two compounds. TCMDC-124223 showed high stability and binding energy in the RBD, while TCMDC-133766 had better binding energy in the cryptic pocket. The study also identified that the interacting residues are conserved, which is crucial for addressing various virus variants. The findings provide insights into the potential of small molecules as drugs against the spike protein.
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Antivirais , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/metabolismo , SARS-CoV-2/efeitos dos fármacos , Humanos , Sítios de Ligação , Antivirais/química , Antivirais/farmacologia , Tratamento Farmacológico da COVID-19 , Ligação Proteica , Domínios Proteicos , COVID-19/virologia , Bibliotecas de Moléculas Pequenas/química , Bibliotecas de Moléculas Pequenas/farmacologiaRESUMO
Candida species are frequently implicated in the development of both superficial and invasive fungal infections, which can impact vital organs. In the quest for novel strategies to combat fungal infections, there has been growing interest in exploring synthetic and semi-synthetic products, particularly chromone derivatives, renowned for their antimicrobial properties. In the analysis of the antifungal activity of the compound (E)-benzylidene-chroman-4-one against Candida, in silico and laboratory tests were performed to predict possible mechanisms of action pathways, and in vitro tests were performed to determine antifungal activity (MIC and MFC), to verify potential modes of action on the fungal cell membrane and wall, and to assess cytotoxicity in human keratinocytes. The tested compound exhibited predicted affinity for all fungal targets, with the highest predicted affinity observed for thymidylate synthase (-102.589 kJ/mol). MIC and CFM values ranged from 264.52 µM (62.5 µg/mL) to 4232.44 µM (1000 µg/mL). The antifungal effect likely occurs due to the action of the compound on the plasma membrane. Therefore, (E)-benzylidene-chroman-4-one showed fungicidal-like activity against Candida spp., possibly targeting the plasma membrane.
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A high prevalence of post-treatment apical periodontitis associated to variables such as endodontic treatment quality and missed canals has been reported. AIM: The aim of this study was to evalúate the quality of endodontic treatment and the frequency of missed canals associated with teeth with apicalperiodontitis (AP) through CBCTin a Colombian sub-population. MATERIAL AND METHOD: This was a cross-sectional study assessing 318 cone beam computed tomography (CBCT) scans of endodontically treated teeth from Colombian individuals. The scans were taken using J Morita X550 (J Morita Corporation, Osaka, Japan), with voxel size 0.125 to 0.20 mm. All endodontically treated teeth were assessed for quality of treatment, presence of missed canals and AP. Allsamples were analyzed bytwo endodontics specialists and an radiology specialist. Chi-square or Fisher 's test and odds ratio were calculated to identify the association and risk relationship between the presence of AP and the study variables. RESULTS: Missed canals were found in 18.61% (86/462), and 95.3% were associated with AP. The frequency of AP was 62.34% (288/462) for all the evaluated teeth. AP was found in 27.43 % (79/288) of the teeth with adequate endodontic treatment, in contrast to 72.57% (209/288) of the teeth with inadequate treatment (P<0.01). The frequency of missed canals was highest in maxillary molars, with 55.23% (58/105), with 96.55% presenting AP. The second mesiobuccal canal wasthe most frequently missed canal, 88.52%o(54/61), with AP in 90.74% (49/54) of the cases. CONCLUSIÓN: There was a high frequency of teeth with missed canals and PA. More than half of the teeth with missed canals were maxillary molars, with MB2 being the most common canal, commonly presenting apical periodontitis.
Uma alta prevalência de periodontite apical pós-tratamento associada a variáveis como qualidade do tratamento endodôntico e fracasso do tratamento é relatada na literatura. O objetivo deste estudo foi avaliar a qualidade do tratamento endodôntico e a frequência e fracasso do tratamento associados a dentes com periodontite apical (PA) por meio de tomografia computadorizada de feixe cônico (TCFC) em uma subpopulação colombiana. MATERIAL E MÉTODO: Este foi um estudo transversal que avaliou 318 tomografias computadorizadas de dentes tratados endodonticamente de indivíduos colombianos. Os exames foram realizados utilizando o tomógrafo J Morita X550, com tamanho de voxel de 0,125 a 0,20 mm. Todos os dentes tratados endodonticamente foram avaliados quanto à qualidade do tratamento, presença de canais não localizados e AP. Todas as amostras foram avaliadas por dois especialistas em endodontia e um especialista em radiologia. Foram calculados o teste qui-quadrado ou de Fisher e a razão de chances para identificar associação e relação de risco entre a presença de PA e as variáveis do estudo. RESULTADOS: Foram encontrados canais não localizados em 18,61% (86/462) e 95,3% estavam associados à PA. A frequência de AP foi de 62,34% (288/462) para todos os dentes avaliados. AP foi encontrada em 27,43% (79/288) dos dentes com tratamento endodôntico adequado, em contraste com 72,57% (209/288) dos dentes com tratamento inadequado (P<0,01). A frequência de canais não localizados foi maior nos molares superiores, com 55,23% (58/105), sendo que 96,55% apresentavam PA. O canal mésio-palatino (MB2) apresentou maior frequência de canal não localizado (88,52% - 54/61), com PA em 90,74% (49/54) dos casos. CONCLUSÃO: Houve alta frequência de dentes com canais não localizados e com PA. Mais da metade dos dentes com canais não localizados eram molares superiores, sendo o MB2 é o canal com a maior frequência, comumente apresentando periodontite apical.
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Periodontite Periapical , Tratamento do Canal Radicular , Humanos , Estudos Transversais , Periodontite Periapical/diagnóstico por imagem , Periodontite Periapical/terapia , Colômbia , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Tomografia Computadorizada de Feixe Cônico , Dente não Vital/diagnóstico por imagem , Cavidade Pulpar/diagnóstico por imagem , Adulto Jovem , Qualidade da Assistência à Saúde , IdosoRESUMO
Tetrahydrolinalool (THL) is an acyclic monoterpene alcohol, produced during linalol metabolism and also a constituent of essential oils. As described in the literature, many monoterpenes present anticonvulsant properties, and thus we became interested in evaluating the anticonvulsant activity of Tetrahydrolinalool using in mice model as well as in silico approaches. Our results demonstrated that THL increased latency to seizure onset and also reduced the mortality, in picrotoxin induced seizure tests. The results may be related to GABAergic regulation, which was also suggested in seizure testing induced by 3-mercapto-propionic acid. In the strychnine-induced seizure testing, none of the groups pretreated with THL modulated the parameters indicative of anticonvulsant effect. The electrophysiological results revealed that THL treatment reduces seizures induced by pentylenetetrazole. The in silico molecular docking studies showed that the interaction between THL and a GABAA receptor model formed a stable complex, in comparison to the crystaligraphic structure of diazepam, a structurally related ligand. In conclusion, all the evidences showed that THL presents effective anticonvulsant activity related to the GABAergic pathway, being a candidate for treatment of epileptic syndromes.
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Monoterpenos Acíclicos , Anticonvulsivantes , Simulação de Acoplamento Molecular , Monoterpenos , Pentilenotetrazol , Convulsões , Anticonvulsivantes/farmacologia , Anticonvulsivantes/química , Anticonvulsivantes/síntese química , Animais , Camundongos , Convulsões/tratamento farmacológico , Monoterpenos/farmacologia , Monoterpenos/química , Monoterpenos/síntese química , Monoterpenos Acíclicos/farmacologia , Monoterpenos Acíclicos/química , Monoterpenos Acíclicos/síntese química , Masculino , Receptores de GABA-A/metabolismo , Receptores de GABA-A/química , Relação Estrutura-Atividade , Comportamento Animal/efeitos dos fármacos , Picrotoxina/farmacologiaRESUMO
This paper presents the first translation and adaptation of the Multidimensional Mentalizing Questionnaire (MMQ) into Spanish for a native Spanish-speaking sample in Chile. The study examines the psychometric properties and internal consistency of the translated MMQ. The instrument undergoes modifications based on a confirmatory factor analysis of the original structure, resulting in the elimination of items with cross-loadings and improvement in model fit. The modified scale is then analyzed, demonstrating strong psychometric properties. Convergent evidence is assessed by correlating MMQ subscales with the Interpersonal Reactivity Index (IRI) and Empathy Quotient (EQ), while divergent evidence is assessed by correlating aggressive traits using the Buss-Perry Aggression Questionnaire (BPAQ). The study also explores gender differences and age. Results reveal positive correlations between good mentalizing and empathy, particularly cognitive empathy, supporting the significance of positive mentalization in empathy. Negative mentalization is associated with difficulties in perspective-taking and social skills, as well as aggressive traits. Gender differences in mentalizing capacities are observed, and negative aspects of mentalization decrease with age. The availability of the Spanish translation of the MMQ, the first self-reporting scale measuring mentalization adapted to Chilean population, contributes to research aiming to understand its relationship with other psychological phenomena in different cultural context and facilitating clinical interventions with different population groups. We therefore encourage further investigation into cultural, gender and age differences in mentalization.
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Mentalização , Chile , Psicometria , Inquéritos e Questionários , Empatia , Reprodutibilidade dos TestesRESUMO
BACKGROUND: During the COVID-19 pandemic, distinct population subsets, including pregnant women, have been differentially affected. While over 90% of COVID-19-infected pregnant women experience a benign course, a subset demonstrates marked clinical exacerbation. Symptomatic pregnant individuals, in particular, present a heightened risk of severe disease in comparison to their non-pregnant counterparts. OBJECTIVE: The objective of this study is to systematically evaluate the epidemiological characteristics of COVID-19 in pregnant women, assess related maternal mortalities, ascertain the case fatality rate, and delineate associated risk factors. DESIGN: This is a comprehensive population-based ecological study. METHODOLOGY: A population-based study was conducted to investigate the epidemiological patterns of COVID-19-associated morbidity and mortality in pregnant women in Ecuador from 27 February 2020 to 14 May 2021. RESULTS: A total of 3274 positive COVID-19 cases were identified among pregnant women, with 22 official fatalities, yielding a case fatality rate of 0.67%. The majority of cases were of Mestizo ethnicity (92.66%); however, the highest case fatality rate was noted among indigenous pregnant women (case fatality rate = 1.25%), those aged between 40 and 44 years (case fatality rate = 2.68%), and those with a history of comorbidities (2.08%). Pregnant women residing at lower altitudes (<2500 m) exhibited a higher incidence rate (0.20/100,000) compared to those at higher altitudes (>2500 m), which stood at 0.17/100,000. CONCLUSION: The COVID-19 pandemic has profoundly impacted pregnant women in Ecuador during the first 14 months, particularly those with comorbidities, older age, and of indigenous ethnicity. These factors have heightened their vulnerability and susceptibility to severe COVID-19 infection and subsequent mortality. This underscores the urgency for comprehensive protective measures, including prioritization for vaccination. Further studies are needed to inform tailored prevention strategies and therapeutic interventions for these high-risk groups.
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COVID-19 , Complicações Infecciosas na Gravidez , Gravidez , Feminino , Humanos , Adulto , COVID-19/epidemiologia , Mortalidade Materna , SARS-CoV-2 , Complicações Infecciosas na Gravidez/epidemiologia , Complicações Infecciosas na Gravidez/prevenção & controle , Pandemias , Equador/epidemiologiaRESUMO
ABSTRACT A high prevalence of post-treatment apical periodontitis associated to variables such as endodontic treatment quality and missed canals has been reported. Aim The aim of this study was to evaluate the quality of endodontic treatment and the frequency of missed canals associated with teeth with apical periodontitis (AP) through CBCT in a Colombian sub-population. Material and Method This was a crosssectional study assessing 318 cone beam computed tomography (CBCT) scans of endodontically treated teeth from Colombian individuals. The scans were taken using J Morita X550 (J Morita Corporation, Osaka, Japan), with voxel size 0.125 to 0.20 mm. All endodontically treated teeth were assessed for quality of treatment, presence of missed canals and AP. All samples were analyzed by two endodontics specialists and an radiology specialist. Chi-square or Fisher's test and odds ratio were calculated to identify the association and risk relationship between the presence of AP and the study variables. Results Missed canals were found in 18.61% (86/462), and 95.3% were associated with AP. The frequency of AP was 62.34% (288/462) for all the evaluated teeth. AP was found in 27.43 % (79/288) of the teeth with adequate endodontic treatment, in contrast to 72.57% (209/288) of the teeth with inadequate treatment (P<0.01). The frequency of missed canals was highest in maxillary molars, with 55.23% (58/105), with 96.55% presenting AP. The second mesiobuccal canal was the most frequently missed canal, 88.52% (54/61), with AP in 90.74% (49/54) of the cases. Conclusion There was a high frequency of teeth with missed canals and PA. More than half of the teeth with missed canals were maxillary molars, with MB2 being the most common canal, commonly presenting apical periodontitis.
RESUMO Uma alta prevalência de periodontite apical pós-tratamento associada a variáveis como qualidade do tratamento endodôntico e fracasso do tratamento é relatada na literatura. O objetivo deste estudo foi avaliar a qualidade do tratamento endodôntico e a frequência e fracasso do tratamento associados a dentes com periodontite apical (PA) por meio de tomografia computadorizada de feixe cônico (TCFC) em uma subpopulação colombiana. Material e Método Este foi um estudo transversal que avaliou 318 tomografias computadorizadas de dentes tratados endodonticamente de indivíduos colombianos. Os exames foram realizados utilizando o tomógrafo J Morita X550, com tamanho de voxel de 0,125 a 0,20 mm. Todos os dentes tratados endodonticamente foram avaliados quanto à qualidade do tratamento, presença de canais não localizados e AP. Todas as amostras foram avaliadas por dois especialistas em endodontia e um especialista em radiologia. Foram calculados o teste qui-quadrado ou de Fisher e a razão de chances para identificar associação e relação de risco entre a presença de PA e as variáveis do estudo. Resultados Foram encontrados canais não localizados em 18,61% (86/462) e 95,3% estavam associados à PA. A frequência de AP foi de 62,34% (288/462) para todos os dentes avaliados. AP foi encontrada em 27,43% (79/288) dos dentes com tratamento endodôntico adequado, em contraste com 72,57% (209/288) dos dentes com tratamento inadequado (P<0,01). A frequência de canais não localizados foi maior nos molares superiores, com 55,23% (58/105), sendo que 96,55% apresentavam PA. O canal mésio-palatino (MB2) apresentou maior frequência de canal não localizado (88,52% - 54/61), com PA em 90,74% (49/54) dos casos. Conclusão Houve alta frequência de dentes com canais não localizados e com PA. Mais da metade dos dentes com canais não localizados eram molares superiores, sendo o MB2 é o canal com a maior frequência, comumente apresentando periodontite apical.
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Pain is characterized by the unpleasant sensory and emotional sensation associated with actual or potential tissue damage, whereas nociception refers to the mechanism by which noxious stimuli are transmitted from the periphery to the CNS. The main drugs used to treat pain are nonsteroidal anti-inflammatory drugs (NSAIDs) and opioid analgesics, which have side effects that limit their use. Therefore, in the search for new drugs with potential antinociceptive effects, essential oils have been studied, whose constituents (monoterpenes) are emerging as a new therapeutic possibility. Among them, linalool and its metabolites stand out. The present study aims to investigate the antinociceptive potential of linalool and its metabolites through a screening using an in silico approach. Molecular docking was used to evaluate possible interactions with important targets involved in antinociceptive activity, such as α2-adrenergic, GABAergic, muscarinic, opioid, adenosinergic, transient potential, and glutamatergic receptors. The compounds in the investigated series obtained negative energies for all enzymes, representing satisfactory interactions with the targets and highlighting the multi-target potential of the L4 metabolite. Linalool and its metabolites have a high likelihood of modulatory activity against the targets involved in nociception and are potential candidates for future drugs.
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Monoterpenos Acíclicos , Analgésicos , Simulação de Acoplamento Molecular , Monoterpenos Acíclicos/química , Monoterpenos Acíclicos/farmacologia , Monoterpenos Acíclicos/metabolismo , Analgésicos/química , Analgésicos/farmacologia , Analgésicos/metabolismo , Humanos , Simulação por Computador , Animais , Dor/tratamento farmacológico , Dor/metabolismo , Monoterpenos/química , Monoterpenos/farmacologiaRESUMO
Introduction: The aim of this study was to assess the effectiveness of filling removal material from the apical third of curved mesial root canals of mandibular molars. Reciprocating instrumentation followed by additional rotary instrumentation with instruments made of alloys with different heat treatments was evaluated. Materials and Methods: Thirty-six mesial roots of mandibular molars were divided into two groups: Group Class IV consisted of 16 roots with two independent canals, and Group Class II consisted of 20 roots with two canals that merged into one at their apical level. Each of these two groups were further divided into two subgroups, according to the additional rotary instrument used after the reciprocating instrumentation: Group RH and Group RM for Hyflex and Mtwo, respectively. After each procedural step, the roots were scanned by micro-tomography. After each step of filling removal, the Wilcoxon matched pair test and the Mann-Whitney test were used for the evaluation between groups. The significance level adopted was 5%. Results: Significant differences were observed between groups with different Class II and Class IV anatomies, regarding filling removal after Reciproc (P<0.05). After the use of an additional rotary instrumentation, no differences were observed between the two groups (P>0.05). Conclusions: In the apical third of mesial roots of mandibular molars with Class II anatomy, an additional rotary instrumentation was shown to be necessary for improving the removal of filling material after using the single-file reciprocating instrumentation technique.
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Delusions are a heterogenous transdiagnostic phenomenon with a higher prevalence in schizophrenia. One of the most fundamental debates surrounding the philosophical understanding of delusions concerns the question about the type of mental state in which reports that we label as delusional are grounded, namely, the typology problem. The formulation of potential answers for this problem seems to have important repercussions for experimental research in clinical psychiatry and the development of psychotherapeutic tools for the treatment of delusions in clinical psychology. Problematically, such alternatives are scattered in the literature, making it difficult to follow the current development and state of the target discussion. This paper offers an updated critical examination of the alternatives to the typology problem currently available in the literature. After clarifying the two main philosophical views underlying the dominant formulation of the debate (interpretivism and functionalism), we follow the usual distinction between doxastic (the idea that delusions are a type of belief) and anti-doxastic views. We then introduce two new sub-distinctions; on the doxastic camp, we distinguish between revisionist and non-revisionist proposals; on the anti-doxastic camp, we distinguish between commonsensical and non-commonsensical anti-doxasticisms. After analyzing the main claims of each view, we conclude with some of the most fundamental challenges that remain open within the discussion. This article is categorized under: Philosophy > Foundations of Cognitive Science Philosophy > Consciousness Philosophy > Psychological Capacities Neuroscience > Cognition.