Neurodengue, a narrative review of the literature.

Dengue fever (DF) is the most frequent arboviral disease globally. Deforestation, armed conflicts, and climate change have caused an unprecedented global spread of DF, raising concerns in healthcare systems worldwide. Systemic manifestations of the disease range from mild to severe and, in some cases, can lead to death. Although neurological complications have been reported over the last few decades, they are often neglected or underreported. The present narrative review aims to describe the most important central and peripheral nervous system complications and provide guidance to neurologists in terms of diagnosis and management.

A dengue é a arbovirose mais frequente no mundo. O desmatamento, os conflitos armados e as mudanças climáticas levaram a uma disseminação global e sem precedentes da dengue, o que gera preocupações na maioria dos sistemas de saúde em todo o mundo. As manifestações sistêmicas variam de leves a graves, incluindo morte. Complicações neurológicas têm sido descritas nas últimas décadas, mas geralmente são negligenciadas ou subnotificadas. O objetivo desta revisão narrativa é descrever as complicações neurológicas centrais e periféricas e auxiliar os neurologistas em seu diagnóstico e manejo.

Revisiting and Updating the Interaction between Human Serum Albumin and the Non-Steroidal Anti-Inflammatory Drugs Ketoprofen and Ketorolac.

Ketoprofen (KTF) and ketorolac (KTL) are among the most primarily used non-steroidal anti-inflammatory drugs (NSAIDs) in humans to alleviate moderate pain and to treat inflammation. Their binding affinity with albumin (the main globular protein responsible for the biodistribution of drugs in the bloodstream) was previously determined by spectroscopy without considering some conventional pitfalls. Thus, the present work updates the biophysical characterization of the interactions of HSA:KTF and HSA:KTL by 1H saturation-transfer difference nuclear magnetic resonance (1H STD-NMR), ultraviolet (UV) absorption, circular dichroism (CD), steady-state, and time-resolved fluorescence spectroscopies combined with in silico calculations. The binding of HSA:NSAIDs is spontaneous, endothermic, and entropically driven, leading to a conformational rearrangement of HSA with a slight decrease in the α-helix content (7.1% to 7.6%). The predominance of the static quenching mechanism (ground-state association) was identified. Thus, both Stern-Volmer quenching constant (KSV) and binding constant (Kb) values enabled the determination of the binding affinity. In this sense, the KSV and Kb values were found in the order of 104 M-1 at human body temperature, indicating moderate binding affinity with differences in the range of 0.7- and 3.4-fold between KTF and KTL, which agree with the previously reported experimental pharmacokinetic profile. According to 1H STD-NMR data combined with in silico calculations, the aromatic groups in relation to the aliphatic moiety of the drugs interact preferentially with HSA into subdomain IIIA (site II) and are stabilized by interactions via hydrogen bonding and hydrophobic forces. In general, the data obtained in this study have been revised and updated in comparison to those previously reported by other authors who did not account for inner filter corrections, spectral backgrounds, or the identification of the primary mathematical approach for determining the binding affinity of HSA:KTF and HSA:KTL.

Performance of a cost-effective olfactory test to evaluate hyposmia in Parkinson's disease patients.

BACKGROUND: Parkinson's disease (PD) causes motor and non-motor symptoms such as hyposmia, which is evaluated through olfactory tests in the clinical practice. OBJECTIVE: To assess the feasibility of using the modified Connecticut Chemosensory Clinical Research Center (mCCCRC) olfactory test and to compare its performance with the Sniffin' Sticks-12 (SS-12, Burghart Messtechnik GmbH, Wedel, Germany) test. METHODS: A transversal case-control study in which the patients were divided into the PD group (PDG) and the control group (CG). The cost and difficulty in handling substances to produce the mCCCRC test kits were evaluated. Sociodemographic characteristics, smoking habits, past coronavirus disease 2019 (COVID-19) infections, self-perception of odor sense, and cognition through the Montreal Cognitive Assessment (MoCA) were also evaluated. The PDG was scored by part III of the Unified Parkinson's Disease Rating Scale (UPDRS-III) and the Hoehn and Yahr Scale (H&Y) scale. Correlations were assessed through the Spearman rank correlation coefficient test (ρ, or rho). RESULTS: The mCCCRC test was easily manufactured and handled at a cost ten times lower compared with the SS-12. The groups (PDG: n = 34; CG: n = 38) were similar in terms of age, sex, level of schooling, smoking habits, and history of COVID-19. The tests results showed moderate correlation (rho = 0.65; p < 0.0001). The CG presented better cognitive performance and scored better in both tests (p < 0.0001). There was a tendency for a negative correlation with age, but good correlation with the MoCA (p = 0.0029). The results of the PDG group showed no correlation with olfactory results and motor performance or disease duration. The self-perception of hyposmia was low in both groups. CONCLUSION: The mCCCRC is an easy-to-apply and inexpensive method that demonstrated a similar performance to that of the SS-12 in evaluating olfaction in PD patients and healthy controls.

ANTECEDENTES: A doença de Parkinson (DP) cursa com sintomas motores e não motores como a hiposmia, que é avaliada por diferentes testes olfativos na prática clínica. OBJETIVO: Avaliar a viabilidade do teste olfatório Connecticut Chemosensory Clinical Research Center modificado (mCCCRC) e compará-la à do teste Sniffin' Sticks-12 (SS-12, Burghart Messtechnik GmbH, Wedel, Alemanha). MéTODOS: Estudo transversal de caso-controle em que os pacientes foram divididos no grupo DP (GDP) e no grupo controle (GC). O custo e as dificuldades no manuseio das substâncias necessárias para a produção dos kits do teste mCCCRC foram avaliados. Características sociodemográficas, tabagismo, histórico de infecção por doença do coronavírus 2019 (coronavírus disease 2019, COVID-19, em inglês), autopercepção do olfato e cognição pelo Montreal Cognitive Assessment (MoCA) também foram avaliados. O GDP foi avaliado pela parte III da Unified Parkinson's Disease Rating Scale (UPDRS-III) e pela escala de Hoehn and Yahr (H&Y). As correlações utilizaram o teste do coeficiente de correlação de postos de Spearman (ρ, ou rho). RESULTADOS: O mCCCRC foi facilmente poroduzido e manipulado com custo dez vezes inferior ao do SS-12. Os grupos (GDP: n = 34; GC: n = 38) eram similares em termos de idade, sexo, escolaridade, tabagismo e histórico de COVID-19. Os resultados obtidos em ambos os testes mostraram excelente correlação (rho = 0.65; p < 0.0001). O GC teve um desempenho cognitivo melhor e pontuou melhor nos dois testes (p < 0.0001). Houve uma tendência a uma correlação negativa com a idade, mas boa correlação com a pontuação no MoCA (p = 0.0029). Os resultados olfativos do GDP não mostraram correlação com desempenho motor ou duração da doença. A autopercepção de hiposmia foi baixa em ambos os grupos. CONCLUSãO: O mCCCRC é um teste de fácil aplicação, baixo custo, e apresentou um desempenho semelhante ao do SS-12 na avaliação olfativa de pacientes com DP e controles saudáveis.

Genetic variants in miR-146a and miR-196a2 in endometriosis: a Brazilian study.

OBJECTIVE: The aim of this study was to determine the allelic and genotypic frequencies of the polymorphisms, rs2910164 miR-146a and rs11614913 miR-196a2, by investigating their association with endometriosis. METHODS: This is a case-control study performed with approximately 120 women. The polymorphisms were determined by real-time polymerase chain reaction. For the statistical analysis, the chi-square and logistic regression tests were used. RESULTS: There were no significant differences in the genotype and allele frequencies of rs2910164 and rs11614913 between cases and controls. The frequencies in both polymorphisms are in accordance with Hardy-Weinberg equilibrium regarding miR-146a (patients: χ2=1.64, p=0.20; controls: χ2=0.25, p=0.62) and miR-196a2 (patients: χ2=0.58, p=0.44; controls: χ2=2.78, p=0.10). No relationship was observed between rs2910164 and rs11614913 and endometriosis in the inheritance models analyzed. CONCLUSION: In this study, our results show that the studied polymorphisms are not implicated in the development of endometriosis.

Genetic variants in miR-146a and miR-196a2 in endometriosis: a Brazilian study

SUMMARY OBJECTIVE: The aim of this study was to determine the allelic and genotypic frequencies of the polymorphisms, rs2910164 miR-146a and rs11614913 miR-196a2, by investigating their association with endometriosis. METHODS: This is a case-control study performed with approximately 120 women. The polymorphisms were determined by real-time polymerase chain reaction. For the statistical analysis, the chi-square and logistic regression tests were used. RESULTS: There were no significant differences in the genotype and allele frequencies of rs2910164 and rs11614913 between cases and controls. The frequencies in both polymorphisms are in accordance with Hardy-Weinberg equilibrium regarding miR-146a (patients: χ2=1.64, p=0.20; controls: χ2=0.25, p=0.62) and miR-196a2 (patients: χ2=0.58, p=0.44; controls: χ2=2.78, p=0.10). No relationship was observed between rs2910164 and rs11614913 and endometriosis in the inheritance models analyzed. CONCLUSION: In this study, our results show that the studied polymorphisms are not implicated in the development of endometriosis.

Performance of a cost-effective olfactory test to evaluate hyposmia in Parkinson's disease patients / Desempenho de um teste de olfato de bom custo-benefício na avaliação de hiposmia em pacientes com doença de Parkinson

Abstract Background Parkinson's disease (PD) causes motor and non-motor symptoms such as hyposmia, which is evaluated through olfactory tests in the clinical practice. Objective To assess the feasibility of using the modified Connecticut Chemosensory Clinical Research Center (mCCCRC) olfactory test and to compare its performance with the Sniffin' Sticks-12 (SS-12, Burghart Messtechnik GmbH, Wedel, Germany) test. Methods A transversal case-control study in which the patients were divided into the PD group (PDG) and the control group (CG). The cost and difficulty in handling substances to produce the mCCCRC test kits were evaluated. Sociodemographic characteristics, smoking habits, past coronavirus disease 2019 (COVID-19) infections, self-perception of odor sense, and cognition through the Montreal Cognitive Assessment (MoCA) were also evaluated. The PDG was scored by part III of the Unified Parkinson's Disease Rating Scale (UPDRS-III) and the Hoehn and Yahr Scale (H&Y) scale. Correlations were assessed through the Spearman rank correlation coefficient test (ρ, or rho). Results The mCCCRC test was easily manufactured and handled at a cost ten times lower compared with the SS-12. The groups (PDG: n= 34; CG: n= 38) were similar in terms of age, sex, level of schooling, smoking habits, and history of COVID-19. The tests results showed moderate correlation (rho = 0.65; p< 0.0001). The CG presented better cognitive performance and scored better in both tests (p< 0.0001). There was a tendency for a negative correlation with age, but good correlation with the MoCA (p= 0.0029). The results of the PDG group showed no correlation with olfactory results and motor performance or disease duration. The self-perception of hyposmia was low in both groups. Conclusion The mCCCRC is an easy-to-apply and inexpensive method that demonstrated a similar performance to that of the SS-12 in evaluating olfaction in PD patients and healthy controls.

Resumo Antecedentes A doença de Parkinson (DP) cursa com sintomas motores e não motores como a hiposmia, que é avaliada por diferentes testes olfativos na prática clínica. Objetivo Avaliar a viabilidade do teste olfatório Connecticut Chemosensory Clinical Research Center modificado (mCCCRC) e compará-la à do teste Sniffin' Sticks-12 (SS-12, Burghart Messtechnik GmbH, Wedel, Alemanha). Métodos Estudo transversal de caso-controle em que os pacientes foram divididos no grupo DP (GDP) e no grupo controle (GC). O custo e as dificuldades no manuseio das substâncias necessárias para a produção dos kits do teste mCCCRC foram avaliados. Características sociodemográficas, tabagismo, histórico de infecção por doença do coronavírus 2019 (coronavírus disease 2019, COVID-19, em inglês), autopercepção do olfato e cognição pelo Montreal Cognitive Assessment (MoCA) também foram avaliados. O GDP foi avaliado pela parte III da Unified Parkinson's Disease Rating Scale (UPDRS-III) e pela escala de Hoehn and Yahr (H&Y). As correlações utilizaram o teste do coeficiente de correlação de postos de Spearman (ρ, ou rho). Resultados O mCCCRC foi facilmente poroduzido e manipulado com custo dez vezes inferior ao do SS-12. Os grupos (GDP: n= 34; GC: n= 38) eram similares em termos de idade, sexo, escolaridade, tabagismo e histórico de COVID-19. Os resultados obtidos em ambos os testes mostraram excelente correlação (rho = 0.65; p< 0.0001). O GC teve um desempenho cognitivo melhor e pontuou melhor nos dois testes (p< 0.0001). Houve uma tendência a uma correlação negativa com a idade, mas boa correlação com a pontuação no MoCA (p= 0.0029). Os resultados olfativos do GDP não mostraram correlação com desempenho motor ou duração da doença. A autopercepção de hiposmia foi baixa em ambos os grupos. Conclusão O mCCCRC é um teste de fácil aplicação, baixo custo, e apresentou um desempenho semelhante ao do SS-12 na avaliação olfativa de pacientes com DP e controles saudáveis.

Neurodengue, a narrative review of the literature / Neurodengue, uma revisão narrativa da literatura

Abstract Dengue fever (DF) is the most frequent arboviral disease globally. Deforestation, armed conflicts, and climate change have caused an unprecedented global spread of DF, raising concerns in healthcare systems worldwide. Systemic manifestations of the disease range from mild to severe and, in some cases, can lead to death. Although neurological complications have been reported over the last few decades, they are often neglected or underreported. The present narrative review aims to describe the most important central and peripheral nervous system complications and provide guidance to neurologists in terms of diagnosis and management.

Resumo A dengue é a arbovirose mais frequente no mundo. O desmatamento, os conflitos armados e as mudanças climáticas levaram a uma disseminação global e sem precedentes da dengue, o que gera preocupações na maioria dos sistemas de saúde em todo o mundo. As manifestações sistêmicas variam de leves a graves, incluindo morte. Complicações neurológicas têm sido descritas nas últimas décadas, mas geralmente são negligenciadas ou subnotificadas. O objetivo desta revisão narrativa é descrever as complicações neurológicas centrais e periféricas e auxiliar os neurologistas em seu diagnóstico e manejo.

Electron impact electronic excitation of benzene: Theory and experiment.

We report experimental differential cross sections (DCSs) for electron impact excitation of bands I to V of benzene at incident energies of 10, 12.5, 15, and 20 eV. They are compared to calculations using the Schwinger multichannel method while accounting for up to 437 open channels. For intermediate scattering angles, the calculations reveal that the most intense band (V) emerges from surprisingly similar contributions from all its underlying states (despite some preference for the dipole-allowed transitions). They further shed light on intricate multichannel couplings between the states of bands I to V and higher-lying Rydberg states. In turn, the measurements support a vibronic coupling mechanism for excitation of bands II and IV and also show an unexpected forward peak in the spin-forbidden transition accounting for band III. Overall, there is decent agreement between theory and experiment at intermediate angles and at lower energies and in terms of the relative DCSs of the five bands. Discrepancies between the present and previous experiment regarding bands IV and V draw attention to the need of additional experimental investigations. We also report measured DCSs for vibrational excitation of combined C-H stretching modes.

HTLV-1 p12 modulates the levels of prion protein (PrPC) in CD4+ T cells.

Introduction: Infection with human T cell lymphotropic virus type 1 (HTLV-1) is endemic in Brazil and is linked with pro-inflammatory conditions including HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), a chronic neuroinflammatory incapacitating disease that culminates in loss of motor functions. The mechanisms underlying the onset and progression of HAM/TSP are incompletely understood. Previous studies have demonstrated that inflammation and infectious agents can affect the expression of cellular prion protein (PrPC) in immune cells. Methods: Here, we investigated whether HTLV-1 infection affected PrPC content in cell lines and primary CD4+cells in vitro using flow cytometry and western blot assays. Results: We found that HTLV-1 infection decreased the expression levels of PrPC and HTLV-1 Orf I encoded p12, an endoplasmic reticulum resident protein also known to affect post-transcriptionally cellular proteins such as MHC-class I and the IL-2 receptor. In addition, we observed a reduced percentage of CD4+ T cells from infected individuals expressing PrPC, which was reflected by IFN type II but not IL-17 expression. Discussion: These results suggested that PrPC downregulation, linked to both HTLV-1 p12 and IFN-γ expression in CD4+ cells, may play a role in the neuropathogenesis of HTLV-1 infection.

Performance of the National Institute of Infectious Diseases disability scale in HTLV-1-associated myelopathy/tropical spastic paraparesis.

HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic disabling disease. However, there is a lack of an adequate and specific health measurement instrument validated and with good performance to assess their degree of physical disability. This led us to carry out this study and to evaluate the performance of Fiocruz's National Institute of Infectious Diseases (IDS) disability scale, a specific instrument for HAM/TSP. Ninety-two HAM/TSP patients participated in the study. One researcher applied the IDS, IPEC scale, Disability Status Scale (DSS), Expanded DSS (EDSS), Osame scale, Beck Depression Inventory, and the WHOQOL-BREF questionnaire. In parallel, blindly, and separately, other researchers applied the IDS. An inter-rater reliability analysis of the IDS, correlation analysis with the other scales, and depression and quality of life questionnaires were performed. The applicability of the IDS was also evaluated. The IDS showed high reliability in all scores. The inter-rater reliability test for the total IDS score was 0.94 (0.82-0.98) on its four dimensions. The scale adequately indicated the different degrees of disability, presenting a distribution similar to normal. There was a high correlation with the other scales (Spearman coefficients > 0.80, p < 0.001). The scale had good acceptance among users and a short application time. IDS for HAM/TSP was reliable, consistent, easy, and fast to use. It can be used for both prospective evaluations and clinical trials. The present study supports the IDS as a valid instrument to measure disability in patients with HAM/TSP compared to previously used scales.

Altered Cerebral Vasoreactivity on Transcranial Color-Coded Sonography Related to Akinetic-Rigid Phenotype of Parkinson's Disease: Interim Analysis of a Cross-Sectional Study.

BACKGROUND: A correlation between worse functional outcomes in Parkinson's disease (PD) patients with cerebrovascular disease (CVD) or the Akinetic-rigid phenotype has been argued in recent studies. We aimed to evaluate the association of cerebral hemodynamics impairments, assessed by Transcranial Color-coded Doppler sonography (TCCS), on PD patients with different phenotypes of the disease and with risk factors for CVD. METHODOLOGY: Idiopathic PD patients (n = 51) were divided into motor subtypes: Akinetic-rigid (AR) (n = 27) and Tremor-dominant (TD) (n = 24) and into two groups regarding vascular risk factors: when ≥2 were present (PDvasc) (n = 18) and <2 (PDnvasc) (n = 33). In a parallel analysis, the Fazekas scale on brain magnetic resonance imaging (MRI) was applied to a sample to assess the degree of leukoaraiosis. TCCS examinations were prospectively performed obtaining middle cerebral artery Mean Flow Velocities (Vm), Resistance Index (RI), and Pulsatility Index (PI). The Breath-Holding Index (BHI) was calculated to assess cerebrovascular reactivity (cVR). Standardized functional scales were administered (UPDRS III and Hoehn&Yahr). RESULTS: The phenotype groups were similar in age, disease duration and demographic parameters, but there were significantly higher H&Y scores than TD group. cVR was impaired in 66.7% of AR vs. 37.5% of TD. AR group exhibited lower BHI (0.53 ± 0.31 vs. 0.91 ± 0.62; p = 0.000), lower Vm after apnea (44.3 ± 9.0 cm/s vs. 53.4 ± 11.4 cm/s; p = 0.003), higher PI (0.91 ± 0.26 vs. 0.76 ± 0.12; p = 0.000) and RI (0.58 ± 0.11 vs. 0.52 ± 0.06; p = 0.021). PDvasc group showed higher PI (0.98 vs. 0.76; p = 0.001) and higher frequency of altered cVR (72.2% vs. 42.2%; p = 0.004). There was a significant predominance of higher values on Fazekas scale in the PDvasc group. We found no difference between the Fazekas scale when comparing motor subtypes groups but there was a trend toward higher scores in the AR phenotype. CONCLUSIONS: TCCS, a cost-effective method, displayed impaired cVR in Parkinsonian patients with risk factors for CVD with higher degree of MRI leukoaraiosis. PD patients with the AR disease phenotype also presented impaired cVR on TCCS and greater functional impairment, although with just a trend to higher scores on MRI Fazekas.

Evaluation of Five Non-Culture-Based Methods for the Diagnosis of Meningeal Sporotrichosis.

Sporotrichosis is the main subcutaneous mycosis worldwide. Several complications, including meningeal forms, can be observed in immunocompromised individuals. The sporotrichosis diagnosis is time-consuming due to the culture's limitations. The low fungal burden in cerebrospinal fluid (CSF) samples is another important drawback in the diagnosis of meningeal sporotrichosis. Molecular and immunological tests can improve the detection of Sporothrix spp. in clinical specimens. Therefore, the following five non-culture-based methods were evaluated for the detection of Sporothrix spp. in 30 CSF samples: (i) species-specific polymerase chain reaction (PCR); (ii) nested PCR; (iii) quantitative PCR; (iv) enzyme-linked immunosorbent assay (ELISA) for IgG detection; and (v) ELISA for IgM detection. The species-specific PCR was unsuccessful in the diagnosis of the meningeal sporotrichosis. The other four methods presented substantial levels of sensitivity (78.6% to 92.9%) and specificity (75% to 100%) for the indirect detection of Sporothrix spp. Both DNA-based methods presented similar accuracy (84.6%). Both ELISA methods were concomitantly positive only for patients with sporotrichosis and clinical signs of meningitis. We suggest that these methods should be implemented in clinical practice to detect Sporothrix spp. in CSF early, which may optimize treatment, augment the chances of a cure, and improve the prognosis of affected individuals.

Neurobrucellosis.

PURPOSE OF REVIEW: Brucellosis is one of the most common zoonosis worldwide, affecting 500 000 people, annually. Neurobrucellosis incidence is approximately 4%, and it is almost always heterogeneous. As there are no typical clinical features, its diagnosis is frequently misdiagnosing by other infections. RECENT FINDINGS: Neurobrucellosis picture includes meningitis, meningoencephalitis, encephalitis, cranial neuropathies, intracranial hypertension, sinus thrombosis, hemorrhages radiculitis, peripheral neuropathy, myelitis, and psychiatric manifestations. The diagnosis should be based on symptoms and signs suggestive of neurobrucellosis, not explained by other neurological disease, cerebrospinal fluid analysis, a positive Brucella serology or culture, and a response to specific antibiotics, with a significant improvement of cerebrospinal fluid parameters. SUMMARY: Neurobrucellosis can be insidious, and despite its global distribution, it is still unrecognized and frequently goes unreported. The understanding of the current epidemiology is necessary for eradication of the disease in humans, as well as the disease control in animals and prevention based on occupational hygiene and food hygiene.

Peracetylation of polyphenols under rapid and mild reaction conditions.

Structural modifications are an important tool for studying the properties of naturally occurring polyphenols. Regarding the preparation of acetyl esters, the presence of hydroxyl groups stabilized by intramolecular hydrogen bonds may pose an obstacle for the peracetylation of these compounds. In this paper, we present a facile protocol for the acetylation of selected polyphenols under mild reaction conditions by using acetic anhydride, catalytic amount 4-dimethylaminopyridine (DMAP) and dimethylformamide (DMF) as solvent. Reaction conditions were adjusted for optimal formation of peracetylated polyphenols while minimizing the formation of byproducts. Butyric anhydride was employed as an alternative acylating agent and showed similar results. Reaction yields varied from 78-97%, and products were obtained in high purity, as determined by LCMS(ESI+), 1H NMR and 13C NMR.

Ethos e produção de subjetividade no "Mundo dos depressivos": uma análise institucional de discurso / Ethos and production of subjectivity in the "World of depressives": an institutional discourse analysis / Ethos et production de subjectivité dans le "Monde des dépressifs": une analyse institutionnelle du discours / Ethos y producción de subjetividad en el "Mundo de los depresivos": un análisis institucional del discurso

O presente artigo se debruça sobre o corpus encontrado no blog "Mundo dos depressivos", em que seu criador apresenta um olhar sobre como é ser um indivíduo deprimido. O objetivo é o de delimitar os contornos de subjetividade que se produzem ali. Este trabalho foi construído a partir da perspectiva da Análise Institucional do Discurso. A estratégia de pensamento, motriz de todo trabalho, organiza-se em torno de conceitos como discurso, cena discursiva, efeitos de reconhecimento e desconhecimento e ethos. Por meio da construção de cenas de antagonismo entre o indivíduo com depressão e a sociedade, o enunciador do blog configura um ethos não como prostração ou abatimento, como se poderia esperar, mas como um lugar de potência e resistência.

This article focuses on the corpus found on the blog "World of Depressives", in which its creator portrays the experience of being a depressed individual. The objective is to delimit the contours of subjectivity within the blog. This work was constructed from the perspective of Institutional Discourse Analysis. The thought strategy driving all work is organized around concepts such as discourse, discursive scene, effects of recognition and ignorance, and ethos. Through the construction of scenes of antagonism between the individual with depression and society, the blog's enunciator shapes an ethos, not as prostration or despondency, as one might expect, but as a place of power and resistance.

Cet article se concentre sur le corpus trouvé sur le blog "Monde des dépressifs", dans lequel son créateur présente un regard sur ce que c'est que d'être un individu dépressif. L'objectif est de délimiter les contours de la subjectivité qui s'y produisent. Ce travail a été construit dans la perspective de l'Analyse Institutionnel du Discours. La stratégie de pensée, moteur de tout travail, s'organise autour de concepts tels que discours, scène discursive, effets de reconnaissance et d'ignorance et d'ethos. Par la construction de scènes d'antagonisme entre l'individu dépressif et la société, l'énonciateur du blog configure un ethos, non comme prostration ou abattement, comme on pourrait s'y attendre, mais comme lieu de pouvoir et de résistance.

Este artículo se centra en el corpus encontrado en el blog "Mundo dos depresivos", donde su creador ofrece una mirada sobre cómo es ser un individuo deprimido. El objetivo es delimitar los contornos de subjetividad que se producen allí. Este trabajo fue construido desde la perspectiva del Análisis Institucional del Discurso. La estrategia de pensamiento, que impulsa todo el trabajo, se organiza en torno a conceptos como discurso, escena discursiva, efectos de reconocimiento e ignorancia, y ethos. A través de la construcción de escenas de antagonismo entre el individuo con depresión y la sociedad, el enunciador del blog configura un ethos, no como postración o disminución, como cabría esperar, sino como lugar de poder y resistencia.

A Novel Protocol for the Synthesis of 1,2,4-Oxadiazoles Active against Trypanosomatids and Drug-Resistant Leukemia Cell Lines.

Cancer and parasitic diseases, such as leishmaniasis and Chagas disease, share similarities that allow the co-development of new antiproliferative agents as a strategy to quickly track the discovery of new drugs. This strategy is especially interesting regarding tropical neglected diseases, for which chemotherapeutic alternatives are extremely outdated. We designed a series of (E)-3-aryl-5-(2-aryl-vinyl)-1,2,4-oxadiazoles based on the reported antiparasitic and anticancer activities of structurally related compounds. The synthesis of such compounds led to the development of a new, fast, and efficient strategy for the construction of a 1,2,4-oxadiazole ring on a silica-supported system under microwave irradiation. One hit compound (23) was identified during the in vitro evaluation against drug-sensitive and drug-resistant chronic myeloid leukemia cell lines (EC50 values ranging from 5.5 to 13.2 µM), Trypanosoma cruzi amastigotes (EC50 = 2.9 µM) and Leishmania amazonensis promastigotes (EC50 = 12.2 µM) and amastigotes (EC50 = 13.5 µM). In silico studies indicate a correlation between the in vitro activity and the interaction with tubulin at the colchicine binding site. Furthermore, ADMET in silico predictions indicate that the compounds possess a high druggability potential due to their physicochemical, pharmacokinetic, and toxicity profiles, and for hit 23, it was identified by multiple spectroscopic approaches that this compound binds with human serum albumin (HSA) via a spontaneous ground-state association with a moderate affinity driven by entropically and enthalpically energies into subdomain IIA (site I) without significantly perturbing the secondary content of the protein.

Lessons from the Cerebrospinal Fluid Analysis of HTLV-1-Infected Individuals: Biomarkers of Inflammation for HAM/TSP Development.

HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a neurodegenerative disease that leads to motor impairment due to a chronic inflammatory process in the central nervous system (CNS). However, the HAM/TSP pathogenesis is not completely clear, and biomarkers to define the disease prognosis are still necessary. Thus, we aimed to identify biomarkers for HAM/TSP and potential mechanisms involved in disease development. To that end, the concentrations of VILIP-1, BDNF, VEGF, ß-NGF, TGF-ß1, fractalkine/CX3CL1, IL-6, IL-18, and TNF-α, and the soluble forms of TREM-1, TREM-2, and RAGE, were assessed using a multiplex bead-based immunoassay in paired cerebrospinal fluid (CSF) and serum samples from HAM/TSP patients (n = 20), asymptomatic HTLV-1 carriers (AC) (n = 13), and HTLV-1-seronegative individuals (n = 9), with the results analyzed according to the speed of HAM/TSP progression. HAM/TSP patients had elevated fractalkine in the serum but not in the CSF, particularly those with low neuroinflammatory activity (CSF/serum ratio of neopterin <1 and of CXCL10 < 2). HAM/TSP patients with normal CSF levels of neurofilament light chain (NfL) showed elevated ß-NGF in serum, and serum BDNF levels were increased in HTLV-1-infected individuals, particularly in HTLV-1 AC. Both HTLV-1 AC and HAM/TSP patients had lower TGF-ß1 levels in CSF compared to uninfected individuals, and HAM/TSP patients with active CNS inflammation showed higher CSF levels of IL-18, which correlated with markers of inflammation, neuronal death, and blood−brain-barrier permeability. Although none of the factors evaluated were associated with the speed of HAM/TSP progression, reduced TGF-ß1 levels in CSF suggest that suppressive responses to control subclinical and/or active neurodegeneration are impaired, while increased CSF IL-18 indicates the involvement of inflammasome-mediated mechanisms in HAM/TSP development.

Chitotriosidase 1 in the cerebrospinal fluid as a putative biomarker for HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) progression.

Human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is an inflammatory neurodegenerative disease that affects motor, urinary, intestinal, and sensory functions. Typically, HAM/TSP is slowly progressive, but it may vary from limited motor disability after decades (very slow progression) to loss of motor function in a few years from disease onset (rapid). In this study, we aimed to identify prognostic biomarkers for HAM/TSP to support patient management. Thus, proteomic analysis of the cerebrospinal fluid (CSF) was performed with samples from HTLV-1 asymptomatic carriers (AC) (n=13) and HAM/TSP patients (n=21) with rapid, typical, and very slow progression using quantitative label-free liquid chromatography/tandem mass spectrometry. Enrichment analyses were also carried out to identify key biological processes associated with distinct neurological conditions in HTLV-1 infection. Candidate biomarkers were validated by ELISA in paired CSF and serum samples, and samples from HTLV-1-seronegative individuals (n=9) were used as controls. CSF analysis identified 602 proteins. Leukocyte/cell activation, immune response processes and neurodegeneration pathways were enriched in rapid progressors. Conversely, HTLV-1 AC and HAM/TSP patients with typical and very slow progression had enriched processes for nervous system development. Differential expression analysis showed that soluble vascular cell adhesion molecule 1 (sVCAM-1), chitotriosidase 1 (CHIT1), and cathepsin C (CTSC) were upregulated in HAM/TSP. However, only CHIT1 was significantly elevated after validation, particularly in HAM/TSP rapid progressors. In contrast, none of these biomarkers were altered in serum. Additionally, CSF CHIT1 levels in HAM/TSP patients positively correlated with the speed of HAM/TSP progression, defined as points in the IPEC-2 HAM/TSP disability scale per year of disease, and with CSF levels of phosphorylated neurofilament heavy chain, neopterin, CXCL5, CXCL10, and CXCL11. In conclusion, higher CSF levels of CHIT1 were associated with HAM/TSP rapid progression and correlated with other biomarkers of neuroinflammation and neurodegeneration. Therefore, we propose CHIT1 as an additional or alternative CSF biomarker to identify HAM/TSP patients with a worse prognosis.

The Sweet Side of Fungal Infections: Structural Glycan Diversity and Its Importance for Pathogenic Adaptation.

Fungal infections are the most common secondary infections in debilitated individuals in a state of chronic disease or immunosuppression. Despite this, most fungal infections are neglected, mainly due to the lower frequency of their more severe clinical forms in immunocompetent individuals with a healthy background. However, over the past few years, several cases of severe fungal infections in healthy individuals have provoked a change in the epidemiological dynamics of fungal infections around the world, both due to recurrent outbreaks in previously infrequent regions and the greater emergence of more pathogenic fungal variants affecting healthy individuals, such as in the Cryptococcus genus. Therefore, before the arrival of a scenario of prevalent severe fungal infections, it is necessary to assess more carefully what are the real reasons for the increased incidence of fungal infection globally. What are the factors that are currently contributing to this new possible epidemiological dynamic? Could these be of a structural nature? Herein, we propose a discussion based on the importance of the virulence factors of glycoconjugate composition in the adaptation of pathogenic fungal species into the current scenario of increasing severity of these infections.