Quantum Biochemistry Screening and In Vitro Evaluation of Leishmania Metalloproteinase Inhibitors.

Leishmanolysin, also known as major promastigote protease (PSP) or gp63, is the most abundant surface glycoprotein of Leishmania spp., and has been extensively studied and recognized as the main parasite virulence factor. Characterized as a metalloprotease, gp63 can be powerfully inactivated in the presence of a metal chelator. In this study, we first used the structural parameters of a 7-hydroxycoumarin derivative, L1 compound, to evaluate the theoretical-computational experiments against gp63, comparing it with an available metal chelator already described. The methodology followed was (i) analysis of the three-dimensional structure of gp63 as well as its active site, and searching the literature and molecular databases for possible inhibitors; (ii) molecular docking simulations and investigation of the interactions in the generated protein-ligand complexes; and (iii) the individual energy of the gp63 amino acids that interacted most with the ligands of interest was quantified by ab initio calculations using Molecular Fraction with Conjugated Caps (MFCC). MFCC still allowed the final quantum balance calculations of the protein interaction to be obtained with each inhibitor candidate binder. L1 obtained the best energy quantum balance result with -2 eV, followed by DETC (-1.4 eV), doxycycline (-1.3 eV), and 4-terpineol (-0.6 eV), and showed evidence of covalent binding in the enzyme active site. In vitro experiments confirmed L1 as highly effective against L. amazonensis parasites. The compound also exhibited a low cytotoxicity profile against mammalian RAW and 3T3 cells lines, presenting a selective index of 149.19 and 380.64 µM, respectively. L1 induced promastigote forms' death by necrosis and the ultrastructural analysis revealed disruption in membrane integrity. Furthermore, leakage of the contents and destruction of the parasite were confirmed by Spectroscopy Dispersion analysis. These results together suggested L1 has a potential effect against L. amazonensis, the etiologic agent of diffuse leishmaniasis, and the only one that currently does not have a satisfactory treatment.

Digital dual test syphilis/HIV detection based on Fourier Descriptors of Cyclic Voltammetry curves.

BACKGROUND: Effective and timely detection is vital for mitigating the severe impacts of Sexually Transmitted Infections (STI), including syphilis and HIV. Cyclic Voltammetry (CV) sensors have shown promise as diagnostic tools for these STI, offering a pathway towards cost-effective solutions in primary health care settings. OBJECTIVE: This study aims to pioneer the use of Fourier Descriptors (FDs) in analyzing CV curves as 2D closed contours, targeting the simultaneous detection of syphilis and HIV. METHODS: Raw CV signals are filtered, resampled, and transformed into 2D closed contours for FD extraction. Essential shape characteristics are captured through selected coefficients. A complementary geometrical analysis further extracts features like curve areas and principal axes lengths from CV curves. A Mahalanobis Distance Classifier is employed for differentiation between patient and control groups. RESULTS: The evaluation of the proposed method revealed promising results with classification performance metrics such as Accuracy and F1-Score consistently achieving values rounded to 0.95 for syphilis and 0.90 for HIV. These results underscore the potential efficacy of the proposed approach in differentiating between patient and control samples for STI detection. CONCLUSION: By integrating principles from biosensors, signal processing, image processing, machine learning, and medical diagnostics, this study presents a comprehensive approach to enhance the detection of both syphilis and HIV. This setts the stage for advanced and accessible STI diagnostic solutions.

Salus Platform: A Digital Health Solution Tool for Managing Syphilis Cases in Brazil-A Comparative Analysis.

(1) Introduction: Syphilis is a sexually transmitted infection (STI) that constitutes a serious public health problem in Brazil and worldwide; (2) Methods: This was a descriptive and exploratory study that sought to analyze and compare the characteristics of Brazilian health systems with a new platform (Salus) developed by the Laboratory of Technological Innovation in Health in the scope of notification and management of disease data, including syphilis. In addition, this analysis aimed to assess whether Salus fully meets the necessary data management fields and can be indicated as a tool to improve health management in the context of syphilis in Brazil. (3) Results: In this study, the Salus functionalities were demonstrated and compared with the current Brazilian systems by discovering the existing gaps in the evaluated systems. The gaps found may explain the delay in meeting demands, the difficulty of making routine therapeutic follow-ups, in addition to interference with the vital purpose of follow-up in the epidemiological surveillance of diseases. As a result, Salus demonstrates functionalities that surpass all others and meet case management demands in a superior way to the systems currently used in the country. (4) Conclusions: The Brazilian health information systems related to the response to syphilis do not fulfill the purpose for which they were developed. Instead, they contribute to the fragmentation of health data and information, delays in diagnosis, incomplete case management, and loss of data due to inconsistencies and inadequate reporting. In addition, they are systems without interconnection, which do not articulate epidemiological surveillance actions with primary health care. All these factors may be obscuring accurate data on syphilis in Brazil, resulting in high and unnecessary public spending and late care for users of the Unified Health System (SUS).

Epidemiological Aspects of the Initial Evolution of COVID-19 in Microregion of Uberlândia, Minas Gerais (MG), Brazil.

COVID-19 is considered by the World Health Organization to be a global public health emergency, which presents regional divergences that affect the epidemiological profile of the disease and are associated with political, economic, social and behavioral aspects. We aimed to analyze the epidemiological characteristics of the disease in the microregion of Uberlândia, Brazil, in order to determine risk factors that contributed to progression of SARS-CoV-2 virus. A cross-sectional study was conducted about micro- and macro-determinants combined with the significance analysis of suspected and confirmed cases in 18 municipalities during the epidemiological weeks (EW) 9 to 26. There were 34,046 notifications, of which 4935 (14.49%) people were diagnosed with COVID-19. Of these, 282 (5.71%) required hospital care and 40 (0.81%) died. Age and presence of associated comorbidities were decisive in the variations of incidence and lethality rates. In general, young people were the most affected and the elderly people, the most exposed to the serious and lethal form (p < 0.0001). Comorbidities such as diabetes and cardiopathies increased 33.5 times the death risk. The dispersion of the virus was centrifugal, in the inter as well as in the intra-municipal level. The disorderly implementation of municipal decrees applied in a decentralized manner in the municipalities seems to have contributed for the incidence rates increasing in the EW 25 and 26.

Direct analysis of naphthenic acids in produced water and crude oil by NH2-surface-modified wooden-tip electrospray ionization mass spectrometry.

This work describes the surface coating of wooden toothpicks with amino groups (NH2) for electrospray ionization mass spectrometry (MS) analysis of naphthenic acids (NAs) in produced water samples and crude oil fractions. NH2 was introduced into the cellulosic material through a silanization reaction using aminopropyltriethoxysilane. An NH2-modified toothpick was inserted into the analyte extraction sample and was subsequently used as an electrospray emitter for MS analysis. The extraction conditions were optimized by analyzing NAs (benzoic acid, 1-naphthoic acid, decanoic acid, 3,5-dimethyladamantane-1-carboxylic acid, and 3,5-dimethyladamantane-1-acetic acid) in pure water, and the best condition was using 5 min of extraction time with the samples under agitation. Modified and unmodified wooden toothpicks were compared, and the intensities of all NAs were higher when using the modified substrates than when using the unmodified ones. Limit of detection (LOD), limit of quantification (LOQ), linearity, precision, and recovery were determined by analyzing decanoic acid in seawater samples. The LOD and LOQ were 2 and 5 µg mL-1, respectively, and a linear correlation (R2 = 0.9927) was obtained with concentrations ranging from 5 to 250 µg mL-1. Precision values ranged from 6 to 13% and recoveries from 89 to 106%. The technique was also employed to analyze three produced water samples, in which decanoic acid was semi-quantified, and the concentrations ranged from 10 to 13 µg mL-1. High abundances of acidic compounds of class O2 with DBEs (double bond equivalents) ranging from 1 to 3 and carbon numbers going from 8 to 12 were detected in the produced water samples. The results suggest that the modification of wooden toothpicks with NH2 might offer a significant advancement in the knowledge of cheap substrates that can improve the sensitivity of analysis of NAs in water samples.

Synthesis of Silver Nanoparticle Employing Corn Cob Xylan as a Reducing Agent with Anti-Trypanosoma cruzi Activity.

BACKGROUND: Chagas disease, also known as American Trypanosomiasis, is caused by the protozoan Trypanosoma cruzi. It is occurring in Americas, including USA and Canada, and Europe and its current treatment involves the use of two drugs as follows: benznidazole (BNZ) and nifurtimox, which present high toxicity and low efficacy during the chronic phase of the disease, thus promoting the search for more effective therapeutic alternatives. Amongst them xylan, a bioactive polysaccharide, extracted from corn cob. METHODS: Ultraviolet-visible spectroscopy, Fourier transform infrared spectroscopy (FITR), Raman spectroscopy, energy-dispersive X-ray spectroscopy (EDS), scanning electron microscopy, atomic force microscopy, plasma optical emission spectroscopy (ICP-OES), dynamic light scattering (DLS) have been used to characterize the silver-xylan nanoparticles (NX). Their cytotoxicity was evaluated with 3-bromo(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) test. MTT and flow cytometry were used to ascertain the anti-Trypanosoma cruzi activity. RESULTS: UV-Vis spectroscopy gave plasmon resonance ranging between 400 and 450 nm while FITC and Raman spectroscopy proved nano interface functionalized with xylan. ICP-OES data showed NX with xylan (81%) and silver (19%). EDS showed NX consisting of carbon (59.4%), oxygen (26.2%) and silver (4.8%) main elements. Spherical NX of 55 nm average size has been depicted with SEM and AFM, while DLS showed 102 ± 1.7 nm NX. The NX displayed negligible cytotoxicity (2000 µg/mL). NX (100 µg/mL) was more effective, regardless of experiment time, in affecting the ability of parasites to reduce MTT than BZN (100 µg/mL). In addition, NX (100 µg/mL) induced death of 95% of parasites by necrosis. CONCLUSION: This is the first time silver nanoparticles are presented as an anti-Trypanosoma cruzi agent and the data point to the potential application of NX to new preclinical studies in vitro and in vivo.

Nosso sistema imune de cada dia e os agrotóxicos de hoje / Our everyday immune system and today's pesticides

O uso massivo dos agrotóxicos nas lavouras deu-se a partir de 1950 com a "Revolução Verde", como resultado da busca por aumento da produtividade e modernização dos campos agrícolas. Diante disso, na década de 1960, foi criado o Programa Nacional de Defensivos Agrícolas (PNDA), que veio para facilitar a introdução dos agroquímicos, colaborando para que, a partir de 2008, o Brasil passasse a ser o país com maiores percentuais de uso destes produtos. Essas substâncias geram efeitos deletérios sobre a resposta imune dos indivíduos expostos, principalmente relacionada aos macrófagos, células B, T e NK. Isso afeta a capacidade de fagocitose, apresentação de antígenos e produção de anticorpos, além de induzir a geração de radicais livres de oxigênio e disfunção mitocondrial, resultando em estresse oxidativo e danos ao DNA celular, apoptose em excesso, mutação no ciclo celular, desordem de regulação e, consequentemente, imunodeficiência. Dessa forma, o desenvolvimento de doenças imunomediadas, como asma e doença pulmonar obstrutiva crônica (DPOC), está estreitamente ligado aos agrotóxicos, uma vez que esses variados mecanismos de toxicidade ao sistema imune induzem, dentre outras, manifestações respiratórias, tais como tosse, sibilo, irritação e inflamação. Além disso, estes pesticidas estão relacionados com doenças não imunomediadas ao alterar a função normal dos hormônios da tireoide, andrógenos e estrógenos. A fim de avaliar estes impactos, o presente estudo consiste em uma revisão integrativa da literatura e, diante da crescente utilização descontrolada dos agrotóxicos, assume grande relevância, refletindo a necessidade de maior atuação da vigilância epidemiológica, ambiental e da saúde do trabalhador.

Beginning in the 1950s, massive pesticide use began in what is called the "Green Revolution", a quest for increased agricultural productivity and modernization. In the 1960s, the Brazilian National Program of Agricultural Defense was created to facilitate the introduction of agrochemicals, leading the country to become one of the world's largest pesticide users by 2008. These substances have deleterious effects on the immune response of exposed individuals, mainly related to macrophages and B, T, and NK cells. This affects phagocytosis and antigen and antibody production, inducing production of oxygen free radicals and mitochondrial dysfunction, which results in oxidative stress and cellular DNA damage, excess apoptosis, cell cycle mutations, regulatory disorders, and, consequently, immunodeficiency. Thus, the development of immune-mediated diseases, such as asthma and chronic obstructive pulmonary disease (COPD), is closely linked to pesticides, since these varied mechanisms of toxicity to the immune system induce respiratory manifestations, such as cough, wheezing, irritation and inflammation. Pesticide use is also related to non-immune-mediated diseases because exposure alters the normal function of thyroid hormones, androgens, and estrogens. To evaluate their impact, the present study performed an integrative review of the literature, which, due to the growing and uncontrolled use of pesticides, is of great relevance and demonstrates the need for greater epidemiological, environmental, and worker health surveillance.

Propriedades psicométricas da Escala de Intenções frente à Infidelidade (EII) / Psychometric properties of the Intentions toward Infidelity Scale (IIS) / Propriedades psicométricas de la Escala de Intención hacia la Infidelidad (EII)

O presente estudo objetivou adaptar ao contexto brasileiro a Escala de Intenções frente à Infidelidade (EII), conhecendo seus parâmetros psicométricos. Realizou-se dois estudos com pessoas que indicaram estar em um relacionamento amoroso. No Estudo 1 participaram 161 pessoas (idade média = 24,9), que responderam a EII e perguntas demográficas. Os resultados indicaram a unifatorialidade desta escala (α = 0,85), cujos itens mostraram-se discriminativos (amplitude do theta variou de -0,5 a 3,0). No Estudo 2 participaram 236 pessoas (média de idade = 25,5), que responderam os mesmos instrumentos. Os resultados apoiaram a estrutura unifatorial (e.g., CFI = 0,95 e TLI = 0,93), que se mostrou invariante quanto ao sexo (ΔCFI e ΔRMSEA <0,01). Concluindo, os achados apoiaram a adequação dos itens da EII, como também indicaram evidências de sua validade fatorial e consistência interna, favorecendo que possa ser utilizada em pesquisas que buscam conhecer os correlatos da infidelidade. (AU)

This study aimed to adapt the Intentions Toward Infidelity Scale (IIS) to the Brazilian context, knowing its psychometric parameters. Two studies were carried out with people who were in a romantic relationship. Study 1 included 161 participants (mean age = 24.9), who responded to the IIS and demographic questions. Results indicated the one-factor solution for this scale (α = 0.85), whose items showed reasonable discriminative power (theta ranging from -0.5 to 3.0). Study 2 included 236 participants (mean age = 25.5), who answered the same instruments. Results supported the one-factor structure (e.g., CFI = .95 and TLI=.93), which showed invariant across sex (ΔCFI and ΔRMSEA < 0.01). In conclusion, the findings supported the adequacy of the IIS items, but also indicated evidence of its factorial validity and internal consistency, favoring its use in studies looking to investigate the correlates of infidelity. (AU)

Este estudio tuvo por objetivo adaptar al contexto brasileño la Escala de Intenciones frente a Infidelidad (EII), conociendo sus parámetros psicométricos. Se realizaron dos estudios con personas que informaron estar en una relación amorosa. En el Estudio 1 participaron 161 personas (edad promedio = 24,9), quienes respondieron a la EII y preguntas demográficas. Los resultados indicaron una estructura unifactorial de la escala (α = 0,85), cuyos ítems fueron discriminatorios (amplitud de theta varió de -0,5 a 3,0). El Estudio 2 contó con 236 personas (edad promedio = 25,5), que respondieron los mismos instrumentos. Los resultados indicaron estructura unifactorial (e.g., CFI = 0,95 y TLI = 0,93), que se mostró invariable con respecto a sexo (ΔCFI y ΔRMSEA < 0,01). Los resultados confirmaron adecuación de los ítems de EII, como también indicaron evidencias de validez factorial y consistencia interna, lo que favorece su uso en investigaciones que procuran conocer conexiones de infidelidad. (AU)