ABSTRACT The incidence and clinical characteristics of NTM diseases in Brazil remain relatively unknown. The present study describes the diagnosis of NTM isolates, the clinical presentation and treatment outcomes. We analyzed NTM isolates in patients of a tertiary hospital in the Southeast region of Brazil, from January 2008 to July 2019. The ATS/IDSA criteria for diagnosis and treatment of these patients was applied. Mycobacterium kansasii were identified in 13/113 (11.5%) patients. In 59/113 (52.2%) patients who met the ATS criteria for disease, 29/59 (49.1%) received treatment, and 22/29 (75.8%) were cured. The major species identified was M. kansasii. The most frequent symptoms among the treated patients were dyspnea and cough, and the proportion of cured patients was high.

Abstract Industrial egg residue (IER) possesses substantial concentrations of calcium and crude protein. The objective of this study was to measure the digestibility and performance of broilers when IER was added to the feed. Four treatments were tested, which caused increasing replacement of calcitic limestone by IER (0, 35, 70 and 100%) during a 42-day production cycle. First, total bird excreta were collected from broilers with and without IER, and we determined dry matter digestibility, apparent metabolizable energy (AME), calcium, and nitrogen retention. The IER presented 7.5% of crude protein, 31% of calcium, 209 kcal/kg of AME and the digestibility coefficients for dry matter, crude protein, and calcium were calculated at 83.95%, 86.20%, and 67%, respectively. After the digestibility test, the effects of IER on performance, carcass and meat yield were evaluated. No significant differences between the treatments were found in terms of performance (weight gain, feed conversion, consumption, and mortality), and no differences were found in terms of carcass or meat yield. A linear decrease in the percentage of abdominal fat was observed with increasing inclusion of IER in feed. These findings suggest that IER can totally replace limestone (calcium carbonate) in broiler diets.

Abstract This article evaluates four statistical methods of multiple imputation to fill in the missing data of daily precipitation in Northeast Brazil (NEB). We used a daily database collected by 94 rain gauges distributed in NEB from January 1, 1986 to December 31, 2015. The methods were: random sampling from the observed values; predictive mean matching, Bayesian linear regression; and bootstrap expectation maximization algorithm (BootEm). To compare these methods, missing data from the original series were initially excluded. The next step was to create three scenarios for each method, in which 10\%, 20\% and 30\% of the data were removed at random. The BootEM method presented the best statistical results. With the average bias between the complete series and the imputed series values ranging between -0.91 and 1.30 mm/day. The values of the Pearson correlation ranging between 0.96, 0.91 and 0.86 respectively for 10\%, 20\% and 30\% missing data. We conclude that this is an adequate method for the reconstruction of historical precipitation data in NEB.

Cancer treatment represents one of the main scientific study targets today, mainly due to the pronounced side effects arising from chemotherapy. This study reports the synthesis, characterization, and anticancer activity of ten compounds from the Morita-Baylis-Hillman reaction. Ethylene glycol diacrylate was used as a double Michael acceptor in reactions with isatin derivatives to give homodimers of 3-hydroxyindolin-2-one core, recognized in the literature for its extensive pharmacological profile. The use of 1,4-diazabicyclo[2,2,2]octane (DABCO) as a catalyst and room temperature were the optimal conditions for the study reaction. The isolated yields were up to 63%, with most reaction times inferior to 24 h, some as fast as 15 min. The anticancer potential of the synthesized dimers was evaluated in vitro against three cancer strains, resulting in average inhibitory concentrations up to 0.72 µM. It was also found that the best performing homodimers are more active than their monomeric counterparts. Considering the promising selectivity indices observed, the preliminary results obtained here act as a basis for broader tests regarding the effectiveness of homodimeric adducts against cancer cells.

Magnesium silicate cement is produced by mixing reactive magnesium oxide with a source of reactive silicon oxide. This cement is an interesting alternative to Portland cement due to the potential for low energy consumption, reduced greenhouse gas emissions, and use of renewable resources. Aluminosilicate-based raw materials can also be utilized to produce this type of cement. Thus, this work aims to study the use of kaolinite clay to produce magnesium aluminosilicate cement. The cement was produced by calcination of magnesium carbonate (MgCO3) and kaolinite clay at a temperature of 800 °C for 45 minutes with MgCO3/kaolin mass ratios of 90/10, 80/20, and 70/30. Mortars and pastes samples were cured at 60 °C for 1, 3, and 7 days. The results showed that the maximum compressive strength (32.7 MPa) was yielded for the 70/30 mortar mix after 3 days of curing. Microstructural studies of pastes indicated the incorporation of aluminum for the formation of magnesium aluminosilicate hydrated products, in addition to the formation of brucite.

Abstract The selection of parents to originate promising base populations, as well as the knowledge of the gene effects controlling agronomic traits by means of diallel, are useful to drive genetic gains in Brazilian tropical wheat breeding programs. The goals of this study were to select tropical wheat parents with a high frequency of favorable alleles and segregating populations with high potential to originate superior progenies through partial diallel analysis. Thus, 14 parents were divided in two groups and crossed in a 7 × 7 partial diallel scheme to originate 49 F1 combinations. After obtaining F2 generation, the populations and the parents were evaluated in the field in the summer of 2021. Days for heading, plant height, rust and yellow spot resistance, and grain yield were evaluated. The data were subjected to partial diallel analysis. There were significant effects of general combining ability for all traits. The specific combining ability effect was significant for days for heading and plant height. The additive gene effects were predominant over the non-additive ones. The parents with the highest frequency of favorable alleles for the traits evaluated were selected in each group. Four populations with high genetic potential to originate superior progenies were selected.

The cariogenic processes are mainly caused by the bacterium Streptococcus mutans (S. mutans) and consist of the demineralization of the tooth that occurs when the acid production overcomes the natural repair or if a problem occurs in the last one. In this work, we performed the synthesis of twenty-one 1,4-naphthoquinones tethered to 1,2,3-1H-triazoles (8a-8k and 9a-9j), antibacterial evaluation against the S. mutans in vitro and the acute toxicity of the better ones in vivo. We observed strong inhibition results in the disc diffusion test ranging, the halos of inhibitions, from 18.66 (± 0.57) to 29 (± 2.64) mm, and good values in the minimum inhibitory concentration (5 to 50 μg), for the compounds 9e, 9h, 9i and 9j: Furthermore, they do not have a cytotoxic effect at the concentrations tested. Besides that, in the in vivo test, they show some slight alteration in the histopathological analyses and the biochemistry. Thus, we found four potential candidates to become instruments for the treatment of cavities.

An experimental and theoretical approach on oxidative metabolism of paracetamol was applied for the pharmaceutical chemistry learning. Classical reactions, functional group identification, structural parameter, and chemical reactivity using frontier orbitals and Fukui index were used explaining the main products between N-acetyl-p-benzosemiquinone (NAPQI) and thiolic compounds. The chemoprotection mechanisms by N-acetyl-cysteine on high dosage of paracetamol are consistent with theoretical and experimental results. The methods also described the relationship between the chemical reactivity of quinone-imine system and the induced-toxicity of paracetamol by Michael reaction. These results can be applied in experimental pharmaceutical chemistry teaching.

Chikungunya virus (CHIKV) is a re-emerging disease caused by an alphavirus of the Togaviridae family. Since its first description in 1952, the disease has spread worldwide, affecting populations in both tropical and temperate countries. To date, there is no licensed vaccine or specific pharmacological treatment. Therefore, there is an increasing urgency in developing new antiviral drugs capable of specifically inhibiting viral replication. In the present work, we report the synthesis and antiviral activity evaluation of nineteen naphthoquinone derivatives, containing a sulfonamide or sulfonate group. Cell viability assays indicated a low toxic potential for all tested compounds and inhibitory assays against CHIKV identified five compounds with potent activity. The compounds were also evaluated for their virucidal potential, and the results demonstrated that compound 11a exhibited a virucidal effect higher than 70% in the treatment with 20 µM. Furthermore, in silico studies were performed to predict the antiviral drug targets.

RESUMO Objetivos: o principal objetivo deste estudo foi descrever pacientes com achados vasculares retinianos temporalmente relacionados à vacinação contra COVID-19. Com maior notificação de possíveis eventos adversos similares, esperamos compreender a real dimensão e relevância do que foi apresentado. Métodos: Onze pacientes com queixas visuais após vacinação contra COVID-19 foram estudados. Os dados analisados foram: idade, gênero, tipo de vacinação, tempo de aparecimento de sintomas, achados sistêmicos, antecedentes pessoais, acuidade visual com melhor correção, biomicroscopia e imagem retiniana multimodal (retinografia colorida, red-free, SD-OCT, OCTA e angiofluoresceinografia). Os critérios de inclusão foram a presença de alterações oftalmológicas ocorridas dentro de 30 dias após a primeira ou segunda dose de qualquer vacina contra COVID-19. Resultados: Onze pacientes foram incluídos: 5 com oclusão arterial (45,4%), 4 com oclusão venosa (36,4%) e 2 (18,2%) com alterações não específicas vasculares sugestivas de isquemia retiniana como exsudatos algodonosos. A idade média dos pacientes foi de 57 anos (DP=16; com intervalo de 27 a 84 anos). A média de tempo de aparecimento de sintomas após a vacinação foi de 10 dias (DP=5,4; com intervalo de 3 a 16 dias). Nove dos onze pacientes eram do sexo feminino (81,8%). Fatores de risco sistêmicos foram observados em 36,4% dos pacientes. Dois pacientes tiveram sintomas neurológicos e visuais, com oclusão arterial. 36,4% dos pacientes tiveram infecção prévia por COVID-19 no último ano. Sete pacientes (63,6%) receberam a vacina ChAdOx1 nCoV-19 (AZD1222). Conclusões: nossos dados sugerem que eventos retinianos temporalmente relacionados à vacinação contra COVID-19 são possíveis, porém raros. A relação entre estes eventos pós-vacinais exigem futura atenção antes de maiores conclusões.

ABSTRACT Purpose: The primary purpose of this study was to assess vascular retinal findings temporally related to COVID-19 vaccination. With greater information regarding all possible future adverse events, we hope to understand the real dimension and relevance of what was presented. Methods: Eleven patients with visual complaints after COVID-19 vaccination were enrolled. Data on the following were included: age, sex, vaccine, time of symptom onset, systemic findings, medical history, best-corrected visual acuity, and ocular findings by slit-lamp biomicroscopy as well as multimodal retinal imaging (color fundus, red-free photography, spectral-domain optical coherence tomography, optical coherence tomography angiography, and fluorescein-angiography). Inclusion criteria were the presence of ophthalmologic signs within 30 days after the first or second dose of any COVID-19 vaccine. Results: Of 11 patients, five had arterial occlusion (45.4%), four had venous occlusion (36.4%), and two (18.2%) had nonspecific vascular alterations suggestive of retinal ischemia such as cotton-wool spots. The mean age was 57 (SD = 16; range: 27-84) years. The mean time of symptoms onset was 10 (SD = 5.4; range: 3-16) days. Nine patients were female (81.8%). Systemic risk factors were observed in 36.4% of patients. Two patients had both neurological and visual symptoms, with arterial occlusion. Overall, 36.4% patients had COVID-19 in the previous year. Seven patients (63.6%) received ChAdOx1 nCoV-19 (AZD1222) vaccine. Conclusions: Our data suggest that retinal events temporally related to COVID-19 vaccination are possible but are very rare. The relationship of these events with post-COVID-19 vaccination warrants further attention to derive a meaningful conclusion.

RESUMO Objetivo: Localizada em São Paulo, a Cracolândia é o maior e mais antigo cenário aberto de uso de drogas do Brasil. Ainda assim, pouco se sabe sobre o perfil dos indivíduos que vivem nessa região e buscam tratamento para crack . O objetivo deste estudo transversal foi descrever características demográficas e clínicas de usuários de crack vivendo na região da Cracolândia que estão em busca de tratamento. Métodos: Noventa e oito indivíduos foram avaliados para transtornos por uso de substâncias do DSM-V, padrão de uso de substâncias, impulsividade e sintomatologia psiquiátrica. O uso recente de crack também foi determinado por meio de coleta de amostras toxicológicas. Resultados: Os resultados indicaram grave vulnerabilidade social, com significativas prevalências de falta de moradia (46,9%), moradia instável (50%), desemprego (60,4%) e abandono escolar precoce (27,5%). A idade média de início do uso de crack foi de 20 anos (DP = 6,9) e a duração média do uso contínuo do crack foi de 15 anos (DP = 9,7). A maioria dos participantes apresentou alguma comorbidade psiquiátrica, particularmente transtorno por uso de álcool (87,8%), bem como altas taxas de sintomatologia psiquiátrica e impulsividade. Mais da metade da amostra relatou pelo menos uma tentativa anterior de tratamento por internação (73,5%) e ambulatorial (65,3%). Conclusão: Os achados desse estudo permitem um maior entendimento do perfil e das necessidades de usuários de crack vivendo na região da Cracolândia e podem ajudar serviços de saúde especializados em dependência química a promoverem uma assistência mais direcionada às demandas específicas dessa população.

ABSTRACT Objective: São Paulo‘s Crackland is the biggest and oldest open drug use scene in Brazil, yet little is known about the profile of crack cocaine treatment-seeking individuals living in this region. The aim of this crossectional study was to describe the demographics and clinical characteristics of treatment-seeking crack users living in the Crackland region. Methods: A sample of nighty eight individuals were screened for DSM-V substance use disorders, including substance use, impulsiveness, and psychiatric symptoms. Recent crack cocaine use was also tested using biologic specimens. Results: Results indicated severe social vulnerability, as participants experienced high rates of homelessness (46.9%), unstable housing (50%), unemployment (60.4%) and early school drop-out (27.5%). The average age of crack use onset was 20 years (SD = 6.9) and the mean duration of continuous crack use was 15 years (SD = 9.7). Most participants presented with concomitant mental health disorders, particularly alcohol use disorder (87.8%), as well high rates of psychiatric symptomatology and impulsiveness. More than half of the sample reported at least one previous inpatient (73.5%) and outpatient (65.3%) addiction treatment attempt. Conclusion: This population profile should inform mental healthcare services, promoting the provision of tailored assistance by targeting specific demands at all levels of treatment.

Acetylated compounds prepared from naphthoquinones have been reported as antitumoral prodrugs. Exploring the synthetic versatility of the naphthoquinone and triazolic nuclei, herein we report a simple and efficient synthetic route to prepare a series of sixteen prodrugs prototype of 1,2,3-triazoles-naphthoquinodoic acetyl derivatives. The compounds 10a-10h and 11a-11h were obtained by oxidative cycloaddition reaction between lawsone and 4-vinyl-1H-1,2,3-triazoles promoted by ceric ammonium nitrate (CAN) in alkaline medium followed by reductive acetylation of the quinones in excess of metallic zinc and acetic anhydride in yields up to > 98%. All derivatives revealed to be hemocompatible and the compound 11e exhibited the most promising profile against Caco-2 cells showing the higher selectivity index. Molecular docking suggests that these compounds could exert their cytotoxic activity through inhibition of one topoisomerase II isoform, at least.

Platonia insignis fruit, popularly known as bacuri, is traditionally used in folk medicine for its anti-inflammatory and antioxidant properties. Therefore, this study determined the chemical composition and biological activities of the bacuri’s shell and seeds extracts, considered residues from its consumption and industrial uses. Four biflavonoids (GB-2a, GB-1a, morelloflavone, and volkensiflavone) were identified in the extracts by high-performance liquid chromatography-diode array detection (HPLC-DAD), liquid chromatography tandem mass spectrometry (LC-MS/MS), and liquid chromatography-solid phase extraction-nuclear magnetic resonance (LC-SPE-NMR) techniques. Morelloflavone was identified as the main compound in the shell ethyl acetate extract, being responsible for the high in vitro antioxidant (50% effective concentration (EC50) ranging from 8.0-10.5 µg mL−1 in different protocols), anti-glycant (80%), and moderate inhibition of nitric oxide (1.56 µg mL−1 for > 90% cell viability) activities. This extract showed promising in vivo anti-inflammatory activity evaluated through the paw edema protocol after its incorporation into a liquid-crystalline drug carrier system, reducing the edema by up to 31%. The results demonstrated the potential of the fruit for the development of drugs of natural origin and corroborated to add economic value to these discarded residues.

Morita-Baylis-Hillman adducts (MBHA) is a class of polyfunctional molecules that has been standing out due to their versatility and expressive biological activities. Therefore, this paper describes the synthesis and antiproliferative activity of some new MBHA/7-choroquinoline hybrids. The Michael acceptors were obtained starting from 4,7-dichloroquinoline which were submitted to the Morita-Baylis-Hillman reaction with ortho, meta and para-nitrobenzaldehyde. The in vitro screening of the synthetized MBHA against NCI-H292, HCT-116 and MCF-7 cancer cells suggests the influence of the spacer chain in its inhibition potential. The 50% inhibitory concentration (IC50) obtained in the antiproliferative assay using MCF-7, HCT-116, HL-60 and NCI-H292 cancer cells indicate expressive cytotoxic potential of the adducts containing nitro group in the ortho position, with IC50 of 4.60 µmol L-1. MBHA/7-choroquinoline hybrids were more active than MBHA described in literature, indicating the improvement of the cytotoxic effect due to 7-chloroquinoline moiety in the molecular structure, with maximum selectivity index values of 11.89.

According to the World Health Organization (WHO), Chagas disease (CD), whose etiological agent is the Trypanosoma cruzi (T. cruzi) parasite, affects about eight million people, mainly in Latin America. The cruzain enzyme is highlighted among the main biological targets, since it is the most abundant of the cysteine protease class from T. cruzi and is involved in the entire life cycle of the parasite, essential in regulating the interaction between parasite and host. The drugs available for the treatment of CD usually have strong side effects, and the nitro(triazole/imidazole)-based heteroarylamide/sulfonamide compounds (HA/S) emerge with high antitrypanosomal potential. In this study, the quantitative structure-activity relationship (QSAR) were built using partial least squares (PLS) regression, and the results were robust and adequate for predicting and proposing five new derivatives according to the statistical parameters. The docking results suggest that the best-scored HA/S derivatives showed hydrogen bonds with the residuals that comprise the catalytic region of the enzyme. The molecular dynamics (MD) simulations, performed with different methods, revealed the strong stability of the compound obtained by the QSAR model of this study, in addition to a better binding free energy value than the HA/S obtained from literature.