Essential role of the CCL2-CCR2 axis in Mayaro virus-induced disease.

Mayaro virus (MAYV) is an emerging arbovirus member of the Togaviridae family and Alphavirus genus. MAYV infection causes an acute febrile illness accompanied by persistent polyarthralgia and myalgia. Understanding the mechanisms involved in arthritis caused by alphaviruses is necessary to develop specific therapies. In this work, we investigated the role of the CCL2/CCR2 axis in the pathogenesis of MAYV-induced disease. For this, wild-type (WT) C57BL/6J and CCR2-/- mice were infected with MAYV subcutaneously and evaluated for disease development. MAYV infection induced an acute inflammatory disease in WT mice. The immune response profile was characterized by an increase in the production of inflammatory mediators, such as IL-6, TNF, and CCL2. Higher levels of CCL2 at the local and systemic levels were followed by the significant recruitment of CCR2+ macrophages and a cellular response orchestrated by these cells. CCR2-/- mice showed an increase in CXCL-1 levels, followed by a replacement of the macrophage inflammatory infiltrate by neutrophils. Additionally, the absence of the CCR2 receptor protected mice from bone loss induced by MAYV. Accordingly, the silencing of CCL2 chemokine expression in vivo and the pharmacological blockade of CCR2 promoted a partial improvement in disease. Cell culture data support the mechanism underlying the bone pathology of MAYV, in which MAYV infection promotes a pro-osteoclastogenic microenvironment mediated by CCL2, IL-6, and TNF, which induces the migration and differentiation of osteoclast precursor cells. Overall, these data contribute to the understanding of the pathophysiology of MAYV infection and the identification future of specific therapeutic targets in MAYV-induced disease.IMPORTANCEThis work demonstrates the role of the CCL2/CCR2 axis in MAYV-induced disease. The infection of wild-type (WT) C57BL/6J and CCR2-/- mice was associated with high levels of CCL2, an important chemoattractant involved in the recruitment of macrophages, the main precursor of osteoclasts. In the absence of the CCR2 receptor, there is a mitigation of macrophage migration to the target organs of infection and protection of these mice against bone loss induced by MAYV infection. Much evidence has shown that host immune response factors contribute significantly to the tissue damage associated with alphavirus infections. Thus, this work highlights molecular and cellular targets involved in the pathogenesis of arthritis triggered by MAYV and identifies novel therapeutic possibilities directed to the host inflammatory response unleashed by MAYV.

Clinical, hematological, biochemical, and histopathological evaluations in domestic cats (Felis catus) infected by Leishmania infantum.

A high frequency of feline leishmaniasis has been reported in several countries. However, much information about disease progression in cats still needs to be clarified. This study aimed to verify the occurrence of clinicopathological changes in cats infected with Leishmania infantum. A total of 60 cats were divided into three groups of 20 animals each: control, suspects, and infected. All 60 cats underwent blood count and biochemical analyses. Serum samples from 20 animals with leishmaniasis were also used to diagnose feline immunodeficiency virus and feline leukemia virus. A total of five of the infected animals underwent necropsy for a histopathological study. The main clinical findings in cats with leishmaniasis were lymphadenomegaly (65%), alopecia (55%), ulcerative skin lesions and weight loss (40%), skin nodules (25%), a significant reduction in red blood cells (p=0.0005) and hematocrit (p=0.0007), hyperplasia in spleen 4/5(80%), presence of Leishmania in the spleen 2/5(40%), hepatitis 3/5(60%), liver degeneration 4/5(80%) and inflammatory nephropathy 3/5(60%). It was concluded that cats with leishmaniasis presented significant clinical, hematological, and histopathological alterations compatible with L. infantum infection. The observation of lymphadenomegaly, weight loss, skin lesions and low concentration of red blood cells, contributes significantly to the diagnosis and analysis of progression of feline leishmaniasis.

Giants of the Amazon: How does environmental variation drive the diversity patterns of large trees?

For more than three decades, major efforts in sampling and analyzing tree diversity in South America have focused almost exclusively on trees with stems of at least 10 and 2.5 cm diameter, showing highest species diversity in the wetter western and northern Amazon forests. By contrast, little attention has been paid to patterns and drivers of diversity in the largest canopy and emergent trees, which is surprising given these have dominant ecological functions. Here, we use a machine learning approach to quantify the importance of environmental factors and apply it to generate spatial predictions of the species diversity of all trees (dbh ≥ 10 cm) and for very large trees (dbh ≥ 70 cm) using data from 243 forest plots (108,450 trees and 2832 species) distributed across different forest types and biogeographic regions of the Brazilian Amazon. The diversity of large trees and of all trees was significantly associated with three environmental factors, but in contrasting ways across regions and forest types. Environmental variables associated with disturbances, for example, the lightning flash rate and wind speed, as well as the fraction of photosynthetically active radiation, tend to govern the diversity of large trees. Upland rainforests in the Guiana Shield and Roraima regions had a high diversity of large trees. By contrast, variables associated with resources tend to govern tree diversity in general. Places such as the province of Imeri and the northern portion of the province of Madeira stand out for their high diversity of species in general. Climatic and topographic stability and functional adaptation mechanisms promote ideal conditions for species diversity. Finally, we mapped general patterns of tree species diversity in the Brazilian Amazon, which differ substantially depending on size class.

Concessão dos benefícios assistenciais para pessoas com paralisia cerebral no Brasil: tendência temporal e análise espacial / Continuous cash benefit for people with cerebral palsy in Brazil: temporal trend and spatial analysis

Objetivo: Analisar a tendência temporal e distribuição espacial dos benefícios concedidos para as pessoas com Paralisia Cerebral. Método: Estudo ecológico em que foram incluídos os benefícios concedidos às pessoas com Paralisia Cerebral, nos períodos de 2004 a 2016, no Brasil. Os dados foram coletados do Instituto Nacional de Seguridade Social e Instituto Brasileiro de Geografia Estatística. Utilizou-se o software Join Point Regression, 4.5.0.1, sendo as tendências classificadas em decrescente; crescente e estacionária. Na distribuição espacial foi realizada Análise Exploratória de Dados Espaciais com o software QGIS versão 3.18. Resultados: Observou-se uma tendência decrescente do BPC do ano de 2004 até o ano de 2016, no Brasil. Na região Norte o número de concessões aumentou de 2004-2010, mas, após isso, houve um decréscimo. Já as regiões Sudeste, Sul e Centro Oeste apresentaram tendência decrescente em todo o período analisado. Na análise espacial, as regiões Norte e Nordeste apresentaram maior frequência de BPC proporcionalmente à população com pessoas até 19 anos, aos domicílios e às famílias com até um salário mínimo nas unidades federativas do Brasil. Conclusão: Foi possível observar a diminuição de concessões do BPC em todas as regiões do país no período de 2004 a 2016. As regiões que possuem os índices mais elevados de distribuição do BPC são Nordeste e Norte, reconhecidamente, as que possuem os maiores indicadores de pobreza e extrema pobreza do país

Objective: To analyze the temporal trend and spatial distribution of benefits granted to people with Cerebral Palsy. Method: An ecological study that included the benefits granted to people with Cerebral Palsy, from 2004 to 2016, in Brazil. Data were recorded from the National Institute of Social Security and the Brazilian Institute of Geography. The software Join Point Regression, 4.5.0.1 was used and the trends were classified as increasing; growing and stationary. In the spatial distribution, Exploratory Spatial Data Analysis was performed with the QGIS software version 3.18. Results: There is a downward trend in BPC from 2004 to 2016 in Brazil. In the North region, the number of concessions increased from 2004-2010, but after that, there was a decline. The regions and Center West, on the other hand, show a decreasing trend throughout the Southeast and South period. In the spatial analysis, the most frequent North and Northeast regions of BPC in proportion to the population with people aged 19 years, to families with units up to one minimum wage in the federative units of Brazil. Conclusion: A decrease in BPC extensions was observed in all regions of the country in the period 2016. Poverty and extreme poverty in the country

Tumour necrosis factor plays a deleterious role in the pathogenesis of chikungunya virus infection.

Arthralgia is a hallmark of chikungunya virus (CHIKV) infection and can be very debilitating and associated with a robust local inflammatory response. Many pathophysiological aspects associated with the disease remain to be elucidated. Here, we describe a novel model of CHIKV infection in immunocompetent mice and evaluate the role of tumour necrosis factor in the pathogenesis of the disease. C57BL/6 wild type (WT) or TNF receptor 1 deficient (TNFR1-/- ) mice were inoculated with 1 × 106 PFU of CHIKV in the paw. Alternatively, etanercept was used to inhibit TNF in infected WT mice. Hypernociception, inflammatory and virological analysis were performed. Inoculation of CHIKV into WT mice induced persistent hypernociception. There was significant viral replication in target organs and local production of inflammatory mediators in early time-points after infection. CHIKV infection was associated with specific humoral IgM and IgG responses. In TNFR1-/- mice, there was a decrease in the hypernociception threshold, which was associated with a milder local inflammatory response in the paw but delayed viral clearance. Local or systemic treatment with etanercept reduced CHIKV-induced hypernociception. This is the first study to describe hypernociception, a clinical correlation of arthralgia, in immunocompetent mice infected with CHIKV. It also demonstrates the dual role of TNF in contributing to viral clearance but driving tissue damage and hypernociception. Inhibition of TNF may have therapeutic benefits but its role in viral clearance suggests that viral levels must be monitored in CHIKV-infected patients and that TNF inhibitors should ideally be used in combination with anti-viral drugs.

Microbiological properties of soils are sensitive to changes provided by organic cultivation of banana 'BRS Princesa' in the semi-arid region

Soil microbiota has a key role in the dynamics of natural and agro-ecosystems and is sensitive to changes in these environments. This study evaluated changes in the microbiological properties of soils under an organic production system of banana 'BRS Princesa' (Musa spp.). The experimental design consisted of completely randomized blocks, with four replications. Treatments consisted of 1) soil cover with green manure and agricultural gypsum at a dose of 2,820 kg ha−1, 2) soil cover with green manure without gypsum application, 3) soil cover with weeds and agricultural gypsum at a dose of 2,820 kg ha−1, 4) soil cover with spontaneous plants without gypsum application, and two controls: 5) soil under native Caatinga and 6) soil under regenerating forest (capoeira). The evaluated properties were ß-glucosidase, arylsulfatase, acid phosphatase, fluorescein diacetate hydrolysis activities (FDA), carbon and phosphorus contents in microbial biomass, basal soil respiration, microbial and metabolic quotients, and arbuscular mycorrhizal fungi spore density. Soil samples were collected from the 0­0.20m depth layer in two seasons. No parameter could distinguish the treatments. Spontaneous plants provided conditions equivalent to those under green manure. Agricultural gypsum application also did not influence the microbial biomass and microbiota activity, in the analyzed soil depth. However, ß-glucosidase and arylsulfatase activities, the carbon content in microbial biomass, and metabolic and microbial quotients were sensitive to land-use changes and could distinguish areas under organic cultivation from those under native vegetation. Therefore, these properties can be considered good indicators for monitoring the quality of these soils. Furthermore, microbial communities of soils under organic cultivation responded with arylsulfatase activity corresponding to that found in soils under regenerating forest, which may indicate that organic management tends to provide the microbiota with a condition similar to that found under situations that are little disturbing to edaphic living.(AU)

Clinical, hematological, biochemical, and histopathological evaluations in domestic cats (Felis catus) infected by Leishmania infantum / Avaliação clínica, hematológica, bioquímica e histopatológica em gatos domésticos (Felis catus) infectados por Leishmania infantum

A high frequency of feline leishmaniasis has been reported in several countries. However, much information about disease progression in cats still needs to be clarified. This study aimed to verify the occurrence of clinicopathological changes in cats infected with Leishmania infantum. A total of 60 cats were divided into three groups of 20 animals each: control, suspects, and infected. All 60 cats underwent blood count and biochemical analyses. Serum samples from 20 animals with leishmaniasis were also used to diagnose feline immunodeficiency virus and feline leukemia virus. A total of five of the infected animals underwent necropsy for a histopathological study. The main clinical findings in cats with leishmaniasis were lymphadenomegaly (65%), alopecia (55%), ulcerative skin lesions and weight loss (40%), skin nodules (25%), a significant reduction in red blood cells (p=0.0005) and hematocrit (p=0.0007), hyperplasia in spleen 4/5(80%), presence of Leishmania in the spleen 2/5(40%), hepatitis 3/5(60%), liver degeneration 4/5(80%) and inflammatory nephropathy 3/5(60%). It was concluded that cats with leishmaniasis presented significant clinical, hematological, and histopathological alterations compatible with L. infantum infection. The observation of lymphadenomegaly, weight loss, skin lesions and low concentration of red blood cells, contributes significantly to the diagnosis and analysis of progression of feline leishmaniasis.(AU)

Uma alta frequência de leishmaniose felina tem sido relatada em vários países. No entanto, muitas informações sobre a progressão da doença em gatos ainda precisam ser esclarecidas. Este estudo teve como objetivo verificar a ocorrência de alterações clinicopatológicas em gatos infectados por Leishmania infantum. Um total de 60 gatos foi dividido em três grupos de 20 animais cada: controle, suspeitos e infectados. Todos os 60 gatos foram submetidos à hemograma e testes bioquímicos. Amostras de soro de 20 animais com leishmaniose também foram utilizadas para diagnosticar o vírus da imunodeficiência felina e o vírus da leucemia felina. Um total de cinco dos animais infectados foram necropsiados para estudo histopatológico. Os principais achados clínicos nos gatos com leishmaniose foram linfadenomegalia (65%), alopecia (55%), lesões ulcerativas na pele e emagrecimento (40%), nódulos cutâneos (25%), redução significativa de hemácias (p=0,0005) e hematócrito (p=0,0007), hiperplasia no baço 4/5(80%), presença de Leishmania no baço 2/5(40%), hepatite 3/5(60%), degeneração hepática 4/5(80%) e nefropatia inflamatória 3/5(60%). Concluiu-se que gatos com leishmaniose apresentaram alterações clínicas, hematológicas e histopatológicas significativas compatíveis com infecção por L. infantum. A observação de linfadenomegalia, emagrecimento, lesões cutâneas e baixa concentração de hemácias, contribui significativamente para o diagnóstico e análise da progressão da leishmaniose felina.(AU)

Alberta infant motor scale in Brazilian research: a bibliometric study / Escala Motora Infantil de Alberta en la investigación brasileña: un estudio bibliométrico / Alberta infant motor scale em pesquisas brasileiras: estudo bibliométrico

ABSTRACT The Alberta infant motor scale (AIMS) is an instrument for assessing the gross motor development of newborns, aged 0-18 months. This study aimed to summarize the Brazilian studies that used the AIMS and identify their objectives to know the main uses of the scale for professionals interested in child motor development. This is a bibliometric study on SciELO, PubMed, Scopus, and Web of Science databases. The searched keywords were "Alberta infant motor scale" and "Brazil," with their equivalents in Portuguese and united by "AND." Inclusion criteria were: use of AIMS with children aged 0-18 months carried out in Brazil. The variables database, journal, year of publication, language, region of the institution linked to the authors, and type of study were analyzed in a descriptive quantitative manner. Content analysis was performed on the objectives described in the articles. In total, 79 articles were included and most of them had a cross-sectional design and were linked to institutions in the South and Southeast regions. Furthermore, most studies were from the last 10 years and in English. The journal Fisioterapia e Pesquisa was the Brazilian journal that most published studies of the sample. The analyzed objectives were distributed into six word classes, with two large groups: psychometric validity (19.1%) and evaluative studies (80.9%). The latter considered the various child populations analyzed. We presented studies that used the AIMS to evaluate the motor development of Brazilian children, reinforcing the importance of this instrument in the national context and also encouraging its use.

RESUMEN La Escala Motora Infantil de Alberta (AIMS) es un instrumento que evalúa el desarrollo motor grueso de los recién nacidos de entre 0 y 18 meses de edad. Este estudio pretendió hacer una síntesis de estudios brasileños que utilizaron la AIMS, así como identificar sus objetivos, con el fin de proporcionar una tabla de los principales usos de la escala a los profesionales interesados en el desarrollo motor infantil. Se trata de un estudio bibliométrico, en el que se realizaron búsquedas en las bases de datos SciELO, PubMed, Scopus y Web of Science. Los descriptores utilizados fueron "escala motora infantil de Alberta" y "Brasil", con sus equivalentes en inglés, unidos por el término booleano "AND". El criterio de inclusión fue la aplicación de la AIMS en Brasil, con niños de entre 0 y 18 meses. Las variables base de datos, revista, año de publicación, idioma, región de la institución vinculada a los autores y tipo de estudio se analizaron de manera cuantitativa y descriptiva. Se realizó un análisis de contenido de los objetivos descritos en los estudios, y se incluyeron 79 estudios, de los cuales la mayoría presentó un diseño transversal y estaba vinculado a instituciones de las regiones Sur y Sudeste de Brasil. La mayoría de las publicaciones son de los últimos 10 años, en inglés, y la revista Fisioterapia e Pesquisa fue la revista nacional que más publicó estudios. Los objetivos analizados se dividieron en seis clases de palabras, que contienen dos grupos principales: validez psicométrica (19,1%) y estudios evaluativos (80,9%). Este último tuvo en cuenta las diversas poblaciones infantiles analizadas. Este estudio presentó las investigaciones que evaluaron la AIMS respecto al desarrollo motor de los niños brasileños. Esto destaca la importancia del citado instrumento en el contexto nacional, además estimula su uso.

RESUMO A Alberta infant motor scale (AIMS) é um instrumento de avaliação do desenvolvimento motor grosso dos recém-nascidos entre 0 e 18 meses de idade. Este estudo buscou sumarizar as pesquisas brasileiras que utilizaram a AIMS e identificar seus objetivos, a fim de fornecer um quadro das principais utilizações da escala aos profissionais interessados no desenvolvimento motor infantil. Trata-se de um estudo bibliométrico realizado por meio de buscas nas bases de dados SciELO, PubMed, Scopus, e Web of Science. Os descritores foram "escala motora infantil de Alberta" e "Brasil", com seus equivalentes em inglês, unidos pelo termo booleano "AND". O critério de inclusão foi a utilização da AIMS no Brasil, com crianças de 0 a 18 meses. As variáveis base de dados, revista, ano de publicação, idioma, região da instituição vinculada aos autores e tipo de estudo foram analisadas de forma quantitativa descritiva. Foi realizada análise de conteúdo dos objetivos descritos nas pesquisas, e foram incluídos 79 estudos, a maioria dos quais apresentou delineamento transversal e estava vinculada a instituições das regiões Sul e Sudeste. Boa parte das publicações era dos últimos 10 anos, em inglês, e a revista Fisioterapia e Pesquisa foi o periódico nacional que mais publicou estudos referentes à amostra. Os objetivos analisados foram distribuídos em seis classes de palavras, contidas em dois grandes grupos: validades psicométricas (19,1%) e estudos avaliativos (80,9%). Este último considerou as várias populações infantis analisadas. O estudo apresentou as pesquisas que utilizaram a AIMS para avaliar o desenvolvimento motor de crianças brasileiras. Isso reforça a importância deste instrumento no contexto nacional, além de estimular sua utilização.

Annexin A1-FPR2/ALX Signaling Axis Regulates Acute Inflammation during Chikungunya Virus Infection.

Chikungunya (CHIKV) is an arthritogenic alphavirus that causes a self-limiting disease usually accompanied by joint pain and/or polyarthralgia with disabling characteristics. Immune responses developed during the acute phase of CHIKV infection determine the rate of disease progression and resolution. Annexin A1 (AnxA1) is involved in both initiating inflammation and preventing over-response, being essential for a balanced end of inflammation. In this study, we investigated the role of the AnxA1-FPR2/ALX pathway during CHIKV infection. Genetic deletion of AnxA1 or its receptor enhanced inflammatory responses driven by CHIKV. These knockout mice showed increased neutrophil accumulation and augmented tissue damage at the site of infection compared with control mice. Conversely, treatment of wild-type animals with the AnxA1 mimetic peptide (Ac2-26) reduced neutrophil accumulation, decreased local concentration of inflammatory mediators and diminished mechanical hypernociception and paw edema induced by CHIKV-infection. Alterations in viral load were mild both in genetic deletion or with treatment. Combined, our data suggest that the AnxA1-FPR2/ALX pathway is a potential therapeutic strategy to control CHIKV-induced acute inflammation and polyarthralgia.

Art and science: impact of semioccluded vocal tract exercises and choral singing on quality of life in subjects with congenital GH deficiency

ABSTRACT Objectives: Currently, not much is known about the interactions between voice and growth hormone (GH). We have described large kindred with isolated GH deficiency (IGHD) due to a GHRH receptor mutation, resulting in severe short stature and high-pitched voice. These IGHD individuals have little interest in GH treatment, as they consider themselves "short long-lived people", rather than patients. Interestingly, they report normal general quality of life, but they rate their Voice-Related Quality of Life (V-RQOL) as low. Here, we assessed the social and auditory-perceptual impacts of artistic-intervention voice therapy with semioccluded vocal tract exercises (SOVTE) and choral singing, on their voices. Material and methods: Seventeen GH-naïve adult IGHD individuals were enrolled in a single-arm interventional pre-post study with 13 weekly sessions of choir singing over 90 days. Outcome measures were V-RQOL scores, self-assessment of voice, and auditory-perceptual analysis (GRBAS scale, G: grade of the severity of dysphonia; R: roughness; B: breathiness; A: asthenia; and S: strain). Results: Marked improvements in total (p = 0.0001), physical (p = 0.0002), and socioemotional (p = 0.0001) V-RQOL scores and in self-assessment of voice (p = 0.004) were found. The general grades of vocal deviation (p = 0.0001), roughness (p = 0.0001), breathiness (p = 0.0001) and strain (p = 0.0001) exhibited accentuated reductions. Conclusions: Voice therapy with semioccluded vocal tract exercises and choral training improved social impact and perceptual voice assessments in IGHD subjects and markedly improved their voice-related quality of life. This is particularly important in a setting where GH replacement therapy is not widely accepted.

Art and science: impact of semioccluded vocal tract exercises and choral singing on quality of life in subjects with congenital GH deficiency.

Objective: Currently, not much is known about the interactions between voice and growth hormone (GH). We have described large kindred with isolated GH deficiency (IGHD) due to a GHRH receptor mutation, resulting in severe short stature and high-pitched voice. These IGHD individuals have little interest in GH treatment, as they consider themselves "short long-lived people", rather than patients. Interestingly, they report normal general quality of life, but they rate their Voice-Related Quality of Life (V-RQOL) as low. Here, we assessed the social and auditory-perceptual impacts of artistic-intervention voice therapy with semioccluded vocal tract exercises (SOVTE) and choral singing, on their voices. Methods: Seventeen GH-naïve adult IGHD individuals were enrolled in a single-arm interventional pre-post study with 13 weekly sessions of choir singing over 90 days. Outcome measures were V-RQOL scores, self-assessment of voice, and auditory-perceptual analysis (GRBAS scale, G: grade of the severity of dysphonia; R: roughness; B: breathiness; A: asthenia; and S: strain). Results: Marked improvements in total (p = 0.0001), physical (p = 0.0002), and socioemotional (p = 0.0001) V-RQOL scores and in self-assessment of voice (p = 0.004) were found. The general grades of vocal deviation (p = 0.0001), roughness (p = 0.0001), breathiness (p = 0.0001) and strain (p = 0.0001) exhibited accentuated reductions. Conclusion: Voice therapy with semioccluded vocal tract exercises and choral training improved social impact and perceptual voice assessments in IGHD subjects and markedly improved their voice-related quality of life. This is particularly important in a setting where GH replacement therapy is not widely accepted.

In-depth characterization of a novel live-attenuated Mayaro virus vaccine candidate using an immunocompetent mouse model of Mayaro disease.

Mayaro virus (MAYV) is endemic in South American countries where it is responsible for sporadic outbreaks of acute febrile illness. The hallmark of MAYV infection is a highly debilitating and chronic arthralgia. Although MAYV emergence is a potential threat, there are no specific therapies or licensed vaccine. In this study, we developed a murine model of MAYV infection that emulates many of the most relevant clinical features of the infection in humans and tested a live-attenuated MAYV vaccine candidate (MAYV/IRES). Intraplantar inoculation of a WT strain of MAYV into immunocompetent mice induced persistent hypernociception, transient viral replication in target organs, systemic production of inflammatory cytokines, chemokines and specific humoral IgM and IgG responses. Inoculation of MAYV/IRES in BALB/c mice induced strong specific cellular and humoral responses. Moreover, MAYV/IRES vaccination of immunocompetent and interferon receptor-defective mice resulted in protection from disease induced by the virulent wt MAYV strain. Thus, this study describes a novel model of MAYV infection in immunocompetent mice and highlights the potential role of a live-attenuated MAYV vaccine candidate in host's protection from disease induced by a virulent MAYV strain.

Pharmacologic potential of new nitro-compounds as antimicrobial agents against nosocomial pathogens: design, synthesis, and in vitro effectiveness.

Nosocomial infections are an important cause of morbi-mortality worldwide. The increase in the rate of resistance to conventional drugs in these microorganisms has stimulated the search for new therapeutic options. The nitro moiety (NO2) is an important pharmacophore of molecules with high anti-infective activity. We aimed to synthesize new nitro-derivates and to evaluate their antibacterial and anti-Candida potential in vitro. Five compounds [3-nitro-2-phenylchroman-4-ol (3); 3-nitro-2-phenyl-2H-chromene (4a); 3-nitro-2-(4-chlorophenyl)-2H-chromene (4b); 3-nitro-2-(4-fluorophenyl)-2H-chromene (4c), and 3-Nitro-2-(2,3-dichlorophenyl)-2H-chromene (4d)] were efficiently synthesized by Michael-aldol reaction of 2-hydroxybenzaldehyde with nitrostyrene, resulting in one ß-nitro-alcohol (3) and four nitro-olefins (4a-4d). The antibacterial and anti-Candida potentials were evaluated by assaying minimal inhibitory concentration (MIC), minimum fungicidal concentration (MFC), and minimum bactericidal concentration (MBC). Mono-halogenated nitro-compounds (4b and 4c) showed anti-staphylococcal activity with MIC values of 15.6-62.5 µg/mL and MBC of 62.5 µg/mL. However, the activity against Gram-negative strains was showed to be considerably lower and our data suggests that this effect was associated with the outer membrane. Furthermore, nitro-compounds 4c and 4d presented activity against Candida spp. with MIC values ranging from 7.8-31.25 µg/mL and MFC of 15.6-500 µg/mL. In addition, these compounds were able to induce damage in fungal cells increasing the release of intracellular material, which was associated with actions on the cell wall independent of quantitative changes in chitin and ß-glucan. Together, these findings show that nitro-compounds can be exploited as anti-staphylococcal and anti-Candida prototypes.

In-depth characterization of congenital Zika syndrome in immunocompetent mice: Antibody-dependent enhancement and an antiviral peptide therapy.

BACKGROUND: Zika virus (ZIKV) infection during pregnancy may cause major congenital defects, including microcephaly, ocular, articular and muscle abnormalities, which are collectively defined as Congenital Zika Syndrome. Here, we performed an in-depth characterization of the effects of congenital ZIKV infection (CZI) in immunocompetent mice. METHODS: Pregnant dams were inoculated with ZIKV on embryonic day 5.5 in the presence or absence of a sub-neutralizing dose of a pan-flavivirus monoclonal antibody (4G2) to evaluate the potential role of antibody-dependent enhancement phenomenon (ADE) during short and long outcomes of CZI. FINDINGS: ZIKV infection induced maternal immune activation (MIA), which was associated with occurrence of foetal abnormalities and death. Therapeutic administration of AH-D antiviral peptide during the early stages of pregnancy prevented ZIKV replication and death of offspring. In the post-natal period, CZI was associated with a decrease in whole brain volume, ophthalmologic abnormalities, changes in testicular morphology, and disruption in bone microarchitecture. Some alterations were enhanced in the presence of 4G2 antibody. INTERPRETATION: Our results reveal that early maternal ZIKV infection causes several birth defects in immunocompetent mice, which can be potentiated by ADE phenomenon and are associated with MIA. Additionally, antiviral treatment with AH-D peptide may be beneficial during early maternal ZIKV infection. FUND: This work was supported by the Brazilian National Science Council (CNPq, Brazil), Minas Gerais Foundation for Science (FAPEMIG), Funding Authority for Studies and Projects (FINEP), Coordination of Superior Level Staff Improvement (CAPES), National Research Foundation of Singapore and Centre for Precision Biology at Nanyang Technological University.

Synthesis and Evaluation of the in vitro Antimicrobial Activity of Triazoles, Morpholines and Thiosemicarbazones.

BACKGROUND: Microbial infections is a global public health problem. The aim of this work was to synthesize and evaluate the antimicrobial activity of novel triazoles, morpholines and thiosemicarbazones. METHODS: Compounds were synthesized using 2,4-Dihydroxyacetophenone and 4-hydroxybenzaldehyde as starting materials. The antimicrobial activity of these compounds against bacteria and yeast was evaluated by the broth microdilution method. RESULTS: The proposed route for synthesis gave high to moderate yields, moreover these compounds were successfully characterized by 1H NMR, 13C NMR and LC-MS. Antimicrobial testing indicated that the thiosemicarbazone and morphine derivatives had the best antimicrobial activity against the microorganisms tested with minimum inhibitory concentrations (MIC) between 0.29 and 5.30 µM. Thiosemicarbazone derivative (12) was able to inhibit the growth of C. tropicalis, with minimum fungicidal concentration (MFC) of 0.55 µM. In addition, this compound was active against E. coli, S. aureus and S. epidermidis, with MIC values ranging from 0.29 to 1.11 µM. Moreover, the morpholine derivative (15) had an MIC value of 0.83 µM against C. albicans and E. coli. CONCLUSION: We have efficiently synthesized a series of eleven novel triazoles, thiosemicarbazones and morpholine derivatives using 2,4-Dihydroxyacetophenone and 4-hydroxybenzaldehyde as starting materials. Thiosemicarbazone derivative (12) showed promising antifungal and antibacterial activity and these findings suggest that this compound can be used as scaffolds to design new antimicrobial drugs.

Fatty acid profile and carcass characteristics in castrated and uncastrated hair lambs.

The aim of this study was to investigate the effects of castration on carcass characteristics and fatty acid profile of visceral fat and meat from lambs. Eighteen six-month-old Santa Inês male lambs (18.9 ± 2.4 kg of body weight (BW)) were used. Animals were assigned to two treatments according to their sexual condition: uncastrated (U) or castrated (C). During a 98-day experimental period, animals were kept on an Andropogon gayanus grass pasture area of 1 ha and supplemented with 200 g/animal/day of concentrate mixture. Water and mineral salt were available ad libitum. The lambs were weighed fortnightly, and at the last day of the trial, they were slaughtered for evaluation of carcass characteristics and fatty acids profile of perirenal fat and longissimus lumborum muscle samples. Castrated lambs showed higher BW than U during most part of the experiment (p < 0.05). Fat deposition was higher in C lambs as evidenced by their increased carcass fat cover. Meat from U lambs showed lower content of C16:0 and higher polyunsaturated fatty acids (PUFA) (p < 0.05) than that from C (U, 14.3 and C, 10.5%). Conjugated linoleic acid (CLA) content was not affected by castration (p > 0.05) (U, 0.74 and C, 0.76%). The cis-9, cis-12 C18:2n-6 (U, 10.6 and C, 6.86%) fatty acid and the PUFA:SFA (saturated fatty acids) ratio (U, 0.36 and C, 0.25) were higher in the muscle of U lambs (p < 0.05), indicating that the meat from U animals may provide more benefits to human health than that of C.