Carboxymethylcellulose biofunctionalized ternary quantum dots for subcellular-targeted brain cancer nanotheranostics.

Among the most lethal forms of cancer, malignant brain tumors persist as one of the greatest challenges faced by oncologists, where nanotechnology-driven theranostics can play a critical role in developing novel polymer-based supramolecular nanoarchitectures with multifunctional and multi-modal characteristics to fight cancer. However, it is virtually a consensus that, besides the complexity of active delivering anticancer drugs by the nanocarriers to the tumor site, the current evaluation methods primarily relying on in vitro assays and in vivo animal models have been accounted for the low translational effectiveness to clinical applications. In this view, the chick chorioallantoic membrane (CAM) assay has been increasingly recognized as one of the best preclinical models to study the effects of anticancer drugs on the tumor microenvironment (TME). Thus, in this study, we designed, characterized, and developed novel hybrid nanostructures encompassing chemically functionalized carboxymethylcellulose (CMC) with mitochondria-targeting pro-apoptotic peptide (KLA) and cell-penetrating moiety (cysteine, CYS) with fluorescent inorganic semiconductor (Ag-In-S, AIS) for simultaneously bioimaging and inducing glioblastoma cancer cell (U-87 MG, GBM) death. The results demonstrated that the CMC-peptide macromolecules produced supramolecular vesicle-like nanostructures with aqueous colloidal stability suitable as nanocarriers for passive and active targeting of cancer tumors. The optical properties and physicochemical features of the nanoconjugates confirmed their suitability as photoluminescent nanoprobes for cell bioimaging and intracellular tracking. Moreover, the results in vitro demonstrated a notable killing activity towards GBM cells of cysteine-bearing CMC conjugates coupled with pro-apoptotic KLA peptides. More importantly, compared to doxorubicin (DOX), a model anticancer drug in chemotherapy that is highly toxic, these innovative nanohybrids nanoconjugates displayed higher lethality against U-87 MG cancer cells. In vivo CAM assays validated these findings where the nanohybrids demonstrated a significant reduction of GBM tumor progression (41% area) and evidenced an antiangiogenic activity. These results pave the way for developing polymer-based hybrid nanoarchitectonics applied as targeted multifunctional theranostics for simultaneous imaging and therapy against glioblastoma while possibly reducing the systemic toxicity and side-effects of conventional anticancer chemotherapeutic agents.

Active Circulation of Madariaga Virus, a Member of the Eastern Equine Encephalitis Virus Complex, in Northeast Brazil.

Madariaga virus (MADV) is a member of the eastern equine encephalitis virus (EEEV) complex that circulates in Central and South America. It is a zoonotic, mosquito-borne pathogen, belonging to the family Togaviridae. Disturbances in the natural transmission cycle of this virus result in outbreaks in equines and humans, leading to high case fatality in the former and acute febrile illness or neurological disease in the latter. Although a considerable amount of knowledge exists on the eco-epidemiology of North American EEEV strains, little is known about MADV. In Brazil, the most recent isolations of MADV occurred in 2009 in the States of Paraíba and Ceará, northeast Brazil. Because of that, health authorities have recommended vaccination of animals in these regions. However, in 2019 an equine encephalitis outbreak was reported in a municipality in Ceará. Here, we present the isolation of MADV from two horses that died in this outbreak. The full-length genome of these viruses was sequenced, and phylogenetic analyses performed. Pathological findings from postmortem examination are also discussed. We conclude that MADV is actively circulating in northeast Brazil despite vaccination programs, and call attention to this arbovirus that likely represents an emerging pathogen in Latin America.

Equine coital exanthema caused by equid alphaherpesvirus 3: a report of an outbreak in northeastern Brazil

ABSTRACT: Equine coital exanthema is a venereal infectious disease poorly reported in horses in Brazil and was never described in the northeastern region of the country. This work aims to describe the clinical and pathological aspects of an outbreak of equine coital exanthema caused by equid alphaherpesvirus 3, occurred in a herd of horses at the semiarid region of the State of Rio Grande do Norte. Main clinical signs consisted of anorexia, hiporexia, fibrinous or purulent secretion in the penis mucosa and vagina. Two mares presented mild to minimal lesions that consisted of scars in the mucosa of the vagina and in the perivulvar region. In a stallion the disease consisted of severe, multifocal, umbilicated-exanthematous ulcers of approximately 1cm in diameter on the penis mucosa. Other areas where ulcers and crusts were focally observed included the skin of the scrotum and on the lips and mucocutaneous junctions of the oral cavity. Histologically, the main lesion consisted of multifocal severe ulcerative and fibrinous necrotizing balanoposthitis and mild multifocal necrotizing, lymphocytic dermatitis in the lips and scrotum. The equide alphaherpesvirus 3 DNA was amplified in blood samples and penis mucosa using the PCR technique. This is the first report of molecular diagnosis of equine coital exanthema affecting horses in northeastern Brazil. Further studies should be carried out in order to investigate the epidemiology and the importance of this herpetic disease in the country.

RESUMO: O exantema coital equino é uma doença infecciosa venérea pouco relatada em equinos no Brasil e nunca descrita na região Nordeste do país. Este trabalho tem como objetivo descrever os aspectos clínicos e patológicos de um surto de exantema coital equino causado pelo alphaherpesvirus equídeo 3, que ocorreu em um haras na região semiárida do Estado do Rio Grande do Norte. Os principais sinais clínicos consistiram em anorexia, hiporexia, secreção fibrinosa ou purulenta na mucosa do pênis e vagina. Duas éguas apresentavam lesões discretas que consistiam em cicatrizes na mucosa da vagina e na região perivulvar. Em um garanhão, a doença consistia em úlceras umbilicadas-exantematosas severas, multifocais, de aproximadamente 1 cm de diâmetro na mucosa do pênis. Outras áreas onde úlceras e crostas foram observadas focalmente incluíram a pele do escroto, lábios e junções mucocutâneas da cavidade oral. Histologicamente, as principais lesões consistiam em balanopostite multifocal ulcerativa e necrosante fibrinosa grave e dermatite linfocítica necrosante multifocal leve nos lábios e escroto. O DNA do alphaherpesvirus equídeo tipo 3 foi amplificado em amostras de sangue e mucosa do pênis pela técnica de PCR. Este é o primeiro relato de diagnóstico molecular de exantema coital equino afetando cavalos no nordeste do Brasil. Novos estudos devem ser realizados a fim de investigar a epidemiologia e a importância dessa doença herpética no país.

Equine coital exanthema caused by equid alphaherpesvirus 3: a report of an outbreak in northeastern Brazil / Exantema coital equino causado pelo alphaherpesvirus equídeo tipo 3: relato de um surto no nordeste do Brasil

Equine coital exanthema is a venereal infectious disease poorly reported in horses in Brazil and was never described in the northeastern region of the country. This work aims to describe the clinical and pathological aspects of an outbreak of equine coital exanthema caused by equid alphaherpesvirus 3, occurred in a herd of horses at the semiarid region of the State of Rio Grande do Norte. Main clinical signs consisted of anorexia, hiporexia, fibrinous or purulent secretion in the penis mucosa and vagina. Two mares presented mild to minimal lesions that consisted of scars in the mucosa of the vagina and in the perivulvar region. In a stallion the disease consisted of severe, multifocal, umbilicated-exanthematous ulcers of approximately 1cm in diameter on the penis mucosa. Other areas where ulcers and crusts were focally observed included the skin of the scrotum and on the lips and mucocutaneous junctions of the oral cavity. Histologically, the main lesion consisted of multifocal severe ulcerative and fibrinous necrotizing balanoposthitis and mild multifocal necrotizing, lymphocytic dermatitis in the lips and scrotum. The equide alphaherpesvirus 3 DNA was amplified in blood samples and penis mucosa using the PCR technique. This is the first report of molecular diagnosis of equine coital exanthema affecting horses in northeastern Brazil. Further studies should be carried out in order to investigate the epidemiology and the importance of this herpetic disease in the country.(AU)

O exantema coital equino é uma doença infecciosa venérea pouco relatada em equinos no Brasil e nunca descrita na região Nordeste do país. Este trabalho tem como objetivo descrever os aspectos clínicos e patológicos de um surto de exantema coital equino causado pelo alphaherpesvirus equídeo 3, que ocorreu em um haras na região semiárida do Estado do Rio Grande do Norte. Os principais sinais clínicos consistiram em anorexia, hiporexia, secreção fibrinosa ou purulenta na mucosa do pênis e vagina. Duas éguas apresentavam lesões discretas que consistiam em cicatrizes na mucosa da vagina e na região perivulvar. Em um garanhão, a doença consistia em úlceras umbilicadas-exantematosas severas, multifocais, de aproximadamente 1 cm de diâmetro na mucosa do pênis. Outras áreas onde úlceras e crostas foram observadas focalmente incluíram a pele do escroto, lábios e junções mucocutâneas da cavidade oral. Histologicamente, as principais lesões consistiam em balanopostite multifocal ulcerativa e necrosante fibrinosa grave e dermatite linfocítica necrosante multifocal leve nos lábios e escroto. O DNA do alphaherpesvirus equídeo tipo 3 foi amplificado em amostras de sangue e mucosa do pênis pela técnica de PCR. Este é o primeiro relato de diagnóstico molecular de exantema coital equino afetando cavalos no nordeste do Brasil. Novos estudos devem ser realizados a fim de investigar a epidemiologia e a importância dessa doença herpética no país.(AU)

Sudden cardiac death: the finish line as a beginning: a true endurance race in a case report.

BACKGROUND: The benefits of exercise are well documented. Intensive exercise for more than 4 h per week is associated with cardiovascular remodelling, including increases in ventricular dimensions, wall thickness, and left ventricular mass. These changes are influenced by sex, ethnicity, and type and duration of exercise. In highly trained endurance athletes, exercise is often associated with electrocardiographic changes at rest. CASE SUMMARY: A well-trained endurance athlete underwent cardiac investigation after his 33-year-old brother died while jogging. A resting 12-lead electrocardiogram showed significant first degree atrioventricular block (AVB), and longer monitoring revealed advanced AVB. This led to further testing and exercise restrictions. DISCUSSION: Although most electrocardiographic changes are related to athletic performance, the distinction between normal variants, often exaggerated by the physiology of the conditioned athlete, and myocardial or electrical disease may be challenging. Athletes should undergo comprehensive cardiovascular evaluation, with management based on these results.

Evaluation of antibacterial, antifungal and modulatory activity of methanol and ethanol extracts of Padina sanctae-crucis.

BACKGROUND: Multi-resistantmicroorganisms such as Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Candida tropicalis e Candida krusei are the main causes of microbial infections. Padina sanctae-crucis is a seaweed often used to check the contamination of ecosystems by materials such as heavy metals, but studies of the antimicrobial activity of the same seaweed were not found. METHODS: The tests for the minimum inhibitory concentration and modulation of microbial resistance, with the use of ethanolic and methanolic extracts of Padina Sanctae-cruces combined with drugs of the class of aminoglycosides and antifungal were used to evaluate the activity against the cited microorganisms. RESULTS: Was observed a modulation of antibiotic activity between the natural products and the E. coli and S. aureus strains, indicating a synergism and antagonism respectively. CONCLUSIONS: The results showed a moderate modulatory effect against some microorganisms studied.