Identification of potent inhibitors of arenavirus and SARS-CoV-2 exoribonucleases by fluorescence polarization assay.

Viral exoribonucleases are uncommon in the world of RNA viruses. To date, they have only been identified in the Arenaviridae and the Coronaviridae families. The exoribonucleases of these viruses play a crucial role in the pathogenicity and interplay with host innate immune response. Moreover, coronaviruses exoribonuclease is also involved in a proofreading mechanism ensuring the genetic stability of the viral genome. Because of their key roles in virus life cycle, they constitute attractive target for drug design. Here we developed a sensitive, robust and reliable fluorescence polarization assay to measure the exoribonuclease activity and its inhibition in vitro. The effectiveness of the method was validated on three different viral exoribonucleases, including SARS-CoV-2, Lymphocytic Choriomeningitis and Machupo viruses. We performed a screening of a focused library consisting of 113 metal chelators. Hit compounds were recovered with an IC50 at micromolar level. We confirmed 3 hits in SARS-CoV-2 infected Vero-E6 cells.

Influence of Nisin-Biogel at Subinhibitory Concentrations on Virulence Expression in Staphylococcus aureus Isolates from Diabetic Foot Infections.

A new approach to diabetic foot infections (DFIs) has been investigated, using a nisin-biogel combining the antimicrobial peptide (AMP) nisin with the natural polysaccharide guar-gum. Since in in vivo conditions bacteria may be exposed to decreased antimicrobial concentrations, known as subinhibitory concentrations (sub-MICs), effects of nisin-biogel sub-MIC values corresponding to 1/2, 1/4 and 1/8 of nisin's minimum inhibitory concentration (MIC) on virulence expression by six Staphylococcus aureus DFI isolates was evaluated by determining bacteria growth rate; expression of genes encoding for staphylococcal protein A (spA), coagulase (coa), clumping factor A (clfA), autolysin (atl), intracellular adhesin A (icaA), intracellular adhesin D (icaD), and the accessory gene regulator I (agrI); biofilm formation; Coa production; and SpA release. Nisin-biogel sub-MICs decreased bacterial growth in a strain- and dose-dependent manner, decreased agrI, atl and clfA expression, and increased spA, coa, icaA and icaD expression. Biofilm formation increased in the presence of nisin-biogel at 1/4 and 1/8 MIC, whereas 1/2 MIC had no effect. Finally, nisin-biogel at sub-MICs did not affect coagulase production, but decreased SpA production in a dose-dependent manner. Results highlight the importance of optimizing nisin-biogel doses before proceeding to in vivo trials, to reduce the risk of virulence factor's up-regulation due to the presence of inappropriate antimicrobial concentrations.

Identifying Training, Diagnostic and Therapeutic Needs From a Comparison in the Distribution of Vestibular Disorders in Primary Care and in a Neurotology Unit.

Introduction: Several epidemiological studies in Neurotology have been previously carried out in the general population. This approach is useful for learning about the most common disorders in clinical population, but it may fail when one is trying to help professionals to guide their training, to optimize their resources and to decide on the highest-priority research objectives. Objective: To identify which of the neurotological diseases are most common in two different populations, those who attended a consultation in the Neurotology Unit of a tertiary level hospital and those who did so in Primary Care in order to infer which of them requires more attention in each context and their specific needs. Methods: All the diagnoses made in Hospital Care between October 15, 2017 and October 14, 2018 were reviewed. These diagnoses were coded and classified into syndromes and diseases. Later, the proportions of each category were compared with the proportions of the neurotological diagnoses made in five Primary Care centers over the same period of time. Results: BPPV is the most common cause of vestibular symptoms in both contexts. Vestibular migraine, ischemic vestibular symptoms, orthostatic hypotension and side effects of drugs are common in Primary Care, whereas Ménière's disease and undifferentiated episodic vestibular syndrome are common in specialized centers. Conclusion: The proportion of diagnoses in neurotologic patients is different in the general population and in the specialized center population, and therefore they have different needs. Primary Care professionals would benefit from training on maneuvers for repositioning otoliths, the treatment of headache, the identification of cardiovascular risk factors, the orthostatic hypotension and the side effects of the most commonly used drugs. The professionals who work in specialized centers need strategies for dealing with cases of BPPV associated to other vestibular diseases and refractory cases and their research should focus on the development of new diagnostic tools for the diagnosis of undifferentiated episodic vestibular syndrome and new therapeutic options for Ménière's disease.

Changes in past global solar radiation based on climate models and remote sensing in the state of Rio de Janeiro, Brazil / Mudanças ocorridas da radiação solar global passada baseado em modelos climáticos e sensoriamento remoto no estado do Rio de Janeiro, Brazil

The objective of this study was to perform a temporal and spatial analysis of the changes in the past global solar radiation based on climate models and remote sensing data in the State of Rio de Janeiro, Brazil for the baseline period (1961-1990). Data from two climate models - the Canadian Centre for Climate Modelling and Analysis and Geophysical Fluid Dynamic Laboratory, were used for the A1B intermediate scenario, data from Conventional Weather Stations and orbital sensor Moderate Resolution Imaging Spectroradiometer (MODIS) MODIS Land Cover Type (MCD12Q1). The results of the Spatial Dependence Degree indicate that the best model to represent the global solar radiation is CCCMA-Exponential dry 70.01 and rainy 0.21 respectively. It was possible to verify that in places where the areas are occupied by forests there was reduction of global solar radiation for both dry and rainy periods of approximately 13 MJ m-2d-1. These results indicate that these forest areas can function as islands of freshness, while maintaining the thermal comfort balanced. It was concluded that the dry period had the highest values of solar radiation compared to the rainy (57%), which can be justified by the occurrence of fires in Rio de Janeiro.

O objetivo deste estudo foi realizar uma análise temporal e espacial das mudanças ocorridas da radiação solar global passada baseado em modelo climáticos e sensoriamento remoto no Estado do Rio de Janeiro, Brasil para o período baseline (1961-1990). Utilizaram-se dados de dois modelos climáticos o Canadian Centre for Climate Modelling and Analysis) e Geophysical Fluid Dynamic Laboratory para o cenário intermediário A1B, dados de Estações Meteorológicas Convencionais e do sensor orbital Moderate Resolution Imaging Spectroradiometer (MODIS) MODIS Land Cover Type (MCD12Q1). Os resultados do Grau de Dependência Espacial indicam que o melhor modelo que representa a radiação solar global é o CCCMA-Exponencial seco 70.01 e chuvoso de 0.21 respectivamente. Foi possível verificar que em locais onde as áreas são ocupadas por florestas houve redução da radiação solar global para os dois períodos seco e chuvoso de aproximadamente 13 MJ.m-2.dia-1. Estes resultados indicam que estas áreas de florestas podem funcionar como ilhas de frescor, mantendo o conforto térmico equilibrado. Conclui-se que o período seco apresentou maiores valores de radiação solar em comparação ao chuvoso (57%), que pode ser justificado pela ocorrência de queimadas no Rio de Janeiro.

Análise clínica e ultrassonográfica dos ombros de pacientes lesados medulares em programa de reabilitação / Shoulders of patients with spinal cord injuriessubmited to rehabilitation program - a clinical and ultrasound-based assessment

O aumento da incidência de traumas de alta energia esta relacionado com o crescimento da prevalência de lesões raquimedulares ocasionando seqüelas motoras nos membros. O programa de reabilitação proporciona perspectiva de melhora da qualidade de vida, colaborando para a reintegração social desses indivíduos. As síndromes dolorosas dos ombros são freqüentes nos pacientes lesados medulares, independentemente do programa de reabilitação adotado. No presente estudo, avaliou-se por meio da ultrassonografia, 32 ombros de 16 pacientes com lesão medular com localização anatômica entre C4 e T12, em reabilitação no DOT/HC-UNICAMP, constatando-se alterações nos tendões dos músculos do manguito rotador em 46,88 por cento e nas tuberosidades umerais em 12,50 por cento dos pacientes estudados. As alterações foram mais prevalentes entre os tetraplégicos. A execução de medidas analgésicas, fortalecimento dos músculos do manguito rotador quando possível e alterações posturais podem significar diminuição na ocorrência das síndromes dolorosas dos ombros, melhorando o aproveitamento do programa de reabilitação e com ganhos na qualidade de vida.

The increasing incidence of high energy traumas is associated to a growing prevalence of spinal cord injuries causing motor sequels on limbs. Rehabilitation programs provide an opportunity for improvement of quality of life, helping on integrating those individuals back into social activities. Shoulder pain is more frequent in individuals with spinal cord injury, regardless of the rehabilitation program adopted. In the current study, 32 shoulders of 16 patients with spinal cord injury levels between C4 and T12 submitted to a rehabilitation program at DOT/UNICAMP were evaluated by using ultrasound. Changes on rotator cuff tendons were detected in 56.25 percent, and 12.50 percent of the patients presented changes in humeral tuberosities. These changes were more prevalent in quadriplegic patients. Analgesic therapies, rotator cuff muscles' strengthening whenever possible, and postural rehabilitation may provide shoulder pain reduction, enhancing the advantages of rehabilitation programs and providing a better quality of life.