Unbalanced networks and disturbed kinetics of serum soluble mediators associated with distinct disease outcomes in severe COVID-19 patients.

The present study applied distinct models of descriptive analysis to explore the integrative networks and the kinetic timeline of serum soluble mediators to select a set of systemic biomarkers applicable for the clinical management of COVID-19 patients. For this purpose, a total of 246 participants (82 COVID-19 and 164 healthy controls - HC) were enrolled in a prospective observational study. Serum soluble mediators were quantified by high-throughput microbeads array on hospital admission (D0) and at consecutive timepoints (D1-6 and D7-20). The results reinforce that the COVID-19 group exhibited a massive storm of serum soluble mediators. While increased levels of CCL3 and G-CSF were associated with the favorable prognosis of non-mechanical ventilation (nMV) or discharge, high levels of CXCL10 and IL-6 were observed in patients progressing to mechanical ventilation (MV) or death. At the time of admission, COVID-19 patients presented a complex and robust serum soluble mediator network, with a higher number of strong correlations involving IFN-γ, IL-1Ra and IL-9 observed in patients progressing to MV or death. Multivariate regression analysis demonstrates the ability of serum soluble mediators to cluster COVID-19 from HC. Ascendant fold change signatures and the kinetic timeline analysis further confirmed that the pairs "CCL3 and G-CSF" and "CXCL10 and IL-6" were associated with favorable or poor prognosis, respectively. A selected set of systemic mediators (IL-6, IFN-γ, IL-1Ra, IL-13, PDGF and IL-7) were identified as putative laboratory markers, applicable as complementary records for the clinical management of patients with severe COVID-19.

Thromboelastometry demonstrates endogenous coagulation activation in nonsevere and severe COVID-19 patients and has applicability as a decision algorithm for intervention.

In patients with severe forms of COVID-19, thromboelastometry has been reported to display a hypercoagulant pattern. However, an algorithm to differentiate severe COVID-19 patients from nonsevere patients and healthy controls based on thromboelastometry parameters has not been developed. Forty-one patients over 18 years of age with positive qRT-PCR for SARS-CoV-2 were classified according to the severity of the disease: nonsevere (NS, n = 20) or severe (S, n = 21). A healthy control (HC, n = 9) group was also examined. Blood samples from all participants were tested by extrinsic (EXTEM), intrinsic (INTEM), non-activated (NATEM) and functional assessment of fibrinogen (FIBTEM) assays of thromboelastometry. The thrombodynamic potential index (TPI) was also calculated. Severe COVID-19 patients exhibited a thromboelastometry profile with clear hypercoagulability, which was significantly different from the NS and HC groups. Nonsevere COVID-19 cases showed a trend to thrombotic pole. The NATEM test suggested that nonsevere and severe COVID-19 patients presented endogenous coagulation activation (reduced clotting time and clot formation time). TPI data were significantly different between the NS and S groups. The maximum clot firmness profile obtained by FIBTEM showed moderate/elevated accuracy to differentiate severe patients from NS and HC. A decision tree algorithm based on the FIBTEM-MCF profile was proposed to differentiate S from HC and NS. Thromboelastometric parameters are a useful tool to differentiate the coagulation profile of nonsevere and severe COVID-19 patients for therapeutic intervention purposes.

Proposal of Henriciella barbarensis sp. nov. and Henriciella algicola sp. nov., stalked species of the genus and emendation of the genus Henriciella.

Two Gram-negative, heterotrophic, aerobic, prosthecated, marine bacteria, designated strains MCS23T and MCS27T, were isolated from seawater samples. NaCl was required for growth. The major polar lipid detected in strain MCS27T was phosphatidylglycerol, whereas those detected in MCS23T were phosphatidylglycerol, sulfoquinovosyl diacylglycerol and 1,2-diacyl-3-α-d-glucuronopyranosyl-sn-glycerol taurineamide. The most abundant cellular fatty acids were C18 : 1ω7 and C16 : 0, hydroxyl-fatty acids were 3-OH C12 : 0 in both strains and 3-OH C11 : 0 in MCS23T. Strains MCS23T and MCS27T had DNA G+C contents of 57.0 and 55.0 mol%, respectively. The two strains shared 99.3 % 16S rRNA gene sequence similarity; levels of similarity with the type strains of species of the genus Henriciella were 99.4-97.8 % but DNA-DNA hybridizations were 53 % or lower. Besides their 16S rRNA gene sequences, the novel strains can be differentiated from other species of the genus Henriciella by cell morphology, lipid and fatty acid patterns and enzyme activities. The data obtained led to the identification of two novel species, for which the names Henriciella barbarensis sp. nov. (type strain MCS23T=LMG 28705T=CCUG 66934T) and Henriciella algicola sp. nov. (type strain MCS27T=LMG 29152T=CCUG 67844T) are proposed. As these two novel species are the first prosthecate species in the genus Henriciella, an emended genus description is also provided.

Calibração do Storm Water Management Model (SWMM) utilizando algoritmos evolucionários multiobjetivo / Storm Water Management Model calibration using multiobjective evolutionary algorithms

RESUMO O estudo teve por objetivo a realização da calibração do modelo hidrológico Storm Water Management Model (SWMM) para a Bacia Hidrográfica do Arroio Cancela, localizada em Santa Maria, Rio Grande do Sul, utilizando o algoritmo evolucionário multiobjetivo R-NSGA. Para tanto, foram realizadas modificações na estrutura do SWMM, de modo que permitisse seu acoplamento como Evolucionary Reference Point Based Non-Dominated Sorting Genetic Algorithm (R-NSGA) em ambiente de programação MATLAB. As funções objetivo utilizadas foram o Coeficiente de Eficiência de Nash-Sutcliffe (COE), o Erro da Vazão de Pico (EQP) e o Erro do Volume Escoado (EVOL) aplicadas simultaneamente na calibração do modelo. Foi proposto um método para determinação da maior compatibilidade de modo a elencar as melhores soluções. Os resultados dos parâmetros calibrados do SWMM foram próximos aos valores físicos da bacia, com exceção dos valores relativos à equação de Horton. As soluções de maior compatibilidade apresentam um melhor comportamento para os eventos de validação, evidenciando a importância da otimização multiobjetivo.

ABSTRACT This paper focused on the calibration of Storm Water Management Model (SWMM) for the Cancela River Basin, located in Santa Maria, Rio Grande do Sul, Brazil, using the multi-objective Evolucionary Reference Point Based Non-Dominated Sorting Genetic Algorithm R-NSGA. Modifications were made in SWMM structure to allow its linking with R-NSGA in MATLAB. The objective functions proposed were the efficiency coefficient of Nash-Sutcliffe (eNS), the Peak Flow Error (EQ) and Runoff Volume error (EVOL), which were applied simultaneously to the model calibration. A method for determining the maximum compatibility to rank the best solutions is proposed. The parameters estimated by SWMM calibration were close to physical values of the basin, except those relating to the Horton equation in the most compatible solutions have a better behavior for the validation event, highlighting the importance of multi-objective optimization.

Coprinuslactone protects the edible mushroom Coprinus comatus against biofilm infections by blocking both quorum-sensing and MurA.

Pathogens embedded in biofilms are involved in many infections and are very difficult to treat with antibiotics because of higher resistance compared with planktonic cells. Therefore, new approaches for their control are urgently needed. One way to search for biofilm dispersing compounds is to look at defense strategies of organisms exposed to wet environments, which makes them prone to biofilm infections. It is reasonable to assume that mushrooms have developed mechanisms to control biofilms on their sporocarps (fruiting bodies). A preliminary screening for biofilms on sporocarps revealed several species with few or no bacteria on their sporocarps. From the edible mushroom Coprinus comatus where no bacteria on the sporocarp could be detected (3R,4S)-2-methylene-3,4-dihydroxypentanoic acid 1,4-lactone, named coprinuslactone, was isolated. Coprinuslactone interfered with quorum-sensing and dispersed biofilms of Pseudomonas aeruginosa, where it also reduced the formation of the pathogenicity factors pyocyanin and rhamnolipid B. Coprinuslactone also damaged Staphylococcus aureus cells in biofilms at subtoxic concentrations. Furthermore, it inhibited UDP-N-acetylglucosamine enolpyruvyl transferase (MurA), essential for bacterial cell wall synthesis. These two modes of action ensure the inhibition of a broad spectrum of pathogens on the fruiting body but may also be useful for future clinical applications.

Macrocyclic trichothecenes as antifungal and anticancer compounds.

Trichothecenes are sesquiterpenoid metabolites produced by fungi and species of the plant genus Baccharis, family Asteraceae. They comprise a tricyclic core with an epoxide at C-12 and C-13 and can be grouped into non-macrocyclic and macrocyclic compounds. While many of these compounds are of concern in agriculture, the macrocyclic metabolites have been evaluated as antiviral, anti-cancer, antimalarial and antifungal compounds. Some known cytotoxic responses on eukaryotic cells include inhibition of protein, DNA and RNA syntheses, interference with mitochondrial function, effects on cell division and membranes. These targets however have been elucidated essentially employing non-macrocyclic trichothecenes and only one or two closely related macrocyclic compounds. For several macrocyclic trichothecenes high selectivity against fungal species and against cancer cell lines have been reported suggesting that the macrocycle and its stereochemistry are of crucial importance regarding biological activity and selectivity. This review is focused on compounds belonging to the macrocyclic type, where a cyclic diester or triester ring binds to the trichothecane moiety at C-4 and C- 15 leading to natural products belonging to the groups of satratoxins, verrucarins, roridins, myrotoxins and baccharinoids. Their biological activities, cytotoxic mechanisms and structure-activity relationships (SAR) are discussed. From the reported data it becomes evident that even small changes in the molecules can lead to pronounced effects on biological activity or selectivity against cancer cells lines. Understanding the underlying mechanisms may help to design highly specific drugs for cancer therapy.

Amaurocine: Anti-Trichomonas vaginalis protein produced by the basidiomycete Amauroderma camerarium.

Trichomonas vaginalis is the causative agent of trichomoniasis, the most common nonviral STD worldwide. This infection can lead to severe health conditions, especially when women are affected. Metronidazole and tinidazole are the only choices of treatment. In this sense, natural bioactive compounds against T. vaginalis are an interesting approach in the search for more efficient therapies. Herein, amaurocine, a 12 kDa protein, produced by the mushroom Amauroderma camerarium was purified and tested against T. vaginalis, including two fresh clinical isolates. Amaurocine presented MIC values at 2.6 µM against the ATCC isolate 30236, and 5.2 µM against the fresh clinical isolates, TV-LACH1 and TV-LACM2. Furthermore, besides increasing human neutrophils nitric oxide release, amaurocine presented a low toxicity toward those cells, suggesting it exerts a proinflammatory character.

Secondary Metabolites Control the Associated Bacterial Communities of Saprophytic Basidiomycotina Fungi.

Fungi grow under humid conditions and are, therefore, prone to biofilm infections. A 16S rRNA fingerprint analysis was performed on 49 sporocarps of Basidiomycotina in order to determine whether they are able to control these biofilms. Ninety-five bacterial phylotypes, comprising 4 phyla and 10 families, were identified. While ectomycorrhizal fungi harbored the highest bacterial diversity, saprophytic fungi showed little or no association with bacteria. Seven fungal species were screened for antimicrobial and antibiofilm activities. Biofilm formation and bacterial growth was inhibited by extracts obtained from saprophytic fungi, which confirmed the hypothesis that many fungi modulate biofilm colonization on their sporocarps.

An 81-year-old male with iliopsoas abscess by Streptococcus sanguis.

Iliopsoas muscle abscess is an uncommon condition, which has been growing in incidence. We describe a primary iliopsoas abscess by Streptococcus sanguis affecting an 81-year-old man cured by antibiotic therapy and aspiration procedure. The objective is to enhance the suspicion index about the iliopsoas abscess that may be mistaken for other causes of acute abdomen. The important diagnostic role of abdominal imaging studies is also emphasised.

Histological evaluation of the cleaning effectiveness of two reciprocating single-file systems in severely curved root canals: Reciproc versus WaveOne.

OBJECTIVE: The aim of this study was to evaluate the cleaning effectiveness achieved with two reciprocating single-file systems in severely curved root canals: Reciproc and WaveOne. MATERIALS AND METHODS: Twenty-five mesial roots of mandibular molars were randomly separated into two groups, according to the instrumentation system used. The negative control group consisted of five specimens that were not instrumented. The mesial canals (buccal and lingual) in Reciproc Group were instrumented with file R25 and the WaveOne group with the Primary file. The samples were submitted to histological processing and analyzed under a digital microscope. RESULTS: The WaveOne group presented a larger amount of debris than the Reciproc Group, however, without statistically significant difference (P > 0.05). A larger amount of debris in the control group was observed, with statistically significant difference to Reciproc and WaveOne groups (P < 0.05). CONCLUSIONS: The two reciprocating single-file instrumentation systems presented similar effectiveness for root canal cleaning.

Effect of passive ultrasonic agitation during final irrigation on cleaning capacity of hybrid instrumentation.

OBJECTIVES: To evaluate the effect of passive ultrasonic agitation on the cleaning capacity of a hybrid instrumentation technique. MATERIALS AND METHODS: Twenty mandibular incisors with mesiodistal-flattened root shape had their crowns sectioned at 1 mm from the cementoenamel junction. Instrumentation was initiated by catheterization with K-type files (Denstply Maillefer) #10, #15, and #20 at 3 mm from the working length. Cervical preparation was performed with Largo bur #1 (Dentsply Maillefer) followed by apical instrumentation with K-type files #15, #20 and #25, and finishing with ProTaper F2 file (Denstply Maillefer). All files were used up to the working length under irrigation with 1 mL of 2.5% sodium hypochlorite (Biodynâmica) at each instrument change. At the end of instrumentation, the roots were randomly separated into 2 groups (n = 10). All specimens received final irrigation with 1 mL of 2.5% sodium hypochlorite. The solution remained in the root canals in Group 1 for one minute; and ultrasonic agitation was performed in Group 2 for one minute using a straight tip inserted at 1 mm from working length. The specimens were processed histologically and the sections were analyzed under optic microscope (×64) to quantify debris present in the root canal. RESULTS: The samples submitted to ultrasonic agitation (Group 2) presented significant decrease in the amount of debris in comparison with those of Group 1 (p < 0.05). CONCLUSIONS: The hybrid instrumentation technique associated with passive ultrasonic agitation promoted greater debris removal in the apical third of the root canals.

Doença de Behçet, anticorpos anticardiolipina, forame oval patente e síndrome de Sweet ? uma associação incomum / Behçet?s disease, anticardiolipin antibodies, patent foramen ovale, and Sweet syndrome ? an uncommon association

Doença de Behçet é condição inflamatória e autoimune infrequente, caracterizada por úlceras orais recorrentes e dois ou mais dos seguintesachados ? úlceras genitais, alterações oculares, lesões cutâneas e teste de patergia positivo. A ocorrência de vasculites e de anticorpos antifosfolípides pode contribuir para o aparecimento de tromboembolismos na doença de Behçet. Mulher de 49 anos, com doença de Behçet associada com diagnóstico prévio de síndrome de anticorpos antifosfolípides, apresentou erupção cutânea consistente com a síndrome de Sweet em um local de punção venosa. Foi introduzida prednisona 20mg/dia ao tratamento com warfarina 5 mg/dia que já utilizava, e a resposta satisfatória foi rápida. Pesquisa de sangue oculto foi positiva nas fezes, com concentração de antígeno carcinoembrionário discretamente elevada, e a colonoscopia revelou pólipos no cólon e no sigmoide. O câncerde cólon é descrito em portadores de doença de Behçet com lesões intestinais. Forame oval patente com shunt esquerdo-direito foi achado incidental no presente caso, e essa anomalia propicia embolias paradoxais em pacientes com estados hipercoaguláveis. A associação de doença de Behçet com síndrome de Sweet é raramente descrita e, embora sem o necessário esclarecimento, alguns autores admitem a possibilidade de mecanismo etiopatogênico comum a essas entidades.

Behçet?s disease is an inflammatory and autoimmune condition, characterized by recurrent oral ulcers and, at least, two of the following findings ? genital ulcers, ocular changes, cutaneous lesions, and positivetest for pathergy. The occurrence of vasculitis and antiphospholipid antibodies may contribute to thromboembolisms in Behçet?s disease. A 49-yearold woman with Behçet?s disease associated with a previous diagnosis of antiphospholipid antibodies syndrome presented with an abrupt cutaneous eruption consistent with the Sweet syndrome at the site of venipuncture. Prednisone 20 mg/day was introduced to the treatment with warfarin 5 mg/day that she was undergoing, resulting in a rapid favorable response. Fecal occult blood test was positive, and the level ofcarcinoembryonic antigen was mildly elevated, and the colonoscopy evaluation revealed colon and sigmoid polyps. Colon cancer may develop in patients with intestinal lesions of Behçet?s disease. Patent foramen ovale with left to right shunt was an incidental finding in the present case study, and this anomaly predisposes to paradoxal embolism in patients with thrombophilic conditions. Association between Behçet?s disease andSweet syndrome has been rarely described and, although without the necessary clarification, some authors believe in a possible common etiopathogenic mechanism.

Evaluation of commercial fluoride solutions on bovine enamel demineralization, using pH-cycling model / Avaliação de soluções fluoretadas comerciais na redução da perda mineral em esmalte bovino, utilizando modelo de ciclagem de pH

Purpose: The aim of this in vitro study was to evaluate the fluoride concentration in mouthrinses and their capacity to intervene with the caries process. Methods: The analysis of the fluoride concentration in the solutions was carried with ion specific electrode connected to an ion analyzer. Bovine incisors enamel blocks with previously known superficial microhardness were submitted to a pH cycling model and treated with fluoridated solutions, and later reanalyzed for microhardness and fluoride incorporation. Results: The fluoride concentration (ppm) found in the solutions SANiFill- Sanikids®, Colgate Plax Fresh Mint®, Oral B®, Sorriso Fresh® and Cepacol® (not fluoridated) were, respectively: 242.91±21.89; 248.42±3.55; 248.29±11.31; 257.61±17.57 and 35.37±10.64. The lowest loss of superficial microhardness was observed with the use Sorriso Fresh® (29.66%± 8.84), followed by Plax Fresh mint® (32.99%±14.09) and Oral B® (43.00%±18.34). Conclusion: The data suggest that fluoride solutions, in proper concentrations, are capable of intervening on the phenomena of demineralization and remineralization, promoting fluoride incorporation and, consequently, decreasing the loss of microhardness on dental enamel.

Objetivo: O objetivo deste estudo in vitro foi analisar a concentração de flúor em diferentes soluções fluoretadas para bochechos e sua capacidade de interferir no processo de cárie. Metodologia: A análise da concentração de flúor nas soluções para bochecho foi realizada com eletrodo específico para íon flúor acoplado a um analisador de íons Orion. Blocos de esmalte de dentes incisivos bovinos com a microdureza superficial conhecida foram submetidos à ciclagem de pH e uso de soluções fluoretadas, sendo, posteriormente, avaliados por uma nova análise de microdureza e também pela incorporação de flúor. Resultados: As concentrações de flúor (ppm) encontradas nas soluções SANiFill®, Colgate® Plax®, Oral B®, Sorriso® e Cepacol® (não fluoretada) foram, respectivamente: 245,94; 247,61; 251,50; 258,01 e 38,44. A menor perda de porcentagem de dureza superficial foi observada com o uso da solução fluoretada Sorriso® (29,7%±14,4), seguida por Colgate® Plax® (33%±14,1) e Oral B® (43%±18,3). Todas as soluções fluoretadas analisadas mostraram capacidade de incorporar flúor no esmalte dental. Conclusão: Os dados sugerem que as soluções fluoretadas foram capazes de interferir nos fenômenos de desmineralização e remineralização, promover incorporação de flúor e, conseqüentemente, diminuir a perda de dureza no esmalte dental.

Análise da confiabilidade entre-examinadores de dois instrumentos que mensuram a amplitude de movimento de flexão da coluna lombar / Analysis of the interexaminer reliability of two clinical tests to measure the flexion range of motion of the lumbar spine

A mensuração da amplitude de movimento de flexão da coluna lombar é uma prática clínica comum. Vários são os métodos para tais medidas, destacando-se entre elas duas ferramentas clínicas: o Inclinômetro Back Range of Motion II (BROM II) e a Régua Flexível. Métodos: O objetivo desse estudo foi analisar a confiabilidade entre-examinadores para as medidas de flexão da coluna lombar utilizando o BROM II e a Régua Flexível. Trinta e sete estudantes de Fisioterapia foram examinados num design teste-reteste duplo-cego Resultados: Os resultados mostraram confiabilidade moderada para as medidas com o BROM II [CCI (2,1) 0,71 (IC 95% 0,49-0,84) p<0,000] e pobre para a Régua Flexível [CCI(2,1) 0,37 (IC 95% 0,06-0,62) p<0,012]. Conclusão: Conclui-se que o BROM II apresentou confiabilidade suficiente para sua utilização na prática clínica.

The measurement of the flexion range of motion of the lumbar spine is a common practice in clinical settings. Many methods are used to carry out these measurements, such as the Back Range of Motion Inclinometer (BROMII) and the Flexible Ruler methods. Objective and Methods: The aim of this study was to analyze the interexaminer reliability for the measurement of the lumbar spine flexion by using the BROMII and the Flexible Ruler methods. Thirty-seven physical therapy students were recruited as volunteers and a double-blind test-retest study design was carried out. Results: The results showed moderate reliability of the BROMII measurements [ICC (2.1) 0.71 (95%CI 0.49-0.84) p<0.000]; however, the reliability of the Flexible Ruler measurements was poor [ICC(2.1) 0.37 (95%CI 0.06-0.62), p<0.012]. Conclusion: The BROM II presented sufficient reliability to be performed in clinical practice.