Genome assembly and variant analysis of two Saccharomyces cerevisiae strains isolated from stingless bee pollen.

Products from stingless bees are rich reservoirs of microbial diversity, including yeasts with fermentative potential. Previously, two Saccharomyces cerevisiae strains, JP14 and IP9, were isolated from Jataí (Tetragonisca angustula) and Iraí (Nannotrigona testaceicornis) bees, respectively, aiming at mead production. Both strains presented great osmotic and sulfite tolerance, and ethanol production, although they have a high free amino nitrogen demand. Herein, their genomes were sequenced, assembled, and annotated, and the variants were compared to the S. cerevisiae S288c reference strain. The final assembly of IP9 and JP14 presented high N50 and BUSCO scores, and more than 6430 protein-coding genes. Additionally, nQuire predicted the ploidy of IP9 as diploid, but the results were not enough to determine the ploidy of JP14. The mitochondrial genomes of IP9 and JP14 presented the same gene content as S288c but the genes were rearranged and fragmented in different patterns. Meanwhile, the genes with mutations of high impact (e.g., indels, gain of stop codon) for both yeasts were enriched for transmembrane transport, electron transfer, oxidoreductase, heme binding, fructose, mannose, and glucose transport, activities related to the respiratory chain and sugar metabolism. The IP9 strain presented copy number gains in genes related to sugar transport and cell morphogenesis; in JP14, genes were enriched for disaccharide metabolism and transport, response to reactive oxygen species, and polyamine transport. On the other hand, IP9 presented copy number losses related to disaccharide, thiamine, and aldehyde metabolism, while JP14 presented depletions related to disaccharide, oligosaccharide, asparagine, and aspartate metabolism. Notably, both strains presented a killer toxin gene, annotated from the assembling of unmapped reads, representing a potential mechanism for the control of other microorganisms population in the environment. Therefore, the annotated genomes of JP14 and IP9 presented a high selective pressure for sugar and nitrogen metabolism and stress response, consistent with their isolation source and fermentative properties.

EVALUATION OF VOLUME AND STRENGTH OF THE QUADRICEPS MUSCLE BEFORE AND AFTER ANTERIOR CRUCIATED LIGAMENT RECONSTRUCTION SURGERY / AVALIAÇÃO DO VOLUME E FORÇA DO MÚSCULO QUADRÍCEPS ANTES E APÓS OPERAÇÃO DE RECONSTRUÇÃO DO LIGAMENTO CRUZADO ANTERIOR

Introduction: The anterior cruciate ligament is one of the main ligaments of the knee, often more susceptible to injuries due to its central position and its vital role in stabilizing this joint. The strength of the quadriceps plays a crucial role, with impact absorption function, helping to reduce load. Objective: To evaluate the volume and strength of the quadriceps muscle before and after reconstruction of the anterior cruciate ligament of the knee, their correlation and which variables predict pre- and postoperative muscle strength. Method: Prospective cohort of 37 patients evaluated preoperatively and 4 months after the operation, using magnetic resonance imaging and isokinetic dynamometry. The measurements of the limb undergoing the operation were compared to the contralateral limb as a control. Result: The volume of the quadriceps muscle was 65.2+13.4cm3 before and 63.4+15.9 cm3 after, significantly lower in the control at both moments, with a reduction of 3.0cm3 (4.1%) in the pre and 7.8 cm3 post (12.0%). Muscle strength was 105.5+29.9N/m before and 100.9+28.6N/m after, significantly lower in the operated limb (126.4+28.2N/m and 129.6+27.6N /m, p<0.001). This reduction was similar in the 2 evaluation moments, on average of 17.5N/m (16.3%) in the pre and 22.8N/m (22.5%) in the post. The loss of strength was greater than the loss of muscle volume, with muscle volume and time of anterior cruciate ligament injury being the main determinants of muscle strength in the pre-op. The strength in the post was mainly determined by that in the pre. Conclusion: The loss of muscle strength was 4 times greater than the loss of volume pre-operatively and 2 times greater post-operatively, indicating the beginning of recovery 4 months post-operatively.

Introdução: O ligamento cruzado anterior é um dos principais ligamentos do joelho, frequentemente mais suscetível às lesões devido à sua posição central e seu papel vital na estabilização desta articulação. A força do quadríceps desempenha papel crucial, com função de absorção de impacto, auxiliando na redução de carga. Objetivo: Avaliar o volume e a força do músculo quadríceps antes e após a reconstrução do ligamento cruzado anterior do joelho, sua correlação e quais as variáveis preditivas da força muscular pré e pós-operatória. Método: Coorte prospectiva de 37 pacientes avaliados no pré-operatório e com 4 meses após a operação, por meio de ressonância magnética e dinamometria isocinética. As medidas do membro submetido à operação foram comparadas ao membro contralateral como controle. Resultado: O volume do músculo quadríceps foi de 65,2+13,4cm3 antes e de 63,4+15,9 cm3 após, significativamente menor no controle nos 2 momentos, com redução de 3,0cm3 (4,1%) no pré e 7,8 cm3 no pós (12,0%). A força muscular foi de 105,5+29,9N/m antes e de 100,9+28,6N/m após, significativamente menor no membro operado (126,4+28,2N/m e 129,6+27,6N/m, p<0,001). Esta redução foi semelhante nos 2 momentos de avaliação, em média de 17,5N/m (16,3%) no pré e de 22,8N/m (22,5%) no pós. A perda de força foi maior que a perda de volume muscular, sendo que o volume muscular e o tempo da lesão do ligamento cruzado anterior foram os principais determinantes da força muscular no pré. A força no pós foi determinada principalmente pela do pré. Conclusão: A perda de força muscular foi 4 vezes maior que a perda de volume no pré e 2 vezes maior no pós, indicando início da recuperação com 4 meses no pós-operatório.

HOW MUCH VOLUMETRIC AND STRENGTH LOSS OF THE QUADRICEPS FEMORAL MUSCLE IS EXPECTED IN THE POST-OPERATIVE RECONSTRUCTION OF THE ANTERIOR CRUCIATED LIGAMENT? / QUANTO DE PERDA VOLUMÉTRICA E DE FORÇA DO MÚSCULO QUADRÍCEPS FEMORAL É ESPERADA NO PÓS-OPERATÓRIO DA RECONSTRUÇÃO DO LIGAMENTO CRUZADO ANTERIOR?

Introduction: When injured and/or reconstructed the anterior cruciate ligament, not only occurs decrease in strength, but also less contraction of the quadriceps, in addition to muscle atrophy. Magnetic resonance imaging and isokinetic dynamometry have offered better evaluation of the pre- and post-surgical periods and can better monitor and predict postoperative rehabilitation. Objectives: To review the role of volume and strength of the quadriceps femoris muscle before and after reconstruction of the anterior cruciate ligament and how these measurements correlate with the predictive variables of pre- and postoperative muscle strength. Method: Integrative review collecting information on virtual platforms. The texts were selected from SciELO, Google Scholar, Pubmed and Scopus. The descriptors related to the topic were the following: anterior cruciate ligament reconstruction; magnetic resonance imaging; quadriceps muscle in Portuguese and English with AND or OR search, considering the title and/or abstract. Results: The entire selected texts were read and 61 articles were included. Conclusion: A loss of volume and strength of the quadriceps muscle was observed after reconstruction. The loss of strength was 4 times greater than the preoperative volume and 2 times greater postoperatively, with improvement 4 months after the operation.

Introdução: Observa-se, quando da lesão e/ou reconstrução do ligamento cruzado anterior, não somente que há diminuição da força, mas também da qualidade e da contração do quadríceps, além de atrofia muscular. A ressonância magnética e dinamometria isocinética têm oferecido melhor avaliação dos períodos pré e pós-cirúrgicos, podendo melhor monitorizar e prever a reabilitação pós-operatória. Objetivos: Revisar o papel do volume e da força do músculo quadríceps femoral antes e após reconstrução do ligamento cruzado anterior e como estas medidas se correlacionam com as variáveis preditivas da força muscular pré e pós-operatória. Método: Revisão integrativa colhendo informações em plataformas virtuais. Os textos foram selecionados do SciELO, Google Scholar, Pubmed e Scopus. Os descritores relacionados ao tema foram os seguintes: reconstrução do ligamento cruzado anterior; ressonância magnética; músculo quadríceps em português e inglês com busca AND ou OR, considerando o título e/ou resumo. Resultados: Foi realizada a leitura da íntegra dos textos selecionados e incluídos 61 artigos. Conclusão: Observou-se perda de volume e força do músculo quadríceps após a reconstrução. A perda da força muscular foi 4 vezes maior que a do volume pré- operatório e 2 vezes maior no pós-operatório com melhora após 4 meses da operação.

Chemical Characterization, Leishmanicidal Activity and In Vitro Cytotoxicity of the Essential Oil Extracted from Pectis brevipedunculata (Gardner) Sch.Bip. and Its Incorporation into Microemulsion Systems.

Pectis brevipedunculata (Gardner) Sch.Bip., known in Brazil as alecrim do campo, is a small Asteraceae family plant with a calming effect and consumed as tea. This species contains components, such as neral and geranial, that display various biological activities, such as leishmanicidal. The aim was to chemically characterize the essential oil (EO) obtained from P. brevipedunculata (EO-PB) by hydrodistillation and a microemulsion formulated with EO (ME-PB), Tween 80 and Transcutol P, assess the leishmanicidal effect against Leishmania (L.) amazonensis promastigotes and cytotoxicity against RAW 264.7. EO-PB and ME-PB were analyzed by Gas Chromatography Mass Spectrometry (GC/MS). Monoterpene hydrocarbons were noteworthy among the identified compounds. The main EO-PB constituents were α-pinene and limonene, followed by neral and geranial, which were maintained in ME-PB. EO-PB presented an inhibitory concentration (IC50) of 20 µg/mL and ME-PB of 0.93 µg/mL. ME-PB inhibition towards the parasite was 20-fold higher than that of EO-PB. This indicated that EO incorporation to the microemulsion resulted in optimized biological activity. Selectivity indices indicate that ME-PB is more selective concerning parasite inhibition. Thus, ME-PB may comprise an adequate approach against Leishmania, as the inhibitory concentration (IC50) promastigotes was lower than that considered toxic for cells cell cytotoxicity of 50% (CC50).

Evaluation of the acute toxicity of ellagic acid and gallic acid incorporated in Poloxamer407® gel, in Zophobas morio larvae.

Gallic acid (GA) has antioxidant, anti-inflammatory and antimicrobial properties, while ellagic acid (EA) demonstrates anticancer, antiviral and photoprotective activity. In this study, the combination of these substances incorporated into a poloxamer gel was tested to verify the individual effect of the substances, in addition to taking advantage of a probable complementary effect, aiming to provide additional therapeutic benefits. As a result of the incorporation, formulations containing GA, EA and GA + EA were obtained, which were evaluated for the effects of the Freeze-thaw cycle on pH, which revealed a significant decrease (p < 0.05) in most samples, including the vehicle (without drug) and the gel containing both drugs. No sample showed variation outside the normal pH range for the skin, with values ranging from 4.8 to 6.0. Regarding conductivity, the GA, EA and GA + EA formulations showed a reduction (p < 0.05) after the freeze-thaw cycle. The drug content in the formulations ranged from 95.86% to 101.35% initially to 91.30% to 101.51% after the freeze-thaw cycle. Regarding the drug release, the results revealed the following cumulative percentages: GA-3% - 92.58% after 1.5 h; AE-3% - 51.60% after 6 h; GA + EA (1.5% = 1.5%) - 99.91% after 2 h; GA + EA- (1.5% = 1.5%) released 57.06%, after 6 h. Regarding toxicity, it was observed that the group treated with GA showed a lower survival rate of the larvae (40%) at the dose 3000 mg/Kg in the formulation. Following the same trend, in the acute lethal concentration (ALC50) test performed using Zophobas morio larvae, an ALC50 of 2191.51 mg/Kg was observed for GA at 48 h. Melanin analysis showed a decrease in concentrations of 30 mg/Kg in the GA group, 3 mg/Kg of EA and 3, 300, 3000 mg/Kg of GA + EA, of the pure drugs. In the groups with the drugs incorporated into the gel, there was a significant decrease (P < 0.05) in melanin in the vehicle (gel), at concentrations of 300 and 3000 mg/Kg of GA and EA. On the other hand, in the combination of GA + EA, a reduction was observed at concentrations of 3 and 30 mg/Kg when compared to the control group. Thus, the gel showed good quality as a pharmaceutical formulation for topical use and low toxicity, making it promising for use in skin therapies.

Uso dos antifúngicos no tratamento da candidíase vulvovaginal: uma revisão integrativa / Use of antifungals in the treatment of vulvovaginal candidiasis: an integrative review

Objective: To identify scientific evidence available in the literature and analyze the action of antifungal drugs used for the treatment of vulvovaginal candidiasis. Methods:Integrative literature review conducted in the databases Medline/PubMed, Embase, Web of Science, Cochrane Library, CINAHL, SCOPUS and VHL; with the descriptors "woman", "antifungal agents"; "vulvovaginal candidiasis". Results:Ten scientific articles published between 1983 and 2020 were obtained. Of these, four were developed in Iran; followed by Mexico, England, Taiwan, Thailand, Denmark, and the United States. In terms of methodological design, most studies are clinical trials (n=8), and two are cross-sectional studies. Regarding the level of evidence, eight are level II, and only two investigations are level IV. Concerning the antifungal drugs used in the treatment, there was a predominance of clotrimazole (n=4; efficacy ranging from 42.4% to 98.3%), followed by econazole (n=2; efficacy between 39% and 89%), combined or not with another antifungal drug. Conclusion: The use of clotrimazole stands out, as it is highly effective in the treatment of vulvovaginal candidiasis. This study contributes to the advancement of knowledge and improvement of the clinical practice of nursing and other health professionals. It is expected that these results will encourage further studies and update clinical practices.Descriptors:Women;Antifungal Agents;Candidiasis, Vulvovaginal

Objective: To identify scientific evidence available in the literature and analyze the action of antifungal drugs used for the treatment of vulvovaginal candidiasis. Methods: Integrative literature review conducted in the databases Medline/PubMed, Embase, Web of Science, Cochrane Library, CINAHL, SCOPUS and VHL; with the descriptors "woman", "antifungal agents"; "vulvovaginal candidiasis". Results:Ten scientific articles published between 1983 and 2020 were obtained. Of these, four were developed in Iran; followed by Mexico, England, Taiwan, Thailand, Denmark, and the United States. In terms of methodological design, most studies are clinical trials (n=8), and two are cross-sectional studies. Regarding the level of evidence, eight are level II, and only two investigations are level IV. Concerning the antifungal drugs used in the treatment, there was a predominance of clotrimazole (n=4; efficacy ranging from 42.4% to 98.3%), followed by econazole (n=2; efficacy between 39% and 89%), combined or not with another antifungal drug. Conclusion:The use of clotrimazole stands out, as it is highly effective in the treatment of vulvovaginal candidiasis. This study contributes to the advancement of knowledge and improvement of the clinical practice of nursing and other health professionals. It is expected that these results will encourage further studies and update clinical practices.Descriptors:Women;Antifungal Agents;Candidiasis, Vulvovaginal

Innovative Microemulsion Loaded with Unusual Dimeric Flavonoids from Fridericia platyphylla (Cham.) L.G. Lohmann Roots.

Fridericia platyphylla (Cham.) L.G. Lohmann is a species native to the Brazilian cerrado, with promising bioactivity. The organic fraction of the roots is rich in unusual dimeric flavonoids, reported as potential candidates for cancer treatment. The exploration of these flavonoids is very important, considering their diverse biological activities and the need for innovative therapeutic options. This work aimed to develop and characterize a microemulsion loaded with a non-polar fraction (DCM). The constituents were chosen, and the pseudo-ternary diagram was constructed to determine the region of microemulsion formation. The microemulsions blank (ME), with 3% (ME3) and 5% (ME5) of fraction DCM, were characterized in terms of droplet size, zeta potential, and polydispersity index. Both MEs showed particle sizes <100 nm; only ME3 exhibited better values for polydispersity index and zeta potential and was therefore selected for further study. The organoleptic and physicochemical characteristics were evaluated, revealing limpidity and transparency typical of these microstructures, physiologically acceptable pH, refractive index of 1.42±0.01, and density of 1.017 g/cm3±0.01. The stability tests showed good stability profiles even after exposure to extreme thermal conditions, with minimal changes in pH and the content of the incorporated fraction. The in vitro release study demonstrated that ME3 enabled the controlled release of the fraction, with a cumulative amount released over 60% within 6 h. Furthermore, fraction DCM and ME3 exhibited no toxicity in Tenebrio molitor larvae. The developed microemulsion exhibited excellent properties, so this study represents the first successful attempt to develop a formulation that incorporates the dimeric flavonoid fraction.

Films composed of white angico gum and chitosan containing chlorhexidine as an antimicrobial agent.

Anadenanthera colubrina, popularly known as white angico, is a species extensively cultivated in Brazil, mainly in the cerrado region, including the state of Piauí. This study examines the development of films composed of white angico gum (WAG) and chitosan (CHI) and containing chlorhexidine (CHX), an antimicrobial agent. The solvent casting method was used to prepare films. Different combinations and concentrations of WAG and CHI were used to obtain films with good physicochemical characteristics. Properties such as the in vitro swelling ratio, the disintegration time, folding endurance, and the drug content were determined. The selected formulations were characterised by scanning electron microscopy, Fourier-transform infrared spectroscopy, differential scanning calorimetry, thermogravimetric analysis, and X-ray diffraction, and the CHX release time and antimicrobial activity were evaluated. CHX showed a homogenous distribution in all CHI/WAG film formulations. The optimised films showed good physicochemical properties with 80% CHX release over 26 h, which is considered promising for local treatment of severe lesions in the mouth. Cytotoxicity tests of the films did not show toxicity. The antimicrobial and antifungal effects were very effective against the tested microorganisms.

Papiliotrema laurentii: general features and biotechnological applications.

Papiliotrema laurentii, previously classified as Cryptococcus laurentii, is an oleaginous yeast that has been isolated from soil, plants, and agricultural and industrial residues. This variety of habitats reflects the diversity of carbon sources that it can metabolize, including monosaccharides, oligosaccharides, glycerol, organic acids, and oils. Compared to other oleaginous yeasts, such as Yarrowia lipolytica and Rhodotorula toruloides, there is little information regarding its genetic and physiological characteristics. From a biotechnological point of view, P. laurentii can produce surfactants, enzymes, and high concentrations of lipids, which can be used as feedstock for fatty acid-derived products. Moreover, it can be applied for the biocontrol of phytopathogenic fungi, contributing to quality maintenance in post- and pre-harvest fruits. It can also improve mycorrhizal colonization, nitrogen nutrition, and plant growth. P. laurentii is also capable of degrading polyester and diesel derivatives and acting in the bioremediation of heavy metals. In this review, we present the current knowledge about the basic and applied aspects of P. laurentii, underscoring its biotechnological potential and future perspectives. KEY POINTS: • The physiological characteristics of P. laurentii confer a wide range of biotechnological applications. • The regulation of the acetyl-CoA carboxylase in P. laurentii is different from most other oleaginous yeasts. • The GEM is a valuable tool to guide the construction of engineered P. laurentii strains with improved features for bio-based products.

Anti-inflamatórios não esteroides tópicos para o alívio da dor artritica, beneficios para idosos / Non-steroid anti-inflammatory topics for arthritic pain relief, benefits for elderly / Temas antiinflamatorios no esteroides para el alívio del dolor artritico, beneficios para personas mayores

Objetivo: Identificar e analisar os anti-inflamatórios não esteroides tópicos para o alívio da dor artrítica, benefícios para idosos. Métodos: Trata-se de uma revisão integrativa realizada nas bases de dados no mês de maio de 2020, mediante consulta às bases de dados MEDLINE/PubMed, CINAHL, EMBASE, Web of Science, SCOPUS e índice bibliométrico LILACS, acessados por meio do Portal Periódicos da Comissão de Aperfeiçoamento de Pessoal de Ensino Superior, utilizando os descritores: idoso (Aged/elderly), anti-inflamatório não esteroide (Anti-Inflammatory Agents, Non-Steroidal) artrite (Arthritides/Polyarthritis). No qual foram selecionados 13 artigos sem limitador para tempo e idioma. Resultados: Detectou se que as variáveis mais evidenciadas foram: inglês (100%); artigos indexados na MEDLINE/PubMed (69,2%); pais com mais publicações Inglaterra (46%). Destaca-se que 69,3% dos artigos foram ensaios clínicos randomizados controlados; anti-inflamatório tópico mais usado diclofenaco sódico (61,5% seguido do cetoprofeno (38,7%). Conclusão: Concluiu se o diclofenaco e o cetoprofeno apresentam eficácia e segurança no alívio da dor artrítica, e baixa toxicidade cutânea local. (AU)

Objective To identify and analyze topical non-steroidal anti-inflammatory drugs for the relief of arthritic pain, benefits for the elderly. Methods: This is an integrative review carried out on the databases in May 2020, by consulting the MEDLINE / PubMed, CINAHL, EMBASE, Web of Science, SCOPUS and LILACS bibliometric index databases, accessed through the Portal Journals of the Higher Education Personnel Improvement Commission, using the descriptors: elderly (Aged / elderly), non-steroidal anti-inflammatory (Anti-Inflammatory Agents, Non Steroidal) arthritis (Arthritides / Polyarthritis). In which 13 articles were selected without time and language limitations. Results: It was found that the most evident variables were: English (100%); articles indexed in MEDLINE / PubMed (69.2%); parents with the most publications in England (46%). It is noteworthy that 69.3% of the articles were randomized controlled clinical trials; most commonly used topical anti-inflammatory diclofenac sodium (61.5% followed by ketoprofen (38.7%). Conclusion: Diclofenac and ketoprofen were concluded to be effective and safe in relieving arthritic pain and low local skin toxicity. (AU)

Objetivo: Identificar y analizar medicamentos antiinflamatorios no esteroideos tópicos para el alivio del dolor artrítico, beneficios para los ancianos. Métodos: Esta es una revisión integradora realizada en las bases de datos en mayo de 2020, consultando las bases de datos del índice bibliométrico MEDLINE / PubMed, CINAHL, EMBASE, Web of Science, SCOPUS y LILACS, a las que se accede a través del Portal Revistas de la Comisión de Mejoramiento del Personal de Educación Superior, utilizando los descriptores: artritis de edad avanzada (Ancianos / ancianos), antiinflamatorios no esteroideos (agentes antiinflamatorios, no esteroideos) (artritis / poliartritis). En el que se seleccionaron 13 artículos sin limitaciones de tiempo e idioma. Resultados: se encontró que las variables más evidentes fueron: inglés (100%); artículos indexados en MEDLINE / PubMed (69,2%); padres con más publicaciones en Inglaterra (46%). Es de destacar que el 69,3% de los artículos fueron ensayos clínicos controlados aleatorios; diclofenaco sódico antiinflamatorio tópico más utilizado (61.5% seguido de ketoprofeno (38.7%). Conclusión: Se concluyó que el diclofenaco y el ketoprofeno son efectivos y seguros para aliviar el dolor artrítico y la baja toxicidad local de la piel. (AU)

SARS-CoV-2 BA.5 vaccine breakthrough risk and severity compared with BA.2: a case-case and cohort study using Electronic Health Records in Portugal

BackgroundIn a context of multiple Omicron lineages circulation, it is relevant to clarify the effect of vaccination and previous infections on the risk of infection and severe post-infection outcomes. MethodsUsing electronic health records and SARS-CoV-2 laboratory surveillance data, we conducted a case-case and a cohort study covering the period of Omicron BA.2/BA.5 lineage replacement in Portugal, to compare vaccine effectiveness of complete primary and booster dose against infection, COVID-19 hospitalization, and mortality. Variant classification was performed through whole-genome sequencing (WGS) or Spike Gene Target Failure (SGTF). FindingsBetween April 25 and June 10, 2022, within a total of 27702 collected samples, 55.5% were classified as BA.2 and the remaining as BA.5. We observed no evidence of reduced vaccine effectiveness for the primary complete vaccination (OR=1.07, CI95%:0.93-1.23) or booster dose vaccination (OR=0.96, CI95%:0.84-1.09) against BA.5 infection compared with BA.2. The protection against reinfection was inferior in BA.5 cases when compared with BA.2 (OR=1.44; CI95%:1.30-1.60). Among those infected with BA.5, booster vaccination was associated with 77% and 88% of reduction in risk of COVID-19 hospitalization and death, respectively, while higher risk reduction was found for BA.2 cases, with 93% and 94%, respectively. InterpretationThis study shows that the SARS-CoV-2 Omicron BA.5 lineage is associated with higher odds of reinfection compared with Omicron BA.2, regardless of the vaccination status. Although less effective compared with BA.2, COVID-19 booster vaccination still offers substantial protection against severe outcomes following BA.5 infection.

B.1.617.2 SARS-CoV-2 (Delta) variant is associated with increased risk of hospitalization and death compared with B.1.1.7 SARS-CoV-2 (Alpha) variant

IntroductionThe B.1.617.2 variant (Delta) was associated with increased transmissibility and lower vaccine effectiveness than the B.1.1.7 variant (Alpha). However, the effect of the B.1.617.2 variant on disease severity remains unclear. This study aims to assess whether infection with the B.1.617.2 variant was associated with a higher risk of serious illness, compared with other co-circulating variants, measured through hospitalization and death by COVID-19 in Portugal. MethodsWe conducted a matched cohort study in adult individuals diagnosed with SARS-CoV-2/COVID-19 infection between March 29 and August 1, 2021. Cases were individuals with a positive PCR test notified to the surveillance system. SARS-CoV-2 variants were classified first by genomic sequencing (WGS) and, if this information was unavailable, by detecting the S gene target failure. Delta (B.1.617.2) and Alpha (B.1.1.7) cases were matched on the week of diagnosis at a 1 to k ratio (k being the maximum number of unexposed available in that week) to maximize the inclusion of unexposed, using the nearest-neighbor algorithm. The hazard risk and 95% confidence intervals of hospitalization and death among those infected with the Delta (B.1.617.2) variant vs. Alpha (B.1.1.7) was estimated using a Cox proportional hazards model, adjusting for confounding for sex, age, and vaccination status. ResultsA total of 2,778 cases were included in the study. Of the total, 1 742 (68%) were identified as B.1.617.2 variant cases and 3 629 (32%) as B.1.1.7 variant. Within the B.1.1.7 variant cases 106 (2.9%) were hospitalized, and 110 (6.3%) within the B.1.617.2 variant cases. A total of 29 deaths were reported, 8 (0.2%) in patients infected with B.1.1.7 variant and 21 (1.2%) in patients with the B.1.617.2 variant. The confounding adjusted risk of hospitalization, in persons infected with the B.1.617.2 variant was 2.44 (95%CI 1.85; 3.20) times higher than the risk of hospitalization among B.1.1.7 variant cases, and the confounding-adjusted risk of death for B.1.617.2 variant cases was 5.20 (95%CI 2.20; 12.29) times higher than the risk of death in patients infected by B.1.1.7 variant. ConclusionThe B.1.617.2 variant is associated with an increased risk of hospitalization and death compared with the B.1.1.7 variant.

Omicron (BA.1) SARS-CoV-2 variant is associated with reduced risk of hospitalization and length of stay compared with Delta (B.1.617.2)

IntroductionEarly reports showed that Omicron (BA.1) SARS-CoV-2 could be less severe. However, the magnitude of risk reduction of hospitalization and mortality of Omicron (BA.1) infections compared with Delta (B.1.617.2) is not yet clear. This study compares the risk of severe disease among patients infected with the Omicron (BA.1) variant with patients infected with Delta (B.1.617.2) variant in Portugal. MethodsWe conducted a cohort study in individuals diagnosed with SARS-CoV-2 infection between 1st and 29th December 2021. Cases were individuals with a positive PCR test notified to the national surveillance system. SARS-CoV-2 variants were classified first by whole genomic sequencing (WGS) and, if this information was unavailable, by detecting the S gene target failure. We considered a hospitalization for all the patients admitted within the 14 days after the SARS-CoV-2 infection; after that period, they were censored. The comparison of the risk of hospitalization between Omicron (BA.1) and Delta (B.1.617.2) VOC was estimated using a Cox proportional hazards model. The mean length of stay was compared using linear regression, and the risk of death between Omicron and Delta patients was estimated with a penalized logistic regression. All models were adjusted for sex, age, previous infection, and vaccination status. ResultsWe included 15 978 participants aged 16 or more years old, 9 397 infected by Delta (B.1.617.2) and 6 581 infected with Omicron (BA.1). Within the Delta (B.1.617.2) group, 148 (1.6%) were hospitalized, and 16 (0.2%) were with the Omicron (BA.1). A total of 26 deaths were reported, all in participants with Delta (B.1.617.2) infection. Adjusted HR for hospitalization for the Omicron (BA.1) variant compared with Delta (B.1.617.2) was 0.25 (95%CI 0.15 to 0.43). The length of stay in hospital for Omicron (BA.1) patients was significantly shorter than for Delta (confounding-adjusted difference -4.0 days (95%CI -7.2 to -0.8). The odds of death were 0.14 (95% CI 0.0011 to 1.12), representing a reduction in the risk of death of 86% when infected with Omicron (BA.1) compared with Delta (B.1.617.2). ConclusionOmicron (BA.1) was associated with a 75% risk reduction of hospitalization compared with Delta (B.1.617.2) and reduced length of hospital stay.

Nanostructured Lipid Carriers as a Novel Strategy for Topical Antifungal Therapy.

Nanostructured lipid carriers (NLC) were developed as an alternative carrier system optimizing limitations found in topical treatments for superficial fungal infections, such as limited permeation through the skin. However, few published studies are focused on standardization and characterization of determinant variables of these lipid nanosystems' quality. Thus, this systematic review aims to compile information regarding the selection of lipids, surfactants, and preparation method that intimately relates to the final quality of this nanotechnology. For this, the search was carried with the following descriptors: 'nanostructured lipid carriers', 'topical', 'antifungal' separated by the Boolean operators 'and', present in the titles of the databases: Science Direct, Scopus and Pubmed. The review included experimental articles focused on the development of nanostructured lipid carriers targeted for topical application with antifungal activity, published from 2015 to 2021. Review articles, clinical studies, and studies on the development of other nanocarriers intended for other routes of administration were excluded from the study. The research included 26 articles, of which 58% were developed in India and Brazil, 53% published in the years 2019 and 2020. As for the selection of antifungal drugs incorporated into NLCs, the azole class had a preference over other classes, voriconazole being incorporated into 5 of the 26 developed NLC studied. It was also observed a predominance of medium chain triglycerides (MCT) as a liquid lipid and polysorbate 80 as a surfactant. Among other results, this review compiles the influences of each of the variables discussed in the quality parameters of NLCs, in order to guide future research involving the development of this technology. Graphical Abstract.

Atividades farmacológicas da manteiga de bacuri (Platonia insignis Mart): revisão integrativa / Pharmacological actions of bacuri butter (Platonia insignis Mart): an integrative review

RESUMO Objetivo identificar as atividades farmacológicas da manteiga de bacuri (Platonia insignis Mart.). Métodos revisão integrativa, realizada nas bases de dados Literatura Latino-americana e do Caribe em Ciências da Saúde, Cumulative Index to Nursing and Allied Health Literature, EMBASE, MEDLINE/PubMed, Web of Science, Cochrane Library e SCOPUS, sem delimitação temporal e de idioma. A seleção se constituiu de 13 ensaios pré-clínicos. A avaliação das informações ocorreu de forma descritiva, confrontando com os achados pertinentes. Resultados observou-se que 50,0% das publicações foram indexadas na MEDLINE/PubMed, maioria das publicações ocorreram na Inglaterra (61,5%), seguidas do Brasil e dos Estados Unidos, ambos com 13,3%. Destaca-se que 100,0% dos artigos foram ensaios pré-clínicos; atividades farmacológicas para antioxidante (38,4%) e antileishmanicidas (30,7%). Registrou-se que 38,4% dos ensaios apresentaram testes de toxicidade. Conclusão a manteiga de bacuri (Platonia insignis Mart.) apresentou atividades farmacológicas em ensaios pré-clínicos, como antioxidantes, antileshimaniose, anticonvulsivante e cicatrização de feridas.

ABSTRACT Objective to identify the pharmacological activities of bacuri butter (Platonia insignis Mart.). Methods an integrative review, carried out in the databases of Latin American and Caribbean Literature in Health Sciences, Cumulative Index to Nursing and Allied Health Literature, EMBASE, MEDLINE/PubMed, Web of Science, Cochrane Library and SCOPUS, without the time and language restriction. The selection consisted of 13 pre-clinical trials. The information assessment descriptively took place, comparing with the pertinent findings. Results it was observed that 50.0% of the publications were indexed in MEDLINE/PubMed, most publications were from England (61.5%), followed by Brazil and the United States, both with 13.3%. It is noteworthy that 100.0% of the articles were pre-clinical trials; pharmacological activities for antioxidants (38.4%) and antileishmanicides (30.7%). It was found that 38.4% of the trials presented toxicity tests. Conclusion bacuri butter (Platonia insignis Mart.) Showed pharmacological activities in pre-clinical trials, such as antioxidants, antileshimaniasis, anticonvulsant and wound healing.

Development of Chlorhexidine Digluconate and Lippia sidoides Essential Oil Loaded in Microemulsion for Disinfection of Dental Root Canals: Substantivity Profile and Antimicrobial Activity.

The dental intracanal disinfection is crucial to achieve the success of endodontic treatment, avoiding the maintenance of endodontic infections. Chlorhexidine digluconate can act as an irrigating agent for it. However, it can cause tissue irritation in high concentrations. Therefore, combinations with other antimicrobial agents and more efficient therapeutic alternatives are studied, which make it possible to administer drugs more safely and with minimal adverse effects. Thus, the objective of this study was the development of a microemulsion containing chlorhexidine digluconate and essential oil of Lippia sidoides to be used for disinfection of dental root canals and to evaluate its profile of substantivity and antimicrobial activity. The microemulsions were obtained through phase diagrams, using the spontaneous formation method. We completed a physical-chemical characterization and evaluate the stability of the microemulsions, in addition to the substantivity profile in a bovine root dentin model, and in vitro antibacterial effect on Enterococcus faecalis. A method for quantifying chlorhexidine was developed using UV-Vis spectroscopy. The microemulsions showed acid pH, conductivity above 1.3 µScm-1, and dispersion index similar to water. The microemulsions showed antimicrobial inhibition halos similar to the commercial gel conventionally used, but with four times more substantivity to dentinal tissues. Microemulsions were obtained as a therapeutic alternative to formulations available on the market, presenting themselves as a system with great potential for the administration of drugs for disinfection of root canals.

Gallic and Ellagic Acids Are Promising Adjuvants to Conventional Amphotericin B for the Treatment of Cutaneous Leishmaniasis.

In this study, we demonstrated the potential associative effect of combining conventional amphotericin B (Amph B) with gallic acid (GA) and with ellagic acid (EA) in topical formulations for the treatment of cutaneous leishmaniasis in BALB/c mice. Preliminary stability tests of the formulations and in vitro drug release studies with Amph B, GA, Amph B plus GA, EA, and Amph B plus EA were carried out, as well as assessment of the in vivo treatment of BALB/c mice infected with Leishmania major After 40 days of infection, the animals were divided into 6 groups and treated twice a day for 21 days with a gel containing Amph B, GA, Amph B plus GA, EA, or Amph B plus EA, and the negative-control group was treated with the vehicle. In the animals that received treatment, there was reduction of the lesion size and reduction of the parasitic load. Histopathological analysis of the treatments with GA, EA, and combinations with Amph B showed circumscribed lesions with the presence of fibroblasts, granulation tissue, and collagen deposition, as well as the presence of activated macrophages. The formulations containing GA and EA activated macrophages in all evaluated parameters, resulting in the activation of cells of the innate immune response, which can generate healing and protection. GA and EA produced an associative effect with Amph B, which makes them promising for use with conventional Amph B in the treatment of cutaneous leishmaniasis.

Isolation of a new Papiliotrema laurentii strain that displays capacity to achieve high lipid content from xylose.

In this work, we isolated and selected oleaginous yeasts from rock field soils from two National Parks in Brazil (Caparaó and Serra dos Órgãos) with the potential to accumulate oil from xylose, the main pentose sugar found in lignocellulosic biomass. From the 126 isolates, two were selected based on their lipid contents. They were taxonomically identified as Papiliotrema laurentii (UFV-1 and UFV-2). Of the two, P. laurentii UFV-1 was selected as the best lipid producer. Under unoptimized conditions, lipid production by P. laurentii UFV-1 was higher in glucose than in xylose. To improve its lipid production from xylose, we applied response surface methodology (RSM) with a face-centered central composite design (CCF). We evaluated the effects of agitation rate, initial cell biomass (OD600), carbon/nitrogen ratio (C/N ratio) and pH on lipid production. P. laurentii UFV-1 recorded the highest lipid content, 63.5% (w/w) of the cell dry mass, under the following conditions: C/N ratio = 100:1, pH value = 7.0, initial OD600 = 0.8 and agitation = 300 rpm. Under these optimized conditions, biomass, lipid titer and volumetric lipid productivity were 9.31 g/L, 5.90 g/L and 0.082 g/L.h, respectively. Additionally, we determined the fatty acid composition of P. laurentii UFV-1 as follows: C14:0 (0.5%), C16:0 (28.4-29.4%), C16:1 (0.2%), C18:0 (9.5-11%), C18:1 (58.6-60.5%), and C20:0 (0.7-0.8%). Based on this composition, the predicted properties of biodiesel showed that P. laurentii UFV-1 oil is suitable for use as feedstock in biodiesel production.

Development of microemulsion of tamsulosin and dutasteride for benign prostatic hyperplasia therapy.

Benign prostatic hyperplasia (BPH) is a condition characterized by a benign enlargement of the prostate that interferes with the normal flow of urine. This disease is treated with the oral administration of combination therapy comprising α-blockers (tamsulosin) and 5α-reductase inhibitors (dutasteride). However, these compounds have low bioavailability. Thus, transdermal microemulsions aimed at promoting permeation and efficient targeted drug delivery through the skin are used. The objectives of this study were to obtain microemulsions of the combined doses of dutasteride and tamsulosin and evaluate their anti-hyperplastic activity in vivo. A phase diagram (4:1) was obtained for the choice of microemulsions. The microemulsions were characterized in terms of the droplet size, rheology, pH, conductivity, refractive index, in vitro release profile, and antihyperplastic effect in vivo. A method for the simultaneous quantification of drugs was developed using UV-vis spectroscopy. The microemulsions had an average size less than 116 nm, an acidic pH and low viscosity. The conductivity ranged from 6.18 to 185.2 µS/cm. The in vitro release profile was sustained for 6 h. Microemulsions promoted the reduction in the size of testosterone-dependent organs (prostate and seminal vesicles). Transdermal formulations for the treatment of BPH were obtained as a therapeutic alternative to conventional treatments.