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PURPOSE: Pulmonary arterial hypertension (PAH) is a progressive disease with a poor prognosis, and its management should be grounded in well-developed clinical practice guidelines (CPG). Thus, we critically assess the methodological quality of the available CPG for pharmacological treatments for PAH. METHODS: A systematic review (CRD42023387168) was performed in PubMed, Cochrane, Embase, and Tripdatabase (Jan-2023). Eligible records were appraised by four reviewers using the Appraisal of Guidelines, Research, and Evaluation Collaboration tool (AGREE II) and the complementary tool for assessing recommendations' quality and certainty, AGREE REX. Descriptive statistics were used to summarize the data. RESULTS: Overall, 31 guidelines, mainly authored by professional societies (90%), targeting only physicians as primary users (84%), were identified. Guidelines presented a moderate overall quality (scores of 63% and 51% in AGREE II and AGREE REX, respectively), with a few domains showing slight improvements over the years. AGREE II "Scope and Purpose" (94%) and "Presentation Clarity" (99%) domains obtained the highest scores. The items related to "Stakeholder involvement," "Editorial independence," and "Clinical applicability" (AGREE REX) were fairly reported. Conversely, CPG lacks rigor in development (32% score, AGREE II), scarcely discusses the role of stakeholders, and provides deficient data on the implementation of recommendations (scores of 35% and 46% in AGREE II and AGREE REX, respectively). No differences in the quality of guidelines published by different developers or countries were observed (p > 0.05). CONCLUSION: Methodological weaknesses are common among guidelines addressing PAH treatment, especially regarding scientific rigor, stakeholders' values and preferences, and facilitators and barriers to implementability. Particular attention should be given to developing future guidelines.

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BACKGROUND: Clinical practice guidelines (CPGs) are statements to assist practitioners and stakeholders in decisions about healthcare. Low methodological quality guidelines may prejudice decision-making and negatively affect clinical outcomes in non-communicable diseases, such as cardiovascular diseases worsted by poor lipid management. We appraised the quality of CPGs on dyslipidemia management and synthesized the most updated pharmacological recommendations. METHODS: A systematic review following international recommendations was performed. Searches to retrieve CPG on pharmacological treatments in adults with dyslipidaemia were conducted in PubMed, Scopus, and Trip databases. Eligible articles were assessed using AGREE II (methodological quality) and AGREE-REX (recommendation excellence) tools. Descriptive statistics were used to summarize data. The most updated guidelines (published after 2019) had their recommendations qualitatively synthesized in an exploratory analysis. RESULTS: Overall, 66 guidelines authored by professional societies (75%) and targeting clinicians as primary users were selected. The AGREE II domains Scope and Purpose (89%) and Clarity of Presentation (97%), and the AGREE-REX item Clinical Applicability (77.0%) obtained the highest values. Conversely, guidelines were methodologically poorly performed/documented (46%) and scarcely provided data on the implementability of practical recommendations (38%). Recommendations on pharmacological treatments are overall similar, with slight differences concerning the use of supplements and the availability of drugs. CONCLUSION: High-quality dyslipidaemia CPG, especially outside North America and Europe, and strictly addressing evidence synthesis, appraisal, and recommendations are needed, especially to guide primary care decisions. CPG developers should consider stakeholders' values and preferences and adapt existing statements to individual populations and healthcare systems to ensure successful implementation interventions.

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AIMS: To map the literature on oral ciprofloxacin's pharmacokinetics and its implications for dose adjustments in specific populations. METHODS: A scoping review was performed according to the Cochrane Collaboration and JBI and reported following the PRISMA-ScR. Systematic searches on electronic databases were conducted to integrate the current evidence on ciprofloxacin's pharmacokinetics. The quality of the included studies was assessed using ClinPK's checklist. RESULTS: The search yielded 55 relevant studies. Within the traditional pharmacokinetics studies (n = 46), 86 profiles were examined (72 involving healthy patients and 14 with various clinical conditions). Oral ciprofloxacin's pharmacokinetics were influenced by covariates such as drug interactions (ferrous ions, calcium carbonate, diclofenac and itraconazole), food interactions (calcium-rich foods), elderly populations and renal impairment. Notably, variability in pharmacokinetic parameters existed among subjects, regardless of their health status, underscoring the need for comprehensive population descriptions. Population pharmacokinetic studies (n = 9) identified significant covariates for hospitalized patients, such as creatinine clearance, plasma bicarbonate, estimated glomerular filtration rate, renal replacement therapy, age, sex, total bilirubin, fat-free mass, dietary factors in renal disease, rifampicin for clearance models and body weight for volume of distribution models. Most pharmacokinetic/pharmacodynamic assessments concluded that 1200 mg/day provides a high probability of target attainment for bacteria with minimum inhibitory concentration <0.5 mg L-1 , aiming for an area under the curve for 24 h/minimum inhibitory concentration >125 h. CONCLUSIONS: This study offers a comprehensive overview regarding oral ciprofloxacin's pharmacokinetics across various health conditions. It highlights the complexities of ciprofloxacin's pharmacokinetics, emphasizing the importance of considering multiple factors in dose adjustments.

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Abstract The Brazilian native species Cestrum intermedium, known as mata-boi, induces hepatotoxicity and death when ingested by cattle. While most studies on this species focus on toxicological features, our study is the first to describe the anatomy and in vitro biological activities of Cestrum intermedium. We investigated adult leaves and stems by histochemistry, described their anatomy, performed physical-chemical analysis, determined in vitro antioxidant and antimicrobial activities, and identified secondary metabolites. A few noteworthy anatomical features were the anomocytic stomata on the abaxial surface and the absence of trichomes, in addition to the circular shaped petiole with two projections on the adaxial surface. Histochemical analysis showed chemical markers such as alkaloids, usually reported as toxic, and terpenoids. Potassium nitrate (ATR-FTIR) and lupeol palmitate (NMR) were detected on the crude stem extract. Thermogravimetric and physical-chemical analysis provided fingerprint parameters for the species. Minimal Inhibitory Concentration (MIC) assay revealed that Staphylococcus aureus, Staphylococcus epidermidis, and Candida albicans were weakly inhibited by extract samples. Chloroform and ethyl acetate fractions presented high phenolic content, which resulted in in vitro antioxidant activity. These novel features expand the knowledge about this species, considering that previous studies mainly focused on its toxicity. Our study also provided characteristics that may help in avoiding misidentification between Cestrum members, especially when taxonomic keys cannot be employed, as in the absence of flowers and fruits.

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Fructooligosaccharides are catalyzed by fructofuranosidase enzyme, produced by many microorganisms. However, in order to achieve a more profitable, low time-consuming process with lower cost, researchers have sought alternatives. This study aimed to select and identify yeasts able to produce fructooligosaccharides and evaluate the influence of pH and temperature on their synthesis. Yeast suspensions, solutions of 500 g L-1 sucrose and three values of pH (4.5, 5.5, and 6.5) and temperature (40, 50, and 60ºC) were tested. Yeast species were identified by molecular techniques. Among 141 yeast isolates from grapes, 65 were able to synthesize fructooligosaccharides. The maximum concentration of fructooligosaccharides was 4.8% (w v-1), and Saccharomyces cerevisiae 222 produced 1-kestose and nystose.(AU)

Fruto-oligossacarídeos são catalisados pelas enzimas β–fructofuranosidase, produzida por muitos micro-organismos. No entanto, para obter processos mais rentáveis, de menor custo e tempo, pesquisadores têm procurado alternativas. Este trabalho tem objetivo de selecionar e identificar leveduras capazes de produzir fruto-oligossacarídeos e avaliar a influência do pH e da temperatura na sua síntese. Suspensões de leveduras, soluções de sacarose de 500 g L-1 e três valores de pH (4,5, 5,5 e 6,5) e de temperaturas de (40, 50 e 60ºC) foram utilizados. As espécies de leveduras foram identificadas por técnicas moleculares. De 141 isolados de leveduras de uvas, 65 foram capazes de sintetizar fruto-oligossacarídeos. A concentração máxima de fruto-oligossacarídeos foi de 4,8% (p v-1), e a levedura Saccharomyces cerevisiae 222 produziu 1-cestose e nistose.(AU)

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Fructooligosaccharides are catalyzed by ß­fructofuranosidase enzyme, produced by many microorganisms. However, in order to achieve a more profitable, low time -consuming process with lower cost, researchers have sought alternatives. This study aimed to select and identify yeasts able to produce fructooligosaccharides and evaluate the influence of pH and temperature on their synthesis. Yeast suspensions, solutions of 500 g L-1 sucrose and three values of pH (4.5, 5.5, and 6.5) and temperature (40, 50, and 60ºC) were tested. Yeast species were identified by molecular techniques. Among 141 yeast isolates from grapes, 65 were able to synthesize fructooligosaccharides. The maximum concentration of fructooligosaccharides was 4.8% (w v-1), and Saccharomyces cerevisiae 222 produced 1-kestose and nystose.

Fruto-oligossacarídeos são catalisados pelas enzimas ß­fructofuranosidase, produzida por muitos micro -organismos. No entanto, para obter processos mais rentáveis, de menor custo e tempo, pesquisadores têm procurado alternativas. Este trabalho tem objetivo de selecionar e identificar leveduras capazes de produzir fruto-oligossacarídeos e avaliar a influência do pH e da temperatura na sua síntese. Suspensões de leveduras, soluções de sacarose de 500 g L- 1 e três valores de pH (4,5, 5,5 e 6,5) e de temperaturas de (40, 50 e 60ºC) foram utilizados. As espécies de leveduras foram identificadas por técnicas moleculares. De 141 isolados de leveduras de uvas, 65 foram capazes de sintetizar fruto-oligossacarídeos. A concentração máxima de fruto-oligossacarídeos foi de 4,8% (p v-1), e a levedura Saccharomyces cerevisiae 222 produziu 1-cestose e nistose.

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The transformation of grape must into wine is a complex microbiological process and is the product of the combined action of several genera and species of yeasts, dominated in the intermediate and final stages of fermentation by an alcohol-tolerant Saccharomyces sp. Current assay characterizes 42 autochthonous yeasts, isolated from the state of Paraná, southern Brazil, according to the following oenological properties: H2S production, fermentation rate, flocculation capacity, and killer phenotype (killer, sensitive and neutral characteristics). Current analysis is the first to evaluate killer phenotype in yeasts isolated from the State of Paraná, Brazil. With regard to their oenological traits, the yeasts evaluated were not suitable for winemaking and suggested that, depending on the harvest, the winemakers may face problems during the spontaneous wine production process.

A transformação do mosto de uva em vinho é um processo microbiológico complexo, resultado da ação combinada de diferentes gêneros e espécies de leveduras, no qual, entretanto, prevalece uma levedura, Saccharomyces sp. álcool-tolerante nos estágios intermediário e final da fermentação alcoólica. O objetivo deste trabalho foi caracterizar 42 leveduras autóctones isoladas da região sul do Brasil (Estado do Paraná) de acordo com as seguintes características enológicas: produção de H2S, taxa de fermentação, capacidade de floculação e fenótipo killer (características killer, sensível e neutra). Este estudo é o primeiro a avaliar fenótipo killer em leveduras isoladas do estado do Paraná. Com relação às características enológicas, as leveduras avaliadas não se mostraram promissoras para vinificação, sugerindo que, conforme a safra, o vinicultor pode enfrentar problemas durante o processo de fermentação espontânea das uvas para a elaboração de vinho.

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The transformation of grape must into wine is a complex microbiological process and is the product of the combined action of several genera and species of yeasts, dominated in the intermediate and final stages of fermentation by an alcohol-tolerant Saccharomyces sp. Current assay characterizes 42 autochthonous yeasts, isolated from the state of Paraná, southern Brazil, according to the following oenological properties: H2S production, fermentation rate, flocculation capacity, and killer phenotype (killer, sensitive and neutral characteristics). Current analysis is the first to evaluate killer phenotype in yeasts isolated from the State of Paraná, Brazil. With regard to their oenological traits, the yeasts evaluated were not suitable for winemaking and suggested that, depending on the harvest, the winemakers may face problems during the spontaneous wine production process.(AU)

A transformação do mosto de uva em vinho é um processo microbiológico complexo, resultado da ação combinada de diferentes gêneros e espécies de leveduras, no qual, entretanto, prevalece uma levedura, Saccharomyces sp. álcool-tolerante nos estágios intermediário e final da fermentação alcoólica. O objetivo deste trabalho foi caracterizar 42 leveduras autóctones isoladas da região sul do Brasil (Estado do Paraná) de acordo com as seguintes características enológicas: produção de H2S, taxa de fermentação, capacidade de floculação e fenótipo killer (características killer, sensível e neutra). Este estudo é o primeiro a avaliar fenótipo killer em leveduras isoladas do estado do Paraná. Com relação às características enológicas, as leveduras avaliadas não se mostraram promissoras para vinificação, sugerindo que, conforme a safra, o vinicultor pode enfrentar problemas durante o processo de fermentação espontânea das uvas para a elaboração de vinho.(AU)

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