Access to Artemisinin-Triazole Antimalarials via Organo-Click Reaction: High In Vitro/In Vivo Activity against Multi-Drug-Resistant Malaria Parasites.

Malaria is one of the most widespread diseases worldwide. Besides a growing number of people potentially threatened by malaria, the consistent emergence of resistance against established antimalarial pharmaceuticals leads to an urge toward new antimalarial drugs. Hybridization of two chemically diverse compounds into a new bioactive product is a successful concept to improve the properties of a hybrid drug relative to the parent compounds and also to overcome multidrug resistance. 1,2,3-Triazoles are a significant pharmacophore system among nitrogen-containing heterocycles with various applications, such as antiviral, antimalarial, antibacterial, and anticancer agents. Several marketed drugs possess these versatile moieties, which are used in a wide range of medical indications. While the synthesis of hybrid compounds containing a 1,2,3-triazole unit was described using Cu- and Ru-catalyzed azide-alkyne cycloaddition, an alternative metal-free pathway has never been reported for the synthesis of antimalarial hybrids. However, a metal-free pathway is a green method that allows toxic and expensive metals to be replaced with an organocatalyst. Herein, we present the synthesis of new artemisinin-triazole antimalarial hybrids via a facile Ramachary-Bressy-Wang organocatalyzed azide-carbonyl [3 + 2] cycloaddition (organo-click) reaction. The prepared new hybrid compounds are highly potent in vitro against chloroquine (CQ)-resistant and multi-drug-resistant Plasmodium falciparum strains (IC50 (Dd2) down to 2.1 nM; IC50 (K1) down to 1.8 nM) compared to CQ (IC50 (Dd2) = 165.3 nM; IC50 (K1) = 302.8 nM). Moreover, the most potent hybrid drug was more efficacious in suppressing parasitemia and extending animal survival in Plasmodium berghei-infected mice (up to 100% animal survival and up to 40 days of survival time) than the reference drug artemisinin, illustrating the potential of the hybridization concept as an alternative and powerful drug-discovery approach.

Semisynthesis of new sulfated heterorhamnan derivatives obtained from green seaweed Gayralia brasiliensis and evaluation of their anticoagulant activity.

Marine green algae produce sulfated polysaccharides with diverse structures and a wide range of biological activities. This study aimed to enhance the biotechnological potential of sulfated heterorhamnan (Gb1) from Gayralia brasiliensis by chemically modifying it for improved or new biological functions. Using controlled Smith Degradation (GBS) and O-alkylation with 3-chloropropylamine, we synthesized partially water-soluble amine derivatives. GBS modification increase sulfate groups (29.3 to 37.5 %) and α-l-rhamnose units (69.9 to 81.2 mol%), reducing xylose and glucose, compared to Gb1. The backbone featured predominantly 3- and 2-linked α-l-rhamnosyl and 2,3- linked α-l-rhamnosyl units as branching points. Infrared and NMR analyses confirmed the substitution of hydroxyl groups with aminoalkyl groups. The modified compounds, GBS-AHCs and GBS-AHK, exhibited altered anticoagulant properties. GBS-AHCs showed reduced effectiveness in the APTT assay, while GBS-AHK maintained a similar anticoagulant activity level to Gb1 and GBS. Increased nitrogen content and N-alkylation in GBS-AHCs compared to GBS-AHK may explain their structural differences. The chemical modification proposed did not enhance its anticoagulant activity, possibly due to the introduction of amino groups and a positive charge to the polymer. This characteristic presents new opportunities for investigating the potential of these polysaccharides in various biological applications, such as antimicrobial and antitumoral activities.

Semisynthesis and characterization of versatile azide intermediates using sodium alginate and its homopolymeric derivatives as starting material.

Alginate, a polyuronic biopolymer composed of mannuronic and guluronic acid units, contain hydroxyl and carboxyl groups as targeting modification sites to obtain structures with new and/or improved biological properties. The copper-catalyzed azide-alkyne cycloaddition (CuAAC) is a versatile click reaction for polymer functionalization, but it typically requires a "pre-click" modification to introduce azide or alkyne groups. Here, we described a straightforward chemical path to selectively modify alginate carboxyl groups producing versatile azido derivatives through N-acylation using 3-azydopropylamine. The resulting azide-functionalized polysaccharides underwent click chemistry to yield amino derivatives, confirmed by NMR and FTIR analyses. The 1H NMR spectrum reveals a characteristic triazole group signal at 8.15 ppm. The absence of the azide FTIR band for all amino derivatives, previously observed for the N-acylation products, indicated reaction success. Antibacterial and antioxidant assessments revealed that the initial polysaccharide lacks E. coli inhibition, while the click chemistry-derived amine products exhibit growth inhibition at 5.0 mg/mL. Lower molecular weight derivatives demonstrate superior DPPH scavenging ability, particularly amino-derivatives (24-33 % at 1.2 mg/mL). This innovative chemical pathway offers a promising strategy for developing polysaccharide structures with enhanced properties, demonstrating potential applications in various fields.

New records of Coronatella (Crustacea, Branchiopoda, Chydoridae) from Colombia with the first report of Coronatella undata and of the male of Coronatella monacantha

Abstract Biological samples obtained from a small temporary pond of northern Colombia yielded the first record Coronatella undata Sousa, Elmoor-Loureiro and Santos, 2015 and of the male of C. monacantha (Sars, 1901) for Colombia. In this study, the morphology of female of Coronatella undata and female and male of C. monacantha was described and compared to other species within the genus. C. undata was originally described from Brazil and, among the species of the Coronatella monacantha complex, seems to be closely related to C. acuticostata (Sars, 1903). C. undata shows some similarities with C. monacantha, but it can be identified by important diagnostic characters such as: 1) posterior-ventral corner of valve with two denticles, 2) seta on exopodite of trunk limb II rudimentary, 3) filter comb of trunk limb II with six setae, 4) ODL seta of trunk limb I shorter than longest seta of IDL. C. monacantha is the most reported species in the Neotropical region and the male most resemble C. paulinae Sousa, Elmoor-Loureiro & Santos, 2015 in relation to (i), length/wide of postabdomen ratio (ii) basal spine almost straight and (iii)) long basal spine reaching the mid-length of basal spine. However, they can be separated by (i) number of lateral seta on the antennule, (ii) postanal angle, (iii) position of gonopore (iv) presence of a denticle on posterior-ventral corner of valve

Resumo Amostras biológicas obtidas de uma pequena lagoa temporária do norte da Colômbia proporcionaram o primeiro registro de Coronatella undata Sousa, Elmoor-Loureiro e Santos, 2015 e do macho de Coronatella monacantha (Sars, 1901) na Colômbia. Neste estudo, foi descrita a morfologia de fêmeas de C. undata e de fêmeas e machos de C. monacantha, comparando-a com outras espécies do gênero. Coronatella undata foi descrita originalmente no Brasil e, entre as espécies do complexo C. monacantha, parece estar intimamente relacionada com Coronatella acuticostata (Sars, 1903). Coronatella undata apresenta algumas semelhanças com C. monacantha, mas pode ser identificada por seus principais caracteres, tais como: 1) ângulo posterior ventral da valva com dois dentículos; 2) cerda rudimentar no exopodito do ramo do tronco II; 3) filtro da gnatobase do apêndice torácico II com seis cerdas; 4) cerda ODL do membro do tronco I mais curta que a cerda mais longa do IDL. Coronatella monacantha é a espécie mais relatada na região neotropical, e o macho se assemelha mais a Coronatella paulinae Sousa, Elmoor-Loureiro & Santos em relação à/ao: (i) razão comprimento / largura do pós-abdômen, (ii) espinho basal quase reto e (iii) espinho basal longo com a metade do comprimento do espinho basal. No entanto, eles podem ser separados pelo/pela: (i) número de cerdas laterais na antênula, (ii) ângulo postanal, (iii) posição do gonóporo e (iv) presença de dentículo no canto ventral posterior da valva.

New records of Coronatella (Crustacea, Branchiopoda, Chydoridae) from Colombia with the first report of Coronatella undata and of the male of Coronatella monacantha / Novos registros de Coronatella (Crustacea, Branchiopoda, Chydoridae) na Colômbia com o primeiro relato de Coronatella undata e o macho de Coronatella monacantha

Biological samples obtained from a small temporary pond of northern Colombia yielded the first record Coronatella undata Sousa, Elmoor-Loureiro and Santos, 2015 and of the male of C. monacantha (Sars, 1901) for Colombia. In this study, the morphology of female of Coronatella undata and female and male of C. monacantha was described and compared to other species within the genus. C. undata was originally described from Brazil and, among the species of the Coronatella monacantha complex, seems to be closely related to C. acuticostata (Sars, 1903). C. undata shows some similarities with C. monacantha, but it can be identified by important diagnostic characters such as: 1) posterior-ventral corner of valve with two denticles, 2) seta on exopodite of trunk limb II rudimentary, 3) filter comb of trunk limb II with six setae, 4) ODL seta of trunk limb I shorter than longest seta of IDL. C. monacantha is the most reported species in the Neotropical region and the male most resemble C. paulinae Sousa, Elmoor-Loureiro & Santos, 2015 in relation to (i), length/wide of postabdomen ratio (ii) basal spine almost straight and (iii)) long basal spine reaching the mid-length of basal spine. However, they can be separated by (i) number of lateral seta on the antennule, (ii) postanal angle, (iii) position of gonopore (iv) presence of a denticle on posterior-ventral corner of valve.

Amostras biológicas obtidas de uma pequena lagoa temporária do norte da Colômbia proporcionaram o primeiro registro de Coronatella undata Sousa, Elmoor-Loureiro e Santos, 2015 e do macho de Coronatella monacantha (Sars, 1901) na Colômbia. Neste estudo, foi descrita a morfologia de fêmeas de C. undata e de fêmeas e machos de C. monacantha, comparando-a com outras espécies do gênero. Coronatella undata foi descrita originalmente no Brasil e, entre as espécies do complexo C. monacantha, parece estar intimamente relacionada com Coronatella acuticostata (Sars, 1903). Coronatella undata apresenta algumas semelhanças com C. monacantha, mas pode ser identificada por seus principais caracteres, tais como: 1) ângulo posterior ventral da valva com dois dentículos; 2) cerda rudimentar no exopodito do ramo do tronco II; 3) filtro da gnatobase do apêndice torácico II com seis cerdas; 4) cerda ODL do membro do tronco I mais curta que a cerda mais longa do IDL. Coronatella monacantha é a espécie mais relatada na região neotropical, e o macho se assemelha mais a Coronatella paulinae Sousa, Elmoor-Loureiro & Santos em relação à/ao: (i) razão comprimento / largura do pós-abdômen, (ii) espinho basal quase reto e (iii) espinho basal longo com a metade do comprimento do espinho basal. No entanto, eles podem ser separados pelo/pela: (i) número de cerdas laterais na antênula, (ii) ângulo postanal, (iii) posição do gonóporo e (iv) presença de dentículo no canto ventral posterior da valva.

Autofluorescent antimalarials by hybridization of artemisinin and coumarin: in vitro/in vivo studies and live-cell imaging.

Malaria is one of our planet's most widespread and deadliest diseases, and there is an ever-consistent need for new and improved pharmaceuticals. Natural products have been an essential source of hit and lead compounds for drug discovery. Antimalarial drug artemisinin (ART), a highly effective natural product, is an enantiopure sesquiterpene lactone and occurs in Artemisia annua L. The development of improved antimalarial drugs, which are highly potent and at the same time inherently fluorescent is particularly favorable and highly desirable since they can be used for live-cell imaging, avoiding the requirement of the drug's linkage to an external fluorescent label. Herein, we present the first antimalarial autofluorescent artemisinin-coumarin hybrids with high fluorescence quantum yields of up to 0.94 and exhibiting excellent activity in vitro against CQ-resistant and multidrug-resistant P. falciparum strains (IC50 (Dd2) down to 0.5 nM; IC50 (K1) down to 0.3 nM) compared to reference drugs CQ (IC50 (Dd2) 165.3 nM; IC50 (K1) 302.8 nM) and artemisinin (IC50 (Dd2) 11.3 nM; IC50 (K1) 5.4 nM). Furthermore, a clear correlation between in vitro potency and in vivo efficacy of antimalarial autofluorescent hybrids was demonstrated. Moreover, deliberately designed autofluorescent artemisinin-coumarin hybrids, were not only able to overcome drug resistance, they were also of high value in investigating their mode of action via time-dependent imaging resolution in living P. falciparum-infected red blood cells.

Hot-wiring dynein-2 establishes roles for IFT-A in retrograde train assembly and motility.

Intraflagellar transport (IFT) trains, built around IFT-A and IFT-B complexes, are carried by opposing motors to import and export ciliary cargo. While transported by kinesin-2 on anterograde IFT trains, the dynein-2 motor adopts an autoinhibitory conformation until it needs to be activated at the ciliary tip to power retrograde IFT. Growing evidence has linked the IFT-A complex to retrograde IFT; however, its roles in this process remain unknown. Here, we use CRISPR-Cas9-mediated genome editing to disable the dynein-2 autoinhibition mechanism in Caenorhabditis elegans and assess its impact on IFT with high-resolution live imaging and photobleaching analyses. Remarkably, this dynein-2 "hot-wiring" approach reignites retrograde motility inside IFT-A-deficient cilia without triggering tug-of-war events. In addition to providing functional evidence that multiple mechanisms maintain dynein-2 inhibited during anterograde IFT, our data establish key roles for IFT-A in mediating motor-train coupling during IFT turnaround, promoting retrograde IFT initiation, and modulating dynein-2 retrograde motility.

Microbiological evaluation of homemade mayonnaise and self-serve acai sold in Araguaína, Tocantins.

Foodborne diseases are common illnesses caused by the consumption of food contaminated with microorganisms, such as viruses, fungi, bacteria, and protozoa. Every year, 600 million people become ill and 420,000 people die as a result of consuming contaminated food. Therefore, food safety is an important issue. In this study, samples of homemade spiced mayonnaise and self-serve acai sold in the city of Araguaína, Tocantins, Brazil were analyzed for microbiological contaminants. Acai was collected from 10 stores, one sample from each store, and tested for mold, yeast, and coliforms, as well as coliform identification and total and thermotolerant coliform counts. Mayonnaise was collected from 20 snack bars, one sample from each. These samples were inoculated on MacConkey and Salmonella Shigella agar plates, and the plates were analyzed for growth. Salmonella spp. were detected in some Mayonnaise samples, and coliforms were detected in all acai samples; 60% of samples had thermotolerant coliforms, and only 40% were within the limits established by ANVISA. The collected samples of mayonnaise and acai were contaminated with molds and yeasts above the established limit of 103 CFU/g. Thus, the analyzed mayonnaise and acai samples were contaminated and unfit for consumption, demonstrating the importance of hygienic-sanitary measures in food handling.

Does the "Entourage Effect" in Cannabinoids Exist? A Narrative Scoping Review.

Background: The concept of an "entourage" effect in the cannabis and cannabinoids' field was first introduced in the late 1990s, during a period when most research on medical cannabinoids focused on the effects of isolated cannabinoids, such as cannabidiol and Δ9-tetrahydrocannabinol. Over the past decade, however, with the increased understanding of the endocannabinoid system, the discovery of other phytocannabinoids and their potential therapeutic uses, the term has gained widespread use in scientific reviews and marketing campaigns. Objective: Critically review the application of the term "entourage effect (EE)" in the literature and its endorsement by certain sectors of the cannabis market. Also, explore the perspectives for further interpretation and elaboration of the term based on current evidence, aiming to contribute to a more nuanced understanding of the concept and its implications for cannabinoid-based medicine. Methods: A comprehensive review of the literature was conducted to evaluate the current state of knowledge regarding the entourage effect. Relevant studies and scientific reviews were analyzed to assess the evidence of clinical efficacy and safety, as well as the regulation of cannabinoid-containing product production. Results: The EE is now recognized as a synergistic phenomenon in which multiple components of cannabis interact to modulate the therapeutic actions of the plant. However, the literature provides limited evidence to support it as a stable and predictable phenomenon. Hence, there is also limited evidence to support clinical efficacy, safety, and appropriate regulation for cannabinoid-containing products based on a "entourage" hypothesis. Conclusion: The EE has significant implications for the medical use of cannabinoid-containing products and their prescription. Nevertheless, a critical evaluation of the term's application is necessary. Further research and evidence are needed to establish the clinical efficacy, safety, and regulatory framework for these products. It's crucial that regulators, the pharmaceutical industry, the media, and health care providers exercise caution and avoid prematurely promoting the entourage effect hypothesis as a scientific proven phenomenon for cannabinoids and other cannabis-derived compound combinations.

Direct oral anticoagulants vs vitamin K antagonist on dementia risk in atrial fibrillation: systematic review with meta-analysis.

Oral anticoagulation significantly reduces the incidence of dementia in atrial fibrillation patients. However, this protective effect has not been compared between Direct Oral Anticoagulants (DOAC) and Vitamin K antagonists' anticoagulants (VKA). We conducted an electronic search for potentially eligible studies through the bibliographic databases MEDLINE, CENTRAL, ClinicalTrials.gov, EMBASE and Web of Science. The outcome of interest was dementia. Random-effects meta-analysis was performed. Nine observational studies were included and 1,175,609 atrial fibrillation patients were enrolled. DOAC therapy was associated with a significant reduction when compared with patients under VKA therapy (hazard ratio 0.89; 95% confidence interval 0.80-0.99). The grade of confidence of our results was very low due to the risk of bias. DOAC therapy is associated with a significant decrease in the risk of dementia when compared with VKA therapy. However, the low certainty of the evidence along with the paucityof clinical trials dedicated to answering this important question underscores a need for global clinical research initiatives.

Antimalarial Agents Derived from Metal-Amodiaquine Complexes with Activity in Multiple Stages of the Plasmodium Life Cycle.

Malaria is the one of the deadliest infectious diseases worldwide. Chemically, quinolines are excellent ligands for metal coordination and are deployed as drugs for malaria treatment. There is a growing body of evidence indicating that metal complexes can be conjugated with antimalarial quinolines to be used as chemical tools to overcome the disadvantages of quinolines, improving their bioactive speciation, cellular distribution, and subsequently broadening the spectrum of activity to multiple stages of the complex Plasmodium life cycle. In this study, four novel complexes of ruthenium(II)- and gold(I)-containing amodiaquine (AQ) were synthesized, and a careful chemical characterization revealed the precise coordination site of AQ to the metals. Their speciation in solution was investigated, demonstrating the stability of the quinoline-metal bond. RuII - and AuI -AQ complexes were demonstrated to be potent and efficacious in inhibiting parasite growth in multiple stages of the Plasmodium life cycle as assayed in vitro and in vivo. These properties could be attributed to the ability of the metal-AQ complexes to reproduce the suppression of heme detoxification induced by AQ, while also inhibiting other processes in the parasite life cycle; this can be attributed to the action of the metallic species. Altogether, these findings indicate that metal coordination with antimalarial quinolines is a potential chemical tool for drug design and discovery in malaria and other infectious diseases susceptible to quinoline treatment.

Prediction of enzymatic function with high efficiency and a reduced number of features using genetic algorithm.

The post-genomic era has raised a growing demand for efficient procedures to identify protein functions, which can be accomplished by applying machine learning to the characteristics set extracted from the protein. This approach is feature-based and has been the focus of several works in bioinformatics. In this work, we investigated the characteristics of proteins, representing the primary, secondary, tertiary, and quaternary structures of the protein, that improve the model's quality by applying dimensionality reduction techniques and using the Support Vector Machine classifier for predicting the enzymes' classes. During the investigation, two approaches were evaluated: feature extraction/transformation, which was performed using the statistical technique Factor Analysis, and feature selection methods. For feature selection, we proposed an approach based on a genetic algorithm to face the optimization conflict between the simplicity and reliability of an ideal representation of the characteristics of the enzymes and also compared and employed other methods for this purpose. The best result was accomplished using a feature subset generated by our implementation of a multi-objective genetic algorithm enriched with features that this work identified as relevant to represent the enzymes. This subset representation reduced the dataset by about 87% and reached 85.78% of F-measure performance, improving the overall quality of the model classification. In addition, we verified in this work a subset addressed with only 28 features out of a total of 424 that reached a performance above 80% of F-measure for four of the six evaluated classes, showing that satisfactory classification performance can be achieved with a reduced number of enzymes's characteristics. The datasets and implementations are openly available.

Characterisation and long-term follow-up of children with Brugada syndrome: experience from a tertiary paediatric referral centre.

AIMS: Brugada syndrome is an inherited condition, which typically presents in young adults. It can also be diagnosed in children, but data in this group remain scarce. This study aims to describe the clinical features, management, and follow-up of children with personal or family history of Brugada syndrome. METHODS: Retrospective study of consecutive patients with Brugada history followed up in a tertiary paediatric referral centre between 2009 and 2021. Patients were assessed according to the phenotype: positive (with variable genotype) or negative (with positive genotype). RESULTS: Thirty patients were included (mean age at diagnosis 7 ± 6 years, 53% male). Within the positive phenotype (n = 16), 81% were male, and 88% had spontaneous type 1 ECG pattern. A genetic test was performed in 88% and was positive in 57%. Fourteen patients had a negative phenotype-positive genotype, 79% female, all diagnosed during family screening; 43% mentioned family history of sudden cardiac death. Although most of the patients were asymptomatic, the prevalence of rhythm/conduction disturbances was not negligible, particularly if a positive phenotype. No clinically significant events were reported in the negative phenotype patients. Three patients were hospitalised due to an arrhythmic cause, all in patients with a positive phenotype. CONCLUSION: In our study, the documentation of rhythm and conduction disturbances was not infrequent, especially in patients with a positive phenotype. Despite the significant family history, phenotype negative patients had no relevant events during follow-up. Nevertheless, the management of these patients is not clear cut, and a personalised therapeutic strategy with close follow-up is essential.

Proximal femur geometry: a major predictor of proximal femur fracture subtypes.

INTRODUCTION: Proximal femur geometry (PFG) represents an important risk factor for the occurrence of hip fractures. There are currently few studies regarding the correlation between PFG and the occurrence of a specific fracture subtype, and those that exist have small cohorts and present with different methodologies and contradictory results. Therefore, there is no consensus in the literature regarding this topic. The present study aimed to establish the contribution of the PFG in the occurrence of different subtypes of proximal femur fractures (PFF): intertrochanteric, neck and subtrochanteric. METHODS: Analysis of 1022 plain anteroposterior pelvic radiographs of patients consecutively admitted to the emergency room of a Level 1 Trauma Centre between 2013 and 2019 after low energy trauma who presented with PFF and underwent surgical treatment. Patients were analysed considering age, gender and subtype of PFF (intertrochanteric, neck or subtrochanteric). Radiological parameters including cervicodiaphyseal angle (CDA), horizontal offset (HO), femoral neck width (FNW), femoral neck length (FNL), great trochanter-pubic symphysis distance (GTPSD), acetabular teardrop distance (ATD) and width of the intertrochanteric region (WIR) were measured and compared between the different subtypes of fractures (7154 measurements). Statistical analysis was conducted recurring to absolute measurements and measurements ratios. The correlation was assessed using t-test. RESULTS: There were statistically significant differences in proximal femur geometry between the different subtypes of fractures. Patients presenting with femoral neck fractures had greater CDA (132.5 ± 6.9 vs. 130.0 ± 7.3; p < 0.001) and lower HO (45.8 ± 7.4 vs. 49.0 ± 8.0; p < 0.001), HO/ATD (0.34 ± 0.068 vs. 0.37 ± 0.072; p < 0.001) and HO/GTPSD (0.26 ± 0.049 vs. 0.28 ± 0.039; p < 0.001) than patients with intertrochanteric/subtrochanteric fractures. CONCLUSIONS: PFG represents an important contributor to the occurrence of different fracture subtypes. Femoral neck fractures are associated with greater CDA and lower HO, HO/ATD and HO/GTPSD when compared to intertrochanteric or subtrochanteric fractures.

Adverse Effects of Oral Cannabidiol: An Updated Systematic Review of Randomized Controlled Trials (2020-2022).

(1) Background: With the massive demand for the use and commercialization of medicinal cannabidiol (CBD) products, new randomized clinical trials (RCTs) are being published worldwide, with a constant need for safety and efficacy evaluation. (2) Methods: We performed an update on a systematic review published in 2020 that focused on analyzing the serious adverse effects (SAEs) of CBD in RCTs and its possible association with drug interactions. We also updated the report of the most prevalent CBD adverse effects (AEs). We systematically searched EMBASE, MEDLINE/PubMed, and Web of Science without language restriction for RCTs that reported adverse effects after repeated oral CBD administration for at least one week in healthy volunteers or clinical samples published from January 2019 to May 2022. The included studies were assessed for methodological quality by the Quality Assessment of Controlled Intervention Studies tool. The present review is registered on PROSPERO, number CRD42022334399. (3) Results: Twelve studies involving 745 randomized subjects analyzed were included (range 1.1-56.8 y). A total of 454 participants used CBD in the trials. The most common AEs of CBD were mild or moderate and included gastrointestinal symptoms (59.5%), somnolence (16.7%), loss of appetite (16.5%), and hypertransaminasemia (ALT/AST) (12.8%). Serious adverse effects include mainly hypertransaminasemia with serum levels elevations greater than three times the upper limit of the normal (6.4%), seizures (1.3%), and rash (1.1%). All SAEs reported in the studies were observed on CBD as an add-on therapy to anticonvulsant medications, including clobazam and valproate. (4) Conclusion: Recent RCTs involving oral CBD administration for at least a week suggest that CBD has a good safety and tolerability profile, confirming previous data. However, it can potentially interact with other drugs and its use should be monitored, especially at the beginning of treatment.

Associação entre temperamento e o uso de práticas da medicina alternativa e complementar / Association between temperament and the use of complementary and alternative medicine practices / Asociación entre temperamento y uso de prácticas de medicina alternativa y complementaria

Trata-se de um estudo brasileiro, transversal, mediado pela Internet com o objetivo de descrever como diferenças temperamentais associam-se ao uso de oito práticas de medicina alternativa e complementar (MAC): ioga, meditação, reiki, acupuntura, massagem, tai chi chuan, homeopatia e floral. A amostra foi composta por 22.415 indivíduos, sendo 69,5% mulheres, com idade média de 28,8 anos (DP = 9,1). As práticas mais utilizadas foram massagem e ioga e as variáveis sexo, idade, renda e diagnóstico psicopatológico ao longo da vida associaram-se a todas as práticas, exceto com tai chi chuan. Análise inferencial se baseou em modelo de regressão logística e os resultados foram calculados com base na razão de chances com intervalo de confiança de 95%. Observou-se que manifestações adaptativas de traços e de tipos psicológicos, associaram-se a maiores chances de praticar MAC. Resultados sugerem que perfis com maior regulação emocional tendem a utilizar mais frequentemente MAC e, possivelmente, obter benefícios. (AU)

The present study is a cross-sectional web-based survey conducted in Brazil aiming to describe how individual differences in temperament traits and types could predict the use of the following eight categories of complementary and alternative medicine (CAM): yoga, meditation, reiki, acupuncture, massage, tai chi chuan, homeopathy, and flower remedies. The sample consisted of 22,415 individuals, 69.5% of whom were women, with a mean age of 28.8 years (SD= 9.1). The most commonly used practices were massage and yoga and the variables sex, age, income, and psychopathological diagnosis throughout life were associated with all practices, except tai chi chuan. The inferential analysis relied on logistic regressions and results were calculated based on the odd ratios with 95% confidence intervals. Adaptive manifestations of psychological traits and types were associated with greater use of complementary and alternative medicine practices. Results suggested that profiles with greater emotional regulation tend to use CAM more frequently and possibly obtain benefits. (AU)

Se trata de un estudio brasileño, transversal, mediado por Internet, con el objetivo de describir cómo las diferencias temperamentales se asocian con el uso de ocho prácticas de medicina alternativa y complementaria (MAC): yoga, meditación, reiki, acupuntura, masaje, tai chi chuan, homeopatía y floral. La muestra estuvo compuesta por 22.415 individuos, de los cuales 69,5 % eran mujeres, con una edad media de 28,8 años (DS= 9,1). Las prácticas más utilizadas fueron el masaje y el yoga, y las variables sexo, edad, renta y diagnóstico psicopatológico a lo largo de la vida se asociaron a todas las prácticas, excepto al tai chi chuan. El análisis inferencial se basó en un modelo de regresión logística y los resultados se calcularon con base en la odds ratio con un intervalo de confianza del 95 %. Se observó que las manifestaciones adaptativas de rasgos y tipos psicológicos se asociaron con mayores posibilidades de practicar MAC. Los resultados sugieren que los perfiles con mayor regulación emocional tienden a usar MAC con mayor frecuencia y, posiblemente, obtienen beneficios. (AU)

Antimalarial Pyrido[1,2-a]benzimidazoles Exert Strong Parasiticidal Effects by Achieving High Cellular Uptake and Suppressing Heme Detoxification.

Pyrido[1,2-a]benzimidazoles (PBIs) are synthetic antiplasmodium agents with potent activity and are structurally differentiated from benchmark antimalarials. To study the cellular uptake of PBIs and understand the underlying phenotype of their antiplasmodium activity, their antiparasitic activities were examined in chloroquine (CQ)-susceptible and CQ-resistant Plasmodium falciparumin vitro. Moreover, drug uptake and heme detoxification suppression were examined in Plasmodium berghei-infected mice. The in vitro potency of PBIs is comparable to most 4-aminoquinolines. They have a speed of action in vitro that is superior to that of atovaquone and an ability to kill rings and trophozoites. The antiparasitic effects observed for the PBIs in cell culture and in infected mice are similar in terms of potency and efficacy and are comparable to CQ but with the added advantage of demonstrating equipotency against both CQ susceptible and resistant parasite strains. PBIs have a high rate of uptake by parasite cells and, conversely, a limited rate of uptake by host cells. The mechanism of cellular uptake of the PBIs differs from the ion-trap mechanism typically observed for 4-aminoquinolines, although they share key structural features. The high cellular uptake, attractive parasiticidal profile, and susceptibility of resistant strains to PBIs are desirable characteristics for new antimalarial agents.

Dynamics of changes in the breed composition of pastoral and agro-pastoral cattle herds in Benin: implications for the sustainable use of indigenous breeds.

Data for concretely analyzing current trends regarding breed composition of cattle herds at the national scale and the logic behind it are lacking in Benin. This study aimed to investigate the factors affecting the dynamics of breed composition in traditional Beninese cattle herds. In this regard, the main reasons for acquiring new breeds by herders and management strategies for animal genetic diversity in herds were targeted. Using a semi-structured questionnaire, a total of 753 cattle herds were surveyed in six pastoral communities along a north-south transect in Benin. Data collection included original breed composition of the herds (at their installation), cattle breeds introduced in the last five years, reasons for introducing new breeds, herders' breed preferences, and perceptions concerning productive and adaptive traits of the existing breeds in the study area. Descriptive analyses of herd composition revealed breed redistribution across the country with the increasing introduction of zebu in the southern region of the country. A high percentage of nondescript crossbreeds was associated with herders' willingness to improve both milk and meat production. In this regard, the analysis of herders' perceptions using the Friedman test ranked most zebu cattle breeds as the most productive. In contrast, the taurine breeds were highly ranked by herders for their adaptive features. This study confirms that herders' breed choices fit their production objectives. In addition, strategies for effectively and efficiently managing genetic diversity within herds are expected to increase animal productivity while conserving adaptive and special traits in local breeds. The effectiveness of herders' knowledge of local cattle breeds as well as their experience may increase the success of such strategies and facilitate their adoption.