Biological and metabolomics-guided isolation of tetrahydrofurofuran lignan from Croton spp. with antiproliferative activity against human melanoma cell line.

The Croton genus (Euphorbiaceae) is recognized as a promising source for identifying bioactive compounds with antiproliferative activity. However, knowledge on the chemical composition and activity of Croton floribundus, Croton echinocarpus, and Croton zehntneri is limited. Thus, this study aimed to investigate the antiproliferative activity of these species on cells derived from tumoral breast, lung, and melanoma cells, and primary fibroblasts derived from human skin. Metabolomic strategies were applied via ultra-performance liquid chromatography coupled with high-resolution mass spectrometry and multivariate statistical analysis to target the main active compound. The C. floribundus leaf extract exhibited the highest activity, with an IC50 value lower than that of the reference drug - temozolomide - in the most responsive cell line - SK-MEL-147 - and in all the evaluated melanoma cell lines (SK-MEL-147, CHL-1 and WM-1366). Four tetrahydrofurofuran lignans were isolated for the first time from the most promising fraction of the C. floribundus extract. According to the metabolomic and multivariate statistical analyses, the isolated lignan epi-yangambin constituted the main antiproliferative compound against SK-MEL-147; furthermore, it exhibited selective antiproliferative activity for this cell line (IC50 = 13.09 µg/mL and selectivity index = 3.82; temozolomide, IC50 = 121.50 µg/mL) due to, at least in part, its ability to inhibit cell cycle progression at G2/M. This is especially relevant considering the high resistance of melanoma cells to available drugs. Thus, epi-yangambin can serve as a prototype for further antiproliferative investigations.

Effects of geographical origin and post-harvesting processing on the bioactive compounds and sensory quality of Brazilian specialty coffee beans.

Specialty coffee beans are those produced, processed, and characterized following the highest quality standards, toward delivering a superior final product. Environmental, climatic, genetic, and processing factors greatly influence the green beans' chemical profile, which reflects on the quality and pricing. The present study focuses on the assessment of eight major health-beneficial bioactive compounds in green coffee beans aiming to underscore the influence of the geographical origin and post-harvesting processing on the quality of the final beverage. For that, we examined the non-volatile chemical profile of specialty Coffea arabica beans from Minas Gerais state, Brazil. It included samples from Cerrado (Savannah), and Matas de Minas and Sul de Minas (Atlantic Forest) regions, produced by two post-harvesting processing practices. Trigonelline, theobromine, theophylline, chlorogenic acid derivatives, caffeine, caffeic acid, ferulic acid, and p-coumaric acid were quantified in the green beans by high-performance liquid chromatography with diode array detection. Additionally, all samples were roasted and subjected to sensory analysis for coffee grading. Principal component analysis suggested that Cerrado samples tended to set apart from the other geographical locations. Those samples also exhibited higher levels of trigonelline as confirmed by two-way ANOVA analysis. Samples subjected to de-pulping processing showed improved chemical composition and sensory score. Those pulped coffees displayed 5.8% more chlorogenic acid derivatives, with an enhancement of 1.5% in the sensory score compared to unprocessed counterparts. Multivariate logistic regression analysis pointed out altitude, ferulic acid, p-coumaric acid, sweetness, and acidity as predictors distinguishing specialty coffee beans obtained by the two post-harvest processing. These findings demonstrate the influence of regional growth conditions and post-harvest treatments on the chemical and sensory quality of coffee. In summary, the present study underscores the value of integrating target metabolite analysis with statistical tools to augment the characterization of specialty coffee beans, offering novel insights for quality assessment with a focus on their bioactive compounds.

Antiproliferative Potential of Essential Oil from the Leaves of Croton floribundus (Euphorbiaceae) Against Human Metastatic Melanoma Cell Lines.

Melanoma is a cancer type with high lethality, metastatic capacity, and limited therapeutic options. Different essential oils have been reported with antitumoral potential. Thus, the essential oil (EO) of the leaves of C. floribundus was obtained by hydrodistillation and analyzed by GC-MS. The majority of substances annotated were ß-selinene, E-Caryophyllene, and Premnaspirodiene. The cytotoxic activity of EO was evaluated on three melanoma cell lines SKMEL-147, WM-1366, and CHL-1, which are representative of metastatic melanoma with different mutation profiles. The IC50 values found for EO were lower than temozolomide (reference drug) in all melanoma cell lines. In addition, the selectivity of EO was upward when compared to the reference drug. Interestingly, the WM-1366 cell line was the most responsive, and these findings are very promising considering that it has shown high resistance to the plethora of compounds. Thus, the C. floribundus EO is a promising source to drive further studies for the development of new treatments for metastatic melanoma, which is urgently relevant given the resistance of this pathology to current treatments.

Untargeted Metabolomic to Access Chemical Differences Induced by Dual Endophyte Cultures Isolated from Euphorbia Umbellata.

Endophytic fungi live asymptomatically inside vegetal tissues, and such uncommon habitat contributes to their exceptional chemical diversity. Isolating natural products from endophytic fungi could fail due to silent biosynthetic gene clusters under ordinary in vitro culture conditions, and co-culturing has been assayed to trigger their metabolism. We carried out single and dual cultures with 13 endophyte strains isolated from Euphorbia umbellata leaves. Multivariate statistics applied to untargeted metabolomics compared the chemical profiles of all endophyte cultures. PCA analysis guided the selection of the Aspergillus pseudonomiae J1 - Porogramme brasiliensis J9 dual culture for its most significant chemical differentiation: Five compounds were putatively annotated in the J1-J9 culture according to UHPLC-HRMS data, kojic acid, haliclonol and its diastereoisomer, caffeic acid, and 2-(3,4-dihydroxyphenyl)acetaldehyde. Analysis by PLS-DA using VIP score showed that kojic acid displayed the most significative importance in discriminating single and dual J1-J9 cultures.

LC-MS/DIA-based strategy for comprehensive flavonoid profiling: an Ocotea spp. applicability case.

We introduce a liquid chromatography - mass spectrometry with data-independent acquisition (LC-MS/DIA)-based strategy, specifically tailored to achieve comprehensive and reliable glycosylated flavonoid profiling. This approach facilitates in-depth and simultaneous exploration of all detected precursors and fragments during data processing, employing the widely-used open-source MZmine 3 software. It was applied to a dataset of six Ocotea plant species. This framework suggested 49 flavonoids potentially newly described for these plant species, alongside 45 known features within the genus. Flavonols kaempferol and quercetin, both exhibiting O-glycosylation patterns, were particularly prevalent. Gas-phase fragmentation reactions further supported these findings. For the first time, the apigenin flavone backbone was also annotated in most of the examined Ocotea species. Apigenin derivatives were found mainly in the C-glycoside form, with O. porosa displaying the highest flavone : flavonol ratio. The approach also allowed an unprecedented detection of kaempferol and quercetin in O. porosa species, and it has underscored the untapped potential of LC-MS/DIA data for broad and reliable flavonoid profiling. Our study annotated more than 50 flavonoid backbones in each species, surpassing the current literature.

Reliability and Acceptability to Caregivers of Telehealth Administration of the Pediatric Evaluation of Disability Inventory - Computer Adaptive Test (PEDI-CAT) for Brazilian Youth with Down Syndrome.

Purpose: To estimate test-retest reliability of the two versions of the PEDI-CAT administered via telehealth to caregivers of Brazilian young people with DS, to compare scores on the two versions, and to determine caregiver acceptance of telehealth administration of the assessment. Method: A methodological study approved by the research ethics committee. Data collection was performed online, with a mean duration of 45.0 minutes for the content-balanced version of the PEDI-CAT and 17.5 minutes for the speedy version. Results: In total, 28 caregivers of individuals with DS up to age 21 years participated (mean = 5.9 years; SD = 4.9 years). Intra-class correlation coefficients for the four domains of the PEDI-CAT content-balanced version and four domains of the PEDI-CAT speedy version ranged from 0.77 to 0.97. There was a statistical difference between the versions in the scores of the social-cognitive domain (p < 0.05). A mean of 105 items (SD = 21) was administered in the content-balanced version and a mean of 51 items (SD = 8) in the speedy version. All the caregivers found the method of administration of the PEDI-CAT acceptable. Conclusions: This study demonstrated that either version of the Brazilian version of the PEDI-CAT can be used by telehealth in clinical practice to assess children, adolescents, and young adults with DS.

Objectif: évaluer la fiabilité test-retest de deux versions du rapport PEDI-CAT utilisé lors de services de télésanté auprès de proches de jeunes brésiliens ayant le syndrome de Down (SD) afin de comparer les scores des deux versions, et déterminer l'acceptation des proches à procéder à cette évaluation par services de télésanté. Méthodologie: étude méthodologique approuvée par le comité d'éthique de la recherche. La collecte des données a été effectuée en ligne et a duré en moyenne 45,0 minutes pour ce qui est de la version au contenu équilibrée du rapport PEDI-CAT et 17,5 minutes pour ce qui est de la version abrégée. Résultats: Au total, 28 proches de personnes de 21 ans ou moins ayant le SD ont participé (moyenne = 5,9 ans; ÉT = 4,9 ans). Le coefficient de corrélation intraclasse des quatre domaines de la version au contenu équilibré du rapport PEDI-CAT et des quatre domaines de la version abrégée du rapport PEDI-CAT se situait entre 0,77 et 0,97. Le score des deux versions comportait une différence statistique dans le domaine sociocognitif (p < 0,05). En moyenne, 105 points (ÉT = 21) ont été évalués dans la version au contenu équilibré, et 51 (ÉT = 8) dans la version abrégée. Tous les proches ont trouvé la méthode d'utilisation du rapport PEDI-CAT acceptable. Conclusions: la présente étude démontre que les deux versions du rapport PEDI-CAT brésilien peuvent être utilisées lors de services de télésanté en pratique clinique pour évaluer les enfants, les adolescents et les jeunes adultes ayant le SD.

Integrative open workflow for confident annotation and molecular networking of metabolomics MSE/DIA data.

Liquid chromatography coupled with high-resolution mass spectrometry data-independent acquisition (LC-HRMS/DIA), including MSE, enable comprehensive metabolomics analyses though they pose challenges for data processing with automatic annotation and molecular networking (MN) implementation. This motivated the present proposal, in which we introduce DIA-IntOpenStream, a new integrated workflow combining open-source software to streamline MSE data handling. It provides 'in-house' custom database construction, allows the conversion of raw MSE data to a universal format (.mzML) and leverages open software (MZmine 3 and MS-DIAL) all advantages for confident annotation and effective MN data interpretation. This pipeline significantly enhances the accessibility, reliability and reproducibility of complex MSE/DIA studies, overcoming previous limitations of proprietary software and non-universal MS data formats that restricted integrative analysis. We demonstrate the utility of DIA-IntOpenStream with two independent datasets: dataset 1 consists of new data from 60 plant extracts from the Ocotea genus; dataset 2 is a publicly available actinobacterial extract spiked with authentic standard for detailed comparative analysis with existing methods. This user-friendly pipeline enables broader adoption of cutting-edge MS tools and provides value to the scientific community. Overall, it holds promise for speeding up metabolite discoveries toward a more collaborative and open environment for research.

Phytochemical investigation of Nigrospora zimmermanii isolated from Poincianella pluviosa (Sibipiruna): metabolites characterisation and screening for anti-inflammatory activity.

Endophytic fungi residing symbiotically in plant tissues are promising sources of bioactive natural products. This study explored the anti-inflammatory potential of an endophytic fungus isolated from the Brazilian medicinal plant Poincianella pluviosa (Sibipiruna). The extract from the endophyte FPD13 exhibited potential ex vivo anti-inflammatory effects by inhibiting prostaglandin E2 (PGE2) release by 75.22%. Phytochemical analysis using High-Performance Liquid Chromatography (HPLC), Nuclear Magnetic Resonance (NMR), and Liquid Chromatography-High Resolution Mass Spectrometry (LC-HRMS) enabled the isolation and identification of three compounds, including the macrolide Nigrosporolide, the phenyl-propanol Tyrosol, and the terpene Decarestrictine A. Morphological characteristics and Internal Transcribed Spacers region (ITS) sequencing classified fungus FPD13 as Nigrospora zimmermanii. The results reveal the anti-inflammatory potential and chemical diversity of P. pluviosa endophytes, warranting further investigation into the bioactivity and structure elucidation of their bioactive metabolites.

Characterization of environmental factors in children and adolescents with cerebral palsy in Minas Gerais: Participa Minas.

OBJECTIVE: To characterize the environmental factors of children and adolescents with Cerebral Palsy (CP) in the state of Minas Gerais (MG), Brazil. METHODS: This is a cross-sectional study involving 164 caregivers of children/adolescents with CP, aged 1-14 years. The Gross Motor Function Classification System (GMFCS) and the Manual Ability Classification System (MACS) were used to classify the participants' functioning, and environmental factors were evaluated by an on-line questionnaire that examined products and technologies, physical environment, services, and systems. A descriptive analysis was performed using percentage and frequency. RESULTS: Most participants had bilateral CP (66.9%) and 45% of them were spastic. Levels II and V of the GMFCS and MACS were the most frequent. About half (49.4%) used anticonvulsants, 27.4% underwent botulinum toxin application, and 29% went through orthopedic surgery in the lower limbs. Among the participants, 71.3% used orthoses in the lower limbs, and 51.8% used the public health care system. Most had access to physiotherapy (91.5%), but found difficulties to access interventions with other professionals, such as psychologists (28%) and nutritionists (37.8%). The school was the most frequently adapted environment (78%), and had the highest level of structural adaptation (42.7%). CONCLUSIONS: The results of this study suggest that the barriers to access health services and barriers to the physical environment may impact participation and social inclusion.

Translation, reliability, and validity of the Brazilian-Portuguese version of the Early Activity Scale for Endurance (EASE).

PURPOSE: Translate, investigate reliability, and construct validity of the Brazilian Early Activity Scale for Endurance (EASE). MATERIALS AND METHODS: Translation followed the international guidelines. Test-retest reliability was tested by 100 parents of children with cerebral palsy (CP): 18 months-5 years and 6-11 years. To determine construct validity, 94 parents of typically children completed the EASE. Statistical analysis included Bland-Altman, Intraclass Correlation Coefficient (ICC), Internal Consistency, and Floor and Ceiling Effect. RESULTS: The majority of the sample consisted of children with CP in GMFCS (IV-V). EASE showed good test-retest reliability for younger (ICC = 0.8) and excellent test-retest reliability for older children with CP (ICC = 0.9), and good internal consistency of 0.7 and 0.8 for the young and older group, respectively. Bland-Altman showed the bias close to zero, with no ceiling or floor effect. Regarding construct validity, younger children showed lower scores when compared to the older children. Endurance differed significantly between children with CP who were walking and those who were not walking and also for age groups. Children with CP showed lower endurance compared to typically participants in the same age group. CONCLUSIONS: Brazilian EASE is reliable and valid to estimate endurance in children with CP. Results provide evidence of construct validity.

Endurance to physical activity is an important construct to be evaluated and that directly interferes with the health and quality of life of children with Cerebral Palsy (CP).The Brazilian-Portuguese version of the 4-item Early Activity Scale for Endurance (EASE) is a valid and reliable scale to assess endurance to physical activity in children with CP.

Evaluation of the anti-inflammatory activity of Acacia polyphylla and identification of a new apigenin-3-C- glycosylated type flavonoid.

Owing to the potentially harmful adverse effects of current anti-inflammatory drugs, there is a need to identify new alternative substances. Thus, this study aimed to perform a phytochemical analysis of A. polyphylla to identify compounds responsible for its anti-inflammatory activity. Several fractions of the A. polyphylla extract were obtained and evaluated in an ex vivo anti-inflammatory assay using fresh human blood. Among the evaluated fractions, the BH fraction displayed the highest percentage of PGE2 inhibition (74.8%) compared to the reference drugs dexamethasone and indomethacin, demonstrating its excellent potential for anti-inflammatory activity. Astragalin (P1), a known 3-O-glucoside of kaempferol, was isolated from the A. polyphylla extract for the first time. In addition, a new compound (P2) was isolated and identified as the apigenin-3-C-glycosylated flavonoid. Astragalin showed moderate PGE2 activity (48.3%), whereas P2 was not anti-inflammatory. This study contributes to the phytochemical studies of A. polyphylla and confirms its anti-inflammatory potential.

Characterization of environmental factors in children and adolescents with cerebral palsy in Minas Gerais: Participa Minas / Caracterização de fatores ambientais de crianças e adolescentes com paralisia cerebral de Minas Gerais: Participa Minas

ABSTRACT Objective: To characterize the environmental factors of children and adolescents with Cerebral Palsy (CP) in the state of Minas Gerais (MG), Brazil. Methods: This is a cross-sectional study involving 164 caregivers of children/adolescents with CP, aged 1-14 years. The Gross Motor Function Classification System (GMFCS) and the Manual Ability Classification System (MACS) were used to classify the participants' functioning, and environmental factors were evaluated by an on-line questionnaire that examined products and technologies, physical environment, services, and systems. A descriptive analysis was performed using percentage and frequency. Results: Most participants had bilateral CP (66.9%) and 45% of them were spastic. Levels II and V of the GMFCS and MACS were the most frequent. About half (49.4%) used anticonvulsants, 27.4% underwent botulinum toxin application, and 29% went through orthopedic surgery in the lower limbs. Among the participants, 71.3% used orthoses in the lower limbs, and 51.8% used the public health care system. Most had access to physiotherapy (91.5%), but found difficulties to access interventions with other professionals, such as psychologists (28%) and nutritionists (37.8%). The school was the most frequently adapted environment (78%), and had the highest level of structural adaptation (42.7%). Conclusions: The results of this study suggest that the barriers to access health services and barriers to the physical environment may impact participation and social inclusion.

RESUMO Objetivo: Caracterizar os fatores ambientais de crianças e adolescentes com paralisia cerebral (PC) no estado de Minas Gerais (MG), Brasil. Métodos: Trata-se de um estudo transversal envolvendo 164 cuidadores de crianças/adolescentes com PC, na faixa etária de um a 14 anos. O Sistema de Classificação da Função Motora Grossa (GMFCS) e o Sistema de Classificação da Habilidade Manual (MACS) foram utilizados para classificar a funcionalidade dos participantes e os fatores ambientais foram avaliados por um questionário on-line que abordou produtos e tecnologias, ambiente físico, serviços e sistemas. Análises descritivas foram realizadas por meio de porcentagem e frequência. Resultados: A maioria dos participantes tinha PC bilateral (66,9%) e 45% deles eram espásticos. Os níveis II e V do GMFCS e MACS foram os mais frequentes. Cerca de metade (49,4%) fazia uso de anticonvulsivantes, 27,4% realizaram aplicação de toxina botulínica e 29% cirurgia ortopédica em membros inferiores. Utilizavam órteses em membros inferiores 71,3% e eram usuários do sistema público de saúde 51,8%. A maioria tinha acesso à fisioterapia (91,5%), mas dificuldade de acesso a intervenções com outros profissionais, como psicólogos (28%) e nutricionistas (37,8%). A escola foi o ambiente mais frequentado (78%) e também mais adaptado estruturalmente (42,7%). Conclusões: Os resultados deste estudo sugerem que barreiras de acesso aos serviços de saúde e barreiras no ambiente físico podem impactar a participação e inclusão social.

Bioprospecting-based untargeted metabolomics identifies alkaloids as potential anti-inflammatory bioactive markers of Ocotea species (Lauraceae).

BACKGROUND: Species within the Ocotea genus (Lauraceae), have demonstrated an interesting profile of bioactivities. Renowned for their diverse morphology and intricate specialized metabolite composition, Ocotea species have re-emerged as compelling candidates for bioprospecting in drug discovery research. However, it is a genus insufficiently studied, particularly regarding anti-inflammatory activity. PURPOSE: To investigate the anti-inflammatory activity of Ocotea spp. extracts and determine the major markers in this genus. METHODS: Extracts of 60 different Ocotea spp. were analysed by an ex vivo anti-inflammatory assay in human whole blood. The experiment estimates the prostaglandin E2 levels, which is one of the main mediators of the inflammatory cascade, responsible for the classical symptoms of fever, pain, and other common effects of the inflammatory process. Untargeted metabolomics analysis through liquid chromatography coupled with high-resolution mass spectrometry was performed, along with statistical analysis, to investigate which Ocotea metabolites are correlated with their anti-inflammatory activity. RESULTS: The anti-inflammatory screening indicated that 49 out of 60 Ocotea spp. extracts exhibited significant inhibition of PGE2 release compared to the vehicle (p < 0.05). Furthermore, 10 of these extracts showed statistical similarity to the reference drugs. The bioactive markers were accurately identified using multivariate statistics combined with a fold change (> 1.5) and adjusted false discovery rate analysis as unknown compounds and alkaloids, with a majority of aporphine and benzylisoquinolines. These alkaloids were annotated with an increased level of confidence since MSE spectra were compared with comprehensive databases. CONCLUSION: This study represents the first bioprospecting report revealing the anti-inflammatory potential of several Ocotea spp. The determination of their anti-inflammatory markers could contribute to drug discovery and the chemical knowledge of the Ocotea genus.

Development of the Gross Motor Function Family Report (GMF-FR) for Children with Cerebral Palsy.

Purpose: To describe the initial steps in the development of a family-completed, modified version of the Gross Motor Function Measure (GMFM-88) to report gross motor function of young people with cerebral palsy in their natural environments. Methods: Development of the Gross Motor Function - Family Report (GMF-FR) was based on expert opinion involving 13 experienced clinicians and researchers, in four steps: (1) item identification to target items that reflect functional gross motor performance; (2) item selection; (3) critical analysis of the items; and (4) item and scoring modification. Results: Several modifications to existing items and scoring were made, including wording changes to optimize ease of families' understanding, the addition of photographs to illustrate all items, changes to the items to enable use of furniture instead of specialized equipment, and modifications to scoring criteria to ensure a focus on functional motor skills. Ultimately, 30 items were selected, and specific testing/scoring instructions were created for each item. Conclusions: GMF-FR is a new family-report tool, based on the GMFM-88. When validated, it can be used as a telehealth outcome measure to capture family-reported functional motor skill performance in home and community environments.

Objectif : décrire les premières étapes de l'élaboration d'une version modifiée de la mesure de la fonction motrice globale (GMFM-88) remplie par la famille pour rendre compte de la fonction motrice globale des jeunes ayant la paralysie cérébrale dans leur environnement naturel. Méthodologie : l'élaboration de l'outil de fonction motrice globale ­ rapport familial (GMF-FR), qui repose sur l'avis d'experts ­ soit 13 cliniciens et chercheurs d'expérience ­, s'est déclinée en quatre étapes : 1) détermination des points, pour cibler ceux qui reflète le rendement de la fonction motrice globale; 2) sélection des points; 3) analyse critique des points et 4) modifications aux points et aux scores. Résultats : les experts ont apporté plusieurs modifications aux points et aux scores en place, y compris de la reformulation pour que les familles comprennent plus facilement, l'ajout de photos pour illustrer tous les points, des changements aux points pour utiliser des meubles plutôt que du matériel spécialisé et la modification des critères des scores afin de se concentrer sur les habiletés motrices fonctionnelles. Au bout du compte, les experts ont retenu 30 points, chacun étant assorti de directives précises sur le test et le score. Conclusions : La mesure GMF-FR est un nouvel outil de déclaration par la famille, inspiré du GMFM-88. Une fois validé, il peut être utilisé comme mesure de résultats en télésanté, afin de saisir le rendement des habiletés motrices fonctionnelles à la maison et dans les environnements communautaires.

Affordances in the home environment of children at risk of developmental delay.

OBJECTIVE: The aim of this study was to verify the adequacy of affordances in the home environment of children at risk of developmental delay and to identify factors associated with their frequency. METHODS: The cross-sectional study included 97 families who responded to the Affordances in the Home Environment for Motor Development - Infant Scale (AHEMD-IS) for 3-18 months (n=63), or AHEMD - Self-Report (AHEMD-SR) for 18-42 months (n=34). The Mann-Whitney U test was used to identify the differences between the frequencies of affordances between the groups. Multiple linear regression was used to verify the association between the child's sex, mother's marital status, education, socioeconomic level, child and mother's ages, house residents' number, per capita income, and AHEMD scores (α=0.05). RESULTS: The home affordances' frequency in the AHEMD-IS ranged from less than adequate to excellent, while in the AHEMD-SR, the highest predominance was medium. The offer of stimuli in the AHEMD-IS was significantly higher. Higher socioeconomic level and house residents' number were associated with greater affordances. CONCLUSIONS: The higher the socioeconomic level and house residents' number, the greater the affordances in the homes of children at risk of delay. It is necessary to provide families with some alternatives to make their home environments richer in affordances that favor child development.

Chemical Composition, Anthelmintic Activity, and Mechanism of Action of Lippia dominguensis Mold. Essential Oil on Haemonchus contortus.

Gastrointestinal nematode parasitism is a major burden to small ruminant production globally, compounded by increasing anthelmintic resistance. Previous studies have identified essential oils (EOs) from the Lippia genus with antiprotozoal and anthelmintic effects. Lippia dominguensis Moldenke (Ld), an endemic specie from the Dominican Republic, has similar popular uses, however, is chemically and pharmacologically yet uncharacterized. Here, we investigated the in vitro anthelmintic activity of LdEO and its ultrastructural effects on eggs and adult nematodes of Haemonchus contortus multidrug-resistant isolated. The GC/MS analysis showed linalool (33.85 %), 1,8-cineole (30.88 %), and δ-terpineol (10.61 %) as the main EO constituents. The LdEO showed an IC50 =0.523 mg/mL in the egg hatch test, and the motility in the adult worm motility test was 95.8 % at 1 mg/mL. The confocal scanning laser microscopy of eggs indicated permeabilization or disruption of egg cell membranes as the possible mechanism of action of LdEO. The scanning electron microscopy of adult worms showed wrinkling, undulations, and cuticular disruptions. The LdEO displayed significant in vitro anthelmintic activity on eggs and adult worms of H. contortus. Additionally, the LdEO showed low oral toxicity in mice at 2,000 mg/kg. Thus, additional in vivo studies are justified to determine its anthelmintic efficacy in small ruminants.

Structure-activity relationship study of antitrypanosomal analogues of gibbilimbol B using multivariate analysis and computation-aided drug design.

Gibbilimbol B and analogues were isolated from the Brazilian plant Piper malacophyllum and displayed activity against trypomastigote forms of Trypanosoma cruzi as well as reduced toxicity against NCTC cells. These results stimulated the preparation of a series of 24 chemically related analogues to study the potential of these compounds against T. cruzi trypomastigotes and explore structure-activity relationships. Initially, 12 compounds were planned, maintaining the same extension of the linear side chain of gibbilimbol B and unsaturation on the C-4 position but changing the functional groups - ester and amide - and variating the substituent at the p-position in the aromatic ring. Other 12 compounds were prepared using a branched side chain containing an ethyl group at the C-2 position. Overall, these structurally-related analogues demonstrated promising activity against trypomastigote forms (EC50 < 20 µM) and no mammalian cytotoxicity to fibroblasts (CC50 > 200 µM). Using multivariate statistics and machine learning analysis, aspects associated with structure/activity were related to their three-dimensional structure and, mainly, to the substituents on the aromatic ring. Obtained results suggested that the presence of t-butyl or nitro groups at p-position with appropriate side chains causes an alteration in the electron topological state, Van der Waals volumes, surface areas, and polarizabilities of tested compounds which seem to be essential for biological activity against T. cruzi parasites.

Development of children, adolescents, and young adults with cerebral palsy according to the ICF: A scoping review.

AIM: To identify and provide a descriptive overview of the development of children, adolescents, and young adults with cerebral palsy (CP) in longitudinal studies; and map areas of focus according to the components of the World Health Organization's International Classification of Functioning, Disability, and Health (ICF). METHOD: Longitudinal studies of the development of children, adolescents, and/or young adults with CP were included in this scoping review. A search for eligible studies was conducted in the databases MEDLINE, PubMed, LILACS, EMBASE, Cochrane, CINAHL, and Scopus, and was restricted to the years 2002 to 2022. All outcome measures of the studies were classified into ICF components. RESULTS: In the 56 studies included, there were 19 438 participants, involving mainly children, followed by adolescents, and lastly young adults. All components of the ICF were investigated and many studies reported outcomes in more than one component. Activity was the most investigated (67.9%; n = 38 studies), followed by body functions and structures (42.9%; n = 24 studies). Participation (14.2%; n = 8 studies) and environmental factors (3.6%; n = 2 studies) were the least studied. None of the studies investigated personal factors as an outcome. INTERPRETATION: This scoping review provides an overview of studies on the development of children, adolescents, and young adults with CP, using the ICF framework, identifying current areas of focus and gaps in the research. Future studies should target participation, contextual factors, and the transition into adulthood. WHAT THIS PAPER ADDS: The International Classification of Functioning, Disability, and Health can be used to map a range of outcomes through developmental studies. The main outcomes investigated in children with cerebral palsy were activity, and body functions and structures. Little has been explored in participation and contextual factors outcomes over time. The main classification used to stratify the participants was the Gross Motor Function Classification System.

Desenvolvimento de crianças, adolescentes e jovens adultos com Paralisia Cerebral de acordo com a CIF? Uma revisão do escopo.

A CIF pode ser usada para mapear uma série de desfechos por meio de estudos de desenvolvimento. Os principais desfechos investigados em crianças com PC foram atividade e estrutura e função corporal. Pouco tem sido explorado os desfechos de participação e fatores contextuais ao longo do tempo. A principal classificação utilizada para estratificar os participantes foi o Sistema de Classificação da Função Motora Grossa. Estudos futuros devem ampliar seu foco para diferentes áreas da CIF, e na transição para a vida adulta. Estudos sobre o desenvolvimento de indivíduos com PC ajudam terapeutas e pais a planejarem abordagens de tratamento e prognóstico futuro. Os principais desfechos investigados em indivíduos com PC foram atividade e estruturas e funções corporais. Pouco tem sido explorado em desfechos de participação e de fatores contextuais ao longo do tempo.

OBJETIVOS: Identificar e fornecer uma visão geral descritiva dos estudos de desenvolvimento de crianças, adolescentes e jovens adultos com paralisia cerebral (PC); e mapear áreas de foco de acordo com os componentes da Classificação Internacional de Funcionalidade, Incapacidade e Saúde (CIF) da OMS. MÉTODO: Estudos longitudinais do desenvolvimento de crianças, adolescentes e/ou jovens adultos com PC foram incluídos nesta revisão de escopo. A busca por estudos elegíveis foi realizada nas bases de dados: MEDLINE, PubMed, LILACS, EMBASE, Cochrane, CINAHL, Scopus, e foi restrita aos anos de 2002-2022. Todas os desfechos dos estudos foram classificados em componentes da CIF. RESULTADOS: Nos 56 estudos incluídos, houve 19.438 participantes, envolvendo principalmente crianças, seguidas de adolescentes e, por último, jovens adultos. Todos os componentes da CIF foram investigados e muitos estudos relataram resultados em mais de um componente. O componente atividade foi o mais investigado (67,9%; n = 38 estudos), seguida da estrutura e função corporal (42,9%; n = 24 estudos). A participação (14,2%; n = 8 estudos) e os fatores ambientais (3,6%; n = 2 estudos) foram os menos estudados. Nenhum dos estudos investigou fatores pessoais como desfecho. INTERPRETAÇÃO: Esta revisão de escopo fornece uma visão geral dos estudos sobre o desenvolvimento de crianças, adolescentes e jovens adultos com PC, usando a estrutura da CIF, identificando áreas atuais de foco e lacunas. Estudos futuros devem visar a participação, os fatores contextuais e a transição para a vida adulta. O QUE ESTE ESTUDO ADICIONA: A CIF pode ser usada para mapear uma série de desfechos por meio de estudos de desenvolvimento. Os principais desfechos investigados em crianças com PC foram atividade e estrutura e função corporal. Pouco tem sido explorado os desfechos de participação e fatores contextuais ao longo do tempo. A principal classificação utilizada para estratificar os participantes foi o Sistema de Classificação da Função Motora Grossa. Estudos futuros devem ampliar seu foco para diferentes áreas da CIF, e na transição para a vida adulta.