Antinociceptive and anti-inflammatory potential, and chemical characterization of the dichloromethane fraction of Solanum lycocarpum (Solanaceae) ripe fruits by LC-DAD-MS.

ETHNOPHARMACOLOGICAL RELEVANCE: Solanum lycocarpum A. St. Hil. (Solanaceae) is a species from the Brazilian Cerrado, exhibiting several medicinal properties, being used by the population in the treatment of ulcers, bronchitis, asthma and hepatitis, which involve inflammatory processes. AIM OF THIS STUDY: This study aimed to chemically characterize the dichloromethane fraction (DCM), as well as verify its antinociceptive, anti-inflammatory and antioxidant potential. MATERIALS AND METHODS: The DCM fraction was obtained by partitioning the ethanol extract. The chemical constituents of the DCM fraction were characterized by LC-DAD-MS. The DPPH and FRAP assays were used to evaluate the antioxidant potential. The carrageenan-induced paw edema model was used to assess the anti-inflammatory effects, and the inflammatory infiltrate was evaluated by qualitative and quantitative histological analyses. The antinociceptive action of the DCM fraction was evaluated by acetic acid-induced abdominal writhing test, formalin-induced nociception and hot-plate test. RESULTS: Steroidal alkaloids solasonine, solasodine and solamargine, as well as the alkaloid peiminine/imperialine and caffeoylquinic acids, were annotated in DCM fraction by LC-DAD-MS. The DCM fraction showed antioxidative action in the in vitro DPPH and FRAP tests, as well as an anti-inflammatory effect for the three evaluated doses of 30, 100 and 300 mg/kg in the fourth and sixth hours after the administration of carrageenan. The histological analyses evidenced considerably reduction in leukocyte migration and the number of polymorphonuclear leukocytes. The study also demonstrated antinociceptive activity for the DCM fraction, which reduced abdominal writhing at three concentrations evaluated, as well as a decrease in paw licking in the formalin-induced nociception test both in the neurogenic phase and the inflammatory phase, with greater effectiveness compared to the anti-inflammatory indomethacin. The DCM fraction also increased the latency time of the animals in the hot plate test 60 min after treatment, although it did not seem to involve the opioidergic system. CONCLUSION: This work evidenced that the dichloromethane fraction of S. lycocarpum fruit possesses antinociceptive and anti-inflammatory potential, which supports its use in folk medicine for management inflammatory conditions.

Phytotherapy: knowledge, experience and prescription in oral healthcare. A cross-sectional survey of dental practitioners / Conhecimento, experiência e prescrição de fitoterapia em saúde bucal: Um levantamento transversal com dentistas clínicos

ABSTRACT Herbal medicine is widely used as an integrative complementary treatment for common chronic diseases, yet potential risks include adverse effects and coprescription Aim This exploratory survey assessed Brazilian dentists' knowledge, attitudes, and practices regarding phytotherapy Material and Method This study used a consecutive sample of registered dentists who were active in clinical practice and attending advanced training for complex oral rehabilitation at a leading dental school in Latin America. Participants responded to a semi-structured 38-item instrument designed to collect data on sociodemographic, professional and health variables, and on their knowledge, use, prescription and opinions of phytotherapy. Quantitative data were analyzed with descriptive and inferential statistics. Qualitative data were described and analyzed with a thematic approach Results A total 53 dentists responded the survey (88.3% response rate). Six dentists reported formal education in phytotherapy and 33 had informal knowledge. Twenty-one dentists (39.6%) reported using herbal medicine, and 17 (32.1%) prescribed phytotherapy to their patients, mostly traditional medicinal plants. A logistic regression model showed that post-graduate degree and personal use of phytotherapy were associated with phytotherapy prescription. Opinions on how to improve the rational use of phytotherapy included the need for research evidence, specific academic education, and knowledge dissemination to clinicians. As a clinical recommendation, it was proposed that questions on herbal medicine should be asked during the dental patient's anamnesis Conclusions Dentists with post-graduate degrees and personal use of phytotherapy prescribe herbal medicines for their patients in real-world clinics, regardless of formal education on the subject. Qualitative findings indicate the need to implement scientific initiatives.

RESUMO A fitoterapia é amplamente utilizada como um tratamento integrativo e complementar para doenças crônicas comuns, mas os riscos potenciais incluem efeitos adversos e co-prescrição Objetivo Esta pesquisa exploratória avaliou o conhecimento, as atitudes e as práticas de cirurgiões-dentistas brasileiros sobre fitoterapia Materiais e Método Uma amostra consecutiva foi composta por dentistas com registro profissional, que eram ativos em prática clínica e frequentavam treinamento avançado para reabilitação oral complexa em uma das principais escolas de odontologia da América Latina. Os participantes responderam a um instrumento semiestruturado de 38 itens para coletar dados sobre variáveis sociodemográficas, profissionais e de saúde, bem como conhecimento, uso, prescrição e opiniões sobre fitoterapia. Os dados quantitativos foram analisados com estatística descritiva e inferencial. Os dados qualitativos foram descritos e analisados com abordagem temática Resultados Um total de 53 dentistas respondeu à pesquisa (taxa de resposta de 88,3%). Seis cirurgiões-dentistas relataram formação em fitoterapia e 33 possuíam conhecimento informal. Vinte e um dentistas (39,6%) relataram o uso de fitoterápicos e 17 (32,1%) prescreveram fitoterapia para seus pacientes, principalmente plantas medicinais tradicionais. Um modelo de regressão logística mostrou que pós-graduação e uso pessoal de fitoterapia estiveram associados à prescrição de fitoterapia. As opiniões para melhorar o uso racional da fitoterapia incluíram a necessidade de evidências de pesquisa, formação acadêmica específica e disseminação do conhecimento para os clínicos. Como recomendação clínica, foram propostas questões sobre fitoterapia para a anamnese odontológica do paciente Conclusões Cirurgiões-dentistas com pós-graduação e uso pessoal de fitoterapia prescrevem mais medicamentos fitoterápicos para seus pacientes em clínicas do mundo real, independentemente da educação formal sobre o assunto. Os resultados qualitativos indicam a necessidade de iniciativas de implementação científica.

Anti-inflammatory and antinociceptive effects, and safety toxicological profile of a new paracetamol analog, LQFM291.

In the scope of a research program with the goal of developing treatments for inflammatory diseases, the pharmacological evaluation of LQFM291, designed by molecular hybridization from butylated hydroxytoluene and paracetamol, was described. The antioxidant profile of LQFM291 was evaluated by electrochemical measurement. Also, acute or repeated treatments with equimolar doses to paracetamol were used to evaluate the antinociceptive and/or anti-inflammatory activities of LQFM291 in animal models. The toxicologic potential of LQFM291 was also evaluated and compared to paracetamol through biochemical and histopathological analysis after the repeated treatment schedule. As a result of the acute treatment, paracetamol showed a similar antinociceptive effect in formalin test compared to LQFM291. Whereas, after the repeated treatment, when carrageenan-induced hyperalgesia and edema tests were performed, paracetamol showed a delayed antinociceptive and anti-inflammatory effect compared to LQFM291. Furthermore, as other advantages the LQFM291 showed a high redox capacity, a gastroprotective activity and a safety pharmacological profile without any liver or kidney damage. These effects can be related to the prevention of oxidative stress by reduction of protein and lipid peroxidation in gastric tissue, maintenance of glutathione levels in hepatic homogenate, and a systemic reduction of pro-inflammatory cytokine levels, which may characterize the LQFM291 as a more viable and effective alternative to relief pain and inflammatory signs in patients with chronic disorders.

The effect of amylase supplementation on individual variation, growth performance, and starch digestibility in broiler chickens.

The objective of this study was to evaluate the variance of starch digestibility in broilers individually fed diets without or with supplemental exogenous amylase. A total of 120 d-of-hatch male chicks were individually reared from 5 to 42 d in metallic cages and fed maize-based basal diets or diets containing 80 kilo-novo-α-amylase units/kg (60 birds or replicates per treatment). Beginning on d 7, feed intake, body weight gain, and feed conversion ratio were recorded; partial excreta collection was conducted every Monday, Wednesday, and Friday until 42 d, when all birds were sacrificed for individual collection of duodenal and ileal digesta. Lower feed intake (4,675 vs. 4,815 g) and feed conversion ratio (1.470 vs. 1.508) were observed in amylase-fed broilers during the overall period (7-43 d; P < 0.01), whereas body weight gain was not affected. Amylase supplementation improved total tract starch (TTS) digestibility (P < 0.05) on each day of excreta collection (except for d 28, where no difference was found), averaging 0.982 vs. 0.973 compared to basal-fed broilers from d 7 to 42. Both apparent ileal starch (AIS) digestibility and apparent metabolizable energy (AMEN) were increased (P <0.05) from 0.968 to 0.976 and from 3,119 to 3,198 kcal/kg, respectively, with enzyme supplementation. Activity of amylase in the duodenum was higher (18.6 vs. 50.1 IU/g of digesta) in supplemented birds. Amylase supplementation led to a reduced coefficient of variation for both TTS (averaged 2.41 vs. 0.92% from 7 to 42 d) and AIS digestibilities (1.96 vs. 1.03%), as well as AMEN (0.49 vs. 0.35%), when compared to the nonsupplemented group, indicating lower individual heterogenity. An age effect was detected for TTS digestibility, as both groups saw an increase during the first weeks (slightly more pronounced in the supplemented group); older birds (d 30 onwards) presented a lower TTS digestibility compared to ages between 7 and 25 d. In conclusion, amylase supplementation in maize diets for broilers can attenuate individual bird variation for starch and energy utilization by increasing amylase activity and enhancing starch digestibility.

Effect of Vitamin D3 Supplementation on Acute Fracture Healing: A Phase II Screening Randomized Double-Blind Controlled Trial.

Nearly half of adult fracture patients are vitamin D deficient (serum 25-hydroxyvitamin D [25(OH)D] levels <20 ng/mL). Many surgeons advocate prescribing vitamin D supplements to improve fracture healing outcomes; however, data supporting the effectiveness of vitamin D3 supplements to improve acute fracture healing are lacking. We tested the effectiveness of vitamin D3 supplementation for improving tibia and femur fracture healing. We conducted a single-center, double-blinded phase II screening randomized controlled trial with a 12-month follow-up. Patients aged 18-50 years receiving an intramedullary nail for a tibia or femoral shaft fracture were randomized 1:1:1:1 to receive (i) 150,000 IU loading dose vitamin D3 at injury and 6 weeks (n = 27); (ii) 4000 IU vitamin D3 daily (n = 24); (iii) 600 IU vitamin D3 daily (n = 24); or (iv) placebo (n = 27). Primary outcomes were clinical fracture healing (Function IndeX for Trauma [FIX-IT]) and radiographic fracture healing (Radiographic Union Score for Tibial fractures [RUST]) at 3 months. One hundred two patients with a mean age of 29 years (standard deviation 8) were randomized. The majority were male (69%), and 56% were vitamin D3 deficient at baseline. Ninety-nine patients completed the 3-month follow-up. In our prespecified comparisons, no clinically important or statistically significant differences were detected in RUST or FIX-IT scores between groups when measured at 3 months and over 12 months. However, in a post hoc comparison, high doses of vitamin D3 were associated with improved clinical fracture healing relative to placebo at 3 months (mean difference [MD] 0.90, 80% confidence interval [CI], 0.08 to 1.79; p = 0.16) and within 12 months (MD 0.89, 80% CI, 0.05 to 1.74; p = 0.18). The study was designed to identify potential evidence to support the effectiveness of vitamin D3 supplementation in improving acute fracture healing. Vitamin D3 supplementation, particularly high doses, might modestly improve acute tibia or femoral shaft fracture healing in healthy adults, but confirmatory studies are required. The Vita-Shock trial was awarded the Orthopaedic Trauma Association's (OTA) Bovill Award in 2020. This award is presented annually to the authors of the most outstanding OTA Annual Meeting scientific paper. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Pharmacological evaluation of antinociceptive and anti-inflammatory activities of LQFM202: a new piperazine derivative.

Advances have been made in the search for new multi-target modulators to control pain and inflammation. Therefore, compound 3,5-di-tert-butyl-4-hydroxyphenyl)(4-methylpiperazin-1-yl)methanone (LQFM202) was synthesised and evaluated. First, in vitro assays were performed for COX-1, COX-2, and 5-LOX enzymes. Subsequently, adult female Swiss albino mice treated orally with LQFM202 at doses of 25-200 mg/kg were subjected to acetic acid-induced writhing, formalin-induced pain, carrageenan-induced hyperalgesia, carrageenan- or zymosan-induced paw oedema, or pleurisy. LQFM202 inhibited COX-1, COX-2, and LOX-5 (IC50 = 3499 µM, 1565 µM, and 1343 µM, respectively). In acute animal models, LQFM202 (50, 100, or 200 mg/kg) decreased the amount of abdominal writhing (29%, 52% and 48%, respectively). Pain in the second phase of the formalin test was reduced by 46% with intermediate dose. LQFM202 (100 mg/kg) reduced the difference in nociceptive threshold in all 4 h evaluated (46%, 37%, 30%, and 26%, respectively). LQFM202 (50 mg/kg) decreased the carrageenan-oedema from the second hour (27%, 31% and 25%, respectively); however, LQFM202 (100 mg/kg) decreased the carrageenan-oedema in all hours evaluated (35%, 42%, 48% and 50%, respectively). When using zymosan, LQFM202 (50 mg/kg) decreased the oedema in all hours evaluated (33%, 32%, 31% and 20%, respectively). In the carrageenan-pleurisy test, LQFM202 (50 mg/kg) reduced significantly the number of polymorphonuclear cells (34%), the myeloperoxidase activity (53%), TNF-α levels (47%), and IL-1ß levels (58.8%). When using zymosan, LQFM202 (50 mg/kg) reduced the number of polymorphonuclear and mononuclear cells (54% and 79%, respectively); and the myeloperoxidase activity (46%). These results suggest antinociceptive and anti-inflammatory effects of LQFM202.

Phytotherapy: knowledge, experience and prescription in oral healthcare. A cross-sectional survey of dental practitioners.

Herbal medicine is widely used as an integrative complementary treatment for common chronic diseases, yet potential risks include adverse effects and coprescription. Aim: This exploratory survey assessed Brazilian dentists' knowledge, attitudes, and practices regarding phytotherapy. Material and Method: This study used a consecutive sample of registered dentists who were active in clinical practice and attending advanced training for complex oral rehabilitation at a leading dental school in Latin America. Participants responded to a semi-structured 38-item instrument designed to collect data on sociodemographic, professional and health variables, and on their knowledge, use, prescription and opinions of phytotherapy. Quantitative data were analyzed with descriptive and inferential statistics. Qualitative data were described and analyzed with a thematic approach. Results: A total 53 dentists responded the survey (88.3% response rate). Six dentists reported formal education in phytotherapy and 33 had informal knowledge. Twenty-one dentists (39.6%) reported using herbal medicine, and 17 (32.1%) prescribed phytotherapy to their patients, mostly traditional medicinal plants. A logistic regression model showed that post-graduate degree and personal use of phytotherapy were associated with phytotherapy prescription. Opinions on how to improve the rational use of phytotherapy included the need for research evidence, specific academic education, and knowledge dissemination to clinicians. As a clinical recommendation, it was proposed that questions on herbal medicine should be asked during the dental patient's anamnesis. Conclusions: Dentists with post-graduate degrees and personal use of phytotherapy prescribe herbal medicines for their patients in real-world clinics, regardless of formal education on the subject. Qualitative findings indicate the need to implement scientific initiatives.

A fitoterapia é amplamente utilizada como um tratamento integrativo e complementar para doenças crônicas comuns, mas os riscos potenciais incluem efeitos adversos e co-prescrição. Objetivo: Esta pesquisa exploratória avaliou o conhecimento, as atitudes e as práticas de cirurgiões-dentistas brasileiros sobre fitoterapia. Materiais e Método: Uma amostra consecutiva foi composta por dentistas com registro profissional, que eram ativos em prática clínica e frequentavam treinamento avançado para reabilitação oral complexa em uma das principais escolas de odontologia da América Latina. Os participantes responderam a um instrumento semiestruturado de 38 itens para coletar dados sobre variáveis sociodemográficas, profissionais e de saúde, bem como conhecimento, uso, prescrição e opiniões sobre fitoterapia. Os dados quantitativos foram analisados com estatística descritiva e inferencial. Os dados qualitativos foram descritos e analisados com abordagem temática. Resultados: Um total de 53 dentistas respondeu à pesquisa (taxa de resposta de 88,3%). Seis cirurgiões-dentistas relataram formação em fitoterapia e 33 possuíam conhecimento informal. Vinte e um dentistas (39,6%) relataram o uso de fitoterápicos e 17 (32,1%) prescreveram fitoterapia para seus pacientes, principalmente plantas medicinais tradicionais. Um modelo de regressão logística mostrou que pós-graduação e uso pessoal de fitoterapia estiveram associados à prescrição de fitoterapia. As opiniões para melhorar o uso racional da fitoterapia incluíram a necessidade de evidências de pesquisa, formação acadêmica específica e disseminação do conhecimento para os clínicos. Como recomendação clínica, foram propostas questões sobre fitoterapia para a anamnese odontológica do paciente. Conclusões: Cirurgiões-dentistas com pós-graduação e uso pessoal de fitoterapia prescrevem mais medicamentos fitoterápicos para seus pacientes em clínicas do mundo real, independentemente da educação formal sobre o assunto. Os resultados qualitativos indicam a necessidade de iniciativas de implementação científica.

New Pregnane Glycosides from Mandevilla dardanoi and Their Anti-Inflammatory Activity.

Mandevilla Lindl. is an important genus of the Apocynaceae family, not only as ornamental plants but also for its medicinal uses. In Brazil, Mandevilla species are indicated to treat asthma and skin infections, their anti-inflammatory potential and wound healing properties are also reported in the literature. Concerning their chemical composition, this group of plants is a conspicuous producer of pregnane glycosides. Mandevilla dardanoi is an endemic species from the Brazilian semiarid region not studied by any phytochemical methods. In view of the medicinal potential of Mandevilla species, this study aimed to isolate new pregnane glycosides from M. dardanoi. To achieve this main goal, modern chromatography techniques were employed. Five new pregnane glycosides, dardanols A-E, were isolated from the roots of M. dardanoi by HPLC. Their structures were determined using extensive 1D and 2D-NMR and mass spectrometry (MSn and HRESIMS) data. The cytotoxicity and the anti-inflammatory potential of these compounds were evaluated. The first was evaluated by measuring proinflammatory cytokines and nitric oxide production by stimulated macrophages. Dardanols were able to inhibit the production of nitric oxide and reduce IL-1ß and TNF-α. The current work demonstrates the chemodiversity of Brazilian semiarid species and contributes to amplifying knowledge about the biological potential of the Mandevilla genus.

Targeted Isolation of Anti-inflammatory Lignans from Justicia aequilabris by Molecular Networking Approach.

Herein, the isolation of secondary metabolites from the aerial parts of Justicia aequilabris guided by HPLC-MSn and molecular networking analyses is reported. Twenty-two known compounds were dereplicated. Three new lignans (aequilabrines A-C (1-3)) and three known compounds (lariciresinol-4'-O-ß-glucose (4), roseoside (5), and allantoin (6)) were obtained. The anti-inflammatory activity of compounds 1-3 was evaluated in vitro by inhibiting the nitric oxide production (NO) and pro-inflammatory activity on the cytokine IL-1ß. Compounds 2 and 3 showed significant inhibitory activity against NO production, with IC50 values of 9.1 and 7.3 µM, respectively. The maximum inhibition of IL-1ß production was 23.5% (1), 27.3% (2), and 32.5% (3).

Alpha-tocopherol-loaded polycaprolactone nanoparticles improve the inflammation and systemic oxidative stress of arthritic rats.

Background and aim: The present study investigated the effects of orally administered α-tocopherol-loaded polycaprolactone nanoparticles on the articular inflammation and systemic oxidative status of middle-aged Holtzman rats with Freund's adjuvant-induced polyarthritis, a model for rheumatoid arthritis. Intraperitoneally administered free α-tocopherol provided the reference for comparison. Experimental procedure: Two protocols of treatment were followed: intraperitoneal administration of free α-tocopherol (100 mg/kg i.p.) or oral administration of free and nanoencapsulated α-tocopherol (100 mg/kg p.o.). Animals were treated during 18 days after arthritis induction. Results: Free (i.p.) and encapsulated α-tocopherol decreased the hind paws edema, the leukocytes infiltration into femorotibial joints and the mRNA expression of pro-inflammatory cytokines in the tibial anterior muscle of arthritic rats, but the encapsulated compound was more effective. Free (i.p.) and encapsulated α-tocopherol decreased the high levels of reactive oxygen species in the brain and liver, but only the encapsulated compound decreased the levels of protein carbonyl groups in these organs. Both free (i.p.) and encapsulated α-tocopherol increased the α-tocopherol levels and the ratio of reduced to oxidized glutathione in these organs. Conclusion: Both intraperitoneally administered free α-tocopherol and orally administered encapsulated α-tocopherol effectively improved inflammation and systemic oxidative stress in middle-aged arthritic rats. However, the encapsulated form should be preferred because the oral administration route does not be linked to the evident discomfort that is caused in general by injectable medicaments. Consequently, α-tocopherol-loaded polycaprolactone nanoparticles may be a promising adjuvant to the most current approaches aiming at rheumatoid arthritis therapy.

Effects of Hearing Loss on Interaural Time Difference Sensitivity at Low and High Frequencies.

While many studies have reported a loss of sensitivity to interaural time differences (ITDs) carried in the fine structure of low-frequency signals for listeners with hearing loss, relatively few data are available on the perception of ITDs carried in the envelope of high-frequency signals in this population. The relevant studies found stronger effects of hearing loss at high frequencies than at low frequencies in most cases, but small subject numbers and several confounding effects prevented strong conclusions from being drawn. In the present study, we revisited this question while addressing some of the issues identified in previous studies. Participants were ten young adults with normal hearing (NH) and twenty adults with sensorineural hearing impairment (HI) spanning a range of ages. ITD discrimination thresholds were measured for octave-band-wide "rustle" stimuli centered at 500 Hz or 4000 Hz, which were presented at 20 or 40 dB sensation level. Broadband rustle stimuli and 500-Hz pure-tone stimuli were also tested. Thresholds were poorer on average for the HI group than the NH group. The ITD deficit, relative to the NH group, was similar at low and high frequencies for most HI participants. For a small number of participants, however, the deficit was strongly frequency-dependent. These results provide new insights into the binaural perception of complex sounds and may inform binaural models that incorporate effects of hearing loss.

Low dose of quercetin-loaded pectin/casein microparticles reduces the oxidative stress in arthritic rats.

AIMS: Quercetin has been investigated as an agent to treat rheumatoid arthritis. At high doses it improves inflammation and the antioxidant status of arthritic rats, but it also exerts mitochondriotoxic and pro-oxidant activities. Beneficial effects of quercetin have not been found at low doses because of its chemical instability and low bioavailability. In the hope of overcoming these problems this study investigated the effects of long-term administration of quercetin-loaded pectin/casein microparticles on the oxidative status of liver and brain of rats with adjuvant-induced arthritis. MAIN METHODS: Particle morphology was viewed with transmission electron microscopy and the encapsulation efficiency was measured indirectly by X-ray diffraction. Quercetin microcapsules (10 mg/Kg) were orally administered to rats during 60 days. Inflammation indicators and oxidative stress markers were measured in addition to the respiratory activity and ROS production in isolated mitochondria. KEY FINDINGS: Quercetin was efficiently encapsulated inside the polymeric matrix, forming a solid amorphous solution. The administration of quercetin microparticles to arthritic rats almost normalized protein carbonylation, lipid peroxidation, the levels of reactive oxygen species as well as the reduced glutathione content in both liver and brain. The paw edema in arthritic rats was not responsive, but the plasmatic activity of ALT and the mitochondrial respiration were not affected by quercetin, indicating absence of mitochondriotoxic or hepatotoxic actions. SIGNIFICANCE: Quercetin-loaded pectin/casein microcapsules orally administered at a low dose improve oxidative stress of arthritic rats without a strong anti-inflammatory activity. This supports the long-term use of quercetin as an antioxidant agent to treat rheumatoid arthritis.

International Multicenter Analysis of Brain Structure Across Clinical Stages of Parkinson's Disease.

BACKGROUND: Brain structure abnormalities throughout the course of Parkinson's disease have yet to be fully elucidated. OBJECTIVE: Using a multicenter approach and harmonized analysis methods, we aimed to shed light on Parkinson's disease stage-specific profiles of pathology, as suggested by in vivo neuroimaging. METHODS: Individual brain MRI and clinical data from 2357 Parkinson's disease patients and 1182 healthy controls were collected from 19 sources. We analyzed regional cortical thickness, cortical surface area, and subcortical volume using mixed-effects models. Patients grouped according to Hoehn and Yahr stage were compared with age- and sex-matched controls. Within the patient sample, we investigated associations with Montreal Cognitive Assessment score. RESULTS: Overall, patients showed a thinner cortex in 38 of 68 regions compared with controls (dmax  = -0.20, dmin  = -0.09). The bilateral putamen (dleft  = -0.14, dright  = -0.14) and left amygdala (d = -0.13) were smaller in patients, whereas the left thalamus was larger (d = 0.13). Analysis of staging demonstrated an initial presentation of thinner occipital, parietal, and temporal cortices, extending toward rostrally located cortical regions with increased disease severity. From stage 2 and onward, the bilateral putamen and amygdala were consistently smaller with larger differences denoting each increment. Poorer cognition was associated with widespread cortical thinning and lower volumes of core limbic structures. CONCLUSIONS: Our findings offer robust and novel imaging signatures that are generally incremental across but in certain regions specific to disease stages. Our findings highlight the importance of adequately powered multicenter collaborations. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Rosmarinus officinalis L. (rosemary) extract has antibiofilm effect similar to the antifungal nystatin on Candida samples.

Candida spp. are naturally opportunistic and can promote infections. These yeasts can form biofilm, after penetration and adhesion to the biotic or abiotic surfaces. Preexisting diseases, treatments with drugs and radiation therapy, medical procedures, and parafunctional habits favor the installation of a fungal infection. Increased resistance to the available antifungals has become a concern. Therefore, alternative methods to control them have been evaluated, including the use of plant substances. In this study, the antibiofilm effect of R. officinalis L. extract was analyzed on C. albicans, C. dubliniensis, C. glabrata, C. krusei, and C. tropicalis. A phytochemical analysis of the extract was performed. Biofilms were formed for 48 h and exposed to the different concentrations of the extract (50, 100, and 200 mg/mL) for 5 min or 24 h. The effect of the plant extract was compared to the antifungal nystatin. Rosmarinus officinalis L. extract was constituted of phenols and flavonoids, highlighting the presence of chlorogenic acid derivatives in its composition. Biofilm reductions were observed after exposure to the plant extract for both periods. The plant extract provided a reduction similar to the antifungal. Thus, R. officinalis L. extract showed antibiofilm effect on Candida spp. comparable to the nystatin.

Effect of age and different doses of dietary vitamin E on breast meat qualitative characteristics of finishing broilers.

The supplementation of vitamin E on broiler chicken diets is essential to the prevention of lipid oxidation reactions in the meat and improvement of meat quality. The objective of this study was to assess the effect of different doses of dietary vitamin E on breast meat quality of broiler chickens in the finishing period. Five doses of vitamin E were used (30, 90, 150, 210, and 270 mg/kg feed) in broilers' diets from 42 to 54 d of age. A completely randomized design was conducted, followed by a split-plot, where the vitamin E dose was considered as the whole plot, and broilers' age at slaughter was the subplot. Breast meat quality was assessed at 4 different ages (45, 48, 51, and 54 d old), using 50 birds per age, totaling 200 birds. Meat quality characteristics evaluated were: pH at 24 h post mortem, color (brightness, redness, and yellowness), water holding capacity, cooking loss, shear force, and lipid peroxidation. There was no interaction between age and dose of vitamin E for meat quality characteristics (P > 0.05). The age at slaughter had a quadratic effect (P < 0.05) on pH, brightness, redness, and water holding capacity. Although pH values were higher in the breast meat of older birds (51 and 52 d old), breast meat of younger birds (48 d) had a more reddish aspect. Shear force value was higher in breast meat of birds slaughtered at later ages (P < 0.01), as a linear age-effect was observed. Brightness increased linearly (P < 0.05) with higher vitamin doses, whereas treatments did not alter yellowness, cooking loss, and lipid peroxidation. In this study, increasing vitamin E doses in the finishing period increased the brightness of broiler breast meat, whereas slaughtering at later ages resulted in greater meat pH and shear force value.

High doses of phytase on growth performance, bone mineralization, diet utilization, and plasmatic myo-inositol of turkey poults.

An experiment was conducted to evaluate the growth performance, bone mineral composition, diet utilization, and plasmatic concentration of myo-inositol (MYO) in turkeys fed different phytase doses from 1 to 28 d. A total of three hundred and twenty 1-day-old turkeys were distributed in a completely randomized design with 4 treatments and 8 replicates of 10 birds each. Treatments included a basal diet without phytase; reduced diet (reduced -0.15% available P and -0.18% Ca) without phytase; reduced diet + 2,000 units of phytase (FYT)/kg; and reduced diet + 4,000 FYT/kg. From day 26 to 28, partial excreta collection was conducted, and on day 28, 7 birds per replicate were euthanized for collection of ileal content and left tibia bones were removed from 2 of the same euthanized birds. Feed, excreta, and ileal digesta samples were analyzed to determine nutrient digestibility and metabolizability, ileal digestible energy, and AME. Tibia bones were analyzed for ash, Ca, and P content, and calculation of Seedor index. On day 28, blood samples were collected from 2 turkeys per replicate to analyze plasmatic MYO concentration. Feed conversion ratio was not affected, but phytase supplementation resulted in higher feed intake and body weight gain compared to turkeys fed the reduced diet (P < 0.05), and both doses were similar to the basal diet. Increasing the phytase dose had a linear effect (P < 0.05) on ileal digestibility of P and metabolizability of DM, CP, Ca, and Na, and also on AME. P content in the tibia bone increased linearly (P < 0.05) with phytase supplementation, and the same linear increase (P < 0.05) was observed for plasmatic MYO. In conclusion, the supplementation of turkey poult's diets with high levels of phytase up to 4,000 FYT/kg improves diet utilization by increasing P digestibility and dietary metabolizability, leading to higher P content in the bone and enhancing MYO provision and absorption.

Effect of different doses of phytase and protein content of soybean meal on growth performance, nutrient digestibility, and bone characteristics of broilers.

This study evaluated the effects of high phytase doses and soybean meal (SBM) with different CP content on growth performance, ileal nutrient digestibility, digestible energy, plasmatic myo-inositol, phosphate release in vitro, and bone composition of broiler chickens. One thousand two hundred 1-day-old broilers were distributed in a 2 × 2 completely randomized factorial arrangement, with 2 phytase doses (1,000 and 2,500 phytase units [FYT]/kg of feed) and 2 SBM with different CP concentrations (45 and 47%), totaling 4 treatments with 12 replicates of 25 birds each. The chickens received feed and water ad libitum. Diets were based on corn and SBM, with different inclusions of soybean hull used to dilute the CP content of SBM according to each treatment. The inclusion of 2,500 FYT increased weight gain from 0 to 21 d (P < 0.05), whereas growth performance from 22 to 42 d was not affected, and SBM had no effect on growth performance. At day 21, ileal digestibility of dry matter, ash, and P, and digestible energy were greater in diets with 2,500 FYT/kg (P < 0.05), as well as phosphate in vitro release (P < 0.01) compared to the lower dose. At day 42, diets with SBM 47% CP and 2,500 FYT/kg promoted greater digestibility of dry matter, ash, CP, Ca, P, and digestible energy (P < 0.001), and greater phosphate release (P < 0.05) in comparison to other treatments. myo-inositol level in the plasma at 21 and 42 d was higher with the use of 2,500 FYT compared to 1,000 FYT (P < 0.05). The higher phytase dose increased tibia ash, toe ash, and Seedor Index (P < 0.05) at day 21, and the Ca content in tibia was higher with 2,500 FYT and SBM 47% CP at day 42. In conclusion, higher phytase doses for broilers improve weight gain, myo-inositol provision, and bone mineral composition. Nutrient ileal digestibility can be enhanced by higher phytase doses when in combination with SBM of greater nutritional quality.

Novel phosphatidylinositol 4-kinases III beta (PI4KIIIß) inhibitors discovered by virtual screening using free energy models.

Herein, the LASSBio Chemical Library is presented as a valuable source of compounds for screening to identify hits suitable for subsequent hit-to-lead optimization stages. A feature of the LASSBio Chemical Library worth highlighting is the fact that it is a smart library designed by medicinal chemists with pharmacological activity as the main priority. The great majority of the compounds part of this library have shown in vivo activity in animal models, which is an indication that they possess overall favorable bioavailability properties and, hence, adequate pharmacokinetic profiles. This, in turn, is supported by the fact that approximately 85% of the compounds are compliant with Lipinski's rule of five and ca. 95% are compliant with Veber's rules, two important guidelines for oral bioavailability. In this work it is presented a virtual screening methodology combining a pharmacophore-based model and an empirical Gibbs free energy-based model for the ligand-protein interaction to explore the LASSBio Chemical Library as a source of new hits for the inhibition of the phosphatidylinositol 4-kinase IIIß (PI4KIIIß) enzyme, which is related to the development of viral infections (including enteroviruses, SARS coronavirus, and hepatitis C virus), cancers and neurological diseases. The approach resulted in the identification of two hits, LASSBio-1799 (7) and LASSBio-1814 (10), which inhibited the target enzyme with IC50 values of 3.66 µM and IC50 and 6.09 µM, respectively. This study also enabled the determination of the structural requirements for interactions with the active site of PI4KIIIß, demonstrating the importance of both acceptor and donor hydrogen bonding groups for forming interactions with binding site residues Val598 and Lys549.

Liberação miofascial no ganho de potência muscular do quadríceps: um estudo controlado e randomizado / Myfascial release in quadriceps muscle power gain: a controlled and randomized study

A prescrição de exercícios para o ganho de força e potência muscular é utilizado com o objetivo de ajudar na reabilitação de lesões musculares e para o aprimoramento físico nas práticas esportivas. Dentre as técnicas que são apontadas como possíveis condutas que poderiam auxiliar no fortalecimento muscular e potência destaca-se a Liberação Miofascial. Deste m o do, o estudo buscou analisar e comparar um programa de treinamento para ganho de potência muscular com fortalecimento muscular resistido isolado e os resultados de sua combinação com a Liberação Miofascial. Trata-se de um estudo quantitativo, transversal, analítico, de caráter experimental, comparativo, controlado e randomizado. A amostra foi composta por 11 mulheres com idade de 18 a 40 anos subdivididas em dois grupos de intervenção. As intervenções ocorerram 3 vezes por semana durante 4 semanas. Os membros do Grupo controle realizaram apenas o fortalecimento muscular com exercício de agachamento a partir de 0 º de flexão de joelhos até o limite de 90º de flexão e retornando ao grau 0. As voluntárias do Grupo Liberação Miofascial associado ao treino de força inicialmente foram submetidas a intervenções de Liberação Miofascial dos músculos quadríceps bilateralmente e posteriormente ao treino de fortalecimento muscular descrito no grupo controle. Foram avaliadas as variáveis distância do salto vertical e carga suportada em 1 Repetição Máxima. A estatística inferencial utilizada foi através do t este T de Student emparelhado para verificar a diferença entre as médias do antes e depois dos tratamentos em cada grupo. Para verificar as diferenças em relação às técnicas utilizadas em grupos diferentes foi realizado o teste T de Student não compartilhado. Os resultados demonstraram não haver diferença estatisticamente significante entre os grupos no que se refere a carga máxima suportada em 1 Repetição Máxima (p=0,484), mesmo sendo essa diferença numericamente de 3,31kg a mais de ganho para o Grupo que utilizou a Liberação Miofascial associada ao treino de força, e não foi encontrada diferença significativa (p=0,068) entre a distância de salto vertical nos grupos, apesar desta distânicia ser 4,35 cm maior também no grupo Liberação Miofascial associada ao treino de força. Foi possível demonstrar, desta form a, que a liberação miofascial não otimiza o ganho da potencia muscular associado ao exercício resistido . Desta forma, através dos resultados deste estudo, não é possível recomendar a utilização da LM como um recurso para ser utilizado pré treino com objetivo de ganho de potência muscular...(AU)

The prescription of exercises to gain muscle strength and power is used to help in the rehabilitation of muscle injuries and for physical improvement in sport practices. Among the techniques that are pointed as possible ways that could help in muscle strengthening and power, Myofascial Release stands out. Thus, the study sought to analyze and compare a training program for muscle power gain with isolated resistance muscle strengthening and the results of its combination with myofascial release. It is a quantitative, cross-sectional, analytical, experimental, comparative, controlled and randomized study. Our sample consisted of 11 women aged 18 to 40 years old, subdivided into two interventio n gro ups. Th e interventions occurred 3 times a week for 4 weeks. Control Group members only perform muscle strengthening with squats from 0º of knee flexion up to the limit of 90º of flexion and return of grade 0. As volunteers of the Myofascial Release Group associated with strength training, t hey were subm it ted t o Myofascial Release of the quadriceps muscles bilaterally and after the muscle st rengt hening t raining described in the control group. The variables vertical jump distance and load supported in 1 Maximum Repetition were evaluated. The inferential statistics used was through the paired Student's T test to verify the difference between the means of before and after treatments in each group. To verify the differences in relation to the techniques used in different groups, the Student's t-test was not shared. T here was n o statistically significant difference between the groups regarding the maximum load supported in 1 Maximum Repeat (p=0.484), even though this difference was numerically 3 .3 1kg m o re gain fo r t he Myofascial Release Group.No significant difference (p=0.068) was found either between t he v ertical jump distance, which was 4.35 cm higher ­ also in the Myofascial Release group. Thus, it was demonstrated that myofascial release does not optimize the gain in muscle power associat ed with resistance exercises. Thus, through the results of this study, it is not possible to recommend the use of SCI as a resource to be used pre-training in order to gain muscle power...(AU)

Bioactive Compounds from the Aerial Parts of Evolvulus linarioides.

Three new caryophyllane-type sesquiterpenoids, linariophyllenes A-C (1-3), two new hamamelitol derivatives, linaritols A (4) and B (5), two new chromones, linariosides A (6) and B (7), and three known chromones, cnidimol C (8), monnieriside A (9), and undulatoside A (10), were identified from the aerial parts of Evolvulus linarioides. The structures of these compounds were elucidated by NMR, MS, and IR data. The absolute configurations of compounds 1-5 and 7 were established via electronic circular dichroism data. The anti-inflammatory potential of compounds 1-5 and 7-10 was evaluated by determining their ability to inhibit the production of nitric oxide (NO) and proinflammatory cytokine IL-1ß by stimulated J774 macrophages. Compounds tested at noncytotoxic concentrations inhibited NO production by macrophages, exhibiting IC50 values between 17.8 and 66.2 µM, and inhibited IL-1ß production by stimulated macrophages by 72.7-96.2%.