Abstract Introduction Fibromyalgia is a complex, generalized, and diffuse chronic musculoskeletal pain. Pharmacological approaches are widely used to relieve pain and increase quality of life. Low-Dose Naltrexone (LDN) was shown to increase the nociceptive threshold in patients with fibromyalgia. Transcranial Direct Current Stimulation (tDCS) is effective for pain management. Objective The purpose of this study was to evaluate the analgesic and neuromodulatory effects of a combination of LDN and tDCS in patients with fibromyalgia. Methods This was a randomized, double-blinded, parallel, placebo/sham-controlled trial (NCT04502251; RBR-7HK8N) in which 86 women with fibromyalgia were included, and written informed consent was obtained from them. The patients were allocated into four groups: LDN + tDCS (n = 21), LDN + tDCS Sham (n = 22), placebo + tDCS (n = 22), and placebo+tDCS Sham (n = 21). The LDN or placebo (p.o.) intervention lasted 26 days; in the last five sessions, tDCS was applied (sham or active, 20 min, 2 mA). The following categories were assessed: sociodemographic, Visual Analog Pain Scale (VAS), Pain Catastrophizing Scale (PCS), State-Trait Anxiety Inventory (STAI), Fibromyalgia Impact Questionnaire (FIQ), Beck Depression Inventory (BDI-II), Profile of Chronic Pain Scale (PCP:S), Pain Pressure Threshold (PPT), and Conditioned Pain Modulation (CPM). Blood samples were collected to analyze BDNF serum levels. Results At baseline, no significant difference was found regarding all measurements. VAS pain was significantly reduced in the LDN + tDCS (p = 0.010), LDN + tDCS Sham (p= 0.001), and placebo+tDCS Sham (p= 0.009) groups. In the PCP:S, the LDN+tDCS group showed reduced pain frequency and intensity (p= 0.001), effect of pain on activities (p= 0.014) and emotions (p= 0.008). Depressive symptoms reduced after all active interventions (p > 0.001). Conclusion Combined LDN+tDCS has possible benefits in reducing pain frequency and intensity; however, a placebo effect was observed in pain using VAS, and further studies should be performed to analyze the possible association.

ABSTRACT Obtaining knowledge about the distribution of spatial variability of soil properties is crucial to the proper site-specific management. One way to improve the quality of soil mapping is by using auxiliary information (covariate). The objective of this study was to test whether remote and proximal sensing data can assist in soil properties mapping through geostatistical prediction. We worked in an experimental area cultivated with sugarcane located in Sao Paulo State, Brazil, and selected five soil properties: organic matter, CEC, base saturation, K and P availability. Two covariates often used to express soil variation were chosen, one obtained by remote sensing (SWIR2 band) and the other by proximal sensing (apparent soil electrical conductivity – ECa). These covariates were individually and together used in geostatistical interpolation method (kriging with external drift). We found that ECa is a more promising covariate than SWIR2 band from orbital imaging. Such proximal sensing can identify the soil short-range spatial variability. However, when the soil property variability is well explained by the sampling procedure, multivariate geostatistical methods may not improve the mapping accuracy.

Although the genus Duguetia is well known for producing alkaloids as chemical constituents, there are no reports of alkaloids identified in the species D. lanceolata. Thus, aiming to identify the chemical composition of this species, the dereplication of alkaloidic phase was performed by use of ultra-high performance liquid chromatography high resolution electrospray ionization tandem mass spectrometry (UHPLC-HR-ESI-MS/MS) and 1H nuclear magnetic resonance (NMR). The chromatographic fractionation of the alkaloid extract from Duguetia lanceolata (Annonaceae) leaves afforded four fractions (I-IV) that were shown to be composed of aporphine alkaloids. 1H NMR analysis and UHPLC-HR-ESI-MS/MS based dereplication allowed the identification of eight alkaloids: glaucine (1), norglaucine (2), isocorydine (3), N-methyllaurotetanine (4), oxoglaucine (5), liriodenine (6), lanuginosine (7), dehydroglaucine (8). Compounds 2,3, 4,6 and 7 were described for the first time in this species, while alkaloids 1,5 and 8 are newly discovered in the genus Duguetia. Additionally, the antiparasitic activity of the four fractions was evaluated in vitro against Leishmania infantum and Trypanosoma cruzi. Fraction I, composed exclusively by 1, displayed activity against Leishmania infantum and Trypanosoma cruzi intracellular amastigotes, with half maximal inhibitory concentration (IC50) values of 7.5 and 28.6 µg mL-1, respectively. Fraction IV (constituted by 2,3 and 4) showed activity against promastigotes of Leishmania infantum with IC50 value of 50.0 µg mL-1, while fraction II (constituted by 5 and 6) showed activity against trypomastigotes of Trypanosoma cruzi, with IC50 values of 83.0 µg mL-1. This work showed that fragmentation in UHPLC-HR-ESI-MS/MS combined with 1H NMR analysis of fractions is useful for identifying alkaloids in mixtures. Additionally, it was also demonstrated the potential of aporphine alkaloids from Duguetia lanceolata St. -Hil (Annonaceae) in the search for new drug candidates for neglected diseases.