Polymeric nanoparticles containing kojic acid induce structural alterations and apoptosis-like death in Leishmania (Leishmania) amazonensis.

Leishmaniasis encompasses a cluster of neglected tropical diseases triggered by kinetoplastid phatogens belonging to the genus Leishmania. Current therapeutic approaches are toxic, expensive, and require long-term treatment. Nanoparticles are emerging as a new alternative for the treatment of neglected tropical diseases. Silk Fibroin is a biocompatible and amphiphilic protein that can be used for formulating nanoemulsions, while kojic acid is a secondary metabolite with antileishmanial actions. Thus, this study evaluated the efficacy of a nanoemulsion, formulated with silk fibroin as the surfactant and containing kojic acid (NanoFKA), against promastigote and amastigote forms of Leishmania (Leishmania) amazonensis. The NanoFKA had an average particle size of 176 nm, Polydispersity Index (PDI) of 0.370, and a Zeta Potential of -32.3 mV. It presented inhibitory concentration (IC50) values of >56 µg/mL and >7 µg/mL for the promastigote and amastigote forms, respectively. Ultrastructural analysis, cell cycle distribution and phosphatidylserine exposure showed that NanoFKA treatment induces apoptosis-like cell death and cell cycle arrest in L. (L.) amazonensis. In addition, NanoFKA exhibited no cytotoxicity against macrophages. Given these results, NanoFKA present leishmanicidal activity against L. (L.) amazonensis.

Development of nanostructured formulation from naringenin and silk fibroin and application for inhibition of lipoxygenase (LOX).

A simple low-energy method was used to obtain polymeric nanoparticles containing silk fibroin (SF), fatty butyl esters (oily phase) and the flavonoid naringenin. Experimental planning (Box-Behnken) was applied to investigate the optimal conditions for three factors (variation of the concentrations of SF, naringenin and fatty butyl ester) at three levels, with evaluation of particle size, polydispersity index (PDI) and zeta potential (ZP) as responses. The results showed that the polymeric particle was formed with sizes of 179.6 to 633.9 nm, PDI of 0.33 to 0.77 and ZP of -60.4 to -38.8 mV. The best responses under the optimized conditions (Nari-SF 9 and 15) were characterized through transmission electron microscopy (TEM), Fourier-transform infrared (FT-IR), visible ultraviolet (UV-vis) and fluorescence, which confirmed that coated nanoparticles had been obtained. It was shown that the nanoformulation had excellent stability, the bioavailability of naringenin had been improved through use of the biopolymer and high inhibition of the enzyme lipoxygenase had been achieved in vitro.

Euterpe oleracea Mart (Açaizeiro) from the Brazilian Amazon: A Novel Font of Fungi for Lipase Production.

Lipases (EC 3.1.1.3) are hydrolases that catalyze triglycerides hydrolysis in free fatty acids and glycerol. Among the microorganisms that produce lipolytic enzymes, the entophytic fungi stand out. We evaluated 32 fungi of different genera, Pestalotiopsis, Aspergillus, Trichoderma, Penicillium, Fusarium, Colletotrichum, Chaetomium, Mucor, Botryodiplodia, Xylaria, Curvularia, Neocosmospora and Verticillium, isolated from Euterpe oleracea Mart. (Açaizeiro) from the Brazilian Amazon for lipase activity. The presence of lipase was evidenced by the deposition of calcium crystals. The endophytic Pestalotiopsis sp. (31) and Aspergillus sp. (24) with Pz 0.237 (++++) and 0.5 (++++), respectively, were the ones that showed the highest lipolytic activity in a solid medium. Lipase activity was rated in liquid medium, in a different range of temperatures (°C), pH and time (days). The values obtained in the production of lipase by the endophytic fungi were 94% for Pestalotiopsis sp. (31) and 93.87% for Aspergillus sp. (24). Therefore, it is emphasized that the endophytic fungus isolated the E. oleracea palm may be a potential candidate to produce enzymes of global commercial interest.

Can mental practice adjunct in the recovery of motor function in the upper limbs after stroke? A systematic review and meta-analysis.

BACKGROUND: Studies indicate that mental practice can be an adjuvant rehabilitation, improving motor functions. AIM: To synthesize the evidence on the intervention with the mental practice for the rehabilitation of the upper limb after stroke in the context of a dependent task. METHODS: The review was registered on the PROSPERO with protocol number: CRD42020166624. We searched the PubMed, Medline, Embase, Central, PEDro, and Web of Science from randomized clinical trials from 1975 to 2022. A literature review was conducted with 13 studies that synthesized findings on mental practice such as adjuvant rehabilitation in the recovery of the upper limb after stroke based on Fugl-Meyer Assessment (FMA) Motor and action research arm test (ARAT) scores. RESULTS: The sample size was 232 were part of the intervention group and 180 of the control group. The findings no showed results in favor of mental practice after stroke accordingly to ARAT and FMA Motor scores (P > 0.05). CONCLUSION: Current evidence does not support the use of the mental practice to increase the recovery of the upper limb after stroke, although the evidence is conflicting for some aspects of the technique.

Green Extraction of Annatto Seed Oily Extract and Its Use as a Pharmaceutical Material for the Production of Lipid Nanoparticles.

This work developd nanomaterials formulated from annatto seed oily extract (ASE), myristic acid (tetradecanoic acid), and their fatty acid esters. The annatto seed oily extract was obtained using only soybean oil (ASE + SO) and Brazil nut oil (ASE + BNO). The UV/VIS analysis of the oily extracts showed three characteristic peaks of the bixin molecule at 430, 456 and 486 nm. The lipid nanoparticles obtained using myristic acid and ASE + BNO or only BNO showed better results than the oil soybean extract, i.e., the particle size was <200 nm, PDI value was in the range of 0.2−0.3, and had no visual physical instability as they kept stable for 28 days at 4 °C. Lipid nanoemulsions were also produced with esters of myristic acid and ASE + BNO. These fatty acid esters significantly influenced the particle size of nanoemulsions. For instance, methyl tetradecanoate led to the smallest particle size nanoemulsions (124 nm), homogeneous size distribution, and high physical stability under 4 and 32 °C for 28 days. This work demonstrates that the chemical composition of vegetable oils and myristic acid esters, the storage temperature, the chain length of fatty acid esters (FAE), and their use as co-lipids improve the physical stability of lipid nanoemulsions and nanoparticles from annatto seed oily extract.

Open monitoring meditation alters the EEG gamma coherence in experts meditators: The expert practice exhibit greater right intra-hemispheric functional coupling.

AIM: This study investigated the differences in frontoparietal EEG gamma coherence between expert meditators (EM) and naïve meditators (NM). MATERIAL AND METHODS: This is a cross-sectional study with a sample of twenty-one healthy adults divided under two groups (experts meditators vs. naive-meditators), with analyzing the intra-hemispheric coherence of frontoparietal gamma oscillations by electroencephalography during the study steps: EEG resting-state 1, during the open presence meditation practice, and EEG resting-state 2. RESULTS: The findings demonstrated greater frontoparietal EEG coherence in gamma for experts meditators in the Fp1-P3, F4-P4, F8-P4 electrode pairs during rest 1 and rest 2 (p ≤ 0.0083). In addition, we evidenced differences in the frontoparietal EEG coherence for expert meditators in F4-P4, F8-P4 during the meditation (p ≤ 0.0083). CONCLUSION: Our results can support evidence that the connectivity of the right frontoparietal network acts as a biomarker of the enhanced Open monitoring meditation training.

Bromazepam increases the error of the time interval judgments and modulates the EEG alpha asymmetry during time estimation.

AIM: This study investigated the bromazepam effects in male subjects during the time estimation performance and EEG alpha asymmetry in electrodes associated with the frontal and motor cortex. MATERIAL AND METHODS: This is a double-blind, crossover study with a sample of 32 healthy adults under control (placebo) vs. experimental (bromazepam) during visual time-estimation task in combination with electroencephalographic analysis. RESULTS: The results demonstrated that the bromazepam increased the relative error in the 4 s, 7 s, and 9 s intervals (p = 0.001). In addition, oral bromazepam modulated the EEG alpha asymmetry in cortical areas during the time judgment (p ≤ 0.025). CONCLUSION: The bromazepam decreases the precision of time estimation judgments and modulates the EEG alpha asymmetry, with greater left hemispheric dominance during time perception. Our findings suggest that bromazepam influences internal clock synchronization via the modulation of GABAergic receptors, strongly relating to attention, conscious perception, and behavioral performance.

Larvicidal activity against Aedes aegypti and molecular docking studies of compounds extracted from the endophytic fungus Aspergillus sp. isolated from Bertholletia excelsa Humn. & Bonpl.

Endophytic fungi are microorganisms capable of colonizing the interior of plant tissues without causing damage to them. The study of the secondary metabolites produced by their vast biodiversity fungal is relevant for the discovery of new products for biotechnological and agrochemical applications. In addition, extract of the endophytic fungus Aspergillus sp., isolated from the almonds of Bertholletia excelsa Humn & Bonlp collected in the Brazilian Amazon, oviposition deterrent, and larvicidal activity of against Aedes aegypti. In the oviposition deterrence test was observed that females able to lay eggs preferred the control oviposition sites (46.6%). Furthermore, the extract showed larvicidal activity with LC50 26.86 µg/mL at 24 h and 18.75 µg/mL at 48 h. Molecular docking studies showed the compound Aspergillol B a potent larvicide by to inhibit the acetylcholinesterase enzyme (- 7.74 kcal/mol). These results indicate that compounds from secondary metabolites of Aspergillus sp., isolated from almonds of B. excelsa, are useful biological potential against vectors A. aegypti.

Non-immersive 3D virtual stimulus alter the time production task performance and increase the EEG theta power in dorsolateral prefrontal cortex.

AIM: The study investigated the cortical activity changes and time production task performance induced by changes in motion speed of a non-immersive 3D virtual stimulus. MATERIAL AND METHODS: Twenty-one individuals were participated in the crossover study with the visual-time reproduction task under three-speed conditions: original, slow and fast virtual stimulus. In addition, the electroencephalographic analysis of the theta band power in the dorsolateral prefrontal cortex was done simultaneously with time production task execution. RESULTS: The results demonstrated that in the slow speed condition, there is an increase in the error in the time production task after virtual reality (p < 0.05). There is also increased EEG theta power in the right dorsolateral prefrontal cortex in all speed conditions (p < 0.05). CONCLUSIONS: We propose that the modulations of speed of virtual stimulus may underlie the accumulation of temporal pulses, which could be responsible for changes in the performance of the production task of the time intervals and a substantial increase in right dorsolateral prefrontal cortex activity related to attention and memory, acting in cognitive domains of supraseconds.

Repetitive transcranial magnetic stimulation changes cognitive/motor tasks performance: An absolute alpha and beta power study.

The voluntary movement demands integration between cognitive and motor functions. During the initial stages of motor learning until mastery of a new motor task, and during a demanding task that is not automatic, cognitive and motor functions can be perceived as independent from each other. Areas used for actually performing motor tasks are essentially the same used by Motor Imagery (MI). The main objective of this study was to investigate inhibition effects on cognitive functions of motor skills induced by low-frequency (1 Hz) Repetitive Transcranial Magnetic Stimulation (rTMS) at the sensory-motor integration site (Cz). In particular, the goal was to examine absolute alpha and beta power changes on frontal regions during Execution, Action observation, and Motor Imagery of finger movement tasks. Eleven healthy, right-handed volunteers of both sexes (5 males, 6 females; mean age 28 ± 5 years), with no history of psychiatric or neurological disorders, participated in the experiment. The execution task consisted of the subject flexing and extending the index finger. The action observation task involved watching a video of the same movement. The motor imagery task was imagining the flexion and extension of the index finger movement. After performing the tasks randomly, subjects were submitted to 15 min of low-frequency rTMS and performed the tasks again. All tasks were executed simultaneously with EEG signals recording. Our results demonstrated a significant interaction between rTMS and the three tasks in almost all analyzed regions showing that rTMS can affect the frontal region regarding Execution, Action observation, and Motor Imagery tasks.

Methylphenidate decreases the EEG mu power in the right primary motor cortex in healthy adults during motor imagery and execution.

This study investigated the effects of dopaminergic drugs on the EEG mu power during motor imagery, action observation, and execution. This is a double-blind, crossover study with a sample of 15 healthy adults under placebo vs. methylphenidate vs. risperidone conditions during motor imagery, action observation, and execution tasks. The participants had drug dosage adjustment based on body weight/dose (mg/kg). We also analyzed the mu band power by electroencephalography during the study steps. The main result is the interaction between the condition and task factors for the C3 and C4 electrodes, with decreasing EEG mu power in the methylphenidate when compared to risperidone (p ≤ 0.0083). Our results can indicate that the methylphenidate decreases the neurophysiological activity in the central cortical regions during the perceptual experience of tasks with or without body movement.

Virtual reality exposure therapy for neuro-psychomotor recovery in adults: a systematic review.

OBJECTIVE: To analyse the virtual reality applications in the subjects' neuro-psychomotor functions rehabilitation with motor and/or neuropsychiatric impairment. METHODS: The search was carried out in nine databases (Scopus, PubMed, Web of Science, ScienceDirect, Cochrane Library, CINAHL, PsycINFO, LILACS, and SciELO), from December 2017 to March 2019. An additional manual search was performed, taking into consideration references of the included papers, through the same eligibility criteria. The methodological quality of the included papers was evaluated using the Physiotherapy Evidence Database (PEDro). RESULTS: One hundred and twenty-two papers were selected by the initial screening, but only 33 studies participated in the final inclusion in the study (11 clinical trials and 14 experimental studies). The data extracted were: the proposed objective, the sample population, the neurological condition treated, the VR modality used in the procedures and the study intervention period. CONCLUSIONS: Virtual reality supports the rehabilitation process of neuro-psychomotor functions, allowing potential gains in the patients' recovery. Therefore, its development facilitates its availability and access in the future.Implications for rehabilitationIt has minimal adverse effects during the virtual therapies performance, such as the presence of vertigo related to cybersickness conditions, suggesting virtual reality as a safe rehabilitation tool, compared to other therapies.Virtual reality use is useful and effective in helping the rehabilitation process of motor, cognitive and psychosocial functions.It plays a role as an adjunctive and complementary therapy in the neuro-psychomotor rehabilitation process to obtain a clinically significant result.

Unskilled shooters improve both accuracy and grouping shot having as reference skilled shooters cortical area: An EEG and tDCS study.

Transcranial direct current stimulation (tDCS) has been used as a non-invasive method for enhanced motor and cognitive abilities. However, no previous study has investigated if the tDCS application in unskilled shooters on cortical sites, selected based on the cortical activity of skilled shooters, improves the accuracy and shot grouping. Sixty participants were selected, which included 10 skilled shooters and 50 unskilled shooters. After we identified the right dorsolateral prefrontal cortex (DLPFC) as the area with the highest activity in skilled shooters, we applied anodal tDCS over the right DLPFC in the unskilled shooters under two conditions: sham-tDCS (placebo) and real-tDCS (anodal tDCS). We also analyzed electroencephalography. Our results indicated that anodal tDCS application enhanced the shot accuracy (p = 0.001). Furthermore, the beta power in the EEG recording was higher in the left DLPFC, left and right parietal cortex (p = 0,001) after applying anodal tDCS, while the low-gamma power was higher in the right DLPFC in sham-tDCS (p = 0.001) and right parietal cortex after anodal-tDCS (p = 0.001). Our findings indicate that anodal tDCS can improve accuracy and shot grouping when applied over the unskilled shooters' right DLPFC. Furthermore, beta and low-gamma bands are influenced by anodal tDCS over the right DLPFC, which may be predictive of skill improvement.

Time estimation exposure modifies cognitive aspects and cortical activity of attention deficit hyperactivity disorder adults.

AIM: This study investigated whether time-estimation task exposure influences the severity of Attention Deficit Hyperactivity Disorder (ADHD), as well as theta band activity in the dorsolateral prefrontal cortex and ventrolateral prefrontal cortex. MATERIAL AND METHODS: Twenty-two patients with ADHD participated in a crossover experiment with a visual time-estimation task under control conditions (without exposure to time estimation tasks) and experimental (thirty days exposure to time-estimation tasks) in association with electroencephalographic analysis of theta band. RESULTS: ADHD patients with thirty days of time-estimation task exposure presented a worse performance of the time-estimation task, as revealed by the measurements of the absolute error and relative error (p ≤ 0.05). However, our findings show the improvement of self-reported symptoms of attention, impulsivity, and emotional control in patients after the time-estimation task exposure (p = 0.0001). Moreover, the theta band oscillations in the right dorsolateral prefrontal cortex and in the ventrolateral prefrontal increased with thirty days of time-estimation task exposure (p ≤ 0.05). CONCLUSION: We propose that the decrease in EEG theta power may indicate an efficient accumulation of temporal pulses, which could be responsible for the improvement in the patient cognitive aspects as demonstrated by the current study. Time-estimation task improves ADHD cognitive symptoms, with a substantial increase in cortical areas activity related to attention and memory, suggesting its use as a tool for cognitive timing function management and non-invasive therapeutic aid in ADHD.

Microenvironment of Mycobacterium smegmatis Culture to Induce Cholesterol Consumption Does Cell Wall Remodeling and Enables the Formation of Granuloma-Like Structures.

Pathogenic species of mycobacteria are known to use the host cholesterol during lung infection as an alternative source of carbon and energy. Mycobacteria culture in minimal medium (MM) has been used as an in vitro experimental model to study the consumption of exogenous cholesterol. Once in MM, different species of mycobacteria start to consume the cholesterol and initiate transcriptional and metabolic adaptations, upregulating the enzymes of the methylcitrate cycle (MCC) and accumulating a variety of primary metabolites that are known to be important substrates for cell wall biosynthesis. We hypothesized that stressful pressure of cultures in MM is able to induce critical adaptation for the bacteria which win the infection. To identify important modifications in the biosynthesis of the cell wall, we cultured the fast-growing and nonpathogenic Mycobacterium smegmatis in MM supplemented with or without glycerol and/or cholesterol. Different from the culture in complete medium Middlebrook 7H9 broth, the bacteria when cultured in MM decreased growth and changed in the accumulation of cell wall molecules. However, the supplementation of MM with glycerol and/or cholesterol recovered the accumulation of phosphatidylinositol mannosides (PIMs) and other phospholipids but maintained growth deceleration. The biosynthesis of lipomannan (LM) and of lipoarabinomannan (LAM) was significantly modulated after culture in MM, independently of glycerol and/or cholesterol supplementation, where LM size was decreased (LM13-25KDa) and LAM increased (LAM37-100KDa), when compared these molecules after bacteria culture in complete medium (LM17-25KDa and LAM37-50KDa). These changes modified the cell surface hydrophobicity and susceptibility against H2O2. The infection of J774 macrophages with M. smegmatis, after culture in MM, induced the formation of granuloma-like structures, while supplementation with cholesterol induced the highest rate of formation of these structures. Taken together, our results identify critical changes in mycobacterial cell wall molecules after culture in MM that induces cholesterol accumulation, helping the mycobacteria to increase their capacity to form granuloma-like structures.

The role of low-frequency rTMS in the superior parietal cortex during time estimation.

The low-frequency repetitive transcranial magnetic stimulation (rTMS) application has been associated with changes in cognitive processes embedded during time perception tasks. Although several studies have investigated the influence of neuromodulation on time perception, the effect of the 1-Hz rTMS application on the superior parietal cortex is not clearly understood. This study analyzes the effect of the low-frequency rTMS on time estimation when applied in the parietal medial longitudinal fissure. For the proposed study, 20 subjects were randomly selected for a crossover study with two conditions (sham and 1 Hz). Our findings reveal that participant underestimate 1-s time interval and overestimate 4-s and 9-s time intervals after 1-Hz rTMS (p ≤ 0.05). We conclude that the 1-Hz rTMS in the parietal medial longitudinal fissure delays short interval and speed up long time intervals. This could be due to the effect of parietal inhibition on the attentional level and working memory functions during time estimation.

Tarsal tunnel syndrome: a still challenge condition / Síndrome do túnel do tarso: uma condição ainda desafiadora

Tarsal tunnel syndrome is a rare, under diagnosed and often confused neuropathy with other clinical entities. There is a lack of population studies on this disease. Herein, we performed a non-systematic review of articles between January 1992 and February 2018. Although with a less complex anatomy comparing to the carpal tunnel, the tarsal tunnel is source of pain and some other conditions. Treatment involves conservative measures such as analgesics and physical therapy rehabilitation or surgical procedures in case of conservative treatment failure. Randomized control studies are lack and mandatory for uncover the best modality of treatment for this condition.

A Síndrome do túnel do tarso é uma rara e subdiagnosticada neuropatia geralmente confundida com outras entidades clínicas. Há falta de estudos populacionais sobre a doença. Assim sendo, realizamos uma revisão da literatura de artigos entre Janeiro de 1992 e fevereiro de 2018. Apesar de possuir uma anatomia de menor complexidade comparada ao túnel do carpo, o túnel do tarso é origem de dor e algumas outras condições. O tratamento envolve medidas conservadoras como analgésicos e terapia de reabilitação ou procedimentos cirúrgicos, em caso de falha do tratamento conservador. Estudos randomizados são escassos e necessários para descoberta da melhor modalidade de tratamento desta condição.

Methylphenidate modifies activity in the prefrontal and parietal cortex accelerating the time judgment.

Methylphenidate produces its effects via actions on cortical areas involved with attention and working memory, which have a direct role in time estimation judgment tasks. In particular, the prefrontal and parietal cortex has been the target of several studies to understand the effect of methylphenidate on executive functions and time interval perception. However, it has not yet been studied whether acute administration of methylphenidate influences performance in time estimation task and the changes in alpha band absolute power in the prefrontal and parietal cortex. The current study investigates the influence of the acute use of methylphenidate in both performance and judgment in the time estimation interpretation through the alpha band absolute power activity in the prefrontal and parietal cortex. This is a double-blind, crossover study with a sample of 32 subjects under control (placebo) and experimental (methylphenidate) conditions with absolute alpha band power analysis during a time estimation task. We observed that methylphenidate does not influence task performance (p > 0.05), but it increases the time interval underestimation by over 7 s (p < 0.001) with a concomitant decrease in absolute alpha band power in the ventrolateral prefrontal cortex and dorsolateral prefrontal cortex and parietal cortex (p < 0.001). Acute use of methylphenidate increases the time interval underestimation, consistent with reduced accuracy of the internal clock mechanisms. Furthermore, acute use of methylphenidate influences the absolute alpha band power over the dorsolateral prefrontal cortex, ventrolateral prefrontal cortex, and parietal cortex.

Low-frequency rTMS stimulation over superior parietal cortex medially improves time reproduction and increases the right dorsolateral prefrontal cortex predominance.

AIM OF THE STUDY: Previous studies have shown that several cortical regions are involved in temporal tasks in multiple timescales. However, the hemispheric predominance of the dorsolateral prefrontal cortex (DLPFC) during time reproduction after repetitive low-frequency transcranial magnetic stimulation (rTMS) is relatively unexplored. Here, we study the effects of 1 Hz rTMS and sham stimulation applied medially over the superior parietal cortex (SPC) on the DLPFC alpha and beta band asymmetry and on time reproduction. MATERIALS AND METHODS: For this purpose, we have combined rTMS with electroencephalography in 20 healthy subjects who performed the time reproduction task in two conditions (sham and 1 Hz). RESULTS: The worst performance was observed in sham and 1Hz conditions for longer time intervals (p < .05), with the 1Hz condition subjects sub-reproducing the time interval, closer to the target interval (p < .05). The right DLPFC hemispheric predominance was found in both conditions, but after low-frequency rTMS, the right hemisphere predominance increased in the 1Hz condition (p < .05). CONCLUSIONS: Results of this study suggest that rTMS applied over the SPC influences time interval interpretation and the DLPFC functions. Future studies would explore the effects of the rTMS application to other cortical areas, and study how it influences time interval interpretation.

The BDNF Val66Met Polymorphism Promotes Changes in the Neuronal Integrity and Alters the Time Perception.

Studies at the molecular level aim to integrate genetic and neurobiological data to provide an increasingly detailed understanding of phenotypes related to the synchronization ability and brain oscillations in time perception. Genetic variation as a modifying factor at cellular and neurochemical levels permeates several neurofunctional aspects in time-lapse duration concentrating from milliseconds to hours. Thus, the review presents the BDNF Val66Met polymorphism association in a dynamic frame of brain neurotrophic factor expression in the adaptation, integrity, and neuronal synchronism processes in the ability to estimate multisensory stimuli at different time intervals. Our study aims to understand the molecular aspects involved in a neurobiological domain pertinent to the time judgment, tracing a genetic profile of association with psychometric functions and behavioral performances related to timing stimuli.