scholarly journals An FMRI-compatible System for Targeted Electrical Stimulation

Author(s):  
Louise Møller Jørgensen ◽  
Anders Ohlhues Baandrup ◽  
Joseph Mandeville ◽  
Andreas Nørgaard Glud ◽  
Jens Christian Hedemann Sørensen ◽  
...  

Abstract BackgroundElectroceutical therapy, applied in various forms, is a rapidly growing therapeutic option to be considered across different medical disorders, particularly within psychiatry, neurology, chronic pain and rehabilitation therapy. Combining targeted electric stimuli with feedback from fMRI can provide valuable information about the mechanisms underlying the therapeutic effects. So far, however, such studies have been hampered by the lack of technology to conduct such experiments in a both accurate and safe manner. We here present a patented system, a fMRI compatible electrical stimulator, developed for fMRI data acquisition during deep brain stimulation (DBS), as well as the first proof-of-concept neuroimaging data in pigs obtained with a prototype of the device.MethodsThe system consists of two modules, placed in the control and scanner room, with corresponding optical modules and signal converters, connected by optical fiber led through wave guides and back looped for quality assurance. The system is also connected to the MRI scanner to timely initiate the stimulation sequence at start of scan. We evaluated the system in four pigs with DBS in the subthalamic nucleus (STN) where we acquired the BOLD response in the STN and neocortex, with stimulation turned on and off in a block design synchronized to the scanning sequence.ResultsWe found that the system delivered a robust electrical stimulus to the implanted electrode during the entire experimental period. The stimulus was confirmed to be in sync with the preprogrammed fMRI block design. All pigs displayed a DBS-STN induced neocortical BOLD response, but none in the site of the implanted electrode. The system solves three major problems related to electrical stimuli and fMRI examinations, namely preventing distortion of the fMRI signal, enabling communication that synchronize the experimental conditions, and surmounting the safety hazards caused by interference from the powerful magnetic field and RF emission. ConclusionsThe patented fMRI compatible electrical stimulator, based on an optic fiber solution, circumvents previous problems related to DBS electroceuticals and fMRI. The system allows flexible modifications for fMRI designs and stimulation parameters but can also be customized to electroceutical applications beyond DBS, applicable for a broad range of medical conditions.

2018 ◽  
Vol 31 (1) ◽  
pp. 1-8
Author(s):  
MARCOS DA SILVA BRUM ◽  
THOMAS NEWTON MARTIN ◽  
VINÍCIUS SANTOS DA CUNHA ◽  
LUIZ FERNANDO TELEKEN GRANDO ◽  
ALEX TAGLIAPIETRA SCHONELL

ABSTRACT The objective of this study was to evaluate the phytomorphological parameters of soybean in a crop-livestock system inoculated with Azospirillum brasilense. The experiment was conducted in Santa Maria, Brazil, for two agricultural years (2 Paper extracted from the doctoral thesis of the first author. 012/2013 and 2013/2014) in a randomized complete block design with three replications. In the winter, the black oat and ryegrass pasture was managed with sheep under different grazing systems: (I) - a conventional grazing (CG) system, where the animals remained in the pasture throughout the experimental period without any pasture height control; (II, III, and IV) - systems with post-grazing pasture heights of 10, 20, and 30 cm, respectively; and (NG) - one control without grazing. All treatments received two nitrogen doses (50 and 100 kg ha-1) and inoculation or no inoculation (A. brasilense). The soybean cultivar BMX Potência RR was sown using no-tillage on 16 November 2012 and 1 December 2013. In each plot, seven rows of plants with spacing of 0.45 m were used, and in four rows, the seeds were inoculated with the bacterium A. brasilense. The phytomorphological variables and grain productivity were evaluated. In a croplivestock system, soybean has better productivity when established on black oat and ryegrass pasture managed with post-grazing pasture heights of between 20 and 30 cm. Areas under conventional grazing in the winter led to smaller soybean plants with lower first and last pod heights. Inoculation with A. brasilense should not be used alone in soybean cultivation.


2021 ◽  
Author(s):  
Moataz Dowaidar

Metabolic syndrome affects 24–42 percent of individuals over the age of 50 in the United States. Dietary treatments tailored to the APOE genotype may help patients with MeS. Both mitotic and meiotic epigenetics are heritable. SREBP 1 and 2 genes overexpress in response to low cholesterol, statins, and insulin tolerance, resulting in decreased fatty acid oxidation, insulin signalling, and HDL-c levels. FTO is a key gene in the metabolic syndrome predisposition which may be a therapeutic option. MicroRNA repression of the VEGF 62 reference gene is prevented by the LncRNA MIAT/miR-150-5p complex. MEG3, a maternally expressed three-letter noncoding RNA, has been related to endothelial cell angiogenesis. Phosphorylation of p38 and JNK improved in the absence of (SRA) lncRNAs, resulting in decreased insulin signaling.Mipomersen is a 20-mer oligonucleotide that binds to the APOB mRNA's coding region. Volanersorsen has finished phase II and III clinical trials, making it the first APOC3 ASO to do so. ASO targeting APOB3 based on next-generation ligands is also in the early stages of research. Angptl3 is another successful genome editing target. Given the role of ANGPTL3 in TRL metabolism, Dr. David Seres suggests that this editing may have additional or synergistic therapeutic effects. He claims that defects in the LDLR gene cause the most common genetic form of hypercholesterolemia, FH.


2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Yanli Liu ◽  
Fen Yang ◽  
Shengying Liang ◽  
Qing Liu ◽  
Sulei Fu ◽  
...  

Peripheral nerve injuries are typically caused by either trauma or medical disorders, and recently, stem cell-based therapies have provided a promising treatment approach. Menstrual blood-derived endometrial stem cells (MenSCs) are considered an ideal therapeutic option for peripheral nerve repair due to a noninvasive collection procedure and their high proliferation rate and immunological tolerance. Here, we successfully isolated MenSCs and examined their biological characteristics including their morphology, multipotency, and immunophenotype. Subsequent in vitro studies demonstrated that MenSCs express high levels of neurotrophic factors, such as NT3, NT4, BDNF, and NGF, and are capable of transdifferentiating into glial-like cells under conventional induction conditions. Moreover, upregulation of N-cadherin (N-cad) mRNA and protein expression was observed after neurogenic differentiation. In vivo studies clearly showed that N-cad knockdown via in utero electroporation perturbed the migration and maturation of mouse neural precursor cells (NPCs). Finally, a further transfection assay also confirmed that N-cad upregulation in MenSCs results in the expression of S100. Collectively, our results confirmed the paracrine effect of MenSCs on neuroprotection as well as their potential for transdifferentiation into glial-like cells and demonstrated that N-cad upregulation promotes the neurogenic differentiation of MenSCs, thereby providing support for transgenic MenSC-based therapy for peripheral nerve injury.


1983 ◽  
Vol 69 (4) ◽  
pp. 305-308 ◽  
Author(s):  
Franco Zunino ◽  
Renato Marchesini ◽  
Elsa Melloni ◽  
Giuseppina Savi ◽  
Gabriella Pezzoni ◽  
...  

The effectiveness of laser photoradiation therapy with hematoporphyrin derivative sensitization was tested in the MS-2 sarcoma. This solid tumor, transplanted into the pad of the hind leg of BALB/c mice, was found to be a sensitive experimental model for a quantitative evaluation of response to phototherapy and for determination of critical parameters in laser phototherapy treatment. Under our experimental conditions, optimal therapeutic effects appeared to be critically dependent on drug dose, number of treatments, light intensity, and irradiation of the peripheral border of the tumor.


2020 ◽  
Author(s):  
Jalise Fabíola Tontini ◽  
Cesar Henrique Espírito Candal Poli ◽  
Viviane da Silva Hampel ◽  
Mariana de Souza Farias ◽  
Neuza Maria Fajardo ◽  
...  

AbstractTropical sward characteristics can alter lamb ingestive behavior. Our study evaluated the ingestive behavior of young lambs in different tropical pastures to identify which variables interfere in their grazing activity. Two years of study were carried out with 54 weaned lambs distributed in three different swards: 1) monoculture of a upright grass, guinea grass (Panicum maximum; GG); 2) monoculture of a shrubby legume pigeon pea (Cajanus cajan; PP) and 3) contiguous areas with half the paddock with GG and half with PP (GP). The experiment was set out in a randomized complete block design. Lamb ingestive behavior was observed from sunrise to sunset with records every 5 minutes. To identify the main variables that affected with the lamb grazing activity, a multivariate analysis of the Decision Tree was performed. Our results showed that there was no difference in the ingestive behavior parameters of young lambs in different swards (P > 0.05). There was interaction among the swards and the experimental periods for the variables idleness time and biting rate (P ≤ 0.05). Grazing time of the animals increased 40% with experimental period progression. The Decision Tree identified leaf:stem ratio as the variable that most influenced lamb grazing time in GG and GP swards while in the PP sward grazing time was directly related to the pasture height. The behavior of young lambs on tropical pasture is variable as there is a change in the behavioral response over time. In addition, the grazing time of these animals can be estimated by means of variables related to pasture structural characteristics (leaf:stem ratio and height) together with chemical variables.


2020 ◽  
Vol 28 ◽  
pp. 364-374
Author(s):  
Gustavo Henrique Miguel da Cruz ◽  
Fernando França da Cunha ◽  
Epitácio José de Souza ◽  
Andrisley Joaquim da Silva ◽  
Roberto Filgueiras

One of the bottlenecks in relation to the production of forest seedlings is irrigation, especially in less-tech nurseries. The small volumes of substrate, where the seedlings develop, lead to low water storage. This fact can lead to water deficit and significant losses in the production of seedlings, generating even mortality. The objective of this study was to determine the best irrigation frequencies for Eucalyptus grandis seedling production in less-tech nurseries. The experiment was conducted between 2013/08/04 and 2013/23/07 (106 days) and conducted in Chapadão do Sul county, Brazil. The experiment was set up in a randomized complete block design, with five replications. Four irrigation frequencies were tested: IF1 (one daily irrigation - 11:00 a.m.), IF2 (two daily irrigations - 11:00 a.m. and 7:00 p.m.), IF3 (three daily irrigations - 07:00 a.m., 11:00 a.m. and 7:00 p.m.) and IF4 (four daily irrigations - 07:00 a.m., 11:00 a.m., 3:00 p.m. and 7:00 p.m.). The sample units were composed of eight seedlings in 50 cm3 conical tubes filled with soil and vermiculite in a volume ratio of 1:1. The irrigation depth was estimated by reference evapotranspiration (Penman-Monteith) multiplied by a crop coefficient equal to two. Plant height, number of definitive leaves, shoot dry mass (root and total), seed quality index, survival and efficiency of water use by eucalyptus seedlings were evaluated. The average daily irrigation depth in the experimental period was 5.2 mm. Based on the results, it is recommended for eucalyptus seedling producers, in less-tech nursery, irrigation management twice per days. (11:00 a.m. and 7:00 p.m.).


2017 ◽  
Vol 69 (4) ◽  
pp. 1039-1046 ◽  
Author(s):  
B.C. Pedreira ◽  
P.L. Barbosa ◽  
L.E.T. Pereira ◽  
M.A. Mombach ◽  
L.F. Domiciano ◽  
...  

ABSTRACT The objective of this study is to verify the population density and the dynamics of tillering in the Marandu palisade grass sward subjected to nitrogen (N) fertilization strategies, characterized by the N supply via urea or bacterial inoculant (Azospirillum brasilense). The treatments comprised of four nitrogen fertilization strategies: (A) Without fertilization, (B) 80 kg N/ha, (C) inoculant (A. brasilense), and (D) 80 kg N/ha + inoculant, distributed in a randomized complete block design, with three replications. The nitrogen supply strategies were evaluated during six periods: October, November, and December (2012) as well as January, March, and April (2013). The nitrogen dose or inoculant had no effect on the tiller appearance rate (TAR), tiller mortality rate (TMR), tiller survival rate (TSR), or tiller population density (TPD). However, these variables were influenced by the season. The TAR and TSR were higher at the beginning of the experimental period (October) and lower towards the end of the period (March-April), whereas, TMR and TPD exhibited the opposite behavior, with lower values in October and higher from January onward. Neither the nitrogen nor the inoculant influenced the population dynamics of the tillers in Marandu palisade grass.


2020 ◽  
Vol 51 (2) ◽  
pp. 129-138
Author(s):  
Ksenija Šandor ◽  
Svjetlana Terzić ◽  
Anja Vujnović ◽  
Eleonora Perak Junaković ◽  
Irena Žarković ◽  
...  

A study of florfenicol (FF) and its metabo- lite florfenicol amine (FFA) in pig cerebrospinal fluid was conducted following repeated intramuscular administration of the original (reference) and a generic veterinary medicinal product (VMP) under the same experimental conditions (20 mg FF/kg body weight, 48-hour interval). Both VMPs are solutions for injection containing FF as an active substance in the concentration of 300 mg/mL and have been authorized in Croatia for use in cattle and pigs. In this study, clinically healthy pigs were randomly divided into three groups. The first group was treated with the reference VMP, the second with the generic VMP, while the third served as the control group. Animals were sacrificed at 216, 288 and 384 hours after the first drug administration. Cerebrospinal fluid samples were analysed by the optimized and validated high-performance liquid chromatography-diode array detector method (HPLC-DAD). The solid-phase extraction (SPE) technique was chosen for sample preparation. The HPLC-DAD method provides good linearity over the concentration range of 0.05 to 5.00 μg/mL for FF and FFA. Limits of detection were 0.0023 μg/mL for FF and 0.0100 μg/mL for FFA. Extraction recoveries of FF were from 86.6% to 111.8%, and of FFA from 91.7% to 98.8%. The SPE-HPLC-DAD method has been demonstrated to be a selective, sensitive and suitable analytical method for the determination of FF and FFA in cerebrospinal fluid. The present study was based on a preliminary study that quantified FF in pig plasma at 216 hours after the first application of reference or generic VMP. However, FF and FFA were not detected in any of the cerebrospinal fluid samples during the experimental period. According to the nature of biological fluids, the SPE-HPLC-DAD method can be suitable for further pharmacokinetic studies of FF in pig plasma and serum after intramuscular administration of VMPs.


Animals ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. 961
Author(s):  
Richard R. Lobo ◽  
Rafaela Vincenzi ◽  
Danny A. Rojas-Moreno ◽  
Annelise A. G. Lobo ◽  
Caroline M. da Silva ◽  
...  

This study aimed to evaluate levels of yerba mate (Ilex paraguariensis) extract (YME), as a feed additive in the diets of growing lambs on serum biochemical parameters and hematological indices, animal performance, body metrics and carcass traits. Thirty-six entire (nine per treatment), male growing lambs, weighing 23.8 ± 3.7 kg, were fed the experimental diets which were treatments consisting of increasing levels of YME (0, 1, 2, and 4% inclusion on a dry matter [DM] basis) during an experimental period of 53 days. The experiment was carried out in a randomized block design, which initial body weight was used as blocking factor and the results were analyzed by orthogonal contrasts (linear, quadratic, and cubic). Yerba mate extract did not change the general health status of the animals; however, inclusions of up to 2% of the extract increased globulins (p = 0.05) and white blood cell count, as segmented neutrophils (p = 0.02) and lymphocytes (p = 0.04). Additionally, inclusion of up to 2% YME increased dry matter intake, final weight gain, total and daily gain (p < 0.05), also tended to increase ribeye area and reduce fat thickness (p < 0.10); however, YME above 2% of inclusion reduced animal productive parameters (p < 0.05). In conclusion, levels up to 2% of YME were beneficial to the health and productive parameters of growing lambs.


2019 ◽  
Vol 97 (Supplement_3) ◽  
pp. 312-312
Author(s):  
Tanner P Price ◽  
Claire B Gleason ◽  
Douglas M Liebe ◽  
Ty C Davis ◽  
Linda Beckett ◽  
...  

Abstract This study assessed how substituting starch energy for fat energy affects equine insulin sensitivity. A randomized, complete block design with 5 groups of 4 horses was used to evaluate responses to isoenergetic diets containing 7.1, 9.2, 11.5, 12.8 or 14.3% starch (dry matter basis, targeting 1.0–2.2 g starch/kg body weight). Horses were fed twice daily for 21 days, housed in individual box stalls, used in regular riding lessons, and blocked by plane of nutrition (PON), targeting +1 or -1 body condition score in 30 d. On d1 and d21, a hyperglycemic clamp was performed; horses received a jugular glucose infusion to double basal blood glucose concentrations ([Glu]) in 2 h. Samples for blood glucose and insulin determination were collected every 5 m until [Glu] was held at double basal for 30 minutes. Insulin sensitivity index (ISI) and quantitative insulin sensitivity check index (QUICI) were analysed using a general linear model with fixed effects for starch percent, PON, their interaction, and a covariate for number of workouts (WN). There was no effect (P &gt; 0.10) of starch percent, PON, their interaction, or WN on initial or final ISI. Change in ISI scores was significantly affected by PON (P = 0.009) with a tendency for diet and PON interaction (P = 0.091). Initial QUICI was significantly affected by WN (P = 0.030), but no other relationships (P &gt; 0.10) were observed for initial or final QUICI. Change in QUICI was affected by WN (P = 0.042) with a tendency for a PON effect (P = 0.082). The QUICI and ISI scores were significantly related (P &lt; 0.001; R2=0.66), and their relationship did not interact with WN (0.751), experimental period (0.348), diet (P = 0.689) or PON (P = 0.200).


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