Design of Transcranial Magnetic Stimulation Coils With Optimized Stimulation Depth

This work presents a framework to develop optimal coils of arbitrary geometry for deep transcranial magnetic stimulation (dTMS). It has been based on a continuous current density inverse boundary element method (IBEM) to generate dTMS coils with depth control and minimum power dissipation. Novel coil geometries that readily adapted to human head have been studied to provide focal stimulation in areas on both prefrontal cortex and right temporal lobe. The designed dTMS coils performance has been numerically validated in a realistic human head model and prototypes have been built for experimental evaluation. The numerical simulations indicate that the proposed dTMS coils focally stimulate the prescribed brain regions with the desired target depth. The calculated metrics demonstrate that the presented designs outperform existing dTMS coils (the stimulation depth can be increased more than 15% compared to conventional dTMS coils with similar focality). Stream function IBEM can be used to develop novel dTMS coils with improved properties for a wide range of geometries. The proposed design method opens up a possibility for exploring new coil solutions based on complex shapes to focally deliver a desired stimulation dose to relatively deep brain targets, which might allow novel and more effective brain stimulation protocols.Plan Andaluz de Investigación, Desarrollo e Innovación (PAIDI 2020), Consejería de Universidad, Investigación e Innovación de la Junta de Andalucía, under Grant ProyExcel−0103

Closed-loop optimization of transcranial magnetic stimulation with electroencephalography feedback

Background: Transcranial magnetic stimulation (TMS) is widely used in brain research and treatment of various brain dysfunctions. However, the optimal way to target stimulation and administer TMS therapies, for example, where and in which electric field direction the stimuli should be given, is yet to be determined. Objective: To develop an automated closed-loop system for adjusting TMS parameters (in this work, the stimulus orientation) online based on TMS-evoked brain activity measured with electroencephalography (EEG). Methods: We developed an automated closed-loop TMS-EEG set-up. In this set-up, the stimulus parameters are electronically adjusted with multi-locus TMS. As a proof of concept, we developed an algorithm that automatically optimizes the stimulation orientation based on single-trial EEG responses. We applied the algorithm to determine the electric field orientation that maximizes the amplitude of the TMS-EEG responses. The validation of the algorithm was performed with six healthy volunteers, repeating the search twenty times for each subject. Results: The validation demonstrated that the closed-loop control worked as desired despite the large variation in the single-trial EEG responses. We were often able to get close to the orientation that maximizes the EEG amplitude with only a few tens of pulses. Conclusion: Optimizing stimulation with EEG feedback in a closed-loop manner is feasible and enables effective coupling to brain activity. (C) 2022 The Author(s). Published by Elsevier Inc.Peer reviewe

Impact of multi-targeted antiretroviral treatment on gut T cell depletion and HIV reservoir seeding during acute HIV infection.

BackgroundLimited knowledge exists on early HIV events that may inform preventive and therapeutic strategies. This study aims to characterize the earliest immunologic and virologic HIV events following infection and investigates the usage of a novel therapeutic strategy.Methods and findingsWe prospectively screened 24,430 subjects in Bangkok and identified 40 AHI individuals. Thirty Thais were enrolled (8 Fiebig I, 5 Fiebig II, 15 Fiebig III, 2 Fiebig IV) of whom 15 completed 24 weeks of megaHAART (tenofovir/emtricitabine/efavirenz/raltegravir/maraviroc). Sigmoid biopsies were completed in 24/30 at baseline and 13/15 at week 24. At baseline, the median age was 29 years and 83% were MSM. Most were symptomatic (87%), and were infected with R5-tropic (77%) CRF01_AE (70%). Median CD4 was 406 cells/mm(3). HIV RNA was 5.5 log(10) copies/ml. Median total blood HIV DNA was higher in Fiebig III (550 copy/10(6) PBMC) vs. Fiebig I (8 copy/10(6) PBMC) (p = 0.01) while the median %CD4+CCR5+ gut T cells was lower in Fiebig III (19%) vs. Fiebig I (59%) (p = 0.0008). After 24 weeks of megaHAART, HIV RNA levels of <50 copies were achieved in 14/15 in blood and 13/13 in gut. Total blood HIV DNA at week 0 predicted reservoir size at week 24 (p<0.001). Total HIV DNA declined significantly and was undetectable in 3 of 15 in blood and 3 of 7 in gut. Frequency of CD4+CCR5+ gut T cells increased from 41% at baseline to 64% at week 24 (p>0.050); subjects with less than 40% at baseline had a significant increase in CD4+CCR5+ T cells from baseline to week 24 (14% vs. 71%, p = 0.02).ConclusionsGut T cell depletion and HIV reservoir seeding increases with progression of AHI. MegaHAART was associated with immune restoration and reduced reservoir size. Our findings could inform research on strategies to achieve HIV drug-free remission

Effect of stimulus orientation and intensity on short-interval intracortical inhibition (SICI) and facilitation (SICF) : A multi-channel transcranial magnetic stimulation study

Publisher Copyright: © 2021 Tugin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Besides stimulus intensities and interstimulus intervals (ISI), the electric field (E-field) orientation is known to affect both short-interval intracortical inhibition (SICI) and facilitation (SICF) in paired-pulse transcranial magnetic stimulation (TMS). However, it has yet to be established how distinct orientations of the conditioning (CS) and test stimuli (TS) affect the SICI and SICF generation. With the use of a multi-channel TMS transducer that provides electronic control of the stimulus orientation and intensity, we aimed to investigate how changes in the CS and TS orientation affect the strength of SICI and SICF. We hypothesized that the CS orientation would play a major role for SICF than for SICI, whereas the CS intensity would be more critical for SICI than for SICF. In eight healthy subjects, we tested two ISIs (1.5 and 2.7 ms), two CS and TS orientations (anteromedial (AM) and posteromedial (PM)), and four CS intensities (50, 70, 90, and 110% of the resting motor threshold (RMT)). The TS intensity was fixed at 110% RMT. The intensities were adjusted to the corresponding RMT in the AM and PM orientations. SICI and SICF were observed in all tested CS and TS orientations. SICI depended on the CS intensity in a U-shaped manner in any combination of the CS and TS orientations. With 70% and 90% RMT CS intensities, stronger PM-oriented CS induced stronger inhibition than weaker AM-oriented CS. Similar SICF was observed for any CS orientation. Neither SICI nor SICF depended on the TS orientation. We demonstrated that SICI and SICF could be elicited by the CS perpendicular to the TS, which indicates that these stimuli affected either overlapping or strongly connected neuronal populations. We concluded that SICI is primarily sensitive to the CS intensity and that CS intensity adjustment resulted in similar SICF for different CS orientations.Peer reviewe

Multi-locus transcranial magnetic stimulation system for electronically targeted brain stimulation

Background: Transcranial magnetic stimulation (TMS) allows non-invasive stimulation of the cortex. In multi-locus TMS (mTMS), the stimulating electric field (E-field) is controlled electronically without coil movement by adjusting currents in the coils of a transducer. Objective: To develop an mTMS system that allows adjusting the location and orientation of the E-field maximum within a cortical region. Methods: We designed and manufactured a planar 5-coil mTMS transducer to allow controlling the maximum of the induced E-field within a cortical region approximately 30 mm in diameter. We developed electronics with a design consisting of independently controlled H-bridge circuits to drive up to six TMS coils. To control the hardware, we programmed software that runs on a field-programmable gate array and a computer. To induce the desired E-field in the cortex, we developed an optimization method to calculate the currents needed in the coils. We characterized the mTMS system and conducted a proof-of-concept motor-mapping experiment on a healthy volunteer. In the motor mapping, we kept the transducer placement fixed while electronically shifting the E-field maximum on the precentral gyrus and measuring electromyography from the contralateral hand. Results: The transducer consists of an oval coil, two figure-of-eight coils, and two four-leaf-clover coils stacked on top of each other. The technical characterization indicated that the mTMS system performs as designed. The measured motor evoked potential amplitudes varied consistently as a function of the location of the E-field maximum. Conclusion: The developed mTMS system enables electronically targeted brain stimulation within a cortical region. (c) 2021 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).Peer reviewe

A Contribution to the Bio and Circular Economy

and Cássia H. Barbosa’s Ph.D. fellowship (2021.08154.BD). MMA thanks the Instituto Superior Técnico for the Scientific Employment contract (contract No: IST-ID/154/2018) under Decree-Law No. 57/2016 and 57/2017. Publisher Copyright: © 2023 by the authors.The development of innovative/sustainable materials capable of enlarging the shelf-life of food products has lately been a focus of research, aiming to reduce food waste. Due to their good antimicrobial properties, zinc oxide nanoparticles (ZnO NPs) can add activity to food packaging, improving its performance. Furthermore, these nanoparticles are considered GRAS by the Food and Drug Administration (FDA), which represents an advantage in their application. Through an innovative and sustainable approach using tomato and passionfruit extracts, ZnO NPs were produced and incorporated into pectin films. The resulting bionanocomposites were tested for their activity via in situ studies, using fresh poultry meat as a food matrix. Overall, the bionanocomposites presented good antimicrobial activity, with the intrinsic antimicrobial properties of pectin having shown to be enhanced by the incorporated ZnO NPs. When used as primary packaging for the meat, the deterioration rate of the poultry meat, measured through microbiological growth and total volatile basic nitrogen content, was reduced. However, the nanoparticles contributed to the increment of discoloration and meat oxidation processes. Nonetheless, it can be concluded that fresh poultry meat protected with the bionanocomposites presented an extension of its shelf-life time, and it was confirmed that this eco-friendly packaging has potential to be employed by the food industry.publishersversionpublishe

The Facet of Human Impact: Solenopsis invicta Buren, 1972 Spreading around the Atlantic Forest

The present investigation deals with some aspects of the diversity of fire ants (Hymenoptera: Formicidae) in their native range. The Red Imported Fire Ant Solenopsis invicta is native to the tropical and subtropical inland territories of South America. In Brazil, it mainly occurs around the Pantanal region and across the Paraguay river, a region composed of grasslands which are seasonally flooded. Recent studies have evidenced this fire ant species is gradually spreading to other regions of Brazil. In the present investigation, we surveyed the molecular diversity of S. invicta populations across fragments of Atlantic Forest in Sao Paulo, Brazil, using mtDNA COI haplotypes. Fire ant nests were sampled along the highways lining the northern and southern slope sides of the mountain range Serra do Mar, SP, Brazil. Four haplotypes were identified (H1-H4), which were assessed for similarity to deposited records by other authors, revealing that the haplotypes H1 and H2 are likely of foreign origin through recent reintroduction via a marine port to the south of the Serra do Mar mountain range. On the other hand, the haplotypes H3 and H4, predominating among the inland samples from the northern side of the mountain range, were most similar to previous records from more central regions of Brazil. Haplotypes clustered into distinct supergroups, further pointing to the occurrence of two separate expansion waves of S. invicta in the region. We suggest the obtained pattern indicates the mountain range may function as a geographical barrier deferring gene flow

Results of an Expert Consensus Survey on the Treatment of Pulmonary Arterial Hypertension With Oral Prostacyclin Pathway Agents

Background Treatment of pulmonary arterial hypertension (PAH) has evolved substantially over the past two decades and varies according to etiology, functional class (FC), hemodynamic parameters, and other clinical factors. Current guidelines do not provide definitive recommendations regarding the use of oral prostacyclin pathway agents (PPAs) in PAH. To provide guidance on the use of these agents, an expert panel was convened to develop consensus statements for the initiation of oral PPAs in adults with PAH. Methods A systematic literature search was conducted using MEDLINE. The established RAND/University of California Los Angeles appropriateness method, which incorporates the Delphi method and the nominal group technique, was used to create consensus statements. Idiopathic, heritable, repaired congenital heart defect, and drug- or toxin-induced PAH (IPAH+) was considered as one etiologic grouping. The process was focused on the use of oral treprostinil or selexipag in patients with IPAH+ or connective tissue disease-associated PAH and FC II or III symptoms receiving background dual endothelin receptor antagonist/phosphodiesterase type 5 inhibitor therapy. Results The panel developed 14 consensus statements regarding the appropriate use of oral PPAs in the target population. The panel identified 13 clinical scenarios in which selexipag may be considered as a treatment option. Conclusions The paucity of clinical evidence overall, and particularly from randomized trials in this setting, creates a gap in knowledge. These consensus statements are intended to aid physicians in navigating treatment options and using oral PPAs in the most appropriate manner in patients with PAH

Currents issues in cardiorespiratory care of patients with post-polio syndrome

Post-polio syndrome (PPS) is a condition that affects polio survivors years after recovery from an initial acute attack of the poliomyelitis virus. Most often, polio survivors experience a gradual new weakening in muscles that were previously affected by the polio infection. The actual incidence of cardiovascular diseases (CVDs) in individuals suffering from PPS is not known. However, there is a reason to suspect that individuals with PPS might be at increased risk. Method: A search for papers was made in the databases Bireme, Scielo and Pubmed with the following keywords: post polio syndrome, cardiorespiratory and rehabilitation in English, French and Spanish languages. Although we targeted only seek current studies on the topic in question, only the relevant (double-blind, randomized-controlled and consensus articles) were considered. Results and Discussion: Certain features of PPS such as generalized fatigue, generalized and specific muscle weakness, joint and/or muscle pain may result in physical inactivity deconditioning obesity and dyslipidemia. Respiratory difficulties are common and may result in hypoxemia. Conclusion: Only when evaluated and treated promptly, somE patients can obtain the full benefits of the use of respiratory muscles aids as far as quality of life is concerned.Ctr Univ Augusto Motta, Programa Posgrad Ciencias Reabilitacao, Rio De Janeiro, RJ, BrazilUniv Severino Sombra, Fac Med, Vassouras, RJ, BrazilUniv Fed Rio de Janeiro, Inst Psiquiatria, Lab Mapeamento Cerebral & EEG, BR-22290140 Rio De Janeiro, RJ, BrazilUniv Fed Fluminense, Hosp Univ Antonio Pedro, Niteroi, RJ, BrazilInst Fed Educ Ciencia & Tecnol Rio de Janeiro, Curso Fisioterapia, Rio De Janeiro, RJ, BrazilUniv Fed Piaui, Parnaiba, PI, BrazilUniv Fed Sao Paulo, Dept Neurol, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Dept Neurol, Sao Paulo, SP, BrazilWeb of Scienc