Biomarkers and neuromodulation techniques in substance use disorders

Addictive disorders are a severe health concern. Conventional therapies have just moderate success and the probability of relapse after treatment remains high. Brain stimulation techniques, such as transcranial Direct Current Stimulation (tDCS) and Deep Brain Stimulation (DBS), have been shown to be effective in reducing subjectively rated substance craving. However, there are few objective and measurable parameters that reflect neural mechanisms of addictive disorders and relapse. Key electrophysiological features that characterize substance related changes in neural processing are Event-Related Potentials (ERP). These high temporal resolution measurements of brain activity are able to identify neurocognitive correlates of addictive behaviours. Moreover, ERP have shown utility as biomarkers to predict treatment outcome and relapse probability. A future direction for the treatment of addiction might include neural interfaces able to detect addiction-related neurophysiological parameters and deploy neuromodulation adapted to the identified pathological features in a closed-loop fashion. Such systems may go beyond electrical recording and stimulation to employ sensing and neuromodulation in the pharmacological domain as well as advanced signal analysis and machine learning algorithms. In this review, we describe the state-of-the-art in the treatment of addictive disorders with electrical brain stimulation and its effect on addiction-related neurophysiological markers. We discuss advanced signal processing approaches and multi-modal neural interfaces as building blocks in future bioelectronics systems for treatment of addictive disorders

Effect of foliar products on the inflorescence yield of lavender and essential oil

Received: January 25th, 2022 ; Accepted: May 1st, 2022 ; Published: May 23rd, 2022 ; Correspondence: [email protected] topic of the effect of foliar fertilization on the productivity and oil content of lavender is relevant, but not sufficiently studied. The present study aims to establish the effect of foliar products on the growth, development and productivity of lavender. The field experiment was carried out at the Agricultural University - Plovdiv with lavender of ‘Jubileina’ variety during 2019–2020. The following variants were included in the study: 1. Untreated control; 2. Treatment with Fertileader Gold (FG) - 3 L ha-1; 3. Treatment with Fertiactyl Trium + Fertileader Vital (FT + FVital) - 1.5 + 1.5 L ha-1; 4. Treatment with Fertileader Viti (FViti) - 3 L ha-1; 5. Treatment with Fertileader Vital (FV) - 3 L ha-1; 6. Treatment with Fertileader Alpha (FA) - 3 L ha-1. Those preparations are bio stimulants for foliar application. The treatments were made in two consecutive lavender vegetation seasons. The first application was carried out in the second growing season (2019) and the second in the next, third growing season (2020). The foliar application of all tested products increased the photosynthetic activity, but it was better expressed when using the plant nutrition products FV, FViti and FT + FVital. A positive effect was also observed in the height and diameter of the bush, but during the third vegetation period. The number of flowering stems increased by 62.9%; 59.4%; 53.3% and 8.4%, respectively, when applying the fertilizers FG, FT + FVital, FViti and FV. The application of FG and FT + FVital increased the yield of fresh inflorescences by 6.1% and 3.7%. The application of the different products affected the oil yield in different ways; the application of FG, FT + FVital and FViti increased it, while FV and FA decreased it by 27 kg ha-1 and 16 kg ha-1, respectively, for the first vegetation and by 43.4 kg ha-1and 33.1 kg ha-1 for the second vegetation. The boron containing products FG, FT + FVital and FViti led to a significant increase in the essential oil yield, while the application of the foliar fertilizers FV and FA reduced it. Based on those results, the first three products are recommended

A Second Order Splitting Algorithm For Thermally-Driven

ABSTRACT A splitting technique for solutions of the Navier-Stokes and the energy equations, in Boussinesq approximation, is presented. The equations are first integrated in time using a splitting procedure and then discretized spatially by means of a high-order spectral element method. The whole technique is validated on the flow in a differentially-heated cavity at intermediate and transitional Rayleigh numbers. The results are in a very good agreement with other available numerical solutions

Combination stem cell therapy for heart failure

Patients with congestive heart failure (CHF) that are not eligible for transplantation have limited therapeutic options. Stem cell therapy such as autologous bone marrow, mobilized peripheral blood, or purified cells thereof has been used clinically since 2001. To date over 1000 patients have received cellular therapy as part of randomized trials, with the general consensus being that a moderate but statistically significant benefit occurs. Therefore, one of the important next steps in the field is optimization. In this paper we discuss three ways to approach this issue: a) increasing stem cell migration to the heart; b) augmenting stem cell activity; and c) combining existing stem cell therapies to recapitulate a "therapeutic niche". We conclude by describing a case report of a heart failure patient treated with a combination stem cell protocol in an attempt to augment beneficial aspects of cord blood CD34 cells and mesenchymal-like stem cells

Rapid prototyping of soft bioelectronic implants for use as neuromuscular interfaces

Neuromuscular interfaces are required to translate bioelectronic technologies for application in clinical medicine. Here, by leveraging the robotically controlled ink-jet deposition of low-viscosity conductive inks, extrusion of insulating silicone pastes and in situ activation of electrode surfaces via cold-air plasma, we show that soft biocompatible materials can be rapidly printed for the on-demand prototyping of customized electrode arrays well adjusted to specific anatomical environments, functions and experimental models. We also show, with the monitoring and activation of neuronal pathways in the brain, spinal cord and neuromuscular system of cats, rats and zebrafish, that the printed bioelectronic interfaces allow for long-term integration and functional stability. This technology might enable personalized bioelectronics for neuroprosthetic applications

Feasibility of combination allogeneic stem cell therapy for spinal cord injury: a case report

Cellular therapy for spinal cord injury (SCI) is overviewed focusing on bone marrow mononuclear cells, olfactory ensheathing cells, and mesenchymal stem cells. A case is made for the possibility of combining cell types, as well as for allogeneic use. We report the case of 29 year old male who suffered a crush fracture of the L1 vertebral body, lacking lower sensorimotor function, being a score A on the ASIA scale. Stem cell therapy comprised of intrathecal administration of allogeneic umbilical cord blood ex-vivo expanded CD34 and umbilical cord matrix MSC was performed 5 months, 8 months, and 14 months after injury. Cell administration was well tolerated with no adverse effects observed. Neuropathic pain subsided from intermittent 10/10 to once a week 3/10 VAS. Recovery of muscle, bowel and sexual function was noted, along with a decrease in ASIA score to "D". This case supports further investigation into allogeneic-based stem cell therapies for SCI

Non-expanded adipose stromal vascular fraction cell therapy for multiple sclerosis

The stromal vascular fraction (SVF) of adipose tissue is known to contain mesenchymal stem cells (MSC), T regulatory cells, endothelial precursor cells, preadipocytes, as well as anti-inflammatory M2 macrophages. Safety of autologous adipose tissue implantation is supported by extensive use of this procedure in cosmetic surgery, as well as by ongoing studies using in vitro expanded adipose derived MSC. Equine and canine studies demonstrating anti-inflammatory and regenerative effects of non-expanded SVF cells have yielded promising results. Although non-expanded SVF cells have been used successfully in accelerating healing of Crohn's fistulas, to our knowledge clinical use of these cells for systemic immune modulation has not been reported. In this communication we discuss the rationale for use of autologous SVF in treatment of multiple sclerosis and describe our experiences with three patients. Based on this rationale and initial experiences, we propose controlled trials of autologous SVF in various inflammatory conditions

Nutraceutical augmentation of circulating endothelial progenitor cells and hematopoietic stem cells in human subjects

The medical significance of circulating endothelial or hematopoietic progenitors is becoming increasing recognized. While therapeutic augmentation of circulating progenitor cells using G-CSF has resulted in promising preclinical and early clinical data for several degenerative conditions, this approach is limited by cost and inability to perform chronic administration. Stem-Kine is a food supplement that was previously reported to augment circulating EPC in a pilot study. Here we report a trial in 18 healthy volunteers administered Stem-Kine twice daily for a 2 week period. Significant increases in circulating CD133 and CD34 cells were observed at days 1, 2, 7, and 14 subsequent to initiation of administration, which correlated with increased hematopoietic progenitors as detected by the HALO assay. Augmentation of EPC numbers in circulation was detected by KDR-1/CD34 staining and colony forming assays. These data suggest Stem-Kine supplementation may be useful as a stimulator of reparative processes associated with mobilization of hematopoietic and endothelial progenitors

A multimodal neuroprosthetic interface to record, modulate and classify electrophysiological correlates of cognitive function

Most mental disorders are characterised by impaired cognitive function and behaviour control. Their often chronic reoccurring nature and the lack of efficient therapies necessitate the development of new treatment strategies. Brain-computer interfaces, equipped with multiple sensing and stimulation abilities, offer a new toolbox, whose suitability for diagnosis and therapy of mental disorders has not yet been explored. Here, we developed a soft and multimodal neuroprosthesis to measure and modulate prefrontal neurophysiological features of neuropsychiatric symptoms. We implanted the device epidurally above the medial prefrontal cortex of rats and obtained auditory event-related brain potentials reflecting intact neural stimulus processing and alcohol-induced neural impairments. Moreover, implant-driven electrical and pharmacological stimulation enabled successful modulation of neural activity. Finally, we developed machine learning algorithms which can deal with sparsity in the data and distinguish effects with high accuracy. Our work underlines the potential of multimodal bioelectronic systems to enable a personalised and optimised therapy

Feasibility investigation of allogeneic endometrial regenerative cells

Endometrial Regenerative Cells (ERC) are a population of mesenchymal-like stem cells having pluripotent differentiation activity and ability to induce neoangiogenesis. In vitro and animal studies suggest ERC are immune privileged and in certain situations actively suppress ongoing immune responses. In this paper we describe the production of clinical grade ERC and initial safety experiences in 4 patients with multiple sclerosis treated intravenously and intrathecally. The case with the longest follow up, of more than one year, revealed no immunological reactions or treatment associated adverse effects. These preliminary data suggest feasibility of clinical ERC administration and support further studies with this novel stem cell type