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

Self-esteem in adolescents

PURPOSE. Self-esteem is an overall evaluation of the person’s value, expressed in a positive or negative orientation towards himself. Its development starts from birth and is constantly changing under the influence of experience (1). Especially important is the role of self-esteem in the process of adolescence. During this period, it correlates with both academic achievement and mental health. The aim of this study is to analyze the correlation between academic achievement and self-esteem among teenagers. Forty 14-year-old students (20 boys and 20 girls) with excellent, very good and good results in school were examined. Methods: Self-Esteem Scale (RSE) (2). The study results show that girls have significantly more negative attitudes towards themselves (x = 32.25) comparing with boys (x = 25.14). These results support the need for further research to explore how individual and contextual factors affect the development of self-esteem over the school years

Trait and state anxiety as factors of threshold and tolerance to experimentally induced pain

Pain is an experience that has physical, psychological and social aspects. Sensitivity to pain is individual and depends on psychological factors. Studies have shown that anxiety is associated with the perception of experimentally induced pain. PURPOSE: The purpose of the present study is to examine the relationship between anxiety, threshold and tolerance to experimentally induced pain in healthy persons. METHODS: 35 healthy persons at the age from 19 to 39, 20 women and 15 men were examined. Methods: Spielberger’s questionnaire, Cold pressor test, Visual Analog Scale for Pain, Descriptive statistics, Correlation analysis, Mann-Whitney’s Test. RESULTS: Significant differences in tolerance to pain were identified depending on the levels of state anxiety (U=12.5, Р=0.037). The state anxiety was greatly related to the intensity of the pain experienced. (Spearman rho=0.49, P=0.008). Significant differences were not found in threshold, tolerance and intensity of pain depending on the levels of trait anxiety in the examined people. CONCLUSIONS: The increased levels of state anxiety in healthy persons exposed to experimentally induced pain suggest a weaker endurance to pain and perceiving it as stronger

Enhanced presentation of MHC class Ia, Ib and class II-restricted peptides encapsulated in biodegradable nanoparticles: a promising strategy for tumor immunotherapy

<p>Abstract</p> <p>Background</p> <p>Many peptide-based cancer vaccines have been tested in clinical trials with a limited success, mostly due to difficulties associated with peptide stability and delivery, resulting in inefficient antigen presentation. Therefore, the development of suitable and efficient vaccine carrier systems remains a major challenge.</p> <p>Methods</p> <p>To address this issue, we have engineered polylactic-co-glycolic acid (PLGA) nanoparticles incorporating: (i) two MHC class I-restricted clinically-relevant peptides, (ii) a MHC class II-binding peptide, and (iii) a non-classical MHC class I-binding peptide. We formulated the nanoparticles utilizing a double emulsion-solvent evaporation technique and characterized their surface morphology, size, zeta potential and peptide content. We also loaded human and murine dendritic cells (DC) with the peptide-containing nanoparticles and determined their ability to present the encapsulated peptide antigens and to induce tumor-specific cytotoxic T lymphocytes (CTL) <it>in vitro</it>.</p> <p>Results</p> <p>We confirmed that the nanoparticles are not toxic to either mouse or human dendritic cells, and do not have any effect on the DC maturation. We also demonstrated a significantly enhanced presentation of the encapsulated peptides upon internalization of the nanoparticles by DC, and confirmed that the improved peptide presentation is actually associated with more efficient generation of peptide-specific CTL and T helper cell responses.</p> <p>Conclusion</p> <p>Encapsulating antigens in PLGA nanoparticles offers unique advantages such as higher efficiency of antigen loading, prolonged presentation of the antigens, prevention of peptide degradation, specific targeting of antigens to antigen presenting cells, improved shelf life of the antigens, and easy scale up for pharmaceutical production. Therefore, these findings are highly significant to the development of synthetic vaccines, and the induction of CTL for adoptive immunotherapy.</p

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

Spitzer + VLTI-GRAVITY Measure the Lens Mass of a Nearby Microlensing Event

We report the lens mass and distance measurements of the nearby microlensing event TCP J05074264+2447555. We measure the microlens parallax vector ${\pi}_{\rm E}$ using Spitzer and ground-based light curves with constraints on the direction of lens-source relative proper motion derived from Very Large Telescope Interferometer (VLTI) GRAVITY observations. Combining this ${\pi}_{\rm E}$ determination with the angular Einstein radius $\theta_{\rm E}$ measured by VLTI GRAVITY observations, we find that the lens is a star with mass $M_{\rm L} = 0.495 \pm 0.063~M_{\odot}$ at a distance $D_{\rm L} = 429 \pm 21~{\rm pc}$. We find that the blended light basically all comes from the lens. The lens-source proper motion is $\mu_{\rm rel,hel} = 26.55 \pm 0.36~{\rm mas\,yr^{-1}}$, so with currently available adaptive-optics (AO) instruments, the lens and source can be resolved in 2021. This is the first microlensing event whose lens mass is unambiguously measured by interferometry + satellite parallax observations, which opens a new window for mass measurements of isolated objects such as stellar-mass black holes.Comment: 3 Figures and 6 Tables Submitted to AAS Journa

Spitzer + VLTI-GRAVITY Measure the Lens Mass of a Nearby Microlensing Event

We report the lens mass and distance measurements of the nearby microlensing event TCP J05074264+2447555 (Kojima-1). We measure the microlens parallax vector π_E using Spitzer and ground-based light curves with constraints on the direction of lens-source relative proper motion derived from Very Large Telescope Interferometer (VLTI) GRAVITY observations. Combining this π_E determination with the angular Einstein radius θ_E measured by VLTI-GRAVITY observations, we find that the lens is a star with mass M_L = 0.495±0.063 M⊙ at a distance D_L = 429 ± 21 pc. We find that the blended light basically all comes from the lens. The lens-source proper motion is Μ_(rel,hel) = 26.55±0.36 mas yr⁻¹, so with currently available adaptive-optics instruments, the lens and source can be resolved in 2021. This is the first microlensing event whose lens mass is unambiguously measured by interferometry + satellite-parallax observations, which opens a new window for mass measurements of isolated objects such as stellar-mass black holes

Chronic multichannel neural recordings from soft regenerative microchannel electrodes during gait

Reliably interfacing a nerve with an electrode array is one of the approaches to restore motor and sensory functions after an injury to the peripheral nerve. Accomplishing this with current technologies is challenging as the electrode-neuron interface often degrades over time, and surrounding myoelectric signals contaminate the neuro-signals in awake, moving animals. The purpose of this study was to evaluate the potential of microchannel electrode implants to monitor over time and in freely moving animals, neural activity from regenerating nerves. We designed and fabricated implants with silicone rubber and elastic thin-film metallization. Each implant carries an eight-by-twelve matrix of parallel microchannels (of 120\u2009 7\u2009110\u2009\u3bcm2 cross-section and 4\u2009mm length) and gold thin-film electrodes embedded in the floor of ten of the microchannels. After sterilization, the soft, multi-lumen electrode implant is sutured between the stumps of the sciatic nerve. Over a period of three months and in four rats, the microchannel electrodes recorded spike activity from the regenerating sciatic nerve. Histology indicates mini-nerves formed of axons and supporting cells regenerate robustly in the implants. Analysis of the recorded spikes and gait kinematics over the ten-week period suggests firing patterns collected with the microchannel electrode implant can be associated with different phases of gait

The State Socialist Mortality Syndrome

Death rates for working-age men in European state socialist countries deviated from general improvements in survival observed in the rest of Europe during the 20th century. The magnitude of structural labor force changes across countries correlates with lagged increases in death rates for men in the working ages. This pattern is consistent with a hypothesis that hyper-development of heavy industry and stagnation (even contraction) of the service sector created anomic conditions leading to unhealthy lifestyles and self-destructive behavior among men moving from primary-sector to secondary-sector occupations. Occupational contrasts within countries similarly show concentration of rising male death rates among blue collar workers. Collapse of state socialist systems produced rapid corrections in labor force structure after 1990, again correlated with a fading of the state socialist mortality syndrome in following decades