A Progressive Addiction Recovery Approach

Abstract Addiction is a complex chronic disease that plagues our society today. Understanding addiction requires a deep understanding of the relationship between the brain, mind, body, soul and others; in turn, its solution requires the same. Current research has made much progress and replaced the previous biomedical model for health and well-being with a biopsychosocial model. This same multi-dimensional approach is beginning to be applied to addiction recovery; however, there is much opportunity for progressive treatments to incorporate new components into current intervention models. Although there have been some studies to research the effects of the psychological component to recovery, other studies to research the effects of physical activity on recovery, those that research the effects of social support, and still others to study the effects of nutrition on recovery, there are little to none that have incorporated them in one treatment plan for the study of its efficaciousness. Psychology, physical activity, nutrition and social support systems are topics of review in this paper for the purpose and support of developing progressive approaches to addiction recovery. The research is promising for combining these four components in order to enhance the current social models that have already shown some success. Keywords: biopsychosocial, holistic, addiction, recovery, substance use, psychology, physical activity, exercise, nutrition, health, well-being, social support system

NOX4-derived ROS are neuroprotective by balancing intracellular calcium stores

Hyperexcitability is associated with neuronal dysfunction, cellular death, and consequently neurodegeneration. Redox disbalance can contribute to hyperexcitation and increased reactive oxygen species (ROS) levels are observed in various neurological diseases. NOX4 is an NADPH oxidase known to produce ROS and might have a regulating function during oxidative stress. We, therefore, aimed to determine the role of NOX4 on neuronal firing, hyperexcitability, and hyperexcitability-induced changes in neural network function. Using a multidimensional approach of an in vivo model of hyperexcitability, proteomic analysis, and cellular function analysis of ROS, mitochondrial integrity, and calcium levels, we demonstrate that NOX4 is neuroprotective by regulating ROS and calcium homeostasis and thereby preventing hyperexcitability and consequently neuronal death. These results implicate NOX4 as a potential redox regulator that is beneficial in hyperexcitability and thereby might have an important role in neurodegeneration.</p

Prognostic value of single-subject grey matter networks in early multiple sclerosis

The identification of prognostic markers in early multiple sclerosis (MS) is challenging and requires reliable measures that robustly predict future disease trajectories. Ideally, such measures should make inferences at the individual level to inform clinical decisions. This study investigated the prognostic value of longitudinal structural networks to predict five-year EDSS progression in patients with relapsing-remitting MS (RRMS). We hypothesized that network measures, derived from magnetic resonance imaging (MRI), outperform conventional MRI measurements at identifying patients at risk of developing disability progression. This longitudinal, multicentre study within the Magnetic Resonance Imaging in MS (MAGNIMS) network included 406 patients with RRMS (mean age = 35.7 ± 9.1 years) followed up for five years (mean follow-up = 5.0 ± 0.6 years). Expanded Disability Status Scale (EDSS) was determined to track disability accumulation. A group of 153 healthy subjects (mean age = 35.0 ± 10.1 years) with longitudinal MRI served as controls. All subjects underwent MRI at baseline and again one year after baseline. Grey matter (GM) atrophy over one year and white matter (WM) lesion load were determined. A single-subject brain network was reconstructed from T1-weighted scans based on GM atrophy measures derived from a statistical parameter mapping (SPM)-based segmentation pipeline. Key topological measures, including network degree, global efficiency and transitivity, were calculated at single-subject level to quantify network properties related to EDSS progression. Areas under receiver operator characteristic (ROC) curves were constructed for GM atrophy, WM lesion load and the network measures, and comparisons between ROC curves were conducted. The applied network analyses differentiated patients with RRMS who experience EDSS progression over five years through lower values for network degree [H(2)=30.0, p<0.001] and global efficiency [H(2)=31.3, p<0.001] from healthy controls but also from patients without progression. For transitivity, the comparisons showed no difference between the groups (H(2)= 1.5, p=0.474). Most notably, changes in network degree and global efficiency were detected independent of disease activity in the first year. The described network reorganization in patients experiencing EDSS progression was evident in the absence of GM atrophy. Network degree and global efficiency measurements demonstrated superiority of network measures in the ROC analyses over GM atrophy and WM lesion load in predicting EDSS worsening (all p-values < 0.05). Our findings provide evidence that GM network reorganization over one year discloses relevant information about subsequent clinical worsening in RRMS. Early GM restructuring towards lower network efficiency predicts disability accumulation and outperforms conventional MRI predictors

Electromagnetic Field Effect or Simply Stress? Effects of UMTS Exposure on Hippocampal Longterm Plasticity in the Context of Procedure Related Hormone Release

Harmful effects of electromagnetic fields (EMF) on cognitive and behavioural features of humans and rodents have been controversially discussed and raised persistent concern about adverse effects of EMF on general brain functions. In the present study we applied radio-frequency (RF) signals of the Universal Mobile Telecommunications System (UMTS) to full brain exposed male Wistar rats in order to elaborate putative influences on stress hormone release (corticosteron; CORT and adrenocorticotropic hormone; ACTH) and on hippocampal derived synaptic long-term plasticity (LTP) and depression (LTD) as electrophysiological hallmarks for memory storage and memory consolidation. Exposure was computer controlled providing blind conditions. Nominal brain-averaged specific absorption rates (SAR) as a measure of applied mass-related dissipated RF power were 0, 2, and 10 W/kg over a period of 120 min. Comparison of cage exposed animals revealed, regardless of EMF exposure, significantly increased CORT and ACTH levels which corresponded with generally decreased field potential slopes and amplitudes in hippocampal LTP and LTD. Animals following SAR exposure of 2 W/kg (averaged over the whole brain of 2.3 g tissue mass) did not differ from the sham-exposed group in LTP and LTD experiments. In contrast, a significant reduction in LTP and LTD was observed at the high power rate of SAR (10 W/kg). The results demonstrate that a rate of 2 W/kg displays no adverse impact on LTP and LTD, while 10 W/kg leads to significant effects on the electrophysiological parameters, which can be clearly distinguished from the stress derived background. Our findings suggest that UMTS exposure with SAR in the range of 2 W/kg is not harmful to critical markers for memory storage and memory consolidation, however, an influence of UMTS at high energy absorption rates (10 W/kg) cannot be excluded

Significant Long-Lasting Improvement after Switch to Incobotulinum Toxin in Cervical Dystonia Patients with Secondary Treatment Failure

Under continuous long-term treatment with abo- or onabotulinum toxin type A (BoNT/A), ~10 to 15% of patients with cervical dystonia (CD) will develop neutralizing antibodies and reduced responsiveness over an ~10-year treatment period. Among the botulinum neurotoxin type A preparations so far licensed for CD, incobotulinum toxin A (incoBoNT/A; Xeomin®) is the only one without complex proteins. Whether CD patients with treatment failure under abo- or onaBoNT/A may still respond to incoBoNT/A is unknown. In this cross-sectional, retrospective study, 64 CD patients with secondary treatment failure after abo- or onaBoNT/A therapy who were switched to incoBoNT/A were compared to 34 CD patients exclusively treated with incoBoNT/A. The initial clinical severity of CD, best outcome during abo- or onaBoNT/A therapy, severity at the time of switching to incoBoNT/A and severity at recruitment, as well as all corresponding doses, were analyzed. Furthermore, the impact of neutralizing antibodies (NABs) on the long-term outcome of incoBoNT/A therapy was evaluated. Patients significantly improved after the switch to incoBoNT/A (p < 0.001) but did not reach the improvement level obtained before the development of partial secondary treatment failure or that of patients who were exclusively treated with incoBoNT/A. No difference between abo- and onaBoNT/A pretreatments or between the long-term outcomes of NAB-positive and NAB-negative patients was found. The present study demonstrates significant long-term improvement after a switch to incoBoNT/A in patients with preceding secondary treatment failure after abo- or onaBoNT/A therapy and confirms the low antigenicity of incoBoNT/A

Skeletal muscle provides the immunological micro-milieu for specific plasma cells in anti-synthetase syndrome-associated myositis

International audienceAbstract Anti-synthetase syndrome (ASyS)-associated myositis is a major subgroup of the idiopathic inflammatory myopathies (IIM) and is characterized by disease chronicity with musculoskeletal, dermatological and pulmonary manifestations. One of eight autoantibodies against the aminoacyl-transferase RNA synthetases (ARS) is detectable in the serum of affected patients. However, disease-specific therapeutic approaches have not yet been established. To obtain a deeper understanding of the underlying pathogenesis and to identify putative therapeutic targets, we comparatively investigated the most common forms of ASyS associated with anti-PL-7, anti-PL-12 and anti-Jo-1. Our cohort consisted of 80 ASyS patients as well as healthy controls ( n = 40), diseased controls ( n = 40) and non-diseased controls ( n = 20). We detected a reduced extent of necrosis and regeneration in muscle biopsies from PL-12 + patients compared to Jo-1 + patients, while PL-7 + patients had higher capillary dropout in biopsies of skeletal muscle. Aside from these subtle alterations, no significant differences between ASyS subgroups were observed. Interestingly, a tissue-specific subpopulation of CD138 + plasma cells and CXCL12 + /CXCL13 + CD20 + B cells common to ASyS myositis were identified. These cells were localized in the endomysium associated with alkaline phosphatase + activated mesenchymal fibroblasts and CD68 + MHC-II + CD169 + macrophages. An MHC-I + and MHC-II + MxA negative type II interferon-driven milieu of myofiber activation, topographically restricted to the perifascicular area and the adjacent perimysium, as well as perimysial clusters of T follicular helper cells defined an extra-medullary immunological niche for plasma cells and activated B cells. Consistent with this, proteomic analyses of muscle tissues from ASyS patients demonstrated alterations in antigen processing and presentation. In-depth immunological analyses of peripheral blood supported a B-cell/plasma-cell-driven pathology with a shift towards immature B cells, an increase of B-cell-related cytokines and chemokines, and activation of the complement system. We hypothesize that a B-cell-driven pathology with the presence and persistence of a specific subtype of plasma cells in the skeletal muscle is crucially involved in the self-perpetuating chronicity of ASyS myositis. This work provides the conceptual framework for the application of plasma-cell-targeting therapies in ASyS myositis