Non-pharmacological treatment of gambling disorder: a systematic review of randomized controlled trials.

BACKGROUND: The main focus of the non-pharmacological treatment of Gambling Disorder (GD) is the behaviour, cognition and motivation of the patient, addressing the psychological determinants of gambling. Although there is not a gold standard non-pharmacological treatment yet, many studies already had promising results, and the outcomes were even better when pharmacotherapies were combined with psychotherapies. This review intended to synthesise the efficacy of various available non-pharmacological therapies for GD evaluated in randomized controlled trials. METHODS: A systematic search was conducted in PubMed and in Cochrane Library for randomized controlled trials. Studies were included if participants had GD as their primary diagnosis and excluded if patients had other comorbidities. RESULTS: From 320 records identified, 22 studies were included in the critical appraisal. They included a total of 1694 patients, with a mean age of 42.94 years, and a 62.31% of males. Seven trials revealed the efficacy of cognitive behaviour therapy in improving significantly the outcomes. Three studies assessing cognitive therapy showed significant improvements in gambling symptoms, while one study showed improvements in gambling behaviour using exposure therapy. Combined or separate motivational interviewing and imaginal desensitization had significant results in 4 trials. Four other studies also showed efficacy for: couples therapy, node-link mapping therapy, 12-step facilitated and personalized feedback intervention. Physical exercise had promising results but did not reach significance. CONCLUSION: The literature included in this review showed the heterogeneity of available psychotherapies. The majority of studies supported the efficacy of the tested therapies, while some of them, due to limitations such as small sample sizes or inadequate control groups, failed to reach significance.

Denervation impairs regeneration of amputated zebrafish fins.

BACKGROUND: Zebrafish are able to regenerate many of its tissues and organs after damage. In amphibians this process is regulated by nerve fibres present at the site of injury, which have been proposed to release factors into the amputated limbs/fins, promoting and sustaining the proliferation of blastemal cells. Although some candidate factors have been proposed to mediate the nerve dependency of regeneration, the molecular mechanisms involved in this process remain unclear. RESULTS: We have used zebrafish as a model system to address the role of nerve fibres in fin regeneration. We have developed a protocol for pectoral fin denervation followed by amputation and analysed the regenerative process under this experimental conditions. Upon denervation fins were able to close the wound and form a wound epidermis, but could not establish a functional apical epithelial cap, with a posterior failure of blastema formation and outgrowth, and the accumulation of several defects. The expression patterns of genes known to be key players during fin regeneration were altered upon denervation, suggesting that nerves can contribute to the regulation of the Fgf, Wnt and Shh pathways during zebrafish fin regeneration. CONCLUSIONS: Our results demonstrate that proper innervation of the zebrafish pectoral fin is essential for a successful regenerative process, and establish this organism as a useful model to understand the molecular and cellular mechanisms of nerve dependence, during vertebrate regeneration.

Differentiated skeletal cells contribute to blastema formation during zebrafish fin regeneration.

The origin of cells that generate the blastema following appendage amputation has been a long-standing question in epimorphic regeneration studies. The blastema is thought to originate from either stem (or progenitor) cells or differentiated cells of various tissues that undergo dedifferentiation. Here, we investigate the origin of cells that contribute to the regeneration of zebrafish caudal fin skeletal elements. We provide evidence that the process of lepidotrichia (bony rays) regeneration is initiated as early as 24 hours post-amputation and that differentiated scleroblasts acquire a proliferative state, detach from the lepidotrichia surface, migrate distally, integrate into the blastema and dedifferentiate. These findings provide novel insights into the origin of cells in epimorphic appendage regeneration in zebrafish and suggest conservation of regeneration mechanisms between fish and amphibians.

Host-derived mannose glycans trigger a pathogenic γδ T cell/IL-17a axis in autoimmunity.

Autoimmune diseases are life-threatening disorders that cause increasing disability over time. Systemic lupus erythematosus (SLE) and other autoimmune diseases arise when immune stimuli override mechanisms of self-tolerance. Accumulating evidence has demonstrated that protein glycosylation is substantially altered in autoimmune disease development, but the mechanisms by which glycans trigger these autoreactive immune responses are still largely unclear. In this study, we found that presence of microbial-associated mannose structures at the surface of the kidney triggers the recognition of DC-SIGN-expressing γδ T cells, inducing a pathogenic interleukin-17a (IL-17a)-mediated autoimmune response. Mice lacking Mgat5, which have a higher abundance of mannose structures in the kidney, displayed increased γδ T cell infiltration into the kidney that was associated with spontaneous development of lupus in older mice. N-acetylglucosamine supplementation, which promoted biosynthesis of tolerogenic branched N-glycans in the kidney, was found to inhibit γδ T cell infiltration and control disease development. Together, this work reveals a mannose-γδ T cell-IL-17a axis in SLE immunopathogenesis and highlights glycometabolic reprogramming as a therapeutic strategy for autoimmune disease treatment.

Mixed Cryoglobulinaemia Vasculitis after Persistent Hepatitis C Virus Eradication.

Mixed cryoglobulinaemia vasculitis (MCV) is a systemic vasculitis of the small and medium-size vessels caused by active hepatitis C (HCV) infection in >80% of cases. Beuthien et al. presented the first case of MCV with undetectable HCV after 10 months of therapy. In the last few years, more authors have described other cases of symptomatic MCV after 1 year of persistent HCV eradication. Here, we present a case report of a 57-year-old man who developed MCV with renal involvement after 3 years of HCV eradication with interferon therapy. LEARNING POINTS: Mixed cryoglobulinaemia can occur after persistent hepatitis C virus eradication.Most cases described in the literature presented mixed cryoglobulinaemia vasculitis (MCV) after 1 year of HCV eradication compared with after 3 years of persistent eradication in our case.The exact mechanism linking HCV and B-cells is not fully understood, but the main factor seems to be the sustained HCV antigenic stimulation of the B-cell compartment.

[Efficacy of ultrasound guided suprascapular block in patients with chronic shoulder pain: retrospective observational study]. / Eficácia do bloqueio do nervo supraescapular guiado por ultrassom em pacientes com dor crônica no ombro: estudo observacional retrospectivo.

INTRODUCTION: Painful shoulder syndrome is a frequent condition among the elderly and an important cause of functional disability. As the conservative is not always effective, ultrasound guided suprascapular nerve blockade presents as an important alternative treatment. OBJECTIVE: To evaluate the efficacy and safety of the use of 0.25% levobupivacaine and 40 mg of triamcinolone in the suprascapular nerve blockade in patients with chronic pain in the shoulder. METHODS: A retrospective, descriptive and analytical study of 71 patients submitted to suprascapular nerve infiltration between August 2014 and March 2017. Surveys were carried out to patients before the technique was performed, after 72 hours, at 1, 3 and 6 months. Pain intensity was assessed using a numeric pain scale (NPS). RESULTS: Out of the 71 patients who underwent a blockade of the suprascapular nerve, 81.2% reported a decrease in pain at 72 hours. In the first, third and sixth month, respectively, 89.8%, 76.1% and 61.8% of the patients presented pain relief. A statistically significant difference (p<0.001) was verified between NPS and the 4 moments assessed after the technique. 43.7% had total pain remission (NPS=0) at six months. Global effectiveness of suprascapular nerve blockade was 60.6% and for the subgroup of patients with rotators' cuff patology was 62.2%. No complications were reported regarding the suprascapular nerve block. CONCLUSION: The results show that ultrasound-guided blockade of the suprascapular nerve using 0.25% levobupivacaine and 40 mg of triamcinolone is a safe and effective treatment in patients with chronic shoulder pain.

Identification of antiparkinsonian drugs in the 6-hydroxydopamine zebrafish model.

Parkinson's disease (PD) is known as a movement disorder due to characteristic motor features. Existing therapies for PD are only symptomatic, and their efficacy decreases as disease progresses. Zebrafish, a vertebrate in which parkinsonism has been modelled, offers unique features for the identification of molecules with antiparkinsonian properties. Here, we developed a screening assay for the selection of neuroactive agents with antiparkinsonian potential. First, we performed a pharmacological validation of the phenotypes exhibited by the 6-hydroxydopamine zebrafish model, by testing the effects of known antiparkinsonian agents. These drugs were also tested for disease-modifying properties by whole mount immunohistochemistry to TH+ neurons and confocal microscopy in the dopaminergic diencephalic cluster of zebrafish. Next, we optimized a phenotypic screening using the 6-hydroxydopamine zebrafish model and tested 1600 FDA-approved bioactive drugs. We found that 6-hydroxydopamine-lesioned zebrafish larvae exhibit bradykinetic and dyskinetic-like behaviours that are rescued by the administration of levodopa, rasagiline, isradipine or amantadine. The rescue of dopaminergic cell loss by isradipine was also verified, through the observation of a higher number of TH+ neurons in 6-OHDA-lesioned zebrafish larvae treated with this compound as compared to untreated lesioned larvae. The phenotypic screening enabled us to identify several compounds previously positioned for PD, as well as, new molecules with potential antiparkinsonian properties. Among these, we selected stavudine, tapentadol and nabumetone as the most promising candidates. Our results demonstrate the functional similarities of the motor impairments exhibited by 6-hydroxydopamine-lesioned zebrafish with mammalian models of PD and with PD patients, and highlights novel molecules with antiparkinsonian potential.

Tapentadol Prevents Motor Impairments in a Mouse Model of Dyskinesia.

The motor features in Parkinson's disease (PD) are associated with the degeneration of dopaminergic cells in the substantia nigra in the brain. Thus, the gold-standard in PD therapeutics still consists of dopamine replacement with levodopa. However, as the disease progresses, this therapeutic option becomes less effective and can be accompanied by levodopa-induced complications. On the other hand, several other neuronal pathways have been implicated in the pathological mechanisms of PD. In this context, the development of alternative therapeutic options that modulate non-dopaminergic targets is emerging as a major goal in the field. In a phenotypic-based screen in a zebrafish model of PD, we identified tapentadol as a candidate molecule for PD. The therapeutic potential of an agent that modulates the opioid and noradrenergic systems has not been explored, despite the implication of both neuronal pathways in parkinsonism. Therefore, we assessed the therapeutic properties of this µ-opioid receptor agonist and norepinephrine reuptake inhibitor in the 6-hydroxydopamine mouse model of parkinsonism. We further submitted 6-hydroxydopamine-lesioned mice to chronic treatment with levodopa and evaluated the effects of tapentadol during levodopa OFF states and on levodopa-induced dyskinesia. Importantly, we found that tapentadol halted the aggravation of dyskinesia and improved the motor impairments during levodopa OFF states. Altogether, our findings raise the hypothesis that concomitant modulation of µ-opioid receptor and norepinephrine transporter might constitute relevant intervention strategies in PD and that tapentadol holds therapeutic potential that may be translated into the clinical practice.

Brown Macroalgae as Valuable Food Ingredients.

Due to the balanced nutritional value and abundance of bioactive compounds, seaweeds represent great candidates to be used as health-promoting ingredients by the food industry. In this field, Phaeophyta, i.e., brown macroalgae, have been receiving great attention particularly due to their abundance in complex polysaccharides, phlorotannins, fucoxanthin and iodine. In the past decade, brown algae and their extracts have been extensively studied, aiming at the development of well-accepted products with the simultaneous enhancement of nutritional value and/or shelf-life. However, the reports aiming at their bioactivity in in vivo models are still scarce and need additional exploration. Therefore, this manuscript revises the relevant literature data regarding the development of Phaeophyta-enriched food products, namely those focused on species considered as safe for human consumption in Europe. Hopefully, this will create awareness to the need of further studies in order to determine how those benefits can translate to human beings.

An Alpha and Theta Intensive and Short Neurofeedback Protocol for Healthy Aging Working-Memory Training.

The present study tested the effects of an intensive and short alpha and theta neurofeedback (NF) protocol in working memory (WM) performance in a healthy elder population and explored the effects of a multimodal approach, by supplementing NF with cognitive tasks. Participants were allocated to four groups: NF (N = 9); neurofeedback supplemented with cognitive training (NFCT) (N = 8); cognitive training (CT) (N = 7) and sham neurofeedback (Sham-NF) (N = 6). The intervention consisted in 30-min sessions for 8 days. The NF group presented post intervention increases of alpha and theta relative power as well as performance in the matrix rotation task. In addition, a successful up training of frontal theta showed positive correlation with an improvement of post-training alpha and a better performance in the matrix rotation task. The results presented herein suggest that an intensive and short NF protocol enables elders to learn alpha and theta self-modulation and already presents moderate improvements in cognition and basal EEG. Also, CT group showed moderate performance gains on the cognitive tasks used during the training sessions but no clear improvements on neurophysiology and behavioral measurements were observed. This study represents a first attempt to study the effects of an intensive and short NF protocol in WM performance of elders. The evidence presented here suggests that an intensive and short NF intervention could be a valid alternative for introduction of older populations to NF methodologies.

Efficacy of ultrasound guided suprascapular block in patients with chronic shoulder pain: observational, retrospective study / Eficácia do bloqueio do nervo supraescapular guiado por ultrassom em pacientes com dor crônica no ombro: estudo observacional retrospectivo

Abstract Introduction: Painful shoulder syndrome is a frequent condition among the elderly and an important cause of functional disability. As the conservative treatment is not always effective, ultrasound guided suprascapular nerve blockade presents as an important alternative treatment. Objective: To evaluate the efficacy and safety of the use of 0.25% levobupivacaine and 40 mg of triamcinolone in the suprascapular nerve blockade in patients with chronic pain in the shoulder. Methods: A retrospective, descriptive and analytical study of 71 patients submitted to suprascapular nerve infiltration between August 2014 and March 2017. Surveys were carried out to patients before the technique was performed, after 72 hours and at 1, 3 and 6 months. Pain intensity was assessed using a numeric pain scale (NPS). Results: Out of the 71 patients who underwent a blockade of the suprascapular nerve, 81.2% reported a decrease in pain at 72 hours. In the first, third and sixth month, respectively, 89.8%, 76.1% and 61.8% of the patients presented pain relief. A statistically significant difference (p < 0.001) was verified between NPS and the 4 moments assessed after the technique. 43.7% had total pain remission (NPS = 0) at six months. Global effectiveness of suprascapular nerve blockade was 60.6% and for the subgroup of patients with rotators' cuff patology was 62.2%. No complications were reported regarding the suprascapular nerve block. Conclusion: The results show that ultrasound-guided blockade of the suprascapular nerve using 0.25% levobupivacaine and 40 mg of triamcinolone is a safe and effective treatment in patients with chronic shoulder pain.

Resumo Introdução: A síndrome do ombro doloroso é uma condição frequente entre os idosos e uma causa importante de incapacidade funcional na população em geral. O tratamento conservador nem sempre é eficaz, pelo que o bloqueio do nervo supraescapular guiado por ecografia apresenta-se como uma opção de tratamento válida. Objetivo: Avaliação da eficácia e segurança do uso de levobupivacaína a 0,25% e 40 mg de triancinolona no bloqueio do nervo supraescapular ecoguiado em doentes com dor crônica no ombro. Métodos: Realizou-se um estudo retrospectivo observacional, descritivo e analítico com 71 doentes submetidos à infiltração do nervo supraescapular entre agosto de 2014 e março de 2017. Foram aplicados questionários antes da realização da técnica, após 72 horas; 1, 2 e 6 meses. A intensidade da dor foi avaliada usando a Escala de Avaliação Numérica (EAN). Resultados: Dos 71 doentes submetidos ao bloqueio do nervo supraescapular; 81,2% referiram diminuição da dor às 72 horas. Aos primeiro, terceiro e sexto mês, respectivamente 89,8%; 76,1% e 61,8% apresentaram melhoria da dor. Verificou-se uma diferença estatisticamente significativa (p < 0,001), entre a EAN inicial e os 4 momentos após a realização da técnica. 43,7% dos doentes tiveram remissão total da dor (EAN = 0) aos seis meses. A eficácia global do bloqueio do nervo supraescapular foi de 60,6% e, para o subgrupo com patologia da coifa dos rotadores, de 62,2%. Nenhuma complicação do bloqueio do NSE foi registrada. Conclusão: Este estudo mostra que o bloqueio eco-guiado do NSE usando levobupivacaína a 0,25% e 40 mg de triancinolona é um procedimento seguro e eficaz em doentes com dor crônica no ombro.

Age effects on EEG correlates of the Wisconsin Card Sorting Test.

Body and brain undergo several changes with aging. One of the domains in which these changes are more remarkable relates with cognitive performance. In the present work, electroencephalogram (EEG) markers (power spectral density and spectral coherence) of age-related cognitive decline were sought whilst the subjects performed the Wisconsin Card Sorting Test (WCST). Considering the expected age-related cognitive deficits, WCST was applied to young, mid-age and elderly participants, and the theta and alpha frequency bands were analyzed. From the results herein presented, higher theta and alpha power were found to be associated with a good performance in the WCST of younger subjects. Additionally, higher theta and alpha coherence were also associated with good performance and were shown to decline with age and a decrease in alpha peak frequency seems to be associated with aging. Additionally, inter-hemispheric long-range coherences and parietal theta power were identified as age-independent EEG correlates of cognitive performance. In summary, these data reveals age-dependent as well as age-independent EEG correlates of cognitive performance that contribute to the understanding of brain aging and related cognitive deficits.

Sonic hedgehog and retinoic acid are not sufficient to induce motoneuron generation in the avian caudal neural tube.

The caudal neural tube (CNT) of the avian embryo is devoid of both dorsal and ventral roots. We show that the lack of ventral roots in the CNT, from somite 48 caudalwards, is due to an absence of post-mitotic motoneurons (MNs). The absence of MNs is not due to a defective notochordal induction since Sonic Hedgehog (SHH) signaling is intact and the caudal notochord is able to induce ectopic MNs when grafted laterally to a host neural tube. The transcription factors involved in MN specification (Pax6, Nkx6.1, and Olig2) are all expressed in the CNT, despite the lower expression level of Pax6, but an overlap between Olig2 and the ventrally expressed transcription factor Nkx2.2 is observed in the CNT. Grafting a quail CNT into the cervical level of a chick host rescues MN generation, demonstrating both the CNT potential for MN generation and the key role of the caudal environment in the MN differentiation blockade. The transplantation of the CNT-flanking somites into the cervical level does not inhibit MN generation. Furthermore, implantation of a retinoic-acid-soaked bead laterally to the CNT does not rescue MN generation. Together, these data indicate that the rostral environment contains a signal different from both SHH and Retinoic Acid that acts on MN differentiation.