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Plasma membrane chloride (Cl-) pathways play an important role in neuronal physiology. Here, we investigated the role of NKCC1 cotransporters (a secondary active Cl- uptake mechanism) in Cl- handling in cultured rat dorsal root ganglion neurons (DRGNs) and motor neurons (MNs) derived from fetal stage embryonic day 14. Gramicidin-perforated patchclamp recordings revealed that DRGNs accumulate intracellular Cl- through a bumetanide- and Na+-sensitive mechanism, indicative of the functional expression of NKCC1. Western blotting confirmed the expression of NKCC1 in both DRGNs and MNs, but immunocytochemistry experiments showed a restricted expression in dendrites of MNs, which contrasts with a homogeneous expression in DRGNs. Both MNs and DRGNs could be readily loaded with or depleted of Cl- during GABAA receptor activation at depolarizing or hyperpolarizing membrane potentials. After loading, the rate of recovery to the resting Cl- concentration (i.e., [Cl-]i decrease) was similar in both cell types and was unaffected by lowering the extracellular Na+ concentration. In contrast, the recovery on depletion (i.e., [Cl-]i increase) was significantly faster in DRGNs in control conditions but not in low extracellular Na+. The experimental observations could be reproduced by a mathematical model for intracellular Cl- kinetics, in which DRGNs show higher NKCC1 activity and smaller Cl--handling volume than MNs. On the basis of these results, we conclude that embryonic DRGNs show a higher somatic functional expression of NKCC1 than embryonic MNs. The high NKCC1 activity in DRGNs is important for maintaining high [Cl-]i, whereas lower NKCC1 activity in MNs allows large [Cl-]i variations during neuronal activity. [ABSTRACT FROM AUTHOR]

Placebo analgesia (PA) is defined as a psychobiological phenomenon triggered by the information surrounding an analgesic drug instead of its inherent pharmacological properties. PA is hypothesized to be formed through either verbal suggestions or conditioning. The present study aims at disentangling the neural correlates of expectations effects with or without conditioning through prior experience using the model of PA. We addressed this question by recruiting two groups of individuals holding comparable verbally-induced expectations regarding morphine analgesia but either (i) with or (ii) without prior experience with opioids. We then contrasted the two groups' neurocognitive response to acute heat-pain induction following the injection of sham morphine using electroencephalography (EEG). Topographic ERP analyses of the N2 and P2 pain evoked potential components allowed to test the hypothesis that PA involves distinct neural networks when induced by expectations with or without prior experience. First, we confirmed that the two groups showed corresponding expectations of morphine analgesia (Hedges' g s  < .4 positive control criteria, g s  = .37 observed difference), and that our intervention induced a medium-sized PA (Hedges' g av  ≥ .5 positive control, g av  = .6 observed PA). We then tested our hypothesis on the recruitment of different PA-associated brain networks in individuals with versus without prior experience with opioids and found no evidence for a topographic N2 and P2 ERP components difference between the two groups. Our results thus suggest that in the presence of verbally-induced expectations, modifications in the PA-associated brain activity by conditioning are either absent or very small., (© 2022 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Introduction: Little is known about the outcomes of subjects with a history of severe acute malnutrition (SAM). We therefore sought to explore the long-term effects of SAM during childhood on human capital in adulthood in terms of education, cognition, self-esteem and health-related disabilities in daily living., Methodology: We traced 524 adults (median age of 22) in the eastern Democratic Republic of the Congo, who were treated for SAM during childhood at Lwiro hospital between 1988 and 2007 (median age 41 months). We compared them with 407 community controls of comparable age and sex. Our outcomes of interest were education, cognitive function [assessed using the Mini Mental State Examination (MMSE) for literate participants, or its modified version created by Ertan et al. (MMSE-I) for uneducated participants], self-esteem (measured using the Rosenberg Self-Esteem Scale) and health-related social and functional disabilities measured using the World Health Organization Disability Assessment Schedule (WHODAS). For comparison, we used the Chi-squared test along with the Student's t-test for the proportions and means respectively., Results: Compared with the community controls, malnutrition survivors had a lower probability of attaining a high level of education (p < 0.001), of reporting a high academic performance (p = 0.014) or of having high self-esteem (p = 0.003). In addition, malnutrition survivors had an overall mean score in the cognitive test that was lower compared with the community controls [25.6 compared with 27.8, p = 0.001 (MMSE) and 22.8 compared with 26.3, p < 0.001(MMSE-I)] and a lower proportion of subjects with a normal result in this test (78.0% compared with 90.1%, p < 0.001). Lastly, in terms of health-related disabilities, unlike the community controls, malnutrition survivors had less social disability (p = 0.034), but no difference was observed as regards activities of daily living (p = 0.322)., Conclusion: SAM during childhood exposes survivors to low human capital as regards education, cognition and behaviour in adulthood. Policy-deciders seeking to promote economic growth and to address various psychological and medico-social disorders must take into consideration the fact that appropriate investment in child health as regards SAM is an essential means to achieve this., Competing Interests: The authors have declared that no competing interests exist.

In 2011, new oral anticoagulants for atrial fibrillation are available and the ABCD3-I score predicting stroke after TIA updates the ABCD2 score. New McDonald criteria allow faster MS diagnosis and the first oral treatment (fingolimod) for MS can be prescribed. A new anti-antiepileptic drug (retigabine) is available and sodium valproate has long term neurological adverse effects after in utero exposure. Among Parkinson disease treatments, deep brain stimulation is extending applications and dopamine agonists with extended release are as efficient and well tolerated as standard forms at long term scale. Monoclonal antibodies and immunosuppressant agents are proposed as good alternatives in the treatment of chronic dysimmune polyneuropathies. Gene therapy for the treatment of genetic myopathies is progressing.

Konzo is an upper motor neuron disease characterized by sudden-onset and irreversible spastic paraparesis occurring in nutritionally compromised people. It is associated with consumption of insufficiently processed cyanogenic-toxic cassava. Cassava, the main caloric source in the Democratic Republic of Congo, has been safely consumed for decades in the Eastern Province of South-Kivu. However, in the context of long-lasting war and violent conflicts, cases of spastic paraparesis resembling konzo appeared in a populous area (Burhinyi). Two field surveys (2003 and 2005) identified 41 subjects meeting clinical criteria of konzo and suffering from (chronic) malnutrition. Their urinary thiocyanate concentrations (median 129, range 20-688, SD 146 μg/L), and cyanogen levels (median 20 ppm, range 5-300 ppm, SD 73 ppm) in cassava roots from their household stocks were high. The source of cyanogenic-toxicity was unprocessed fresh cassava roots during harvest period, but probably also insufficiently processed roots. This first report of konzo in South-Kivu concludes that occurrence of konzo was triggered by food shortages because of the longstanding state of insecurity. Contributory factors included the introduction of new varieties of (bitter) cassava, but konzo may actually be caused by a combination of factors that are yet to be understood., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Despite the recognized role of traditional healers in helping patients with mental health problems, there is a need for modern mental healthcare facilities in Africa. When made available, these are used by the local population, but less by those at remote locations. Data from the SOSAME centre indicate the high prevalence of mental diseases, especially in urban population and during the active decades of life. To decrease the burden imposed on mental health institutions by patients consulting for non-mental problems, it is desirable to integrate these institutions with the other components of the healthcare system.