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Dementia is a global public health problem with increasing prevalence and incidence worldwide. The African continent is expected to bear the biggest brunt of the burden of dementia by 2050 because of the rapid demographic changes, including rapid population growth, an increase in life expectancy, and ageing. However, French-speaking Sub-Saharan African (FS-SSA) countries are underrepresented in research on dementia in Africa. While the reasons are diverse and complex, linguistic and cultural barriers to research, disproportionately affect these countries and may be significant factors. Any efforts, therefore, to redress the burden of dementia in Africa must consider the specific demographic, cultural, and linguistic characteristics of FS-SSA countries. This scoping review explores the current state of knowledge in dementia and cognitive impairment in Sub-Saharan Africa, highlighting research gaps and specific patterns unique to FS-SSA Africa. We identify pathways for research to bridge the knowledge gaps on dementia in FS-SSA as part of the global endeavor to tackle dementia worldwide.

Background and aims: Porphyrias constitute a group of rare genetic diseases due to various, mostly autosomal dominant mutations, causing enzymatic deficiency in heme biosynthesis. As a result, neurotoxic porphyrin precursors and light-sensitive porphyrins accumulate, while dysfunction in their targets determines the disease symptoms. Variegate porphyria (VP), one of the acute hepatic porphyrias, is caused by a protoporphyrinogen oxidase (PPOX) mutation. During acute attacks, among other factors, triggered by drugs, stressors, or fasting, an increase in urinary and fecal porphobilinogen (PBG), aminolevulinic acid (ALA), and porphyrins occurs, damaging the autonomous, peripheral, or central nervous system. The disease remains often latent or displays minimal symptoms usually overlooked, exposing undiagnosed patients to potentially serious complications in the presence of the aforementioned triggers.Case report: This 46-year-old woman presented, some days after a bariatric surgery, with severe flaccid tetraparesis and neuropathic pain, initially misdiagnosed as a functional neurological disorder. The severe axonal sensorimotor polyneuropathy led to further investigations, disclosing high urinary porphobilinogen, ALA, and porphyrin levels due to a new PPOX mutation. Retrospectively, it appeared that the patient had had typical VP symptoms (abdominal pain, fragile skin, and dark urine episodes) for years prior to the surgery. Treated with carbohydrate load, neurorehabilitation, and analgesics, she slowly recovered to full mobility, with partial autonomy in her daily life activities, although fatigue and severe pain persisted, preventing her from returning to work.Conclusion: This case documents gastric bypass surgery as a trigger of severe VP invalidating neurological symptoms and illustrates how the delayed diagnosis and post-interventional complications could have been prevented by screening for porphyria cardinal symptoms prior to the intervention. Likewise, this cost-effective screening should be performed before any treatment influencing the diet, which would dramatically improve the porphyria diagnosis rate and outcome.

BACKGROUND Chronic pain is a complex problem for many older adults that affects both physical functioning and psychological well-being. Mobile health (mHealth) technologies have shown promise in supporting older persons in managing chronic conditions. Cognitive behavior therapy is recommended for older people with chronic pain. However, web-based treatment programs for chronic pain are not aimed at the needs of older people and offer standard therapies without providing tailored treatment for this population. OBJECTIVE To address this problem, we aim to develop a psychological web-based intervention for ecological monitoring of daily life experiences with chronic pain called EMMA to support self-management of chronic pain in older adults. METHODS The key clinical and engagement features of the intervention were established through the integration of evidence-based material from cognitive behavioral therapy for the treatment of chronic pain in older adults. The development process uses a co-design approach and actively involves end-users in the design process by incorporating feedback from focus groups with older adults in order to inform a user-centered intervention design. For the co-design process, we will include 10 older adults with chronic pain, who will discuss the requirements for the app in workshops in order to ensure suitability of the app for older adults with chronic pain. In order to test the feasibility and acceptability of the intervention, we will include a sample of 30 older adults with chronic pain who will test all features of the intervention for a period of 8 consecutive weeks. After the trial period, validated instruments will be used to assess usability and acceptability, as well as influence on pain levels and associated physical and psychological symptoms. Participants will be invited to take part in a semistructured telephone interviews after the trial period to explore their experiences using the app. RESULTS Digitalization of the pain diary and psychotherapeutic content has started. Recruitment of participants for the co-design workshops will start as soon as we have a functioning prototype of the electronic pain diary and EMMA intervention, which is expected to be in September 2021. The feasibility study will start as soon as the co-design process is finished and required changes have been implemented into the pain diary and the EMMA intervention. We expect to start the feasibility study early in 2022. CONCLUSIONS Required changes to assure usability and acceptability will be directly implemented in the app. EMMA brings together a strong body of evidence using cognitive behavioral and self-management theory with contemporary mHealth principles, allowing for a cost-effective intervention that can be used to target chronic pain anywhere and anytime by older adults. Given the ubiquity of mHealth interventions for chronic conditions, the results of this study may serve to inform the development of tailored self-management interventions. INTERNATIONAL REGISTERED REPORT PRR1-10.2196/26930

In neuronal cells, GABA evokes an increase in chloride conductance by activating GABA(A) and GABA(C) receptors. In mature neurons, this increase in conductance generally has a hyperpolarizing and inhibitory action. Using gramicidin-based perforated patch recordings, we show that in cultured motor neurons GABA-induced currents are significantly altered following activation of GABA receptors coinciding with changes in membrane potential. Changes in intracellular chloride concentration constituted the mechanism for this modulation. Because of low resting chloride conductance and low activity of chloride transporters, changes in intracellular chloride concentration and hence GABA response were long-lasting (time constant of recovery was about 2.5 min). Cultured dorsal horn and hippocampal neurons exhibited a similar response pattern, suggesting a general property of cultured neuronal cells. These long-lasting changes in GABA responsiveness may have major implications on neuronal excitability.

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 patch-clamp 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 GABA(A) 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. ispartof: FASEB Journal vol:23 issue:4 pages:1168-1176 ispartof: location:United States status: published

Sweet dysgeusia, a rare taste disorder, may be encountered in severe anti-acetylcholine receptor antibody (AChRAb)-myasthenia gravis (MG). A 42 year-old man reported progressive loss of sweet taste evolving for almost 10 weeks, revealing an AChRAb-positive MG with thymoma. Improvement of sweet perception paralleled reduction of the MG composite score during the 15 months follow up period, with immunosuppressive and surgical treatments. We suggest that sweet dysgeusia is a non-motor manifestation of MG that may result from a thymoma-dependent autoimmune mechanism targeting gustducin-positive G-protein-coupled taste receptor cells, in line with recent data from MRL/MpJ-Fas lpr/ (MRL/lpr) transgenic mice with autoimmune disease.