Treatment and prevention of epilepsy in onchocerciasis-endemic areas is urgently needed.

BACKGROUND: There is increasing epidemiological evidence supporting the association between onchocerciasis and seizures, reinforcing the concept of onchocerciasis-associated epilepsy (OAE). The aim of this paper is to provide an update on the new knowledge about OAE and to propose recommendations to the World Health Organization how to address this public health problem. MAIN TEXT: During the 2nd International Workshop on OAE held on 19-21 September, 2023, in Antwerp, Belgium, participants recognised OAE as a substantial yet neglected public health problem, particularly in areas of sub-Saharan Africa where onchocerciasis remains hyperendemic. Evidence from prospective population-based studies suggest that strengthening onchocerciasis elimination efforts leads to a significant reduction of OAE incidence. There is a need to validate an OAE case definition to estimate the burden of disease and identify onchocerciasis-endemic areas requiring intensification of onchocerciasis elimination programmes and integration of epilepsy care. It is expected that raising awareness about OAE will boost the population uptake of ivermectin. The implementation of a community-based epilepsy treatment programme offering free anti-seizure medications (ASMs) has shown high effectiveness in reducing the frequency of seizures and improving the overall quality of life of people with epilepsy. CONCLUSIONS: To reduce OAE burden, enhanced collaboration between onchocerciasis and mental health programmes at community, national, and international levels is required. Urgent efforts are needed to ensure the uninterrupted provision of free ASMs in onchocerciasis-endemic areas. Furthermore, OAE should be included in the quantification of the onchocerciasis disease burden.

Excitatory amino acids, possible causative agents of nodding syndrome in eastern Africa.

BACKGROUND: Nodding syndrome (NS) is one type of epilepsy and a progressive disease characterized by nodding symptoms with children in sub-Saharan Africa. The burden for NS children is heavy, not only mentally but financially for themselves and their families, and yet, the cause and cure of NS remain unknown. The kainic acid-induced model in experimental animals is a well-known epilepsy model that is useful for studying human diseases. In this study, we examined similarities of clinical symptoms and histological brain changes between NS patients and kainic acid-treated rats. In addition, we argued for kainic acid agonist as one of the causes of NS. METHODS: Clinical signs in rats were studied after kainic acid administration, and histological lesions including the expression of tau protein and gliosis, were examined at 24 h, 8 days, and 28 days after dosing. RESULTS: Kainic acid-induced epileptic symptoms were observed in rats, including nodding accompanied by drooling and bilateral neuronal cell death in the hippocampus and piriform cortex regions. In the regions that exhibited neuronal cell death, an increase in tau protein expression and gliosis were found immunohistochemically. The symptoms and brain histology were similar in the NS and kainic acid-induced rat models. CONCLUSION: The results suggest that kainic acid agonist may be one of the causative substances for NS.

Stigma and epilepsy in onchocerciasis-endemic regions in Africa: a review and recommendations from the onchocerciasis-associated epilepsy working group.

BACKGROUND: In onchocerciasis-endemic areas, particularly in those with a sub-optimal onchocerciasis control programme, a high prevalence of epilepsy is observed. Both onchocerciasis and epilepsy are stigmatizing conditions. The first international workshop on onchocerciasis-associated epilepsy (OAE) was held in Antwerp, Belgium (12-14 October 2017) and during this meeting, an OAE alliance was established. In this paper, we review what is known about epilepsy-associated stigma in onchocerciasis-endemic regions, and present the recommendations of the OAE alliance working group on stigma. MAIN BODY: For this scoping review, literature searches were performed on the electronic databases PubMed, Scopus and Science Direct using the search terms "epilepsy AND onchocerciasis AND stigma". Hand searches were also undertaken using Google Scholar, and in total seven papers were identified that addressed epilepsy-related stigma in an onchocercisasis-endemic area. Due to the limited number of published research papers on epilepsy-associated stigma in onchocerciasis-endemic areas, other relevant literature that describes important aspects related to stigma is discussed. The thematic presentation of this scoping review follows key insights on the barriers to alleviating the social consequences of stigma in highly affected onchocerciasis-endemic areas, which were established by experts during the working group on stigma and discrimination at the first international workshop on OAE. These themes are: knowledge gaps, perceived disease aetiology, access to education, marriage restrictions, psycho-social well-being, burden on the care-giver and treatment seeking behaviour. Based on the literature and expert discussions during the OAE working group on stigma, this paper describes important issues regarding epilepsy-related stigma in onchocerciasis-endemic regions and recommends interventions that are needed to reduce stigma and discrimination for the improvement of the psycho-social well-being of persons with epilepsy. CONCLUSIONS: Educating healthcare workers and communities about OAE, strengthening onchocerciasis elimination programs, decreasing the anti-epileptic treatment gap, improving the care of epilepsy-related injuries, and prioritising epilepsy research is the way forward to decreasing the stigma associated with epilepsy in onchocerciasis-endemic regions.

Second-order nonlinear optical susceptibilities of nonelectrically poled DR1-PMMA guest-host polymers.

Guest-host nonlinear optical polymers have attracted considerable interest due to their applications in fast electro-optical modulators and wavelength converters. In general, the electrical poling procedures, for which high DC external fields are applied, are necessary for aligning guest chromophores in polar order and activating the second-order nonlinearity. We present the nonelectrical poling behaviors for guest-host polymers: DR1 (4-[ethyl (2-hydroxyethyl) amino]-4'-nitroazobenzene) is the guest, and PMMA (poly (methyl methacrylate)) is the host. Second-order nonlinear optical susceptibility was induced in the conventional guest-host polymers after annealing at temperatures above the glass transition points of the host polymer even without applying the external fields. This phenomenon did not occur in the side-chain polymers, where the guests were directly bonded to the host chains. The guest polar alignments were most likely generated from the guest hydroxyl groups chemisorbing on the substrates. The polar alignments of the guest formed not only near the surface of the substrate, but also inside the host polymers. The optimized conditions for the SHG conversion were examined in the context of the polymer film thickness and guest concentration. The nonelectrical poling techniques described in this study are useful for enhancing the surface nonlinearity in the several materials, and they will be useful for further developments in nanophotonics and plasmonics.

Comprehension of terminal differentiation and dedifferentiation of chondrocytes during passage cultures.

A high density collagen type I coated substrate (CL substrate) was used to evaluate the chondrocyte phenotypes in passaged cultures. With increasing age of cell population (population doubling (PD)=0-14.5), the frequency of non-dividing spindle shaped cells without ALP activity increased, accompanied with an increase in gene expression of collagen type I, meaning the senescence of dedifferentiated cells. At the middle age of cell population (PD=5.1 and 6.6), the high frequency of polygonal shaped cells with ALP activity existed on the CL substrate together with up-regulated expressions of collagen types II and X, indicating the terminal differentiation of chondrocytes. When the chondrocytes passaged up to the middle age were embedded in collagen gel, the high frequency of single hypertrophic cells with collagen type II formation was recognized, which supports the thought that the high gene expression of collagen type II was attributed to terminal differentiation rather than redifferentiation. These results show that the CL substrate can draw out the potential of terminal differentiation in chondrocytes, which is unattainable by a polystyrene surface, and that the CL substrate can be a tool to evaluate cell quality in three-dimensional culture with the collagen gel.

Morphological evaluation of chondrogenic potency in passaged cell populations.

The present study describes the morphological assessment of chondrogenic potency during a cell expanding process through serial subculturing of rabbit chondrocytes at different levels of population doublings (PD) in a T-flask with a conventional polystyrene surface. The passaged populations were seeded on a high-density collagen surface (CL surface) and in a collagen gel (CL gel) scaffold to evaluate the planar and spatial morphologies of the chondrocytes, respectively, as well as the gene expressions of mRNA for collagen types I and II. The planar morphological estimation was based on roundness (R(c)) of chondrocyte cells at different PD values after 1 day incubation on the CL surface. The frequency of round-shaped cells with R(c)>0.9 (f(R)) decreased with increasing PD values, accompanied by an increase in collagen type I mRNA level. At PD=17.8, the frequency reached f(R)=0.12, which was less than one-sixth of that at PD=0. A similar trend was found with respect to the passaged chondrocytes embedded in the CL gels by estimating the spatial morphology in terms of sphericity (S(c)) determined 4 days after seeding. With an increase in PD value, the frequency in spherical-shaped cells with S(c)>0.9 (f(S)) decreased and the mRNA expression of collagen type I increased, giving f(S)=0.28 at PD=17.8 which was less than a quarter of that at PD=0. From these results, the cell morphologies on the CL surface and in the CL gel were proposed as indicators for understanding chondrogenic potentials concerning the phenotypes and differentiated states in the population during cell expansion, ultimately leading to quality control of tissue-engineered cartilage.

Characterization of spatial growth and distribution of chondrocyte cells embedded in collagen gels through a stereoscopic cell imaging system.

The stereoscopic image analysis of fluorescence-labeled chondrocyte cells for cytoplasm and nucleus was performed for the quantitative determination of spatial cell distribution as well as cell aggregate size in the collagen-embedded culture. The three-dimensional histomorphometric data indicated that the cells in the gels formed aggregates by cell division, and the size of aggregates increased with elapsed culture time. In the culture seeded at 2.0 x 10(6) cells/cm(3), the cells showed a semilunar shape that is a typical chondrocytic morphology, and formed the dense cell aggregates producing collagen type II. From the quantitative analysis of aggregate size, in addition, it was found that the cell division caused the aggregate growth with an increase of cell number in respective aggregates at 7 days, and some of aggregates made coalescence at 14 days. In the gel surface region, further coalescence of aggregates accompanied with cell division produced larger cell clusters, creating cell layers on the gel surface at the end of culture (21 days). In the culture seeded at 2.0 x 10(5) cells/cm(3), the different manner of aggregation was observed. At 14 days, the loose clusters of spindle-shaped cells emerged in the deeper region of gels, suggesting that the cell migration and gathering occurred in the gels. This loose-clustered aggregates did not produce collagen type II. Our results suggest that the seeding density is a factor to cause different mechanisms of cell distribution accompanied with the formation of aggregates as well as collagen type II.

Effect of transforming growth factor-beta1 on morphological characteristics relating to migration and differentiation of rabbit chondrocytes cultured in collagen gels.

The influence of transforming growth factor-beta1 (TGFbeta1) on the behavior of rabbit chondrocytes embedded in collagen gels was examined in terms of cell migration and consequent architecture of cell aggregation. In a low-seeding density culture (X(0)=2.0 x 10(5) cells/cm(3)) TGFbeta1 (0-10.0 ng/ml) was added and observed during a 14-d culture period. Stereoscopic observation was performed on 5 d employing the morphology-related parameter of sphericity (S(c)) for individual cells in the gels. The frequency of migrating cells with S(c) less than 0.95 increased in a dose-dependent manner in response to TGFbeta1. Moreover, the frequency of migrating cells in the culture with 10.0 ng/ml TGFbeta1 was 0.32, two times higher than that in the reference culture without TGFbeta1, while the frequency of dividing cells in the same culture was less than half of that in the reference culture. The histological observation of cultured gels on 14 d revealed that the starburst and loose aggregates with the spindle-shaped cells emerged in the TGFbeta1-free culture, accompanying the poor production of collagen type II by the cells. On the other hand, the spherical-shaped cells were observed in the starburst aggregates with rich excretion of collagen type II in the culture with 5.0 ng/ml TGFbeta1. Moreover, the mRNA levels of differentiation-marker genes (collagen types I and II) were regulated in accordance with the morphological analyses concerning the cell migration and aggregation in the cultures with and without TGFbeta1. From these results, it was concluded that TGFbeta1 had a culture time-dependent effect on the morphological characteristics relating to the migration and differentiation of the chondrocytes in the collagen gel-embedded cultures seeded at low density, that is, the growth factor promotes cell migration with deteriorated proliferation in the early culture phase, and accelerates the transformation of spindle-shaped cells to spherical-shaped ones in the prolonged culture.