Cerebellar Pathology in an Inducible Mouse Model of Friedreich Ataxia

Friedreich ataxia (FRDA) is an autosomal recessive neurodegenerative disorder caused by deficiency of the mitochondrial protein frataxin. Lack of frataxin causes neuronal loss in various areas of the CNS and PNS. In particular, cerebellar neuropathology in FRDA patients includes loss of large principal neurons and synaptic terminals in the dentate nucleus (DN), and previous studies have demonstrated early synaptic deficits in the Knockin-Knockout mouse model of FRDA. However, the exact correlation of frataxin deficiency with cerebellar neuropathology remains unclear. Here we report that doxycycline-induced frataxin knockdown in a mouse model of FRDA (FRDAkd) leads to synaptic cerebellar degeneration that can be partially reversed by AAV8-mediated frataxin restoration. Loss of cerebellar Purkinje neurons and large DN principal neurons are observed in the FRDAkd mouse cerebellum. Levels of the climbing fiber-specific glutamatergic synaptic marker VGLUT2 decline starting at 4 weeks after dox induction, whereas levels of the parallel fiber-specific synaptic marker VGLUT1 are reduced by 18-weeks. These findings suggest initial selective degeneration of climbing fiber synapses followed by loss of parallel fiber synapses. The GABAergic synaptic marker GAD65 progressively declined during dox induction in FRDAkd mice, while GAD67 levels remained unaltered, suggesting specific roles for frataxin in maintaining cerebellar synaptic integrity and function during adulthood. Expression of frataxin following AAV8-mediated gene transfer partially restored VGLUT1/2 levels. Taken together, our findings show that frataxin knockdown leads to cerebellar degeneration in the FRDAkd mouse model, suggesting that frataxin helps maintain cerebellar structure and function

ANALISIS KESALAHAN SISWA DALAM MENYELESAIKAN SOAL OPERASI PECAHAN BENTUK ALJABAR SMP

According to the national examination (UN) scores for Junior High School in East Sumba in 2019, it can be seen that the percentage of student’s math scores based on the comparison of test scores with graduation standards is still very low. In view of the problem, studies are conducted to describe a student’s error, describing the factors that cause students to make mistakes in solving problems, and planning follow-up actions to minimize student errors when operating addition and subtraction of algebraic fraction. This type of research is qualitative approach. The technique of determining the student’s research subject uses the cluster sampling technique with sample 5 students. The technique of collecting data is done by writing tests, interviews and documentary studies. The results showed that according to Newman’s five types of errors, student made 5 types of errors, and the most common mistakes were in encoding error of 1,53%, then processing skill error 2,33%; transformation error 2,5%; comprehension error and reading error 3,1%

Profil des germes impliqués dans les infections cervicovaginales chez la femme en âge de procréer à l’hôpital de district de Bonassama.

Introduction : Les infections cervico-vaginales constituent l'un des motifs de consultation les plus courants en gynécologie. Ces infections ont un impact majeur sur la santé. Pourtant dans le contexte Camerounais, de rares études se sont penchées sur cette problématique. Le but de cette étude était de déterminer la sensibilité des germes et les facteurs associés aux infections cervico-vaginales chez la femme en âge de procréer à l’hôpital de District de Bonassama en 2014. Méthodologie : Il s’agissait d’une étude transversale, prospective et descriptive qui s’est déroulée de février à juin 2014 à l’hôpital de District de Bonassama. L’échantillonnage était de type consécutif et un questionnaire pré-testé avait permis la collecte des données, avant que des prélèvements vaginaux aient été faits sur les sujets. Les tests du Chi 2 et de Student avaient permis de définir les associations entre variables et le taux de significativité était de 0,05. Résultats : Sur les 102 femmes incluses, 18 étaient enceintes. L’âge moyen des femmes était de 28,7 ans ± 6,98. Parmi elles, 49,02% avaient fait des études supérieures et 50 % étaient mariées. La prévalence des infections était de 70,59%. Les germes rencontrés étaient Candida albicans 32,35%, Gardnerella vaginalis 30,39%, Staphylococcus aureus 8,82%, Streptococcus spp 1,96%, les entérobactéries 11,78% et le trichomonas vaginalis 1%. C.albicans a montré une résistance à l’Amphotéricime B 41 ,94 % et au Fluconazole 46, 88 %. La Nystatine et l’Econazole conservaient une bonne sensibilité avec respectivement 80,7% et 74,07 %. La présence de G .vaginalis était liée à l’absence de grossesse (p=0 ,02) et celle de C.albicans au niveau d’éducation (p=0 ,04). Conclusion : Les germes les plus représentés étaient Candida albicans et Gardnerella vaginalis. L’éducation sanitaire de la population en ce qui concerne ces infections doit être renforcée.Mots-clés : infection ; cervico-vaginal ; germes ; Bonassama ; 201

Ethics preparedness : facilitating ethics review during outbreaks : recommendations from an expert panel

BackgroundEnsuring that countries have adequate research capacities is essential for an effective and efficient response to infectious disease outbreaks. The need for ethical principles and values embodied in international research ethics guidelines to be upheld during public health emergencies is widely recognized. Public health officials, researchers and other concerned stakeholders also have to carefully balance time and resources allocated to immediate treatment and control activities, with an approach that integrates research as part of the outbreak response. Under such circumstances, research ethics preparedness constitutes an important foundation for an effective response to infectious disease outbreaks and other health emergencies.Main textA two-day workshop was convened in March 2018 by the World Health Organisation Global Health Ethics Team and the African coaLition for Epidemic Research, Response and Training, with representatives of National Ethics Committees, to identify practical processes and procedures related to ethics review preparedness. The workshop considered five areas where work might be undertaken to facilitate rapid and sound ethics review: preparing national ethics committees for outbreak response; pre-review of protocols; multi-country review; coordination between national ethics committees and other key stakeholders; data and benefit sharing; and export of samples to third countries.In this paper, we present the recommendations that resulted from the workshop. In particular, the participants recommended that Ethics Committees would develop a formal national standard operating procedure for emergency response ethical review; that there is a need to clarify the terminology and expectations of pre-review of generic protocols and agree upon specific terminology; that there is a need to explore mechanisms for multi-country emergency ethical consultation, and to establish procedures for communication between national ethics committees and other oversight bodies and public health authorities. In addition, it was suggested that ethics committees should request from researchers, at a minimum, a preliminary data sharing and sample sharing plan that outlines the benefit to the population from which data and samples are to be drawn. This should be followed in due time by a full plan.ConclusionIt is hoped that the national ethics committees, supported by the WHO, relevant collaborative research consortia and external funding agencies, will work towards bringing these recommendations into practice, for supporting the conduct of effective research during outbreaks