The Education of Children with Special Needs in Cameroon : The Role of Teachers and parent towards Inclusive Education

The education of children with Special Needs is a world wide phenomenon which many international bodies, governments and organisations have come to realise its importance thereby striving for the need for inclusion. Laws, legislations and policies have been put forward to encourage the education of these children in regular schools. In most cases these laws are made without taking into consideration the training capacities of the teachers, suitable physical school environment in terms of infrastructures for accessibility, the large classroom sizes in relation to the student/teacher ratio and most importantly instructional materials and resources. The core implementers of this policy are the teachers whose role is very vital for the education of children in regular school settings. Parents on the other hand as one of the stakeholders of education have a great role to play in their children’s schooling. They act as partners to the teachers and their role cannot be minimized even though schools have traditionally kept them at arm’s length. What is commonly seen in most schools is that parents are been instructed with a view to the physical and moral welfare of their children without listening to what the parents have to contribute. The purpose of this study was to investigate and explore the role of Teachers and Parents towards the education of children with disabilities in Regular Secondary Schools in the Cameroonian setting. The study was conducted in two schools in the Buea District in Cameroon. The main informants were four teachers and two parents. A case study design orientated to qualitative research approach using several research methods was used to collect empirical data. The methods include interviews as the main research method, and supportive methods such as document consultation, field notes and informal talks as additional sources. The results obtained show that teachers’ views of the understanding of the concept of inclusive education vary. Some of the teachers were aware of the theoretical understanding and meaning while others could not identify with the concept appellation. Also the study shows that generally teachers in regular schools turn to be very slow when teaching in class so as to give room for those students with disabilities to meet up with the lessons. The teachers stated that punctuality was one of the greatest challenges children with disability face. The teachers themselves lacked the training in special education and they also expressed the challenges of insufficient funding, resources, materials and infrastructures which could accommodate students with disabilities in regular schools. Moreover, the study shows that teachers who were interviewed have a positive attitude towards inclusive education because they have the human heart to feel for those who have disabilities. The study also indicated that parents were against the education of children with disabilities in special schools. This was because of the stereotype stigma attributed to those centres by the society. Also parents are aware of the positive gains children have from learning and playing in the same environment, thus their greatest ambition is to send their children to regular school where they could share in peer support and instil in them the spirit of motivation. The information gotten from the study also highlight the need for financial, moral and material support to schools, children with disabilities, their parents and a review of the educational system. The result also show that there is a lot to be done by the government of Cameroon to improve on the education of children with disabilities in regular secondary schools such as the need for the training for more teachers in special education and the adaptation of the curriculum to suit the individual needs of children with disabilities. The teachers also have to change their mentality in favour of inclusion and to see into it that the needs of the children are taken care of. Parents on the other hand have to support the teachers by acting as partners to teachers so that the education of their children will be successful in regular school settings

Single-dose intrathecal dorsal root ganglia toxicity of onasemnogene abeparvovec in cynomolgus monkeys

Intravenous onasemnogene abeparvovec is approved for the treatment of spinal muscular atrophy in children \u3c 2 years. For later-onset patients, intrathecal onasemnogene abeparvovec may be advantageous over intravenous administration. Recently, microscopic dorsal root ganglion (DRG) changes were observed in nonhuman primates (NHPs) following intrathecal onasemnogene abeparvovec administration. To characterize these DRG findings, two NHP studies evaluating intrathecal onasemnogene abeparvovec administration were conducted: a 12-month study with a 6-week interim cohort and a 13-week study with a 2-week interim cohort. The latter investigated the potential impact of prednisolone or rituximab plus everolimus on DRG toxicity. An additional 6-month, single-dose, intravenous NHP study conducted in parallel evaluated onasemnogene abeparvovec safety (including DRG toxicity) with or without prednisolone coadministration. Intrathecal onasemnogene abeparvovec administration was well tolerated and not associated with clinical observations. Microscopic onasemnogene abeparvovec-related changes were observed in the DRG and trigeminal ganglion (TG) and included mononuclear cell inflammation and/or neuronal degeneration, which was colocalized with high vector transcript expression at 6 weeks postdose. Incidence and severity of DRG changes were generally decreased after 52 weeks compared with 6 weeks postdose. Other onasemnogene abeparvovec-related microscopic findings of axonal degeneration, mononuclear cell infiltrates and/or gliosis in the spinal cord, dorsal spinal nerve root/spinal nerves, and/or peripheral nerves were absent or found at decreased incidences and/or severities after 52 weeks. DRG and/or TG microscopic findings following intravenous onasemnogene abeparvovec dosing included minimal to slight neuronal degeneration and mononuclear cell inflammation at 6 weeks and 6 months postdose. Nervous system microscopic findings following intrathecal onasemnogene abeparvovec (≥1.2 × 1

Hepatotoxicity following administration of onasemnogene abeparvovec (AVXS-101) for the treatment of spinal muscular atrophy

BACKGROUND & AIMS: Spinal muscular atrophy (SMA) is an autosomal recessive, childhood-onset motor neuron disease. Onasemnogene abeparvovec (OA) is a gene therapy designed to address SMA\u27s root cause. In pivotal mouse toxicology studies, the liver was identified as a major site of OA toxicity. Clinical data reflect elevations in serum aminotransferase concentrations, with some reports of serious acute liver injury. Prophylactic prednisolone mitigates these effects. Herein, we aim to provide pragmatic, supportive guidance for identification, management, and risk mitigation of potential drug-induced liver injury. METHODS: Data from 325 patients with SMA who had received OA through 31 December 2019, in 5 clinical trials, a managed access program (MAP), and a long-term registry (RESTORE), and through commercial use, were analyzed. Liver-related adverse events, laboratory data, concomitant medications, and prednisolone use were analyzed. RESULTS: Based on adverse events and laboratory data, 90 of 100 patients had elevated liver function test results (alanine aminotransferase, and/or aspartate aminotransferase, and/or bilirubin concentrations). Of these, liver-associated adverse events were reported for 34 of 100 (34%) and 10 of 43 (23%) patients in clinical trials and MAP/RESTORE, respectively. Two patients in MAP had serious acute liver injury, which resolved completely. While all events in the overall population resolved, prednisolone treatment duration varied (range: 33-229 days), with a majority receiving prednisolone for 60-120 days. More than 60% had elevations in either alanine aminotransferase, aspartate aminotransferase, or bilirubin concentrations prior to dosing. Greater than 40% received potentially hepatotoxic concomitant medications. CONCLUSIONS: Hepatotoxicity is a known risk associated with OA use. Practitioners should identify contributing factors and mitigate risk through appropriate monitoring and intervention. LAY SUMMARY: Onasemnogene abeparvovec is a type of medicine called a gene therapy, which is used to treat babies and young children who have a rare, serious inherited condition called spinal muscular atrophy (SMA). It works by supplying a fully functioning copy of the survival motor neuron or SMN gene, which then helps the body produce enough SMN protein. However, it can cause an immune response that could lead to an increase in enzymes produced by the liver. This article provides information about the liver injury and how to prevent and recognize if it happens, so that it may be treated properly

Clinical trial and postmarketing safety of onasemnogene abeparvovec therapy

INTRODUCTION: This is the first description of safety data for intravenous onasemnogene abeparvovec, the only approved systemically administered gene-replacement therapy for spinal muscular atrophy. OBJECTIVE: We comprehensively assessed the safety of intravenous onasemnogene abeparvovec from preclinical studies, clinical studies, and postmarketing data. METHODS: Single-dose toxicity studies were performed in neonatal mice and juvenile or neonatal cynomolgus nonhuman primates (NHPs). Data presented are from a composite of preclinical studies, seven clinical trials, and postmarketing sources (clinical trials, n = 102 patients; postmarketing surveillance, n = 665 reported adverse event [AE] cases). In clinical trials, safety was assessed through AE monitoring, vital-sign and cardiac assessments, laboratory evaluations, physical examinations, and concomitant medication use. AE reporting and available objective clinical data from postmarketing programs were evaluated. RESULTS: The main target organs of toxicity in mice were the heart and liver. Dorsal root ganglia (DRG) inflammation was observed in NHPs. Patients exhibited no evidence of sensory neuropathy upon clinical examination. In clinical trials, 101/102 patients experienced at least one treatment-emergent AE. In total, 50 patients experienced serious AEs, including 11 considered treatment related. AEs consistent with hepatotoxicity resolved with prednisolone in clinical trials. Transient decreases in mean platelet count were detected but were without bleeding complications. Thrombotic microangiopathy (TMA) was observed in the postmarketing setting. No evidence of intracardiac thrombi was observed for NHPs or patients. CONCLUSIONS: Risks associated with onasemnogene abeparvovec can be anticipated, monitored, and managed. Hepatotoxicity events resolved with prednisolone. Thrombocytopenia was transient. TMA may require medical intervention. Important potential risks include cardiac AEs and DRG toxicity

Clinical Trial and Postmarketing Safety of Onasemnogene Abeparvovec Therapy

INTRODUCTION: This is the first description of safety data for intravenous onasemnogene abeparvovec, the only approved systemically administered gene-replacement therapy for spinal muscular atrophy. OBJECTIVE: We comprehensively assessed the safety of intravenous onasemnogene abeparvovec from preclinical studies, clinical studies, and postmarketing data. METHODS: Single-dose toxicity studies were performed in neonatal mice and juvenile or neonatal cynomolgus nonhuman primates (NHPs). Data presented are from a composite of preclinical studies, seven clinical trials, and postmarketing sources (clinical trials, n = 102 patients; postmarketing surveillance, n = 665 reported adverse event [AE] cases). In clinical trials, safety was assessed through AE monitoring, vital-sign and cardiac assessments, laboratory evaluations, physical examinations, and concomitant medication use. AE reporting and available objective clinical data from postmarketing programs were evaluated. RESULTS: The main target organs of toxicity in mice were the heart and liver. Dorsal root ganglia (DRG) inflammation was observed in NHPs. Patients exhibited no evidence of sensory neuropathy upon clinical examination. In clinical trials, 101/102 patients experienced at least one treatment-emergent AE. In total, 50 patients experienced serious AEs, including 11 considered treatment related. AEs consistent with hepatotoxicity resolved with prednisolone in clinical trials. Transient decreases in mean platelet count were detected but were without bleeding complications. Thrombotic microangiopathy (TMA) was observed in the postmarketing setting. No evidence of intracardiac thrombi was observed for NHPs or patients. CONCLUSIONS: Risks associated with onasemnogene abeparvovec can be anticipated, monitored, and managed. Hepatotoxicity events resolved with prednisolone. Thrombocytopenia was transient. TMA may require medical intervention. Important potential risks include cardiac AEs and DRG toxicity

Synergistic drug-cytokine induction of hepatocellular death as an in vitro approach for the study of inflammation-associated idiosyncratic drug hepatotoxicity

Idiosyncratic drug hepatotoxicity represents a major problem in drug development due to inadequacy of current preclinical screening assays, but recently established rodent models utilizing bacterial LPS co-administration to induce an inflammatory background have successfully reproduced idiosyncratic hepatotoxicity signatures for certain drugs. However, the low-throughput nature of these models renders them problematic for employment as preclinical screening assays. Here, we present an analogous, but high-throughput, in vitro approach in which drugs are administered to a variety of cell types (primary human and rat hepatocytes and the human HepG2 cell line) across a landscape of inflammatory contexts containing LPS and cytokines TNF, IFNγ, IL-1α, and IL-6. Using this assay, we observed drug–cytokine hepatotoxicity synergies for multiple idiosyncratic hepatotoxicants (ranitidine, trovafloxacin, nefazodone, nimesulide, clarithromycin, and telithromycin) but not for their corresponding non-toxic control compounds (famotidine, levofloxacin, buspirone, and aspirin). A larger compendium of drug–cytokine mix hepatotoxicity data demonstrated that hepatotoxicity synergies were largely potentiated by TNF, IL-1α, and LPS within the context of multi-cytokine mixes. Then, we screened 90 drugs for cytokine synergy in human hepatocytes and found that a significantly larger fraction of the idiosyncratic hepatotoxicants (19%) synergized with a single cytokine mix than did the non-hepatotoxic drugs (3%). Finally, we used an information theoretic approach to ascertain especially informative subsets of cytokine treatments for most highly effective construction of regression models for drug- and cytokine mix-induced hepatotoxicities across these cell systems. Our results suggest that this drug–cytokine co-treatment approach could provide a useful preclinical tool for investigating inflammation-associated idiosyncratic drug hepatotoxicity.Pfizer Inc.Institute for Collaborative BiotechnologiesMIT Center for Cell Decision ProcessesNational Institute of Mental Health (U.S.) (grant P50-GM68762)National Institute of Mental Health (U.S.) (grant T32-GM008334)Massachusetts Institute of Technology. Biotechnology Process Engineering CenterMassachusetts Institute of Technology. Center for Environmental Health SciencesNational Institute of Mental Health (U.S.) (grant U19ES011399)Whitaker Foundatio

Peculiarities off socially important diseases spread among schoolchildren depending on their sex and age

The article under consideration presents the analysis of initial and general morbidity with socially important diseases of schoolchildren for the five-year period from 2008 to 2012.В статье представлен анализ первичной и общей заболеваемости социально значимыми заболеваниями детей школьного возраста за пятилетний период 2008-2012 г

Occupational and medical aspects of occupational morbidity in men with neurosensory hearing loss

Occupational neurosensory hearing loss is one of the most common occupational diseases. So far, there have been no studies in the scientific literature devoted to a retrospective analysis of professional conditions and conditions of medical care organization in case this pathology is detected in workers served by the system of health care institutions of FMBA of Russia.Нейросенсорная тугоухость профессионального генеза является одним из наиболее распространенных профессиональных заболеваний. До сих пор в научной литературе не встречалось исследований, посвященных ретроспективному анализу профессиональных условий и условий организации медицинской помощи в случае выявления этой патологии у работников, обслуживаемых системой учреждений здравоохранения ФМБА России

Health statistics indicators as a factor in accounting for occupational morbidity

Introduction When analyzing the risk of the impact of harmful factors on the health of employees, some researchers explain the low incidence of occupational diseases in Russia by errors in their detection during preventive examinations, lack of interest of employers and employees in the detection and registration of these diseases, and other reasons. At the same time, we did not find any works in the literature devoted to errors in coding of diagnoses of occupational diseases and their registration. The purpose of the work is to identify the cause of poor accounting of occupational diseases in Russia. Materials and methods The work was carried out on the basis of the Industrial Register of persons with occupational diseases. The registry was developed by the A.I. Burnazyan Federal Medical and Biological Center and has been in commercial operation since 2011. As of 31.12.2020, the register contains information about 2 300 patients with occupational diseases from among the employees of enterprises and organizations served by the health care institutions of FMBA of Russia. Directive documents on identification and registration of occupational diseases were analyzed. Results and discussion Analysis of the health of the working contingent and the subsequent creation of plans for medical and rehabilitation measures to reduce the incidence of occupational diseases among persons working at enterprises and organizations that are on dispensary registration in health care institutions of FMBA of Russia, requires knowledge of correct morbidity indicators about them. For this purpose, it is necessary to improve the registration of occupational diseases in Russia by switching to the diagnosis coding system adopted in the country’s sanitary statistics, and to make appropriate changes in policy documents. Conclusion One of the reasons for errors in recording occupational diseases is the violation of classification principles in the Order of the Ministry of Health and Social Development of Russia No 417n.Введение. Анализируя риск влияния на здоровье работников предприятий вредных факторов производства, некоторые исследователи объясняют низкую заболеваемость профессиональными болезнями в России ошибками их выявления на профилактических осмотрах, отсутствием заинтересованности работодателей и работников в выявлении и регистрации этих заболеваний и другими причинами. В то же время в литературе мы не встретили работ, посвященных ошибкам кодирования диагнозов профессиональных заболеваний и их учета. Цель работы – выявление причин некачественного учета профессиональных заболеваний в России. Материалы и методы. Работа выполнена на базе Отраслевого регистра лиц, имеющих профессиональные заболевания. Регистр разработан ФМБЦ им. А.И. Бурназяна и находится в промышленной эксплуатации с 2011 г. По состоянию на 31.12.2020 в регистре содержится информация о 2 300 больных профессиональными заболеваниями из числа работников предприятий и организаций, обслуживаемых учреждениями здравоохранения ФМБА России. Проведен анализ директивных документов по выявлению и учету профессиональных заболеваний. Результаты и обсуждение. Анализ здоровья работающего контингента и последующее создание планов медико-реабилитационных мероприятий по снижению заболеваемости профессиональными болезнями среди лиц, работающих на предприятиях и в организациях, состоящих на диспансерном учете в учреждениях здравоохранения ФМБА России, требует знаний корректных показателей заболеваемости о них. Для этого необходимо усовершенствовать учет профессиональных болезней в России путем перехода на систему кодирования диагнозов, принятую в санитарной статистике страны, и внести соответствующие изменения в директивные документы. Заключение. Одной из причин ошибок учета профессиональных болезней является нарушение принципов классификации в Приказе Минздравсоцразвития России № 417н

Cytokine-associated drug toxicity in human hepatocytes is associated signaling network dysregulation

Refer to Web version on PubMed Central for supplementary material.Idiosyncratic drug hepatotoxicity is a major problem in pharmaceutical development due to poor prediction capability of standard preclinical toxicity assessments and limited knowledge of its underlying mechanisms. Findings in animal models have shown that adverse effects of numerous drugs with idiosyncratic hepatotoxicity in humans can be reproduced in the presence of coincident inflammatory cytokine signaling. Following these observations, we have recently developed an in vitro drug/inflammatory cytokine co-treatment approach that can reproduce clinical drug hepatotoxicity signatures—particularly for idiosyncratic drugs—in cultured primary human hepatocytes. These observations have suggested that drug-induced stresses may interact with cytokine signaling to induce hepatic cytotoxicity, but the hepatocyte signaling mechanisms governing these interactions are poorly understood. Here, we collect high-throughput phosphoprotein signaling and cytotoxicity measurements in cultured hepatocytes, from multiple human donors, treated with combinations of hepatotoxic drugs (e.g. trovafloxacin, clarithromycin) and cytokines (tumor necrosis factor-α, interferon-γ, interleukin-1α, and interleukin-6). We demonstrate, through orthogonal partial least-squares regression (OPLSR) modeling of these signal-response data, that drug/cytokine hepatic cytotoxicity is integratively controlled by four key signaling pathways: Akt, p70 S6 kinase, MEK–ERK, and p38–HSP27. This modeling predicted, and experimental studies confirmed, that the MEK–ERK and p38–HSP27 pathways contribute pro-death signaling influences in drug/cytokine hepatic cytotoxicity synergy. Further, our four-pathway OPLSR model produced successful prediction of drug/cytokine hepatic cytotoxicities across different human donors, even though signaling and cytotoxicity responses were both highly donor-specific. Our findings highlight the critical role of kinase signaling in drug/cytokine hepatic cytotoxicity synergies and reveal that hepatic cytotoxicity responses are governed by multi-pathway signaling network balance.Pfizer Inc.Institute for Collaborative BiotechnologiesMIT Center for Cell Decision ProcessesNational Institute of Mental Health (U.S.) (grant P50-GM68762)Massachusetts Institute of Technology. Biotechnology Process Engineering CenterMassachusetts Institute of Technology. Center for Environmental Health SciencesNational Institute of Mental Health (U.S.) (grant U19ES011399)Whitaker Foundatio