Confounding adjustment methods for multi-level treatment comparisons under lack of positivity and unknown model specification.

Imbalances in covariates between treatment groups are frequent in observational studies and can lead to biased comparisons. Various adjustment methods can be employed to correct these biases in the context of multi-level treatments (> 2). Analytical challenges, such as positivity violations and incorrect model specification due to unknown functional relationships between covariates and treatment or outcome, may affect their ability to yield unbiased results. Such challenges were expected in a comparison of fire-suppression interventions for preventing fire growth. We identified the overlap weights, augmented overlap weights, bias-corrected matching and targeted maximum likelihood as methods with the best potential to address those challenges. A simple variance estimator for the overlap weight estimators that can naturally be combined with machine learning is proposed. In a simulation study, we investigated the performance of these methods as well as those of simpler alternatives. Adjustment methods that included an outcome modeling component performed better than those that focused on the treatment mechanism in our simulations. Additionally, machine learning implementation was observed to efficiently compensate for the unknown model specification for the former methods, but not the latter. Based on these results, we compared the effectiveness of fire-suppression interventions using the augmented overlap weight estimator.

[Sexuality assessment of homozygous adult sickle cell patients with a history of priapism in Senegal]. / Évaluation de la sexualité des drépanocytaires adultes homozygotes ayant des antécédents de priapisme au Sénégal.

OBJECTIVES: The objective of this study was to evaluate the sexuality of SS sickle cell patients with a history of priapism. METHODS: This was a case-control study of adult SS sickle cell patients. The occurrence of priapism as well as the nature of the priapism had been investigated. The patients were subdivided into three groups: Group 1 (no priapism), Group 2 (intermittent priapism) and Group 3 (acute priapism). The patients' sexuality was studied using the IIEF-15 questionnaire. RESULTS: We interviewed 191 SS sickle cell patients. The mean age was 27.1±7.1 years. Priapism was observed in 43.5 %. Only 77 patients were eligible for the IIEF15 questionnaire. Groups 1 and 2 performed significantly better than group 3 on erectile function (EF) and orgasmic function (OF) scores. There was no significant difference in the EF and OF scores between groups 1 and 2. No significant difference was observed between the three groups for the scores of sexual desire (SD), intercourse satisfaction (IS), and overall satisfaction (OS). The impairment of erectile function in group 2 was related to the age of the first episode of priapism and the last episode. The impairment of erectile function in group 3 was related to the duration of evolution (P<0.05). CONCLUSION: This study shows that priapism is responsible for impaired erectile function in SS adult sickle cell patients. A program to prevent intermittent episodes of priapism should be put in place.

Demographics and outcomes of laboratory-confirmed COVID-19 cases during the first epidemic wave in Senegal.

BACKGROUND: Few studies have focused on the effects of COVID-19 on African populations. During the first epidemic wave in Senegal (May 1 to July 31, 2020), COVID-19 cases were isolated in treatment centers of epidemics (TCEs). We described the demographics and outcomes of COVID-19 cases in TCEs. PATIENTS AND METHODS: All cases with laboratory-confirmed COVID-19 in Thiès medical region of Senegal were included. RESULTS: COVID-19 was confirmed in 600 cases. Median age of cases (men: 357, 59.5%; women: 243, 40.5%) was 34.0years. The incidence was 12 per 100,000 inhabitants per month. Overall, 46 (7.7%) cases had a severe or critical form of the disease, and nine of them died. Of 455 cases quarantined in non-hospital TCEs, 340 (74.7%) had no symptom and 115 (25.3%) had mild or moderate symptoms. CONCLUSION: In this African retrospective cohort, COVID-19 cases were young and mostly asymptomatic with a low case fatality rate.

Factors Associated with Foot Lesions in Diabetic Patients at Saint-Louis Hospital (Senegal): A Case-Control Study Protocol.

INTRODUCTION: Diabetes prevalence has increased over the past years. In Senegal, this prevalence is 4% in the general population. However, the region of Saint-Louis (in the north of the country) has the highest rate with 10.4%. The main prognosis problem is the occurrence foot lesions that can lead to lower-limbs amputation. Diabetic foot is a real public health issue, due to its economic burden and its serious repercussions on patients, leading to poor quality of life. The objective of this case-control study is to identify factors associated with foot lesions in diabetic patients. METHODS AND ANALYSIS: It will be a case-control study from January to December 2021. The patients will be recruited from the departments of general surgery, internal medicine, and emergency. An univariate then multivariate analysis (logistic regression) will allow us to select the variables associated with foot lesions in our study population. The parameters included in the logistic regression will be those with a p < 0.20 in the univariate analysis. Finally, a binary logistic regression analysis (with the calculation of Odds Ratios (OR) with confidence intervals (CI)) according to the backward stepwise method will identify the factors independently associated to foot lesions in diabetic patients. ETHICS AND DISSEMINATION: This research protocol will be submitted to the Ethics Committee of our institution for approval. The knowledge of factors causing diabetic foot will help to communicate with policymakers to raise the awareness in our community. Finally, it will help to prevent lower limb amputations. HIGHLIGHTS: Diabetes is the leading cause of non-traumatic lower-limb amputation in the world.The region of Saint-Louis (Senegal) has the highest prevalence of diabetes.Controlling factors associated with foot lesions in diabetic patients can prevent from amputation.

Profile of Patients with Gallstone Disease in a Sub-Saharan African General Surgery Department: A Retrospective Cohort Study Protocol.

INTRODUCTION: Gallstone disease is a disorder characterised by the formation of stones in the biliary tract. It is the most common biliary condition accounting for more than 98% of all gallbladder and biliary tract disorders. In Africa, previous studies have shown a relative rarity of this condition with a prevalence less than 5%; since it is between 2 and 5 times higher in other continents. A good knowledge of the profile of patient with gallstone disease in a surgical setting could allow to reduce gallstone disease complications and to tailor better the treatment. To our knowledge, there was no previous study about gallstone disease in this region even if there is a high prevalence of metabolic factors of gallstone disease. METHODS: This study objective is to describe the epidemiological, diagnostic and therapeutic profile of patients with gallstone disease at the Department of General Surgery of Saint-Louis Hospital (Senegal). It will be a single-centre retrospective cohort study in a period of 5 years (January 2015 - December 2020). The patients' record of the department of general surgery will be consulted and the patient contacted if there are missing data. Patients with gallstone disease diagnosed with imaging (ultrasonography and/or CT scan) regardless the presentation (asymptomatic, biliary colic, cholecystitis, common bile duct lithiasis, angio-cholitis, pancreatitis) will be included. Adults and paediatric patients will be enrolled. Patient records lacking sufficient data will be excluded. Studied parameters will be epidemiological, clinical, paraclinical and therapeutic aspects. ETHICS AND DISSEMINATION: Anonymity and confidentiality of information collected in patients will be respected. This research protocol will be submitted to the Ethics Committee of our institution for approval. The knowledge of the profile of patients with gallstone disease in a surgical setting could allow to reduce gallstone disease complications and to tailor better the treatment. Finally, it will help to reduce the burden of gallstone disease. HIGHLIGHTS: Gallstone disease is the most common biliary tract conditionTo our knowledge, there was no previous study about gallstone disease in this region even if there is a high prevalence of risk factors of gallstone disease (sickle cell disease, diabetes, obesity, hypercholesterolemia)Good knowledge of the profile of patients with gallstone disease in a surgical setting could allow to reduce gallstone disease complications and to tailor better the treatment.

Hemophilia care in Africa: Status and challenges.

Haemophilia care remains challenging especially in resource-limited settings where haemophilia and other non-communicable diseases may not be considered a healthcare priority, in comparison to malaria, HIV/AIDS and other infectious diseases. This article is a review of the evolution in haemophilia care in Africa, with focus on countries with varying degrees of care (Cameroon with budding care; Senegal with more evolved care and Egypt with a more longstanding history of care). The indispensable role of the World Federation of Haemophilia is highlighted in all the contexts of care.

Transfusion and sickle cell anemia in Africa.

Sickle cell anemia (SCA) is the commonest life-threatening genetic disorder in tropical regions, particularly in sub-Saharan Africa. It has been estimated that between 50-90% of SCA children will die in Africa before the age of 5, corresponding to a number of 150,000-300,000 annual SCA child deaths, which represents 5-10% of total child mortality. Transfusion support remains an essential component in the management of patients with SCA and has made a significant contribution to improving patient morbidity and mortality. In Africa where the majority of patients with SCA reside, many blood transfusion challenges remains, including shortage of blood supplies, risks related to infectious and immunologic potential side effects and limitation on the diagnosis and management of post-transfusion iron overload. The proportion of transfused SCA patients varies from different studies, between 30% and 90%. This variation can be related to environmental factors, disease genetic factors and other factors including the low availability of blood, difficulties in accessing to health care and inadequacies of the transfusion system. Because blood transfusion therapy is an integral component of the management of SCA, improved efforts and strategies to overcome these challenges and optimize blood transfusion practices are needed in African countries.

Mise en place d'un centre de traitement des épidémies (CTE) pour COVID-19 dans un service de Médecine Interne; les leçons apprises / Establishment of an Outbreak Center for Covid-19 (OCC), in an Internal Medicine department

Introduction: La fulgurante progression de la pandémie à covid -19 a imposé au Sénégal l'adoption de stratégies de riposte parmi lesquelles la mise en place de centres de traitement des épidémies (CTE) au sein des hôpitaux . Nous nous proposons d'évaluer les activités d'un CTE Covid-19 implanté dans un service de médecine interne et les leçons tirées de ce vécu. Méthodologie : Le CTE Covid -19 a été installé dans le service de médecine interne de l'Hôpital Régional de Thiès (HRT), mais avec conservation de lits dédiés aux patients non atteints de Covid-19. Les étudiants en année de doctorat affectés dans le service de médecine interne étaient responsables de la gestion quotidienne du CTE sous la supervision des spécialistes en médecine interne Ce service était subdivisé en deux parties: le CTE qui prenait en charge les cas de Covid -19 et le reste du service qui devait continuer à accueillir les patients atteints d'autres affections ou qui y étaient régulièrement suivies. Résultats : Du 1er mai au 30 octobre 2020, 237 patients ont été admis dans le CTE. Ils étaient âgés de 7 à 88 ans avec une moyenne d'âge de 53,41 ans et un sexe ratio de 1,60. Les motifs d'admission étaient une désaturation en oxygène inférieure à 90%, la présence d'au moins une comorbidité (autres infections, diabète , hypertension artérielle , obésité, maladies auto-immunes, cancers…). L'âge avancé mais aussi les patients ne pouvant être à domicile faisaient également partie des critères d'admission . Trois (3) cas de co-infection Covid-19 et tuberculose pulmonaire ont été relevés et trois (3) patients avaient un portage chronique du virus de l'hépatite B. Dans le cadre des hospitalisations non Covid -19, les affections suivantes ont été retrouvées : 8 cas de diabète déséquilibrés et autant d'hépatopathie (6,10%); l'accès palustre dans 3, 05% (n=3) ; la tuberculose pulmonaire (3,81%, n=3) ; 3 cas (2,29 %) d'anémie de type biermerien et de lupus érythémateux systémique. De même, 1 cas (0,76%) d 'empyème cérébral ; une polyarthrite rhumatoïde (0,76 %), une (01) maladie rénale chronique , 1 cas de défaillance cardiaque ont également été enregistrées. Cinq (5) cas (3,81 %) non affectés par l'infection à Covid -19 , à leur admission l'ont été au cours de leur hospitalisation et donc transférés au niveau de la zone rouge du CTE. Conclusion: La mise en place du CTE au niveau du service de Médecine interne , a permis une adaptation efficiente dans la prise en charge des patients concernés mais aussi de ceux qui étaient suivis pour des pathologies chroniques comme les urgences médicales reçues durant la période. La continuité des soins a été assurée et les liens avec les autres secteurs de la pyramide sanitaire du Sénégal ont été raffermis.

Introduction : The fast progression of covid -19 throughout the world has forced Senegal to adopt response strategies including the establishment of Outbreak Center for Covid- 19 (OCC ) within hospitals . We propose to evaluate the activi ties of an OCC implemented in an internal medicine department and the lessons learned from this experience. Methodology: The center for care of Covid-19 has been installed in the Internal Medicine department of the Thies Regional Hospital (HRT ), but with dedicated beds for patients non affected by the pandemic . Fifteen doctoral students were assigned, by local medical school , to the Department of Internal Medicine in order to be responsible for the day-to-day management of the OCC. They were supervised by internal medicine specialists . This service was divided into two parts: the OCC that handled Covid -19 cases and the rest of the service , which was to continue to take care of patients with other conditions or who were regularly monitored. Results: From May 1 to October 30, 2020, 237 patients were admitted to the CTE They ranged from 7 to 88 years old with an average age of 53.41 and a sex ratio of 1.60 .The reasons for admission were an oxygen desaturation of less than 90%, the presence of at least one comorbidity (other infections, diabetes, arterial hypertension, obesity, autoimmune diseases, cancers, etc .). Advanced age but also patients who could not be at home were also part of the admission criteria. Three (3) cases of Covid -19 co -infection and pulmonary tuberculosis were identified and three (3) patients had a chronic carriage of the hepatitis B virus. In the context of non -Covid -19 hospitalizations, the following conditions have been found: 8 cases of unbalanced diabetes and as many hepatopathy (6.10%); malaria access in 3.05% (n = 3); pulmonary tuberculosis (3.81%, n = 3); 3 cases (2.29%) of biermeric type anemia and systemic lupus erythematosus. Similarly, 1 case (0.76 %) of cerebral empyema; rheumatoid arthritis (0.76%), one (01) chronic kidney disease, 1 case of heart failure were also recorded Five (5) cases (3.81%) not affected by Covid-19 infection, on admission, were during their hospitalization and therefore transferred to the red zone of the CTE. Conclusion : The establishment of the OCC in the internal medicine service allowed an efficient adaptation in the care of the patients affected by covid disease but also of those who were followed for chronic pathologies or admitted for other medical emergencies This strategy has improved and strengthened the links with other sectors of Senegal 's health pyramid.

Diagnosis Dilemma of Angioimmunoblastic T-Cell Lymphoma in Tuberculosis Endemic Region.

Angioimmunoblastic T-cell lymphoma (AITL) is a rare hematologic malignancy recognized in the WHO 2016 classification as a clinical and histological entity. It is a very poorly described disease in Africa due to its rarity and diagnostic difficulties, particularly differential diagnosis with tuberculosis. Here, we report a 57-year-old man who presented with fever, weight loss, and lymphadenopathies. The diagnosis of tuberculosis was carried out based on lymph node fine needle aspiration showing the image of tuberculous adenitis and CT images in favor of necrotic lymphadenopathies. The presence of autoantibodies and the failure of tuberculosis treatment led us to perform a biopsy with immunostaining that confirmed pathological features of AITL. The patient was treated by CHOP-based chemotherapy, and complete remission was achieved. This case highlights the difficulty of recognizing AITL and the importance of considering other potential differential diagnoses of tuberculosis in the endemic region.

Impact of seasonal malaria chemoprevention in children aged 3 to 59 months in the Kangaba and Kolokani health districts between 2013 and 2015.

INTRODUCTION: Malaria is a public health problem in Mali. Seasonal chemo prevention (SCP) is of particular importance, hence its introduction by the WHO since 2012 in children aged 3 to 59 months from the start of the transmission season. This study aims to demonstrate the impact of SCP on malaria in the health districts of Kangaba and Kolokani. MATERIALS AND METHODS: Our retrospective study was carried out from 2013 to 2015 in the health districts of Kangaba and Kolokani using the databases of the NGO AMCP / ALIMA. Data from 2014 and 2015 were compared to data from 2013. RESULTS: The number of malaria cases in children under 5year in the area covered by the SCP shows a considerable decrease in Kangaba of 52% in 2014 and 49% in 2015, compared to the reference period being the year 2013. In Kolokani the decrease is 57% in 2014 and 40% in 2015 compared to the year 2013. Compared to deaths, a decrease of 50.5% was recorded in 2014 and 60.4% in 2015 compared to the year 2013, i.e. 51 and 61 fewer deaths compared to 2013, respectively, in health facilities. CONCLUSION: The SCP had made it possible to reduce significant mortality and malaria morbidity in the two health districts of Kangaba and Kolokani.

INTRODUCTION: le paludisme est un problème majeur de santé publique au Mali. La chimio prévention saisonnier a une importance particulière d'où son instauration par l'OMS depuis 2012 chez les enfants de 3 à 59 mois à partir du début de la saison de transmission. Cette étude vise à démontrer l'impact de la CPS sur le paludisme dans les districts sanitaires de Kangaba et de Kolokani. MATÉRIELS ET MÉTHODES: Notre étude rétrospective a été réalisée de 2013 à 2015 dans les districts sanitaires de Kangaba et de Kolokani en utilisant les bases de données de l'ONG AMCP/ALIMA. Les données de 2014 et 2015 ont été comparés à ceux de 2013. RÉSULTATS: Le nombre de cas de paludisme chez les enfants de moins de 5 ans dans la zone couverte par la CPS montre une baisse considérable à Kangaba de 52% en 2014 et 49% en 2015, par rapport à la période de référence étant l'année 2013. A Kolokani la baisse est de 57% en 2014 et 40% en 2015 par rapport à 2013. Par rapport aux décès, une baisse de 50,5% a été enregistrée en 2014 et 60,4% en 2015 par rapport à 2013, soit respectivement 51 et 61 décès en moins comparé à 2013, dans les structures de santé. CONCLUSION: La CPS avait permis une réduction de la mortalité importante et de la morbidité palustre dans les deux districts sanitaires de Kangaba et de Kolokani.

First-year results of an expanded humanitarian aid programme for haemophilia in resource-constrained countries.

INTRODUCTION: The gaps in haemophilia treatment around the world are enormous; approximately 60% of an estimated 475 000 individuals are not identified. Of the 187 000 diagnosed, 30% (57 000) access clotting factor replacement therapy. Since 1996, humanitarian aid distributed by the World Federation of Hemophilia (WFH) has played a minor, yet vital role providing life-saving clotting factor to countries in emergency situations. Donated amounts have been small and sporadic, often salvaging short-dated products, providing little opportunity to leverage donations with governments. In 2015, a prospective donation programme of 100 million I.U. per year of extended half-life factor VIII and IX over 10 years was established, necessitating the development of new logistics and training programmes by WFH. AIM: To measure the impact of a greatly expanded haemophilia humanitarian aid program. MATERIALS AND METHODS: In 2016, the first full year of the expanded programme, WFH, distributed products to 58 countries with factor VIII usage <1 I.U. per capita, a level incompatible with long-term survival and far below the 4 I.U. FVIII per capita minimum established in Europe. RESULTS: The scope of the programme and utilization data for 2016 indicate primarily use for acute bleeding, orthopaedic and emergency surgeries. Compared to 2014, 2016 data showed substantial increases in patients served (5.9-fold, from 2119 to 14 579), surgeries performed (37-fold) and bleeds treated (6.9-fold). Patients on prophylaxis rose from 0 to 852, including 458 children under 10 years old. DISCUSSION: The expanded humanitarian aid programme impacts an estimated 10% of individuals with haemophilia previously unable to access treatment. CONCLUSION: This programme represents an unprecedented public-private partnership to deliver medicines to individuals with no access. Further, the programme offers the prospective opportunity to engage governments to take more responsiblity for increasing training, medical management, and product supply in 58 resource constrained countries.

Does smallpox vaccination modify HIV disease progression among ART-naive people living with HIV in Africa?

We examined the association between a history of smallpox vaccination and immune activation (IA) in a population of antiretroviral therapy-naïve people living with HIV (PLHIV). A cross-sectional study was conducted in Senegal from July 2015 to March 2017. Smallpox vaccination was ascertained by the presence of smallpox vaccine scar and IA by the plasma level of ß-2-microglobulin (ß2m). The association was analysed using logistic regression and linear regression models. The study population comprised 101 PLHIV born before 1980 with a median age of 47 years (interquartile range (IQR) = 42-55); 57·4% were women. Smallpox vaccine scar was present in 65·3% and the median ß2m level was 2·59 mg/l (IQR = 2·06-3·86). After adjustment, the presence of smallpox vaccine scar was not associated with a ß2m level ⩾2·59 mg/l (adjusted odds ratio 0·94; 95% confidence interval 0·32-2·77). This result was confirmed by the linear regression model. Our study does not find any association between the presence of smallpox vaccine scar and the ß2m level and does not support any association between a previous smallpox vaccination and HIV disease progression. In this study, IA is not a significant determinant of the reported non-targeted effect of smallpox vaccination in PLHIV.

Efficacy and Safety of Manual Partial Red Cell Exchange in the Management of Severe Complications of Sickle Cell Disease in a Developing Country.

INTRODUCTION: The realization of red cell exchange (RCE) in Africa faces the lack of blood, transfusion safety, and equipment. We evaluated its efficacy and safety in severe complications of sickle cell disease. PATIENTS AND METHOD: Manual partial RCE was performed among sickle cell patients who had severe complications. Efficacy was evaluated by clinical evolution, blood count, and electrophoresis of hemoglobin. Safety was evaluated on adverse effects, infections, and alloimmunization. RESULTS: We performed 166 partial RCE among 44 patients including 41 homozygous (SS) and 2 heterozygous composites SC and 1 S/ß0-thalassemia. The mean age was 27.9 years. The sex ratio was 1.58. The regression of symptoms was complete in 100% of persistent vasoocclusive crisis and acute chest syndrome, 56.7% of intermittent priapism, and 30% of stroke. It was partial in 100% of leg ulcers and null in acute priapism. The mean variations of hemoglobin and hematocrit rate after one procedure were, respectively, +1.4 g/dL and +4.4%. That of hemoglobin S after 2 consecutive RCE was -60%. Neither alloimmunization nor viral seroconversion was observed. CONCLUSION: This work shows the feasibility of manual partial RCE in a low-resource setting and its efficacy and safety during complications of SCD outside of acute priapism.

Turnover of Lipidated LC3 and Autophagic Cargoes in Mammalian Cells.

Macroautophagy (usually referred to as autophagy) is the most important degradation system in mammalian cells. It is responsible for the elimination of protein aggregates, organelles, and other cellular content. During autophagy, these materials (i.e., cargo) must be engulfed by a double-membrane structure called an autophagosome, which delivers the cargo to the lysosome to complete its degradation. Autophagy is a very dynamic pathway called autophagic flux. The process involves all the steps that are implicated in cargo degradation from autophagosome formation. There are several techniques to monitor autophagic flux. Among them, the method most used experimentally to assess autophagy is the detection of LC3 protein processing and p62 degradation by Western blotting. In this chapter, we provide a detailed and straightforward protocol for this purpose in cultured mammalian cells, including a brief set of notes concerning problems associated with the Western-blotting detection of LC3 and p62.

Fluorescent FYVE Chimeras to Quantify PtdIns3P Synthesis During Autophagy.

Autophagy is the major cellular process of degradation and is modulated by several signaling pathways. Phosphatidylinositol 3-kinase (PtdIns3K) class III (Vps34) and PtdIns3K class I regulate the autophagy pathway positively and negatively, respectively. Both classes of PtdIns3K participate in the synthesis of phosphatidylinositol 3-phosphate (PtdIns3P), which plays a crucial role in autophagosome biogenesis and membrane traffic. PtdIns3P is a membrane phospholipid that is associated with endogenous FYVE domain-containing proteins. Indeed, such interactions facilitate autophagosome fusion with lysosomes and subsequent cargo degradation. During starvation-induced autophagy, the expression of FYVE domain-containing proteins increases, and their binding to PtdIns3P is strengthened. Nonetheless, not all FYVE domain proteins are related to the induction of autophagy. This method report presents the quantification of PtdIns3P synthesis by using cells either transiently transfected with or stably expressing FYVE-dsRed.

Sustainable conversion of agriculture wastes into activated carbons: energy balance and arsenic removal from water.

The aims of this study are to investigate the production of activated carbons (AC) from Senegal agricultural wastes such as cashew shells, millet stalks and rice husks and to implement them in adsorption processes devoted to arsenic (V) removal. AC were produced by a direct physical activation with water steam without other chemicals. This production of AC has also led to co-products (gas and bio-oil) which have been characterized in terms of physical, chemical and thermodynamical properties for energy recovery. Considering the arsenic adsorption results and the energy balance for the three studied biomasses, the first results have shown that the millet stalks seem to be more interesting for arsenate removal from natural water and an energy recovery with a GEEelec of 18.9%. Cashew shells, which have shown the best energy recovery (34.3%), are not suitable for arsenate removal. This global approach is original and contributes to a recycling of biowastes with a joint recovery of energy and material.

Mitochondria-Associated Membranes (MAMs): Overview and Its Role in Parkinson's Disease.

Mitochondria-associated membranes (MAMs) are structures that regulate physiological functions between endoplasmic reticulum (ER) and mitochondria in order to maintain calcium signaling and mitochondrial biogenesis. Several proteins located in MAMs, including those encoded by PARK genes and some of neurodegeneration-related proteins (huntingtin, presenilin, etc.), ensure this regulation. In this regard, MAM alteration is associated with neurodegenerative diseases such as Parkinson's (PD), Alzheimer's (AD), and Huntington's diseases (HD) and contributes to the appearance of the pathogenesis features, i.e., autophagy dysregulation, mitochondrial dysfunction, oxidative stress, and lately, neuronal death. Moreover,, ER stress and/or damaged mitochondria can be the cause of these disruptions. Therefore, ER-mitochondria contact structure and function are crucial to multiple cellular processes. This review is focused on the molecular interaction between ER and mitochondria indispensable to MAM formation and on MAM alteration-induced etiology of neurodegenerative diseases.