The role of membrane trafficking and retromer complex in Parkinson's and Alzheimer's disease.

Membrane trafficking is a physiological process encompassing different pathways involved in transporting cellular products across cell membranes to specific cell locations via encapsulated vesicles. This process is required for cells to mature and function properly, allowing them to adapt to their surroundings. The retromer complex is a complex composed of nexin proteins and peptides that play a vital role in the endosomal pathway of membrane trafficking. In humans, any interference in normal membrane trafficking or retromer complex can cause profound changes such as those seen in neurodegenerative disorders such as Alzheimer's and Parkinson's. Several studies have explored the potential causative mechanisms in developing both disease processes; however, the role of retromer trafficking in their pathogenesis is becoming increasingly significant with promising therapeutic applications. This manuscript describes the processes involved in membrane transport and the roles of the retromer in the onset and progression of Alzheimer's and Parkinson's. Moreover, we will also explore how these aberrant mechanisms may serve as possible avenues for treatment development in both diseases and the prospect of its future application.

Inequitable access to Ebola vaccines and the resurgence of Ebola in Africa: A state of arts review.

The Ebola virus, a member of the filoviridae family of viruses, is responsible for causing Ebola Virus Disease (EVD) with a case fatality rate as high as 50%. The largest EVD outbreak was recorded in West Africa from March 2013 to June 2016, leading to over 28 000 cases and 11 000 deaths. It affected several countries, including Nigeria, Senegal, Guinea, Liberia, and Sierra Leone. Until then, EVD was predominantly reported in remote villages in central and west Africa close to tropical rainforests. Human mobility, behavioral and cultural norms, the use of bushmeat, burial customs, preference for traditional remedies and treatments, and resistance to health interventions are just a few of the social factors that considerably aid and amplify the risk of transmission. The scale and persistence of recent ebola outbreaks, as well as the risk of widespread global transmission and its ability for bioterrorism, have led to a rethinking of public health strategies to curb the disease, such as the expedition of Ebola vaccine production. However, as vaccine production lags in the subcontinent, among other challenges, the risk of another ebola outbreak is likely and feared by public health authorities in the region. This review describes the inequality of vaccine production in Africa and the resurgence of EVD, emphasizing the significance of health equality.

Deep brain stimulation in Parkinson's disease: A scientometric and bibliometric analysis, trends, and research hotspots.

Parkinson disease (PD), a prevalent neurodegenerative ailment in the elderly, relies mainly on pharmacotherapy, yet deep brain stimulation (DBS) emerges as a vital remedy for refractory cases. This study performs a bibliometric analysis on DBS in PD, delving into research trends and study impact to offer comprehensive insights for researchers, clinicians, and policymakers, illuminating the current state and evolutionary trajectory of research in this domain. A systematic search on March 13, 2023, in the Scopus database utilized keywords like "Parkinson disease," "PD," "Parkinsonism," "Deep brain stimulation," and "DBS." The top 1000 highly cited publications on DBS in PD underwent scientometric analysis via VOS Viewer and R Studio's Bibliometrix package, covering publication characteristics, co-authorship, keyword co-occurrence, thematic clustering, and trend topics. The bibliometric analysis spanned 1984 to 2021, involving 1000 cited articles from 202 sources. The average number of citations per document were 140.9, with 31,854 references. "Movement Disorders" led in publications (n = 98), followed by "Brain" (n = 78) and "Neurology" (n = 65). The University of Oxford featured prominently. Thematic keyword clustering identified 9 core research areas, such as neuropsychological function and motor circuit electrophysiology. The shift from historical neurosurgical procedures to contemporary focuses like "beta oscillations" and "neuroethics" was evident. The bibliometric analysis emphasizes UK and US dominance, outlining 9 key research areas pivotal for reshaping Parkinson treatment. A discernible shift from invasive neurosurgery to DBS is observed. The call for personalized DBS, integration with NIBS, and exploration of innovative avenues marks the trajectory for future research.

Exploring the role of Orexin-A neuropeptide in Parkinson's disease: A systematic review and meta-analysis.

BACKGROUND: Parkinson's disease (PD) is a progressive neurological condition that affects movement and coordination. Orexin-A (OXA) is an excitatory neuropeptide that is found throughout the central nervous system. There is growing interest in investigating the potential diagnostic and therapeutic utility of OXA in PD. To date, studies have reported a wide range of OXA concentrations in patients with PD. In this review, we discuss the current understanding of the dysregulation of OXA in PD and analyze its levels in the CSF. METHODS: We searched six databases (PubMed, Scopus, Web of Science, EMBASE, ProQuest, and EBSCOHost) and preprint servers using a predetermined search strategy through 4th March 4, 2023. The search keywords included "Parkinson's disease", "Orexin-A", "Hypocretin-1", "cerebrospinal fluid", and "CSF". Studies that reported OXA/Hypocretin-1 levels in the CSF of patients with PD were included. Two researchers independently reviewed the records and extracted data. FINDINGS: Eighteen studies involving 244 patients were analyzed. CSF Orexin-A concentrations were lower in patients with Parkinson's disease than in controls, with a mean difference of -59.21 (95 % CI: -89.10 to -29.32). The mean OXA levels were 281.52 (95 % CI: 226.65-336.40). CONCLUSION: Our analysis reveals lower concentrations of orexin-A in the cerebrospinal fluid of Parkinson's disease patients compared to controls, but within the normal range. These findings suggest a potential, but not significant, disruption in the orexinergic system associated with the disease.

The potential of phosphorylated α-synuclein as a biomarker for the diagnosis and monitoring of multiple system atrophy.

INTRODUCTION: Multiple system atrophy (MSA) is a rapidly progressive neurodegenerative disorder characterized by the presence of glial cytoplasmic inclusions (GCIs) containing aggregated α-synuclein (α-Syn). Accurate diagnosis and monitoring of MSA present significant challenges, which can lead to potential misdiagnosis and inappropriate treatment. Biomarkers play a crucial role in improving the accuracy of MSA diagnosis, and phosphorylated α-synuclein (p-syn) has emerged as a promising biomarker for aiding in diagnosis and disease monitoring. METHODS: A literature search was conducted on PubMed, Scopus, and Google Scholar using specific keywords and MeSH terms without imposing a time limit. Inclusion criteria comprised various study designs including experimental studies, case-control studies, and cohort studies published only in English, while conference abstracts and unpublished sources were excluded. RESULTS: Increased levels of p-syn have been observed in various samples from MSA patients, such as red blood cells, cerebrospinal fluid, oral mucosal cells, skin, and colon biopsies, highlighting their diagnostic potential. The α-Syn RT-QuIC assay has shown sensitivity in diagnosing MSA and tracking its progression. Meta-analyses and multicenter investigations have confirmed the diagnostic value of p-syn in cerebrospinal fluid, demonstrating high specificity and sensitivity in distinguishing MSA from other neurodegenerative diseases. Moreover, combining p-syn with other biomarkers has further improved the diagnostic accuracy of MSA. CONCLUSION: The p-syn stands out as a promising biomarker for MSA. It is found in oligodendrocytes and shows a correlation with disease severity and progression. However, further research and validation studies are necessary to establish p-syn as a reliable biomarker for MSA. If proven, p-syn could significantly contribute to early diagnosis, disease monitoring, and assessing treatment response.

Extracellular vesicle-mediated drug delivery in breast cancer theranostics.

Breast cancer (BC) continues to be a significant global challenge due to drug resistance and severe side effects. The increasing prevalence is alarming, requiring new therapeutic approaches to address these challenges. At this point, Extracellular vesicles (EVs), specifically small endosome-released nanometer-sized EVs (SEVs) or exosomes, have been explored by literature as potential theranostics. Therefore, this review aims to highlight the therapeutic potential of exosomes in BC, focusing on their advantages in drug delivery and their ability to mitigate metastasis. Following the review, we identified exosomes' potential in combination therapies, serving as miRNA carriers and contributing to improved anti-tumor effects. This is evident in clinical trials investigating exosomes in BC, which have shown their ability to boost chemotherapy efficacy by delivering drugs like paclitaxel (PTX) and doxorubicin (DOX). However, the translation of EVs into BC therapy is hindered by various challenges. These challenges include the heterogeneity of EVs, the selection of the appropriate parent cell, the loading procedures, and determining the optimal administration routes. Despite the promising therapeutic potential of EVs, these obstacles must be addressed to realize their benefits in BC treatment.

The paradoxical role of cytokines and chemokines at the tumor microenvironment: a comprehensive review.

Tumor progression and eradication have long piqued the scientific community's interest. Recent discoveries about the role of chemokines and cytokines in these processes have fueled renewed interest in related research. These roles are frequently viewed as contentious due to their ability to both suppress and promote cancer progression. As a result, this review critically appraised existing literature to discuss the unique roles of cytokines and chemokines in the tumor microenvironment, as well as the existing challenges and future opportunities for exploiting these roles to develop novel and targeted treatments. While these modulatory molecules play an important role in tumor suppression via enhanced cancer-cell identification by cytotoxic effector cells and directly recruiting immunological effector cells and stromal cells in the TME, we observed that they also promote tumor proliferation. Many cytokines, including GM-CSF, IL-7, IL-12, IL-15, IL-18, and IL-21, have entered clinical trials for people with advanced cancer, while the FDA has approved interferon-alpha and IL-2. Nonetheless, low efficacy and dose-limiting toxicity limit these agents' full potential. Conversely, Chemokines have tremendous potential for increasing cancer immune-cell penetration of the tumor microenvironment and promoting beneficial immunological interactions. When chemokines are combined with cytokines, they activate lymphocytes, producing IL-2, CD80, and IL-12, all of which have a strong anticancer effect. This phenomenon opens the door to the development of effective anticancer combination therapies, such as therapies that can reverse cancer escape, and chemotaxis of immunosuppressive cells like Tregs, MDSCs, and TAMs.

Utilizing indocyanine green video angiography to bridge intracranial aneurysm treatment gaps in low- and middle-income countries: a mini-review.

Intracranial aneurysms, affecting 2%-5% of the population, pose a significant challenge to neurosurgeons due to their potential to cause subarachnoid haemorrhage and high mortality rates. Intraoperative angiography is necessary for effective surgical planning and indocyanine green video angiography (ICG-VA) has emerged as a useful tool for real-time visualization of aneurysmal blood flow, aiding in better planning for potential blood flow and detection of aneurysm remnants. This mini narrative review explores the application of ICG-VA in intracranial aneurysm surgery. Compared with conventional dye-based angiography, ICG-VA is safer, more effective and more cost-effective. It can assess haemodynamic parameters, cerebral flow during temporary artery occlusion, completeness of clipping and patency of branch vessels. However, implementing ICG-VA in low- and middle-income countries presents challenges such as financial constraints, limited access to training and expertise, patient selection and consent issues. Addressing these obstacles requires capacity-building, training programmes for neurosurgeons and multidisciplinary teams, technology transfer, equipment donations, public-private partnerships, continued research and development, reducing conventional dye usage, reducing ICG wastage, exploring mechanisms to reuse ICG dyes and advocating for increased government funding and healthcare budgets.

Inaccessibility and low maintenance of medical data archive in low-middle income countries: Mystery behind public health statistics and measures.

INTRODUCTION: Africa bears the largest burden of communicable and non-communicable diseases globally, yet it contributes only about 1 % of global research output, partly because of inaccessibility and low maintenance of medical data. Data is widely recognized as a crucial tool for improvement of population health. Despite the introduction of electronic health data systems in low-and middle-income countries (LMICs) to improve data quality, some LMICs still lack an efficient system to collect and archive data. This study aims to examine the underlying causes of data archive inaccessibility and poor maintenance in LMICS, and to highlight sustainable mitigation measures. METHOD: Authors conducted a comprehensive search on PubMed, Google scholar, organization websites using the search string "data archive" or "medical data" or "public health statistics" AND "challenges" AND "maintenance" AND "Low Middle Income Countries" or "LMIC". to Identify relevant studies and reports to be included in our review. All articles related data archive in low and middle income countries were considered without restrictions due to scarcity of data. RESULT: Medical data archives in LMICs face challenges impacting data quality. Insufficient training, organizational constraints, and limited infrastructure hinder archive maintenance. To improve, support for public datasets, digital literacy, and technology infrastructure is needed. Standardization, cloud solutions, and advanced technologies can enhance data management, while capacity building and training programs are crucial. CONCLUSION: The creation and maintenance of data archives to facilitate the storage of retrospective datasets is critical to create reliable and consistent data to better equip the development of resilient health systems and surveillance of diseases in LMICs.

Neurological disorders in pregnant women in low- and middle-income countries-Management gaps, impacts, and future prospects: A review perspective.

Neurological disorders during pregnancy are a substantial threat to women's health, particularly in low- and middle-income countries. Furthermore, a critical shortage of mental health workers and neurologists exacerbates the already pressing issue, where a lack of coordination of respective healthcare among multidisciplinary teams involved in managing these conditions perpetuates the current state of affairs. Financial restrictions and societal stigmas associated with neurological disorders in pregnancy amplify the situation. Addressing these difficulties would necessitate a multifaceted approach comprising investments in healthcare infrastructure, healthcare professional education and training, increased government support for research, and the implementation of innovative care models. Improving access to specialized treatment and coordinated management of antenatal neurological diseases will precipitate improved health outcomes for women and their families in low- and middle-income countries.

A reflection of Africa's cardiac surgery capacity to manage congenital heart defects: a perspective.

Congenital heart defects (CHDs) are birth abnormalities that may drastically alter the structure and functionality of the heart. For 70% of infants with congenital disorders to survive or maintain a better quality of life, surgery is necessary. Over 500 000 of the 1.5 million CHD cases reported annually, or 1% of all live births, occur in Africa, according to the WHO. A surmounted 90% of these patients are from Africa, and as a consequence, 300 000 infants die annually as a result of poor care or difficulty accessing adequate healthcare. However, the high prevalence of CHDs, precipitated by a plethora of aetiologies worldwide, is particularly pronounced in Africa due to maternal infectious diseases like syphilis and rubella amongst the pregnant populace. In low- and middle-income countries, especially in Africa, where foreign missions and organizations care for the majority of complicated cardiac surgical patients, access to secure and affordable cardiac surgical therapy is a substantial issue. Interventions for CHDs are very expensive in Africa as many of the continent's domiciles possess low expenditures and funding, thereby cannot afford the costs indicated by associated surgical treatments. Access to management and healthcare for CHDs is further hampered by a lack of trained surgical personnel, specialized tools, infrastructure, and diagnostic facilities in Africa.

Vascular multiple sclerosis: addressing the pathogenesis, genetics, pro-angiogenic factors, and vascular abnormalities, along with the role of vascular intervention.

Dysfunction in the epithelium, breakdown of the blood-brain barrier, and consequent leukocyte and T-cell infiltration into the central nervous system define Vascular Multiple Sclerosis. Multiple sclerosis (MS) affects around 2.5 million individuals worldwide, is the leading cause of neurological impairment in young adults, and can have a variety of progressions and consequences. Despite significant discoveries in immunology and molecular biology, the root cause of MS is still not fully understood, as do the immunological triggers and causative pathways. Recent research into vascular anomalies associated with MS suggests that a vascular component may be pivotal to the etiology of MS, and there can be actually a completely new entity in the already available classification of MS, which can be called 'vascular multiple sclerosis'. Unlike the usual other causes of MS, vascular MS is not dependent on autoimmune pathophysiologic mechanisms, instead, it is caused due to the blood vessels pathology. This review aims to thoroughly analyze existing information and updates about the scattered available findings of genetics, pro-angiogenetic factors, and vascular abnormalities in this important spectrum, the vascular facets of MS.

Periodic Fever in Children: Etiology and Diagnostic Challenges.

Periodic fever in children is an autoinflammatory illness with an unknown cause. Symptoms include frequent episodes of fever that are followed by an increase in inflammatory markers. A genetic background for periodic fever of unknown origin has been hypothesized, based on its family clustering and parallels to other autoinflammatory illnesses such as familial Mediterranean fever. Genome analysis has been used in studies to look for related gene variations in periodic fever of unknown origin in the pediatric population.  Children with periodic fevers might be a diagnostic challenge. After ruling out the most prevalent causes, a wide variety of other possibilities are investigated. Infectious and noninfectious causes of periodic fever in children are discussed in this article. Inflammasomes (intracellular proteins that activate interleukin (IL)-1b and IL-18) and genetic/hereditary variations are thought to be implicated in the pathogenesis of periodic fever. Evaluation and ruling out possible infective or noninfective causes is vital in the diagnosis of periodic fever in children. Investigations demonstrate that there isn't a single gene linked to it, suggesting that it may have a multifactorial or polygenic origin, with an environmental trigger causing inflammasome activation and fever flares. Treatment is usually symptomatic, with drugs such as colchicine and cimetidine having shown promising results in trials. We explored the literature on periodic fever in children for its epidemiology, pathophysiology, the role of various genes and how they influence the disease and associated complications, and its various treatment modalities.

Association between Mesenchymal Stem Cells and COVID-19 Therapy: Systematic Review and Current Trends.

Background: The novel coronavirus first emerged in Wuhan, China, and quickly spread across the globe, spanning various countries and resulting in a worldwide pandemic by the end of December 2019. Given the current advances in treatments available for COVID-19, mesenchymal stem cell (MSC) therapy seems to be a prospective option for management of ARDS observed in COVID-19 patients. This present study is aimed at exploring the therapeutic potential and safety of using MSC obtained by isolation from health cord tissues in the treatment of patients with COVID-19. Methods: A systematic search was done based on the guidelines of the PRISMA 2020 statement. A literature search was executed using controlled vocabulary and indexing of trials to evaluate all the relevant studies involving the use of medical subject headings (MeSH) in electronic databases like PubMed, Embase, Scopus, Cochrane Central Register of Controlled Trials (CENTRAL), and clinicaltrials.gov up to 31 December 2021. The protocol was registered in the PROSPERO register with ID CRD42022301666. Findings. After screening finally, 22 remaining articles were included in this systematic review. The studies revealed that MSC exosomes are found to be superior to MSC alone in terms of safety owing to being smaller with a lesser immunological response which leads to free movement in blood capillaries without clumping and also cannot further divide, thus reducing the oncogenic potential of MSC-derived exosomes as compared to MSC only. The studies demonstrated that the lungs healed with the use of exosomes compared to how they presented initially at the hospital. MSCs are found to increase the angiogenesis process and alveolar reepithelization, reducing markers like TNF alpha, TGF beta, and COL I and III, reducing the growth of myofibroblasts and increasing survivability of endothelium leading to attenuated pulmonary fibrosis and even reversing them. Interpretation. We can conclude that the use of mesenchymal stem cells or their derived exosomes is safe and well-tolerated in patients with COVID-19. It improves different parameters of oxygenation and helps in the healing of the lungs. The viral load along with different inflammatory cells and biomarkers of inflammation tend to decrease. Chest X-ray, CT scan, and different radiological tools are used to show improvement and reduced ongoing destructive processes.