Lingering challenges in malaria elimination efforts in sub-Saharan Africa: Insights and potential solutions.

Introduction: Between 2000 and 2015, significant gains were recorded in reducing the global burden of malaria due to enhanced global collaboration and increased funding. However, progress has stagnated post-2015, and the COVID-19 pandemic seems to have reversed some of these gains, necessitating a critical reevaluation of interventions. This paper aims to analyze the setbacks and offer recommendations for advancement in malaria control and prevention in sub-Saharan Africa. Methods: We conducted searches on Google Scholar, PubMed, and relevant organization websites to identify relevant studies on malaria control and prevention and associated challenges in sub-Saharan Africa from 2015 to the present. Additionally, studies on individual sub-Saharan African countries were reviewed to ensure comprehensiveness. Data from selected studies were extracted and analyzed using a narrative synthesis approach to offer a concise overview of the evidence. Findings: We observe that the halt in progress of malaria control in sub-Saharan Africa has deep roots in socioeconomic, political, and environmental factors. These challenges are exacerbated by the population explosion in the region, low coverage of interventions due to funding deficits and incessant crises, and the degradation of the efficacy of existing malaria commodities. Conclusion: Sub-Saharan Africa is at a crossroads in its fight against malaria. Promising new frontiers such as malaria vaccines, preventive monoclonal antibodies, new-generation insecticide-treated nets, and potentially artificial intelligence-driven technologies offer hope in advancing malaria control and prevention in the region. Through commitment and collaboration, leveraging these opportunities can help surmount challenges and ultimately eliminate malaria in sub-Saharan Africa.

Recurrent artery of Heubner aneurysms in focus: insights into occurrence and current treatment paradigms.

INTRODUCTION: The recurrent artery of Heubner (RAH), also known as the medial striate artery, is the most clinically important perforator of the anterior cerebral artery. RAH aneurysm is relatively rare, with 11 cases found in the present literature review, but poses significant clinical challenges due to potential impact on cognitive and motor functions. This systematic review explored available case reports to comprehensively understand clinical presentation, diagnosis, management and outcome in RAH aneurysm. MATERIALS AND METHODS: Following PRISMA guidelines, this systematic review extensively explored RAH aneurysms, covering demographics, symptoms, diagnosis, treatments and outcomes. Comprehensive searches on PubMed, Scopus, Google Scholar, and Science Direct employed keywords such as "recurrent artery of Heubner aneurysm" and "Heubner's artery." RESULTS: After extensive screening, 9 qualifying studies were identified, with 11 patients diagnosed with rare RAH aneurysm. Median age was 55 years (standard deviation, 15.3 years), with 54.5% males. 45.5% of patients presented risk factors, including Moyamoya disease in 2 patients. The majority were classified as grade I/II on the Hunt and Hess (H&H) and World Federation of Neurological Societies (WFNS) systems. Aneurysms were predominantly located in the A1 segment, with a mean size of 4.7 mm. Treatments varied, with clipping being the most frequent (63.6%). The mortality rate was 18.2%. Clipping was associated with favorable outcomes but higher rates of infarction. CONCLUSION: This analysis highlighted the various symptoms, therapy methods and outcomes of RAH aneurysm, with A1 being the predominant origin. Future research should explore potential genetic predisposition factors and novel therapeutic interventions to address gaps in our knowledge.

Bridging Minds and Machines: The Recent Advances of Brain-Computer Interfaces in Neurological and Neurosurgical Applications.

Brain-Computer Interfaces (BCIs), a remarkable technological advancement in neurology and neurosurgery, mark a significant leap since the inception of electroencephalography (EEG) in 1924. These interfaces effectively convert central nervous system signals into commands for external devices, offering revolutionary benefits to patients with severe communication and motor impairments due to a myriad of neurological conditions like stroke, spinal cord injuries, and neurodegenerative disorders. BCIs enable these individuals to communicate and interact with their environment, using their brain signals to operate interfaces for communication and environmental control. This technology is especially crucial for those completely locked in, providing a communication lifeline where other methods fall short. The advantages of BCIs are profound, offering autonomy and an improved quality of life for patients with severe disabilities. They allow for direct interaction with various devices and prostheses, bypassing damaged or non-functional neural pathways. However, challenges persist, including the complexity of accurately interpreting brain signals, the need for individual calibration, and ensuring reliable, long-term use. Additionally, ethical considerations arise regarding autonomy, consent, and the potential for dependence on technology. Despite these challenges, BCIs represent a transformative development in neurotechnology, promising enhanced patient outcomes and a deeper understanding of brain-machine interfaces.

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.

Early intervention and care for Diabetic Foot Ulcers in Low and Middle Income Countries: Addressing challenges and exploring future strategies: A narrative review.

Background and Aims: Diabetic Foot Ulcers (DFUs) are a significant health concern, particularly in Low- and Middle-Income Countries (LMICs). This review explores key strategies for managing DFUs in LMICs, including integrating podiatry, endocrinology, and wound care services, educating patients, promoting self-care, and preventive measures to reduce amputation rates. Methods: A comprehensive literature review was conducted, focusing on studies conducted in Low and Middle Income Countries to facilitate a qualitative analysis. The review examined the aetiology and risk factors to developing DFUs, clinical presentation, multidisciplinary management and evidence based interventions, challenges to the provision of care and future directions, all pertaining to DFUs in low and middle income countries. Results: The aetiology and risk factors contributing to the development of DFUs are complex and multifaceted. Factors such as limited access to health care, inadequate diabetes management, and socioeconomic disparities significantly influence the incidence of DFUs. Clinical presentation varies, with patients often presenting at advanced stages of the disease due to delayed or missed diagnoses. Multidisciplinary management, incorporating podiatry, endocrinology, and wound care services, has exhibited substantial promise in enhancing patient outcomes. Evidence-based interventions, including offloading techniques, wound debridement, and the use of advanced wound dressings, have proven effective in promoting ulcer healing. Conclusion: The burden of DFUs in LMICs requires comprehensive strategies. Integrating podiatry, endocrinology, and wound care services, along with patient education and self-care practices, is essential for reducing amputations and improving patients' quality of life. Regular follow-up and early detection are vital for effective DFU management, emphasizing the need for ongoing research and investment in LMIC health care infrastructure. Embracing these multidisciplinary, patient-centered approaches can effectively address the challenge of DFUs in LMICs, leading to better patient outcomes and improved quality of life.

Recent Outcomes and Challenges of Artificial Intelligence, Machine Learning, and Deep Learning in Neurosurgery.

Neurosurgeons receive extensive technical training, which equips them with the knowledge and skills to specialise in various fields and manage the massive amounts of information and decision-making required throughout the various stages of neurosurgery, including preoperative, intraoperative, and postoperative care and recovery. Over the past few years, artificial intelligence (AI) has become more useful in neurosurgery. AI has the potential to improve patient outcomes by augmenting the capabilities of neurosurgeons and ultimately improving diagnostic and prognostic outcomes as well as decision-making during surgical procedures. By incorporating AI into both interventional and non-interventional therapies, neurosurgeons may provide the best care for their patients. AI, machine learning (ML), and deep learning (DL) have made significant progress in the field of neurosurgery. These cutting-edge methods have enhanced patient outcomes, reduced complications, and improved surgical planning.

Clearing the Fog: A Review of Antipsychotics for Parkinson's-Related Hallucinations: A Focus on Pimavanserin, Quetiapine and Clozapine.

Parkinson's disease is a progressive neurodegenerative disorder characterized by motor and non-motor symptoms, including hallucinations. The use of antipsychotic medications is a common strategy to manage hallucinations associated with Parkinson's disease psychosis (PDP). However, careful consideration is necessary when selecting the most appropriate drug due to the potential risks associated with the available treatment options. Atypical antipsychotics (AAPs), such as Pimavanserin and Clozapine, have effectively controlled PDP symptoms. On the contrary, the support for utilizing quetiapine is not as substantial as other antipsychotics because research studies specifically investigating its application are still emerging and relatively recent. The broad mechanisms of action of AAPs, involving dopamine and serotonin receptors, provide improved outcomes and fewer side effects than typical antipsychotics. Conversely, other antipsychotics, including risperidone, olanzapine, aripiprazole, ziprasidone, and lurasidone, have been found to worsen motor symptoms and are generally not recommended for PDP. While AAPs offer favorable benefits, they are associated with specific adverse effects. Extrapyramidal symptoms, somnolence, hypotension, constipation, and cognitive impairment are commonly observed with AAP use. Clozapine, in particular, carries a risk of agranulocytosis, necessitating close monitoring of blood counts. Pimavanserin, a selective serotonin inverse agonist, avoids receptor-related side effects but has been linked to corrected QT (QTc) interval prolongation, while quetiapine has been reported to be associated with an increased risk of mortality. This review aims to analyze the benefits, risks, and mechanisms of action of antipsychotic medications to assist clinicians in making informed decisions and enhance patient care.

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.

Exploring the current landscape of single-cell RNA sequencing applications in gastric cancer research.

Gastric cancer (GC) represents a major global health burden and is responsible for a significant number of cancer-related fatalities. Its complex nature, characterized by heterogeneity and aggressive behaviour, poses considerable challenges for effective diagnosis and treatment. Single-cell RNA sequencing (scRNA-seq) has emerged as an important technique, offering unprecedented precision and depth in gene expression profiling at the cellular level. By facilitating the identification of distinct cell populations, rare cells and dynamic transcriptional changes within GC, scRNA-seq has yielded valuable insights into tumour progression and potential therapeutic targets. Moreover, this technology has significantly improved our comprehension of the tumour microenvironment (TME) and its intricate interplay with immune cells, thereby opening avenues for targeted therapeutic strategies. Nonetheless, certain obstacles, including tumour heterogeneity and technical limitations, persist in the field. Current endeavours are dedicated to refining protocols and computational tools to surmount these challenges. In this narrative review, we explore the significance of scRNA-seq in GC, emphasizing its advantages, challenges and potential applications in unravelling tumour heterogeneity and identifying promising therapeutic targets. Additionally, we discuss recent developments, ongoing efforts to overcome these challenges, and future prospects. Although further enhancements are required, scRNA-seq has already provided valuable insights into GC and holds promise for advancing biomedical research and clinical practice.

Exoscope-assisted spine surgery: Current applications and future directions.

Spine surgery is continually evolving, with the application of new technologies often serving as a catalyst for improved clinical outcomes. Exoscope-assisted spinal surgery has recently emerged as a notable technological advancement offering a refined approach to visualisation, thereby potentially contributing to improved surgical precision, reduced complication rates, and optimised patient outcomes. The application of exoscopes have improved spine surgeries such as spinal fusion procedures, decompression surgeries, instrumentation surgeries, minimally invasive and complex surgeries. These improvements include enhanced visualisation, improved ergonomics, improved surgical precision, reduced operation times and postoperative infection rates. The integration of robotics in exoscope-assisted spine surgery enables autofocus function, ensuring the integrity of the sterile field, providing superior image quality, resolution, and three-dimensional perception. However, challenges such as decrease in depth perception and the lack of long-term follow-up data hinder its widespread adoption. Ethical considerations regarding patient safety, technology dependency, and health inequity add another dimension to these challenges. Despite these challenges, exoscope-assisted spine surgery holds significant potential for transforming clinical practice and improving patient outcomes. This review seeks to provide a concise overview of the benefits and limits of exoscope-assisted spine surgeries, while highlighting its challenges and ethical considerations. Addressing these limitations by conducting large-scale clinical trials and exploring the integration of artificial intelligence (AI) could assist in realising the potential of exoscopes in spine surgery."

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.

Terrorism's impact on low and middle-income countries' healthcare services: A perspective.

Terrorism has emerged as an increasingly pressing global issue, giving rise to escalating casualties and devastating implications for peace and security. The low- and middle-income countries (LMICs), already grappling with inadequate healthcare services and an estimated annual mortality toll ranging from 5.7 to 8.4 million, face further setbacks as terrorism exacerbates their prevailing healthcare deficiencies. Among the aspects of how terrorism affects healthcare in LMICs are high morbidity, mortality, and treatment wait times. The four principal areas of reverberation encompass amplified vulnerabilities in healthcare systems, financial shortfalls in LMIC healthcare systems, worsened personnel shortages in healthcare, and the devastating impact on healthcare facilities. In response to these challenges, international organizations and countries have played a pivotal role in mitigating the impact of terrorism on healthcare systems. Additionally, to improve healthcare in these regions, investing in infrastructure, supporting healthcare workers, and ensuring safety are paramount. Implementing mobile health interventions, traditional medicine, and mobile laboratories may enhance healthcare accessibility. Further, employing blockchain technology for data security and supply chain management may strengthen healthcare systems in these areas.

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.

Hereditary spastic paraplegia: Novel insights into the pathogenesis and management.

Hereditary spastic paraplegia is a genetically heterogeneous neurodegenerative disorder characterised primarily by muscle stiffness in the lower limbs. Neurodegenerative disorders are conditions that result from cellular and metabolic abnormalities, many of which have strong genetic ties. While ageing is a known contributor to these changes, certain neurodegenerative disorders can manifest early in life, progressively affecting a person's quality of life. Hereditary spastic paraplegia is one such condition that can appear in individuals of any age. In hereditary spastic paraplegia, a distinctive feature is the degeneration of long nerve fibres in the corticospinal tract of the lower limbs. This degeneration is linked to various cellular and metabolic processes, including mitochondrial dysfunction, remodelling of the endoplasmic reticulum membrane, autophagy, abnormal myelination processes and alterations in lipid metabolism. Additionally, hereditary spastic paraplegia affects processes like endosome membrane trafficking, oxidative stress and mitochondrial DNA polymorphisms. Disease-causing genetic loci and associated genes influence the progression and severity of hereditary spastic paraplegia, potentially affecting various cellular and metabolic functions. Although hereditary spastic paraplegia does not reduce a person's lifespan, it significantly impairs their quality of life as they age, particularly with more severe symptoms. Regrettably, there are currently no treatments available to halt or reverse the pathological progression of hereditary spastic paraplegia. This review aims to explore the metabolic mechanisms underlying the pathophysiology of hereditary spastic paraplegia, emphasising the interactions of various genes identified in recent network studies. By comprehending these associations, targeted molecular therapies that address these biochemical processes can be developed to enhance treatment strategies for hereditary spastic paraplegia and guide clinical practice effectively.

Current trends and challenges: The landscape of perioperative mortality in intracranial surgeries in low- and middle-income settings: A narrative review.

Background and Aims: Intracranial surgeries are pivotal in treating cerebral pathologies, particularly in resource-limited contexts, utilizing techniques such as craniotomy, transsphenoidal approaches, and endoscopy. However, challenges in low and middle income countries (LMICs), including resource scarcity, diagnostic delays, and a lack of skilled neurosurgeons, lead to elevated perioperative mortality (POM). This review seeks to identify major contributors to these challenges and recommend solutions for improved patient outcomes in neurosurgical care within LMICs. Methods: This review examines POM in LMICs using a detailed literature search, focusing on studies from these regions. Databases like PubMed, EMBASE, and Google Scholar were utilized using specific terms related to "intracranial surgery," "perioperative mortality," "traumatic brain injuries," and "LMICs." Inclusion criteria covered various study designs and both pediatric and adult populations while excluding stand-alone abstracts and case reports. Results: POM rates for intracranial surgeries differ widely across many low and middle-income regions: Africa sees rates from 2.5% to 39.1%, Asia between 3.6% and 34.8%, and Latin America and the Caribbean have figures ranging from 1.3% to 12%. The POM rates in LMICs were relatively higher compared to most first-world countries. The high POM rates in LMICs can be attributed to considerable delays and compromises in neurosurgical care delivery, exacerbated by late diagnoses and presentations of neurosurgical pathologies. This, coupled with limited resources, underdeveloped infrastructure, and training gaps, complicates intracranial disease management, leading to elevated POM. Conclusion: Intracranial POM is a pronounced disparity within the neurosurgical field in LMICs. To mitigate intracranial POM, it is imperative to bolster healthcare infrastructure, amplify personnel training, foster global partnerships, and harness technologies like telemedicine. Tackling socioeconomic obstacles and prioritizing early detection through sustained funding and policy shifts can substantially enhance patient outcomes.

Insights into craniosynostosis management in low- and middle-income countries: A narrative review of outcomes, shortcomings and paediatric neurosurgery capacity.

Craniosynostosis, marked by premature cranial suture fusion, necessitates prompt intervention to avert developmental, neurological, and aesthetic issues. While high-income countries have advanced in managing this condition, low- and middle-income countries grapple with substantial healthcare access disparities. This narrative review explores current craniosynostosis management in low- and middle-income countries. The review focused on studies published between 2008 and 2023. The focus was neurosurgical outcomes, and the search utilised databases like PubMed, EMBASE, Google Scholar, the Cochrane Library and Scopus, incorporating specific keywords and phrases. An in-depth analysis of 21 included studies reveals noteworthy positive outcomes, including low mortality, successful corrections and sustained efficacy. These advancements stem from enhanced pre-operative strategies, surgical techniques and postoperative care. Nonetheless, challenges persist, encompassing complications, mortality, reoperations, and treatment disparities, particularly in low- and middle-income countries constrained by financial and expertise limitations. The enhancement of clinical practice and the formulation of effective policies in the future entail several key strategies. These include the reinforcement of specialised healthcare infrastructure and diagnostic capabilities, the ongoing training and retention of neurosurgeons, the improvement of funding mechanisms, and the promotion of equitable access. Additionally, a crucial focus is placed on fortifying paediatric neurosurgical care in low- and middle-income countries. The recommendations underscore the importance of collaborative initiatives, the development of specialised healthcare infrastructure, and the implementation of strategic policies to not only advance pediatric neurosurgical care but also to address existing gaps in management.