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.

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.

Advancements and progress in juvenile idiopathic arthritis: A Review of pathophysiology and treatment.

Juvenile idiopathic arthritis (JIA) is a chronic clinical condition characterized by arthritic features in children under the age of 16, with at least 6 weeks of active symptoms. The etiology of JIA remains unknown, and it is associated with prolonged synovial inflammation and structural joint damage influenced by environmental and genetic factors. This review aims to enhance the understanding of JIA by comprehensively analyzing relevant literature. The focus lies on current diagnostic and therapeutic approaches and investigations into the pathoaetiologies using diverse research modalities, including in vivo animal models and large-scale genome-wide studies. We aim to elucidate the multifactorial nature of JIA with a strong focus towards genetic predilection, while proposing potential strategies to improve therapeutic outcomes and enhance diagnostic risk stratification in light of recent advancements. This review underscores the need for further research due to the idiopathic nature of JIA, its heterogeneous phenotype, and the challenges associated with biomarkers and diagnostic criteria. Ultimately, this contribution seeks to advance the knowledge and promote effective management strategies in JIA.

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.

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.

Fluorescence visualization for cancer DETECTION: EXPERIENCE and perspectives.

The current review focuses on the latest advances in the improvement and application of fluorescence imaging technology. Near-infrared (NIR) fluorescence imaging is a promising new technique that uses non-specific fluorescent agents and targeted fluorescent tracers combined with a dedicated camera to better navigate and visualize tumors. Fluorescence-guided surgery (FGS) is used to perform various tasks, helping the surgeon to distinguish lymphatic vessels and nodes from surrounding tissues easily and quickly assess the perfusion of the planned resection area, including intraoperative visualization of metastases. The results of the insertion of fluorescence visualization as an auxiliary method to cancer detection and high-risk metastatic lesions in clinical practice have demonstrated enthusiastic results and huge potential. However, intraoperative fluorescence visualization must not be considered as a main diagnostic or treatment method but as an aid to the surgeon. Thus, fluorescence study does not dispense the diagnostic gold standards of benign or malignant tumors (conventional examination, biopsy, ultrasonography and computed tomography, etc.) and can be done usually during intraoperative treatment. Moreover, as fluorescence surgery and fluorescence diagnostic techniques continue to improve, it is likely that they will evolve towards targeted fluorescence imaging probes that will increasingly target a specific type of cancer cell. The most important point remains the search for highly selective messengers of fluorescent labels, which make it possible to identify tumor cells exclusively in the affected organs and indicate to surgeons the boundaries of their spread and metastasis.

Prognostic variables predict clinical outcome after decompressive craniectomy: A single institute experience; A retrospective study.

Decompressive craniectomy (DC) is a well-established neurosurgical intervention in patients with high intracranial pressure who fail to respond to medical treatment. Data on predictive factors for functional outcomes in patients with DC who have malignant middle cerebral artery (MCA) infarction as opposed to intracranial hemorrhage (ICH) are scarce. Eighty-four patients who underwent DC treatment for ICH and malignant MCA infarction were examined. All patients underwent surgery in the Bahrain Salmaniya Medical Complex Neurosurgery Unit between January 2017 and June 2021. To determine whether any of these demonstrated a link to the functional outcome, radiographic factors were compared with clinical data. The postsurgical midline shift (MLS) (ICH group) showed the strongest correlation (ρ = 0.434; P = .006), as in the MCA infarction group as well (ρ = 0.46; P = .005). Further analyses using binary logistic regression with postsurgical basal cistern status and ∆ MLS, and it was observed to be statistically significant (odds ratios: 0.067, 95% CI: 0.007, 0.67; P = .021). The initial Glasgow coma scale, postsurgical MLS, basal cistern status, and ∆ are Measurable variables that can be used to predict outcomes in the groups with ICH and MCA infarction.

Beyond symptoms: Unlocking the potential of coronary calcium scoring in the prevention and treatment of coronary artery disease.

Coronary Artery Disease (CAD) represents a persistent global health menace, particularly prevalent in Eastern European nations. Often asymptomatic until its advanced stages, CAD can precipitate life-threatening events like myocardial infarction or stroke. While conventional risk factors provide some insight into CAD risk, their predictive accuracy is suboptimal. Amidst this, Coronary Calcium Scoring (CCS), facilitated by non-invasive computed tomography (CT), emerges as a superior diagnostic modality. By quantifying calcium deposits in coronary arteries, CCS serves as a robust indicator of atherosclerotic burden, thus refining risk stratification and guiding therapeutic interventions. Despite certain limitations, CCS stands as an instrumental tool in CAD management and in thwarting adverse cardiovascular incidents. This review delves into the pivotal role of CCS in CAD diagnosis and treatment, elucidates the involvement of calcium in atherosclerotic plaque formation, and outlines the principles and indications of utilizing CCS for predicting major cardiovascular events.

RNA in cardiovascular disease: A new frontier of personalized medicine.

Personalized medicine has witnessed remarkable progress with the emergence of RNA therapy, offering new possibilities for the treatment of various diseases, and in particular in the context of cardiovascular disease (CVD). The ability to target the human genome through RNA manipulation offers great potential not only in the treatment of cardiac pathologies but also in their diagnosis and prevention, notably in cases of hyperlipidemia and myocardial infarctions. While only a few RNA-based treatments have entered clinical trials or obtained approval from the US Food and Drug Administration, the growing body of research on this subject is promising. However, the development of RNA therapies faces several challenges that must be overcome. These include the efficient delivery of drugs into cells, the potential for immunogenic responses, and safety. Resolving these obstacles is crucial to advance the development of RNA therapies. This review explores the newest developments in medical studies, treatment plans, and results related to RNA therapies for heart disease. Furthermore, it discusses the exciting possibilities and difficulties in this innovative area of research.

The impact of air quality on cardiovascular health: A state of the art review.

Air pollution is a global health challenge, increasing the risk of cardiovascular diseases such as heart disease, stroke, and arrhythmias. Particulate matter (PM), particularly PM2.5 and ultrafine particles (UFP), is a key contributor to the adverse effects of air pollution on cardiovascular health. PM exposure can lead to oxidative stress, inflammation, atherosclerosis, vascular dysfunction, cardiac arrhythmias, and myocardial injury. Reactive oxygen species (ROS) play a key role in mediating these effects. PM exposure can also lead to hypertension, a significant risk factor for cardiovascular disease. The COVID-19 pandemic resulted in a significant reduction of air pollutants, leading to a decline in the incidence of heart attacks and premature deaths caused by cardiovascular diseases. This review highlights the relationship between environmental air quality and cardiovascular health, elucidating the pathways through which air pollutants affect the cardiovascular system. It also emphasizes the need for increased awareness, collective efforts to mitigate the adverse effects of air pollution, and strategic policies for long-term air quality improvement to prevent the devastating effects of air pollution on global cardiovascular health.

A review of functional pancreatic neuroendocrine tumors: Exploring the molecular pathogenesis, diagnosis and treatment.

Pancreatic neuroendocrine tumors (PanNETs) are a rare subtype of pancreatic cancer and can be divided into functional (30-40%) and nonfunctional subtypes. The different subtypes of functional PanNETs (F-PanNETs) have a variety of classical presentations that raise suspicion for an underlying PanNET. It is estimated that 90% of PanNETs are sporadic, and the PI3K-Akt-mTOR and ATRX/DAXX signaling pathways have been recognized as key genetic pathways implicated in the pathogenesis. The other 10% of PanNETs may occur in the context of familial cancer syndromes such as MEN1. Chromogranin A is the most useful biomarker currently; however, several studies have shown limitations with its use, especially its prognostic value. Synaptophysin is a novel biomarker which has shown promising preliminary results however its use clinically has yet to be established. Blood tests assessing hormone levels, cross-sectional imaging, and endoscopic ultrasound remain at the core of establishing a diagnosis of F-PanNET. The treatment options for F-PanNETs include surgical methods such as enucleation, systemic therapies like chemotherapy and novel targeted therapies such as everolimus. The prognosis for F-PanNETs is more favorable than for nonfunctional PanNETs, however metastatic disease is associated with poor survival outcomes. Researchers should also focus their efforts on identifying novel pathways implicated in the pathogenesis of F-PanNETs in order to develop new targeted therapies that may reduce the need for surgical intervention and on the establishment of novel biomarkers that may reduce the need for invasive testing and allow for earlier detection of F-PanNETs.

Respiratory arrest after posterior fossa decompression in patients with Chiari malformations: An overview.

Background: Chiari malformation type 1 (CM1) is a structural abnormality in the skull and cerebellum, causing cerebellar tonsils to shift downward. Decompression of the posterior fossa is a common surgical method to relieve symptoms and prevent neurological deterioration. After posterior fossa decompression (PFD), individuals with CM1 were more likely to have respiratory arrest. Here, we present, for the first time, a comprehensive overview of the potential risk factors and causes of respiratory arrest following PFD. Methods: A review of the literature highlighting the risk factors for postoperative respiratory arrest in CM1 patients was conducted in the databases of PubMed, Medline, and Google Scholar. Results: Patients with syringomyelia and CM1 are at increased risk for respiratory arrest due to a number of factors, including impaired respiratory mechanics, central respiratory center dysfunction from edema or ischemia, intraoperative brain stem ischemia, and delayed gastric emptying from autonomic dysfunction. Occipitalization of the first cervical vertebra, basilar impression, and fusion of C2-C3 are all risk factors for respiratory arrest. Conclusion: Implications for CM1 patient care and prospects for further investigation of postoperative respiratory arrest's causes and risk factors were discussed.

ER and COX2 expression in endometrial hyperplasia processes.

Endometrial hyperplastic processes (EHPs) encompass various morphological changes, characterized by an increased ratio of endometrial glands to stroma. These changes manifest as endometrial hyperplasia (EH) and endometrial polyps. The objective of this study was to investigate the expressions of ER and Cyclooxygenase-2 (COX2) in EH and endometrial polyps, and determine their correlation with histological and anthropometric parameters. Tissue samples were obtained during hysteroresectoscopy and divided into 3 groups: non-atypical EH, glandular EP, and glandular-fibrous EP. We examined the immunoprofile of epithelial and stromal cells using rabbit polyclonal anti-COX2 antibodies and rabbit monoclonal anti-ER antibodies (clone SP1). Our results indicate that there is no association between the expressions of ER and COX2 and the type of EHP. Furthermore, the expression levels of ER and COX2 are not influenced by the patients anthropometric parameters. However, tissues with EHPs exhibited significantly higher COX2 expression compared to intact tissues. We also observed a direct correlation between ER and COX2 expression in the endometrial epithelium. The variability in ER and COX2 expressions observed in hyperplastic processes of the endometrium potentially suggests their synergistic involvement in the initiation and progression of EHPs, as well as their potential role in subsequent tumor transformation.

Challenges and opportunities in prostate cancer surgery in South America: Insights into robot-assisted radical prostatectomies-A perspective.

Background and Aims: Prostate cancer imposes a significant health burden, particularly in South America with its high incidence and mortality rates. This article explores the emergence of robot-assisted radical prostatectomy (RARP) as a potential solution in the region. Methods: This study relies on a comprehensive review of relevant literature. The analysis highlights the advantages of RARP, identifies impediments to its implementation, and proposes strategies to overcome these barriers. Results: RARP demonstrates notable benefits, including improved functional outcomes, reduced complications, and minimized incisions. However, the integration of RARP in South America is hindered by challenges such as regional disparities, financial limitations, and data gaps. Limited healthcare infrastructure and a scarcity of skilled professionals further compound the issues. Conclusion: Despite its potential, RARP faces obstacles to widespread adoption in South America. Strategic solutions encompassing technology investment, healthcare infrastructure enhancement, and workforce training are imperative. Overcoming these challenges can establish RARP as a crucial tool in managing prostate cancer in the region, ultimately enhancing patient care and treatment outcomes.

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.

The Use of Cardioprotective Devices and Strategies in Patients Undergoing Percutaneous Procedures and Cardiac Surgery.

In the United States, about one million people are seen to visit the operating theater for cardiac surgery annually. However, nearly half of these visits result in complications such as renal, neurological, and cardiac injury of varying degrees. Historically, many mechanisms and approaches have been explored in attempts to reduce injuries associated with cardiac surgery and percutaneous procedures. Devices such as cardioplegia, mechanical circulatory support, and other methods have shown promising results in managing and preventing life-threatening cardiac-surgery-related outcomes such as heart failure and cardiogenic shock. Comparably, cardioprotective devices such as TandemHeart, Impella family devices, and venoarterial extracorporeal membrane oxygenation (VA-ECMO) have also been proven to show significant cardioprotection through mechanical support. However, their use as interventional agents in the prevention of hemodynamic changes due to cardiac surgery or percutaneous interventions has been correlated with adverse effects. This can lead to a rebound increased risk of mortality in high-risk patients who undergo cardiac surgery. Further research is necessary to delineate and stratify patients into appropriate cardioprotective device groups. Furthermore, the use of one device over another in terms of efficacy remains controversial and further research is necessary to assess device potential in different settings. Clinical research is also needed regarding novel strategies and targets, such as transcutaneous vagus stimulation and supersaturated oxygen therapy, aimed at reducing mortality among high-risk cardiac surgery patients. This review explores the recent advances regarding the use of cardioprotective devices in patients undergoing percutaneous procedures and cardiac surgery.

Appraising war's impacts on neurosurgical delivery in Ukraine.

The conflict in Ukraine, which started when Russia invaded and violated its sovereignty, has led to the country's worst war since the annexation of Crimea in 2014. The war has resulted in a significant number of casualties, displaced millions of people, and damaged the healthcare system, which was already struggling before the conflict. The neurosurgical field, in particular, has been severely affected, with infrastructure and healthcare systems routinely demolished or interrupted in conflict zones, making fundamental medical operations unavailable to victims of armed conflict. As a result, neurosurgeons have been compelled to conduct surgeries outside of their areas of competence, in makeshift settings or under challenging conditions, with limited access to materials and equipment. The war has also severely damaged specialised neurosurgery facilities, causing a severe shortage of crucial supplies and equipment. To address the challenges facing neurosurgery care in Ukraine, it is essential to rebuild and repair the damaged neurosurgical centres and provide them with the necessary equipment and supplies to successfully administer neurosurgical treatments. Training programs for neurosurgeons and other medical specialists must also be organised to manage complex neurosurgical problems under difficult conditions.