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.

Doctors' pay in the United Kingdom: evaluating the broader impacts of change.

The United Kingdom's National Health Service (NHS) faces a mounting workforce crisis, with compensation being a focal point of discontent. This editorial explores the real-term erosion of doctors' salaries in the UK, using the Retail Price Index as a more comprehensive measure of inflation. Comparisons with international standards reveal significant disparities, contributing to the emigration of medical talent. The NHS's increased reliance on agency locum doctors poses financial strain and affects continuity of patient care. Economic considerations debunk common counterarguments against pay restoration, emphasising the broader implications for healthcare delivery and societal well-being. The editorial concludes by advocating for policy measures to address this pay disparity as both an economic imperative and a strategic necessity to sustain the NHS.

Escalating competition in NHS: implications for healthcare quality and workforce sustainability.

The UK's National Health Service (NHS) faces escalating competition ratios for specialty training positions, with application rates dramatically outpacing the growth in available posts. This trend contributes to systemic bottlenecks and challenges traditional career progression pathways within medicine. In this evolving landscape, the once-certain career progression within medicine is now increasingly uncertain. This commentary explores the complex dynamics of increased medical school admissions against stagnant specialty training placements and the broader strategic implications for workforce planning within the NHS. It critically evaluates the implications of current funding policies, which seem to prioritise an expansion of nondoctor healthcare roles over the development of specialist training, raising concerns about the long-term patient care quality and safety. Key recommendations include a reassessment of medical education expansion, a review of funding allocation, increased support for specialty training, and government accountability for healthcare workforce planning. The urgent need for strategic policy reform is underscored to ensure that NHS can sustain a high-quality, specialist-led healthcare provision in the face of rising competition and workforce pressures.

The role of medical schools in UK students' career intentions: findings from the AIMS study.

OBJECTIVES: To investigate differences in students' career intentions between UK medical schools. DESIGN: Cross-sectional, mixed-methods online survey. SETTING: The primary study included all 44 UK medical schools, with this analysis comprising 42 medical schools. PARTICIPANTS: Ten thousand four hundred eighty-six UK medical students. MAIN OUTCOME MEASURES: Career intentions of medical students, focusing on differences between medical schools. Secondary outcomes included variation in medical students' satisfaction with a prospective career in the NHS, by medical school. RESULTS: 2.89% of students intended to leave medicine altogether, with Cambridge Medical School having the highest proportion of such respondents. 32.35% of respondents planned to emigrate for practice, with Ulster medical students being the most likely. Of those intending to emigrate, the University of Central Lancashire saw the highest proportion stating no intentions to return. Cardiff Medical School had the greatest percentage of students intending to assume non-training clinical posts after completing FY2. 35.23% of participating medical students intended to leave the NHS within 2 years of graduating, with Brighton and Sussex holding the highest proportion of these respondents. Only 17.26% were satisfied with the prospect of working in the NHS, with considerable variation nationally; Barts and the London medical students had the highest rates of dissatisfaction. CONCLUSIONS: This study reveals variability in students' career sentiment across UK medical schools, emphasising the need for attention to factors influencing these trends. A concerning proportion of students intend to exit the NHS within 2 years of graduating, with substantial variation between institutions. Students' intentions may be shaped by various factors, including curriculum focus and recruitment practices. It is imperative to re-evaluate these aspects within medical schools, whilst considering the wider national context, to improve student perceptions towards an NHS career. Future research should target underlying causes for these disparities to facilitate improvements to career satisfaction and retention.

The current landscape of intracranial aneurysms in Africa: management outcomes, challenges, and strategies-a narrative review.

Intracranial aneurysms (IAs) pose complex and potentially life-threatening challenges in Africa, where limited resources, restricted access to specialised healthcare facilities, and disparities in healthcare provision amplify the difficulties of management. Timely diagnosis and treatment are pivotal in preventing complications, including subarachnoid haemorrhage. Treatment options encompass observation, surgical clipping, endovascular coiling, and flow diversion. Positive outcomes observed in IA management in Africa include high survival rates, favourable functional outcomes, successful treatment techniques, and the absence of complications in some cases. However, negative outcomes such as postoperative complications, reduced quality of life, perioperative mortality, and the risk of recurrence persist. Challenges in IA management encompass limited access to diagnostic tools, a scarcity of specialised healthcare professionals, and an unequal distribution of services. Addressing these challenges requires interventions focused on improving access to diagnostic tools, expanding the number of trained professionals, and establishing specialised IA treatment centres. Collaboration, research, and capacity-building efforts hold significant importance in improving patient outcomes and reducing disparities in IA management across Africa.

From adversity to advancement: leveraging war-tested approaches for the post-conflict reformation of the Ukrainian healthcare landscape.

The Russo-Ukrainian Conflict has had significant repercussions on Ukraine's healthcare system, resulting in civilian casualties and damage to healthcare institutions. The disruption of personnel, medical supplies, and patient transportation has created considerable challenges for healthcare services. However, there are successful approaches from comparable contexts that can serve as a catalyst for post-conflict healthcare reformation in Ukraine. Key strategies include improving healthcare accessibility for marginalized populations through standardized essential health and surgical care packages, rehabilitating damaged facilities, strengthening primary care provisions, and supporting war survivors with disabilities. By adopting these proven practices, Ukraine can strengthen its healthcare system and facilitate a sustainable recovery, contributing to the country's resilience and ensuring essential healthcare services for its population.

Unusual presentation of Ramsay-Hunt Syndrome in kidney transplant patient.

Herpes Zoster (HZ) is caused by reactivation of latent varicella zoster virus (VZV) in craniospinal sensory neurons and is characterized by a painful erythematous rash in the affected dermatome. Although kidney transplant recipients who are chronically maintained on immunosuppressive regimens are considered at risk, there are only a few cases described. We report a well-documented case of a 50-year-old male kidney transplant recipient who presented Ramsay-Hunt syndrome with atypical neurological finds.

The role of the physician associate in the United Kingdom.

Physician associates (PAs) were introduced in the United Kingdom to address staffing shortages and fill service gaps, aiming to unburden doctors. Notably, in the backdrop of recent high-profile cases involving professional negligence and misconduct by PAs, the government has outlined a plan to expand the PA workforce and broaden their scope of practice. This commentary critically assesses the role, training, and regulation of PAs, juxtaposing the UK's approach with the US model. Concerns regarding disparities in training between PAs and doctors, potential impact on patient care quality, and lessons from the US experience raise substantial questions. Recommendations are provided to align with patient safety, professional standards, and the unique demands of the National Health Service (NHS). Despite the government's efforts to expand the PA workforce and its scope, uncertainties persist regarding their contribution to patient care and the implications for medical profesionals.

Mitochondrial DNA: Inherent Complexities Relevant to Genetic Analyses.

Mitochondrial DNA (mtDNA) exhibits distinct characteristics distinguishing it from the nuclear genome, necessitating specific analytical methods in genetic studies. This comprehensive review explores the complex role of mtDNA in a variety of genetic studies, including genome-wide, epigenome-wide, and phenome-wide association studies, with a focus on its implications for human traits and diseases. Here, we discuss the structure and gene-encoding properties of mtDNA, along with the influence of environmental factors and epigenetic modifications on its function and variability. Particularly significant are the challenges posed by mtDNA's high mutation rate, heteroplasmy, and copy number variations, and their impact on disease susceptibility and population genetic analyses. The review also highlights recent advances in methodological approaches that enhance our understanding of mtDNA associations, advocating for refined genetic research techniques that accommodate its complexities. By providing a comprehensive overview of the intricacies of mtDNA, this paper underscores the need for an integrated approach to genetic studies that considers the unique properties of mitochondrial genetics. Our findings aim to inform future research and encourage the development of innovative methodologies to better interpret the broad implications of mtDNA in human health and disease.

Variants in mitochondrial disease genes are common causes of inherited peripheral neuropathies.

BACKGROUND: Peripheral neuropathies in mitochondrial disease are caused by mutations in nuclear genes encoding mitochondrial proteins, or in the mitochondrial genome. Whole exome or genome sequencing enable parallel testing of nuclear and mtDNA genes, and it has significantly advanced the genetic diagnosis of inherited diseases. Despite this, approximately 40% of all Charcot-Marie-Tooth (CMT) cases remain undiagnosed. METHODS: The genome-phenome analysis platform (GPAP) in RD-Connect was utilised to create a cohort of 2087 patients with at least one Human Phenotype Ontology (HPO) term suggestive of a peripheral neuropathy, from a total of 10,935 patients. These patients' genetic data were then analysed and searched for variants in known mitochondrial disease genes. RESULTS: A total of 1,379 rare variants were identified, 44 of which were included in this study as either reported pathogenic or likely causative in 42 patients from 36 families. The most common genes found to be likely causative for an autosomal dominant neuropathy were GDAP1 and GARS1. We also detected heterozygous likely pathogenic variants in DNA2, MFN2, DNM2, PDHA1, SDHA, and UCHL1. Biallelic variants in SACS, SPG7, GDAP1, C12orf65, UCHL1, NDUFS6, ETFDH and DARS2 and variants in the mitochondrial DNA (mtDNA)-encoded MT-ATP6 and MT-TK were also causative for mitochondrial CMT. Only 50% of these variants were already reported as solved in GPAP. CONCLUSION: Variants in mitochondrial disease genes are frequent in patients with inherited peripheral neuropathies. Due to the clinical overlap between mitochondrial disease and CMT, agnostic exome or genome sequencing have better diagnostic yields than targeted gene panels.

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 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.

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.

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.

A Homozygous NDUFS6 Variant Associated with Neuropathy and Optic Atrophy.

Background: The NADH dehydrogenase [ubiquinone] iron-sulfur protein 6 (NDUFS6) gene encodes for an accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (complex I). Bi-allelic NDUFS6 variants have been linked with a severe disorder mostly reported as a lethal infantile mitochondrial disease (LMID) or Leigh syndrome (LS). Objective: Here, we identified a homozygous variant (c.309 + 5 G > A) in NDUFS6 in one male patient with axonal neuropathy accompanied by loss of small fibers in skin biopsy and further complicated by optic atrophy and borderline intellectual disability. Methods: To address the pathogenicity of the variant, biochemical studies (mtDNA copy number quantification, ELISA, Proteomic profiling) of patient-derived leukocytes were performed. Results: The analyses revealed loss of NDUFS6 protein associated with a decrease of three further mitochondrial NADH dehydrogenase subunit/assembly proteins (NDUFA12, NDUFS4 and NDUFV1). Mitochondrial copy number is not altered in leukocytes and the mitochondrial biomarker GDF15 is not significantly changed in serum. Conclusions: Hence, our combined clinical and biochemical data strengthen the concept of NDUFS6 being causative for a very rare form of axonal neuropathy associated with optic atrophy and borderline intellectual disability, and thus expand (i) the molecular genetic landscape of neuropathies and (ii) the clinical spectrum of NDUFS6-associated phenotypes.

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.

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.

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.