British Journal of Biomedical Science最新文献

Breast cancer remains a leading cause of mortality among women globally, with disproportionately high incidence, aggressive subtypes and poor outcomes in African and African-ancestry populations. While inherited BRCA1/BRCA2 mutations drive hereditary risk, recent evidence highlights the critical role of BRCA1 promoter methylation especially in sporadic and triple-negative breast cancers (TNBC), which disproportionately affect African-descended women. This review synthesises the genetic and epigenetic landscape of breast cancer susceptibility in African and diaspora cohorts, emphasising unique mutation spectra, elevated BRCA1 methylation frequencies and their prognostic/treatment implications. Systemic barriers including limited screening infrastructure, workforce shortages, structural racism, and cultural challenges exacerbate late diagnosis and inequities. We evaluate emerging solutions such as telemedicine, AI-enhanced diagnostics, and mobile platforms, alongside the need for context-specific research and investment to integrate molecular insights with innovative health system interventions. This synthesis underscores the urgency of addressing biological and structural drivers to close breast cancer outcome gaps in Africa and similar low- and middle-income settings.

Background: Ageing, a physiological process, and obesity, a pathological condition, are both associated with several metabolic alterations including energy imbalance, altered body composition, chronic low-grade inflammation, lipotoxicity, glucotoxicity, insulin resistance and mitochondrial dysfunctions. During ageing mitochondrial capacity declines and oxidative stress increases. However, the biphasic model of age-associated mitochondrial functions indicates that, before the ageing-associated decrease in mitochondrial respiration, this parameter increases in the transition from young adult to middle-aged, with a concomitant mild increase in ROS production that stimulates an antioxidant response, limiting the ageing-associated damages. Ageing-associated body composition changes can lead to sarcopenia, one of the most debilitating dysfunctions in the elderly. The sarcopenia is a known geriatric syndrome characterized by the loss of muscle mass and strength and mitochondria dysfunctions. These alterations of the disease can be exacerbated by obesity. Here, in an experimental animal model of diet-induced obesity, we evaluated the time-course changes in body composition, inflammatory and oxidative stress parameters, mitochondrial functions and antioxidant responses.

Methods: Male Wistar rats at 60 days of age were divided into two experimental groups: the first group received a standard diet; the second group received a high-fat diet (HFD). The animals from both groups were fed with the appropriate diet for 1, 3, 6, 12, or 24 weeks (n = 6 for each group and time point). At each time point, the animals were sacrificed and dissected to obtain the organs and tissues needed for analysis.

Results: Our results clearly showed the contribution of high-fat diet in anticipating and worsening the metabolic and inflammatory alterations associated with age, in particular, highlighting the role of mitochondria in attempting the regulation of physiological alterations typical of aging.

Conclusion: In the HFD group the antioxidant defences fail their job because of the additional inflammation and oxidative stress due to the diet. HFD is related to decreased animals' activity. Thus, cannot be excluded that the reduced physical activity may contribute, at least in part, to the impaired mitochondrial functions in the skeletal muscle of HFD rats. Altogether, our results clearly highlighted the contribution of HFD in anticipating and worsening the metabolic and inflammatory alterations associated with aging, including sarcopenia.

Increased pulmonary vascular pressures due to vascular remodeling, elevated vascular resistance, and vasoconstriction characterize Pulmonary Arterial Hypertension (PAH). The narrowing of the pulmonary arteries and obstruction of blood flow increase the Right Ventricular (RV) afterload, forcing the RV to undergo structural and functional changes. While adaptive remodeling leads to RV compensation by maintaining function, maladaptive remodeling leads to RV decompensation, characterized by worsening function and eventual failure. At present, there is no effective treatment for these patients as therapies for left ventricular failure are ineffectual, and there are no therapies specifically targeting the RV. Therefore, there is a clear need to understand the pathophysiology of RV failure and to identify the differences between adaptive and maladaptive RV remodeling. This study analyzes changes in polyadenylation site usage, a process known as alternative polyadenylation (APA), in RV failure. APA is a mechanism used to regulate mRNA maturation that can result in either shortening or elongation of the mRNA 3'UTR. By analyzing APA patterns in RV tissue from donor controls and patients with compensated and decompensated RV failure, we demonstrate a pattern of 3'UTR elongation that is present in decompensated RV failure and not in compensated or control RVs. Further, altered APA was also detected in 3 distinct rat models of PH, where 15 transcripts had shared APA alterations across both rat models and human disease. Our study provides an unbiased approach to identifying the molecular changes leading to RV dysfunction while pinpointing novel therapeutic targets that can be leveraged for intervention. These APA signatures may serve as biomarkers to distinguish adaptive from maladaptive RV remodeling. In addition, the RNA-processing machinery that regulates APA, such as NUDT21 and CPSF6, represents potential therapeutic targets for RNA-based interventions. Together, our findings link RNA processing to diagnostic and therapeutic opportunities in right heart failure.

Widening participation among the clinical laboratory scientific workforce is essential to meet future needs of healthcare systems. The advantages of more diversity in this clinically pivotal workforce include better decision making, improved diagnostics and a wider pool of appropriately trained applicants for new and advanced posts. This review summarises a sustainable "trickle up approach" to increase diversity and widen participation at all levels of the career pathway for clinical laboratory scientists with a focus on socioeconomically disadvantaged and minoritised scientists. Issues of access to appropriate degrees are present years in advance of university application and can be addressed through meaningful outreach programmes from universities and professional bodies. Interventions to broaden degree entry access including foundation routes have proven efficacy, whereas the role of degree apprenticeships in widening participation appears to be minimal, currently. There is a higher proportion of ethnic minorities, particularly black students, who don't complete their degree programme or attain lower awards than colleagues. Contributory factors include curriculum design along with psychosocial deficiencies in delivery. Decolonising and making biomedical science curricula and delivery more inclusive have proven effective in reducing these risks. Furthermore, socioeconomically disadvantaged students face a new challenge from generative artificial intelligence tools, where those that can pay get access to more powerful tools, creating a new gap, unless these tools are used judiciously and free at point of use. A graduate is required to complete training in a clinical laboratory to gain HCPC or equivalent registration, these places are competitive, and often unpaid. This appears to be a key barrier to widening participation, with a majority of graduates not pursuing careers as Biomedical Scientists. A state and financially supported training programme is required to broaden involvement at and post-registration. There is a paucity of information regarding the makeup of the workforce at promotional grades. However, an analysis of postgraduate study and research avenues reveals challenges for those from minoritised backgrounds and working mothers. These can be addressed through diversity in academic institutions and tailored, personalised approaches to research for working mothers to maximise participation at management and clinical leadership roles in the diagnostic laboratory.

The poor solubility and permeability of Biopharmaceutics Classification System (BCS) Class IV drugs pose major challenges to achieving sufficient oral bioavailability and therapeutic efficacy. Improving drug dissolution is a key strategy to enhance bioavailability, which in turn can enable more effective targeting of drugs to their site of action. To address this, we formulated cefdinir, a model BCS Class IV compound, using three amorphisation strategies; solid dispersions, mesoporous silica dispersions, and co-amorphous systems to assess the impact of formulation on stability and dissolution. Formulations were prepared via spray drying and solvent immersion using different drug-to-polymer ratios, with miscibility predicted using Flory-Huggins theory. The amorphous nature of each system was confirmed using differential scanning calorimetry (DSC), polarised light microscopy (PLM), and powder X-ray diffraction (PXRD). Dissolution studies revealed significantly enhanced drug release from all formulations compared to crystalline cefdinir. Among them, solid dispersion and co-amorphous systems exhibited the greatest improvement in dissolution rates, attributed to their ability to maintain supersaturation and inhibit crystallisation via kinetic stabilisation. These systems also showed better physical stability under non-sink aqueous conditions. However, mesoporous silica dispersions demonstrated superior long-term stability, retaining over 95% drug content and preserving their amorphous structure across three storage conditions (25 °C/0% RH, 40 °C/0% RH, and 40 °C/75% RH) for 6 months. This was attributed to the confinement of the drug within silica pores and the absence of hygroscopic excipients. Overall, this study highlights the distinct advantages of each approach, emphasising the importance of balancing dissolution enhancement with solid-state stability, and supports the use of theoretical modelling to guide rational formulation design for poorly soluble drugs to improve oral bioavailability and enable more targeted therapeutic outcomes.

Antimicrobial resistance (AMR) has caused a global public health crisis, contributing to approximately five million deaths in 2019 and predicted deaths of approximately ten million annually by 2050. This equates to approximately 1.4-fold more deaths annually from AMR in 2050 than the entire COVID-19 pandemic to date. To tackle this AMR pandemic, regulatory and policy frameworks have been prepared at local, national and international levels with multi-faceted proposals and advances encompassing surveillance, diagnostics, infection prevention, antibiotic prescribing and variation of existing and novel treatment approaches. This narrative review primarily focuses on research and development which have been documented over the last five years in relation to therapeutic approaches at various stages in clinical development and the potential role that vaccines can play in the fight against AMR. This review provides an overview on antibacterial drugs, including novel classes of antibiotics, which have been recently approved, as well as combination antibiotic therapy and the potential of repurposed drugs. The potential role of novel antimicrobial, antibiofilm and quorum sensing inhibitors, such as antimicrobial peptides, nanomaterials and compounds from the extreme and natural environments, as well as ethnopharmacology including the antimicrobial effects of plants, spices, honey and venoms are explored. Novel therapeutic approaches are critically discussed in terms of their realistic clinical potential, detailing recent and ongoing trials to highlight the current interest of these approaches, including immunotherapy, bacteriophage therapy, antimicrobial photodynamic therapy (aPDT), antimicrobial sonodynamic therapy (aSDT), nitric oxide therapy and microbiome manipulation including faecal microbiota transplantation (FMT). The potential of predatory bacteria as living antimicrobial agents is also discussed. Importantly, there have been many technological developments which have enhanced bioprospecting and research and development of novel antimicrobials which this review draws attention to, including artificial intelligence, machine learning and Organ-on-a-Chip devices. Finally, key messages from the recent World Health Organization report into the role of vaccines against AMR provides an interesting perspective relating to prevention which can be of significance in tackling the AMR burden.

Introduction: The final year Professional Development for Biomedical Scientists module at Aston University strives to create competent practitioners upon graduation. Recent research identified that 93% of NHS pathology employers within the United Kingdom, do not believe that new Biomedical Scientist graduates possess the skills required for a Band 5 interview. Additionally, 73% of these employers believed students were not fully prepared for the NHS interview process. Therefore, Aston University redeveloped an existing mock interview component to align directly with NHS interview processes. This research aimed to evaluate the effectiveness of the redesigned "Job interview" assessment upon student understanding of their own transferable skills and readiness for future laboratory employment.

Methods: Researchers evaluated the effectiveness of the assessment through a mixed-method approach survey. The survey was launched to students following their completion of the Medical Laboratory Assistant video interview, using the interview software Interview360. The survey sought to identify if after the interview assessment students felt they could demonstrate with examples, using the STAR technique, several key skills sought by employers.

Results: Data was collected from both the 2023-2024 and 2024-2025 final year Biomedical Science cohort. Collected data has been overwhelmingly positive, with 97% of students agreeing that they "understand the types of questions they would be asked in an NHS interview" (p < 0.0001). In terms of the key skills sought for by employers, 93% of respondents agreed or strongly agreed that they felt they could communicate within a specific situation example their understanding of "Basic equipment skills" (p < 0.0001) and their "understanding of laboratory results" (p < 0.0001). Whilst 99% of respondents agreed or strongly agreed that they could demonstrate their "understanding of laboratory health and safety" (p < 0.0001). Furthermore, respondents reported that the job interview assessment assisted them to demonstrate their transferable skills, including teamwork (81.6%) and organisational skills (71.05%).

Discussion: Student responses identify a positive change to their job interview skills and understanding of the NHS interview process. Here, researchers present the re-modelled graded job interview assessment with the NHS aligned mark scheme, along with four pre-assessment workshops as a process to embed employability into the Biomedical Science curriculum.

Introduction: Research shows completing a placement year is associated with improved academic and employment outcomes. For Biomedical science courses, pathology placements allow completion of the Institute of Biomedical Science (IBMS) registration training portfolio and obtaining Health and Care Professions Council (HCPC) registration post-graduation. This study sought to identify the barriers biomedical science students across the West Midlands region of England face when completing a placement year, to identify strategies which promote inclusivity to overcome these barriers.

Materials and methods: Level 5 and Level 6 students from Aston, Coventry, Keele and Wolverhampton universities were invited to complete a questionnaire which included a mixture of Likert scale and free-text responses. A range of questions assessed student perceptions on the importance of placement opportunities, as well as identifying factors which were important when pursuing a placement year. Likert scale data was analysed quantitatively, and a Mann Whitney U or Kruskal Wallis test were used to infer significance, whereas free text responses were analysed using thematic analysis.

Results: A total of 107 students completed the questionnaire. Students who declared a disability were less likely to undertake an unpaid placement compared to their peers (p = 0.013). Of those students who declared caring responsibilities, 33.3% chose not to apply for a placement year compared to 18.2% of those who did not have caring responsibilities (p = 0.020). Participants reported that funding was important when deciding whether to pursue a placement (88.8%). Thematic analysis revealed several recurring themes deterring student placement applications, including financial support and placement availability within their geographical area. Students valued the importance of professional recognition following the placement and the development of technical and transferable skills.

Discussion: Many of the barriers are fuelled by financial constraints which deter students from applying to placement positions. Despite the need to increase the Biomedical Scientist workforce, the strategies to increase training opportunities are not well established. Equity in placement funding from centralised sources is key to ensuring Biomedical Scientists can excel in their professional careers. Through availability of funding, marginalised populations will have the same opportunities as their peers therefore producing more employable graduates to meet pathology workforce demands.

Introduction: Urbanization often correlates with reduced diversity in human gut microbiota, with notable variations observed between the gut microbiota among the Indigenous communities in rural villages and urban citizens residing in modern settings. Although research has been conducted on the gut microbiota of healthy adults in Malaysia, there has been no study characterising the gut microbiota of Sarawak's Indigenous communities to date. This study aims to fill this gap by examining the gut microbiota profile of the Sarawak Indigenous groups (specifically Orang Ulu subethnic groups Kayan and Kenyah), comparing them with semi-urbanized Selangor Indigenous communities from Peninsular Malaysia (represented by Proto Malay subtribe Temuan) and Urban communities from Kuala Lumpur.

Methods: We conducted a cross-sectional study and collected stool samples from 86 Indigenous participants from Sarawak and compared them with published data from 45 Malaysian Indigenous participants from Selangor and 18 Urban citizens living in Kuala Lumpur City. DNA was extracted from the stool samples, and subsequently, the V4 hypervariable region of the 16S rRNA gene was sequenced. The raw sequence data were analyzed using the Quantitative Insights into Microbial Ecology 2 (QIIME2) bioinformatics platform.

Results and discussion: Analysis revealed that the Sarawak Indigenous community exhibited the highest gut microbial diversity, followed by the Peninsular Indigenous and Urban groups. The Prevotella/Bacteroides (P/B) ratio revealed that the Sarawak Indigenous community showed the highest presence of Prevotella at 88.3%, while Kuala Lumpur Urban residents had a predominantly Bacteroides composition at 61%. The Selangor Indigenous community also exhibited a Prevotella-dominant profile at 75.5%. VANISH microbes (Prevotella, Faecalibacterium, and Succinivibrio) were identified as dominant genera in the Sarawak Indigenous gut microbiota, contrasting with the BIoSSUM microbe (Bacteroidaceae) found in the Kuala Lumpur cohort.

Conclusion: This study sheds light on the distinct gut microbiota composition of Sarawak's Indigenous community, which has not been previously explored. It highlights the impact of urbanization on gut microbiota composition during lifestyle transitions.