Within allied-health programs, gross anatomy is widely regarded as a foundational and content-dense course challenging instructors and students alike to manage an overwhelming volume of information within an increasingly constrained curriculum. In the late 1960's, the Duke University medical curriculum was redesigned to produce 'scientists-doctors' intensifying the instructional challenges of gross anatomy. In the wake of a series of unsuccessful experiments, comparative anatomists Matt Cartmill and James Shafland were recruited to develop and teach a medical gross anatomy course at Duke. Drawing on comparative anatomy, embryology, and evolutionary theory, Cartmill and colleagues developed a distinctive pedagogical framework organized around an idealized vertebrate metameric Bauplan-the Typical Body Segment (TBS)-with an accompanying textbook: Human Structure. Rather than trying to memorize details about sprawling sets of isolated structures, the TBS approach transforms learning gross anatomy into a series of stories about how evolution and development regionally pattern and differentiate Typical Body Segments into functionally specialized, interconnected modules. This article discusses the circumstances leading to the emergence of Cartmill's course-directorship and the TBS approach to teaching gross anatomy at Duke. We argue that the consistent use of a central homological schema as a starting point for narratives about the complex human form offers many pedagogical advantages, including reduced cognitive load, improved organization of anatomical knowledge, as well as a better grasp on patterns of interaction and variation among parts. Drawing on qualitative data from student course evaluations at High Point University, we further illustrate how this approach appears to shift students' orientation from rote memorization toward a conceptual understanding of anatomy. Finally, we document the diffusion and transformation of the TBS paradigm through faculty lineages, postdoctoral training, and allied health programs, highlighting its enduring influence on contemporary anatomy education. Together, this history and analysis underscore the value of centering evolutionary and developmental narratives in the teaching of human anatomy and documents the major contributions from Cartmill and other gross anatomists who taught with the TBS approach at Duke University.
The authors present an overview of the current evidence and management recommendations for evaluation and treatment of adults with acute ischemic stroke from distal- and medium-vessel occlusion (DMVO) for endovascular thrombectomy (EVT). The intended audiences are prehospital care providers, physicians, and allied health professionals. The Society of Vascular and Interventional Neurology Guidelines and Practice Standards committee formed a writing group to conduct a structured literature review on EVT for DMVO-related acute ischemic stroke and to draft practice recommendations in accordance with the Society of Vascular and Interventional Neurology Guidelines and Practice Algorithm. A structured literature search was conducted across PubMed, MEDLINE, and the Cochrane Library from January 2015 through February 2026, supplemented by manual review of reference lists from key studies and conferences. Recommendations were developed with consensus from an expert panel and the Guidelines and Practice Standards committee, with final approval by the Society of Vascular and Interventional Neurology Board of Directors. Data from all randomized controlled trials, prior meta-analyses, and subgroup analyses were extracted to evaluate the latest evidence on the safety and efficacy of EVT in patients presenting with DMVO acute ischemic stroke. The guideline outlines practical considerations for patient selection, procedural technique, and systems of care. These guidelines provide focused practical recommendations based on recent evidence regarding patient selection and decision-making for EVT in patients presenting with acute DMVO. Routine EVT for DMVO is not supported by current evidence; however, performing EVT in patients with disabling acute dominant M2 occlusion remains reasonable.
To map existing scientific evidence on the relationship between clinical supervision and burnout and burnout-related outcomes among nurses in clinical practice. Scoping review. The review followed the Joanna Briggs Institute methodology for scoping reviews. A total of 1396 records were identified and imported into Rayyan for screening. Data were synthesised descriptively using absolute and relative frequencies and presented in narrative and tabular form. Searches were conducted in February 2025 in CINAHL Complete, Nursing & Allied Health Collection: Comprehensive, MedicLatina, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, PubMed, and Web of Science Core Collection. Grey literature was searched in OpenGrey and the Portuguese Open Access Scientific Repository (RCAAP). No time or language restrictions were applied. Twenty studies were included. The evidence base was heterogeneous and predominantly cross-sectional. Clinical supervision in Nursing (CSN) was mainly delivered face-to-face and most frequently in group formats, with considerable variability in frequency, duration and theoretical grounding. Burnout was primarily assessed using validated instruments, particularly the Maslach Burnout Inventory. Nine studies reported inverse statistical associations between CSN and burnout or burnout-related outcomes. Clinical supervision is frequently associated with burnout and burnout-related indicators among nurses. Clearer intervention reporting, stronger theoretical grounding, and research designs capable of exploring temporal and contextual dynamics are needed to advance the field. Clinical supervision may represent a context-sensitive organisational support strategy within broader workforce well-being frameworks, particularly when structurally defined and supported by leadership. This review clarifies how clinical supervision has been conceptualised and evaluated, identifying reporting gaps and priorities for future research. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Review. No stakeholder consultation was undertaken. Future research should consider involving practising nurses and supervisors to define core CSN components. The protocol was registered in the Open Science Framework.
Incivility is a persistent challenge in nursing education with serious consequences for faculty well-being, student learning, and program climate. Research remains fragmented and inconsistently grounded in theory. To map the extent, range, and nature of research on academic incivility in nursing education, identify key themes, and highlight gaps to inform future research and practice. A scoping review guided by the Population-Concept-Context framework was conducted across PubMed, the Cumulative Index to Nursing and Allied Health Literature, PsycINFO, and Scopus (2000-2025). Studies included quantitative, qualitative, mixed-methods, and review articles addressing uncivil behaviors in academic and clinical settings. Forty-five studies met the inclusion criteria. Academic incivility was multifactorial and bidirectional, with negative effects on faculty well-being, student learning, relationships, and program climate. Gaps included inconsistent measurement, limited theoretical grounding, and minimal intervention testing. Findings underscore the need for theoretically informed, empirically tested strategies to foster civility and support healthy learning environments in nursing education.
This cross-sectional study investigates healthcare practitioners' perceptions of the implementation of artificial intelligence (AI) to enhance patient safety culture in Riyadh, Saudi Arabia, conducted from March to June 2025. The focus is on understanding how AI is perceived in the context of improving patient safety culture and aligning with Saudi Vision 2030 goals. The study employed a cross-sectional design and administered self-administered online surveys via convenience sampling among healthcare practitioners across multiple healthcare settings in Riyadh. The study targeted a population including doctors, nurses, and allied health professionals. A structured questionnaire was developed to assess perceptions of AI, including key variables such as perceived AI benefits, concerns about data privacy, and the necessity of training. Descriptive statistics were computed to characterize the sample, including age, gender, and profession. Findings revealed that most participants perceived AI as supportive of patient safety through improved diagnostic accuracy, reduced medical errors, and streamlined workflows, which participants believed may contribute to a stronger patient safety culture. Descriptive analyses suggested variation in perceptions across professional groups. The study found that healthcare practitioners in Riyadh generally perceived AI as a potentially valuable tool for supporting patient safety culture, particularly through improving diagnostic accuracy and reducing errors; however, concerns about data privacy and insufficient training remain significant barriers that must be addressed to ensure effective and safe AI integration. This study highlighted healthcare practitioners' positive perception of AI's role in enhancing patient safety culture in Riyadh. While AI is seen as beneficial in improving accuracy and reducing errors, challenges such as data privacy concerns and a lack of training were identified as barriers to its implementation. Not applicable.
To explore the experiences and factors associated with exclusive breastfeeding among women with postpartum depression (PPD). Following Arksey and O'Malley's methodological framework for scoping studies, searches were conducted in the CINAHL (Cumulative Index to Nursing and Allied Health Literature), PubMed, ScienceDirect, Scopus, EBSCO, Virtual Health Library, and Taylor & Francis databases. Full-text articles published in English, Spanish, and Portuguese between 2015 and 2024 on breastfeeding experiences among women up to 6 months postpartum with PPD. In total, 14 articles met the inclusion criteria. Data were charted using a spreadsheet matrix, which included the following information: authors, year of publication, country, study population, objectives, methods, and main findings. Extracted data were collated and analyzed using thematic synthesis to group recurring patterns into conceptual themes. Consequently, a variety of experiences with exclusive breastfeeding were identified among women with PPD and classified into three main categories: (a) rewarding, characterized by emotional bonding and a sense of accomplishment; (b) frustrating, often involving latching difficulties, low supply, or feelings of inadequacy; or (c) supportive, highlighting the critical role of health care provider encouragement and perseverance. These experiences were influenced by sociocultural, physical, psycho-emotional, and health care-related factors. The experiences of women with PPD who exclusively breastfeed are shaped by multiple interrelated factors that affect the breastfeeding process. Health care systems and public policies must integrate emotional and physical support strategies to strengthen breastfeeding, especially among women experiencing PPD.
Radical cystectomy with urinary diversion can substantially affect sexual function, body image, and intimate relationships. Structured sexual rehabilitation guidance that is specific to cystectomy and usable within nursing and rehabilitation pathways remains limited, especially for women and for patients living with urinary diversion. To develop a practice-oriented, evidence-informed and consensus-based framework for sexual rehabilitation across the cystectomy care pathway. We conducted a targeted narrative review of literature published between January 2000 and June 2025 in the Medical Literature Analysis and Retrieval System Online via PubMed, Embase, Cumulative Index to Nursing and Allied Health Literature, and the Cochrane Library, supplemented by cancer survivorship, ostomy, pelvic rehabilitation and sexual medicine guidance. Two reviewers screened records and mapped evidence by recovery phase, sex-related anatomy, diversion type, presenting problem and delivery setting. Recommendations were refined through two rounds of multidisciplinary author-panel consensus. The work was aligned with the Scale for the Assessment of Narrative Review Articles, intervention reporting principles from the Template for Intervention Description and Replication checklist, selected Appraisal of Guidelines for Research and Evaluation principles, and sex- and gender-sensitive reporting guidance. The revised framework is organised into prehabilitation, early postoperative care and late rehabilitation. It distinguishes nurse-led, shared interdisciplinary and specialist-only actions; specifies transition criteria between phases; integrates diversion-specific intimacy planning; and provides safety precautions for pelvic floor, manual therapy, pharmacological and psychosexual interventions. Outcome monitoring uses the International Index of Erectile Function, 5-item version; the Female Sexual Function Index, 19-item version; and the Body Image Scale, supplemented by goal-based and process indicators. The framework offers a cautious, adaptable route for integrating sexual health assessment, education, pelvic rehabilitation, stoma-related support, psychosexual communication and referral into routine cystectomy survivorship care. It should be implemented with local scope-of-practice governance and evaluated prospectively, including patient-partner co-design and long-term outcomes beyond 12 months.
To review and evaluate the literature for upstream, structural interventions that seek to improve maternal mortality rates among Black birthing people in the United States. Searches were conducted in PubMed, Embase, and Cumulative Index of Nursing and Allied Health Literature (CINAHL) using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Of the 883 articles returned, 623 abstracts were screened, and 7 articles met the criteria for inclusion. Articles were eligible for inclusion if they assessed the impact of structural interventions on maternal mortality, including among Black birthing people. Data were extracted on study designs, intervention type, outcomes, and health equity implications using a standardized template. Findings were synthesized thematically according to intervention type and included Access to reproductive health care and Social investment as effective maternal health policy. The findings revealed that maternal mortality is largely preventable and responsive to structural interventions. Interventions that addressed upstream determinants such as racism and social conditions demonstrated the greatest impact in reducing maternal mortality and improving equity. Targeted policy and programmatic interventions that address social and structural determinants of maternal health are essential to mitigating the maternal mortality crisis. Efforts that extend health care access, invest in public health infrastructure, and promote reproductive justice are particularly effective in improving outcomes for Black birthing people.
In this study, we sought to conduct a systematic review and meta-analysis of mental health outcomes in survivors of neurocritical illness. Literature databases [PubMed, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), and PsycInfo] were searched for terms relating to critical illness, intensive care, and outcomes from January 1970 to June 2024. English-language studies of adults with critically illness with a primary neurological diagnosis were included if they reported on mental health outcomes [specifically, depression, anxiety, post-traumatic stress (PTS), or general mental health]. Data extraction was performed, in duplicate, for prespecified variables related to study outcomes. Random effects meta-analyses were conducted to estimate pooled prevalence and symptom severity. Of more than 33,000 abstracts screened, 24 publications reported on mental health outcomes: 19 reported on depression outcomes, 11 on anxiety, 7 on PTS, and 8 on general mental health. The median [interquartile range (IQR)] time to first depression, anxiety, and/or PTS assessment was 3 (1.75, 12), 4.5 (1.1, 7.5), and 3 (0, 3) months, respectively. The most common assessment tools were the Hospital Anxiety and Depression Scale, Depression Subscale (HADS-D; n = 8) and the Hospital Anxiety and Depression Scale, Anxiety Subscale HADS-A (n = 8), and Post-traumatic Stress Disorder Checklist for the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (PCL-5)/Post-traumatic Stress Disorder Checklist, Civilian Version (PCL-C) for PTS (n = 4). General mental health outcomes were studied using seven unique tools at a median (IQR) follow-up time of 3 (0.5, 6) months. Pooled depression prevalence [95% confidence interval (CI)] was 24% (20-29%) among publications using HADS-D and 26% (16-38%) in publications using any assessment tool. Pooled anxiety prevalence was 37% (21-56%) using HADS-A and was 32% (18-51%) using any assessment tool. PTS prevalence was 14% (8-21%). Heterogeneity of assessment tools precluded a pooled analysis of general mental health. These findings highlight the burden of mental health symptoms following neurocritical care illness, with prevalences higher than the general population. These findings were impacted by substantial between-study heterogeneity-particularly in assessment tools and timing of evaluations-limiting precise prevalence estimation.
To explore Practice Development interventions and associated contextual factors to understand their impact on patient and staff outcomes and experiences in healthcare settings. Systematic review. Preferred Reporting Items for Systematic Reviews and Meta-analysis informed design, conduct and management. A systematic approach was taken, utilising multiple reviewers and consensus methods. Mixed Methods Appraisal Tool informed quality appraisal. Qualitative findings were analysed using Reflexive Thematic Analysis. Quantitative results are presented as a narrative summary. CINAHL; MEDLINE; PubMed; Scopus; ScienceDirect; Nursing and Allied Health; Cochrane Library; Internurse.com; The Kings Fund; GOV.UK and Trip Database were searched between 1st January 1980 to 5th January 2026. Twenty-nine studies were included. Eighteen studies met all quality assessment criteria. Limited quantitative data was available, and inconsistent outcome measures constrained quantitative analysis. Qualitative analysis generated three themes: (1) Shaping Practice: the interplay of organisational context, culture, and structure, (2) Enablers and constraints in Practice Development, (3) Collective empowerment. Across diverse study designs, the majority of studies indicate that PD contributes positively to staff working environments and the contexts in which patient care is delivered. However, current findings do not demonstrate consistent improvements in clinical outcomes or quality of life. Practice Development may contribute to improvements in care environments for patients and staff, respectively. This review highlights knowledge gaps in the generalisability and transferability of Practice Development that would benefit from further exploration. Practice Development may enhance healthcare environments, but further research is needed to determine if these benefits impact upon clinical outcomes. Preferred Reporting Items for Systematic reviews and Meta-Analyses. No patient or public contribution. PROSPERO registration number: CRD42024557949.
Health, immigration status, race, and gender are intersecting concepts that reveal higher rates of acute and chronic mental health concerns among women. This qualitative systematic review aimed to identify, critically appraise, and synthesize qualitative evidence on how women living with diverse immigration statuses experience mental health interventions in Canada. Literature was searched using Medline (Ovid) and then translated into each of the following databases: Cumulative Index for Nursing and Allied Health Literature (CINAHL Ebsco), PsycINFO (Ebsco), Web of Science, CINAHL, Medline and PsycINFO; and Web of Science. Using Joanna Briggs Institute (JBI) methods and Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, studies published between 2003 and 2025 were identified and screened within Covidence for quality using the standard JBI critical appraisal checklist for qualitative research. A total of 107 findings consisting of participants' verbatim quotes were extracted from 18 studies and aggregated into the following synthesized findings: (1) Women's socio-emotional well-being, (2) Culturally misaligned mental health care among racialized women, (3) Women's cultural preferences and access conditions, and (4) Women's recommendations for improving mental health care and support. Implications of the review findings address gaps in equity-informed mental health services tailored to women living at the intersections of racism and diverse immigration status in Canada.
ContextPhysical inactivity is a major contributor to chronic disease, disability, and premature mortality in the United States and is associated with substantial healthcare expenditures. Although regular physical activity improves health outcomes, individuals with chronic conditions often require structured supervision to exercise safely and effectively. Building upon this context, the objective of this review is to synthesize evidence on the clinical, psychosocial, and economic impacts of supervised exercise interventions (SEIs) and to examine policy and implementation factors influencing their adoption. To achieve this objective, a structured literature review was conducted, guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) framework.Eligibility CriteriaStudies published in English between 2010 and 2024 that involved adults aged 18 years or older and evaluated supervised exercise interventions with reported clinical, psychosocial, economic, or policy-related outcomes were included.Study SelectionPubMed, Web of Science, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) were searched using predefined keywords. Reference lists of relevant studies were also reviewed to identify additional eligible articles.Main Outcome MeasuresClinical outcomes (eg, mortality, aerobic capacity, HbA1c), psychosocial outcomes (eg, adherence, depression, quality of life), and economic and policy outcomes (eg, cost-effectiveness, reimbursement).ResultsTwenty studies met the inclusion criteria. Across cardiovascular, metabolic, oncologic, pulmonary, and geriatric populations, SEIs were associated with improved clinical outcomes, including reduced rehospitalization and mortality, enhanced aerobic capacity, improved glycemic control, and reductions in fatigue and depressive symptoms. SEIs were cost-effective across disease categories, with several studies reporting healthcare cost savings within 1 year. However, disparities in referral and participation persisted among racial and ethnic minorities, rural populations, and individuals with lower socioeconomic status.ConclusionSEIs are effective and scalable strategies for managing chronic diseases and preventing secondary complications. Evidence indicates that supervised exercise improves clinical, psychosocial, and economic outcomes across diverse populations. Expanding reimbursement and strengthening integration within health systems will be critical to improving equitable access to SEIs.
The Imposter Phenomenon (IP)-doubting one's abilities despite clear achievements-is well-documented among healthcare professionals but has never been studied among practicing chiropractors, who face unique challenges including professional isolation and ambiguous healthcare identity. This study aimed to determine IP prevalence among South African chiropractors and investigate associations with age, gender, years of experience, and province. A cross-sectional survey using the validated Clance Imposter Phenomenon Scale (CIPS) was distributed via email to all 960 chiropractors registered with the Allied Health Professions Council of South Africa. Data were collected online from 25 March to 17 May 2024. Descriptive statistics, independent-samples t-tests, and one-way ANOVA were used; results are interpreted through effect sizes (Cohen's d) and 95% confidence intervals, with exact p-values reported as continuous evidence measures. Cronbach's alpha assessed reliability. The study followed STROBE and CHERRIES guidelines. Of 159 chiropractors (16.6% response rate), mean age was 37.8 years (SD = 10.8); 61.6% were female. Mean CIPS score was 50.78 (SD = 16.82), indicating moderate IP. Severity distribution: 33.3% few, 39.0% moderate, 22.6% frequent, 5.0% intense IP (66.6% at or above moderate threshold). Females scored higher than males (55.66 vs. 42.93; t(147.69)= - 5.25, p < 0.001; d = 0.85). Chiropractors  ≤ 35 years scored higher than those  > 35 years (53.52 vs. 47.95; t(152) = 2.05, p = 0.042; d = 0.33). Chiropractors with ≤ 10 years of experience showed a non-significant trend toward higher IP scores than those with  > 10 years (52.90 vs. 47.94; two-tailed p = 0.066; d = 0.30). No provincial differences were found (F(3,155) = 0.62, p = 0.601). Cronbach's α was 0.94. Moderate to intense IP affects two-thirds of chiropractors in this South African sample, particularly females and early-career practitioners. These findings highlight the need for targeted mental health interventions, mentorship, and peer support. This first study of IP among practicing chiropractors provides evidence for practitioner well-being initiatives with implications for chiropractic education, professional development, and retention.
Ferroptosis resistance is a major challenge in cancer therapy, contributing to poor prognosis and unsatisfactory treatment outcomes. Thus, identifying key regulators of ferroptosis is essential for developing strategies to overcome this limitation. Mixed lineage kinase domain-like protein (MLKL) is well established as the executioner of necroptosis, but emerging evidence suggests broader functions beyond necroptosis. A previous study demonstrated that MLKL regulates ferroptosis in an acute kidney injury model. However, its role in ferroptosis regulation in cancer remains largely unexplored. Bioinformatics analyses revealed that MLKL expression positively correlates with glutathione metabolism-related genes in colorectal cancer (CRC) patients and with reduced sensitivity to GPX4 inhibitors across pan-cancer cell lines. Functional studies demonstrated that MLKL depletion sensitizes not only CRC cells but also multiple cancer cell types to ferroptosis induced by GPX4 inhibitors. Mechanistically, MLKL-deficient CRC cells exhibited reduced intracellular glutathione levels and dysregulation of the NRF2/KEAP1/SLC7A11 antioxidant axis. However, KEAP1 knockdown in MLKL-depleted cells partially reduced ferroptosis sensitivity, indicating that additional mechanisms are involved. Proteomic analysis identified CHMP5, a component of the ESCRT-III membrane repair machinery, as a key downstream effector associated with MLKL. MLKL depletion suppressed CHMP5 expression and impaired its translocation to the plasma membrane during ferroptosis induction. Consistent with defective membrane repair, MLKL-knockdown CRC cells exhibited increased HMGB1 release following GPX4 inhibitor treatment, indicating enhanced membrane damage. Notably, CHMP5 overexpression reduced ferroptosis in MLKL-knockdown cells, highlighting that MLKL regulates ferroptosis susceptibility in part through CHMP5-dependent ESCRT-III signaling. This study reveals a previously unrecognized role for MLKL in ferroptosis regulation through coordinating NRF2/KEAP1/SLC7A11-mediated glutathione metabolism and ESCRT-III-dependent membrane repair. These findings identify MLKL as a potential regulator of ferroptosis resistance and warrant further studies to evaluate the therapeutic relevance of MLKL-targeting strategies in colorectal cancer.
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Leishmaniasis is a neglected tropical disease (NTD) affecting millions worldwide. Current treatments have limitations, highlighting the need for new strategies for leishmaniasis drug discovery. Herein, we utilized a benchmarking-informed structure-based virtual screening (SBVS) strategy against Leishmania major folate pathway, especially via targeting pteridine reductase 1 (PTR1). Firstly, representative bioactive molecules against Lm-PTR1 were compiled. Secondly, a challenging DEKOIS 2.0 benchmark set was generated to assess the screening performance of three docking tools, FRED, AutoDock Vina, and PLANTS. Interestingly, FRED showed the best screening performance, with pROC-AUC of 0.84 and EF 1% of 12.5. Consequently, as an example, an ensemble VS of NANPDB using FRED against PTR1 was conducted. The results nominated three candidates for further investigations, namely Anastatin A, valoneic acid dilactone, and 1,6-di-O-galloyl glucose. To assess the binding stability of the candidates, four MD simulations for 500 ns including folic acid - PTR1 complex system as a reference were conducted. Consequently, MM-GBSA calculations and MD profiles confirmed the stable binding of valoneic dilactone and 1,6-di-O-galloyl glucose and ranked them superior to the reference folic acid. These results suggest the ability of both candidates to hinder the access of folic acid to the cofactor NADPH and hence modulate the catalytic function of Lm-PTR1. The identified candidates are recommended for subsequent in vitro evaluations in future investigations. Overall, this benchmarking strategy against Lm-PTR1 can be broadly applied to any accessible compound database for SBVS campaigns. The benchmark dataset for Lm-PTR1 will be made publicly accessible on www.dekois.com.
Cytoskeletal proteins play a crucial role in providing mechanical support and regulating key cellular processes such as cell proliferation, migration, and invasion. Cytoskeletal damage has been increasingly regarded as a contributing factor in impairing these cellular processes in cancer. Moreover, induction of cell death pathways has been linked to cytoskeletal destabilization. However, the effect of cytoskeletal disruption on cell death mechanisms in ovarian cancer (OC) remains elusive. Several natural compounds have been demonstrated to initiate cytoskeletal destabilization as a mechanism to promote cell death. We have previously shown that one such natural compound derived from marine sources, Malformin A1 (MA1), exhibits high toxicity toward both cisplatin-sensitive (A2780S) and cisplatin-resistant (A2780CP) OC cell lines. Thus, here we evaluate the impact of cytoskeletal destabilization by MA1 treatment on OC cell death by analyzing the expression levels of apoptosis, autophagy, and DNA damage-related genes. Our findings show MA1 treatment significantly downregulated key cytoskeletal proteins while also decreasing the expression of pro-apoptotic markers, suggesting alternative cell death mechanisms. Autophagy-related analyses demonstrated enhanced LC3BI to LC3BII processing, indicating autophagy activation with elevated γ-H2AX levels confirming substantial DNA damage in MA1-treated cells. Notably, MA1 was able to induce pyroptotic cell death, as evidenced by increased caspase-1 expression. Moreover, molecular docking analysis revealed that MA1 displayed the strongest binding affinity for vimentin, GAPDH, and β-tubulin, providing mechanistic insights into its ability to disrupt cytoskeletal integrity and induce nonapoptotic cell death through multiple pathways, highlighting MA1's potential as a promising therapeutic candidate.
In addition to a gap detection threshold, an auditory gap detection task also provides information on response time. This study investigated the association of response time from an adaptive gap detection task with two validated measures of cognitive processing speed as well as scores from a cognitive screener, while accounting for the effects of age, peripheral hearing ability, and HIV status. Participants (age 17-45 years) were from a prospective cohort study in Dar es Salaam, Tanzania with normal hearing ability and no reported neurological diseases. The final sample included 283 unique subjects (158 living with HIV, 125 without HIV) matched on age and sex. Multiple linear regression models were employed to assess the relationship between gap response time and cognitive processing speed scores from the Tests of Variables of Attention, Cogstate test battery, and Montreal Cognitive Assessment. Regression analysis showed significant relationships between gap response time and all processing speed scores, except one. Age showed varying degrees of association with different processing speed measures, but peripheral hearing ability did not show any significant relationship with speed measures. This study identifies a link between cognitive processing speed and gap detection response times. With further validation, gap detection response times could emerge as a straightforward yet informative measure of cognitive processing speed and would expand the clinical usefulness of the gap test. In the audiology clinic, this measure may hold promise as a tool for detecting and monitoring cognitive decline.
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Wellbore instability driven by reactive clay swelling remains a critical and costly challenge in the application of water-based drilling fluids. The core objective of this study is to evaluate the fundamental clay hydration inhibition potential of CeO2-Bi2O3 bimetallic nanocomposite to ensure robust operational stability. The nanomaterial was synthesized via co-precipitation, subjected to 1-hour ultrasonic homogenization and 1-week static aging, and subsequently evaluated using dynamic light scattering, zeta potential, static filtration (100 psi, 60 °C), and hot rolling tests (105 °C). Experimental results demonstrated that an optimal nanocomposite concentration of 500 ppm fundamentally arrests clay hydration via double-layer compression (- 38.7 mV) and pore plugging, yielding an exceptional dynamic shale cutting recovery of 93%, significantly outperforming the standard 3 wt% KCl benchmark (78%). System compatibility assessments proved the additive acts as a non-damaging agent, maintaining vital plastic viscosity and yield point parameters while improving API filtration control in polymeric (9.5 to 7.8 mL) and weighted mud systems. In conclusion, the CeO2-Bi2O3 nanocomposite serves as a highly efficient chemical inhibitor that mechanically stabilizes wellbores and prevents fluid invasion, presenting a viable, non-damaging alternative for advanced drilling fluid formulations.