In mechanically ventilated patients, the clinical and echocardiographic presentation of pericardial tamponade differs from the classic spontaneous-breathing paradigm. Positive-pressure ventilation (PPV) increases pleural and pericardial pressures, narrows the transmural filling gradient, augments ventricular interdependence, and can precipitate tamponade physiology at smaller effusion volumes. Consequently, the classic Doppler cues, such as large respiratory variation in mitral/tricuspid inflow, are commonly blunted, reversed, or absent, and right-sided chamber collapse can be intermittent or phase-shifted across the ventilatory cycle. Therefore, diagnosis depends on integrating clinical suspicion, hemodynamics, and multiple echocardiographic features, including effusion morphology (often loculated/posterior in the postoperative setting), right-atrial systolic and right-ventricular diastolic collapse (timed to the cardiac cycle), venous congestion surrogates (inferior vena cava plethora and superior vena cava/hepatic venous Doppler findings), and direct evidence of reduced stroke volume. Transthoracic echocardiography (TTE) is fast and, when the window is good, can provide a safe guide to life-saving pericardiocentesis. Thus, TTE is established as a first-line approach in both intra-hospital emergencies and in prehospital settings. However, in the context of PPV, tamponade may be underrecognized because suboptimal acoustic windows, postoperative dressings, emphysema, thoracic trauma, or prone positioning can limit TTE. Across 40 physiological, diagnostic accuracy, and impact studies, early TTE after cardiac surgery showed only modest performance in surgically confirmed tamponade (area under the curve of approximately 0.64 and a positive predictive value of approximately 58%). Meanwhile, about half of the postoperative effusions were predominantly posterior or loculated. In mechanically ventilated intensive care unit cohorts, transesophageal echocardiography (TEE) resolved almost all prespecified clinical questions and changed therapy more often than TTE (97% vs. 38% and 36% vs. 16%, respectively). These findings support a physiology-anchored approach in which TTE remains first-line; meanwhile, TEE should be considered early when clinical suspicion is moderate-to-high, and TTE is nondiagnostic or when posterior/loculated or regional tamponade is suspected during PPV.
Allergic conjunctivitis (AC) is an ocular surface disease characterized by immune-mediated inflammation that can significantly impair quality of life. This review explores recent advances in understanding the immunological and molecular mechanisms underlying AC, highlighting local and systemic immune responses and their roles in disease pathogenesis and progression. Particular attention is given to the influence of genetic and epigenetic factors, which may contribute to individual susceptibility and variability in clinical presentation. Finally, this review discusses emerging evidence on clinical phenotypes and immunological endotypes in ocular allergy, emphasizing their relevance for the development of targeted, personalized, and precision therapies.
Heart failure with preserved ejection fraction (HFpEF) has emerged as the predominantform of heart failure (HF) worldwide and is increasingly recognized as a systemic syndrome closely linked to metabolic dysfunction. Furthermore, metabolic dysfunction-associated steatotic liver disease (MASLD), a highly prevalent yet often underrecognized comorbidity in patients with HFpEF, has attracted increasing attention. Accumulating epidemiological evidence demonstrates a significant association between MASLD and HFpEF, suggesting shared pathophysiological foundations that extend beyond coincidental coexistence. Mechanistically, MASLD contributes to the development and progression of HFpEF through a network of interconnected pathways, including chronic low-grade inflammation, insulin resistance (IR), dysregulated lipid metabolism, endothelial dysfunction, the gut-liver-heart axis, and as liver-derived mediators that influence cardiac structure and function. These overlapping mechanisms underlie the pronounced clinical and phenotypic heterogeneity of HFpEF and may help explain the limited efficacy of conventional heart failure therapies. This review summarizes current diagnostic and therapeutic strategies for HFpEF and MASLD and proposes an integrated, multiorgan framework to improve clinical recognition and management. A deeper understanding of liver-heart interactions is essential to redefining cardiometabolic disease, shifting from an organ-centric perspective toward a more integrated, mechanism-based approach.
Contemporary classification systems differ in their conceptualization of ADHD as either an externalizing or neurodevelopmental condition, with both perspectives promoting the common cause model as an explanation of ADHD's comorbidity. An alternative theory, dynamic mutualism, proposes that ADHD's comorbidity emerges through reciprocal interactions among symptoms over time, as opposed to a common cause. We tested the common cause and the dynamic mutualism theories in explaining the associations between aspects of ADHD (i.e., ADHD, inattention, hyperactivity/impulsivity, cognitive disengagement) and the neurodevelopmental and externalizing spectra across four waves of the Adolescent Brain Cognitive Development (ABCD) Study data (n = 11,878 youths aged 9-10 at baseline; 48% female). Results largely supported the common cause theory in explaining the developmental links between ADHD and both the externalizing and neurodevelopmental spectra. Findings varied across ADHD subdimensions, although not substantially, with hyperactivity/impulsivity more closely linked to the externalizing spectrum and cognitive disengagement more closely linked to the neurodevelopmental spectrum. ADHD is best conceptualized as a disorder that bridges both the externalizing and neurodevelopmental domains, rather than fitting exclusively within either category. Given the assessment structure of the ABCD Study, there was more support for the common cause model compared with dynamic mutualism.
Downbeat nystagmus varies with head position, a phenomenon termed gravity-dependent modulation. We aimed to clarify its mechanism using a velocity-storage model. In 10 patients with downbeat nystagmus due to cerebellar disorders, we recorded eye movements at different pitch- and roll-axis head positions. Sine-wave fitting of the nystagmus intensity as a function of head position decomposed the slow-phase velocity of nystagmus into a gravity-dependent component-the amplitude and phase shift of the sine-wave term-and a gravity-independent constant offset. To probe mechanisms, we applied a velocity-storage model simulating the estimation of rotational velocity, gravity orientation, and inertial acceleration, and incorporated a gravity-estimator lesion that produced a gravity-estimation bias. The gravity-dependent component during pitch-axis modulation had a median amplitude of 3.8°/s (interquartile range [IQR] = 2.6) and a phase shift of 158.5° (57.9). During roll-axis modulation, it had an amplitude of 2.1°/s (1.5) and a phase shift of -0.9° (147.6), with two subgroups showing phase shifts near ±90°. The amplitude was significantly larger during pitch- than roll-axis modulation (p < 0.05). The lesion model generated persistent rotational cues that modulated downbeat nystagmus intensity as observed in the patients and additionally explained the interindividual variation in phase shifts and the weaker modulation of downbeat nystagmus during head roll. These findings refine our understanding of cerebellar vestibular processing and provide a computational framework for positional modulation of downbeat nystagmus. The concept of a biased gravity estimate may further account for several clinical phenomena, including atypical patterns of positional nystagmus.
Acute intracerebral hemorrhage (ICH) often induces a hyperadrenergic response, resulting in a significantly increased cardiac workload. This study aimed to assess the relationship between early cardiac workload and long-term outcomes following ICH, utilizing the rate-pressure product (RPP) as a simple surrogate indicator. We conducted an analysis of data from a large multicenter, prospective cohort comprising 1364 ICH patients. Heart rate (HR) and systolic blood pressure (SBP) were recorded to calculate the RPP. Multivariable logistic regression and Cox proportional hazards models were used to evaluate the associations of RPP with unfavorable functional outcome (modified Rankin Scale score >3) and all-cause mortality at 90 days and 1 year, respectively. Elevated RPP was independently associated with unfavorable functional outcomes and all-cause mortality at 90 days and 1 year (all p < 0.05). RPP exhibited superior predictive performance, as indicated by higher C-statistics for all outcomes when compared to HR or SBP alone (all p < 0.05). A significant interaction was noted with in-hospital β-blocker treatment (p for interaction < 0.05), indicating that the association between high RPP and primary outcomes was attenuated in patients receiving β-blockers. Early cardiac workload, quantified by the RPP, is a potent independent predictor of long-term unfavorable functional outcome and all-cause mortality in patients with ICH.
Intraoperative cerebral ischemia is a critical complication that can arise during cerebral aneurysm clipping surgery. Although intraoperative neuromonitoring (IONM) can detect resulting functional deficits, these alerts may occur minutes after the initial ischemic event. We aimed to demonstrate the clinical utility of laser speckle contrast imaging (LSCI) for continuous, real-time monitoring of cerebral blood flow (CBF) during aneurysm surgery. In this case study, a 67-year-old female underwent a craniotomy for a left-sided cerebral aneurysm. A microscope-integrated LSCI system was used to continuously monitor cortical perfusion. After surgery, LSCI data were correlated with IONM alerts, indocyanine green angiography (ICGA), and surgical events, including an ischemic period following clip placement. A paired t-test, mixed effects model, and changepoint analysis were used to compare mean perfusion between the pre-ischemic and ischemic periods across seven regions of interest (ROIs) on the cortical surface. LSCI detected a widespread drop in cortical perfusion immediately following the application of an aneurysm clip. This perfusion deficit was detected by LSCI ∼ 8    min before the corresponding IONM alert. During the ischemic period, blood flow decreased across six of the seven ROIs, with reductions ranging from 7.9% to 28.0%. The overall decrease in perfusion from the pre-ischemic to the ischemic period was statistically significant ( p < 0.0001 ). LSCI can provide continuous imaging of tissue perfusion during surgery, enabling the detection of developing ischemia before functional deficits may be evident on IONM. The ability of LSCI to track tissue perfusion changes highlights its potential as a valuable complementary tool for enhancing surgical safety alongside IONM and ICGA.
Arts-based interventions create meaningful opportunities for emotional expression, strengthening personal competencies that can enhance prison social climate and support reintegration. This study examined the perceived feasibility and acceptability of RadioACTIVITY, a co-creative arts-based program combining radio theatre production with participatory practices (RadioLAB, RadioSTUDIO, RadioDIFFUSION), implemented across three 10-month editions in a Portuguese prison. Twenty-eight incarcerated individuals (53.6% female; 46.4% male) participated in focus groups. Thematic analysis indicated that feasibility was supported by sustained engagement facilitated through non-judgmental facilitation, collaborative processes, and dynamic sessions. Acceptability was reflected in positive evaluations of the program as meaningful and appropriate, alongside interest in its continuation. Participants also reported intrapersonal (e.g., self-regulation, language skills) and interpersonal (e.g., empathy) gains, as well as perceived social impacts, including reduced stigma. Findings highlight the potential of arts-based approaches to foster rehabilitation and more constructive prison environments. A Participant-Led Radio Program in Prison: What Worked and WhyCreative arts programs can help people in prison express their thoughts and emotions, build personal skills, and improve relationships with others. These benefits may also contribute to a more positive prison environment and support successful reintegration into society. This study explored how people in prison experienced RadioACTIVITY, an innovative arts-based program that uses radio theatre and collaborative creative activities. RadioACTIVITY was implemented over three editions (i.e., three groups of participants), each lasting 10 months, in a Portuguese prison. The program involved three main stages: experimenting with ideas and voices (RadioLAB), creating radio productions together (RadioSTUDIO), and sharing the final content with others (RadioDIFFUSION). A total of 28 incarcerated participants (men and women) took part in group discussions to share their views about the program. Overall, participants found the program easy to engage with and highly meaningful. They highlighted the importance of facilitators who showed respect, listened without judgment, and worked collaboratively with the group. The creative and varied structure of the sessions also helped maintain motivation and interest. Participants reported several personal benefits. On an individual level, they described improvements in emotional control, self-discipline, and language skills. On a social level, they noted better understanding of others, increased empathy, and more positive interactions. Beyond personal change, participants felt the program had a wider impact by helping to challenge negative stereotypes about people in prison and by creating content that could be shared with other prisons. These findings suggest that arts-based programs like RadioACTIVITY can play an important role in rehabilitation by fostering personal growth, improving relationships, and contributing to healthier and more constructive prison environments.
We present a systematic and exhaustive exploration of transition metal tetramer low-energy minima (M, M' = Fe, Ru, Os, Co, Rh, Ir, Ni, Pd, Pt, Cu, Ag, Au, x = 0-4), combining stochastic structural searches with density functional theory. Our results reveal a pronounced structural diversity, multiple low-lying spin states, and widespread fluxionality at the subnanometric scale. While binding energies broadly follow periodic trends, selected heterometallic combinations exhibit enhanced cohesion, identifying "magic" compositions with increased stability. Time-dependent DFT calculations predict intense UV-visible absorptions in several tetramers and distinctive and potentially useful optical signatures in a number of Ni-containing heterotetramers. Conceptual DFT descriptors uncover a wide range of electrophilic and nucleophilic behaviors across the series, offering initial, qualitative insights into potential reactivity patterns across the series. These results establish clear links between atomic-scale composition, geometry, and functionality in transition metal subnanoclusters, providing transferable insights relevant to nanocatalysis, optical nanomaterials, and the rational design of functional nanoalloys.
Understanding resilience in pre-adolescence is important for informing interventions to promote good mental health. Middle childhood is a critical developmental phase, characterised by significant emotional and behavioural development. However, there is limited research on children's perceptions and diverse experiences of resilience which could inform interventions. Qualitative methods can enable meaningful engagement of children and provide rich insights into perceptions of resilience. This study involved Muslim children in East London, a population disproportionately affected by deprivation and racial and cultural discrimination yet underrepresented in resilience research. This study aimed to explore (1) children's perceptions, meanings and experiences of resilience, and (2) the factors and resources that constrain and contribute to resilience in Black and South Asian Muslim children aged 7-12 living in East London. Data were collected through a one-day workshop at a community centre, during which one of the activities was body mapping with children (n = 12). Body mapping, a visual arts-based research method, was used to explore children's subjective and embodied experiences of resilience. Here, we report on the findings from body mapping with children. Themes were developed using systematic visuo-textual analysis and reflexive thematic analysis. Findings are grouped into (1) Conceptualising resilience and (2) Personal and social resources for resilience. Children viewed resilience as personal strength, and related it to nature, sports and physical health. External support from family, friends, teachers and role models was also highlighted as important for resilience. This study provides insights into how children conceptualise resilience and the resources they view as important for promoting it. The findings contribute to understanding resilience in middle childhood and highlight the value of resource-oriented approaches for resilience-supporting interventions. Body mapping emerged as an effective method for engaging children creatively and non-verbally on this topic.
During land colonisation, plants evolved new microtubule structures that have no functional analogues in opisthokonts, namely animals and fungi. The appearance of these unique structures, such as cortical microtubule arrays, the preprophase band, and the phragmoplast, coincided with the family expansion of kinesin motors. While most plant kinesins are classified into the same families as their opisthokont orthologues, many plant kinesins have not only increased functional redundancy but acquired additional or completely new functionality in various cellular processes. Although many opisthokont kinesins have been scrutinised down to the mechanics of a single motor, much less is known about the molecular details of plant kinesins. Insights from opisthokont kinesins are often used to infer how their corresponding plant kinesin counterparts might work in vivo with little molecular verification. In this review, we summarise current advances in in vitro characterisation of plant kinesins and highlight examples of how A. thaliana kinesins have diverged functionally. These examples illustrate that insights from opisthokont kinesins cannot be easily transferred to plant kinesins. Furthermore, they motivate the in vitro characterisation of each individual plant kinesin, a challenge we hope to overcome by promoting the use of reconstituted plant-kinesin assays.
Olea europaea L. (olive tree) stands as an enduring emblem of Mediterranean culture and a treasure trove of structurally diverse phytochemicals with profound biological potential. This review presents a structured, data-driven overview of over 300 metabolites previously reported across various olive sources, including leaves, fruits, olive oil, pomace, flowers, etc. These compounds are systematically classified into 15 chemical classes, each described through its basic skeleton and position numbering, highlighting structural features that allow clear differentiation between closely related compounds. Secoiridoids emerge as the dominant class, with oleuropein and ligustroside serving as key representatives, and biosynthetic intermediates such as tyrosol, hydroxytyrosol, and elenolic acid playing central roles. The distribution of metabolites across organs revealed that leaves represent the most abundant source, followed by fruits and olive oil, while pomace also contained a considerable amount, emphasizing its potential value as a by-product for future exploitation. For each metabolite, comprehensive chemical identifiers (PubChem ID, SMILES, InChI, formula, and exact mass) and, for the first time, an analytical confidence level (validated via a five-level scoring system) are provided in the SI. This analysis reveals a predominance of moderately validated compounds (Level 3), highlighting a critical need for further structural elucidation. Collectively, this robust and cheminformatics-ready dataset serves as an accessible resource, poised to accelerate future studies in virtual screening, molecular docking, and network pharmacology. It also critically guides efforts to expand structural validation for low-confidence compounds and encourages exploration of underrepresented organs, thereby significantly enriching the landscape of therapeutic mapping. Additionally, this review integrates recent insights into isolation yields, impurity profiles, and toxicological aspects of Olea europaea metabolites, thereby providing a holistic framework for their therapeutic evaluation and safe exploitation.
Persistent local tissue hypoperfusion and chronic inflammation are central challenges in diabetic wound management. The development of effective therapeutic strategies to mitigate prolonged inflammation and enhance tissue vascularization is crucial for accelerating diabetic wound healing. This study aimed to develop soluble microneedle materials that simultaneously target both aspects to improve the clinical prognosis of diabetic wounds. A stable macrophage cell line overexpressing basic fibroblast growth factor (bFGF) was established using lentiviral transfection. After M2 polarization was induced with interleukin-4 (IL-4) and IL-10, exosomes were isolated via ultracentrifugation and surface-functionalized with arginine-glycine-aspartic acid (RGD)-targeting peptides. The reparative effects of these exosomes on human umbilical vein endothelial cells (HUVECs) with high glucose-induced injury were evaluated using scratch test, 5-ethynyl-2'-deoxyuridine (EdU) staining, and cell counting kit-8 assays. A delivery system based on soluble hyaluronic acid microneedles (MNs) loaded with engineered exosomes was then developed. Its therapeutic efficacy was evaluated in a diabetic wound mouse model, and the underlying mechanisms were explored via ribonucleic acid (RNA) sequencing. Targeted engineered exosomes (TE-Exos) derived from bFGF-overexpressing M2 macrophages with surface RGD modification were successfully prepared. Assays revealed that TE-Exos exhibited specific targeting to HUVECs with high glucose-induced injury and significantly enhanced cellular proliferation, migration, and tube formation. Furthermore, the polarization ratio of macrophages improved after TE-Exos treatment. In vivo, the MN-mediated delivery of TE-Exos markedly accelerated diabetic wound healing by enhancing re-epithelialization, collagen deposition, and angiogenesis. Furthermore, the treatment modulated the wound microenvironment by reducing the infiltration of proinflammatory M1 macrophages while increasing the proportion of reparative M2 macrophages. RNA sequencing analysis indicated that the therapeutic effects were mediated primarily through the inhibition of excessive inflammation and the activation of angiogenesis-related signaling pathways. This innovative strategy breaks the vicious cycle of impaired angiogenesis and chronic inflammation in diabetic wounds through a synergistic mechanism involving 'angiogenesis, inflammation regulation, and precise delivery'. The combination of targeted exosome engineering with an MN delivery system not only overcomes the limitations of conventional growth factor therapies but also enables intelligent modulation of the wound microenvironment, offering novel theoretical insights and practical approaches for clinical translation.
The bidirectional relationship between depression and type 2 diabetes (T2D) is well-established. Women are disproportionately affected by their co-occurrence, particularly during midlife, yet sex- and age-specific studies on phenotypic and mechanistic factors underlying risk for their co-occurrence are limited. The purpose of this study was to identify combined risk profiles (i.e., depression, T2D) in women during midlife and to determine if microRNAs (miRs) that are associated with high-risk profiles provide mechanistic insights into multimorbidity. This study included baseline data from women during midlife (ages 40-64 years) who participated in the Diabetes Prevention Program (DPP) (n = 603). Unsupervised k-means clustering was used to identify multimorbid risk profiles. Clinical characteristics included for risk profiling included Beck Depression Inventory (BDI-I), age, BMI, waist circumference, triglycerides, high HDL, FBG, and HbA1c. Associations between risk profiles and individual miRs and principal components of co-expressed miRs were determined via logistic regression models adjusted for participant race and ethnicity. False discovery rate (q< 0.05) was used to control for multiple comparisons. Two distinct profiles were identified, with the high-risk profile characterized by younger age yet higher adiposity, glycemic biomarkers, and depression symptom burden compared to the low-risk profile. MiR-320a and miR-320c were associated with increased odds of high-risk profile assignment, and a co-expression cluster enriched for miRs belonging to the miR-320 family (PC3) was significantly associated with increased odds of high-risk profile assignment. Across all models, Black race demonstrated at least threefold higher odds of high-risk profile assignment. These findings highlight distinct multimorbid risk profiles in women during midlife, emphasizing the potential utility of integrated, multidimensional approaches for risk stratification. Findings also revealed mechanisms that may underly risk for co-occurrence of T2D and depression in women during midlife and potential therapeutic targets for prevention and treatment.
Poly(adenosine diphosphate-ribose) polymerase 1 (PARP1) is a pivotal target for treating homologous recombination-deficient cancers through the mechanism of synthetic lethality. While machine learning has accelerated the identification of novel inhibitors, many models lack experimental validation and high-resolution mechanistic insights. In this study, we evaluated the predictive robustness of the PARP1pred model using a hierarchical pipeline. Initial bioactivity predictions for candidates in unseen chemical space were validated through biochemical and cellular sensitivity assays using a panel of isogenic TK6 cell lines. Subsequently, molecular docking, 100-ns molecular dynamics simulations, and molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) energetic analysis were performed to provide a structural and thermodynamic rationale for the observed inhibitory potencies. The workflow successfully identified ZINC49069486 as a highly potent nanomolar lead that induced selective synthetic lethality in BRCA1-deficient cells. Crucially, the pipeline correctly classified ZINC67913374 as biologically inactive [median inhibitory concentration (IC50) > 100 μM], successfully identifying a false positive previously proposed in the literature as a potential inhibitor. MM-PBSA analysis revealed that the inactivity of ZINC67913374 was driven by an excessive polar solvation penalty that outweighed its favorable docking score. While ZINC98208034 and ZINC8793749 showed moderate enzymatic inhibition, they failed to induce a synthetic lethality response. These results confirm that the PARP1pred-driven hierarchical framework effectively prioritizes experimentally validated lead compound while filtering out deceptive computational hits, providing an accessible and robust strategy for PARP1 inhibitor discovery.
This qualitative study explores the barriers and facilitators experienced by adults with hearing loss in accessing hearing-related information and services. Findings were interpreted using the Theoretical Domains Framework, which will be used to inform the design of a novel consumer-centred website-Hear4Health. A total of 13 participants (19-78 years) were recruited. Nine consumers with hearing loss participated in the focus groups, four of whom also served as representatives of consumer organisations. 12 of the 13 participants were subsequently interviewed (51.25 ± 20.35 years), including seven consumers, two consumer organisation representatives, and three who fulfilled dual roles. Nine themes emerged from the interviews under seven theoretical domains: knowledge, environmental context and resources, social influence, beliefs about capabilities, beliefs about consequences, social/professional role and identity, and behavioural regulation. Barriers to access included the themes poor awareness of hearing loss, low-quality information, mistrust in the hearing industry, stigma, unrealistic expectations for hearing technologies, and deaf identity. Facilitators identified included peer support and the value of lived experience, informed decision-making, and self-efficacy. These findings provide crucial insights for the development of Hear4Health. Grounded in the Theoretical Domains Framework, this research underscores the importance of addressing both individual and systemic factors to improve digital access to hearing healthcare and empower adults with hearing loss to make confident and informed choices.
Heart failure remains a major cause of morbidity and mortality worldwide despite substantial advances in pharmacological and device-based therapies. Distinct phenotypes, including heart failure with reduced ejection fraction, mildly reduced ejection fraction, and preserved ejection fraction, differ markedly in underlying pathophysiology, clinical presentation, and therapeutic responsiveness. Therefore, a deeper understanding of disease mechanisms is essential for guiding evolving management strategies and identifying novel therapeutic targets. This narrative review synthesizes contemporary evidence on the pathogenesis and management of heart failure, integrating mechanistic biology with phenotype-specific treatment effects and acute-chronic disease transitions to provide a translational framework for care. Key clinical trials, guideline documents, and mechanistic studies were identified through structured searches of major medical databases and review of international guideline updates, with emphasis on recent advances in disease-modifying therapies, inflammatory mechanisms, and emerging treatment strategies across heart failure phenotypes. Heart failure with reduced ejection fraction is characterized predominantly by myocyte loss, adverse ventricular remodeling, and neurohormonal activation, with robust evidence supporting combined disease-modifying pharmacotherapy and selected device-based interventions. In contrast, heart failure with preserved ejection fraction is driven largely by systemic comorbidities, endothelial dysfunction, and myocardial fibrosis, contributing to impaired ventricular compliance and limited evidence-based treatment options. Sodium-glucose cotransporter 2 inhibitors have demonstrated consistent reductions in symptoms and hospitalizations across the spectrum of ejection fractions, representing a major advance in management. However, translation of mechanistic insights into effective therapies has been variable. Broad anti-inflammatory strategies targeting cytokine pathways have yielded mixed or neutral outcomes. In contrast, more targeted approaches, including interleukin-1 inhibition, inflammasome modulation, and mitochondrial-directed therapies, show emerging but heterogeneous signals that warrant phenotype-specific evaluation. Heart failure is a heterogeneous syndrome that requires biologically informed, phenotype-specific approaches. Thus, by linking dominant mechanisms to therapeutic response and highlighting the limitations of current evidence, this review aims to advance understanding beyond descriptive summaries and to outline priorities for future precision-oriented heart failure care.
 Medicine shortages and governance failures in low- and middle-income countries continue to hinder progress towards universal health coverage.  To explore healthcare professionals' perceptions and experiences of medicines governance in South African healthcare facilities.  The study was conducted at the public healthcare sectors in Eastern Cape province, South Africa.  A qualitative exploratory cross-sectional design was used. Twenty healthcare professionals were purposively selected. Semi-structured interviews were conducted, audio-recorded, transcribed verbatim and thematically analysed using Braun and Clarke's framework.  Four major themes emerged: systemic governance constraints; pharmaceutical supply chain vulnerabilities; weak accountability mechanisms; and gaps in protocol implementation. Key determinants of medicine shortages included weak budget governance, supplier payment delays, limited pharmacy support staff and inconsistent implementation of standard treatment guidelines (STG) and limited functionality of Pharmacy and Therapeutics Committees (PTCs).  Medicine shortages result from systemic governance failures rather than isolated logistical issues. Strengthening pharmaceutical governance requires transparent budgeting, timely supplier payment systems, functional PTCs, and STG training to improve equitable access to essential medicines.Contribution: This study deepens the understanding of pharmaceutical governance, revealing systemic, interrelated factors that collectively lead to the shortage of pharmaceuticals in South Africa. Unlike previous research that focused primarily on supply chain logistics, the study showed that stock-outs were rooted not simply in operational inefficiency, but also in structural governance weaknesses. This study presents practical insights to strengthen pharmaceutical governance and supports national efforts to achieve universal health coverage by identifying specific governance obstacles and proposing system-level reforms.
Ferroptosis is a distinct form of regulated cell death (RCD) characterized primarily by iron dysregulation and lipid peroxidation. Emerging evidence indicates ferroptosis critically contributes to the initiation and progression of multiple cardiovascular diseases (CVDs), including atherosclerosis (AS), myocardial ischemia/reperfusion (MI/R) injury, myocardial infarction (MI), cardiomyopathy, and heart failure (HF). With growing recognition of ferroptosis's role in CVD pathogenesis, targeting ferroptosis has become a promising therapeutic strategy for these diseases. Traditional Chinese medicine (TCM) is characterized by multicomponent, multitarget, and holistic regulatory properties. Studies have demonstrated that bioactive constituents, such as 6-gingerol, curcumin, ginsenoside Rg3, paeoniflorin, and stachydrine, and TCM compound formulations, including Danshentongluo-Detoxification Decoction, Yiqi Fumai Injection, Shexiang Baoxin Pill, and Shensong Yangxin Capsule, exert cardioprotective effects. These effects operate by suppressing ferroptosis via the modulation of iron metabolism, inhibition of lipid peroxidation, and enhancement of anti-oxidant defense systems. Accordingly, this review systematically summarizes the molecular mechanisms of ferroptosis and its pathological roles in various CVDs while placing a particular emphasis on recent advances in TCM-based ferroptosis interventions. This summary provides theoretical insights and potential research strategies both for the prevention and treatment of CVD, and for the development of related therapeutics.
So far, combining gastroscopy with biopsy remains the gold-standard for screening gastric cancer. Recently, the study of circulating microRNAs (miRNAs or miRs) has yielded valuable insights into gastric cancer prognosis. However, because these molecules are common to multiple cancer types, their clinical applicability remains uncertain. We investigated the pertinent literature dealing with gastric juice microRNAs in gastric cancer patients. Only five original articles have investigated the feasibility of using gastric juice miRNAs as potential biomarkers to assist in screening for gastric cancer. Gastric juice microRNAs proved correlated with high reliability, high sensitivity, high specificity and relative stability. MicroRNAs found in gastric juice may offer a promising alternative approach for gastric cancer screening without the need for biopsy. More studies are needed to reach safe conclusions. However, it seems that this novel potential biomarkers' testing is reliable and reproducible.