Despite invasive methods are the gold standard for intracranial pressure (ICP) measurement, several non-invasive techniques (nICP) have been proposed as surrogate, although their use remains insufficiently recognized in clinical practice. These include transcranial Doppler blood flow velocity assessment (arterial or venous), optic nerve sheath diameter (ONSD), automated pupillometry, measurement of skull expansion and compliance, brain imaging, double-depth ophthalmic artery blood flow velocity, and ultrasound time-of-flight. The main limitations of all indirect methods are calibration and zeroing, which constrain the absolute accuracy of non-invasive ICP monitoring. For transcranial Doppler-based methods, the 95
The purpose of this review is to synthesize literature investigating the relationship between type 2 diabetes (T2D) and obstructive airway diseases and to identify implications for clinical care. Type 2 diabetes is a common and challenging comorbidity in patients with asthma and chronic obstructive pulmonary disease (COPD). Basic, translational and clinical studies support a bidirectional association between T2D and the lung. In animal models and human studies, insulin resistance and hyperglycemia are associated with pulmonary inflammation, respiratory exacerbation risk and disease severity. Corticosteroids are a mainstay for respiratory disease control and exacerbation treatment but promote ongoing metabolic dysregulation. Randomized, placebo-controlled trials of glucose-lowering medications for asthma are actively ongoing. Additional studies addressing clinical pathways to co-manage respiratory and metabolic risk are needed. Patients with comorbid T2D and asthma or COPD are at risk for worse outcomes. There are opportunities to improve cross-disciplinary care, potentially reducing risk and multimorbidity associated with both conditions.
Extracorporeal membrane oxygenation (ECMO) is increasingly being utilized for life-threatening cardiac and/or respiratory failure refractory to conventional treatment. Acute kidney injury (AKI) and fluid balance disorders commonly occur both before and during ECMO, with approximately half of cases receiving treatment with continuous renal replacement therapy (CRRT). Acute kidney injury, fluid balance disorders, and CRRT influence both short- and long-term outcomes in this population. The 36th Acute Disease Quality Initiative (ADQI) meeting was held in June 2025 to develop multidisciplinary international expert recommendations for AKI, fluid balance, and CRRT during ECMO across the age spectrum. This work encompassed five working groups: 1) epidemiology, risk factors, and outcomes of AKI and CRRT, 2) fluid management and outcomes, 3) indications for CRRT and fluid removal during ECMO, 4) best practices for performing CRRT during ECMO, and 5) biomarkers, extracorporeal blood purification, and drug pharmacokinetics and pharmacodynamics. As part of this work, knowledge gaps and research priorities were identified.
Intestinal stem cells (ISCs) continuously renew the gut epithelium by producing specialised cell types, yet the mechanisms that couple ISC renewal with lineage commitment remain poorly characterised. Here, we identify a self-limiting transcriptional program, mediated by the zinc-finger transcription factor Chronophage (Cph), that promotes both ISC maintenance and differentiation into enteroendocrine (EE) cells in the Drosophila midgut. Cph expression is transiently induced by the proneural factor scute at the onset of ISC-to-EE specification. Genetic and single-cell transcriptomic approaches revealed that Cph is required to reprogramme ISCs and sustain normal lifespan. Cph binds to genes involved in proliferation and differentiation, and directly represses its own expression. This autoinhibitory feedback safeguards ISCs from accumulating autophagosomes and undergoing cell death, thus preserving ISC function. Our findings uncover a key regulatory mechanism that balances stem cell maintenance and differentiation, highlighting principles relevant to regenerating tissues.
Dysregulated ribosome biogenesis and p53 mutations are known to play oncogenic roles in various cancers, including pancreatic cancer. In this study, we demonstrated the therapeutic potential of BMH-21, a pharmacologic inhibitor of RNA polymerase I, against pancreatic cancer by uncovering a novel molecular mechanism involving RPA194-mediated ubiquitination of mutant p53 without affecting the ubiquitination of wild-type p53. Our key findings are that (i) BMH-21 selectively induces apoptosis and cell growth inhibition of pancreatic cancer cells with no effect on normal human pancreatic ductal epithelial cells; (ii) BMH-21 degrades RPA194; (iii) BMH-21 inhibits recruitment of both RPA194 and RPA135 on rDNA to suppress pre-rRNA synthesis; (iv) RPA194 physically interacts with p53 and BMH-21-induced degradation of RPA194 selectively exposes truncated and mutated p53 for ubiquitination with no effect on ubiquitination of wild-type p53 in pancreatic cancer cells; and (v) BMH-21 treatment significantly reduces the growth of orthotopic xenograft pancreatic tumors in athymic nude mice with no observed toxicity. Altogether, these findings suggest that BMH-21 is a promising, nontoxic therapeutic agent for patients with pancreatic cancer with aberrant ribosome biogenesis and mutant p53, offering a potential new avenue for targeted treatment.
