Cyclin O controls entry into the cell-cycle variant required for multiciliated cell differentiation.

Multiciliated cells (MCCs) ensure fluid circulation in various organs. Their differentiation is marked by the amplification of cilia-nucleating centrioles, driven by a genuine cell-cycle variant, which is characterized by wave-like expression of canonical and non-canonical cyclins such as Cyclin O (CCNO). Patients with CCNO mutations exhibit a subtype of primary ciliary dyskinesia called reduced generation of motile cilia (RGMC).

Optical coherence tomography in secondary progressive multiple sclerosis: cross-sectional and longitudinal exploratory analysis from the MS-SMART randomised controlled trial.

Background: Optical coherence tomography (OCT) inner retinal metrics reflect neurodegeneration in multiple sclerosis (MS). We explored OCT measures as biomarkers of disease severity in secondary progressive MS (SPMS).

Methods: We investigated people with SPMS from the Multiple Sclerosis-Secondary Progressive Multi-Arm Randomisation Trial OCT substudy, analysing brain MRIs, clinical assessments and OCT at baseline and 96 weeks.

Carnosine Supplementation Has No Effect on Inflammatory Markers in Adults with Prediabetes and Type 2 Diabetes: A Randomised Controlled Trial.

Background/objectives: In vitro studies suggest that carnosine reduces inflammation by upregulating anti-inflammatory mediators and downregulating pro-inflammatory cytokines. However, human clinical trials examining the effects of carnosine on inflammatory biomarkers are scant. We conducted a secondary analysis of a double-blind randomised controlled trial (RCT) to examine the effects of carnosine supplementation on inflammatory markers and adipokines in participants with prediabetes or well-controlled type 2 diabetes (T2D).

Exploring the feasibility of home-delivered capsule endoscopy with 5G support: innovations and carbon footprint insights.

Introduction: Colorectal cancer (CRC) poses a significant global health threat, necessitating early detection. Traditional diagnostic tools like optical colonoscopy have limitations prompting our '5G-SUCCEEDS' initiative to explore a novel approach involving remote colon capsule endoscopy (CCE).

Methods: This prospective feasibility study was conducted at a single hospital in England.

Brain reserve and physical disability in secondary progressive multiple sclerosis.

Background: The brain reserve hypothesis posits that larger maximal lifetime brain growth (MLBG) may confer protection against physical disability in multiple sclerosis (MS). Larger MLBG as a proxy for brain reserve, has been associated with reduced progression of physical disability in patients with early MS; however, it is unknown whether this association remains once in the secondary progressive phase of MS (SPMS). Our aim was to assess whether larger MLBG is associated with decreased physical disability progression in SPMS.

Arrhythmogenic Mitral Valve Prolapse: Can We Risk Stratify and Prevent Sudden Cardiac Death?

Ventricular arrhythmias associated with mitral valve prolapse (MVP) and the capacity to cause sudden cardiac death (SCD), referred to as 'malignant MVP', are an increasingly recognised, albeit rare, phenomenon. SCD can occur without significant mitral regurgitation, implying an interaction between mechanical derangements affecting the mitral valve apparatus and left ventricle. Risk stratification of these arrhythmias is an important clinical and public health issue to provide precise and targeted management.

Environmental behaviour of iron and steel slags in coastal settings.

Iron and steel slags have a long history of both disposal and beneficial use in the coastal zone. Despite the large volumes of slag deposited, comprehensive assessments of potential risks associated with metal(loid) leaching from iron and steel by-products are rare for coastal systems. This study provides a national-scale overview of the 14 known slag deposits in the coastal environment of Great Britain (those within 100 m of the mean high-water mark), comprising geochemical characterisation and leaching test data (using both low and high ionic strength waters) to assess potential leaching risks.

Real-world total cost of care by line of therapy in relapsed/refractory diffuse large B-cell lymphoma.

Aims: There are multiple recently approved treatments and a lack of clear standard-of-care therapies for relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). While total cost of care (TCC) by the number of lines of therapy (LoTs) has been evaluated, more recent cost estimates using real-world data are needed. This analysis assessed real-world TCC of R/R DLBCL therapies by LoT using the IQVIA PharMetrics Plus database (1 January 2015-31 December 2021), in US patients aged ≥18 years treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or an R-CHOP-like regimen as first-line therapy.

Methods of measurement for pneumothorax in pediatric patients: a systematic review.

Accurate measurement of pneumothorax (PTX) size is necessary to guide clinical decision making; however, there is no consensus as to which method should be used in pediatric patients. This systematic review seeks to identify and evaluate the methods used to measure PTX size with CXR in pediatric patients. A systematic review of the literature through 2021 following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) was conducted using the following databases: Ovid/MEDLINE, Scopus, Cochrane Database of Controlled Trials, Cochrane Database of Systematic Reviews, and Google Scholar.

Structure-activity relationships for alkyl-phenanthrenes support two independent but interacting synergistic models for PAC mixture potency.

Multiple lines of evidence at whole animal, cellular and molecular levels implicate polycyclic aromatic compounds (PACs) with three rings as drivers of crude oil toxicity to developing fish. Phenanthrene (P0) and its alkylated homologs (C1- through C4-phenanthrenes) comprise the most prominent subfraction of tricyclic PACs in crude oils. Among this family, P0 has been studied intensively, with more limited detail available for the C4-phenanthrene 1-methyl-7-isopropyl-phenanthrene (1-M,7-IP, or retene).

Carnosine supplementation improves glucose control in adults with pre-diabetes and type 2 diabetes: A randomised controlled trial.

Background And Aims: Type 2 diabetes (T2DM) is a major cause of morbidity and mortality globally. Carnosine, a naturally occurring dipeptide, has anti-inflammatory, antioxidant, and anti-glycating effects, with preliminary evidence suggesting it may improve important chronic disease risk factors in adults with cardiometabolic conditions.

Methods And Results: In this randomised controlled trial, 43 adults (30%F) living with prediabetes or T2DM consumed carnosine (2 g) or a matching placebo daily for 14 weeks to evaluate its effect on glucose metabolism assessed via a 2-h 75 g oral glucose tolerance test.

Carnosine Did Not Affect Vascular and Metabolic Outcomes in Patients with Prediabetes and Type 2 Diabetes: A 14-Week Randomized Controlled Trial.

Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of morbidity and mortality in patients with prediabetes and type 2 diabetes mellitus (T2DM). Carnosine has been suggested as a potential approach to reduce ASCVD risk factors. However, there is a paucity of human data.

Biological Responses of Pacific Herring Embryos to Crude Oil Are Quantifiable at Exposure Levels Below Conventional Limits of Quantitation for PAHs in Water and Tissues.

Pacific herring (), a cornerstone of marine food webs, generally spawn on marine macroalgae in shallow nearshore areas that are disproportionately at risk from oil spills. Herring embryos are also highly susceptible to toxicity from chemicals leaching from oil stranded in intertidal and subtidal zones. The water-soluble components of crude oil trigger an adverse outcome pathway that involves disruption of the physiological functions of cardiomyocytes in the embryonic herring heart.

A spectroscopic liquid biopsy for the earlier detection of multiple cancer types.

Background: A rapid, low-cost blood test that can be applied to reliably detect multiple different cancer types would be transformational.

Methods: In this large-scale discovery study (n = 2092 patients) we applied the Dxcover® Cancer Liquid Biopsy to examine eight different cancers. The test uses Fourier transform infrared (FTIR) spectroscopy and machine-learning algorithms to detect cancer.

Global serum profiling: an opportunity for earlier cancer detection.

The advances in cancer research achieved in the last 50 years have been remarkable and have provided a deeper knowledge of this disease in many of its conceptual and biochemical aspects. From viewing a tumor as a 'simple' aggregate of mutant cells and focusing on detecting key cell changes leading to the tumorigenesis, the understanding of cancer has broadened to consider it as a complex organ interacting with its close and far surroundings through tumor and non-tumor cells, metabolic mechanisms, and immune processes. Metabolism and the immune system have been linked to tumorigenesis and malignancy progression along with cancer-specific genetic mutations.

Bioretention filtration prevents acute mortality and reduces chronic toxicity for early life stage coho salmon (Oncorhynchus kisutch) episodically exposed to urban stormwater runoff.

As the human population of western North America continues to expand, widespread patterns of urban growth pose increasingly existential threats to certain wild stocks of Pacific salmon and steelhead (Oncorhynchus sp.). Rainfall previously absorbed into the soils of forests and grasslands falls instead on pavement and other hardened surfaces.

Dobutamine effects on systolic and diastolic left ventricular long-axis excursion and timing - significance for the interpretation of s' and e'.

Background: Dobutamine effects on the relationships of the peak velocity of left ventricular (LV) long-axis systolic motion (s') with systolic excursion (SExc), systolic duration (SDur) and heart rate, of LV long-axis early diastolic excursion (EDExc) with SExc, and of the peak velocity of LV long-axis early diastolic motion (e') with EDExc, early diastolic duration (EDDur) and isovolumic relaxation time (IVRT') are unknown.

Methods: Two groups of adult subjects, one young and healthy ( = 10), and one with impaired LV long-axis function ( = 10), were studied, with the aim of identifying consistent findings for the two groups and for the septal and lateral walls. Dobutamine was infused at doses of 5 and 10 µg/kg/min.

Decrements of mobility and power in recreationally active septuagenarians is related to loss of force, but not slowing of the muscle: a 5-year longitudinal study.

A lesser 6-min walk distance (6MWD) and timed up-and-go (TUG) in old compared with young adults was previously linked to slowing of muscle contractile properties. The purpose of the present study was to determine whether any further reductions in 6MWD and TUG over a 5-year period in septuagenarians are associated with further slowing of muscle contractile properties. We measured muscle function by a countermovement jump, isometric maximal knee extensor strength (MVC) on a dynamometer and quadriceps muscle size by magnetic resonance imaging (MRI) in 17 older women (71.

Liquid biopsies: the future of cancer early detection.

Cancer is a worldwide pandemic. The burden it imposes grows steadily on a global scale causing emotional, physical, and financial strains on individuals, families, and health care systems. Despite being the second leading cause of death worldwide, many cancers do not have screening programs and many people with a high risk of developing cancer fail to follow the advised medical screening regime due to the nature of the available screening tests and other challenges with compliance.

Neutrophils and macrophages drive TNF-induced lethality via TRIF/CD14-mediated responses.

TNF mediates a variety of biological processes including cellular proliferation, inflammatory responses, and cell death and is therefore associated with numerous pathologies including autoinflammatory diseases and septic shock. The inflammatory and cell death responses to TNF have been studied extensively downstream of TNF-R1 and are believed to rely on the formation of proinflammatory complex I and prodeath complex II, respectively. We recently identified a similar multimeric complex downstream of TLR4, termed the TRIFosome, that regulates inflammation and cell death in response to LPS or .