Novel Naphthyridones Targeting Pannexin 1 for Colitis Management.

Pannexin 1 (PANX1) forms cell-surface channels capable of releasing signaling metabolites for diverse patho-physiological processes. While inhibiting dysregulated PANX1 has been proposed as a therapeutic strategy for many pathological conditions, including inflammatory bowel disease (IBD), low efficacy, or poor specificity of classical PANX1 inhibitors introduces uncertainty for their applications in basic and translational research. Here, hit-to-lead optimization is performed and a naphthyridone, compound 12, is identified as a new PANX1 inhibitor with an IC of 0.

Assessing how restoration can facilitate 30×30 goals for climate-resilient coastal ecosystems in the United States.

Ecosystems globally have reached critical tipping points because of climate change, urbanization, unsustainable resource consumption, and pollution. In response, international agreements have set targets for conserving 30% of global ecosystems and restoring 30% of degraded lands and waters by 2030 (30×30). In 2021, the United States set a target to jointly conserve and restore 30% of US lands and waters by 2030, with a specific goal to restore coastal ecosystems, namely wetlands, seagrasses, coral and oyster reefs, and mangrove and kelp forests, to increase resilience to climate change.

Ultrastructural Remodeling of Cardiomyocytes in Postinfarction Myocardium of Rats in the Late Stages of the Disease.

Identifying factors that contribute to the transition to the dilated phase in cardiac ischemia is a critical challenge in heart failure treatment. Currently, no effective therapies exist for this ischemic complication, and the mechanisms driving left ventricular dilatation during chronic post-infarction remodeling remain poorly understood. One potential pathological process leading to ventricular dilatation involves specific compensatory rearrangements in the border zone adjacent to the infarct, which isolates the intact myocardium from inflammation at the scar edge.

Classification of direct threats to the conservation of ecosystems and species 4.0.

Identifying and assessing the magnitude of direct threats to ecosystems and species are critical steps to prioritizing, planning, implementing, and assessing conservation actions. Just as medical clinicians and researchers need a standard way to talk about human diseases, conservation practitioners and scientists need a common and comprehensive language to talk about the threats they are facing to facilitate joint action, evaluation, and learning. To meet this need, in 2008 the IUCN Species Survival Commission and the Conservation Measures Partnership produced the first version of a common threats classification with the understanding that it would be periodically updated to take into account new information and learning.

Proton Pump Inhibitor Use and Incident Cardiovascular Disease in Older Postmenopausal Women.

Background: Epidemiological studies have been inconsistent regarding an association between proton pump inhibitor (PPI) use and risk of primary cardiovascular disease (CVD) events.

Methods: We studied 85,189 postmenopausal women (mean age 63 years at baseline) without known CVD at enrollment into the Women's Health Initiative Observational Study (1993-1998). PPI use was determined from medication inventories at baseline and Year-3.

Preclinical Experience Using 4D Intracardiac Echocardiography to Guide Cardiac Electrophysiology Procedures.

Introduction: Intracardiac echocardiography (ICE) is an essential imaging modality for electrophysiology procedures, allowing intraprocedural monitoring, real-time catheter manipulation guidance, and visualization of complex anatomic structures. Four-dimentional (4D) ICE is the next stage in the evolution of the technology, permitting 360° rotation of the imaging plane, simultaneous multiplanar imaging, and volumetric acquisition, similar to transesophageal echocardiography (TEE). In this study, we report our experience with a novel 4D ICE catheter (NuVision, Biosense Webster) in structural electrophysiology procedures and difficult ventricular ablations in a swine preclinical model.

Solvation Dynamics of Thermoresponsive Polymer Films: The Influence of Salt Series in Water and Mixed Water/Methanol Atmosphere.

Understanding the salt effects on solvation behaviors of thermoresponsive polymers is crucial for designing and optimizing responsive systems suitable for diverse environments. In this work, the effect of potassium salts (CHCOOK, KCl, KBr, KI, and KNO) on solvation dynamics of poly(4-(N-(3'-methacrylamidopropyl)-N,N-dimethylammonio) butane-1-sulfonate) (PSBP), poly(N-isopropylmethacrylamide) (PNIPMAM), and PSBP-b-PNIPMAM films is investigated under saturated water and mixed water/methanol vapor via advanced in situ neutron/optical characterization techniques. These findings reveal that potassium salts enhance the films' hygroscopicity or methanol-induced swellability.

EZH2 deletion does not impact acinar regeneration but restricts progression to pancreatic cancer in mice.

Enhancer of Zeste Homologue 2 (EZH2) is part of the Polycomb Repressor Complex 2, which promotes trimethylation of lysine 27 on histone 3 (H3K27me3) and genes repression. EZH2 is overexpressed in many cancers and studies in mice attributed both pro-oncogenic and tumor suppressive functions to EZH2 in pancreatic ductal adenocarcinoma (PDAC). EZH2 deletion enhances de novo KRAS-driven neoplasia following pancreatic injury, while increased EZH2 expression in PDAC patients is correlated to poor prognosis, suggesting a context-dependant effect for EZH2 in PDAC progression.

Optimized GVHD Prevention in HLA-Mismatched Unrelated Allogeneic HCT Using a PTCY-Based Approach.

Although post-transplant cyclophosphamide (PTCY)-based prophylaxis has become a widely adopted strategy for preventing graft-versus-host disease (GVHD) in 9 out of 10 HLA-mismatched unrelated donors (MMUDs), allogeneic hematopoietic cell transplants (allo-HCTs), data on the safety and efficacy of PTCY in this setting remain limited. This single-center study investigates the outcomes of 94 adults with hematological malignancies undergoing MMUD allo-HCT with PTCY and tacrolimus (Tac) (PTCY-Tac) between 2014 and 2023. The median age was 53 years, and 60.

Revisiting the phylogeny of royal ferns (Osmundales) through the lens of character dependence and restudied fossil taxa questions existing family and subfamily concepts.

The royal ferns (Osmundales) are a morphologically diverse group of leptosporangiate ferns, the fossil record of which dates back to the Permian. Despite there being numerous described permineralized species, the phylogenetic relationships between extinct species remain contentious. Although several analytical approaches have been applied to infer well-resolved phylogenetic hypotheses-even methods that are arguably conceived to be better at dealing with data conflict and uncertainty, many taxa have not been assigned to specific taxonomic categories.

The Demographic Basis of Population Growth: A 32-Year Transient Life Table Response Experiment.

It has recently been recognised that populations are rarely in demographic equilibrium, but rather in a 'transient' state. To examine how transient dynamics influence our empirical understanding of the links between changes in demographic rates and population growth, we conducted a 32-year study of Columbian ground squirrels. The population increased rapidly for 10 years, followed by a 2-year crash, and a gradual 19-year recovery.

Factors associated with the presence and abundance of Aedes albopictus and Aedes aegypti (Diptera: Culicidae): Perspectives from larval habitat-scale and neighbourhood-scale analyses in the Argentine subtropics.

Aedes albopictus (Skuse) and Aedes aegypti L. (Diptera: Culicidae) are invasive species known for their notable expansion capacity, which makes them relevant in the context of public health due to their role as vectors. In Argentina, these species coexist in a limited subtropical area in Northeastern part of the country.

Coefficients in Taylor's law increase with the time scale of water clarity measurements in a global suite of lakes.

Identifying the scaling rules describing ecological patterns across time and space is a central challenge in ecology. Taylor's law of fluctuation scaling, which states that the variance of a population's size or density is proportional to a positive power of the mean size or density, has been widely observed in population dynamics and characterizes variability in multiple scientific domains. However, it is unclear if this phenomenon accurately describes ecological patterns across many orders of magnitude in time, and therefore links otherwise disparate observations.

Willingness to Use Oral and Long-Acting Injectable PrEP in Substance-Using Men who have Sex with Men (SU-MSM) in High HIV Incidence Southern U.S. Cities: A NIDA Clinical Trials Network Study.

In Southern U.S. states with high HIV incidence and low HIV Pre-Exposure Prophylaxis (PrEP) uptake, enhanced efforts to increase interest in and willingness to use PrEP are needed.

Validation of a hand-held ultrasound device in the evaluation of aortic stenosis.

Hand-held ultrasound devices (HHUD) are increasingly used in routine clinical practice, though they lacked continuous (CW) Doppler capability until recent times. There is limited evidence on the utility of HHUD in assessing aortic stenosis (AS) in real-world settings. Our goal was to validate a new HHUD with CW Doppler assessing AS hemodynamic severity.

Community pharmacists' perceptions of their challenges in relation to older adults prescribed psychotropic medications: a focus-group study.

Background: The management of psychotropic medication in older adults is a challenge for every healthcare professional, but data concerning community pharmacists are scarce in the literature.

Aim: Our objectives were i) to understand the difficulties encountered by community pharmacists in managing older adults on psychotropic medication, and ii) to identify potential solutions to the difficulties discussed.

Method: A qualitative study by focus group was proposed to all community pharmacists in the vicinity of the university hospital of Angers, France, between May and June 2023.

Transjugular Intrahepatic Portosystemic Shunt (TIPS): A Bridge to Bariatric Surgery in Morbidly Obese Patients with Cirrhosis and Clinically Significant Portal Hypertension.

Background: In cirrhotic patients, portal hypertension increases mortality after surgery. We evaluated the impact of pre-operative transjugular intrahepatic portosystemic shunt (TIPS) on the outcomes of bariatric surgery in cirrhosis.

Methods: Multicentric retrospective cohort.

Late-onset axial spondyloarthritis: data from Reuma-check cohort.

Objectives: To estimate the prevalence of late-onset axial spondyloarthritis (lo-axSpA) and to identify clinical, laboratory, and imaging features associated with this phenotype.

Methods: This single-center, observational study included patients diagnosed with axSpA from the "Reuma-check" SpA program. Patients with a symptom onset ≥ 45 years were classified as lo-axSpA, as opposed to early-onset axSpA (eo-axSpA, onset < 45 years).

Psoriasis treatments in the stabilization of atherosclerosis: a systematic review.

This systematic review explores the relationship between achieving minimal disease activity in psoriasis and the progression of atherosclerosis. It investigates how biologic therapies and other treatments impact atherosclerosis markers, offering insights into therapeutic strategies. A comprehensive search of PubMed, Embase, and Web of Science was conducted from January 1, 2000, to April 1, 2023, using terms such as psoriasis, psoriatic arthritis, atherosclerosis, biologic therapy, vascular stiffness, carotid intima-media thickness (CIMT), and coronary computed tomography angiography (CCTA).

Key steps in exposure techniques for robotic total mesorectal excision (TME).

Aim: The use of robotic surgery is increasing significantly. Specific training is fundamental to achieve high quality and better oncological outcomes. This work defines key exposure techniques in robotic total mesorectal excision (TME).

Personalized modeling of gut microbiome metabolism throughout the first year of life.

Background: Early-life exposures including diet, and the gut microbiome have been proposed to predispose infants towards multifactorial diseases later in life. Delivery via Cesarian section disrupts the establishment of the gut microbiome and has been associated with negative long-term outcomes. Here, we hypothesize that Cesarian section delivery alters not only the composition of the developing infant gut microbiome but also its metabolic capabilities.

Lacustrine sedimentation patterns at the Northern Antarctic Peninsula and surroundings as a response to late Holocene and Modern Climate changes.

The Northern Antarctic Peninsula (NAP) and the West Antarctic Ice Sheet (WAIS) are likely to respond rapidly to climate changes by increasing the collapse of peripheral ice shelves and the number of days above 0 °C. These facts make this region a representative hotspot of the global sea level rise and the location of one of the global climate tipping points (thresholds in the Earth system whose changes may become irreversible, if exceeded). Understanding the climate evolution of the NAP, based on past evidences, may help infer its future scenario.