Association Between Baseline Driving Pressure and Mortality in Very Old Patients with Acute Respiratory Distress Syndrome
Because of the effects of aging on the respiratory system, it is conceivable that the association between driving pressure and mortality depends on age. We endeavored to evaluate whether the association between driving pressure and mortality of patients with acute respiratory distress syndrome (ARDS) varies across the adult lifespan, hypothesizing that it is stronger in older, including very old (⩾80 yr), patients. We performed a secondary analysis of individual patient-level data from seven ARDS Network and PETAL Network randomized controlled trials ("ARDSNet cohort"). We tested our hypothesis in a second, independent, national cohort ("Hellenic cohort"). We performed both binary logistic and Cox regression analyses including the interaction term between age (as a continuous variable) and driving pressure at baseline (i.e., the day of trial enrollment) as the predictor and 90-day mortality as the dependent variable. On the basis of data from 4,567 patients with ARDS included in the ARDSNet cohort, we found that the effect of driving pressure on mortality depended on age ( = 0.01 for the interaction between age as a continuous variable and driving pressure). The difference in driving pressure between survivors and nonsurvivors significantly changed across the adult lifespan ( < 0.01). In both cohorts, a driving pressure threshold of 11 cm HO was associated with mortality in very old patients. Data from randomized controlled trials with strict inclusion criteria suggest that the effect of driving pressure on the mortality of patients with ARDS may depend on age. These results may advocate for a personalized age-dependent mechanical ventilation approach.
Enhanced Rock Weathering as a Source of Metals to Promote Methanogenesis and Counteract CO Sequestration
Enhanced weathering of (ultra)mafic rocks has been proposed as a promising approach to sequester atmospheric CO and mitigate climate change. However, these silicate rocks contain varying amounts of trace metals, which are essential cofactors of metallaenzymes in methanogens. We found that weathering of crushed peridotite and basalt significantly promoted the growth and methanogenesis of a model methanogen─ C2A under the condition of excess substrate. The released trace metals from peridotite and basalt, especially Fe, Ni, and Co, accounted for the promotion effect. Observation at different spatial scales showed a close association between the rocks and cells. Proteomic analysis revealed that rock amendment significantly enhanced the expression of core metalloenzymes in the methylotrophic methanogenesis pathway. Our study uncovers a previously unrecognized but important negative effect of enhanced rock weathering on methane production, which may counteract the carbon sequestration effort.
Concomitant Factors Associated With Tillaux-Chaput Fractures in Adults: A Case-Control Study
Tillaux-Chaput fractures (TCFs) consist of fractures of the anterolateral distal tibia. They rarely occur in isolation in adults. When TCFs are missed, there is a risk of chronic pain, instability, and ankle osteoarthritis. This study aimed to identify which factors are related to the presence of TCFs in ankle injuries.
Enhanced CO Coordinates the Spatial Recruitment of Diazotrophs in Rice Via Root Development
Understanding the reciprocal interaction between root development and coadapted beneficial microbes in response to elevated CO (eCO) will facilitate the identification of nutrient-efficient cultivars for sustainable agriculture. Here, systematic morphological, anatomical, chemical and gene expression assays performed under low-nitrogen conditions revealed that eCO drove the development of the endodermal barrier with respect to L-/S-shaped lateral roots (LRs) in rice. Next, we applied metabolome and endodermal-cell-specific RNA sequencing and showed that rice adapts to eCO by spatially recruiting diazotrophs via flavonoid secretion in L-shaped LRs. Using the rice Casparian strip mutant Oscasp1-1, we confirmed that reduced lignin deposition selectively recruits the diazotrophic family of Oxalobacteraceae to confer tolerance to low nitrogen availability.
Adaptive trade-offs between vertebrate defence and insect predation drive Amazonian ant venom evolution
Stinging ants have diversified into various ecological niches, and selective pressures may have contributed to shape the composition of their venom. To explore the drivers underlying venom variation in ants, we sampled 15 South American rainforest species and recorded a range of traits, including ecology, morphology and venom bioactivities. Principal component analysis of both morphological and venom bioactivity traits reveals that stinging ants display two functional strategies where species have evolved towards either an exclusively offensive venom or a multi-functional venom. Additionally, phylogenetic comparative analysis indicates that venom function (predatory, defensive or both) and mandible morphology correlate with venom bioactivity and volume. Further analysis of the venom biochemistry of the 15 species revealed switches between cytotoxic and neurotoxic venom compositions among species. Our study supports an evolutionary trade-off between the ability of venom to deter vertebrate predators and to paralyse insect prey which are correlated with different venom compositions and life-history strategies among Formicidae.
Mechanistic basis for the emergence of EPS1 as a catalyst in salicylic acid biosynthesis of Brassicaceae
Salicylic acid (SA) production in Brassicaceae plants is uniquely accelerated from isochorismate by EPS1, a newly identified enzyme in the BAHD acyltransferase family. We present crystal structures of EPS1 from Arabidopsis thaliana in both its apo and substrate-analog-bound forms. Integrating microsecond-scale molecular dynamics simulations with quantum mechanical cluster modeling, we propose a pericyclic rearrangement lyase mechanism for EPS1. We further reconstitute the isochorismate-derived SA biosynthesis pathway in Saccharomyces cerevisiae, establishing an in vivo platform to examine the impact of active-site residues on EPS1 functionality. Moreover, stable transgenic expression of EPS1 in soybean increases basal SA levels, highlighting the enzyme's potential to enhance defense mechanisms in non-Brassicaceae plants lacking an EPS1 ortholog. Our findings illustrate the evolutionary adaptation of an ancestral enzyme's active site to enable a novel catalytic mechanism that boosts SA production in Brassicaceae plants.
A rare case of synchronous bilateral ovarian cancer with combined clear cell and mucinous carcinomas and brain metastases
Although ovarian cancer is generally unilateral, a few cases of bilateral ovarian cancer have been reported, most of which originate from metastases of unilateral ovarian cancer. However, synchronous primary bilateral ovarian cancer (SBOC), comprising two different histological types of ovarian cancer, is extremely rare, with limited reports on its clinical course and prognosis. Herein, we report the case of a 56-year-old postmenopausal Japanese woman with stage IVB SBOC with combined left ovarian clear cell and right ovarian mucinous carcinomas. The patient underwent surgery and received postoperative taxane/platinum-based chemotherapy, which temporarily reduced the tumor size. However, an increase in tumor size and brain metastases were subsequently identified. Treatment was accordingly discontinued, and the patient died of the disease 12 months after diagnosis. In this case report, we detail the clinical course of a case of SBOC. To the best of our knowledge, this is the first report of SBOC with combined histological types of clear cell and mucinous carcinomas, and it is also the first report of SBOC with the eventual discovery of brain metastases.
Assessing the Influence of Long-Term Gender-Affirming Hormone Therapy on Cardiovascular Risk in Transgender Men through Carotid Intima-Media Thickness
Transgender men use exogenous androgen for male pattern virilization. Hysterectomy and bilateral salpingo-oophorectomy (HBSO) is performed to stop the endogenous estrogen secretion. Cardiovascular disease (CVD) risk has been shown to increase with long-term use of androgens and the removal of estrogen. We aimed to investigate the CVD risk in these individuals by measuring internal and common carotid artery intima-media thicknesses (CIMT). In this cohort study, data were collected from transgender men who had undergone HBSO and used androgens for at least two years (median treatment duration was 5 years in our research). Cisgender women in the same age range were selected as the control group. Demographics, vital signs, and hematological values of transgender patients and cisgender women subjects in the control group were noted. CVD markers were compared with sonographically measured CIMT values. The mean age and body mass index (BMI) of the study group were 32.6 and 25.3, respectively. Weight, systolic-diastolic blood pressure, hemoglobin, hematocrit, low-density lipoprotein (LDL), serum triglyceride (TG), HbA1c levels, internal CIMT, and common CIMT values of the study group were higher, while the high-density lipoprotein (HDL) level was significantly lower compared the control group (p1 = 0.025, p2 = 0.010, p3 = 0.002, p4 = 0.001, p5 = 0.001, p6 = 0.012, p7 = 0.008, p8 = 0.007, p9 = 0.013, and p10 = 0.001). There was also an increase in the body weight, BMI, LDL, and TG levels of the study group after the testosterone treatment (p1 = 0.025, p2 = 0.019, p3 = 0.001, p4 = 0.001, and p5 = 0.001). We demonstrated that the use of testosterone therapy in transgender men is associated with higher CIMT values. While further investigation is needed to assess morbidity and mortality rates, we recommend that regular clinical and radiological examinations be performed in these individuals to accurately evaluate the risk of CVD.
The Dual Burden: Exploring Cardiovascular Complications in Chronic Kidney Disease
Chronic kidney disease (CKD) represents a significant global health challenge, affecting millions of individuals and leading to substantial morbidity and mortality. This review aims to explore the epidemiology, cardiovascular complications, and management strategies associated with CKD, emphasizing the importance of preventing cardiovascular disease and early intervention. CKD is primarily driven by conditions such as diabetes mellitus, hypertension, and cardiovascular diseases, which often coexist and exacerbate renal impairment. Effective management requires a multifaceted approach, including lifestyle modifications, pharmacological interventions, and regular monitoring. Dietary changes, such as sodium restriction and a controlled intake of phosphorus and potassium, play a vital role in preserving renal function. Pharmacological therapies, particularly angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and emerging agents like SGLT2 inhibitors, have shown efficacy in slowing disease progression and improving patient outcomes. Furthermore, patients undergoing dialysis face increased cardiovascular risk, necessitating comprehensive management strategies to address both renal and cardiac health. As the landscape of CKD treatment evolves, ongoing research into novel therapeutic options and personalized medical approaches are essential. This review underscores the urgent need for awareness, education, and effective preventive measures to mitigate the burden of CKD and enhance the quality of life for affected individuals.
Machine learning and radiomics for ventricular tachyarrhythmia prediction in hypertrophic cardiomyopathy: insights from an MRI-based analysis
Myocardial fibrosis is often detected in patients with hypertrophic cardiomyopathy (HCM), which causes left ventricular (LV) dysfunction and tachyarrhythmias.
Ultrafast and Highly Selective Sequestration of Radioactive Barium Ions by a Layered Thiostannate
As a simulant of hazardous Ra, the simultaneously selective and rapid elimination of radioactive Ba ions from geothermal water is necessary but still challenging. In this paper, we demonstrated the usability of a layered thiostannate with facile synthesis and inexpensive cost, namely, KSnS (KTS-3, = 0.65-1), for the remediation of radioactive Ba in multiple conditions, including sorption isotherm, kinetics, and the influences of competitive inorganic/organic ions, pH values, and dosages. KTS-3 has a strong barium uptake ability (171.3 mg/g) and an ultrafast adsorption kinetics (about 2 min). Impressively, it can achieve a high preference for barium regardless of the excessive interference ions (Na, K, Mg, Ca, and humic acid) and acidic/alkaline environments, with the largest distribution coefficient value reaching 6.89 × 10 mL/g. Also, the Ba-laden products can be easily eluted by a concentrated KCl solution, and its adsorption performances for barium resist well even after five consecutive cycles. In addition, owing to the regular appearance and excellent mechanical strength, the prepared KTS-3/PAN (PAN = polyacrylonitrile) granule displays a good removal efficiency in the flowing ion-exchange column. These advantages mentioned above render it very promising for the effective and efficient cleanup of radioactive Ba-contaminated wastewater.
Dietary pro-oxidant therapy by a vitamin K precursor targets PI 3-kinase VPS34 function
Men taking antioxidant vitamin E supplements have increased prostate cancer (PC) risk. However, whether pro-oxidants protect from PC remained unclear. In this work, we show that a pro-oxidant vitamin K precursor [menadione sodium bisulfite (MSB)] suppresses PC progression in mice, killing cells through an oxidative cell death: MSB antagonizes the essential class III phosphatidylinositol (PI) 3-kinase VPS34-the regulator of endosome identity and sorting-through oxidation of key cysteines, pointing to a redox checkpoint in sorting. Testing MSB in a myotubular myopathy model that is driven by loss of -the phosphatase antagonist of VPS34-we show that dietary MSB improved muscle histology and function and extended life span. These findings enhance our understanding of pro-oxidant selectivity and show how definition of the pathways they impinge on can give rise to unexpected therapeutic opportunities.
Quantitation of metabolic activity from isotope tracing data using automated methodology
Modern Challenges in Type 2 Diabetes: Balancing New Medications with Multifactorial Care
Type 2 diabetes mellitus (T2DM) is a prevalent chronic metabolic disorder characterized by insulin resistance and progressive beta cell dysfunction, presenting substantial global health and economic challenges. This review explores recent advancements in diabetes management, emphasizing novel pharmacological therapies and their physiological mechanisms. We highlight the transformative impact of Sodium-Glucose Cotransporter 2 inhibitor (SGLT2i) and Glucagon-Like Peptide 1 Receptor Agonist (GLP-1RA), which target specific physiological pathways to enhance glucose regulation and metabolic health. A key focus of this review is tirzepatide, a dual agonist of the glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptors. Tirzepatide illustrates how integrating innovative mechanisms with established physiological pathways can significantly improve glycemic control and support weight management. Additionally, we explore emerging treatments such as glimins and glucokinase activators (GKAs), which offer novel strategies for enhancing insulin secretion and reducing glucose production. We also address future perspectives in diabetes management, including the potential of retatrutide as a triple receptor agonist and evolving guidelines advocating for a comprehensive, multifactorial approach to care. This approach integrates pharmacological advancements with essential lifestyle modifications-such as dietary changes, physical activity, and smoking cessation-to optimize patient outcomes. By focusing on the physiological mechanisms of these new therapies, this review underscores their role in enhancing T2DM management and highlights the importance of personalized care plans to address the complexities of the disease. This holistic perspective aims to improve patient quality of life and long-term health outcomes.
Analysis of Wall Thickness and Absorption Characteristics of Ammonium Nitrate(V) from Various Sources
This study investigates the wall thickness and specific surface area (S) of ammonium nitrate(V) samples of varying provenance. The research focuses on both fertilizer-grade ammonium nitrate(V) and three porous prill samples obtained from different manufacturers. The samples were analyzed using tomography scanning and two distinct porosimetry methods. The wall thickness analysis revealed that fertilizer-grade ammonium nitrate(V) possesses thicker walls, ranging from 0.05 to 0.40 mm, compared to porous prill-type ammonium nitrate(V), which predominantly exhibited wall thicknesses between 0.05 and 0.025 mm, with occasional thicker regions up to 0.040 mm. These variations in wall thickness are likely attributable to differences in manufacturing processes and prilling conditions specific to the ammonium nitrate(V) porous prill-type samples. The specific surface area (S), derived from nitrogen adsorption measurements, indicated that the samples exhibited surface areas ranging from 0.011 to 0.466 m·g, suggesting that these samples do not exhibit particularly high absorption capacities. However, the S values obtained from the mercury intrusion method suggested significantly higher absorption capacities, falling within the range of 4.87-18.29 m·g. These findings suggest that mercury porosimetry may provide a more accurate assessment of the porosity and absorption potential of ammonium nitrate(V) samples.
Hypermobile Anterior Horn of the Lateral Meniscus: A Retrospective Case-Series Study of Presentation, Imaging, Treatment, and Outcomes
: Hypermobility of the lateral meniscus is typically associated with the posterior part of this structure, with occurrences in the anterior part rarely reported. However, a hypermobile anterior horn of the lateral meniscus can manifest clinical symptoms. This study aimed to increase awareness regarding hypermobility in the anterior horn of the lateral meniscus by presenting its clinical presentations, magnetic resonance imaging (MRI) findings, arthroscopic findings, treatment approaches, postoperative protocols, and clinical outcomes. : A retrospective case-series involving patients diagnosed as having hypermobile anterior horn of the lateral meniscus through arthroscopy. The clinical presentations, preoperative image findings, arthroscopic findings, treatments, postoperative protocols, and clinical outcomes following meniscal stabilization were all reviewed. : A total of 17 patients (17 knees) with a mean age of 45.9 ± 18.4 years were analyzed. The mean follow-up period was 18.2 ± 7.6 months (range, 6-24 months). Primary symptoms included anterior lateral knee pain, tenderness in the lateral joint lines, and a locking sensation in six of the knees. MRI revealed hypodense lesions anterior to the meniscus, fluid accumulation, degenerative changes, and anterior horn deformities. Following meniscal stabilization, the Lysholm Knee Scoring Scale score increased from 65.8 ± 12.7 before surgery to 91.1 ± 9.6 at the final follow-up ( < 0.001). All the analyzed knees achieved a full range of motion by the final follow-up, with no patient experiencing any complication or requiring reoperation. : There is no specific sign or test that can be used to detect a hypermobile anterior horn of the lateral meniscus. A thorough arthroscopic examination is essential for diagnosing hypermobility in the anterior horn of the lateral meniscus. Arthroscopic meniscal stabilization yields favorable outcomes.
Late Hepatocellular Carcinoma Occurrence in Patients Achieving Sustained Virological Response After Direct-Acting Antiviral Therapy: A Matter of Follow-Up or Something Else?
: Despite achieving a sustained virological response (SVR) with direct-acting antivirals (DAAs), an unexpected increase in the occurrence rate of hepatocellular carcinoma (HCC) has been observed among HCV-treated patients. This study aims to assess the long-term follow-up of HCV patients treated with DAAs who achieved an SVR to investigate the potential for late-onset HCC. : In this prospective multicenter study, we enrolled consecutive HCV patients treated with DAAs following Italian ministerial guidelines between 2015 and 2018. Exclusion criteria included active HCC on imaging, prior HCC treatment, HBV or HIV co-infection, or liver transplant recipients. Monthly follow-ups occurred during treatment, with subsequent assessments every 3 months for at least 48 months. Abdominal ultrasound (US) was performed within two weeks before starting antiviral therapy, supplemented by contrast-enhanced ultrasonography (CEUS), dynamic computed tomography (CT), or magnetic resonance imaging (MRI) to evaluate incidental liver lesions. : Of the 306 patients completing the 48-months follow-up post-treatment (median age 67 years, 55% male), all achieved an SVR. A sofosbuvir-based regimen was administered to 72.5% of patients, while 20% received ribavirin. During follow-up, late-onset HCC developed in 20 patients (cumulative incidence rate of 6.55%). The pattern of HCC occurrence varied (median diameter 24 mm). Multivariate and univariate analyses identified liver stiffness, diabetes, body mass index, and platelet levels before antiviral therapy as associated factors for late HCC occurrence. : Our findings suggest that late HCC occurrence may persist despite achieving SVR. Therefore, comprehensive long-term follow-up, including clinical, laboratory, and expert ultrasonography evaluations, is crucial for all HCV patients treated with DAAs.
Advances in the Insulin-Heart Axis: Current Therapies and Future Directions
The insulin-heart axis plays a pivotal role in the pathophysiology of cardiovascular disease (CVD) in insulin-resistant states, including type 2 diabetes mellitus. Insulin resistance disrupts glucose and lipid metabolism, leading to systemic inflammation, oxidative stress, and atherogenesis, which contribute to heart failure (HF) and other CVDs. This review was conducted by systematically searching PubMed, Scopus, and Web of Science databases for peer-reviewed studies published in the past decade, focusing on therapeutic interventions targeting the insulin-heart axis. Studies were selected based on their relevance to insulin resistance, cardiovascular outcomes, and the efficacy of pharmacologic treatments. Key findings from the review highlight the efficacy of lifestyle modifications, such as dietary changes and physical activity, which remain the cornerstone of managing insulin resistance and improving cardiovascular outcomes. Moreover, pharmacologic interventions, such as metformin, sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide-1 receptor agonists, and dipeptidyl peptidase-4 inhibitors, have shown efficacy in reducing cardiovascular risk by addressing metabolic dysfunction, reducing inflammation, and improving endothelial function. Furthermore, emerging treatments, such as angiotensin receptor-neprilysin inhibitors, and mechanical interventions like ventricular assist devices offer new avenues for managing HF in insulin-resistant patients. The potential of these therapies to improve left ventricular ejection fraction and reverse pathological cardiac remodeling highlights the importance of early intervention. However, challenges remain in optimizing treatment regimens and understanding the long-term cardiovascular effects of these agents. Future research should focus on personalized approaches that integrate lifestyle and pharmacologic therapies to effectively target the insulin-heart axis and mitigate the burden of cardiovascular complications in insulin-resistant populations.
[Sympathetic fire and rhythm of death "Spiked Helmet" in the Takotsubo cardiomyopathy. Case report]
The electrocardiographic sign "Spiked Helmet" (SHS) has been described in critically ill patients and is associated with a high risk of death. We present the case of a young individual with Marfan syndrome, who developed a Takotsubo cardiomyopathy and the electrocardiographic manifestation of SHS, 72 hours after the postoperative period for a ruptured abdominal aorta aneurysm. In this case, the factors that may justify the presentation of this electrocardiographic pattern are the thoraco-abdominal surgical intervention and Takotsubo cardiomyopathy, which together activated the sympathetic system, triggering the clinical-electrocardiographic manifestation.
Observation of the decay
Using proton-proton collision data corresponding to an integrated luminosity of collected by the CMS experiment at , the decay is observed for the first time, with a statistical significance exceeding 5 standard deviations. The relative branching fraction, with respect to the decay, is measured to be , where the first uncertainty is statistical, the second is systematic, and the third is related to the uncertainties in and .
