Overload

Calcium ion (Ca2+ ) dysregulation is one of the main causes of neuronal cell death and brain damage after cerebral ischemia. During ischemic stroke, the ability of neurons to maintain Ca2+ homeostasis is compromised. Ca2+ regulates various functions of the nervous system, including neuronal activity and adenosine triphosphate (ATP) production. Disruptions in Ca2+ homeostasis can trigger a cascade of events, including activation of the unfolded protein response (UPR) pathway, which is associated with endoplasmic reticulum (ER) stress and mitochondrial dysfunction...

The changes of inflammation and metabolism are two features in nonalcoholic steatohepatitis (NASH). However, how they interact to regulate NASH progression remains largely unknown. Our works have demonstrated the importance of solute carrier family 7 member 11 (SLC7A11) in inflammation and metabolism. Nevertheless, whether SLC7A11 regulates NASH progression through mediating inflammation and metabolism is unclear. In this study, we found that SLC7A11 expression was increased in liver samples from patients with NASH...

PURPOSE: To assess liver and spleen characteristics of a population with Gaucher disease (GD) using multiparametric MRI and MR elastography (MRE) for evaluation of diffuse liver and spleen disease, which includes liver fat fraction, liver and spleen volume and iron deposition, and liver and spleen stiffness correlated with DS3 Severity Scoring System for Gaucher disease (GD-DS3). METHODS: We prospectively evaluated 41 patients with type 1 Gaucher disease using a 3...

Patients treated with deferiprone for transfusional iron overload may experience idiosyncratic drug-induced neutropenia (IDIN) that may put them at risk of infection. The purpose of this analysis was to examine the rates of severe IDIN and risk of serious infections at different ANC levels in patients treated with deferiprone. Events of severe IDIN (ANC <0.5×109/L) and associated serious infections from clinical trials and postmarketing setting were analyzed by 3 discrete ANC levels: Group 1, 0.2-0...

IMPORTANCE: Recent sepsis trials suggest that fluid-liberal vs fluid-restrictive resuscitation has similar outcomes. These trials used generalized approaches to resuscitation, and little is known about how clinicians personalize fluid and vasopressor administration in practice. OBJECTIVE: To understand how clinicians personalize decisions about resuscitation in practice. DESIGN, SETTING, AND PARTICIPANTS: This survey study of US clinicians in the Society of Critical Care Medicine membership roster was conducted from November 2022 to January 2023...

OBJECTIVE: To investigate the effect of formal leadership training of academic radiology leaders within an academic center on their own burnout and professional fulfillment. METHODS: The study cohort was academic radiology leaders within one of the largest academic organizations of academic radiologists within the United States. All academic radiology leaders within the organization were electronically mailed a weblink to a confidential IRB-approved survey in April 2021...

INTRODUCTION: In the past year, the use of large language models (LLMs) has generated significant interest and excitement because of their potential to revolutionise various fields, including medical education for aspiring physicians. Although medical students undergo a demanding educational process to become competent health care professionals, the emergence of LLMs presents a promising solution to challenges like information overload, time constraints and pressure on clinical educators...

This research evaluated the relationship between daily new Coronavirus Disease 2019 (COVID-19) cases and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) concentrations in wastewater, followed by effects of differential SARS-CoV-2 shedding loads across various COVID-19 outbreaks. Linear regression analyses were utilized to examine the lead time of the SARS-CoV-2 signal in wastewater relative to new COVID-19 clinical cases. During the Delta wave, no lead time was evident, highlighting limited predictive capability of wastewater monitoring during this phase...

BACKGROUND AND AIMS: The clinical introduction of hepcidin25 (Hep25) has led to a more detailed understanding of its relationship with ferroportin (FP) and divalent metal transporter1 in primary iron overload syndromes (PIOSs). In 2012, we proposed a classification of PIOSs based on the Hep25/FP system, which consists of prehepatic aceruloplasminemia, hepatic hemochromatosis (HC), and posthepatic FP disease (FP-D). However, in consideration of accumulated evidence on PIOSs, we aimed to renew the classification...

Recent integrative multilevel models offer novel insights into the etiology and course of neurodegenerative conditions. The predictive coding of allostatic-interoception theory posits that the brain adapts to environmental demands by modulating internal bodily signals through the allostatic-interoceptive system. Specifically, a domain-general allostatic-interoceptive network exerts adaptive physiological control by fine-tuning initial top-down predictions and bottom-up peripheral signaling. In this context, adequate adaptation implies the minimization of prediction errors thereby optimizing energy expenditure...

A 58-year-old female was found to have hyperferritinemia (Serum ferritin:1683 ng/mL) during work-up for mild normocytic anemia. Transferrin saturation(TSAT) was low-normal. Magnetic resonance imaging (MRI) abdomen showed evidence of hepatic iron deposition. Liver biopsy showed 4 + hepatic iron deposition without any evidence of steatosis or fibrosis. Quantitative liver iron was elevated at 348.3 µmol/g dry liver weight [Reference range(RR): 3-33 µmol/g dry liver weight]. She was presumptively diagnosed with tissue iron overload, cause uncertain...

Photoactivable chemotherapy (PACT) using metallic complexes provides spatiotemporal selectivity over drug activation for targeted anticancer therapy. However, the poor absorption in near-infrared (NIR) light region of most metallic complexes renders tissue penetration challenging. Herein, we present an NIR light triggered di-nuclear photoactivable Ru(II) complex (Ru2) and comprehensively investigated the antitumor mechanism. The introduction of a donor-acceptor-donor (D-A-D) linker greatly enhances the intramolecular charge transition, resulting in a high molar extinction coefficient in the NIR region with an extended triplet excited state lifetime...

INTRODUCTION: Acute ischemic stroke (AIS) significantly contributes to severe disability and mortality among the elderly. This study aims to explore the association between longitudinal fluid balance (FB) trajectories and clinical outcomes in elderly patients with AIS. Our hypothesis posits the existence of multiple latent trajectories of FB in patients with AIS during the initial 7 days following ICU admission. METHODS: Patients (age ≥ 65 years) with AIS and continuous FB records were identified from two large databases...

We established myocardial injury models in vivo and in vitro to investigate the cardioprotective effect of gomisin D obtained from Schisandra chinensis . Gomisin D significantly inhibited isoproterenol-induced apoptosis and hypertrophy in H9C2 cells. Gomisin D decreased serum BNP, ANP, CK-MB, cTn-T levels and histopathological alterations, and inhibited myocardial hypertrophy in mice. In mechanisms research, gomisin D reversed ISO-induced accumulation of intracellular ROS and Ca2+ . Gomisin D further improved mitochondrial energy metabolism disorders by regulating the TCA cycle...

While network abrupt breakdowns due to overloads and cascading failures have been studied extensively, the critical exponents and the universality class of such phase transitions have not been discussed. Here, we study breakdowns triggered by failures of links and overloads in networks with a spatial characteristic link length ζ. Our results indicate that this abrupt transition has features and critical exponents similar to those of interdependent networks, suggesting that both systems are in the same universality class...

Psychological characterization of patients affected by Inflammatory Bowel Disease (IBD) focuses on comorbidity with psychiatric disorders, somatization or alexithymia. Whereas IBD patients had higher risk of stable anxiety and depression for many years after the diagnosis of the disease, there is a lack of studies reporting a comprehensive psychosomatic assessment addressing factors of disease vulnerability, also in the long-term. The objective of this investigation is to fill this gap in the current literature...

As one of the most common iron-chelating agents, deferoxamine (DFO) rapidly chelates iron in the body. Moreover, it does not compete for the iron characteristic of hemoglobin in the blood cells, which is common in the clinical treatment of iron poisoning. Iron is a trace element necessary to maintain organism normal life activities. Iron deficiency can lead to anemia, whereas iron overload can cause elevated levels of cellular oxidative stress and cell damage. As a consequence, detection of the iron content in tissues and blood is of great significance...

Mitochondrial dysregulation is pivotal in Alzheimer's disease (AD) pathogenesis. Calcium governs vital mitochondrial processes impacting energy conversion, oxidative stress, and cell death signaling. Disruptions in mitochondrial calcium (m Ca2+ ) handling induce calcium overload and trigger the opening of mitochondrial permeability transition pore, ensuing energy deprivation and resulting in AD-related neuronal cell death. However, the role of m Ca2+ in non-neuronal cells (microglia, astrocytes, oligodendrocytes, endothelial cells, and pericytes) remains elusive...

Exposure to PM2.5 is correlated with cardiac remodeling, of which cardiac hypertrophy is one of the main clinical manifestations. Ferroptosis plays an important role in cardiac hypertrophy. However, the potential mechanism of PM2.5 -induced cardiac hypertrophy through ferroptosis remains unclear. This study aimed to explore the molecular mechanism of cardiac hypertrophy caused by PM2.5 and the intervention role of MitoQ involved in this process. The results showed that PM2.5 could induce cardiac hypertrophy and dysfunction in mice...

Iron overload can lead to oxidative stress and intestinal damage and happens frequently during blood transfusions and iron supplementation. However, how iron overload influences intestinal mucosa remains unknown. Here, the aim of current study was to investigate the effects of iron overload on the proliferation and differentiation of intestinal stem cells (ISCs). An iron overload mouse model was established by intraperitoneal injection of 120 mg/kg body weight iron dextran once a fortnight for a duration of 12 weeks, and an iron overload enteroid model was produced by treatment with 3 mM or 10 mM of ferric ammonium citrate for 24 h...