Palbociclib Is Safe for Breast Cancer Patients With Mild Hepatic Impairment: A Multicenter Retrospective Study Using Real-World Data.

The liver is crucial for metabolizing the anticancer drug palbociclib, but limited information is available on the impact of hepatic impairment on its toxicity and efficacy, with no real-world data available. This study aims to evaluate how hepatic impairment affects hematological toxicity and progression-free survival (PFS) of palbociclib in advanced hormone receptor-positive/human epidermal growth factor receptor 2-negative breast cancer, using the National Cancer Institute scoring system, in a large real-world dataset. This multicenter retrospective observational study included female patients treated with palbociclib between August 2017 and February 2024.

Return-to-Learn for the K-12 Student: a Mixed-Methods Systematic Review.

Objective: Our aim was to perform a systematic review of Return-to-Learn literature with the intent of determining what items are necessary to form a comprehensive Return-to-Learn policy.

Data Sources: We searched CINAHL, Embase, PubMed, Scopus, Google Scholar, and WorldWideScience.org using 25 search terms including return to learn, adolescents, concussion management, concussion AND children, concussion AND department of education, concussion AND secondary schools, concussion AND middle school, concussion AND primary school, concussion AND policy AND procedures, concussion AND 504 plans.

Glutamine sensing licenses cholesterol synthesis.

The mevalonate pathway produces essential lipid metabolites such as cholesterol. Although this pathway is negatively regulated by metabolic intermediates, little is known of the metabolites that positively regulate its activity. We found that the amino acid glutamine is required to activate the mevalonate pathway.

Busulfan Exposure Target Attainment in Adults Undergoing Allogeneic Hematopoietic Cell Transplantation: A Single Day Versus a Multiple Day Therapeutic Drug Monitoring Regimen.

Busulfan exposure has previously been linked to clinical outcomes, hence the need for therapeutic drug monitoring (TDM). Study objective was to evaluate the effect of day 1 TDM-guided dosing (regimen d1) versus days 1 + 2 TDM-guided dosing (regimen d1 + 2) on attaining adequate busulfan exposure. In this observational study, we included all adults who received an allogeneic HCT with intravenous once daily busulfan over 4 days as part of the conditioning regimen at the University Medical Centre Utrecht or between July 31, 2014 and November 12, 2021.

SPRING licenses S1P-mediated cleavage of SREBP2 by displacing an inhibitory pro-domain.

Site-one protease (S1P) conducts the first of two cleavage events in the Golgi to activate Sterol regulatory element binding proteins (SREBPs) and upregulate lipogenic transcription. S1P is also required for a wide array of additional signaling pathways. A zymogen serine protease, S1P matures through autoproteolysis of two pro-domains, with one cleavage event in the endoplasmic reticulum (ER) and the other in the Golgi.

SPRING is a Dedicated Licensing Factor for SREBP-Specific Activation by S1P.

SREBP transcription factors are central regulators of lipid metabolism. Their proteolytic activation requires ER to the Golgi translocation and subsequent cleavage by site-1-protease (S1P). Produced as a proprotein, S1P undergoes autocatalytic cleavage from its precursor S1P to mature S1P form.

Documentation of the Patient Characteristics Morbid Obesity and Bariatric Surgery in the Hospital Information System and the Influence on the Number of Medication-Related Problems.

Background: As a result of pharmacokinetic changes, individuals with morbid obesity and/or with bariatric surgery may require dose adjustments, additional monitoring or medication should be avoided. Clinical decision support (CDS) may provide automated alerts enabling correct prescribing but requires documentation of these patient characteristics in the Hospital Information System (HIS) to prevent medication-related problems (MRPs).

Objective: The primary objective is to determine the proportion of patients with documentation of the patient characteristics morbid obesity and bariatric surgery in the HIS.

[Optimizing pharmaceutical care in bariatric surgery patients].

Bariatric surgery is a popular surgical method for weight loss. Due to the operation, changes are made in the gastrointestinal tract, which can potentially cause malabsorption of orally administrated drugs. Therefore it is important to evaluate each prescription of orally administrated drugs, taking the available evidence in consideration but also the wishes of the individual patient.

Hepatic SREBP signaling requires SPRING to govern systemic lipid metabolism in mice and humans.

The sterol regulatory element binding proteins (SREBPs) are transcription factors that govern cholesterol and fatty acid metabolism. We recently identified SPRING as a post-transcriptional regulator of SREBP activation. Constitutive or inducible global ablation of Spring in mice is not tolerated, and we therefore develop liver-specific Spring knockout mice (LKO).

Overview of Cardiac Arrhythmias and Treatment Strategies.

Maintenance of normal cardiac rhythm requires coordinated activity of ion channels and transporters that allow well-ordered propagation of electrical impulses across the myocardium. Disruptions in this orderly process provoke cardiac arrhythmias that may be lethal in some patients. Risk of common acquired arrhythmias is increased markedly when structural heart disease caused by myocardial infarction (due to fibrotic scar formation) or left ventricular dysfunction is present.

Busulfan target exposure attainment in children undergoing allogeneic hematopoietic cell transplantation: a single day versus a multiday therapeutic drug monitoring regimen.

Busulfan exposure has previously been linked to clinical outcomes, hence the need for therapeutic drug monitoring (TDM). Study objective was to evaluate the effect of day 1 TDM-guided dosing (regimen d1) versus days 1 + 2 TDM-guided dosing (regimen d1 + 2) on attaining adequate busulfan exposure. In this observational study, we included all children receiving busulfan-based allogeneic hematopoietic cell transplantation.

Sterol-regulated transmembrane protein TMEM86a couples LXR signaling to regulation of lysoplasmalogens in macrophages.

Lysoplasmalogens are a class of vinyl ether bioactive lipids that have a central role in plasmalogen metabolism and membrane fluidity. The liver X receptor (LXR) transcription factors are important determinants of cellular lipid homeostasis owing to their ability to regulate cholesterol and fatty acid metabolism. However, their role in governing the composition of lipid species such as lysoplasmalogens in cellular membranes is less well studied.

Adult gene reinstatement restores the learning and plasticity deficits of knockout mice.

With the recent findings that mutations in the gene encoding the α-subunit of calcium/calmodulin-dependent protein kinase II (CAMK2A) causes a neurodevelopmental disorder (NDD), it is of great therapeutic relevance to know if there exists a critical developmental time window in which CAMK2A needs to be expressed for normal brain development, or whether expression of the protein at later stages is still beneficial to restore normal functioning. To answer this question, we generated an inducible mouse model, which allows us to express CAMK2A at any desired time. Here, we show that adult expression of CAMK2A rescues the behavioral and electrophysiological phenotypes seen in the knock-out mice, including spatial and conditional learning and synaptic plasticity.

Implications of Bariatric Surgery on the Pharmacokinetics of Antiretrovirals in People Living with HIV.

Bariatric surgery is increasingly applied among people living with HIV to reduce obesity and the associated morbidity and mortality. In people living with HIV, sufficient antiretroviral exposure and activity should always be maintained to prevent development of resistance and disease progression. However, bariatric surgery procedures bring various gastrointestinal modifications including changes in gastric volume, and acidity, gastrointestinal emptying time, enterohepatic circulation and delayed entry of bile acids.

Oral drug dosing following bariatric surgery: General concepts and specific dosing advice.

Bariatric or weight-loss surgery is a popular option for weight reduction. Depending on the surgical procedure, gastric changes like decreased transit time and volume and increased pH, decreased absorption surface in the small intestine, decreased exposure to bile acids and enterohepatic circulation, and decreased gastrointestinal transit time may be expected. In the years after bariatric surgery, patients will also substantially lose weight.

Effect of endothelin on sex-dependent regulation of tone in coronary resistance vessels.

Background/aims: Sex dependent differences in coronary artery vasoregulation may be due to variations in responses to endogenous vasoactive compounds including endothelin (ET-1) and nitric oxide (NO).

Methods: Septal coronary arteries (<200 μm) from healthy, sexually mature male, female and ovariectomized (i.e.

Regulation of intestinal LDLR by the LXR-IDOL axis.

Background And Aims: Cholesterol metabolism is tightly regulated by transcriptional and post-transcriptional mechanisms. Accordingly, dysregulation of cholesterol metabolism is a major risk factor for the development of coronary artery disease and associated complications. In recent years, it has become apparent that next to the liver, the intestine plays a key role in systemic cholesterol metabolism by governing cholesterol absorption, secretion, and incorporation into lipoprotein particles.

Effect of Platelet GPIIb/IIIa Receptor Blockade With MK383 on Infarct Size and Myocardial Blood Flow in a Canine Reocclusion Model.

Platelet activation and aggregation during ischemia influence reperfusion-related myocyte necrosis, myocardial perfusion at the microvascular level, and thereby eventual recovery of cardiac performance. Inhibition of platelet activity therefore represents a worthwhile target to reduce cellular injury. The current study examined the effects of MK383 (tirofiban), a potent inhibitor of platelet aggregation, on infarct size and myocardial perfusion in canine subjects to either reocclusion (ie, 120-minute + 60-minute ischemia with intervening reperfusion) or prolonged occlusion (ie, 3 hours) followed by reperfusion (180 minutes).

A behavioral test battery for mouse models of Angelman syndrome: a powerful tool for testing drugs and novel mutants.

Background: Angelman syndrome (AS) is a neurodevelopmental disorder caused by mutations affecting UBE3A function. AS is characterized by intellectual disability, impaired motor coordination, epilepsy, and behavioral abnormalities including autism spectrum disorder features. The development of treatments for AS heavily relies on the ability to test the efficacy of drugs in mouse models that show reliable, and preferably clinically relevant, phenotypes.

Balance- and Strength-Training Protocols to Improve Chronic Ankle Instability Deficits, Part II: Assessing Patient-Reported Outcome Measures.

Context:   Assessing global, regional, and fear-of-reinjury outcomes in individuals with chronic ankle instability (CAI) is critical to understanding the effectiveness of clinical interventions.

Objective:   To determine the improvement of patient-reported outcomes after balance- and strength-training and control protocols among participants with CAI.

Design:   Randomized controlled clinical trial.

Balance- and Strength-Training Protocols to Improve Chronic Ankle Instability Deficits, Part I: Assessing Clinical Outcome Measures.

Context:   Functional rehabilitation may improve the deficits associated with chronic ankle instability (CAI).

Objective:   To determine if balance- and strength-training protocols improve the balance, strength, and functional performance deficits associated with CAI.

Design:   Randomized controlled clinical trial.

Inhibition of Na/H Exchanger With EMD 87580 does not Confer Greater Cardioprotection Beyond Preconditioning on Ischemia-Reperfusion Injury in Normal Dogs.

Postischemic accumulation of intracellular Na promotes calcium overload and contributes to cellular necrosis. Cardioprotection afforded by pharmacologic blockade of the sodium-hydrogen exchanger subtype 1 (NHE1) is thought to be more remarkable than that obtained by ischemic conditioning (IC). The window of protection provided by IC pretreatment is maintained even when performed up to 48 hours before ischemia.

The Physiopathology of Cardiorenal Syndrome: A Review of the Potential Contributions of Inflammation.

Inter-organ crosstalk plays an essential role in the physiological homeostasis of the heart and other organs, and requires a complex interaction between a host of cellular, molecular, and neural factors. Derangements in these interactions can initiate multi-organ dysfunction. This is the case, for instance, in the heart or kidneys where a pathological alteration in one organ can unfavorably affect function in another distant organ; attention is currently being paid to understanding the physiopathological consequences of kidney dysfunction on cardiac performance that lead to cardiorenal syndrome.