Uncovering multilevel drivers of cancer disparities among Latinos in the United States.

Cancer disparities among Latinos in the United States persist as a significant public health challenge, characterized by inequitable outcomes throughout the cancer continuum. Latinos experience elevated rates and poorer prognoses in certain cancers compared to other populations, driven by complex, multilevel interactions involving environmental exposures, genetic factors, cultural practices, and systemic inequalities. Recognizing the substantial heterogeneity among Latinos-including differences in national origin, immigration experiences, socioeconomic status, language, and race-is crucial, as oversimplification risks masking key disparities.

Unfolded von Willebrand factor binds protein S and reduces anticoagulant activity.

The critical plasma anticoagulant protein S (PS) circulates in 2 functionally distinct pools: free (anticoagulant) or bound to complement component 4b-binding protein (C4BP; anti-inflammatory). Acquired free PS deficiency is detected in several viral infections, but its cause is unclear. Here, we used biochemical approaches and human patient plasma samples to identify an interaction between PS and von Willebrand factor (VWF), which causes free PS deficiency and reduced PS anticoagulant activity.

TNF-α impairs platelet function by inhibiting autophagy and disrupting metabolism via syntaxin 17 downregulation.

Platelets play a dual role in hemostasis and inflammation-associated thrombosis and hemorrhage. Although the mechanisms linking inflammation to platelet dysfunction remain poorly understood, our previous work demonstrated that TNF-α alters mitochondrial mass, platelet activation, and autophagy-related pathways in megakaryocytes. Here, we hypothesized that TNF-α impairs platelet function by disrupting autophagy, a process critical for mitochondrial health and cellular metabolism.

A Tour in the Chemistry of a Tricoordinate Rh(-I) Complex.

The finding of the unprecedented 16-e tricoordinate planar rhodium(-Ι) complex, K[Rh(IPr)(dvtms)] (K[1]) (IPr = 1,3-bis(2,6-diisopropylphenyl)imidazolyl-2-ylidene, dvtms = divinyltretramethyldisiloxane) prompted us to explore its reactivity. K[1] reacts as a nucleophile with methyliodide to give [Rh(IPr)(dvtms)Me], a Rh(Ι) compound with an exceptional trigonal-pyramidal structure. Other haloalkanes abstract one electron from K[1] to give the previously reported [Rh(IPr)(dvtms)] complex.

Mitochondrial-Mediated Platelet Activation in Polymyalgia Rheumatica.

Objective: Platelet activation is thought to participate in polymyalgia rheumatica (PMR) pathogenesis. Upon platelet activation, mitochondria are expelled into the extracellular space. However, whether extracellular mitochondria are present in patients with PMR and whether they can induce platelet activation is not known.

The Polyanalgesic Consensus Conference (PACC)®: Updates on Clinical Pharmacology and Comorbidity Management in Intrathecal Drug Delivery for Cancer Pain.

Introduction: The International Neuromodulation Society convened a multispecialty group of physicians based on expertise with international representation to establish evidence-based guidance on using intrathecal drug delivery in chronic pain treatment. This Polyanalgesic Consensus Conference (PACC)® project's scope is to provide evidence-based guidance for clinical pharmacology and best practices for intrathecal drug delivery for cancer pain.

Materials And Methods: Authors were chosen on the basis of their clinical expertise, familiarity with the peer-reviewed literature, research productivity, and contributions to the neuromodulation literature.

Filamin A regulates platelet shape change and contractile force generation via phosphorylation of the myosin light chain.

Platelets are critical mediators of hemostasis and thrombosis. Platelets circulate as discs in their resting form but change shape rapidly upon activation by vascular damage and/or soluble agonists such as thrombin. Platelet shape change is driven by a dynamic remodeling of the actin cytoskeleton.

Transposon DNA sequences facilitate the tissue-specific gene transfer of circulating tumor DNA between human cells.

The exchange of genes between cells is known to play an important physiological and pathological role in many organisms. We show that circulating tumor DNA (ctDNA) facilitates cell-specific gene transfer between human cancer cells and explain part of the mechanisms behind this phenomenon. As ctDNA migrates into the nucleus, genetic information is transferred.

Removal of endothelial surface-associated von villebrand factor suppresses accelerate datherosclerosis after myocardial infarction.

Background: Thromboinflammation involving platelet adhesion to endothelial surface-associated von Willebrand factor (VWF) has been implicated in the accelerated progression of non-culprit plaques after MI. The aim of this study was to use arterial endothelial molecular imaging to mechanistically evaluate endothelial-associated VWF as a therapeutic target for reducing remote plaque activation after myocardial infarction (MI).

Methods: Hyperlipidemic mice deficient for the low-density lipoprotein receptor and Apobec-1 underwent closed-chest MI and were treated chronically with either: (i) recombinant ADAMTS13 which is responsible for proteolytic removal of VWF from the endothelial surface, (ii) N-acetylcysteine (NAC) which removes VWF by disulfide bond reduction, (iii) function-blocking anti-factor XI (FXI) antibody, or (iv) no therapy.

Cold temperature induces a TRPM8-independent calcium release from the endoplasmic reticulum in human platelets.

The detection of temperature by the human sensory system is life-preserving and highly evolutionarily conserved. Platelets are sensitive to temperature changes and are activated by a decrease in temperature, akin to sensory neurons. However, the molecular mechanism of this temperature-sensing ability is unknown.

Unfolded Von Willebrand Factor Binds Protein S and Reduces Anticoagulant Activity.

Protein S (PS), the critical plasma cofactor for the anticoagulants tissue factor (TF) pathway inhibitor (TFPI) and activated protein C (APC), circulates in two functionally distinct pools: free (anticoagulant) or bound to complement component 4b-binding protein (C4BP) (anti-inflammatory). Acquired free PS deficiency is detected in several viral infections, but its cause is unclear. Here, we identified a shear-dependent interaction between PS and von Willebrand Factor (VWF) by mass spectrometry.

Redox-Transmetalation Reactions: Easy Access to Homo- and Heterodimetallic d,d Complexes.

The ability of the imine PyCH═N-CHPy (Py = 2-pyridyl, bpi) to behave as a heteroditopic ligand, which is suitable for creating two separate compartments to host metals in different oxidation states, has been developed by studying the reactions of the mixed-valence complexes [(cod)M(μ-bpi)M(cod)] (M = Rh, Ir) with [M'(Cl)(PPh)] (M' = Pd, Ni). The results depend on the molar ratio of the reagents used (1:1 or 1:2) to give the heterometallic complexes {d-M',d-M}-[(PPh)(Cl)M'(μ-bpi)M(cod)] (Pd,Rh, ; Pd,Ir, ; Ni,Rh, ; Ni,Ir, ) and the two-electron mixed-valent compounds [(PPh)(Cl)M'(μ-bpi)M'(Cl)] (M' = Ni, ; Pd, ), respectively. A redox process occurs in the replacement of the low-valent [(cod)M] fragment, whereas the exchange of the [(cod)M] fragment is redox-neutral.

Molecular hydrogen and water activation by transition metal frustrated Lewis pairs containing ruthenium or osmium components: catalytic hydrogenation assays.

The transition metal frustrated Lewis pair compounds [(Cym)M(κS,P,N-HL1)][SbF] (Cym = η--MeCHiPr; H2L1 = -(-tolyl)-'-(2-diphenylphosphanoethyl)thiourea; M = Ru (5), Os (6)) have been prepared from the corresponding dimer [{(Cym)MCl}(μ-Cl)] and H2L1 by successive chloride abstraction with NaSbF and AgSbF and NH deprotonation with NaHCO. Complexes 5 and 6 and the previously reported phosphano-guanidino compounds [(Cym)M(κP,N,N'-HL2)][SbF] [H2L2 = ,'-bis(-tolyl)-''-(2-diphenylphosphanoethyl) guanidine; M = Ru (7), Os (8)] and pyridinyl-guanidino compounds [(Cym)M(κN,N',N''-HL3)][SbF] [H2L3 = ,'-bis(-tolyl)-''-(2-pyridinylmethyl) guanidine; M = Ru (9), Os (10)] heterolytically activate H in a reversible manner affording the hydrido complexes [(Cym)MH(H2L)][SbF] (H2L = H2L1; M = Ru (11), Os (12); H2L = H2L2; M = Ru (13), Os (14); H2L = H2L3; M = Ru (15), Os (16)). DFT calculations carried out on the hydrogenation of complex 7 support an FLP mechanism for the process.

Intracellular tPA-PAI-1 interaction determines VLDL assembly in hepatocytes.

Apolipoprotein B (apoB)-lipoproteins initiate and promote atherosclerotic cardiovascular disease. Plasma tissue plasminogen activator (tPA) activity is negatively associated with atherogenic apoB-lipoprotein cholesterol levels in humans, but the mechanisms are unknown. We found that tPA, partially through the lysine-binding site on its Kringle 2 domain, binds to the N terminus of apoB, blocking the interaction between apoB and microsomal triglyceride transfer protein (MTP) in hepatocytes, thereby reducing very-low-density lipoprotein (VLDL) assembly and plasma apoB-lipoprotein cholesterol levels.

Low-density lipoprotein promotes microvascular thrombosis by enhancing von Willebrand factor self-association.

von Willebrand factor (VWF) mediates primary hemostasis and thrombosis in response to hydrodynamic forces. We previously showed that high shear promoted self-association of VWF into hyperadhesive strands, which can be attenuated by high-density lipoprotein (HDL) and apolipoprotein A-I. In this study, we show that low-density lipoprotein (LDL) binds VWF under shear and enhances self-association.

Cold temperature induces a TRPM8-independent calcium release from the endoplasmic reticulum in human platelets.

Platelets are sensitive to temperature changes and akin to sensory neurons, are activated by a decrease in temperature. However, the molecular mechanism of this temperature-sensing ability is unknown. Yet, platelet activation by temperature could contribute to numerous clinical sequelae, most importantly to reduced quality of -stored platelets for transfusion.

Distinct platelet F-actin patterns and traction forces on von Willebrand factor versus fibrinogen.

Upon vascular injury, platelets form a hemostatic plug by binding to the subendothelium and to each other. Platelet-to-matrix binding is initially mediated by von Willebrand factor (VWF) and platelet-to-platelet binding is mediated mainly by fibrinogen and VWF. After binding, the actin cytoskeleton of a platelet drives its contraction, generating traction forces that are important to the cessation of bleeding.

Mixed-Valence Tetrametallic Iridium Chains.

Neutral [X-{Ir }-{Ir }-X] (X=Cl, Br, SCN, I) and dicationic [L-{Ir }-{Ir }-L] (L=MeCN, Me CO) tetrametallic iridium chains made by connecting two dinuclear {Ir } units ({Ir }=[Ir (μ-OPy) (CO) ], OPy=2-pyridonate) by an iridium-iridium bond are described. The complexes exhibit fractional averaged oxidation states of +1.5 and electronic delocalization along the metallic chain.

Elevated LDL Cholesterol Increases Microvascular Endothelial VWF and Thromboinflammation After Myocardial Infarction.

Background: In reperfused myocardial infarction, VWF (von Willebrand factor)-mediated platelet adhesion contributes to impaired microvascular reflow and possibly also to postmyocardial infarction inflammation. We hypothesized that postischemic thromboinflammatory processes are worsened by elevated LDL (low-density lipoprotein) cholesterol.

Methods: Myocardial ischemia-reperfusion or sham procedure was performed in wild-type mice and hyperlipidemic mice deficient for the LDL receptor and Apobec-1 (apolipoprotein-B mRNA editing enzyme catalytic polypeptide-1; DKO [double knockout]).

Plasma Interleukin-6 (IL-6), Angiopoietin-2, and C-Reactive Protein Levels Predict Subsequent Type 1 Myocardial Infarction in Persons With Treated HIV Infection.

Background: HIV infection leads to endothelial activation, promoting platelet adhesion, and accelerating atherosclerosis. Our goal was to determine whether biomarkers of endothelial activation and hemostasis/thrombosis were elevated in people with treated HIV (PWH) before myocardial infarction (MI).

Methods: In a case-control study nested within the CFAR Network of Integrated Clinical Systems (CNICS) cohort, we compared 69 adjudicated cases with type 1 MI with 138 controls matched for antiretroviral therapy regimen.

Iridium-Catalyzed Regio- and Diastereoselective Synthesis of C-Substituted Piperazines.

Piperazine rings are essential motifs frequently found in commercial drugs. However, synthetic methodologies are mainly limited to -substituted piperazines, preventing structural diversity. Disclosed herein is a straightforward catalytic method for the synthesis of complex C-substituted piperazines based on an uncommon head-to-head coupling of easily prepared imines.

Reduced Proteolytic Cleavage of von Willebrand Factor Leads to Aortic Valve Stenosis and Load-Dependent Ventricular Remodeling.

We hypothesized that excess endothelial-associated von Willebrand factor (vWF) and secondary platelet adhesion contribute to aortic valve stenosis (AS). We studied hyperlipidemic mice lacking ADAMTS13 ( ), which cleaves endothelial-associated vWF multimers. On echocardiography and molecular imaging, compared with control strains had increased aortic endothelial vWF and platelet adhesion and developed hemodynamically significant AS, arterial stiffening, high valvulo-aortic impedance, and secondary load-dependent reduction in LV systolic function.

The Awake Craniotomy: A Patient's Experience and A Literature Review.

We present a case report and a literature review of the awake craniotomy procedure for mass resection, with emphasis on the historical aspects, anatomical and surgical considerations, and, uniquely, a patient's experience undergoing this procedure. This procedure is a safe and effective method for lesion resection when working in and around eloquent brain. We have described our process of guiding a patient through an awake craniotomy procedure and detailed the patient's experience in this study.