Size-dependent shape distributions of platinum nanoparticles.

While it is well established that nanoparticle shape can depend on equilibrium thermodynamics or growth kinetics, recent computational work has suggested the importance of thermal energy in controlling the distribution of shapes in populations of nanoparticles. Here, we used transmission electron microscopy to characterize the shapes of bare platinum nanoparticles and observed a strong dependence of shape distribution on particle size. Specifically, the smallest nanoparticles (<2.

Exploring discordant low amyloid beta and high neocortical tau positron emission tomography cases.

Introduction: Neocortical 3R4R (3-repeat/4-repeat) tau aggregates are rarely observed in the absence of amyloid beta (Aβ). F-MK6240 binds specifically to the 3R4R form of tau that is characteristic of Alzheimer's disease (AD). We report four cases with negative Aβ, but positive tau positron emission tomography (PET) findings.

Assessment of Alcohol and Other Substance Use in Patients With Chronic Liver Disease.

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Pharmacokinetic, pharmacodynamic, and transcriptomic analysis of chronic levetiracetam treatment in 5XFAD mice: A MODEL-AD preclinical testing core study.

Introduction: Hyperexcitability and epileptiform activity are commonplace in Alzheimer's disease (AD) patients and associated with impaired cognitive function. The anti-seizure drug levetiracetam (LEV) is currently being evaluated in clinical trials for ability to reduce epileptiform activity and improve cognitive function in AD. The purpose of our studies was to establish a pharmacokinetic/pharmacodynamic (PK/PD) relationship with LEV in an amyloidogenic mouse model of AD to enable predictive preclinical to clinical translation, using the rigorous preclinical testing pipeline of the Model Organism Development and Evaluation for Late-Onset Alzheimer's Disease Preclinical Testing Core.

Hydrophobic cavity-directed azide-acetyllysine photochemistry for profiling non-histone interacting partners of bromodomain protein 1.

Bromodomain containing protein 1 (BRD1) plays critical roles in chromatin acetylation, gene transcription, erythropoiesis, and brain development. BRD1 is also implicated in several human conditions and is a therapeutic target for cancer. Although, the bromodomain is known to bind acetylated histones, how the function of BRD1 is regulated via non-histone acetylation is unexplored.

Myocardin-related transcription factor's interaction with serum-response factor is critical for outgrowth initiation, progression, and metastatic colonization of breast cancer cells.

Breast cancer (BC)-related mortality primarily results from metastatic colonization of disseminated cells. Actin polymerization plays an important role in driving post-extravasation metastatic outgrowth of tumor cells. This study examines the role of myocardin-related transcription factor (MRTF)/serum-response (SRF), a transcription system well known for regulation of cytoskeletal genes, in metastatic colonization of BC cells.

Genetic confirmation of a hybrid between two highly divergent cardinalid species: A rose-breasted grosbeak () and a scarlet tanager ().

Using low-coverage whole-genome sequencing, analysis of vocalizations, and inferences from natural history, we document a first-generation hybrid between a rose-breasted grosbeak () and a scarlet tanager (). These two species occur sympatrically throughout much of eastern North America, although were not previously known to interbreed. Following the field identification of a putative hybrid, we use genetic and bioacoustic data to show that a rose-breasted grosbeak was the maternal parent and a scarlet tanager was the paternal parent of the hybrid, whose song was similar to the latter species.

Managing surgery in hemophilia with recombinant factor VIII Fc and factor IX Fc: Data on safety and effectiveness from phase 3 pivotal studies.

Background: Surgical procedures impose hemostatic risk to people with hemophilia, which may be minimized by optimal factor (F) replacement therapy.

Methods: This analysis evaluates the efficacy and safety of extended half-life factor replacement recombinant FVIII and FIX Fc fusion proteins (rFVIIIFc and rFIXFc) during surgery in phase 3 pivotal (A-LONG/Kids A-LONG and B-LONG/Kids B-LONG) and extension (ASPIRE and B-YOND) studies. Dosing regimens were determined by investigators.

Homeostatic response to sleep deprivation and circadian rhythmicity are intact in older adults with insomnia.

Study Objectives: We examined whether homeostatic sleep drive and circadian rhythmicity differ in older adults with insomnia (OAI) compared to older good sleepers (GS).

Methods: OAI (n = 37) and GS (n = 30) participated in a 60-h in-lab study with sleep deprivation and constant routine paradigms. Homeostatic sleep drive was assessed by examining the effect of sleep deprivation on delta EEG power and theta EEG power, and repeated sleep latency tests.

Characteristics Associated With Growth Differentiation Factor 15 in Heart Failure With Preserved Ejection Fraction and the Impact of Pirfenidone.

Background Growth differentiation factor 15 (GDF-15) is elevated in heart failure with preserved ejection fraction and is associated with adverse outcome, but its relationship with myocardial fibrosis and other characteristics remains unclear. We sought to evaluate the effect of pirfenidone, a novel antifibrotic agent, on GDF-15 in heart failure with preserved ejection fraction and identify characteristics that associate with GDF-15 and with change in GDF-15 over 1 year. Methods and Results Among patients enrolled (n=107) in the PIROUETTE (Pirfenidone in Patients With Heart Failure and Preserved Left Ventricular Ejection Fraction) trial, GDF-15 was measured at baseline and at prespecified time points in patients randomized (n=94) to pirfenidone or placebo.

Cell Sorter Cleaning Practices and Their Impact on Instrument Sterility.

Cells isolated using electrostatic cell sorters are subsequently evaluated in a variety of in vitro and in vivo applications. Thus, manipulations to the cells during the pre- and post-sort processing as well as when the cells are being analyzed by and passing through the sorter fluidics has the potential to affect the experimental results. There are many variables to consider when seeking to preserve cellular integrity and function during the cell-sorting process.

Illustrated State-of-the-Art Capsules of the ISTH 2022 Congress.

The ISTH London 2022 Congress is the first held (mostly) face-to-face again since the COVID-19 pandemic took the world by surprise in 2020. For 2 years we met virtually, but this year's in-person format will allow the ever-so-important and quintessential creativity and networking to flow again. What a pleasure and joy to be able to see everyone! Importantly, all conference proceedings are also streamed (and available recorded) online for those unable to travel on this occasion.

Improved hospitalization rates in a specialty center for heart failure with preserved ejection fraction and pulmonary hypertension.

Heart failure with preserved ejection fraction can be complicated by pulmonary hypertension. We designed a retrospective study to provide supporting evidence for referral to specialty care centers. Specialty care centers improved hospitalizations but not mortality-in part due to more aggressive medication management and guideline-directed monitoring.

Percutaneous lumbar annular puncture: A rat model to study intervertebral disc degeneration and pain-related behavior.

Background: Previous animal models of intervertebral disc degeneration (IDD) rely on open surgical approaches, which confound the degenerative response and pain behaviors due to injury to surrounding tissues during the surgical approach. To overcome these challenges, we developed a minimally invasive percutaneous puncture procedure to induce IDD in a rat model.

Methods: Ten Fischer 344 male rats underwent percutaneous annular puncture of lumbar intervertebral discs (IVDs) at L2-3, L3-4, and L4-5.

Investigation into the anti-inflammatory properties of metformin in intervertebral disc cells.

Introduction: Intervertebral disc degeneration (IDD) is closely related to heightened inflammation in the annulus fibrosis (AF) and nucleus pulposus (NP) cells in the intervertebral disc. An imbalanced matrix homeostasis has been shown to contribute to disc degeneration and associated discogenic low back pain. Metformin, a diabetes medication, has been noted to exhibit anti-inflammatory properties through upregulation of the AMPK pathway, leading to various anti-inflammatory-related responses in hepatocytes.

Misdiagnosis of Thoracic Aortic Emergencies Occurs Frequently Among Transfers to Aortic Referral Centers: An Analysis of Over 3700 Patients.

Background Acute aortic syndromes may be prone to misdiagnosis by nonreferral aortic centers with less diagnostic experience. We evaluated regional variability in these misdiagnosis trends among patients transferred to different regional quaternary care centers with presumed acute aortic syndromes. Methods and Results Two institutional aortic center databases were retrospectively reviewed for emergency transfers in patients diagnosed with acute aortic dissection, intramural hematoma, penetrating aortic ulcer, thoracic aortic aneurysm, or aortic pseudoaneurysm between 2008 and 2020.

Functional amyloids from bacterial biofilms - structural properties and interaction partners.

Protein aggregation and amyloid formation have historically been linked with various diseases such as Alzheimer's and Parkinson's disease, but recently functional amyloids have gained a great deal of interest in not causing a disease and having a distinct function . Functional bacterial amyloids form the structural scaffold in bacterial biofilms and provide a survival strategy for the bacteria along with antibiotic resistance. The formation of functional amyloids happens extracellularly which differs from most disease related amyloids.

C2-ketonylation of carbohydrates excited-state palladium-catalyzed 1,2-spin-center shift.

C2-ketonyl-2-deoxysugars, sugars with the C2-hydroxyl group replaced by a ketone side chain, are important carbohydrate mimetics in glycobiology and drug discovery studies; however, their preparation remains a vital challenge in organic synthesis. Here we report the first direct strategy to synthesize this class of glycomimetics from readily available 1-bromosugars and silyl enol ethers an excited-state palladium-catalyzed 1,2-spin-center shift (SCS) process. This step-economic reaction features broad substrate scope, has a high functional group tolerance, and can be used in late-stage functionalization of natural product- and drug-glycoconjugates.

Association of Race and Ethnicity on the Management of Acute Non-ST-Segment Elevation Myocardial Infarction.

Background Prior studies have reported disparities by race in the management of acute myocardial infarction (MI), with many studies having limited covariates or now dated. We examined racial and ethnic differences in the management of MI, specifically non-ST-segment-elevation MI (NSTEMI), in a large, socially diverse cohort of insured patients. We hypothesized that the racial and ethnic disparities in the receipt of coronary angiography or percutaneous coronary intervention would persist in contemporary data.

Social Determinants of Health Factors for Gene-Environment COVID-19 Research: Challenges and Opportunities.

The characteristics of a person's health status are often guided by how they live, grow, learn, their genetics, as well as their access to health care. Yet, all too often, studies examining the relationship between social determinants of health (behavioral, sociocultural, and physical environmental factors), the role of demographics, and health outcomes poorly represent these relationships, leading to misinterpretations, limited study reproducibility, and datasets with limited representativeness and secondary research use capacity. This is a profound hurdle in what questions can or cannot be rigorously studied about COVID-19.