Basic Science and Pathogenesis.

Background: In AD, neurofibrillary tangles (NFTs) develop earliest in the limbic system before spreading to neocortical areas. When accounting for covariates of AD pathology, such as age and APOE, there remains interindividual variation in NFT spread in the brain. We therefore used a machine-learning approach to investigate whether age-independent DNA methylation (DNAm) changes in brain associate with histopathological differences in AD.

Basic Science and Pathogenesis.

Background: Alzheimer's disease (AD) is characterized by neocortical dissemination of neurofibrillary tangles (NFTs) while primary age-related tauopathy (PART) has NFTs largely confined to the hippocampus and adjacent structures. Thus, PART and AD represent two extremes of a spectrum of NFT spread. We investigated epigenetic mechanisms of interindividual variation in NFT spread.

Nonheme Mononuclear and Dinuclear Iron(II) and Iron(III) Fluoride Complexes and Their Fluorine Radical Transfer Reactivity.

The nonheme iron(II) complexes containing a fluoride anion, Fe(BNPAO)(F) () and [Fe(BNPAOH)(F)(THF)](BF) (), were synthesized and structurally characterized. Addition of dioxygen to either or led to the formation of a fluoride-bridged, dinuclear iron(III) complex [Fe(BNPAO)(F)(μ-F)] (), which was characterized by single-crystal X-ray diffraction, H NMR, and elemental analysis. An iron(II)(iodide) complex, Fe(BNPAO)(I) (), was prepared and reacted with O to give the mononuclear complex -Fe(BNPAO)(OH)(I) ().

The NCR1 transporter is an antimalarial target that exports cholesterol from the parasite's plasma membrane.

Malaria, a devastating parasitic infection, is the leading cause of death in many developing countries. Unfortunately, the most deadliest causative agent of malaria, , has developed resistance to nearly all currently available antimalarial drugs. The Niemann-Pick type C1-related (PfNCR1) transporter has been identified as a druggable target, but its structure and detailed molecular mechanism are not yet available.

Repeated fasting events sensitize enhancers, transcription factor activity and gene expression to support augmented ketogenesis.

Mammals withstand frequent and prolonged fasting periods due to hepatic production of glucose and ketone bodies. Because the fasting response is transcriptionally regulated, we asked whether enhancer dynamics impose a transcriptional program during recurrent fasting and whether this generates effects distinct from a single fasting bout. We found that mice undergoing alternate-day fasting (ADF) respond profoundly differently to a following fasting bout compared to mice first experiencing fasting.

Malaria parasites require a divergent heme oxygenase for apicoplast gene expression and biogenesis.

Malaria parasites have evolved unusual metabolic adaptations that specialize them for growth within heme-rich human erythrocytes. During blood-stage infection, parasites internalize and digest abundant host hemoglobin within the digestive vacuole. This massive catabolic process generates copious free heme, most of which is biomineralized into inert hemozoin.

Revisiting the Plasmodium falciparum druggable genome using predicted structures and data mining.

The identification of novel drug targets for the purpose of designing small molecule inhibitors is key component to modern drug discovery. In malaria parasites, discoveries of antimalarial targets have primarily occurred retroactively by investigating the mode of action of compounds found through phenotypic screens. Although this method has yielded many promising candidates, it is time- and resource-consuming and misses targets not captured by existing antimalarial compound libraries and phenotypic assay conditions.

Influence of the second coordination sphere on O activation by a nonheme iron(II) thiolate complex.

The synthesis and characterization of a new ligand, 1-(bis(pyridin-2-ylmethyl) amino)-2-methylpropane-2-thiolate (BPAS) and its nonheme iron complex, Fe(BPAS)Br (1), is reported. Reaction of 1 with O at -20 °C generates a high-spin iron(III)-hydroxide complex, [Fe(OH)(BPAS)(Br)] (2), that was characterized by UV-vis, Fe Mössbauer, and electron paramagnetic resonance (EPR) spectroscopies, and electrospray ionization mass spectrometry (ESI-MS). Density functional theory (DFT) calculations were employed to support the spectroscopic assignments.

Epigenetic signatures of regional tau pathology and cognition in the aging and pathological brain.

Primary age-related tauopathy (PART) and Alzheimer's disease (AD) share hippocampal phospho-tau (p-tau) pathology but differ in p-tau extent and amyloid presence. As a result, PART uniquely enables investigation of amyloid-independent p-tau mechanisms during brain aging. We conducted the first epigenome-wide association (EWAS) study of PART, which yielded 13 new and robust p-tau/methylation associations.

Elevating diversity, inclusion, and health equity in Pediatric Heart Network Scholars grant funding: unique opportunities and lessons learned.

There is a growing awareness that diversity, health equity, and inclusion play a significant role in improving patient outcomes and advancing knowledge. The Pediatric Heart Network launched an initiative to incorporate diversity, health equity, and inclusion into its 2021 Scholar Award Funding Opportunity Announcement. This manuscript describes the process of incorporating diversity, health equity, and inclusion into the Pediatric Heart Network Scholar Award and the lessons learned.

Using Z Codes to Document Social Risk Factors in the Electronic Health Record: A Scoping Review.

Introduction: Individual-level social risk factors have a significant impact on health. Social risks can be documented in the electronic health record using ICD-10 diagnosis codes (the "Z codes"). This study aims to summarize the literature on using Z codes to document social risks.

Quantifying NO Emission Sources in Houston, Texas Using Remote Sensing Aircraft Measurements and Source Apportionment Regression Models.

Air quality managers in areas exceeding air pollution standards are motivated to understand where there are further opportunities to reduce NO emissions to improve ozone and PM air quality. In this project, we use a combination of aircraft remote sensing (i.e.

Adipocyte Apoptosis Following a Novel Method for Double Chin Reduction: A Pilot Human Histology Study.

Background: Submental fullness is perceived as unattractive by both men and women. The noninvasive simultaneous delivery of HIFES and synchronized radiofrequency+ (Sync RF+) technologies aims to address the submental fullness by concurrently targeting the skin, adipose tissue, and weakened anterior belly of the digastric muscle, the three contributing layers to the double chin appearance.

Aims: This study aims to investigate the histological changes to adipose tissue related to cell morphology, caspase-7, and Bcl-2 levels to detect adipocyte apoptosis following the HIFES and Sync RF+ treatment on human subjects.

Boronic Acid-Based Glucose Detection for Liver Three-Dimensional Cellular Models.

Liver 3D cell models are regularly employed as a screening platform for predicting the metabolic safety of drugs, by monitoring the physiological responses of the spheroids, through the measurement of relevant markers of normal liver physiology, notably glucose. Measuring glucose levels within the spheroids and their surroundings provides insight into the metabolic homeostasis of liver cells and may be employed as an indication of potential drug-induced toxicity. Several ortho-aminomethyl phenylboronic acid (PDBA) glucose sensors have been developed.

Melasma Management: A Comprehensive Review of Treatment Strategies Including BTX-A.

Background: Botulinum toxin A (BTX-A) is a widely utilized protein derived from the bacterium Clostridium botulinum, known for its effectiveness in treating various medical conditions involving muscle spasticity, involuntary muscle movements, and pain disorders. Beyond its therapeutic applications, BTX-A is also commonly used in cosmetic procedures to address dynamic wrinkles, hyperhidrosis, sebum production, pore size, and overall skin texture. While the use of neurotoxins like BTX-A for treating conditions such as UVB-induced hyperpigmentation, specifically melasma, is an emerging area of interest, it is not yet a widely recognized treatment for this dermatologic condition.

Telomere length and chronotype among women in the California Teachers Study (CTS).

While links between certain chronotypes and poorer health outcomes have been well established in previous studies, few studies have examined the relationship between chronotype and cellular aging. Using data from the California Teachers Study (CTS), the present study evaluates the relationship between cellular aging and chronobiology through an analysis of leukocyte telomere length (LTL) and chronotype among 817 predominantly postmenopausal women with no history of cancer and occupations not associated with night-shift work. Unconditional logistic regression models were run to estimate odds ratios (ORs) for each chronotype category, adjusted for age, ethnicity, and smoking status.

The Dallas Donation after Circulatory Death Transplantation Summit: expanding donation after circulatory death procedures through process improvement, broader utilization, and innovation.

Despite a significant increase in utilization over the past decade, the number of donation after circulatory death (DCD) organs that are procured and transplanted in the United States (US) remains well below its potential. There is still room for expansion, as utilizing DCD organs to the fullest extent is currently the most viable solution to the persistent mismatch between supply and demand in transplantation. We convened a multidisciplinary transplantation summit to examine various aspects of DCD, with faculty members from around the world with clinical and academic interest in DCD donation and transplantation, including abdominal and cardiothoracic surgeons, organ procurement organization directors, hepatologists, and gastroenterologists.

Trends in general surgeon operative practice patterns in a modern cohort.

Introduction: Analyzing general surgeons' operative case mix can provide an update on contemporary practice patterns and inform pragmatic residency training.

Methods: We performed a retrospective cohort study of general surgeons in Florida, Iowa, and Maryland, 2016-2020. Cases were identified using billing codes.

Associations Between Exercise Capacity and Psychological Functioning in Children and Adolescents with Fontan Circulation.

Individuals with Fontan circulation (FC) often have diminished exercise capacity and are at risk for psychological problems. The current study examines associations between exercise capacity and psychological functioning in children and adolescents with FC. A multidisciplinary team evaluated participants in a clinic for pediatric patients with FC.

Predicting long-term survival among patients with HCC.

Background: Prognosticating survival among patients with HCC and cirrhosis must account for both the tumor burden/stage, as well as the severity of the underlying liver disease. Although there are many staging systems used to guide therapy, they have not been widely adopted to predict patient-level survival after the diagnosis of HCC. We sought to develop a score to predict long-term survival among patients with early- to intermediate-stage HCC using purely objective criteria.

Implementation of Measurement-Based Care in Mental Health Service Settings for Youth: A Systematic Review.

Measurement-Based Care (MBC) is the systematic use of patient-reported data to inform care decisions and monitor treatment progress. MBC has been shown to improve patient outcomes across medical and mental health treatment settings for adults and youth. While many studies have examined the use of MBC in specific care settings, few have focused on the implementation of MBC among youth populations or across care settings.