Maternal Dietary Deficiencies in Folic Acid and Choline Change Metabolites Levels in Offspring after Ischemic Stroke.

: Ischemic stroke is a major health concern, and nutrition is a modifiable risk factor that can influence recovery outcomes. This study investigated the impact of maternal dietary deficiencies in folic acid (FADD) or choline (ChDD) on the metabolite profiles of offspring after ischemic stroke. : A total of 32 mice (17 males and 15 females) were used to analyze sex-specific differences in response to these deficiencies.

Molecular Imaging of p53 in Mouse Models of Cancer Using a Radiolabeled Antibody TAT Conjugate with SPECT.

Mutations of p53 protein occur in over half of all cancers, with profound effects on tumor biology. We present the first-to our knowledge-method for noninvasive visualization of p53 in tumor tissue in vivo, using SPECT, in 3 different models of cancer. Anti-p53 monoclonal antibodies were conjugated to the cell-penetrating transactivator of transcription (TAT) peptide and a metal ion chelator and then radiolabeled with In to allow SPECT imaging.

The ACE inhibitor captopril inhibits ACN-1 to control dauer formation and aging.

The renin-angiotensin-aldosterone system (RAAS) plays a well-characterized role regulating blood pressure in mammals. Pharmacological and genetic manipulation of the RAAS has been shown to extend lifespan in Caenorhabditis elegans, Drosophila and rodents, but its mechanism is not well defined. Here, we investigate the angiotensin-converting enzyme (ACE) inhibitor drug captopril, which extends lifespan in worms and mice.

[I]CC1: A PARP-Targeting, Auger Electron-Emitting Radiopharmaceutical for Radionuclide Therapy of Cancer.

Poly(adenosine diphosphate ribose) polymerase (PARP) has emerged as an effective therapeutic strategy against cancer that targets the DNA damage repair enzyme. PARP-targeting compounds radiolabeled with an Auger electron-emitting radionuclide can be trapped close to damaged DNA in tumor tissue, where high ionizing potential and short range lead Auger electrons to kill cancer cells through the creation of complex DNA damage, with minimal damage to surrounding normal tissue. Here, we report on [I]CC1, an I-labeled PARP inhibitor for radioligand therapy of cancer.

Connecting Contemporary Trauma Care to Florence Nightingale's Visionary Work.

The impact of Florence Nightingale's visionary work continues to influence the delivery of nursing care in the contemporary emergency department (ED). Her foundational work in the Crimean War resulted in data-based recommendations for using the environment to promote healing and wellness among sick and wounded British soldiers. She advocated for attention to environmental details, including ventilation, air, warmth, drainage, cleanliness, natural light, and low noise levels.

The ACE-inhibitor drug captopril inhibits ACN-1 to control dauer formation and aging.

Unlabelled: The renin-angiotensin-aldosterone system (RAAS) plays a well-characterized role regulating blood pressure in mammals. Pharmacological and genetic manipulation of the RAAS has been shown to extend lifespan in , , and rodents, but its mechanism is not well defined. Here we investigate the angiotensin-converting enzyme (ACE) inhibitor drug captopril, which extends lifespan in worms and mice.

Imaging DNA damage response by γH2AX predicts treatment response to Lutetium-177 radioligand therapy and suggests senescence as a therapeutically desirable outcome.

An effective absorbed dose response relationship is yet to be established for Lutetium-177 based radionuclide therapies such as Lu-DOTATATE and Lu-PSMA. The inherent biological heterogeneity of neuroendocrine and prostate cancers may make the prospect of establishing cohort-based dose-response relationships unobtainable. Instead, an individual-based approach, monitoring the dose-response within each tumor could provide the necessary metric to monitor treatment efficacy.

A radioiodinated rucaparib analogue as an Auger electron emitter for cancer therapy.

Introduction: Radioligand therapy (RLT) is an expanding field that has shown great potential in the fight against cancer. Radionuclides that can be carried by selective ligands such as antibodies, peptides, and small molecules targeting cancerous cells have demonstrated a clear improvement in the move towards precision medicine. Poly (ADP-ribose) polymerase (PARP) is a family of enzymes involved in DNA damage repair signalling pathway, with PARP inhibitors olaparib, talazoparib, niraparib, veliparib, and rucaparib having FDA approval for cancer therapy in routine clinical use.

Correlation between molar activity, injection mass and uptake of the PARP targeting radiotracer [F]olaparib in mouse models of glioma.

Purpose: Radiopharmaceuticals targeting poly(ADP-ribose) polymerase (PARP) have emerged as promising agents for cancer diagnosis and therapy. PARP enzymes are expressed in both cancerous and normal tissue. Hence, the injected mass, molar activity and potential pharmacological effects are important considerations for the use of radiolabelled PARP inhibitors for diagnostic and radionuclide therapeutic applications.

Patterns of Healthcare Use and Mortality After Alzheimer's Disease or Related Dementia Diagnosis Among Alaska Native Patients: Results of a Cluster Analysis in a Tribal Healthcare Setting.

Background: Alaska Native and American Indian (AN/AI) people represent a rapidly aging population with disproportionate burdens of Alzheimer's disease and related dementias (ADRD) risk factors.

Objective: To characterize healthcare service use patterns and mortality in the years following ADRD diagnosis for patients in an Alaska Native Tribal health system.

Methods: The study sample included all AN/AI patients aged 55 or older with an ADRD diagnosis who were seen between 2012-2018 ( = 407).

Imaging PARP with [F]rucaparib in pancreatic cancer models.

Purpose: Rucaparib, an FDA-approved PARP inhibitor, is used as a single agent in maintenance therapy to provide promising treatment efficacy with an acceptable safety profile in various types of BRCA-mutated cancers. However, not all patients receive the same benefit from rucaparib-maintenance therapy. A predictive biomarker to help with patient selection for rucaparib treatment and predict clinical benefit is therefore warranted.

A model for abolitionist narrative medicine pedagogy.

To use narrative medicine as a means for action towards social justice in medical education, we need a renewal of our pedagogical methods that grapples not just with the worlds concocted within a text, but also our own world beyond the text. We propose a model for narrative medicine pedagogy that is oriented towards abolition. First, the composition of the classroom and syllabus must employ radical inclusion through recruitment of diverse voices and selection of diverse texts.

Novel Coronavirus Infection (COVID-19) Related Thrombotic and Bleeding Complications in Critically Ill Patients: Experience from an Academic Medical Center.

Introduction: Thrombosis and bleeding are recognized complications of the novel coronavirus infection (COVID-19), with a higher incidence described particularly in the critically ill.

Methods: A retrospective review of COVID-19 patients admitted to our intensive care units (ICU) between 1 January 2020 and 31 December 2020 was performed. Primary outcomes included clinically significant thrombotic and bleeding events (according to the ISTH definition) in the ICU.

Characteristics and Outcomes of COVID-19 Patients Admitted to Intensive Care Units in a Large Health System in Western Pennsylvania.

Importance Despite growing literature, there is still limited understanding of factors that can predict outcomes in coronavirus disease 2019 (COVID-19) patients who require intensive care. Objective To evaluate the characteristics of COVID-19 patients admitted to the intensive care unit (ICU) and identify their associations with outcomes. Background There are limited data on the outcomes in COVID-19 patients in Pennsylvania.

Therapy outcomes for neurodiverse couples: Exploring a solution-focused approach.

The need for clinical approaches that address romantic relationship concerns of adults with autism spectrum disorder (ASD) has been essentially overlooked. There are a growing number of recommendations in the available literature to increase the availability and evaluation of treatment approaches that are appropriate for couples that include an adult with ASD. The aim of the present study was to explore clinical outcomes of a neurodiverse couple who participated in twelve sessions of solution-focused brief therapy.

Global, cell non-autonomous gene regulation drives individual lifespan among isogenic .

Across species, lifespan is highly variable among individuals within a population. Even genetically identical reared in homogeneous environments are as variable in lifespan as outbred human populations. We hypothesized that persistent inter-individual differences in expression of key regulatory genes drives this lifespan variability.

Thinking with two brains: Student perspectives on the presentation of race in pre-clinical medical education.

Context: There is growing concern that during their education medical students come to believe that 'race' is a biological construct and that differential treatment of patients based on 'race' is clinically beneficial. How 'race' is presented to medical students may influence both their implicit biases and future clinical practices, potentially widening racial disparities in care.

Methods: We conducted in-depth interviews with twenty-two pre-clinical mostly non-White medical students attending a public medical school in a major metropolitan area in the northeastern United States.

Radiolabeled cCPE Peptides for SPECT Imaging of Claudin-4 Overexpression in Pancreatic Cancer.

Overexpression of tight-junction protein claudin-4 has been detected in primary and metastatic pancreatic cancer tissue and is associated with better prognosis in patients. Noninvasive measurement of claudin-4 expression by imaging methods could provide a means for accelerating detection and stratifying patients into risk groups. enterotoxin (CPE) is a natural ligand for claudin-4 and holds potential as a targeting vector for molecular imaging of claudin-4 overexpression.

"It's Like Plan B but for HIV!" Design and Evaluation of a Media Campaign to Drive Demand for PEP.

Post-exposure Prophylaxis (PEP) is an effective yet underutilized HIV prevention tool. PEPTALK developed and evaluated a media campaign to drive demand for PEP among men who have sex with men (MSM) and transgender women (TW) living in high HIV prevalence areas in New York City. Formative qualitative research (38 in-depth interviews and five focus groups [N = 48]) with Black or African-American MSM or TW who reported condomless sex with a HIV-positive/unknown status man was conducted to inform campaign design.

[F]AZD2461, an Insight on Difference in PARP Binding Profiles for DNA Damage Response PET Imaging.

Background: Poly (ADP-ribose) polymerase (PARP) inhibitors are extensively studied and used as anti-cancer drugs, as single agents or in combination with other therapies. Most radiotracers developed to date have been chosen on the basis of strong PARP1-3 affinity. Herein, we propose to study AZD2461, a PARP inhibitor with lower affinity towards PARP3, and to investigate its potential for PARP targeting in vivo.