Multiomic analysis implicates FOXO4 in genetic regulation of chick lens fiber cell differentiation.

A classic model for identification of novel differentiation mechanisms and pathways is the eye lens that consists of a monolayer of quiescent epithelial cells that are the progenitors of a core of mature fully differentiated fiber cells. The differentiation of lens epithelial cells into fiber cells follows a coordinated program involving cell cycle exit, expression of key structural proteins and the hallmark elimination of organelles to achieve transparency. Although multiple mechanisms and pathways have been identified to play key roles in lens differentiation, the entirety of mechanisms governing lens differentiation remain to be discovered.

Multiomics Analysis Reveals Novel Genetic Determinants for Lens Differentiation, Structure, and Transparency.

Recent advances in next-generation sequencing and data analysis have provided new gateways for identification of novel genome-wide genetic determinants governing tissue development and disease. These advances have revolutionized our understanding of cellular differentiation, homeostasis, and specialized function in multiple tissues. Bioinformatic and functional analysis of these genetic determinants and the pathways they regulate have provided a novel basis for the design of functional experiments to answer a wide range of long-sought biological questions.

Autophagy Requirements for Eye Lens Differentiation and Transparency.

Recent evidence points to autophagy as an essential cellular requirement for achieving the mature structure, homeostasis, and transparency of the lens. Collective evidence from multiple laboratories using chick, mouse, primate, and human model systems provides evidence that classic autophagy structures, ranging from double-membrane autophagosomes to single-membrane autolysosomes, are found throughout the lens in both undifferentiated lens epithelial cells and maturing lens fiber cells. Recently, key autophagy signaling pathways have been identified to initiate critical steps in the lens differentiation program, including the elimination of organelles to form the core lens organelle-free zone.

Repurposing a Cyclin-Dependent Kinase 1 (CDK1) Mitotic Regulatory Network to Complete Terminal Differentiation in Lens Fiber Cells.

Purpose: During lens fiber cell differentiation, organelles are removed in an ordered manner to ensure lens clarity. A critical step in this process is removal of the cell nucleus, but the mechanisms by which this occurs are unclear. In this study, we investigate the role of a cyclin-dependent kinase 1 (CDK1) regulatory loop in controlling lens fiber cell denucleation (LFCD).

Patterns of Crystallin Gene Expression in Differentiation State Specific Regions of the Embryonic Chicken Lens.

Purpose: Transition from lens epithelial cells to lens fiber cell is accompanied by numerous changes in gene expression critical for lens transparency. We identify expression patterns of highly prevalent genes including ubiquitous and enzyme crystallins in the embryonic day 13 chicken lens.

Methods: Embryonic day 13 chicken lenses were dissected into central epithelial cell (EC), equatorial epithelial cell (EQ), cortical fiber cell (FP), and nuclear fiber cell (FC) compartments.

Changes in DNA methylation hallmark alterations in chromatin accessibility and gene expression for eye lens differentiation.

Background: Methylation at cytosines (mCG) is a well-known regulator of gene expression, but its requirements for cellular differentiation have yet to be fully elucidated. A well-studied cellular differentiation model system is the eye lens, consisting of a single anterior layer of epithelial cells that migrate laterally and differentiate into a core of fiber cells. Here, we explore the genome-wide relationships between mCG methylation, chromatin accessibility and gene expression during differentiation of eye lens epithelial cells into fiber cells.

Ex vivo generation of regulatory T cells from liver transplant recipients using costimulation blockade.

The potential of adoptive cell therapy with regulatory T cells (Tregs) to promote transplant tolerance is under active exploration. However, the impact of specific transplant settings and protocols on Treg manufacturing is not well-delineated. Here, we compared the use of peripheral blood mononuclear cells (PBMCs) from patients before or after liver transplantation to the use of healthy control PBMCs to determine their suitability for Treg manufacture using ex vivo costimulatory blockade with belatacept.

Improving Health Professions Students' Understanding of Interprofessional Roles Through Participation in a Patient Stabilization Simulation.

To teach interprofessional communication and teamwork skills to health professions students through a standardized patient simulation on acute patient stabilization and measure the impact on learners' perceptions of interprofessional collaboration. Medical and pharmacy students in their final year and post-licensure nurses in their initial six-month probationary period worked together to stabilize a simulated acutely ill standardized patient. Perceptions of IPE were assessed pre- and post-simulation using the Student Perceptions of Interprofessional Clinical Education-Revised Instrument, version 2 (SPICE-R2).

A functional map of genomic HIF1α-DNA complexes in the eye lens revealed through multiomics analysis.

Background: During eye lens development the embryonic vasculature regresses leaving the lens without a direct oxygen source. Both embryonically and throughout adult life, the lens contains a decreasing oxygen gradient from the surface to the core that parallels the natural differentiation of immature surface epithelial cells into mature core transparent fiber cells. These properties of the lens suggest a potential role for hypoxia and the master regulator of the hypoxic response, hypoxia-inducible transcription factor 1 (HIF1), in the regulation of genes required for lens fiber cell differentiation, structure and transparency.

Mechanisms of organelle elimination for lens development and differentiation.

A hallmark feature of lens development and differentiation is the complete elimination of organelles from the center of the eye lens. A long unanswered question in lens biology is what are the mechanisms that control the elimination of organelles during the terminal remodeling program to form mature lens fiber cells? Recent advances have expanded our understanding of these mechanisms including newly discovered signaling pathways, proteasomal regulators, autophagy proteins, transcription factors and the hypoxic environment of the lens itself. These recent discoveries suggest that distinct mechanisms coordinate the elimination of the nucleus, mitochondria, endoplasmic reticulum and Golgi apparatus during lens fiber cell differentiation.

Concentrated Learning Experiences Across Two Different Health-Systems.

Background: While many public pharmacy schools have an adjoining health-system to accommodate their students, some pharmacy programs form partnerships with non-affiliated health-systems to precept students. These health-systems often afford students the opportunity to complete multiple rotations within a single organization, offering decreased onboarding time and more longitudinal experiences.

Innovation: Two autonomous partnerships were developed with independent healthcare systems for concentrated learning experiences during the advanced pharmacy practice experiences year.

Accomplishing CAPE Domain 3 During APPE Rotations: Student Perceptions.

Introduction: The purpose of this study is to examine student perceptions of accomplishment among 6 subdomains of Center for Advancement of Pharmacy Education (CAPE) Domain 3 "Approach to Practice and Care" outcomes in Advanced Pharmacy Practice Experiences (APPE) across distinct geographical regions.

Methods: An 18-item electronic survey was distributed to 88 student pharmacists at a private university completing APPEs in 5 distinct regions and 2 concentrated learning experiences during their penultimate rotation. The survey assessed whether students had at least 1 opportunity to achieve Domain 3 outcomes.

Novel mitochondrial derived Nuclear Excisosome degrades nuclei during differentiation of prosimian Galago (bush baby) monkey lenses.

The unique cellular organization and transparent function of the ocular lens depend on the continuous differentiation of immature epithelial cells on the lens anterior surface into mature elongated fiber cells within the lens core. A ubiquitous event during lens differentiation is the complete elimination of organelles required for mature lens fiber cell structure and transparency. Distinct pathways have been identified to mediate the elimination of non-nuclear organelles and nuclei.

Hypoxia regulates the degradation of non-nuclear organelles during lens differentiation through activation of HIF1a.

Formation of the eye lens depends on the continuous differentiation of lens epithelial cells into lens fiber cells. To attain their mature structure and transparent function, nascent lens fiber cells must complete a precise cellular remodeling program hallmarked by the complete elimination of organelles to form the core lens organelle-free zone (OFZ). Lacking a blood supply, the lens resides in a hypoxic environment that results in a decreasing oxygen concentration from the lens surface to the lens core.

Evaluation of a Resident-led Residency Preparation Series for Fourth Year Pharmacy Students.

Description Of Problem: The increased interest in residency programs nationwide has made the application process more competitive and complex.

Statement Of Innovation: In 2015, Wake Forest Baptist Health (WFBH) created a resident-led residency preparatory series (RPS) to assist advanced pharmacy practice experience (APPE) students in preparing for residency applications. This study sought to evaluate the perceived value of the resident-led RPS by fourth year APPE students.

Cultural Sensitivity and Global Pharmacy Engagement in the Arab World.

To create a resource on cultural sensitivity for schools and colleges of pharmacy that are currently engaged or considering future outreach opportunities in the Arab world. A literature review (2000-2018) of databases and Internet searches with specific keywords and terms were conducted. Authors who had experience in travelling to and hosting students and professionals from the Arab world and authors with local work experience in the Arab world were solicited.

An Introduction to Cultural Sensitivity and Global Pharmacy Engagement.

Global engagement between schools and colleges of pharmacy in the United States and many regions of the world is increasing. For an enriching and fruitful interaction, sensitivity toward the cultural, ethical, educational, religious, historical, political, regulatory, and practice issues is critical. Lack of sensitivity may negatively impact engagement among students, professionals and other people from different regions of the world.

Cultural Sensitivity and Global Pharmacy Engagement in the United States.

To provide a resource for schools and colleges of pharmacy in different regions of the world that are considering sending their students and faculty members to the United States for training. A literature review (2000-2018) was conducted that involved database and Internet searches using specific keywords and terms. Information was also solicited from authors in different regions of the United States who have hosted international students and faculty members.

Lens differentiation is characterized by stage-specific changes in chromatin accessibility correlating with differentiation state-specific gene expression.

Changes in chromatin accessibility regulate the expression of multiple genes by controlling transcription factor access to key gene regulatory sequences. Here, we sought to establish a potential function for altered chromatin accessibility in control of key gene expression events during lens cell differentiation by establishing genome-wide chromatin accessibility maps specific for four distinct stages of lens cell differentiation and correlating specific changes in chromatin accessibility with genome-wide changes in gene expression. ATAC sequencing was employed to generate chromatin accessibility profiles that were correlated with the expression profiles of over 10,000 lens genes obtained by high-throughput RNA sequencing at the same stages of lens cell differentiation.

Creating a Pharmacy Internship: A Toolbox for Success.

Objective: To describe available compensated student internships and provide guidance for new program development.

Methods: A search was conducted using PubMed, MEDLINE, and Google with the following search terms: pharmacy, intern, internship, and student. All English language publications were considered for inclusion.

Pharmacy Internships: We Can Do Better.

The pharmacist's role in patient care is expanding, and the profession must prepare its graduates for direct patient care. Internships can help facilitate this training outside of the formal pharmacy curriculum. Intern roles can expand beyond distributive tasks to compliment the full range of pharmacist activities, providing value to the student and institution.

BNIP3L/NIX is required for elimination of mitochondria, endoplasmic reticulum and Golgi apparatus during eye lens organelle-free zone formation.

The formation and life-long growth of the ocular lens depends on the continuous differentiation of lens epithelial cells into lens fiber cells. To achieve their mature structure and transparent function, newly formed lens fiber cells undergo a series of cellular remodeling events including the complete elimination of cellular organelles to form the lens organelle-free zone (OFZ). To date, the mechanisms and requirements for organelle elimination by lens fiber cells remain to be fully elucidated.

Infusion of Alloanergized Donor Lymphocytes after CD34-selected Haploidentical Myeloablative Hematopoietic Stem Cell Transplantation.

Allogeneic hematopoietic stem-cell transplantation (HSCT) is a curative treatment for many hematologic cancers. Use of haploidentical (mismatched) donors increases HSCT availability but is limited by severe graft-versus-host disease (GvHD) and delayed immune reconstitution. Alloanergization of donor T cells is a simple approach to rebuild immunity while limiting GvHD after haploidentical HSCT, but the optimal T-cell dose and impact on immune reconstitution remain unknown.

Heart failure in the elderly: ten peculiar management considerations.

Chronic heart failure (HF) is a disease with significantly higher prevalence in the elderly or patients older than 65 years old. Typically, older patients have more risk factors for HF, more comorbidities, and are more likely to have recurrent admissions for acute decompensations. With HF burden on health care systems primarily related to hospital and nursing home costs, it is critical that elderly patients are approached with a clear understanding of certain unique clinical, laboratory, imaging, and pharmacokinetic differences that can alter their management and outcomes.