Programmable mRNA therapeutics for controlled epigenomic modulation of single and multiplexed gene expression in diverse diseases.

Pathogenic gene dysregulation can be attributed to chromatin state change that pre-transcriptionally regulates expression. Recent breakthroughs elucidating the rules governing this DNA control layer, an epigenetic code, unlock a modality in precision medicine to target gene dysregulation across myriad diseases. Here we present a modular platform to design programmable mRNA therapeutics, Epigenomic Controllers (EC), that control gene expression through directed epigenetic change.

Obesity increases DNA damage in the breast epithelium.

Obesity is a modifiable risk factor for breast cancer. Yet, how obesity contributes to cancer initiation is not fully understood. The goal of this study was to determine if the body mass index (BMI) and metabolic hallmarks of obesity are related to DNA damage in normal breast tissue.

Farnesol Emulsion as an Effective Broad-Spectrum Agent against ESKAPE Biofilms.

The family of ESKAPE pathogens is comprised of , and . Together they are the main contributors of nosocomial infections and are well established for their ability to "escape" antibiotics. Farnesol is an FDA-approved cosmetic and flavoring agent with significant anti-biofilm properties.

Enlarged Breast Size (Macromastia) and Associated Neurologic Risks: A Scoping Review.

Background And Objectives: Symptomatic macromastia (enlarged breasts) is a syndrome of persistent headache, neck and shoulder pain, thoracic kyphosis, painful shoulder grooving from bra straps, inframammary rash, backache, and upper extremity paresthesias. Up to 89% of the 100,000 US women undergoing breast reduction surgery (reduction mammoplasty) annually report headache preoperatively with many endorsing postoperative headache improvement. Headache is one insurance indication to cover surgical reduction, and peak prevalence of migraine matches the average age of women with macromastia at time of surgery.

Farnesol repurposing for prevention and treatment of biofilms.

has emerged as a multidrug-resistant (MDR) superbug by causing severe infections, with high mortality rates. The ability of to form biofilms significantly contributes to its persistence in diverse environmental and hospital settings. Here we report that farnesol, an FDA-approved commercial cosmetic and flavoring agent, demonstrates efficacy for both inhibition of biofilm formation, and disruption of established biofilms.

Repurposing Farnesol for Combating Drug-Resistant and Persistent Single and Polymicrobial Biofilms.

Biofilm-associated infections caused by drug-resistant and persistent bacteria remain a significant clinical challenge. Here we report that farnesol, commercially available as a cosmetic and flavoring agent, shows significant anti-biofilm properties when dissolved in ethanol using a proprietary formulation emulsion technique. Farnesol in the new formulation inhibits biofilm formation and disrupts established biofilms for Gram-positive and Gram-negative , including their polymicrobial biofilms, and, moreover, kills persister cells that have developed tolerance to antibiotics.

Acute Care Advanced Practice Providers' Use of Telehealth During the COVID-19 Pandemic.

Advanced practice registered nurses and physician assistants, collectively termed advanced practice providers (APPs), have been part of telehealth for many years. During the COVID-19 pandemic, APPs experienced the growth in roles, responsibilities, and tools used for telehealth care delivery. This article uses examples from 3 health systems to highlight the ways in which telehealth use was expanded due to the pandemic, how APP roles were altered across the United States during and after the pandemic, and implications for future practice.

Health Care Provider Bias in Estimating the Health Literacy of Caregivers in a Pediatric Emergency Department.

Background: Health literacy is a growing concern because of its effects on communication and health outcomes. One aspect of this communication is the ability of the health care provider to estimate the health literacy of a patient or their caregiver. The objectives of this study are to quantify misestimation of caregiver health literacy by providers and identify potential descriptive or demographic factors that might be related to those misestimations.

The Impact of Postoperative Antibiotic and Duration After Implant-Based Breast Reconstruction on Resistance Among Cultured Species.

Background: There is a growing presence of literature within plastic surgery that establishes best practice for postoperative antibiotics after implant-based breast reconstruction (IBBR), although it has not been widely adopted or translated into clinical practice. This study aims to determine how antibiotic and duration affects patient outcomes. We hypothesize that IBBR patients who receive a longer duration of postoperative antibiotics will demonstrate higher rates of antibiotic resistance as compared with the institutional antibiogram.

Extent of Tissue Washing Can Significantly Alter the Composition of Adipose-Derived Stromal Vascular Fraction Cell Preparations: Implications for Clinical Translation.

Stromal vascular fraction (SVF) cell preparations have recently attracted much interest as a form of autologous cell therapy. These heterogenous cell populations typically include some proportion of blood-derived cells (BDCs)-including both red blood cells (RBCs) and leukocytes (WBCs). The objectives of this paper were to evaluate the effects of tissue washing and hypotonic RBC lysis-separately and together-on BDC concentrations within SVF, and further to explore whether BDCs can confer detectable and modifiable effects on adipose-derived cell activity.

Realizations of vascularized tissues: From platforms to grafts.

Vascularization is essential for realizing thick and functional tissue constructs that can be utilized for study platforms and grafts. The vasculature enables the transport of nutrients, oxygen, and wastes and is also indispensable to organ functional units such as the nephron filtration unit, the blood-air barrier, and the blood-brain barrier. This review aims to discuss the latest progress of organ-like vascularized constructs with specific functionalities and realizations even though they are not yet ready to be used as organ substitutes.

Comparing Outcomes in the Therapeutic and Prophylactic Breast for Bilateral Mastectomy With Implant-Based Breast Reconstruction.

Background: Increasingly patients with unilateral breast cancer elect to undergo bilateral mastectomy with subsequent reconstruction. Studies have aimed to better identify the risks associated with performing mastectomy on the noncancerous breast. Our study aims to identify differences in complications between therapeutic and prophylactic mastectomy in patients undergoing implant-based breast reconstruction.

The effects of prolonged intraoperative hypothermia on patient outcomes in immediate implant-based breast reconstruction.

Background: The importance of thermoregulation in surgical procedures has become a recent focus for anesthesiologists and surgeons to improve patient outcomes. In breast surgery, maintenance of normothermia has been shown to reduce surgical-site infections. However, there is a paucity of information evaluating the relationship between intraoperative core body temperatures and reconstructive surgical outcomes.

The Language of Implant-based Breast Reconstruction: Can We Do Better?

The management of breast cancer has experienced tremendous changes in the last half-century. In today's multimodal approach to breast cancer, patients have the prospect of achieving a sense of normalcy after mastectomy thanks to advancements in oncology and breast reconstruction. Although the oncologic management of breast cancer has evolved over multiple centuries, implant-based breast reconstruction (IBBR) has only been around since the 1960s.

Recurrent Skin and Soft Tissue Infection following Breast Reduction Surgery Caused by : A Case Report.

The expanding knowledge of the breast microbiome and its constituents necessitates understanding of how it plays into human disease. Consideration of how to identify novel organisms in breast tissue is a topic of hot debate. We report a case of a 26-year-old woman with repeat incisional break-down and sanguinopurulent drainage who required repeat incision and drainage procedures after bilateral breast reduction.

Quantity of Acellular Dermal Matrix in Immediate Breast Reconstruction and Outcomes.

Purpose: This study aimed to determine the impact of the quantity of acellular dermal matrix (ADM), "ADM burden," used in implant-based breast reconstruction on infection, drain duration, and seroma formation.

Methods: A single-institution, retrospective review from 2015 to 2020 was conducted for patients who underwent immediate, implant-based breast reconstruction after mastectomy. Three cohorts were generated based on the amount of ADM used: (1) total ADM, (2) sling ADM, and (3) no ADM.

Viewing stromal vascular fraction de novo vessel formation and association with host microvasculature using the rat mesentery culture model.

Objective: The objective of the study is to demonstrate the innovation and utility of mesenteric tissue culture for discovering the microvascular growth dynamics associated with adipose-derived stromal vascular fraction (SVF) transplantation. Understanding how SVF cells contribute to de novo vessel growth (i.e.

An Ex Vivo Tissue Culture Method for Discovering Cell Dynamics Involved in Stromal Vascular Fraction Vasculogenesis Using the Mouse Mesentery.

Stromal vascular fraction (SVF), isolated from adipose tissue, identifies as a rich cell source comprised of endothelial cells, endothelial progenitor cells, pericytes, smooth muscle cells, fibroblasts, and immune cells. SVF represents a promising therapeutic heterogonous cell source for growing new blood microvessels due to its rich niche of cells. However, the spatiotemporal dynamics of SVF within living tissues remain largely unknown.

Differences of embedding adipose-derived stromal cells in natural and synthetic scaffolds for dermal and subcutaneous delivery.

Background: In recent years, adipose-derived stromal cells (ASCs) have been heavily studied for soft tissue regeneration, augmentation, and dermal wound healing.

Methods: In this review, we investigated the trends in injectable scaffolds for ASC delivery in the dermis, and injectable or implantable scaffolds for ASC delivery in the subcutis. A total of 547 articles were screened across three databases; of these, 22 studies were found to be eligible and were included.

A clinical perspective on adipose-derived cell therapy for enhancing microvascular health and function: Implications and applications for reconstructive surgery.

Restoration of form and function requires apposition of tissues in the form of flaps to reconstitute local perfusion. Successful reconstruction relies on flap survival and its integration with the recipient bed. The flap's precariously perfused hypoxic areas undergo adaptive microvascular changes both internally and in connection with the recipient bed.

Autologous Fat Transfer for Scar Prevention and Remodeling: A Randomized, Blinded, Placebo-controlled Trial.

Unlabelled: Autologous fat transfer-also referred to as fat grafting-has been reported to provide beneficial effects to overlying scar and skin. Despite procedural frequency, there is a paucity of high-level evidence guiding the surgeon in technique, patient selection, and efficacy.

Methods: A multicenter, double-blinded, randomized, internally placebo-controlled trial was performed with an aim to qualitatively and quantitatively evaluate the impact of autologous fat transfer on the quality of overlying scar tissue.

Detecting Common Eye Diseases Using the First Teleophthalmology GlobeChek Kiosk in the United States: A Pilot Study.

Purpose: The aim of this study was to assess the benefit and feasibility of the teleophthalmology GlobeChek kiosk in a community-based program.

Design: Single-site, nonrandomized, cross-sectional, teleophthalmologic study.

Methods: Participants underwent comprehensive evaluation that consists of a questionnaire form, brief systemic evaluation, screening visual field (VF), and GlobeChek kiosk screening, which included but not limited to intraocular pressure, pachymetry, anterior segment optical coherence tomography, posterior segment optical coherence tomography, and nonmydriatic fundus photography.

Ex vivo-expanded autologous adipose tissue-derived stromal cells ensure enhanced fat graft retention in breast augmentation: A randomized controlled clinical trial.

Autologous fat grafting and implant surgery are used for volume restoration in plastic surgery. With the aim of producing a treatment superior to current solutions, we report a randomized, controlled, data assessor-blinded clinical trial comparing fat grafts enriched with ex vivo-expanded autologous adipose-derived stromal cells (ASCs) to nonenriched fat grafts in breast augmentation. The intervention group received ASC-enriched fat grafts (≥20 × 10 viable ex vivo-expanded ASCs per milliliter fat), and the control group received conventional nonenriched fat grafts.

A novel tissue culture model for evaluating the effect of aging on stem cell fate in adult microvascular networks.

In vitro models of angiogenesis are valuable tools for understanding the underlying mechanisms of pathological conditions and for the preclinical evaluation of therapies. Our laboratory developed the rat mesentery culture model as a new tool for investigating mechanistic cell-cell interactions at specific locations across intact blood and lymphatic microvascular networks ex vivo. The objective of this study was to report a method for evaluating the effect of aging on human stem cell differentiation into pericytes during angiogenesis in cultured microvascular networks.

Safety of Human Adipose Stromal Vascular Fraction Cells Isolated with a Closed System Device in an Immunocompetent Murine Pressure Ulcer Model.

Pressure ulcers (PUs) result in part due to ischemia-reperfusion injury to the skin and present frequently in elderly or quadriplegic patients with reduced mobility. Despite the high economic and societal cost of this condition, PU therapy relies primarily on preventive strategies and invasive surgical intervention. A growing body of clinical literature suggests that localized injection of adipose-derived cells can accelerate and enhance the closure of PUs.