Closing the Workforce Staffing Chasm by Breaking Boundaries: Innovative Partnerships and Strategies Between Recruitment and Nursing.

As hospitals are experiencing a nursing shortage, nursing leaders must build innovative partnerships and strategies between nursing and recruitment to close the workforce gap. One large health care system was experiencing a high vacancy rate. To improve recruitment and retention efforts, nursing leaders partnered with the recruitment department and other key stakeholders to develop strategies. Together, they designed a candidate-centric recruiting and hiring process, designed innovative recruitment campaigns including recruiting former employed nurses, recruitment of traveling nurses into employees, increased graduate nurse recruitment efforts, and implementation of a registered nurse (RN) Ambassador program. The team improved work process efficiency for recruiters and candidates. Retention efforts focused on engaging nurses in the work environment, decreasing nurse leader workload to allow a focus on staff relationships, and improving exit processes in an effort to retain the nurse. The actual vacancy rate was as high as 20.9% in July 2021 to 8% in September 2022, indicating the system is closing the vacancy rate and nearing the goal of 5%.

Resident immune cells of the avascular lens: Mediators of the injury and fibrotic response of the lens.

Tissues typically harbor subpopulations of resident immune cells that function as rapid responders to injury and whose activation leads to induction of an adaptive immune response, playing important roles in repair and protection. Since the lens is an avascular tissue, it was presumed that it was absent of resident immune cells. Our studies now show that resident immune cells are a shared feature of the human, mouse, and chicken lens epithelium. These resident immune cells function as immediate responders to injury and rapidly populate the wound edge following mock cataract surgery to function as leader cells. Many of these resident immune cells also express MHCII providing them with antigen presenting ability to engage an adaptive immune response. We provide evidence that during development immune cells migrate on the ciliary zonules and localize among the equatorial epithelial cells of the lens adjacent to where the ciliary zonules associate with the lens capsule. These findings suggest that the vasculature-rich ciliary body is a source of lens resident immune cells. We identified a major role for these cells as rapid responders to wounding, quickly populating each wound were they can function as leaders of lens tissue repair. Our findings also show that lens resident immune cells are progenitors of myofibroblasts, which characteristically appear in response to lens cataract surgery injury, and therefore, are likely agents of lens pathologies to impair vision like fibrosis.

Immune cells in lens injury repair and fibrosis.

Immune cells, both tissue resident immune cells and those immune cells recruited in response to wounding or degenerative conditions, are essential to both the maintenance and restoration of homeostasis in most tissues. These cells are typically provided to tissues by their closely associated vasculatures. However, the lens, like many of the tissues in the eye, are considered immune privileged sites because they have no associated vasculature. Such absence of immune cells was thought to protect the lens from inflammatory responses that would bring with them the danger of causing vision impairing opacities. However, it has now been shown, as occurs in other immune privileged sites in the eye, that novel pathways exist by which immune cells come to associate with the lens to protect it, maintain its homeostasis, and function in its regenerative repair. Here we review the discoveries that have revealed there are both innate and adaptive immune system responses to lens, and that, like most other tissues, the lens harbors a population of resident immune cells, which are the sentinels of danger or injury to a tissue. While resident and recruited immune cells are essential elements of lens homeostasis and repair, they also become the agents of disease, particularly as progenitors of pro-fibrogenic myofibroblasts. There still remains much to learn about the function of lens-associated immune cells in protection, repair and disease, the knowledge of which will provide new tools for maintaining the core functions of the lens in the visual system.

The local wound environment is a key determinant of the outcome of TGFß signaling on the fibrotic response of CD44+ leader cells in an ex vivo post-cataract-surgery model.

The cytokine transforming growth factor beta (TGFß) has a role in regulating the normal and pathological response to wound healing, yet how it shifts from a pro-repair to a pro-fibrotic function within the wound environment is still unclear. Using a clinically relevant ex vivo post-cataract surgery model that mimics the lens fibrotic disease posterior capsule opacification (PCO), we investigated the influence of two distinct wound environments on shaping the TGFß-mediated injury response of CD44+ vimentin-rich leader cells. The substantial fibrotic response of this cell population occurred within a rigid wound environment under the control of endogenous TGFß. However, TGFß was dispensable for the role of leader cells in wound healing on the endogenous basement membrane wound environment, where repair occurs in the absence of a major fibrotic outcome. A difference between leader cell function in these distinct environments was their cell surface expression of the latent TGFß activator, αvß3 integrin. This receptor is exclusively found on this CD44+ cell population when they localize to the leading edge of the rigid wound environment. Providing exogenous TGFß to bypass any differences in the ability of the leader cells to sustain activation of TGFß in different environments revealed their inherent ability to induce pro-fibrotic reactions on the basement membrane wound environment. Furthermore, exposure of the leader cells in the rigid wound environment to TGFß led to an accelerated fibrotic response including the earlier appearance of pro-collagen + cells, alpha smooth muscle actin (αSMA)+ myofibroblasts, and increased fibrotic matrix production. Collectively, these findings show the influence of the local wound environment on the extent and severity of TGFß-induced fibrotic responses. These findings have important implications for understanding the development of the lens fibrotic disease PCO in response to cataract surgery wounding.

Patients Typing Their Own Visit Agendas Into an Electronic Medical Record: Pilot in a Safety-Net Clinic.

Collaborative visit agenda setting between patient and doctor is recommended. We assessed the feasibility, acceptability, and utility of patients attending a large primary care safety-net clinic typing their agendas into the electronic visit note before seeing their clinicians. One hundred and one patients and their 28 clinicians completed post-visit surveys. Patients and clinicians agreed that the agendas improved patient-clinician communication (patients 79%, clinician 74%), and wanted to continue having patients type agendas in the future (73%, 82%). Enabling patients to type visit agendas may enhance care by engaging patients and giving clinicians an efficient way to prioritize patients' concerns.

Ophthalmology patients' interest in online access to clinic notes at three US clinics.

PURPOSE: This study aimed to understand patients' perceptions about potential benefits and harms of accessing their own ophthalmology clinic notes via an electronic patient portal as part of the OpenNotes initiative. METHODS: The authors conducted a cross-sectional, in-person survey of ophthalmology patients at three US eye clinics. The paper survey was self-administered or administered with assistance from study staff before or after patients' clinical visits. The authors used descriptive statistics to summarise patient characteristics and patient attitudes about accessing their ophthalmology notes online. Chi-square and t-tests were performed to assess differences in patient responses between clinic locations. RESULTS: Four hundred and fifty-one patients responded (response rate 65%). Most patients thought that accessing doctors' notes online was a good idea (95%), wanted to view their clinic notes online (94%), and agreed online access would increase their understanding of their eye problems (95%) and help them better remember their care plan (94%); 14% said online access would increase their worry; 43% had privacy concerns; and 96% indicated they would show or discuss their notes with at least one other person. Non-white patients were more likely than white patients to perceive online clinic notes as a useful tool, but they were also more likely to worry and to express greater privacy concerns. CONCLUSIONS: Patients at three US eye clinics were strongly in favour of online access to ophthalmology notes and were optimistic this access would improve their understanding and self-care. Ophthalmologists should consider offering online access to their notes to enhance doctor-patient communication and improve clinical outcomes.

The impact of opening visitation access on patient and family experience.

Restrictive visiting hours have been an obstacle to family participation in care. To support increased and consistent access to patients, Baylor Health Care System implemented a system-wide approach to open access for visitation across all facilities. Nursing and medical leadership led the communication efforts, and shared nursing governance guided revisions to existing policies. Data collected from 13 hospitals demonstrated that patients and families felt more informed; that the nursing staff were more courteous and respectful and explained things in a way that could be understood; that the staff attitude toward visitors was markedly improved; and that comfort and accommodations for guests were extended and improved. The resources needed to deploy these changes are outlined as well as the iterative process needed to create a positive impact on the family partnership in care.

The Hippo signaling pathway is required for salivary gland development and its dysregulation is associated with Sjogren's syndrome.

Sjogren's syndrome (SS) is a complex autoimmune disease that primarily affects salivary and lacrimal glands and is associated with high morbidity. Although the prevailing dogma is that immune system pathology drives SS, increasing evidence points to structural defects, including defective E-cadherin adhesion, to be involved in its etiology. We have shown that E-cadherin has pivotal roles in the development of the mouse salivary submandibular gland (SMG) by organizing apical-basal polarity in acinar and ductal progenitors and by signaling survival for differentiating duct cells. Recently, E-cadherin junctions have been shown to interact with effectors of the Hippo signaling pathway, a core pathway regulating the organ size, cell proliferation, and differentiation. We now show that Hippo signaling is required for SMG-branching morphogenesis and is involved in the pathophysiology of SS. During SMG development, a Hippo pathway effector, TAZ, becomes increasingly phosphorylated and associated with E-cadherin and α-catenin, consistent with the activation of Hippo signaling. Inhibition of Lats2, an upstream kinase that promotes TAZ phosphorylation, results in dysmorphogenesis of the SMG and impaired duct formation. SMGs from non-obese diabetic mice, a mouse model for SS, phenocopy the Lats2-inhibited SMGs and exhibit a reduction in E-cadherin junctional components, including TAZ. Importantly, labial specimens from human SS patients display mislocalization of TAZ from junctional regions to the nucleus, coincident with accumulation of extracellular matrix components, fibronectin and connective tissue growth factor, known downstream targets of TAZ. Our studies show that Hippo signaling has a crucial role in SMG-branching morphogenesis and provide evidence that defects in this pathway are associated with SS in humans.

Unique precursors for the mesenchymal cells involved in injury response and fibrosis.

We investigated an alternative pathway for emergence of the mesenchymal cells involved in epithelial sheet wound healing and a source of myofibroblasts that cause fibrosis. Using a mock cataract surgery model, we discovered a unique subpopulation of polyploid mesenchymal progenitors nestled in small niches among lens epithelial cells that expressed the surface antigen G8 and mRNA for the myogenic transcription factor MyoD. These cells rapidly responded to wounding of the lens epithelium with population expansion, acquisition of a mesenchymal phenotype, and migration to the wound edges where they regulate the wound response of the epithelium. These mesenchymal cells also were a principal source of myofibroblasts that emerged following lens injury and were responsible for fibrotic disease of the lens that occurs following cataract surgery. These studies provide insight into the mechanisms of wound-healing and fibrosis.

Immune Responses Induced at One Hour Post Cataract Surgery Wounding of the Chick Lens.

While the lens is an avascular tissue with an immune-privileged status, studies have now revealed that there are immune responses specifically linked to the lens. The response to lens injury, such as following cataract surgery, has been shown to involve the activation of the resident immune cell population of the lens and the induction of immunomodulatory factors by the wounded epithelium. However, there has been limited investigation into the immediate response of the lens to wounding, particularly those induced factors that are intrinsic to the lens and its associated resident immune cells. Using an established chick embryo ex vivo cataract surgery model has made it possible to determine the early immune responses of this tissue to injury, including its resident immune cells, through a transcriptome analysis. RNA-seq studies were performed to determine the gene expression profile at 1 h post wounding compared to time 0. The results provided evidence that, as occurs in other tissues, the resident immune cells of the lens rapidly acquired a molecular signature consistent with their activation. These studies also identified the expression of many inflammatory factors by the injured lens that are associated with both the induction and regulation of the immune response.

Fibrosis-the tale of H3K27 histone methyltransferases and demethylases.

Fibrosis, or excessive scarring, is characterized by the emergence of alpha-smooth muscle actin (αSMA)-expressing myofibroblasts and the excessive accumulation of fibrotic extracellular matrix (ECM). Currently, there is a lack of effective treatment options for fibrosis, highlighting an unmet need to identify new therapeutic targets. The acquisition of a fibrotic phenotype is associated with changes in chromatin structure, a key determinant of gene transcription activation and repression. The major repressive histone mark, H3K27me3, has been linked to dynamic changes in gene expression in fibrosis through alterations in chromatin structure. H3K27-specific homologous histone methylase (HMT) enzymes, Enhancer of zeste 1 and 2 (EZH1, EZH2), which are the alternative subunits of the Polycomb Repressive Complex 2 (PRC2) and demethylase (KDM) enzymes, Ubiquitously transcribed tetratricopeptide repeat, X chromosome (UTX), and Lysine demethylase 6B (KDM6B), are responsible for regulating methylation status of H3K27me3. In this review, we explore how these key enzymes regulate chromatin structure to alter gene expression in fibrosis, highlighting them as attractive targets for the treatment of fibrosis.

Changes in nascent chromatin structure regulate activation of the pro-fibrotic transcriptome and myofibroblast emergence in organ fibrosis.

Cell reprogramming to a myofibroblast responsible for the pathological accumulation of extracellular matrix is fundamental to the onset of fibrosis. Here, we explored how condensed chromatin structure marked by H3K72me3 becomes modified to allow for activation of repressed genes to drive emergence of myofibroblasts. In the early stages of myofibroblast precursor cell differentiation, we discovered that H3K27me3 demethylase enzymes UTX/KDM6B creates a delay in the accumulation of H3K27me3 on nascent DNA revealing a period of decondensed chromatin structure. This period of decondensed nascent chromatin structure allows for binding of pro-fibrotic transcription factor, Myocardin-related transcription factor A (MRTF-A) to nascent DNA. Inhibition of UTX/KDM6B enzymatic activity condenses chromatin structure, prevents MRTF-A binding, blocks activation of the pro-fibrotic transcriptome, and results in an inhibition of fibrosis in lens and lung fibrosis models. Our work reveals UTX/KDM6B as central coordinators of fibrosis, highlighting the potential to target its demethylase activity to prevent organ fibrosis.

A Skp2 autoinduction loop and restriction point control.

We describe a self-amplifying feedback loop that autoinduces Skp2 during G1 phase progression. This loop, which contains Skp2 itself, p27(kip1) (p27), cyclin E-cyclin dependent kinase 2, and the retinoblastoma protein, is closed through a newly identified, conserved E2F site in the Skp2 promoter. Interference with the loop, by knockin of a Skp2-resistant p27 mutant (p27(T187A)), delays passage through the restriction point but does not interfere with S phase entry under continuous serum stimulation. Skp2 knock down inhibits S phase entry in nontransformed mouse embryonic fibroblasts but not in human papilloma virus-E7 expressing fibroblasts. We propose that the essential role for Skp2-dependent degradation of p27 is in the formation of an autoinduction loop that selectively controls the transition to mitogen-independence, and that Skp2-dependent proteolysis may be dispensable when pocket proteins are constitutively inactivated.

Evaluating the impact of patients' online access to doctors' visit notes: designing and executing the OpenNotes project.

BACKGROUND: Providers and policymakers are pursuing strategies to increase patient engagement in health care. Increasingly, online sections of medical records are viewable by patients though seldom are clinicians' visit notes included. We designed a one-year multi-site trial of online patient accessible office visit notes, OpenNotes. We hypothesized that patients and primary care physicians (PCPs) would want it to continue and that OpenNotes would not lead to significant disruptions to doctors' practices. METHODS/DESIGN: Using a mixed methods approach, we designed a quasi-experimental study in 3 diverse healthcare systems in Boston, Pennsylvania, and Seattle. Two sites had existing patient internet portals; the third used an experimental portal. We targeted 3 key areas where we hypothesized the greatest impacts: beliefs and attitudes about OpenNotes, use of the patient internet portals, and patient-doctor communication. PCPs in the 3 sites were invited to participate in the intervention. Patients who were registered portal users of participating PCPs were given access to their PCPs' visit notes for one year. PCPs who declined participation in the intervention and their patients served as the comparison groups for the study. We applied the RE-AIM framework to our design in order to capture as comprehensive a picture as possible of the impact of OpenNotes. We developed pre- and post-intervention surveys for online administration addressing attitudes and experiences based on interviews and focus groups with patients and doctors. In addition, we tracked use of the internet portals before and during the intervention. RESULTS: PCP participation varied from 19% to 87% across the 3 sites; a total of 114 PCPs enrolled in the intervention with their 22,000 patients who were registered portal users. Approximately 40% of intervention and non-intervention patients at the 3 sites responded to the online survey, yielding a total of approximately 38,000 patient surveys. DISCUSSION: Many primary care physicians were willing to participate in this "real world" experiment testing the impact of OpenNotes on their patients and their practices. Results from this trial will inform providers, policy makers, and patients who contemplate such changes at a time of exploding interest in transparency, patient safety, and improving the quality of care.

PI3K Isoform-Specific Regulation of Leader and Follower Cell Function for Collective Migration and Proliferation in Response to Injury.

To ensure proper wound healing it is important to elucidate the signaling cues that coordinate leader and follower cell behavior to promote collective migration and proliferation for wound healing in response to injury. Using an ex vivo post-cataract surgery wound healing model we investigated the role of class I phosphatidylinositol-3-kinase (PI3K) isoforms in this process. Our findings revealed a specific role for p110α signaling independent of Akt for promoting the collective migration and proliferation of the epithelium for wound closure. In addition, we found an important role for p110α signaling in orchestrating proper polarized cytoskeletal organization within both leader and wounded epithelial follower cells to coordinate their function for wound healing. p110α was necessary to signal the formation and persistence of vimentin rich-lamellipodia extensions by leader cells and the reorganization of actomyosin into stress fibers along the basal domains of the wounded lens epithelial follower cells for movement. Together, our study reveals a critical role for p110α in the collective migration of an epithelium in response to wounding.

The Pro-fibrotic Response of Mesenchymal Leader Cells to Lens Wounding Involves Hyaluronic Acid, Its Receptor RHAMM, and Vimentin.

Hyaluronic Acid/Hyaluronan (HA) is a major component of the provisional matrix deposited by cells post-wounding with roles both in regulating cell migration to repair a wound and in promoting a fibrotic outcome to wounding. Both are mediated through its receptors CD44 and RHAMM. We now showed that HA is present in the provisional matrix assembled on the substrate surface in a lens post-cataract surgery explant wound model in which mesenchymal leader cells populate the wound edges to direct migration of the lens epithelium across the adjacent culture substrate onto which this matrix is assembled. Inhibiting HA expression with 4-MU blocked assembly of FN-EDA and collagen I by the wound-responsive mesenchymal leader cells and their migration. These cells express both the HA receptors CD44 and RHAMM. CD44 co-localized with HA at their cell-cell interfaces. RHAMM was predominant in the lamellipodial protrusions extended by the mesenchymal cells at the leading edge, and along HA fibrils organized on the substrate surface. Within a few days post-lens wounding the leader cells are induced to transition to αSMA+ myofibroblasts. Since HA/RHAMM is implicated in both cell migration and inducing fibrosis we examined the impact of blocking HA synthesis on myofibroblast emergence and discovered that it was dependent on HA. While RHAMM has not been previously linked to the intermediate filament protein vimentin, our studies with these explant cultures have shown that vimentin in the cells' lamellipodial protrusions regulate their transition to myofibroblast. PLA studies now revealed that RHAMM was complexed with both HA and vimentin in the lamellipodial protrusions of leader cells, implicating this HA/RHAMM/vimentin complex in the regulation of leader cell function post-wounding, both in promoting cell migration and in the transition of these cells to myofibroblasts. These results increase our understanding of how the post-wounding matrix environment interacts with receptor/cytoskeletal complexes to determine whether injury outcomes are regenerative or fibrotic.

The Pro-Fibrotic Response to Lens Injury Is Signaled in a PI3K Isoform-Specific Manner.

The signaling inputs that function to integrate biochemical and mechanical cues from the extracellular environment to alter the wound-repair outcome to a fibrotic response remain poorly understood. Here, using a clinically relevant post-cataract surgery wound healing/fibrosis model, we investigated the role of Phosphoinositide-3-kinase (PI3K) class I isoforms as potential signaling integrators to promote the proliferation, emergence and persistence of collagen I-producing alpha smooth muscle actin (αSMA+) myofibroblasts that cause organ fibrosis. Using PI3K isoform specific small molecule inhibitors, our studies revealed a requisite role for PI3K p110α in signaling the CD44+ mesenchymal leader cell population that we previously identified as resident immune cells to produce and organize a fibronectin-EDA rich provisional matrix and transition to collagen I-producing αSMA+ myofibroblasts. While the PI3K effector Akt was alone insufficient to regulate myofibroblast differentiation, our studies revealed a role for Rac, another potential PI3K effector, in this process. Our studies further uncovered a critical role for PI3K p110α in signaling the proliferation of CD44+ leader cells, which is important to the emergence and expansion of myofibroblasts. Thus, these studies identify activation of PI3K p110α as a critical signaling input following wounding to the development and progression of fibrotic disease.

Hypoglycosylated E-cadherin promotes the assembly of tight junctions through the recruitment of PP2A to adherens junctions.

Epithelial cell-cell adhesion is controlled by multiprotein complexes that include E-cadherin-mediated adherens junctions (AJs) and ZO-1-containing tight junctions (TJs). Previously, we reported that reduction of E-cadherin N-glycosylation in normal and cancer cells promoted stabilization of AJs through changes in the composition and cytoskeletal association of E-cadherin scaffolds. Here, we show that enhanced interaction of hypoglycosylated E-cadherin-containing AJs with protein phosphatase 2A (PP2A) represents a mechanism for promoting TJ assembly. In MDCK cells, attenuation of cellular N-glycosylation with siRNA to DPAGT1, the first gene in the N-glycosylation pathway, reduced N-glycosylation of surface E-cadherin and resulted in increased recruitment of stabilizing proteins gamma-catenin, alpha-catenin, vinculin and PP2A to AJs. Greater association of PP2A with AJs correlated with diminished binding of PP2A to ZO-1 and claudin-1 and with increased pools of serine-phosphorylated ZO-1 and claudin-1. More ZO-1 was found in complexes with occludin and claudin-1, and this corresponded to enhanced transepithelial resistance (TER), indicating physiological assembly of TJs. Similar maturation of AJs and TJs was detected after transfection of MDCK cells with the hypoglycosylated E-cadherin variant, V13. Our data indicate that E-cadherin N-glycans coordinate the maturity of AJs with the assembly of TJs by affecting the association of PP2A with these junctional complexes.

Dynamics of the lens basement membrane capsule and its interaction with connective tissue-like extracapsular matrix proteins.

The lens, suspended in the middle of the eye by tendon-like ciliary zonule fibers and facing three different compartments of the eye, is enclosed in what has been described as the thickest basement membrane in the body. While the protein components of the capsule have been a subject of study for many years, the dynamics of capsule formation, and the region-specific relationship of its basement membrane components to one another as well as to other matrix molecules remains to be explored. Through high resolution confocal and super-resolution imaging of the lens capsule and 3D surface renderings of acquired z-stacks, our studies revealed that each of its basement membrane proteins, laminin, collagen IV, nidogen and perlecan, has unique structure, organization, and distribution specific both to the region of the lens that the capsule is located in and the position of the capsule within the eye. We provide evidence of basal membrane gradients across the depth of the capsule as well as the synthesis of distinct basement membrane lamella within the capsule. These distinctions are most prominent in the equatorial capsule zone where collagen IV and nidogen span the capsule depth, while laminin and perlecan are located in two separate lamellae located at the innermost and outermost capsule domains. We discovered that an extracapsular matrix compartment rich in the connective tissue-like matrix molecules fibronectin, tenascin-C, and fibrillin is integrated with the superficial surface of the lens capsule. Each matrix protein in this extracapsular zone also exhibits region-specific distribution with fibrils of fibrillin, the matrix protein that forms the backbone of the ciliary zonules, inserting within the laminin/perlecan lamella at the surface of the equatorial lens capsule.

Specification of the patterning of a ductal tree during branching morphogenesis of the submandibular gland.

The development of ductal structures during branching morphogenesis relies on signals that specify ductal progenitors to set up a pattern for the ductal network. Here, we identify cellular asymmetries defined by the F-actin cytoskeleton and the cell adhesion protein ZO-1 as the earliest determinants of duct specification in the embryonic submandibular gland (SMG). Apical polarity protein aPKCζ is then recruited to the sites of asymmetry in a ZO-1-dependent manner and collaborates with ROCK signaling to set up apical-basal polarity of ductal progenitors and further define the path of duct specification. Moreover, the motor protein myosin IIB, a mediator of mechanical force transmission along actin filaments, becomes localized to vertices linking the apical domains of multiple ductal epithelial cells during the formation of ductal lumens and drives duct maturation. These studies identify cytoskeletal, junctional and polarity proteins as the early determinants of duct specification and the patterning of a ductal tree during branching morphogenesis of the SMG.