A global perspective of advanced practice nursing research: A review of systematic reviews.

INTRODUCTION: The World Health Organization (WHO) called for the expansion of all nursing roles, including advanced practice nurses (APNs), nurse practitioners (NPs) and clinical nurse specialists (CNSs). A clearer understanding of the impact of these roles will inform global priorities for advanced practice nursing education, research, and policy. OBJECTIVE: To identify gaps in advanced practice nursing research globally. MATERIALS AND METHODS: A review of systematic reviews was conducted. We searched CINAHL, Embase, Global Health, Healthstar, PubMed, Medline, Cochrane Library, DARE, Joanna Briggs Institute EBP, and Web of Science from January 2011 onwards, with no restrictions on jurisdiction or language. Grey literature and hand searches of reference lists were undertaken. Review quality was assessed using the Critical Appraisal Skills Program (CASP). Study selection, data extraction and CASP assessments were done independently by two reviewers. We extracted study characteristics, country and outcome data. Data were summarized using narrative synthesis. RESULTS: We screened 5840 articles and retained 117 systematic reviews, representing 38 countries. Most CASP criteria were met. However, study selection by two reviewers was done inconsistently and language and geographical restrictions were applied. We found highly consistent evidence that APN, NP and CNS care was equal or superior to the comparator (e.g., physicians) for 29 indicator categories across a wide range of clinical settings, patient populations and acuity levels. Mixed findings were noted for quality of life, consultations, costs, emergency room visits, and health care service delivery where some studies favoured the control groups. No indicator consistently favoured the control group. There is emerging research related to Artificial Intelligence (AI). CONCLUSION: There is a large body of advanced practice nursing research globally, but several WHO regions are underrepresented. Identified research gaps include AI, interprofessional team functioning, workload, and patients and families as partners in healthcare. PROSPERO REGISTRATION NUMBER: CRD42021278532.

Electronic Health Record Concordance with Survey-Reported Military Sexual Trauma Among Younger Veterans: Associations with Health Care Utilization and Mental Health Diagnoses.

Introduction: Military sexual trauma (MST) is more common among post-9/11 Veterans and women versus older Veterans and men. Despite mandatory screening, the concordance of electronic health record (EHR) documentation and survey-reported MST, and associations with health care utilization and mental health diagnoses, are unknown for this younger group. Materials and Methods: Veterans' Health Administration (VHA) EHR (2001-2021) were merged with data from the observational, nationwide WomenVeterans Cohort Study (collected 2016-2020, n = 1058; 51% women). Experiencing MST was defined as positive endorsement of sexual harassment and/or assault. From the EHR, we derived Veterans' number of primary care and mental health visits in the initial two years of VHA care and diagnoses of posttraumatic stress disorder (PTSD), depression, and anxiety. First, the concordance of EHR MST screening and survey-reported MST was compared. Next, multivariate analyses tested the cross-sectional associations of EHR screening and survey-reported MST with Veterans' health care utilization, and compared the likelihood of PTSD, depression, and anxiety diagnoses by MST group, while covarying demographics and service-related characteristics. With few MST cases among men, multivariate analyses were only pursued for women. Results: Overall, 29% of women and 2% of men screened positive for MST in the EHR, but 64% of women and 9% of men had survey-reported MST. Primary care utilization was similar between women with concordant, positive MST reports in the EHR and survey versus those with survey-reported MST only. Women with survey-reported MST only were less likely to have a PTSD or depression diagnosis than those with concordant, positive MST reports. There was no group difference in women's likelihood of anxiety. Conclusions: EHR MST documentation is discordant for many post-9/11 Veterans-both for men and women. Improving MST screening and better supporting MST disclosure are each critical to provide appropriate and timely care for younger Veterans, particularly women.

Postpartum Obesity Is Associated With Increases in Child Adiposity in Midchildhood in a Cohort of Black and Dominican Youth.

Background: Obesity disproportionately affects marginalized and low-income populations. Birth parent obesity from the prenatal period and childhood has been associated with child obesity. It is unknown whether prenatal or postnatal birth parent obesity has differential effects on subsequent changes in adiposity and metabolic health in children. Objectives: We evaluated how birth parent obesity 7 y after delivery was associated with child body composition changes and cardiometabolic health in midchildhood and further assessed the influence of the perinatal and postpartum period on associations. Methods: Black and Dominican pregnant individuals were enrolled, and dyads (n = 319) were followed up at child age 7 and 9 y. Measures included, height, weight, waist circumference (WC), and percent body fat (BF%). Multiple linear regression was used to relate postpartum weight status with child outcomes accounting for attrition, and a series of secondary analyses were conducted with additional adjustment for perinatal weight status, gestational weight gain (GWG), and/or long-term weight retention to evaluate how these factors influenced associations. Results: Almost one-quarter (23%) of birth parents and 24.1% children were classified with obesity at child age 7 y, while at 9 y, 30% of children had obesity. Birth parent obesity at child age 7 y was associated with greater changes, from ages 7 to 9 y, in child BMI z-score (ß: 0.13; 95% CI: 0.02, 0.24) and BF% (ß: 1.15; 95% CI: 0.22, 2.09) but not obesity at age 9 y. All observed associations crossed the null after additional adjustment for prenatal factors. Conclusions: Birth parent obesity at 7-y postpartum is associated with greater gains in child BMI z-score and BF% in midchildhood. These associations diminish after accounting for prenatal size, suggesting a lasting impact of the perinatal environment and that interventions supporting families from the prenatal period through childhood are needed.

Reduction in Balloon Pump Size Reduces Axillary Intraaortic Balloon Pump Failure Risk.

Axillary artery intra-aortic balloon pump (axIABP) placement has been implemented as a bridging solution before heart transplantation. This study evaluates complications associated with axIABP support and describes an approach to minimize adverse events. We previously described a percutaneous approach for axIABP placement. However, patients receiving axIABP between September 1, 2017, and September 26, 2019 (n = 32) demonstrated a high rate of balloon pump malfunction (8/32; 25%) and other complications (totaling 15/32; 47%). Sixty-four patients were sequentially treated under a revised protocol. Compared to the initial cohort, no significant differences in demographics were noted. A significant reduction in rate of balloon malfunction (8/32, 25% vs. 1/64, 2%; p < 0.001) and total complications (15/32, 47% vs. 10/64, 16%; p = 0.0025) during the period of support were noted after intervention. Subsequent analysis of total complications per device size (40 vs. ≤ 34 ml balloon) revealed significantly reduced complications in patients with smaller devices (40% vs. 13%, respectively; p = 0.0022). This study provides guidelines to limit complications in patients supported with axIABP, facilitating a protracted period of bridging support.

Subsequent Malignancies after CD19-Targeted Chimeric Antigen Receptor T cells in Patients with Lymphoma.

Chimeric antigen receptor (CAR) T cells are an established treatment for B cell non-Hodgkin lymphomas (B-NHL). With the remarkable success in improving survival, understanding the late effects of CAR T cell therapy is becoming more relevant. The aim of this study is to determine the incidence of subsequent malignancies in adult patients with B-NHL. We retrospectively studied 355 patients from two different medical centers treated with four different CAR T cell products from 2016 to 2022. The overall cumulative incidence for subsequent malignancies at 36 months was 14% (95% CI: 9.2%, 19%). Subsequent malignancies were grouped into three primary categories: solid tumor, hematologic malignancy, and dermatologic malignancy with cumulative incidences at 36 months of 6.1% (95% CI: 3.1%-10%), 4.5% (95% CI: 2.1%-8.1%) and 4.2% (95% CI: 2.1%-7.5%) respectively. Notably, no cases of T cell malignancies were observed. In univariable analysis, increasing age was associated with higher risk for subsequent malignancy. While the overall benefits of CAR T products continue to outweigh their potential risks, more studies and longer follow ups are needed to further demonstrate the risks, patterns, and molecular pathways that lead to the development of subsequent malignancies.

IGF-1 Peptide Mimetic-functionalized Hydrogels Enhance MSC Survival and Immunomodulatory Activity.

Human mesenchymal stem cells (MSCs) have demonstrated promise when delivered to damaged tissue or tissue defects for their cytokine secretion and inflammation modulation behaviors that can promote repair. Insulin-like growth factor 1 (IGF-1) has been shown to augment MSCs' viability and survival and promote their secretion of cytokines that signal to endogenous cells, in the treatment of myocardial infarction, wound healing, and age-related diseases. Biomaterial cell carriers can be functionalized with growth factor-mimetic peptides to enhance MSC function while promoting cell retention and minimizing off-target effects seen with direct administration of soluble growth factors. Here, we functionalized alginate hydrogels with three distinct IGF-1 peptide mimetics and the integrin-binding peptide, cyclic RGD. One IGF-1 peptide mimetic (IGM-3) was found to activate Akt signaling and support survival of serum-deprived MSCs. MSCs encapsulated in alginate hydrogels that presented both IGM-3 and cRGD showed a significant reduction in pro-inflammatory cytokine secretion when challenged with interleukin-1ß. Finally, MSCs cultured within the cRGD/IGM-3 hydrogels were able to blunt pro-inflammatory gene expression of human primary cells from degenerated intervertebral discs. These studies indicate the potential to leverage cell adhesive and IGF-1 growth factor peptide mimetics together to control therapeutic secretory behavior of MSCs. Significance Statement: Insulin-like growth factor 1 (IGF-1) plays a multifaceted role in stem cell biology and may promote proliferation, survival, migration, and immunomodulation for MSCs. In this study, we functionalized alginate hydrogels with integrin-binding and IGF-1 peptide mimetics to investigate their impact on MSC function. Embedding MSCs in these hydrogels enhanced their ability to reduce inflammatory cytokine production and promote anti-inflammatory gene expression in cells from degenerative human intervertebral discs exposed to proteins secreted by the MSC. This approach suggests a new way to retain and augment MSC functionality using IGF-1 peptide mimetics, offering an alternative to co-delivery of cells and high dose soluble growth factors for tissue repair and immune- system modulation.

The use of point of care gastric ultrasound and anesthesia management in pediatric patients with preoperative fasting non-adherence scheduled for elective surgical procedures: a retrospective study.

BACKGROUND: Failure to adhere to perioperative fasting requirements increases aspiration risk and can lead to delay or cancellation of surgery. Point of care gastric ultrasound may guide decision-making to delay, cancel or proceed with surgery. METHODS: This study aimed to describe gastric contents using point of care gastric ultrasound in pediatric patients with known fasting guideline violations presenting for elective surgery. This was a single-center retrospectivechart review of gastric ultrasound scans in patients presenting for elective surgeries with "nothing by mouth" violation (per fasting guidelines) or unclear fasting status. The primary outcome is description of gastric contents using point of care ultrasound. The ultrasound findings were classified as low-risk for aspiration (empty, clear fluid < 1.5 ml/kg), high-risk (solids, clear fluid > 1.5 ml/kg), or inconclusive study. Gastric ultrasound findings were communicated to the attending anesthesiologist. For patients proceeding without delay the estimated time saved was defined as the difference between ultrasound scan time and presumed case start time based on American Society of Anesthesiologists fasting guidelines. RESULTS: We identified 106 patients with a median age of 4.8 years. There were 31 patients (29.2%) that had ultrasound finding of high-risk gastric contents. These patients had cases that were delayed, cancelled or proceeded with rapid sequence intubation. Sixty-six patients (62.3%) were determined to be low-risk gastric contents and proceeded with surgery without delay. For these patients, a median of 2.6 h was saved. No aspiration events were recorded for any patients. CONCLUSIONS: It is feasible to use preoperative point of care gastric ultrasound to determine stomach contents and risk-stratify pediatric patients presenting for elective surgical procedures with fasting non-adherence. Preoperative gastric ultrasound may have a role in determining changes in anesthetic management in this patient population.

Alleviating tiling effect by random walk sliding window in high-resolution histological whole slide image synthesis.

Multiplex immunofluorescence (MxIF) is an advanced molecular imaging technique that can simultaneously provide biologists with multiple (i.e., more than 20) molecular markers on a single histological tissue section. Unfortunately, due to imaging restrictions, the more routinely used hematoxylin and eosin (H&E) stain is typically unavailable with MxIF on the same tissue section. As biological H&E staining is not feasible, previous efforts have been made to obtain H&E whole slide image (WSI) from MxIF via deep learning empowered virtual staining. However, the tiling effect is a long-lasting problem in high-resolution WSI-wise synthesis. The MxIF to H&E synthesis is no exception. Limited by computational resources, the cross-stain image synthesis is typically performed at the patch-level. Thus, discontinuous intensities might be visually identified along with the patch boundaries assembling all individual patches back to a WSI. In this work, we propose a deep learning based unpaired high-resolution image synthesis method to obtain virtual H&E WSIs from MxIF WSIs (each with 27 markers/stains) with reduced tiling effects. Briefly, we first extend the CycleGAN framework by adding simultaneous nuclei and mucin segmentation supervision as spatial constraints. Then, we introduce a random walk sliding window shifting strategy during the optimized inference stage, to alleviate the tiling effects. The validation results show that our spatially constrained synthesis method achieves a 56% performance gain for the downstream cell segmentation task. The proposed inference method reduces the tiling effects by using 50% fewer computation resources without compromising performance. The proposed random sliding window inference method is a plug-and-play module, which can be generalized for other high-resolution WSI image synthesis applications. The source code with our proposed model are available at https://github.com/MASILab/RandomWalkSlidingWindow.git.

Sub-Saharan Africa Surveillance Metrics and History of the COVID-19 Pandemic: Updated Epidemiological Assessment.

BACKGROUND: This study updates the COVID-19 pandemic surveillance in Sub-Saharan Africa (SSA) we first conducted in 2020 by providing two additional years of data for the region. OBJECTIVE: First, we aim to measure whether there was an expansion or contraction in the pandemic in SSA when the World Health Organization (WHO) declared the end of the public health emergency for the COVID-19 pandemic on May 5, 2023. Second, we use dynamic and genomic surveillance methods to describe the history of the pandemic in the region and situate the window of the WHO declaration within the broader history. Third, we aim to provide historical context for the course of the pandemic in SSA. METHODS: In addition to updates of traditional surveillance data and dynamic panel estimates from the original study by Post et al. (2021), this study used data on sequenced SARS-CoV-2 variants from the Global Initiative on Sharing All Influenza Data (GISAID) to identify the appearance and duration of variants of concern. We used Nextclade nomenclature to collect clade designations from sequences and Pangolin nomenclature for lineage designations of SARS-CoV-2. Finally, we conducted a one-sided t-test for whether regional weekly speed was greater than an outbreak threshold of ten. We ran the test iteratively with a rolling, six month-window of data across the sample period. RESULTS: Speed for the region remained well below the outbreak threshold before and after the WHO declaration. Acceleration and jerk were also low and stable. The 7-day persistence coefficient remained somewhat large (1.11) and statistically significant. However, both shift parameters for the weeks around the WHO declaration were negative, meaning the clustering effect of new COVID-19 cases had become recently smaller. From November 2021 onward, Omicron was the predominant variant of concern in sequenced viral samples. The rolling t-test of speed equal to ten was insignificant for the entire sample period. CONCLUSIONS: While COVID-19 continues to circulate in SSA, the region never reached outbreak status, and the weekly transmission rate had remained below one case per 100,000 population for well over one year ahead of the WHO declaration. COVID-19 is endemic in the region and no longer reaches the threshold of a pandemic definition. Both standard and enhanced surveillance metrics confirm that the pandemic had ended in SSA by the time of the WHO declaration.

FITT Odyssey: A Scoping Review of Exercise Programs for Managing Rotator Cuff Related Shoulder Pain.

OBJECTIVE: To summarize the FITT (frequency, intensity, time, type) components of exercise programs included in randomized controlled trials (RCTs) that compared 2 or more programs for managing rotator cuff related shoulder pain (RCRSP). DESIGN: Scoping review. LITERATURE SEARCH: Electronic searches were conducted up to May 2023. STUDY SELECTION CRITERIA: RCTs comparing the effects of 2 or more types of exercise programs, differing in prescription according to the FITT principle, in people with RCRSP. DATA SYNTHESIS: We extracted data from each trial report so that we could answer items 1-10 and 13-15 from the Consensus on Exercise Reporting Template (CERT). Descriptive analysis of the exercise programs was performed by summarising and presenting the FITT characteristics, and other relevant CERT characteristics (material, provider, delivery, tailoring). RESULTS: FITT characteristics from 46 exercise programs included in 22 trials were extracted. The exercise programs were divided into 4 categories (defined in accordance to the original authors' description and proposed rationale): motor control (n=8), scapula-focused (n=7), eccentric (n=8), and non-specific exercise programs (n=28). Five programs were allocated to 2 different categories. The different program types had similar parameters. Exercise programs frequency ranged from 2 to 7 times per week, dose ranged from 1 to 3 sets and 4 to 30 repetitions per sets and exercise program duration ranged from 4 to 16 weeks. CONCLUSION: There was considerable variability in the parameters used to prescribe exercises for RCRSP. Clinicians seeking guidance on FITT parameters derived from trials should do so cautiously because there was no one size-fits-all approach.

GEOMETRIC CHARACTERIZATION OF RAT URINARY BLADDER WALL DURING EX-VIVO FILLING USING MICRO-COMPUTED TOMOGRAPHY (MICRO-CT).

Current mechanical models of the bladder largely idealize the bladder as spherical with uniform thickness. This present study aims to investigate this idealization using micro-CT to generate 3D reconstructed models of rat bladders at 10-20 micrometer resolution in both voided and filled states. Applied to three rat bladders, this approach identifies shape, volume, and thickness variations under different pressures. These results demonstrate the filling/voiding process is far from the idealized spherical inflation/contraction. However, the geometry idealizations may be reasonable in cases where the filled bladder geometry is of importance, such as in studies of growth and remodeling.

Revisiting the Historic Strontium-90 Ingestion Beagle Study Conducted at the University of California-Davis: Opportunity in Archival Materials.

Strontium-90 is a radionuclide found in high concentrations in nuclear reactor waste and nuclear fallout from reactor accidents and atomic bomb explosions. In the 1950s, little was known regarding the health consequences of strontium-90 internalization. To assess the health effects of strontium-90 ingestion in infancy through adolescence, the Atomic Energy Commission and Department of Energy funded large-scale beagle studies at the University of California-Davis. Conducted from 1956 to 1989, the strontium-90 ingestion study followed roughly 460 beagles throughout their lifespans after they were exposed to strontium-90 in utero (through feeding of the mother) and fed strontium-90 feed at varying doses from weaning to age 540 days. The extensive medical data and formalin-fixed paraffin-embedded tissues were transferred from UC Davis to the National Radiobiology Archive in 1992 and subsequently to the Northwestern University Radiobiology Archive in 2010. Here, we summarize the design of the strontium-90 ingestion study and give an overview of its most frequent recorded findings. As shown before, radiation-associated neoplasias (osteosarcoma, myeloproliferative syndrome and select squamous cell carcinomas) were almost exclusively observed in the highest dose groups, while the incidence of neoplasias most frequent in controls decreased as dose increased. The occurrence of congestive heart failure in each dose group, not previously assessed by UC Davis researchers, showed a non-significant increase between the controls and lower dose groups that may have been significant had sample sizes been larger. Detailed secondary analyses of these data and samples may uncover health endpoints that were not evaluated by the team that conducted the study.

High-risk human papilloma virus status & outcomes for penile squamous cell carcinoma: A single institution experience.

OBJECTIVES: There is a paucity of data on North American cohorts of patients with penile squamous cell carcinoma (pSCC). Herein, we aimed to assess the sensitivity of various modalities to identify human papillomavirus (HPV) status, determine the prevalence of high-risk HPV-positivity, and evaluate the prognostic impact of relevant clinicopathologic variables. METHODS: Patients with pSCC (n = 121) consecutively treated with partial/total penectomy (2000-2022) at a single institution were included. HPV status (based on immunohistochemistry [IHC], in situ hybridization [ISH], and panviral metagenomic sequencing [PMS]), histologic features, and outcomes were reviewed. Outcome events included death due to disease and progression. RESULTS: The majority of patients were white (105/121, 86.8%). Thirty-seven (30.6%) were high-risk HPV-positive, and morphologic evaluation had a sensitivity of 97.3% (95% confidence interval [CI], 86.2-99.5) for predicting high-risk HPV status compared to IHC/ISH/PMS. Disease progression was more common among high-risk HPV-negative compared to high-risk HPV-positive patients (HR 2.74, CI 1.12-8.23, P = 0.03). Moreover, among high-risk HPV-negative patients, those with moderate-poorly differentiated tumors had increased disease-specific mortality (32.6%, CI 17.1-48.1) compared to those with well-differentiated tumors (0%). Among high-risk HPV-positive patients, those with basaloid morphology had lower disease-specific mortality (0% vs 14.4%, CI 0.0-33.1). CONCLUSIONS: We demonstrate high-risk HPV-positivity in approximately one-third of patients with pSCC. Morphologic evaluation alone had a high sensitivity in correctly determining HPV status. Our results suggest that high-risk HPV status and morphologic features (differentiation in high-risk HPV-negative, and basaloid subtype in high-risk HPV-positive pSCC) may have prognostic value.

MHC-II presentation by oral Langerhans cells impacts intraepithelial Tc17 abundance and Candida albicans oral infection via CD4 T cells.

In a murine model (LCΔMHC-II) designed to abolish MHC-II expression in Langerhans cells (LCs), ∼18% of oral LCs retain MHC-II, yet oral mucosal CD4 T cells numbers are unaffected. In LCΔMHC-II mice, we now show that oral intraepithelial conventional CD8αß T cell numbers expand 30-fold. Antibody-mediated ablation of CD4 T cells in wild-type mice also resulted in CD8αß T cell expansion in the oral mucosa. Therefore, we hypothesize that MHC class II molecules uniquely expressed on Langerhans cells mediate the suppression of intraepithelial resident-memory CD8 T cell numbers via a CD4 T cell-dependent mechanism. The expanded oral CD8 T cells co-expressed CD69 and CD103 and the majority produced IL-17A [CD8 T cytotoxic (Tc)17 cells] with a minority expressing IFN-γ (Tc1 cells). These oral CD8 T cells showed broad T cell receptor Vß gene usage indicating responsiveness to diverse oral antigens. Generally supporting Tc17 cells, transforming growth factor-ß1 (TGF-ß1) increased 4-fold in the oral mucosa. Surprisingly, blocking TGF-ß1 signaling with the TGF-R1 kinase inhibitor, LY364947, did not reduce Tc17 or Tc1 numbers. Nonetheless, LY364947 increased γδ T cell numbers and decreased CD49a expression on Tc1 cells. Although IL-17A-expressing γδ T cells were reduced by 30%, LCΔMHC-II mice displayed greater resistance to Candida albicans in early stages of oral infection. These findings suggest that modulating MHC-II expression in oral LC may be an effective strategy against fungal infections at mucosal surfaces counteracted by IL-17A-dependent mechanisms.

A CPF-like phosphatase module links transcription termination to chromatin silencing.

The interconnections between co-transcriptional regulation, chromatin environment, and transcriptional output remain poorly understood. Here, we investigate the mechanism underlying RNA 3' processing-mediated Polycomb silencing of Arabidopsis FLOWERING LOCUS C (FLC). We show a requirement for ANTHESIS PROMOTING FACTOR 1 (APRF1), a homolog of yeast Swd2 and human WDR82, known to regulate RNA polymerase II (RNA Pol II) during transcription termination. APRF1 interacts with TYPE ONE SERINE/THREONINE PROTEIN PHOSPHATASE 4 (TOPP4) (yeast Glc7/human PP1) and LUMINIDEPENDENS (LD), the latter showing structural features found in Ref2/PNUTS, all components of the yeast and human phosphatase module of the CPF 3' end-processing machinery. LD has been shown to co-associate in vivo with the histone H3 K4 demethylase FLOWERING LOCUS D (FLD). This work shows how the APRF1/LD-mediated polyadenylation/termination process influences subsequent rounds of transcription by changing the local chromatin environment at FLC.