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Osteoblast Transcriptome Changes During Iron Deficiency
Get PDFIntroduction:Chronic kidney disease (CKD) often results in iron deficiency anemia and bone loss. Previously, iron deficiency was found to impede normal osteoblast differentiation. To investigate regulatory mechanisms elicited by iron deficiency we utilized unbiased RNA-sequencing to evaluate transcriptome-level changes over the course of differentiation.
Methods:Mouse progenitor clone 2 (MPC-2) cells were differentiated in osteogenic media with or without an iron chelator, deferoxamine (DFO; 5 μM). RNA was extracted at 3, 7, and 14 days after initiating differentiation. Library generation and sequence alignment was performed by the Center for Medical Genomics (CMG). Count-based algorithms implemented in R packages (edgeR and limma-voom; default parameters) identified differentially expressed genes between cells in the control and DFO treatment.
Results:RNA sequencing illustrated transcriptome changes due to iron deficiency including 63 upregulated/81 downregulated genes at day 3, 371 upregulated/780 downregulated genes at day 7, and 342 upregulated/739 downregulated genes at day 14. Importantly, day 14 controls clustered as transcriptional distinct whereas day 14 DFO treated cells clustered with early time points. As expected, genes involved in bone mineralization were suppressed with DFO including Dmp1 (logFC: -5.92, p= 5.7e-10) and Phex (logFC: -4.17, p= 5.5e-16). Interestingly, genes such as Ces2e, Gdf15, and Ano3, not previously found associated with osteoblasts, were significantly upregulated after 3 days with DFO (logFC: 5.14, 2.7, and 2.5 respectively).
Conclusions:Transcriptomic changes occur even within 3 days of exposure to iron deficiency. Next steps include performing functional enrichment analysis, and validating expression level changes in vitro as well as within in vivo models of CKD-mediated bone loss.
Scientific Impact and implications:Iron deficiency is intricately linked to impaired osteoblast function. Understanding the underlying molecular mechanisms could elucidate novel avenues for anabolic bone therapies in CKD
Assessing the Severity of Portal Hypertension: Is Liver or Spleen Stiffness Measurement an Alternative to the Gold Standard, Hepatic Vein or Porto-Systemic Pressure Gradient?
Get PDFIntroduction: Liver stiffness measurement (LSM) and spleen stiffness measurement (SSM) are increased in patients with cirrhosis and portal hypertension (PH). However, increased SSM values are associated with presence of esophageal varices. Currently, the gold standard for risk stratification in patients with compensated advanced chronic liver disease (cACLD) is by measurement of portal pressure through assessment of hepatic vein or porto-systemic pressure gradient (HVPG and PSPG). However, these procedures are invasive, and either LSM or SSM may be a non-invasive alternative.
Aim: We aimed to investigate the relationship between LSM or SSM and HVPG/PSPG and examined the diagnostic accuracy for identification of clinically significant PH (≥10 mm Hg) or severe PH (≥12 mm Hg).
Methods: A retrospective study (IRB Protocol #19230) allowed us to identify patients who had who undergone portal pressure measurements (HVPG or PSPG). A total of 36 patients also had SSM values. Of these, 29 patients carried a hepatic cause of PH, while the remaining had pre-hepatic (n=4) and post-hepatic (n=3) etiology.
Results: The median age was 58 years (range: 25-71) with 52% male and 83% with cirrhosis. The median LSM and SSM were 35.7 kPa (range:7.4-75.0, normal ≤7.0 kPa) and 43.8 kPa (range: 20.7-100, normal ≤ 21.0 kPa). Both LSM (r = 0.42, P-value = 0.02) and SSM (r = 0.45, P-value: 0.01) correlated significantly with HVPG/PSPG. The diagnostic accuracy for both LSM and SSM for clinically significant PH was good for LSM (AUROC 0.76, 95% CI:0.58-0.94) and excellent for SSM (AUROC: 0.81, 95% CI:0.65-0.98). The diagnostic accuracy of LSM and SSM was lower for severe PH [AUROC 0.71 (P-value = 0.06) and 0.67 (P-value = 0.1) for LSM and SSM, respectively].
Conclusion: Both LSM and SSM correlate with portal pressure measurements and provide diagnostic accuracy to identify patients with clinically significant, but not severe, PH
Social Determinants of Health and 30-Day Readmissions in an Urban Community Hospital in Northwest Indiana
Get PDFBackground: Hospital readmission within 30 days of discharge is a quality of care indicator with implications for healthcare systems, payers, and patients. The Hospital Readmission Reduction Program enacted in 2012 aimed to reduce preventable readmissions. Yet in 2018, there were 3.8 million adult 30-day readmissions with an average rate of 14% and estimated cost of $15,200 per readmission. This study examined the influence of social determinants of health (SDOH), demographics, and health behaviors on 30-day readmissions at an urban hospital in Northwest Indiana. This is part of a Community-Based Participatory Research (CBPR) partnership between Indiana University School of Medicine-Northwest and St. Mary Medical Center (SMMC) to address SDOH.
Methods: This retrospective study analyzed a limited dataset generated by SMMC in EPIC™ with SDOH, demographics, health behaviors, and health outcomes measures from inpatient admissions between January 2021 to March 2023. Data analysis consisted of descriptive, bivariate (Chi-Square; p<0.05), and multivariate (binary logistic regression; p<0.05) analyses in SPSS 29.0. This study was exempted by the Indiana University Human Research Protection Program (IRB #14040).
Results: The sample consisted of 7445 patients, majority 65 years and above (56.5%), white (77.47%), and publicly insured (76.83%). 30-day readmissions represented 10.5% of admissions. The bivariate analysis revealed statistically significant associations between 30-dayreadmissions and age (p<0.001), language (p=0.008), insurance type (p<0.001), veteran status (p=0.017), and smoking (p<0.001). The multivariate analysis found that age (OR=1.008; p=0.004), being a non-English speaker (OR=1.866; p=0.009), public insurance (OR=2.096; p<0.001), and former smoking (OR=1.243; p=0.011) remained significantly associated with 30-day readmission.
Conclusions: Social and behavioral factors were associated with 30-day readmissions in an urban community hospital. Incorporating SDOH and behavioral interventions into hospital readmission reduction programs may reinforce these programs. The upcoming CBPR phase will conduct advanced analysis on these findings to uncover new relationships relevant to SMMC’s objectives
Viability of Transplanted De Novo Retinal Ganglion Cells in Human Donor Eyes Maintained Under Elevated Intraocular Pressure
Get PDFPurpose: Glaucoma is a group of optic neuropathies characterized by visual field loss, classically due to increased intraocular pressure (IOP) and retinal ganglion cell (RGC) degeneration. Current treatment options reduce IOP, but RGC degeneration persists. De novoRGCs can be differentiated from reprogrammed human corneal fibroblasts and transplanted into the retina to potentially restore vision in patients with late-stage disease when most RGCs are irreversibly damaged. We investigate the survival of these human induced pluripotent stem cell (IPSC) derived RGCs after culturing them in human donor eyes under conditions of elevated and normal IOP using the ocular translaminar autonomous system (TAS) chamber.
Methods: Human iPSCs were generated by reprogramming human donor corneal fibroblasts using Sendai viral vectors with Yamanaka factors. These iPSCs were then differentiated into retinal organoids from which RGCs were obtained. The RGCs were transduced with AAV2-GFP and transplanted into donor human eyes obtained from control individuals. They were pressurized for approximately 5 days, with the left eye maintained at normal IOP and right eye at elevated IOP. Viability was measured by expression levels of pro-survival pathways via qRTPCR, immunohistochemistry staining, and electroretinography for retinal function (ERG).
Results: We successfully transplanted human RGCs into human donor eyes and visualized them after GFP transduction. We maintained a pressure differential between the two eyes for approximately 5 days using the TAS model. Differential expression of survival, inflammatory and apoptotic genes was identified between normal and high IOP. We identified retinal function changes under normal and high IOP after RGC transplantation.
Conclusions: Human iPSC derived RGCs provide a potential strategy to overcome vision loss in patients with diseases that damage RGCs such as glaucoma, Parkinson’s, Alzheimer\u27s, multiple sclerosis, and traumatic optic neuropathy. Future investigation would involve integration of transplanted RGCs and directing their axons towards visual centers in the brain
Diffuse Midline H3 K27-Altered Gliomas in the Spinal Cord: A Systematic Review
Get PDFBackground: Gliomas account for 80-90% of all intramedullary spinal cord tumors (IMSCTs). Though rare compared to brain tumors, spinal cord gliomas can cause significant morbidity and mortality. Diffuse midline gliomas (DMGs) with H3 K27M-mutation, first introduced in the 2016 WHO classification, are high-grade tumors with aggressive behavior and poor prognosis. The 2021 updated WHO classification renamed them "diffuse midline glioma, H3 K27-altered" to include other molecular changes. Limited single-institution data on spinal cord DMGs (DMGSCs) hinder comprehensive understanding and optimal treatment protocols. In this review, we summarize clinical and molecular features, management strategies, and survival impact in patients with DMG-SCs.
Project Methods: A systematic review was performed following the (PRISMA) guidelines. PubMed, Ovid EMBASE, Scopus, and Web of Science were searched. Clinical characteristics, treatment protocols, and outcomes were analyzed.
Results: A total of 26 studies with 259 patients were included. Most patients were male (63%), diagnosed at a mean age of 32 years (range, 4-72), and tumors were predominately located in the cervical (32%) or thoracic (43%) regions of the spinal cord. Primary management included surgical resection (97%), radiotherapy (78%), and chemotherapy (62%). Most common combination of treatment included surgical resection, radiotherapy, and chemotherapy (47%). The mean overall and progression free survival were 25 (range, 0.1-48) and 14 (range, 0.1-25) months, respectively. Gene alterations included p53 mutation (61%), loss of ATRX (46%), Olig- 2 positive (100%), and GFAP positive (80%). The mean Ki-67/MIB-1 was 23% (12-40%).
Conclusion/Impact: DMG-SCs affect mostly the adult population and appear to resemble adult DMGs in terms of molecular features, management, and prognosis
The Added Value of Student Affairs in Retention Prediction Models
Get PDFFor this inquiry we supplemented typical academic variables to evaluate the degree to which several student affairs variables add value in a machine learning model predicting first-year retention. Findings indicated that living on campus, being Greek, as well as engaging in recreational sports all had positive contributions to predicting retention. Higher education leaders should use this study to advocate for and enact the inclusion of student affairs variables into predictive models of student success
Contributions of Leading Student Affairs Assessment Associations and Organizations
Get PDFProfessional organizations have historically and currently played a foundational role in advancing and supporting the field of student affairs assessment through setting standards, professional development, and creating spaces for communities of practice. This article examines the contributions of key student affairs organizations by (a) highlighting their unique efforts to provide professional support and resource dissemination, (b) addressing contemporary challenges collaboratively, (c) advancing the field through strategic partnerships and research, and (d) a call to action to continue to lead in the field and sustain impactful assessment and professional practices
Social Work Boundary Issues in the Digital Age: Reflections of an Ethics Expert
Get PDFThroughout social work’s history, practitioners have faced challenging boundary issues. Boundary issues occur when social workers encounter actual or potential conflicts between their professional duties and their social, sexual, religious, collegial, or business relationships. Today\u27s social workers face a wide range of boundary challenges that are unprecedented because of practitioners’ and clients’ widespread use of digital and other forms of internet-enabled technologies. This article presents a typology of boundary-related challenges arising out of social workers’ and clients\u27 use of technology; reviews and applies emerging ethical and practice standards; and discusses risk-management protocols designed to protect clients and social workers. The author offers practical recommendations to protect clients and practitioners, including compliance with state-of-the-art ethics standards related to technology use and development of a comprehensive social media policy
Observed Risks of Client Safety by Social Care Professionals in Finland: Trend Analysis for 2016-2020
Get PDFTo promote client safety, Finland’s Social Welfare Act requires social services employees to notify superiors of the observed risks in implementing clients’ social welfare. This study provides the first retrospective trend analysis of reports from a care reporting system (SPro-system) in Finland. Reports (n=1,433) were made by social work employees in the city of Helsinki in Finland, from October 2016 to December 2020. The statistical analysis focused on investigating trends in the reports. Most commonly reporters were practical nurses or other care workers (31.0%, n=444) or social advisors or other advisors of social work (23%, n=329). The total of observed risks or threats increased annually, except in 2019. The content of reports mainly related to a lack of realization of the status and rights of clients (32.5%, n=475) with the consequence for clients being moderate harm (28.3%, n=406). Information and discussion about client safety events (55.1%, n=860) were perceived as the most important ways to prevent the recurrence of such incidences. More empirical research is needed on client safety from the social work perspective. Risks in social care are diverse, but professionals’ observations may help to prevent them. Thus, reporting practices relating to client safety risks should be strongly encouraged, if not mandated
Keeping Community During a Pandemic: LGBTQ+ Older Adults and the Virtual Senior Center
Get PDFThe purpose of this qualitative exploratory study was to better understand how LGBTQ+ senior centers created virtual communities and implemented organizational adaptation in the earliest stages of the pandemic. Three focus groups (n=22) were conducted with program facilitators and senior center employees to better understand how these key stakeholders contributed to the transition from in person senior center to virtual senior center programming in March of 2020. The experiences of LGBTQ+ program facilitators and senior center staff varied based on the nature of their assigned roles. Latent pattern content analysis of the focus groups unveiled both shared and divergent categories and themes from the two cohorts. Themes identified for program facilitators included: adaptation, interconnectedness, some not served, and virtual preference. Themes identified for senior center staff included: communication, the blurring of the personal/professional, urgent needs, and future planning