Federal Cutbacks and Working AFDC Recipients: A Preliminary Impact Analysis in Rural Minnesota.

Prepared by the Center for Urban and Regional Affairs and the Center for Health Services Research, University of Minnesota, with funding from the Bush Foundation, Hennepin County, the Minneapolis Foundation, Minnesota Department of Energy, Planning and D

Premature differentiation of nephron progenitor cell and dysregulation of gene pathways critical to kidney development in a model of preterm birth

Preterm birth is a leading cause of neonatal morbidity. Survivors have a greater risk for kidney dysfunction and hypertension. Little is known about the molecular changes that occur in the kidney of individuals born preterm. Here, we demonstrate that mice delivered two days prior to full term gestation undergo premature cessation of nephrogenesis, resulting in a lower glomerular density. Kidneys from preterm and term groups exhibited differences in gene expression profiles at 20- and 27-days post-conception, including significant differences in the expression of fat-soluble vitamin-related genes. Kidneys of the preterm mice exhibited decreased proportions of endothelial cells and a lower expression of genes promoting angiogenesis compared to the term group. Kidneys from the preterm mice also had altered nephron progenitor subpopulations, early Six2 depletion, and altered Jag1 expression in the nephrogenic zone, consistent with premature differentiation of nephron progenitor cells. In conclusion, preterm birth alone was sufficient to shorten the duration of nephrogenesis and cause premature differentiation of nephron progenitor cells. These candidate genes and pathways may provide targets to improve kidney health in preterm infants

Puncture Capsulotomy Technique for Hip Arthroscopy: Midterm Functional Outcomes

Background: The most common surgical approaches in hip arthroscopy are interportal and T-capsulotomy. However, these methods may introduce capsular instability. Puncture capsulotomy preserves capsuloligamentous integrity by avoiding iatrogenic transection of the iliofemoral capsular ligament. Purpose: To present minimum 2-year functional outcomes for patients who underwent arthroscopic treatment for acetabular labral tears and concomitant femoroacetabular impingement using the puncture capsulotomy technique. Study design: Case series; Level of evidence, 4. Methods: The authors conducted a retrospective review of prospectively collected data on patients who underwent arthroscopic acetabular labral tear treatment between December 2013 and May 2019. Included were patients aged ≥18 years who underwent hip arthroscopy by a single surgeon and completed a minimum of 2 years of patient-reported outcome measure (PROM) surveys. Intraoperatively, patients underwent hip arthroscopy via puncture capsulotomy to treat labral tears and any concomitant femoroacetabular impingement. Clinical outcome data consisted of PROMs. Results: A total of 163 hips were included; the mean patient follow-up was 30.4 months (range, 24-60 months; 95% CI, 28.5-32.3 months). Patients had a mean age of 37.9 years (range, 36.1-39.6 years), with a mean body mass index of 25.9 (range, 25.2-26.5). There were significant improvements in mean [95% CI] baseline to final follow-up scores for the 33-Item International Hip Outcome Tool (iHOT-33) (39.6 [36.8-42.4] vs 76.1 [72.7-79.6]), Hip Outcome Score-Activities of Daily Living (70.0 [67.0-73.0] vs 89.3 [87.3-91.3]), modified Harris Hip Score (60.1 [57.9-62.4] vs 84.9 [82.5-87.2]), and Hip Outcome Score-Sports Specific Subscale (41.8 [37.9-45.6] vs 75.7 [71.7-79.7]) (P \u3c .001 for all). Additionally, the mean [95% CI] visual analog scale pain scores were noted to significantly improve throughout the duration of the postoperative period (from 6.3 [5.9-6.7] to 2.2 [1.8-2.6]; P \u3c .001). There were no incidences of infection, avascular necrosis of the femoral head, dislocation/instability, or femoral neck fracture. At the 2-year follow-up, 81.0%, 62.0%, and 58.9% of hips achieved previously published clinically meaningful iHOT-33 thresholds for minimally clinically important difference, Patient Acceptable Symptom Score, and substantial clinical benefit, respectively. Conclusion: Puncture capsulotomy demonstrated significantly improved functional and clinically meaningful outcomes at a minimum 2-year follow-up, along with a minimal complication rate

Identification of Kinases Regulating Prostate Cancer Cell Growth Using an RNAi Phenotypic Screen

As prostate cancer progresses to castration-resistant disease, there is an increase in signal transduction activity. Most castration-resistant prostate tumors continue to express the androgen receptor (AR) as well as androgen-responsive genes, despite the near absence of circulating androgen in these patients. The AR is regulated not only by its cognate steroid hormone, but also by interactions with a constellation of co-regulatory and signaling molecules. Thus, the elevated signaling activity that occurs during progression to castration resistance can affect prostate cancer cell growth either through the AR or independent of the AR. In order to identify signaling pathways that regulate prostate cancer cell growth, we screened a panel of shRNAs targeting 673 human kinases against LNCaP prostate cancer cells grown in the presence and absence of hormone. The screen identified multiple shRNA clones against known and novel gene targets that regulate prostate cancer cell growth. Based on the magnitude of effect on growth, we selected six kinases for further study: MAP3K11, DGKD, ICK, CIT, GALK2, and PSKH1. Knockdown of these kinases decreased cell growth in both androgen-dependent and castration-resistant prostate cancer cells. However, these kinases had different effects on basal or androgen-induced transcriptional activity of AR target genes. MAP3K11 knockdown most consistently altered transcription of AR target genes, suggesting that MAP3K11 affected its growth inhibitory effect by modulating the AR transcriptional program. Consistent with MAP3K11 acting on the AR, knockdown of MAP3K11 inhibited AR Ser 650 phosphorylation, further supporting stress kinase regulation of AR phosphorylation. This study demonstrates the applicability of lentiviral-based shRNA for conducting phenotypic screens and identifies MAP3K11, DGKD, ICK, CIT, GALK2, and PSKH1 as regulators of prostate cancer cell growth. The thorough evaluation of these kinase targets will pave the way for developing more effective treatments for castration-resistant prostate cancer

Proton Pump Inhibitor Use Affects Pseudarthrosis Rates and Influences Patient-Reported Outcomes.

Study Design: Retrospective cohort review. Objectives: Cervical pseudarthrosis is a frequent cause of need for revision anterior cervical discectomy and fusion (ACDF) and may lead to worse patient-reported outcomes. The effect of proton pump inhibitors on cervical fusion rates are unknown. The purpose of this study was to determine if patients taking PPIs have higher rates of nonunion after ACDF. Methods: A retrospective cohort review was performed to compare patients who were taking PPIs preoperatively with those not taking PPIs prior to ACDF. Patients younger than 18 years of age, those with less than 1-year follow-up, and those undergoing surgery for trauma, tumor, infection, or revision were excluded. The rates of clinically diagnosed pseudarthrosis and radiographic pseudarthrosis were compared between PPI groups. Patient outcomes, pseudarthrosis rates, and revision rates were compared between PPI groups using either multiple linear or logistic regression analysis, controlling for demographic and operative variables. Results: Out of 264 patients, 58 patients were in the PPI group and 206 were in the non-PPI group. A total of 23 (8.71%) patients were clinically diagnosed with pseudarthrosis with a significant difference between PPI and non-PPI groups (P = .009). Using multiple linear regression, PPI use was not found to significantly affect any patient-reported outcome measure. However, based on logistic regression, PPI use was found to increase the odds of clinically diagnosed pseudarthrosis (odds ratio 3.552, P = .014). Additionally, clinically diagnosed pseudarthrosis negatively influenced improvement in PCS-12 scores (P = .022). Conclusions: PPI use was found to be a significant predictor of clinically diagnosed pseudarthrosis following ACDF surgery. Furthermore, clinically diagnosed pseudarthrosis negatively influenced improvement in PCS-12 scores