Prenatal Buprenorphine/Naloxone or Methadone Use on Neonatal Outcomes in Michigan

Background: Maternal opioid exposure during pregnancy has various effects on neonatal health. Buprenorphine/naloxone and methadone are examples of medications for opioid use disorder (MOUD) used for the treatment of opioid use disorder (OUD). Research comparing the impacts of these MOUD modalities on neonatal outcomes when used to treat pregnant people with OUD remains limited. We evaluated the differences in outcomes between neonates with in-utero exposure to buprenorphine/naloxone versus methadone. Methodology: We performed a retrospective cohort chart review between October 15, 2008, and October 15, 2019, evaluating mother/neonate dyads at two medical centers in Michigan. The charts of female patients, aged 18+, with OUD and buprenorphine/naloxone or methadone treatment, were examined. The charts of the corresponding neonates were also examined. Multiple regression analysis was performed. Results: In total, 343 mother/infant dyads were included: 99 patients were treated with buprenorphine/naloxone and 232 patients were treated with methadone. The buprenorphine/naloxone group had significant differences in maternal age, hepatitis status, asthma, gestational age in weeks, neonatal intensive care unit (NICU) length of stay (LOS), neonatal opioid withdrawal syndrome (NOWS) peak score, birth head circumference, and birth weight compared to the methadone group at baseline. Adjusted multivariable regression analysis demonstrated neonates with exposure to buprenorphine/naloxone had a NOWS peak score 3.079 points less (95% confidence interval (CI): -4.525, 1.633; p = 0.001) and NICU LOS 8.955 days less (95% CI: -14.399, -3.511; p = 0.001) than neonates exposed to methadone. Conclusions: Neonates with in-utero exposure to buprenorphine/naloxone had significantly lower NOWS scores and shorter NICU LOS compared to neonates with in-utero exposure to methadone. These findings demonstrate that buprenorphine/naloxone is potentially a more favorable treatment for the reduction in metrics representing adverse neonatal outcomes in pregnant people with OUD than methadone

COVID-19 Virus and Vaccination Attitudes among Healthcare Workers in Michigan: A Cross-Sectional Study

Background: Defining the characteristics of healthcare worker (HCW) attitudes toward the coronavirus disease 2019 (COVID-19) vaccine can provide insights into vaccine hesitancy. This study’s goal is to determine HCWs’ attitudes regarding the COVID-19 vaccination and reasons for vaccine hesitancy. Methods: This cross-sectional study surveyed HCWs working in institutions in Saginaw, Sanilac, and Wayne counties in Michigan (N = 120) using tipping-scale questions. Analysis of variance and t-test were used to measure HCWs’ attitudes toward the COVID-19 virus and vaccines. Results: Most HCWs received (95.9%) and recommended (98.3%) a COVID-19 vaccine. The top three factors that HCWs cited for recommending a COVID-19 vaccine were: (1) efficacy of the vaccine, (2) current exposure to patients with active COVID-19 infection and risk of virus spread, and (3) safety of vaccine and long-term follow-up. Female HCWs or HCWs aged 25–54 years were more concerned about contracting COVID-19. Physicians or HCWs aged 55–64 were less concerned regarding the effectiveness and side effects of the vaccine. Conclusions: Gender, age, ethnicity, provider type, and medical specialty showed statistically significant differences among COVID-19 attitudes. Focusing educational efforts on HCW demographics who are more likely to have negative attitudes can potentially decrease vaccine hesitancy

MiR 208a Regulates Mitochondrial Biogenesis in Metabolically Challenged Cardiomyocytes

Metabolic syndrome increases the risk for cardiovascular disease including metabolic cardiomyopathy that may progress to heart failure. The decline in mitochondrial metabolism is considered a critical pathogenic mechanism that drives this progression. Considering its cardiac specificity, we hypothesized that miR 208a regulates the bioenergetic metabolism in human cardiomyocytes exposed to metabolic challenges. We screened in silico for potential miR 208a targets focusing on mitochondrial outcomes, and we found that mRNA species for mediator complex subunit 7, mitochondrial ribosomal protein 28, stanniocalcin 1, and Sortin nexin 10 are rescued by the CRISPR deletion of miR 208a in human SV40 cardiomyocytes exposed to metabolic challenges (high glucose and high albumin-bound palmitate). These mRNAs translate into proteins that are involved in nuclear transcription, mitochondrial translation, mitochondrial integrity, and protein trafficking. MiR 208a suppression prevented the decrease in myosin heavy chain α isoform induced by the metabolic stress suggesting protection against a decrease in cardiac contractility. MiR 208a deficiency opposed the decrease in the mitochondrial biogenesis signaling pathway, mtDNA, mitochondrial markers, and respiratory properties induced by metabolic challenges. The benefit of miR 208a suppression on mitochondrial function was canceled by the reinsertion of miR 208a. In summary, miR 208a regulates mitochondrial biogenesis and function in cardiomyocytes exposed to diabetic conditions. MiR 208a may be a therapeutic target to promote mitochondrial biogenesis in chronic diseases associated with mitochondrial defects

Novel biomarkers of arterial and venous ischemia in microvascular flaps.

The field of reconstructive microsurgery is experiencing tremendous growth, as evidenced by recent advances in face and hand transplantation, lower limb salvage after trauma, and breast reconstruction. Common to all of these procedures is the creation of a nutrient vascular supply by microsurgical anastomosis between a single artery and vein. Complications related to occluded arterial inflow and obstructed venous outflow are not uncommon, and can result in irreversible tissue injury, necrosis, and flap loss. At times, these complications are challenging to clinically determine. Since early intervention with return to the operating room to re-establish arterial inflow or venous outflow is key to flap salvage, the accurate diagnosis of early stage complications is essential. To date, there are no biochemical markers or serum assays that can predict these complications. In this study, we utilized a rat model of flap ischemia in order to identify the transcriptional signatures of venous congestion and arterial ischemia. We found that the critical ischemia time for the superficial inferior epigastric fasciocutaneus flap was four hours and therefore performed detailed analyses at this time point. Histolgical analysis confirmed significant differences between arterial and venous ischemia. The transcriptome of ischemic, congested, and control flap tissues was deciphered by performing Affymetrix microarray analysis and verified by qRT-PCR. Principal component analysis revealed that arterial ischemia and venous congestion were characterized by distinct transcriptomes. Arterial ischemia and venous congestion was characterized by 408 and 1536>2-fold differentially expressed genes, respectively. qRT-PCR was used to identify five candidate genes Prol1, Muc1, Fcnb, Il1b, and Vcsa1 to serve as biomarkers for flap failure in both arterial ischemia and venous congestion. Our data suggests that Prol1 and Vcsa1 may be specific indicators of venous congestion and allow clinicians to both diagnose and successfully treat microvascular complications before irreversible tissue damage and flap loss occurs

Validation of microarray data using qRT-PCR analysis.

<p>qRT-PCR performed on 5 differentially expressed genes (<i>Prol1, Muc1, Vcsa1, Fcnb, Il1b</i>) for flaps undergoing both arterial ischemia and venous congestion for 4 hours compared to control. <i>n = </i>5 and performed in duplicate. Data are expressed as means ± SE and analyzed by unpaired <i>t</i>-test. *<i>P</i><0.05, **<i>P</i><0.01, ***<i>P</i><0.001, cf. control flaps; ^§<i>P<</i>0.05, cf. arterial ischemia flaps.</p

Global transcriptome profiles in ischemic flaps.

<p>A) PCA diagram B) Venn diagram of differentially expressed genes upon 4 hours of arterial ischemia and venous congestion C) Hierarchical cluster analysis of the differentially expressed genes in rats following 4 hours of arterial ischemia and venous congestion.</p

Temporal expression profile of selected genes under venous congestion.

<p>qRT-PCR performed on <i>Prol1, Muc1, Vcsa1, Fcnb, Il1b</i> for flaps undergoing venous congestion compared to control at <i>t = </i>1, 3, 4 hrs. Data are expressed as means ± SE and analyzed by unpaired <i>t</i>-test. *<i>P</i><0.05, **<i>P</i><0.01, ***<i>P</i><0.001.</p

Top GO classes of differentially expressed genes.

<p>Top GO classes of differentially expressed genes.</p

Microarray data of genes demonstrating highest and lowest fold change.

<p>Microarray data of genes demonstrating highest and lowest fold change.</p

Ingenuity Pathway Analysis results for differentially expressed genes in rat composite microvascular flaps undergoing 4 hours of arterial ischemia and venous congestion compared to control flaps.

<p>Ingenuity Pathway Analysis results for differentially expressed genes in rat composite microvascular flaps undergoing 4 hours of arterial ischemia and venous congestion compared to control flaps.</p