Recent Research Publications- November 2022
Schrepf A, Kaplan C, Harris RE, Williams DA, Clauw DJ, As-Sanie S, Till S, Clemens JQ, Rodriguez LV, Van Bokhoven A, Landis R, Gallop R, Naliboff B, Pontari M, O'Donnell M, Luo Y, , Harte SE; See MAPP masthead.
Pain. 2022 Oct 19. doi: 10.1097/j.pain.0000000000002813. Epub ahead of print. PMID: 36279178; PMCID: PMC10106356.
Interstitial cystitis/bladder pain syndrome (IC/BPS) is a common and debilitating disease with poor treatment outcomes. Studies from the multidisciplinary approach to the study of chronic pelvic pain research network established that IC/BPS patients with chronic overlapping pain conditions (COPCs) experience poorer quality of life and more severe symptoms, yet the neurobiological correlates of this subtype are largely unknown. We previously showed that ex vivo toll-like receptor 4 (TLR4) cytokine/chemokine release is associated with the presence of COPCs, as well as widespread pain and experimental pain sensitivity women with IC/BPS. Here, we attempt to confirm these findings in the multisite multidisciplinary approach to the study of chronic pelvic pain Symptom Patterns Study using TLR4-stimulated whole blood (female IC/BPS patients with COPC n = 99; without n = 36). Samples were collected in tubes preloaded with TLR4 agonist, incubated for 24 hours, and resulting supernatant assayed for 7 cytokines/chemokines. These were subject to a principal components analysis and the resulting components used as dependent variables in general linear models. Controlling for patient age, body mass index, and site of collection, we found that greater ex vivo TLR4-stimulated cytokine/chemokine release was associated with the presence of COPCs ( P < 0.01), extent of widespread pain ( P < 0.05), but not experimental pain sensitivity ( P > 0.05). However, a second component of anti-inflammatory, regulatory, and chemotactic activity was associated with reduced pain sensitivity ( P < 0.01). These results confirm that the IC/BPS + COPCs subtype show higher levels of ex vivo TLR4 cytokine/chemokine release and support a link between immune priming and nociplastic pain in IC/BPS.
Biobehavioral factors predict an exosome biomarker of ovarian carcinoma disease progression.
Lutgendorf SK, Thaker PH, , Arevalo JMG, Chowdhury MA, Noble AE, Dahmoush L, Slavich GM, Penedo FJ, Sood AK, Cole SW.
Cancer. 2022 Oct 17. doi: 10.1002/cncr.34496. Epub ahead of print. PMID:
36251340; PMCID: PMC9744596.
Background: Biobehavioral factors such as social isolation and depression have been associated with disease progression in ovarian and other cancers. Here, the authors developed a noninvasive, exosomal RNA profile for predicting ovarian cancer disease progression and subsequently tested whether it increased in association with biobehavioral risk factors.
- Exosomes were isolated from plasma samples from 100 women taken before primary surgical resection or neoadjuvant (NACT) treatment of ovarian carcinoma and 6 and 12 months later. Biobehavioral measures were sampled at all time points. Plasma from 76 patients was allocated to discovery analyses in which morning presurgical/NACT exosomal RNA profiles were analyzed by elastic net machine learning to identify a biomarker predicting rapid (≤6 months) versus more extended disease-free intervals following initial treatment. Samples from a second subgroup of 24 patients were analyzed by mixed-effects linear models to determine whether the progression-predictive biomarker varied longitudinally as a function of biobehavioral risk factors (social isolation and depressive symptoms).
- An RNA-based molecular signature was identified that discriminated between individuals who had disease progression in ≤6 months versus >6 months, independent of clinical variables (age, disease stage, and grade). In a second group of patients analyzed longitudinally, social isolation and depressive symptoms were associated with upregulated expression of the disease progression propensity biomarker, adjusting for covariates.
Conclusion: These data identified a novel exosome-derived biomarker indicating propensity of ovarian cancer progression that is sensitive to biobehavioral variables. This derived biomarker may be potentially useful for risk assessment, intervention targeting, and treatment monitoring.
SSRI use in pregnancy: Moving towards collaborative, evidence-based decision-making.
Gumusoglu SB, Santillan MK.
Pregnancy Hypertens. 2022 Oct 7;30:146-147. doi: 10.1016/j.preghy.2022.10.001. Epub ahead of print.2022 Oct 7. PMID: 36219941; PMCID: PMC10158533.
Foreword: Maternity Care in Rural America.
Hunter SK.
Clin Obstet Gynecol. 2022 Dec 1;65(4):786-787. doi: 10.1097/GRF.0000000000000764. Epub 2022 Oct 20. PMID: 36260012.
Thompson DA, Cwiertny DM, Davis HA, Grant A, Land D, Landsteiner SJ, Latta DE, , Jones MP, Lehmler H,
Environmental Advances, Volume 9, October 2022, 100306. doi: 10.1016/j.envadv.2022.100306
Chronic ingestion of excess sodium has been associated with high blood pressure, heart disease, and stroke. Limited research has suggested a relationship between increased sodium intake and the development of preeclampsia. This study investigated the association between elevated sodium in drinking water with preeclampsia using a hospital-based case-control study of 10,114 pregnant women in Iowa in the United States. Health records of women who delivered at the University of Iowa Hospitals and Clinics in Iowa City, Iowa, USA, between May 2009 and August 2020 were obtained from the Intergenerational Health Knowledgebase. Water quality data for community water systems from Safe Drinking Water Act compliance reporting and Consumer Confidence Reports (CCR) were used to estimate maternal exposure to sodium in drinking water. Logistic regression models were calculated to estimate the odds of preeclampsia based on median sodium concentrations reported by public water systems from 2000 to 2019. Preeclampsia was associated with a 38% increased odds (adjusted odds ratio (aOR) 1.38, 95% confidence interval (CI) 1.13-1.69) when women were exposed to concentrations between 20-69 milligrams per liter (mg/L), above EPA's recommendation for individuals on a very low sodium diet. Increased odds of 5% and 16% were also found at concentrations between 70-102 mg/L and greater than 256 mg/L but were not statistically significant. The lower odds at higher sodium concentrations may be due to consumers using alternative drinking water sources due to taste issues that are noted to arise between 30-60 mg/L. Preeclampsia diagnosis was strongly associated with gestational age, parity, newborn count, and body mass index. Better data on individual exposure through drinking water is needed to account for factors like home softeners, which can greatly increase sodium levels at the tap, or those users seeking out alternative water supplies (like bottled water) due to taste issues arising from greater salinity.
Rural Maternal Health Care Outcomes, Drivers, and Patient Perspectives.
Anglim AJ, Radke SM.
Clin Obstet Gynecol. 2022 Dec 1;65(4):788-800. doi: 10.1097/GRF.0000000000000753. Epub 2022 Oct 3. PMID: 36260013.
Rural communities are a vital segment of the US population; however, these communities are shrinking, and their population is aging. Rural women experience health disparities including increased risk of maternal morbidity and mortality. In this article, we will explore these trends and their determinants both within and external to the health care system. Health care providers, public health professionals, and policymakers should be aware of these social and structural factors that influence health outcomes and take action to reduce generational cycles of health disparity. Opportunities to improve the health and pregnancy outcomes for rural women and rural populations are highlighted.
A Case of Persistent Human Pegivirus Infection in Two Separate Pregnancies of a Woman.
Garand M, Huang SSY, Goessling LS, Brar A, Wylie TN, Wylie KM, Eghtesady P.
Microorganisms. 2022 Sep 28;10(10):1925. doi: 10.3390/microorganisms10101925. PMID: 36296201; PMCID: PMC9610878.
Human pegivirus (HPgV) is best known for persistent, presumably non-pathogenic, infection and a propensity to co-infect with human immunodeficiency virus or hepatitis C virus. However, unique attributes, such as the increased risk of malignancy or immune modulation, have been recently recognized for HPgV. We have identified a unique case of a woman with high levels HPgV infection in two pregnancies, which occurred 4 years apart and without evidence of human immunodeficiency virus or hepatitis C virus infection. The second pregnancy was complicated by congenital heart disease. A high level of HPgV infection was detected in the maternal blood from different trimesters by RT-PCR and identified as HPgV type 1 genotype 2 in both pregnancies. In the second pregnancy, the decidua and intervillous tissue of the placenta were positive for HPgV by PCR but not the chorion or cord blood (from both pregnancies), suggesting no vertical transmission despite high levels of viremia. The HPgV genome sequence was remarkably conserved over the 4 years. Using VirScan, sera antibodies for HPgV were detected in the first trimester of both pregnancies. We observed the same anti-HPgV antibodies against the non-structural NS5 protein in both pregnancies, suggesting a similar non-E2 protein humoral immune response over time. To the best of our knowledge, this is the first report of persistent HPgV infection involving placental tissues with no clear indication of vertical transmission. Our results reveal a more elaborate viral-host interaction than previously reported, expand our knowledge about tropism, and opens avenues for exploring the replication sites of this virus.
Need for Improved Collection and Harmonization of Rural Maternal Healthcare Data
Santillan DA, Davis HA, Faro EZ, Knosp BM, Santillan MK.
Clin Obstet Gynecol. 2022 Dec 1;65(4):856-867. doi: 10.1097/GRF.0000000000000752. Epub 2022 Oct 20. PMID: 36260014; PMCID: PMC9586468.
Representation in data sets is critical to improving healthcare for the largest possible number of people. Unfortunately, pregnancy is a very understudied period of time. Further, the gap in available data is wide between pregnancies in urban areas versus rural areas. There are many limitations in the current data that is available. Herein, we review these limitations and strengths of available data sources. In addition, we propose a new mechanism to enhance the granularity, depth, and speed with which data is made available regarding rural pregnancy.
Kesić V, Vieira-Baptista P,
Cancers (Basel). 2022 Oct 18;14(20):5088. doi: 10.3390/cancers14205088. PMID: 36291873; PMCID: PMC9600382.