Umbilical Cord Milking Versus Delayed Cord Clamping in Infants 28 to 32 Weeks: A Randomized Trial.

OBJECTIVES: To determine whether rate of severe intraventricular hemorrhage (IVH) or death among preterm infants receiving placental transfusion with UCM is noninferior to delayed cord clamping (DCC). METHODS: Noninferiority randomized controlled trial comparing UCM versus DCC in preterm infants born 28 to 32 weeks recruited between June 2017 through September 2022 from 19 university and private medical centers in 4 countries. The primary outcome was Grade III/IV IVH or death evaluated at a 1% noninferiority margin. RESULTS: Among 1019 infants (UCM n = 511 and DCC n = 508), all completed the trial from birth through initial hospitalization (mean gestational age 31 weeks, 44% female). For the primary outcome, 7 of 511 (1.4%) infants randomized to UCM developed severe IVH or died compared to 7 of 508 (1.4%) infants randomized to DCC (rate difference 0.01%, 95% confidence interval: (-1.4% to 1.4%), P = .99). CONCLUSIONS: In this randomized controlled trial of UCM versus DCC among preterm infants born between 28 and 32 weeks' gestation, there was no difference in the rates of severe IVH or death. UCM may be a safe alternative to DCC in premature infants born at 28 to 32 weeks who require resuscitation.

Piloting an Oral History Approach to Investigate Cancer Perspectives Among Residents of Appalachian Kentucky.

Introduction: Kentucky ranks first in the U.S. in overall cancer incidence and mortality rates. Areas of the state that fall within the Appalachian Region, along Kentucky's eastern border, experience disproportionately high rates of cancer compared to non-Appalachian counties. Purpose: This pilot study investigates whether oral history interviews can be used to understand perspectives on cancer among residents of Appalachian Kentucky. Methods: In 2020, participants (n = 5) who identified as being from and/or having strong connections to Appalachian Kentucky were recruited to participate in this pilot study. Participants included individuals working in cancer-related fields, oncology professionals, and those with personal cancer experience. Using an oral history approach, subjects were asked about challenges within Appalachia that contribute to high rates of cancer regionally. Interviews were analyzed using qualitative content analysis, and data were condensed into themes, subthemes, and subtopics. Relational content analysis was then used to illustrate relationships between the problems being faced in Appalachia and their contributing factors, with potential solutions to those problems. Results: Six key themes emerged from analysis of the oral history interviews: (1) problems being faced in Appalachia; (2) contributing factors; (3) potential solutions; (4) Appalachian disposition; (5) experiences with and thoughts on cancer; and (6) defining success v. the future without changes (intervention). A further 25 subthemes were identified from within these themes. Taken together, these themes and subthemes point to potential areas for specific intervention to shift Appalachia's cancer burden. Implications: This pilot study demonstrates potential benefit in using oral history interviews to elucidate Appalachian Kentuckians' perspectives on cancer. From the nuanced insights gained through this method, a set of culturally appropriate interventions were identified that could address the disproportionate cancer burden in the region. Future studies using an oral history approach could aim to reveal other specific aspects of how cancer impacts individuals, families, and communities.

Real-World Utilization of an Intrauterine, Vacuum-Induced, Hemorrhage-Control Device.

OBJECTIVE: To assess the real-world effectiveness and safety of a U.S. Food and Drug Administration (FDA)-cleared intrauterine vacuum-induced-hemorrhage control device for postpartum hemorrhage (PPH) management. METHODS: Sixteen centers in the United States participated in this observational, postmarket registry medical record review (October 2020 through March 2022). The primary effectiveness outcome was treatment success , defined as bleeding control after insertion with no treatment escalation or bleeding recurrence. Additional outcomes included blood loss, time to device insertion, indwelling time, bleeding recurrence, and time to bleeding control. Treatment success and severe maternal morbidity measures (transfusion of 4 or more units of red blood cell, intensive care unit admission, and hysterectomy) were evaluated by blood loss before insertion. To assess safety, serious adverse events (SAEs) and adverse device effects were collected. All outcomes were summarized by mode of delivery; treatment success was summarized by bleeding cause (all causes, any atony, isolated atony, nonatony). RESULTS: In total, 800 individuals (530 vaginal births, 270 cesarean births) were treated with the device; 94.3% had uterine atony (alone or in combination with other causes). Median total blood loss at device insertion was 1,050 mL in vaginal births and 1,600 mL in cesarean births. Across all bleeding causes, the treatment success rate was 92.5% for vaginal births and was 83.7% for cesarean births (95.8% [n=307] and 88.2% [n=220], respectively, in isolated atony). Median indwelling time was 3.1 hours and 4.6 hours, respectively. In vaginal births, 14 SAEs were reported among 13 individuals (2.5%). In cesarean births, 22 SAEs were reported among 21 individuals (7.8%). Three (0.4%) SAEs were deemed possibly related to the device or procedure. No uterine perforations or deaths were reported. CONCLUSION: For both vaginal and cesarean births in real-world settings, rapid and effective bleeding control was achieved with an FDA-cleared intrauterine vacuum-induced hemorrhage-control device. The safety profile was consistent with that observed in the registrational trial (NCT02883673), and SAEs or adverse device effects were of the nature and severity expected in the setting of PPH. This device is an important new tool for managing a life-threatening condition, and timely utilization may help to improve obstetric hemorrhage outcomes. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov , NCT04995887.

Engaging Appalachian Youth: Lessons Learned From a Virtual Tobacco Prevention and Advocacy Training.

Engaging youth is recommended as a key component of comprehensive tobacco control to bring voice to youth perspective and to connect to community impact. Yet, limited research exists to showcase practical lessons learned in supporting skill development and engagement of youth. This practice note describes how a tailored prevention and advocacy virtual training can serve to engage and empower rural Appalachian high school students to participate in tobacco control efforts. Specifically, we describe the implementation and practical lessons learned from a two-session virtual tobacco prevention and advocacy training led by college facilitators. Participating high school students (N = 20) strongly agreed that tobacco use was a major problem facing their community and that addressing tobacco use should be prioritized. After participating in the training, students' interpersonal confidence improved and participation in self-reported advocacy increased. Students also liked the virtual platform, interaction with college students, and the opportunity to apply information learned. Youth-focused tailored training promotes skill-building and enhances self-efficacy to engage in tobacco control. Youth engagement should be integral to supporting community health initiatives, including tobacco prevention.

Incidental detection of malignancy on point-of-care renal ultrasound: A case series.

Renal point-of-care ultrasound (POCUS) is an increasingly common initial imaging modality in the diagnostic workup of renal colic. The primary use of renal POCUS is to assess for hydronephrosis; however, other significant findings suggestive of malignancy can also be identified. We present three cases of unexpected findings identified initially on POCUS in the emergency department, which subsequently led to new diagnoses of malignancy. As renal POCUS becomes more frequently used in clinical practice, physicians must be able to recognise abnormal images that indicate possible malignancy and the need for further workup.

Regional multidisciplinary team approach to the management of placenta accreta spectrum disorder.

OBJECTIVE: Patients with suspected placenta accreta spectrum (PAS) disorder are often referred to specialized medical centers for antepartum management and definitive treatment via cesarean hysterectomy. In 2019, our institution formed the only multidisciplinary team for the management of PAS within two of the largest counties in California. The purpose of this study was to evaluate the effects of the multidisciplinary team on patient volume and surgical outcomes for patients with PAS. METHODS: This was a single center retrospective cohort study, based in the only tertiary referral center within two of the largest counties in California. Patients who underwent cesarean hysterectomy for suspected PAS from January 2014 to April 2021 were included and divided into two groups, based on management by the multidisciplinary team from January 2019 and onward or routine care prior to that time. The outcomes of interest were quantitative blood loss, total units of packed red blood cell transfusion, referral volume, and diagnostic accuracy as well as ICU admission, bladder injury, and postoperative length of stay. Furthermore, we wanted to determine if patient's distance to the hospital impacted outcomes. Normally distributed variables were compared between groups using the t-test. Categorical variables were compared between the two groups using the chi square test. RESULTS: A total of 114 patients were included in the cohort, 59 patients were from January 2014 to December 2018 and 55 patients were from January 2019 to April 2021. Since the establishment of the multidisciplinary center, there was a 2.5-fold increase in the total patient volume (0.8 case/month to 2 cases/month) and a 2.8-fold increase in the referred patient volume. Patients undergoing cesarean hysterectomy since the establishment of the multidisciplinary team had less quantitative blood loss (1500 mL vs 2000 mL, p = .005) and required less units of packed red blood cell transfusion (2 vs 4 units, p < .001). In addition, blood loss of ≥2000 mL decreased from 57.6% to 38.2% (p = .04) and diagnostic accuracy improved from 35.6% to 83.6% (p < .001). Furthermore, we found that patient distance to the hospital did not significantly impact surgical outcomes. CONCLUSIONS: Since the establishment of the multidisciplinary team, our center experienced an increase in PAS volume and was able to demonstrate a statistically significant improvement in patient outcomes.

The Prevalence of Low-Value Prostate Cancer Screening in Primary Care Clinics: A Study Using the National Ambulatory Medical Care Survey.

INTRODUCTION: There has been an increasing focus on improving value in health care and deimplementing the use of low-value services, such as prostate cancer (PC) screening for men aged >70 years. The objectives of this study are to (1) identify the proportion of primary care visits at which low-value PC screening is ordered, and (2) identify predisposing, enabling, and health care need characteristics associated with low-value PC screening in the United States. METHODS: This was a secondary analysis of the National Ambulatory Medicare Care Survey datasets from 2013 to 2016 and 2018. Andersen's Behavioral Model of Health Services Use guided independent variable selection. Weighted multivariable logit models were used to analyze data. RESULTS: There were 6.71 low-value prostate-specific antigens (PSAs) per 100 visits and 1.65 low-value digital rectal exams (DREs) per 100 visits. For each additional service ordered by primary care providers, the odds of ordering a low-value PSA increased by 49%, and the odds of performing a low-value DRE increased by 37%. CONCLUSIONS: The use of low-value PSAs and DREs was sizable during the observed time period. Organizations who want to reduce low-value PSAs and DREs may want to focus interventions on providers who order a high number of tests.

Umbilical cord milking in nonvigorous infants: a cluster-randomized crossover trial.

BACKGROUND: Delayed cord clamping and umbilical cord milking provide placental transfusion to vigorous newborns. Delayed cord clamping in nonvigorous newborns may not be provided owing to a perceived need for immediate resuscitation. Umbilical cord milking is an alternative, as it can be performed more quickly than delayed cord clamping and may confer similar benefits. OBJECTIVE: We hypothesized that umbilical cord milking would reduce admission to the neonatal intensive care unit compared with early cord clamping in nonvigorous newborns born between 35 and 42 weeks' gestation. STUDY DESIGN: This was a pragmatic cluster-randomized crossover trial of infants born at 35 to 42 weeks' gestation in 10 medical centers in 3 countries between January 2019 and May 2021. The centers were randomized to umbilical cord milking or early cord clamping for approximately 1 year and then crossed over for an additional year or until the required number of consented subjects was reached. Waiver of consent as obtained in all centers to implement the intervention. Infants were eligible if nonvigorous at birth (poor tone, pale color, or lack of breathing in the first 15 seconds after birth) and were assigned to umbilical cord milking or early cord clamping according to their birth hospital randomization assignment. The baseline characteristics and outcomes were collected following deferred informed consent. The primary outcome was admission to the neonatal intensive care unit for predefined criteria. The main safety outcome was hypoxic-ischemic encephalopathy. Data were analyzed by the intention-to-treat concept. RESULTS: Among 16,234 screened newborns, 1780 were eligible (905 umbilical cord milking, 875 early cord clamping), and 1730 had primary outcome data for analysis (97% of eligible; 872 umbilical cord milking, 858 early cord clamping) either via informed consent (606 umbilical cord milking, 601 early cord clamping) or waiver of informed consent (266 umbilical cord milking, 257 early cord clamping). The difference in the frequency of neonatal intensive care unit admission using predefined criteria between the umbilical cord milking (23%) and early cord clamping (28%) groups did not reach statistical significance (modeled odds ratio, 0.69; 95% confidence interval, 0.41-1.14). Umbilical cord milking was associated with predefined secondary outcomes, including higher hemoglobin (modeled mean difference between umbilical cord milking and early cord clamping groups 0.68 g/dL, 95% confidence interval, 0.31-1.05), lower odds of abnormal 1-minute Apgar scores (Apgar ≤3, 30% vs 34%, crude odds ratio, 0.72; 95% confidence interval, 0.56-0.92); cardiorespiratory support at delivery (61% vs 71%, modeled odds ratio, 0.57; 95% confidence interval, 0.33-0.99), and therapeutic hypothermia (3% vs 4%, crude odds ratio, 0.57; 95% confidence interval, 0.33-0.99). Moderate-to-severe hypoxic-ischemic encephalopathy was significantly less common with umbilical cord milking (1% vs 3%, crude odds ratio, 0.48; 95% confidence interval, 0.24-0.96). No significant differences were observed for normal saline bolus, phototherapy, abnormal 5-minute Apgar scores (Apgar ≤6, 15.7% vs 18.8%, crude odds ratio, 0.81; 95% confidence interval, 0.62-1.06), or a serious adverse event composite of death before discharge. CONCLUSION: Among nonvigorous infants born at 35 to 42 weeks' gestation, umbilical cord milking did not reduce neonatal intensive care unit admission for predefined criteria. However, infants in the umbilical cord milking arm had higher hemoglobin, received less delivery room cardiorespiratory support, had a lower incidence of moderate-to-severe hypoxic-ischemic encephalopathy, and received less therapeutic hypothermia. These data may provide the first randomized controlled trial evidence that umbilical cord milking in nonvigorous infants is feasible, safe and, superior to early cord clamping.

Evaluating Surgical Complexity of Endoscopic Hysterectomy: An Inter-rater and Intra-rater Agreement Study of Novel Scoring Tool.

STUDY OBJECTIVE: Evaluate inter-rater and intrarater reliability of a novel scoring tool for surgical complexity assessment of endoscopic hysterectomy. DESIGN: Validation study. SETTING: Academic medical center. PARTICIPANTS: Total of 11 academic obstetrician-gynecologists with varying years of postresidency training, clinical practice, and surgical volumes. INTERVENTIONS: Application of a novel scoring tool to evaluate surgical complexity of 150 sets of images taken in a standardized fashion before surgical intervention (global pelvis, anterior cul-de-sac, posterior cul-de-sac, right adnexa, left adnexa). Using only these images, raters were asked to assess uterine size, number, and location of myomas, adnexal and uterine mobility, need for ureterolysis, and presence of endometriosis or adhesions in relevant locations. Surgical complexity was staged on a scale of 1 to 4 (low to high complexity). MEASUREMENTS AND MAIN RESULTS: Number of postresidency years in practice for participating surgeons ranged from 2 to 15, with an average of 8 years. A total of 8 obstetrician-gynecologists (72.7%) had completed a fellowship in minimally invasive gynecologic surgery. Six (54.6%) reported an annual volume of >50 hysterectomies. Raters reported that 95.4% of the images were satisfactory for assessment. Of the 150 sets of images, most were found to be stage 1 to 2 complexity (stage 1: 23.8%, stage 2: 41.6%, stage 3: 32.8%, stage 4: 1.8%). The level of inter-rater agreement regarding stage 1 to 2 vs 3 to 4 complexity was moderate (κ = 0.49; 95% confidence interval [CI], 0.42-0.56). Moderate inter-rater agreement was also found between surgeon raters with an annual hysterectomy volume >50 (κ = 0.49; 95% CI, 0.40-0.57) as well as between surgeon raters with fellowship experience (κ = 0.50; 95% CI, 0.42-0.58). Intrarater agreement averaged 80.2% among all raters and also achieved moderate agreement (mean weighted κ = 0.53; range, 0.38-0.72). CONCLUSION: This novel scoring tool uses clinical assessment of preintervention anatomic images to stratify the surgical complexity of endoscopic hysterectomy. It has rich and comprehensive evaluation capabilities and achieved moderate inter-rater and intrarater agreement. The tool can be used in conjunction with or instead of traditional markers of surgical complexity such as uterine weight, estimated blood loss, and operative time.

Losses, Gains, and Changes to the Food Environment in a Rural Kentucky County during the COVID-19 Pandemic.

The COVID-19 pandemic has caused alterations to be made in the way many people access, prepare, and consume food. Rural communities are particularly impacted due to pre-existing structural vulnerabilities, i.e., poverty, lack of infrastructure, and limited fresh food options. This study aimed to characterize experiences of one rural Appalachian community's changes to the food environment during the pandemic. In April 2021, six focus groups were conducted with residents of Laurel County, Kentucky. Using grounded theory, we identified losses, gains, and overall changes to the community food environment since the onset of COVID-19. Seventeen Laurel Countians (17 female; ages 30-74) participated in the six focus groups. Three main themes emerged regarding food environment changes-(1) modifications of community food and nutrition resources, (2) expansion and utilization of online food ordering, and (3) implications of the home food environment. Rural communities faced considerable challenges during the COVID-19 pandemic, in part, due to gaps in existing infrastructure and loss of pre-existing resources. This study illustrates the complexity of changes occurring during COVID-19. Using the preliminary data obtained, we can better understand pre-existing issues in Laurel County and suggestions for future programming to address the inequitable access and response during public health emergencies and beyond.

Initial clinical characteristics of gravid severe acute respiratory syndrome coronavirus 2-positive patients and the risk of progression to severe coronavirus disease 2019.

BACKGROUND: Available data suggest that the obstetric population is particularly vulnerable to severe respiratory syndrome coronavirus 2 infection, with a variable clinical course leading to severe respiratory failure. However, established early warning scores designed to identify patients at risk of clinical deterioration were never validated in the obstetric population. OBJECTIVE: This retrospective cohort study sought to evaluate the initial clinical characteristics of pregnant patients diagnosed with severe acute respiratory syndrome coronavirus 2 infection and to develop a pregnancy-specific early warning score to identify patients at risk for clinical deterioration and requiring advanced respiratory support. STUDY DESIGN: This was a single center, retrospective cohort study of pregnant patients diagnosed with severe acute respiratory syndrome coronavirus 2 infection between April 2020 and December 2020. A total of 50 patients with severe acute respiratory syndrome coronavirus 2 infection between April 2020 and November 2020 were used to create the prediction model. Initial clinical characteristics identified at the time of diagnosis were compared between patients who required advanced respiratory support and those who were asymptomatic or had mild symptoms for those diagnosed during the period of April 2020 to November 2020. Risk factors associated with a requirement for advanced respiratory support were used to create the Obstetric Warning Score system. The Obstetric Warning Score system was then validated using 30 patients diagnosed with severe acute respiratory syndrome coronavirus 2 infection in December 2020. A receiver operating characteristic curve was generated to evaluate the test characteristics of the Obstetric Warning Score system compared with other scoring systems including the Early Warning Score, the National Early Warning Score 2, and the Maternal Early Warning Criteria. RESULTS: Women who required advanced respiratory support were more likely to present with dyspnea (100% vs 33.3%; P<.001), have a higher heart rate (113.4 beats per minute vs 93 beats per minute; P<.001), respiratory rate (23.5 breaths per minute vs 17.7 breaths per minute; P<.001), temperature (99.1°F vs 98.3°F; P=.004), and C-reactive protein level (7.4 mg/dL vs 2.4 mg/dL; P<.001). Furthermore, 88.2% of patients requiring advanced respiratory support showed chest x-ray findings consistent with pneumonia, compared with 20.0% of the patients not requiring advanced respiratory support (P<.001). All patients requiring advanced respiratory support presented with at least 1 coronavirus disease 2019 symptom, whereas only 51.5% of patients not requiring advanced respiratory support were symptomatic (P<.001). The Obstetrical Warning Score model allocated 1 point each for a hazard ratio of >100 beats per minute, temperature of >99.0°F, C-reactive protein level of >2.0 mg/dL, respiratory rate between 20 and 24 breaths per minute, complaints of dyspnea, and a positive chest x-ray. A respiratory rate of >24 breaths per minute was assigned 2 points. The area under the curve for the Obstetric Warning Score system was 0.97 compared with 0.72 for the Early Warning Score system, 0.92 for the National Early Warning Score 2 system, and 0.85 for the Maternal Early Warning Criteria system. An Obstetric Warning Score of ≥3 was predictive of a requirement for advanced respiratory support with a sensitivity of 100%, specificity 64%, and a positive predictive value of 36%. CONCLUSION: The Obstetric Warning Score system presents a validated method for providers to identify pregnant patients who are at risk for respiratory failure and a requirement for advanced respiratory support.

Semiautonomous Treatment Algorithm for the Management of Severe Hypertension in Pregnancy.

OBJECTIVE: To evaluate whether implementation of a semiautonomous treatment algorithm was associated with improved compliance with American College of Obstetricians and Gynecologists guidelines for rapid administration of antihypertensive therapy in the setting of sustained severe hypertension. METHODS: This was a single-center retrospective cohort study of admitted pregnant and postpartum patients treated for severe hypertension between January 2017 and March 2020. The semiautonomous treatment algorithm, which included vital sign monitoring, blood pressure thresholds for diagnosis of severe hypertension, and automated order sets for recommended first-line antihypertensive therapy were implemented between May 2018 and March 2019. The primary outcomes were the administration of antihypertensive therapy within 15, 30 and 60 minutes of diagnosis of severe hypertension. Comparisons were made between the preimplementation, during implementation, and postimplementation groups using χ2. Analysis was limited to the first episode of severe hypertension treated. Statistical significance was defined as P<.05. RESULTS: In total, there were 959 obstetric patients treated for severe hypertension, with 373 (38.9%) treated preimplementation, 334 (34.8%) during implementation, and 252 (26.2%) after implementation. Treatment of severe hypertension within 15 minutes was 36.5% preimplementation, 45.8% during implementation, and 55.6% postimplementation (P=.001). Treatment within 30 minutes was 65.9% in the preimplementation group, 77.8% during implementation, and 79.0% in the postimplementation group (P=.004). There was no difference in percentage of patients treated within 60 minutes (86.3% before, 87.7% during and 92.9% after implementation, P=.12). CONCLUSION: Implementation of a semiautonomous treatment algorithm for severe hypertension was associated with a higher percentage of pregnant and postpartum patients receiving the first dose of antihypertensive therapy within 15 and 30 minutes. Implementation of similar algorithms for this and other obstetric indications may decrease time to appropriate therapy and help improve care equity.

Nidogen 1 regulates proliferation and migration/invasion in murine claudin-low mammary tumor cells.

Nidogen 1 (NID1) is a glycoprotein found in basement membranes involved in cross-linking collagen IV and laminin. The role of NID in breast cancer has only been evaluated in a small number of studies and the findings of these studies have been inconsistent. Our previous work revealed that highly tumorigenic murine mammary tumor cells express high levels of Nid1 while weakly tumorigenic mammary tumor cells express low levels of Nid1. To investigate Nid1, two stable knockdown lines were created, and Nid1 knockdown was confirmed at both the mRNA and protein level. Nid1 knockdown significantly reduced cell proliferation and migration/invasion and these reductions in proliferation and migration/invasion could be rescued by conditioned media containing NID1 protein. The reduced migration/invasion observed in the Nid1 knockdown cells was not associated with significant alterations in the epithelial gene Cdh1 or the mesenchymal genes Snai1, Snai2, Twist1, Twist2, Zeb1 and Zeb2. Therefore, suppression of Nid1 expression reduces proliferation and migration/invasion in claudin-low murine mammary tumor cells.

Through the Lens: Youth Experiences with Cancer in Rural Appalachian Kentucky Using Photovoice.

Rural Appalachian Kentucky experiences disproportionately high cancer incidence and mortality rates. This cancer burden is due to social determinants of health and cultural factors prominent in the region. The firsthand experiences of community members-especially young people-can highlight these factors and identify areas for improvement. The purpose of this study was to encourage Appalachian Kentucky youth to consider determinants of cancer and visualize the effects that cancer has on their families or communities by asking them to take photographs of cancer-related objects around them. Content analysis was performed on 238 photographs submitted by 25 students, and photographs were organized into themes, subthemes, and subtopics. The six themes that emerged were risk factors and exposures, marketing, awareness and support, health care, experiences, and metaphorical representations. Many of the submitted photographs aligned with cultural, environmental and/or situational factors prevalent in Appalachian Kentucky. Of the submitted photographs, 54 were displayed as an installment in two Kentucky art galleries. Viewer comments at the exhibitions demonstrated that young community members can educate and motivate change in those around them. Ultimately, this project demonstrates that young community members can recognize cancer-related issues around them and connect personal experiences back to the larger Appalachian Kentucky cancer disparity while also having an impact on other community members.

Vitamin-D dysregulation in early- and late-onset preeclampsia: A gestational-age matched study.

Vitamin D deficiency has been associated with preeclampsia, however, vitamin D supplementation studies have shown equivocal data on amelioration of this disease. We hypothesize that women with preeclampsia have an altered endogenous vitamin D homeostasis that counteracts the beneficial effects of vitamin D supplementation. Our study population consisted of 66 maternal/neonate dyads: 16 early-onset (<34 weeks) preeclampsia (EOP), 16 early-onset controls (EOC), 17 late-onset (≥34 weeks) preeclampsia (LOP), and 17 late-onset controls (LOC). Plasma levels of 25-OH-D and the bioactive metabolite 1α,25-(OH)2-D were studied by ELISA. Placental expression of vitamin D transporters (cubulin and megalin), metabolic genes (CYP2R1, CYP27B1, CYP24A1), and vitamin D binding protein (GC), were studied by real-time PCR, and the nuclear and cytosolic levels of the vitamin D receptor (VDR) protein were analyzed by immunoblotting. Maternal admission, maternal postpartum, and umbilical cord blood levels of 1α,25-(OH)2-D and placental nuclear vitamin D receptor protein levels, were significantly lower in EOP compared to EOC. In contrast LOP was characterized by lower 25-OH-D levels in maternal postpartum and cord blood, and decreased placental cubulin expression compared to LOC. Both EOP and LOP showed decreased placental expression of CYP2R1 and GC compared to controls. Multivariable linear regression analysis demonstrated that preeclampsia was a significant predictor of decreased 1α,25-(OH)2-D levels in early-onset subjects, while maternal BMI, but not preeclampsia, was the main predictor of decreased 25-OH-D in late-onset subjects. The highest positive correlation between the two vitamin D metabolites was observed in LOC umbilical cord blood. Finally, paired analysis of maternal metabolites before and after delivery indicated that women without preeclampsia had better maintenance of vitamin D levels. We conclude that EOP is characterized by decreased bioactivation of vitamin D and VDR in association with fetal growth restriction (FGR). In contrast, LOP is characterized by decreased 25-OH-D levels in association with decreased placental CYP2R1 and cubulin expression; and uncoupling of the 25-OH-D with the 1α,25-(OH)2-D metabolite.

Polycomb repressor complex 2 function in breast cancer (Review).

Epigenetic modifications are important contributors to the regulation of genes within the chromatin. The polycomb repressive complex 2 (PRC2) is a multi­subunit protein complex that is involved in silencing gene expression through the trimethylation of lysine 27 at histone 3 (H3K27me3). The dysregulation of this modification has been associated with tumorigenicity through the increased repression of tumour suppressor genes via condensing DNA to reduce access to the transcription start site (TSS) within tumor suppressor gene promoters. In the present review, the core proteins of PRC2, as well as key accessory proteins, will be described. In addition, mechanisms controlling the recruitment of the PRC2 complex to H3K27 will be outlined. Finally, literature identifying the role of PRC2 in breast cancer proliferation, apoptosis and migration, including the potential roles of long non­coding RNAs and the miR­200 family will be summarized as will the potential use of the PRC2 complex as a therapeutic target.

Vitamin D status and metabolism in an ovine pregnancy model: effect of long-term, high-altitude hypoxia.

Vitamin D status increases during healthy mammalian pregnancy, but the molecular determinants remain uncharacterized. The first objective of this study was to determine the effects of pregnancy, and the second objective was to examine the role of chronic hypoxia on vitamin D status and metabolism in an ovine model. We analyzed the plasma levels of cholecalciferol, 25-OH-D, and 1α,25-(OH)2D in nonpregnant ewes, near-term pregnant ewes, and their fetuses exposed to normoxia (low altitude) or hypoxia (high-altitude) for 100 days. Hypoxic sheep had increased circulating levels of 25-OH-D and 1α,25-(OH)2D compared with normoxic sheep. Hypoxia increases in 25-OH-D were associated with increased expression of renal 25-hydroxylases CYP2R1 and CYP2J. Pregnancy did not increase further the plasma levels of 25-OH-D, but it significantly increased those of the active metabolite, 1α,25-(OH)2D, in both normoxic and hypoxic ewes. Increased bioactivation of vitamin D correlated with increased expression of the vitamin D-activating enzyme CYP27b1 and decreased expression of the inactivating enzyme CYP24a1 in maternal kidneys and placentas. Hypoxia increased parathyroid hormone levels and further increased renal CYP27b1. Pregnancy and hypoxia decreased the expression of vitamin D receptor (VDR) in maternal kidney and lung, with opposite effects on placental VDR. We conclude that ovine pregnancy is a model of increased vitamin D status, and long-term hypoxia further improves vitamin D status due to pregnancy- and hypoxia-specific regulation of VDR and metabolic enzymes.

What is hiding behind the pessary?

Vaginal pessaries are routinely used for initial management of pelvic organ prolapse and for women who are poor surgical candidates. Serious complications of long-term use without routine follow-up include erosion into surrounding organs and the development of fistulas. It is unclear however, if long-term use and chronic irritation could potentially contribute to development or delay the diagnosis of vaginal or cervical cancers. A 72-year-old Caucasian woman with a vaginal pessary retained for 3 years, who presented with leukocytosis and coagulopathy, was discovered to have stage II vaginal adenosquamous carcinoma upon surgical pessary removal. Chronic irritation and lack of follow-up with pessary use may contribute to masking the development and delaying the diagnosis of vaginal cancer in women with risk factors. Pessary use requires frequent follow-up to prevent complications.

The incidence of depression by fertility status in overweight and obese Latina women.

The link between depression, obesity, and fertility status is poorly understood among Latina women. The Patient Health Questionnaire 9 (PHQ-9) is routinely administered in the Diabetes and Obesity in Reproductive Age women Clinic. We describe median PHQ-9 score and PHQ-9 score ≥10 [indicative of Major Depressive Disorder (MDD)] by fertility status. Of the 76 eligible new patients seen between June 2008 and 2009, 18.4% (n = 14) had PHQ-9 scores indicative of MDD. Infertile women had marginally significantly higher PHQ-9 scores than non-infertile women (p = 0.08). 26.5% of infertile women and 12.2% of non-infertile women had a PHQ-9 score indicative of MDD (p = 0.14). Number of previous births was inversely correlated with PHQ-9 score (R = -0.34, p = 0.002), those with no previous births had higher PHQ-9 scores (p = 0.001) and were more likely to have a PHQ-9 score indicative of MDD than those with previous births (28.6 vs. 9.8%, p = 0.04). Among non-infertile women, postpartum women had significantly lower PHQ-9 scores than non-postpartum women (p = 0.002). 4.6% of postpartum women and 21.1% of non-postpartum women had a PHQ-9 indicative of MDD (p = 0.19). Further investigation is needed to determine if reproductive success is protective against MDD among overweight and obese urban Latinas. Overall, depression is common among overweight and obese reproductive-age Latinas and thus routine screening is recommended.