Psychiatric disorders among employment requiring firearms.

Individuals who carry guns as a requirement of employment frequently experience hazards that can be stress inducing, violent, traumatizing, or cause personal injury. This study used data from the Collaborative Psychiatric Epidemiological Surveys (CPES; n = 20,013), to examine mental health diagnoses of individuals that ever worked at a job requiring a firearm. Consistent with existing literature, the findings indicated that those who worked in professions requiring a firearm showed similar risk of mental health diagnoses as law enforcement officers which includes symptoms of trauma, mood disorders, and alcohol use. Further, race/ethnic differences emerged in patterns of mental health diagnoses, suggesting sociocultural differences influence diagnoses. These findings indicate the necessity for further investigation of the understudied area of mental health of those within employment positions that require firearms.

Factors contributing to delay or absence of alveolar bone grafting.

INTRODUCTION: Alveolar bone grafting (ABG) delay can lead to suboptimal outcomes. This study seeks to categorize reasons patients with cleft lip and palate have no record of ABG or who underwent later than typical ABG (≥13 years). METHODS: At a single tertiary care center, a retrospective review was performed of all patients with unilateral, complete cleft lip and palate, born 1998-2005. Database query identified which patients had timely, late, or no record of ABG. The retrospective cohort study was performed to categorize ABG delay or absence of recorded ABG. RESULTS: Of 135 participants, 82 (61%) had timely, 8 (6%) had late, and 45 (33%) had no record of ABG. The primary factor for late ABG was noncompliance or refusal (n = 5 of 8, 63%), comorbidity or medical complexity (n = 1 of 8, 13%), orthodontic unpreparedness (n = 1 of 8, 13%), or inaccurate prior assessment of alveolar sufficiency (n = 1 of 8, 13%). The primary factor for ABG record absence was loss to follow-up (n = 40 of 45, 89%), noncompliance or refusal (n = 3 of 45, 7%), comorbidity or medical complexity (n = 1 of 45, 2%), or orthodontic unpreparedness (n = 1 of 45, 2%). Racial majority (White, Asian) patients received preferred care (timely ABG or medically appropriate absence or delay) at a significantly higher rate (67%) than underrepresented minorities (African American, Hispanic, Native American, other) (35%, P = 0.016). Families with private insurance and those who were self-pay received preferred care at a significantly higher rate (77%) than families with Medicaid (42%) (P <0.001). CONCLUSIONS: The high number of patients lost to follow-up highlights the impact of poor retention on ABG completion. Possible health disparities based on race and insurance status warrant clinical focus.

Upregulation of histone H3K9 methylation in fetal endothelial cells from preeclamptic pregnancies.

Adverse intrauterine environment has been considered a predisposing factor for fetal programming in preeclampsia. Using human umbilical vein endothelial cells (HUVECs), we specifically explored if aberrant histone methylation occurs in fetal endothelial cells in preeclampsia. Strikingly, we found that increased di-, and tri-methylation of histone H3 lysine 9 (H3K9me2 and H3K9me3) expression were associated with upregulation of methyltransferase G9a and downregulation of endothelial nitric oxide synthase and CuZn-SOD expression in preeclamptic HUVECs. We further demonstrated that hypoxia-induced hypermethylation of H3K9 and reduced CuZn-SOD expression mimicked what were seen in preeclamptic HUVECs and inhibition of G9a could attenuate these hypoxia-induced adverse events. Our study was the first to identify hypermethylation status in fetal endothelial cells in preeclampsia, which provides plausible evidence that increased oxidative stress in the intrauterine environment is likely a mechanism to induce aberrant histone modification in fetal endothelial cells which may have a significant impact on fetal programming in preeclampsia.

Deviant Cyber-Sexual Activities in Young Adults: Exploring Prevalence and Predictions Using In-Person Sexual Activities and Social Learning Theory.

Technology has shifted some human interactions to the virtual world. For many young adults, sexual encounters now occur through virtual means, as social media, picture exchanges, sexually explicit Web sites, and video chatting have become popular alternative outlets for these activities to occur. This study used the self-report responses of 812 undergraduate students (282 men and 530 women), collected from an online survey. In addition to using 10 personal demographic control variables, this study used five sexual activity/relationship characteristics (number of sexual partners, relationship status, age to first use pornography, frequency of sexual activity/intercourse, and frequency of masturbation), and the four constructs of Akers' social learning theory (identified as differential association, differential reinforcement, imitation/modeling, and definitions favorable) to predict a seven-item count of deviant cyber-sexual activities, and two measures of "sexting" behaviors. Gender, self-esteem, sexual orientation, race, and religion were strongly significant predictors in the models, but Akers' four elements of social learning performed the strongest in predicting the two measures of sexting and the overall deviant cyber-sexual activities scale. This finding indicates that peer associations and peer reinforcements have a strong influence on individuals' willingness to engage in deviant cyber-sexual activities. This study explored different avenues for young adults' engagement in sexual deviancy and the results suggest that sexual behaviors performed in-person may not be the strongest predictors of online sexual behavior.

Interpersonal Subtypes Within Social Anxiety: The Identification of Distinct Social Features.

Although social anxiety disorder is defined by anxiety-related symptoms, little research has focused on the interpersonal features of social anxiety. Prior studies (Cain, Pincus, & Grosse Holtforth, 2010; Kachin, Newman, & Pincus, 2001) identified distinct subgroups of socially anxious individuals' interpersonal circumplex problems that were blends of agency and communion, and yet inconsistencies remain. We predicted 2 distinct interpersonal subtypes would exist for individuals with high social anxiety, and that these social anxiety subtypes would differ on empathetic concern, paranoia, received peer victimization, perspective taking, and emotional suppression. From a sample of 175 undergraduate participants, 51 participants with high social anxiety were selected as above a clinical cutoff on the social phobia scale. Cluster analyses identified 2 interpersonal subtypes of socially anxious individuals: low hostility-high submissiveness (Cluster 1) and high hostility-high submissiveness (Cluster 2). Cluster 1 reported higher levels of empathetic concern, lower paranoia, less peer victimization, and lower emotional suppression compared to Cluster 2. There were no differences between subtypes on perspective taking or cognitive reappraisal. Findings are consistent with an interpersonal conceptualization of social anxiety, and provide evidence of distinct social features between these subtypes. Findings have implications for the etiology, classification, and treatment of social anxiety.

Cleft and Craniofacial Multidisciplinary Team Clinic: A Look at Attrition Rates for Patients With Complete Cleft Lip and Palate and Nonsyndromic Single-Suture Craniosynostosis.

OBJECTIVE: To evaluate attrition rates prior to expected completion of team care for children with complete cleft lip and palate (cleft) or nonsyndromic single-suture craniosynostosis (synostosis). DESIGN: A single-institution retrospective review of attendance data from 2002 to 2016. SETTING: Single cleft and craniofacial center in the United States. PATIENTS/PARTICIPANTS: A sample of 983 patients with either cleft or synostosis. Patients who were more than 2 to 3 years from their last visit were considered lost to follow-up. Patients with cleft older than 16 years or synostosis over 11 years were considered graduated from team care. RESULTS: Survival analysis shows that in our patients with cleft, 25% leave before age 8 and over 60% are lost from team by age 16. In patients with synostosis, 25% leave before age 6 and 45% are lost by age 11. Cox regression showed underrepresented minorities being 1.7 times more likely to become lost in the cleft group (hazard ratio: 1.66, 95% confidence interval [CI]: 1.01-2.74). CONCLUSIONS: Overall, attrition rates were high at our institution. Many patients are lost to follow-up prior to receiving key medical interventions. Improved family education and personalized care are needed to help ensure continuity of care.

Moving on: Exploring the implications of leader departure and incoming temporary leaders for collective turnover and unit performance.

While leader departures from work units frequently occur within organizations and are assumed to negatively impact unit functioning, the collective reaction to a leader departure event can vary across time. While a common expectation of leader departure models is that the incoming leader is permanent, it is unclear how unit-level reactions, such as collective turnover and unit performance, might change over time in response to a departure event when the departing leader is replaced with a temporary leader. We draw on context emergent turnover (CET) theory and literature on leader departures to develop and empirically test specific hypotheses exploring relationships among leader departures, collective turnover, and unit performance over time. In addition, we examine the extent to which these relationships are influenced by the temporary status of the incoming leader. Using discontinuous growth models, we examine a longitudinal data set from 324 units within a large Latin American operation of a global direct sales company (N = 3,082 performance periods). Findings indicate that, after a leader departs, there is an immediate increase in collective turnover and that unit performance decreases over time. Further, when the incoming leader is temporary, unit performance increases briefly, but the rate of performance drops over time. Overall, our research offers insights with regard to how leader departures impact unit outcomes, as well as how long such effects last. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Eclampsia, HELLP and PRES in a 16-week partial molar pregnancy.

Eclampsia spectrum disorders are a set of serious complications of pregnancy that commonly present after 20 weeks of gestation. There is an association between molar pregnancy, a gestational trophoblastic disease resulting from abnormal fertilisation and gametogenesis, and eclampsia spectrum disorders which can result in manifestation of pre-eclamptic symptomatology earlier than 20 weeks of gestation. We report a case of a gravida 1 para 0 in her mid 20s at 16-weeks gestation presenting with partial hydatidiform mole who developed eclampsia, haemolysis, elevated liver enzymes and low platelets syndrome and posterior reversible encephalopathy syndrome. Ultrasound findings were consistent with molar pregnancy and pathology confirmed partial molar pregnancy with triploid 69, XYY karyotype. This case highlights the early onset potential of eclampsia spectrum disorders in molar pregnancies while suggesting screening such patients for hypertensive disorders.

Oxidative stress contributes to hypermethylation of Histone H3 lysine 9 in placental trophoblasts from preeclamptic pregnancies.

Background and objective: Aberrant epigenetic regulation and increased oxidative stress in the placenta play a significant role in placental pathophysiology and fetal programming in preeclampsia, a hypertensive disorder in human pregnancy. The purpose of the study is to investigate if hypermethylation of histone H3K9 occurs in placental trophoblasts from preeclampsia. Methods: Trophoblasts were isolated and cultured from 14 placentas, 7 from normotensive pregnant women and 7 from preeclamptic pregnancies. Methylated H3K9 expression and antioxidant superoxide dismutase expression were determined by Western blot. We also examined consequences of oxidative stress and the downstream effects of histone methyltransferase inhibition on H3K9 expression associated with antioxidant CuZn-SOD and Mn-SOD expression in placental trophoblasts. Results: We found that expression of mono-, di-, and tri-methylation of histone H3 lysine 9 (H3K9me1, H3K9me2 and H3K9me3) was significantly increased, p<0.01, which correlated with downregulation of antioxidant superoxide dismutase CuZn-SOD and Mn-SOD expression, in trophoblasts from preeclamptic placentas compared to those from uncomplicated control placentas. We further demonstrated hypoxia could promote histone H3K9 methylation in placental trophoblasts, and hypoxia-induced upregulation of H3K9me1, H3K9me2 and H3K9me3 expression was reversible when hypoxic condition was removed. In addition, we also uncovered that inhibition of methyltransferase not only prevented hypoxia-induced upregulation of H3K9me1, H3K9me2 and H3K9me3 expression, but also abolished hypoxia-induced downregulation of CuZn-SOD and Mn-SOD expression in placental trophoblasts. Conclusions: These findings are noteworthy and provide further evidence that increased oxidative stress in the intrauterine environment is likely a mechanism to induce aberrant histone modification in placental trophoblasts in preeclampsia. Moreover, CuZn-SOD and Mn-SOD expression/activity are possibly H3K9 methylation-dependent in placental trophoblasts, which further suggest that oxidative stress and aberrant histone modification have significant impact on placental trophoblasts/fetal programming in preeclampsia.

Safety of Ancestral Monovalent BNT162b2, mRNA-1273, and NVX-CoV2373 COVID-19 Vaccines in US Children Aged 6 Months to 17 Years.

Importance: Active monitoring of health outcomes after COVID-19 vaccination provides early detection of rare outcomes that may not be identified in prelicensure trials. Objective: To conduct near-real-time monitoring of health outcomes after COVID-19 vaccination in the US pediatric population. Design, Setting, and Participants: This cohort study evaluated 21 prespecified health outcomes after exposure before early 2023 to BNT162b2, mRNA-1273, or NVX-CoV2373 ancestral monovalent COVID-19 vaccines in children aged 6 months to 17 years by applying a near-real-time monitoring framework using health care data from 3 commercial claims databases in the US (Optum [through April 2023], Carelon Research [through March 2023], and CVS Health [through February 2023]). Increased rates of each outcome after vaccination were compared with annual historical rates from January 1 to December 31, 2019, and January 1 to December 31, 2020, as well as between April 1 and December 31, 2020. Exposure: Receipt of an ancestral monovalent BNT162b2, mRNA-1273, or NVX-CoV2373 COVID-19 vaccine dose identified through administrative claims data linked with Immunization Information Systems data. Main Outcomes and Measures: Twenty-one prespecified health outcomes, of which 15 underwent sequential testing and 6 were only monitored descriptively due to lack of historical rates. Results: Among 4 102 016 vaccinated enrollees aged 6 months to 17 years, 2 058 142 (50.2%) were male and 3 901 370 (95.1%) lived in an urban area. Thirteen of 15 sequentially tested outcomes did not meet the threshold for a statistical signal. Statistical signals were detected for myocarditis or pericarditis after BNT162b2 vaccination in children aged 12 to 17 years and seizure after vaccination with BNT162b2 and mRNA-1273 in children aged 2 to 4 or 5 years. However, in post hoc sensitivity analyses, a statistical signal for seizure was observed only after mRNA-1273 when 2019 background rates were selected; no statistical signal was observed when 2022 rates were selected. Conclusions and Relevance: In this cohort study of pediatric enrollees across 3 commercial health insurance databases, statistical signals detected for myocarditis or pericarditis after BNT162b2 (ages 12-17 years) were consistent with previous reports, and seizures after BNT162b2 (ages 2-4 years) and mRNA-1273 vaccinations (ages 2-5 years) should be further investigated in a robust epidemiologic study with confounding adjustment. The US Food and Drug Administration concludes that the known and potential benefits of COVID-19 vaccination outweigh the known and potential risks of COVID-19 infection.

Evidence of kidney injury in preeclampsia: Increased maternal and urinary levels of NGAL and KIM-1 and their enhanced expression in proximal tubule epithelial cells.

Background and objective: Proteinuria and glomerular endotheliosis are characteristics of glomerular injury in preeclampsia, a hypertensive disorder in human pregnancy. Neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) are biomarkers of acute/chronic renal tubule injury. To determine if tubule injury occurs in preeclampsia, we determined maternal plasma and urine NGAL and KIM-1 levels and evaluated NGAL and KIM-1 expression in kidney biopsy specimens from women with preeclampsia. Methods: Prenatal and postpartum maternal blood and urinary samples were collected from three groups of pregnant women: normal pregnancy (n = 100), preeclampsia (n = 83), and pregnancy complicated with chronic hypertension (n = 20). Plasma and urine levels of NGAL and KIM-1 were measured by ELISA. Kidney biopsy tissue sections from patients with preeclampsia (n = 5) were obtained from Pathology Archives and processed to determine NGAL and KIM-1 expression by immunostaining and high kidney solution images were assessed by electron microscopy (EM). Results: Prenatal plasma and urine levels of NGAL and KIM-1 were significantly higher in preeclamptic than in normal controls, p < 0.01. In normal pregnancy, both plasma and urine levels of NGAL and KIM-1 at 24-48 h after delivery and 6-8 weeks postpartum were relatively comparable to that of antenatal levels. In preeclampsia, urine, but not plasma, NGAL levels were reduced at 6-8 weeks postpartum compared to the antenatal levels, p < 0.05. Although maternal and urine KIM-1 levels were reduced at 6-8 weeks postpartum compared to the antenatal levels in preeclampsia, the levels were still higher than those in normal pregnancy. Positive expression of NGAL and KIM-1 was detected in proximal tubule epithelial cells in kidney tissue specimens from preeclampsia but not in non-pregnancy controls. EM examination showed glomerular and tubular injury in preeclampsia. Conclusion: Our findings of increased maternal levels and urine secretion of NGAL and KIM-1, along with the upregulation of NGAL and KIM-1 expression in tubular epithelial cells in preeclampsia, provide plausible evidence that tubular injury exists in preeclampsia. The higher postpartum NGAL and KIM-1 levels in preeclamptic pregnancies indicate that tubular injury would not resolve within 2-3 months after delivery and suggest that proper follow-up and management of kidney function in women with preeclampsia would be necessary to reduce chronic kidney diseases in those women later in life.

Safety of the BNT162b2 COVID-19 Vaccine in Children Aged 5 to 17 Years.

Importance: Active monitoring of health outcomes after COVID-19 vaccination offers early detection of rare outcomes that may not be identified in prelicensure trials. Objective: To conduct near-real-time monitoring of health outcomes following BNT162b2 COVID-19 vaccination in the US pediatric population aged 5 to 17 years. Design, Setting, and Participants: This population-based study was conducted under a public health surveillance mandate from the US Food and Drug Administration. Participants aged 5 to 17 years were included if they received BNT162b2 COVID-19 vaccination through mid 2022 and had continuous enrollment in a medical health insurance plan from the start of an outcome-specific clean window until the COVID-19 vaccination. Surveillance of 20 prespecified health outcomes was conducted in near real time within a cohort of vaccinated individuals from the earliest Emergency Use Authorization date for the BNT162b2 vaccination (December 11, 2020) and was expanded as more pediatric age groups received authorization through May and June 2022. All 20 health outcomes were monitored descriptively, 13 of which additionally underwent sequential testing. For these 13 health outcomes, the increased risk of each outcome after vaccination was compared with a historical baseline with adjustments for repeated looks at the data as well as a claims processing delay. A sequential testing approach was used, which declared a safety signal when the log likelihood ratio comparing the observed rate ratio against the null hypothesis exceeded a critical value. Exposure: Exposure was defined as receipt of a BNT162b2 COVID-19 vaccine dose. The primary analysis assessed primary series doses together (dose 1 + dose 2), and dose-specific secondary analyses were conducted. Follow-up time was censored for death, disenrollment, end of the outcome-specific risk window, end of the study period, or a receipt of a subsequent vaccine dose. Main Outcomes: Twenty prespecified health outcomes: 13 were assessed using sequential testing and 7 were monitored descriptively because of a lack of historical comparator data. Results: This study included 3 017 352 enrollees aged 5 to 17 years. Of the enrollees across all 3 databases, 1 510 817 (50.1%) were males, 1 506 499 (49.9%) were females, and 2 867 436 (95.0%) lived in an urban area. In the primary sequential analyses, a safety signal was observed only for myocarditis or pericarditis after primary series vaccination with BNT162b2 in the age group 12 to 17 years across all 3 databases. No safety signals were observed for the 12 other outcomes assessed using sequential testing. Conclusions and Relevance: Among 20 health outcomes that were monitored in near real time, a safety signal was identified for only myocarditis or pericarditis. Consistent with other published reports, these results provide additional evidence that COVID-19 vaccines are safe in children.

Cell-type specific distribution and activation of type I IFN pathway molecules at the placental maternal-fetal interface in response to COVID-19 infection.

Background and objective: COVID-19 infection in pregnancy significantly increases risks of adverse pregnancy outcomes. However, little is known how the innate immunity at the placental maternal-fetal interface responds to COVID-19 infection. Type I IFN cytokines are recognized as a key component of the innate immune response against viral infection. In this study, we specifically evaluated expression of IFN antiviral signaling molecules in placentas from women infected with COVID-19 during pregnancy. Methods: Expression of IFN activation signaling pathway molecules, including cyclic GMP-AMP synthase (cGAS), stimulator of interferon genes (STING), interferon regulatory factor 3 (IRF3), Toll-like receptor 7 (TLR7), mitochondrial antiviral-signaling protein (MAVS), and IFNß were determined in formalin-fixed paraffin embedded (FFPE) placental tissue sections (villous and fetal membrane) by immunostaining. A total of 20 placentas were examined, 12 from COVID-19 patients and 8 from non-COVID-19 controls. Patient demographics, clinical data, and placental pathology report were acquired via EPIC medical record review. Results: Except BMI and placental weight, there was no statistical difference between COVID and non-COVID groups in maternal age, gestational age at delivery, gravity/parity, delivery mode, and newborn gender and weight. In COVID-exposed group, the main pathological characteristics in the placental disc are maternal and fetal vascular malperfusion and chronic inflammation. Compared to non-COVID controls, expression of IFN activation pathway molecules were all upregulated with distinct cell-type specific distribution in COVID-exposed placentas: STING in villous and decidual stromal cells; IRF3 in cytotrophoblasts (CTs) and extra-villous trophoblasts (EVTs); and TLR7 and MAVS in syncytiotrophoblasts (STs), CTs, and EVTs. Upregulation of STING, MAVS and TLR7 was also seen in fetal endothelial cells. Conclusions: STING, IRF3, TLR7, and MAVS are key viral sensing molecules that regulate type I IFN production. Type I IFNs are potent antiviral cytokines to impair and eradicate viral replication in infected cells. The finding of cell-type specific distribution and activation of these innate antiviral molecules at the placental maternal-fetal interface provide plausible evidence that type I IFN pathway molecules may play critical roles against SARS-CoV-2 infection in the placenta. Our findings also suggest that placental maternal-fetal interface has a well-defined antiviral defense system to protect the developing fetus from SARS-CoV-2 infection.

When helping hurts: COVID-19 critical incident involvement and resource depletion in health care workers.

A focus on helping others is generally lauded, particularly in medicine, but in the context of a pandemic when health care professionals are facing increased risk, loss, and trauma, this focus can potentially be detrimental. In this study, we sought to (a) examine if health care workers intensely involved in the coronavirus 2019 (COVID-19) pandemic are experiencing negative psychological and emotional outcomes, and (b) investigate if helping related factors (prosocial motivation and perceived prosocial impact) exacerbate and mitigate relationships to negative outcomes in a crisis situation. Using data collected from doctors and nurses before and during the COVID-19 pandemic, we examine the relationship between intensity of involvement in the COVID-19 pandemic response and emotional exhaustion and depression, as well as the moderating effects of prosocial motivation and perceived prosocial impact. Data was collected at three time points (T1 and T2 prepandemic, and T3 during COVID-19), with prosocial motivation and controls collected at T1/T2 and predictors and outcomes collected during the pandemic. We find that intensity of involvement does associate with emotional exhaustion at work and that higher prosocial motivation exacerbates this relationship. Supplemental analyses suggest that the exposure to self-dimension of involvement is positively associated with emotional exhaustion and depression. Understanding the roles of prosocial motivation and prosocial impact in managing regulatory resources has important ramifications for health care workers on the frontlines of health crises responses, as these resources are necessary to manage the associated trauma. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Impact of Breast Reconstruction Patients on Cosmetic Practice.

Postmastectomy breast reconstruction can often restore a patient's self-image. A notable percentage of women will go on to seek elective aesthetic procedures to further improve their perceived appearance. The purpose of this study was to determine the percentage of primary breast reconstruction patients who go on to receive a cosmetic procedure. We identify factors that may increase the likelihood that a patient subsequently chooses to pursue a cosmetic procedure. METHODS: A retrospective review of primary breast reconstruction patients of the two senior authors was conducted from January 2014 through December 2015. Demographics, types of cosmetic procedures received, and time to first cosmetic procedure were obtained. Time to first cosmetic procedure was assessed from date of mastectomy through December 2017. Logistic regression was performed to identify factors associated with obtaining cosmetic procedures. RESULTS: There were 289 patients in our cohort with ~10% who subsequently sought a cosmetic procedure at our practice. The average time to conversion was ~9 months after mastectomy. The majority (67%) underwent noninvasive procedures only. Patients with lower-staged breast cancers were more likely to undergo a cosmetic procedure (P < 0.042). CONCLUSIONS: At least 10% of patients undergoing primary breast reconstruction over a year period went on to have a cosmetic procedure during the study period. The majority of patients pursued noninvasive cosmetic procedures. Reconstruction of women with higher cancer stages was associated with a lower likelihood of pursuing a cosmetic procedure during the time period studied.

Downregulation of miR-126-3p expression contributes to increased inflammatory response in placental trophoblasts in preeclampsia.

MiR-126-3p is a prototype of an endothelial miRNA and has protective effects on endothelial cells. However, little is known about the effects of miR-126-3p on placental trophoblasts. In the present study, we tested the hypothesis that aberrant miR-126-3p expression is present in preeclamptic placenta which contributes to increased inflammatory response in trophoblasts. Placentas were obtained immediately after delivery from normotensive and preeclamptic pregnancies. Villous tissue was either fixed with formalin or used for trophoblast isolation. Trophoblast miR-126-3p expression was assessed by in situ hybridization of formalin-fixed tissue sections and by RT-PCR in cultured syncytiotrophoblasts. Culture medium was collected for measurement of IL-6, TNFα, and 8-Isoprostane production by ELISA and total cellular protein was collected for evaluation of HIF1α expression by Western blot. Effects of overexpression of miR-126-3p in trophoblasts on cytokine production were tested by transfection of pre-mir-126, a precursor of miR-126, into primary isolated trophoblasts. We found that downregulation of miR-126-3p expression was associated with increased IL-6 and TNFα production in trophoblasts from preeclamptic placentas vs. normal placentas. Moreover, transient overexpression of miR-126-3p significantly reduced IL-6 and TNFα production in trophoblasts from both normal and preeclamptic placentas. We further found that increase in miR-126-3p expression not only suppressed hypoxia-induced increases in IL-6 and TNFα production, but also attenuated hypoxia-induced increases in HIF1α expression and 8-Isoprostane production in trophoblasts cultured under hypoxic condition. These results provide plausible evidence that downregulation of miR-126-3p expression reduces anti-inflammatory and anti-oxidative stress activities in placental trophoblasts in preeclampsia.

Maternal soluble PD-1 levels are significantly increased in women with preeclampsia.

PROBLEM: Programmed cell death-1 (PD-1) and its ligand (PD-L1) have emerged as key players in regulating immune tolerance. Preeclampsia is associated with maladaptation of immune tolerance during pregnancy. This study aimed to determine if maternal soluble PD-1 (sPD-1) and soluble PD-L1 (sPD-L1) levels are altered in preeclampsia. METHOD OF STUDY: Maternal sPD-1 and sPD-L1 levels were measured by ELISA in 172 pregnant women (86 normotensive and 86 preeclampsia). The differences in sPD-1 and sPD-L1 levels between normotensive and preeclamptic pregnant women, <34 vs >34 weeks, and fetal gender differences were assessed. Data were analyzed by unpaired t test or chi-square. A probability level of <.05 was considered statistically significant. RESULTS: Maternal sPD-1 levels were significantly higher in preeclamptic than in normotensive pregnant women, 6262 ± 1860 vs 1134 ± 349 pg/mL, P < .01. sPD-1 levels were not statistically different between <34 and >34 weeks of gestation in both normotensive and preeclamptic groups. sPD-1 levels were relatively higher in mothers with female fetus than with male fetus in the preeclamptic group: 8104 ± 3054 vs 3802 ± 2177 pg/mL, but relatively lower in mothers with female fetus than with male fetus in the normotensive group: 425 ± 134 vs 625 ± 182 pg/mL. Maternal sPD-L1 levels were relatively higher in preeclamptic than in normotensive pregnant women: 143 ± 52 vs 69 ± 13 pg/mL. CONCLUSION: Aberrant sPD-1/sPD-L1 signaling is present in preeclampsia. Whether increased maternal sPD-1 and sPD-L1 levels were associated with fetal gender difference or immune tolerance dissimilarity during pregnancy in women with preeclampsia warrants further investigation.

Niacin biological challenge: A paradigm to evaluate social concerns.

BACKGROUND AND OBJECTIVES: Anxiety sensitivity (AS) social concerns, the fear of observable anxiety symptoms is posited as a risk factor for social anxiety by increasing fear reactivity in social situations when observable anxiety symptoms are present. Experimental evaluation of AS social concerns is limited. The current study utilized several manipulations designed to be relevant to AS social concerns or fear of negative evaluation (FNE), a distinct social anxiety risk factor. The effects of these manipulations on fear reactivity to a speech were examined. METHODS: Participants (N = 124 students; M age = 19.44, SD = 2.45; 64.5% female) were randomized to one of four conditions in a 2 (100 mg niacin vs 100 mg sugar pill) X 2 (instructional set) design. For the instructional set manipulation, participants were told their speech performance would be evaluated by a judge based on their performance (i.e., FNE-relevant) or their observable anxiety symptoms (i.e., AS social concerns-relevant). RESULTS: There was a main effect for vitamin condition with participants in the niacin condition reporting higher panic symptoms post-speech relative to those in the placebo condition. There was no main effect for speech instructions. As hypothesized, these effects were qualified by an interaction indicating that AS social concerns significantly predicted panic symptoms for those receiving niacin. LIMITATIONS: Limitations include the reliance on self-reports of outcome variables and the use of an undergraduate student sample. CONCLUSIONS: These findings highlight a distinct role of AS social concerns in fear responding to socially evaluative situations in the context of physically observable arousal.

Downregulation of vitamin D receptor and miR-126-3p expression contributes to increased endothelial inflammatory response in preeclampsia.

PROBLEM: To investigate whether downregulation of miR-126-3p and vitamin D receptor (VDR) expression contributes to increased endothelial inflammatory response in preeclampsia. METHODS OF STUDY: Maternal vessel miR-126-3p expression was assessed by in situ hybridization. VDR expression and VCAM-1 expression were determined by immunostaining. Subcutaneous adipose tissue sections from normotensive and preeclamptic pregnant women were used. HUVECs from normotensive deliveries were used to test anti-inflammatory effects of vitamin D and miR-126-3p in endothelial cells (ECs) treated with TNFα in vitro. 1,25(OH)2 D3 was used as bioactive vitamin D. Transient overexpression of miR-126-3p in ECs was induced by transfection of pre-mir-126 precursor. Endothelial VCAM-1 and SOCS-3 expression or production was determined by Western blotting or by ELISA, respectively. RESULTS: Reduced VDR and miR-126-3p expression, but increased VCAM-1 expression, was observed in maternal vessel endothelium in tissue sections from women with preeclampsia compared to normotensive pregnant controls. Transient overexpression of miR-126-3p not only attenuated upregulation of VCAM-1 expression and production, but also preserved downregulation of SOCS-3 expression, induced by TNFα in ECs. VDR expression and miR-126-3p expression were significantly upregulated in cells treated with 1,25(OH)2 D3 , but not in cells transfected with VDR siRNA. CONCLUSION: Downregulation of VDR and miR-126-3p expression was associated with upregulation of VCAM-1 expression in systemic vessel endothelium in preeclampsia. The finding of increased anti-inflammatory property by 1,25(OH)2 D3 through promotion of VDR and miR-126-3p expression in ECs provide plausible evidence that vitamin D deficiency and downregulation of VDR expression could contribute to increased inflammatory phenotypic changes in maternal vasculature in preeclampsia.

Lower-order anxiety sensitivity and intolerance of uncertainty dimensions operate as specific vulnerabilities for social anxiety and depression within a hierarchical model.

Within a hierarchical framework for depressive and anxiety disorders, negative affect (NA) is posited to be indirectly related to social anxiety and depression through cognitive vulnerabilities, including intolerance of uncertainty (IU) and anxiety sensitivity (AS). However, few prior studies have considered whether the lower-order dimensions of IU (i.e., prospective and inhibitory IU) and AS (i.e., physical, cognitive, and social concerns) better explain the indirect relation between NA and social anxiety and depression. The indirect relations between NA and social anxiety and depression through these cognitive vulnerabilities were examined using structural equation modeling in a clinical sample (N=298). NA and social anxiety symptoms were indirectly related through AS social concerns and inhibitory IU, although a direct effect of NA was also found. Only AS social concerns explained the relation between NA and a social anxiety disorder diagnosis. AS cognitive concerns was the only cognitive vulnerability factor to indirectly explain the relation between NA and depressive symptoms, although a direct effect of NA was also found. These findings suggest that the lower-order dimensions of AS and IU demonstrate more specific and less transdiagnostic associations with social anxiety and depression.