Prenatal Predictors for Pulmonary Balloon Valvuloplasty in the Newborn.

Pulmonary balloon valvuloplasty (PBV) is the treatment of choice for subjects with isolated pulmonary valve stenosis (IPS). The purpose of this study was to define fetal echocardiographic features associated with an inpatient PBV prior to newborn hospital discharge and characterize resource utilization of IPS fetuses among participating centers. Six center, retrospective case series of singleton fetuses identified between 2010 and 2020 with IPS. Third-trimester echocardiogram data was compared with postnatal data, included pulmonary valve Doppler velocities, pulmonary valve insufficiency and ductus arteriosus flow direction. Comparison between subjects who underwent inpatient PBV during their newborn hospital admission versus those infants referred for outpatient PBV after initial hospital discharge. We analyzed data by logistic regression, student t test and Chi-Square testing with a p value of ≤ 0.05 considered statistically significant. Forty-nine IPS fetuses were identified. Thirty-eight (78%) underwent inpatient PBV at 5 (range 1-58) days and 11 (22%) underwent outpatient PBV at 51.8 (11-174) days. Newborns requiring an inpatient PBV were more likely to have one or more characteristics on 3rd-trimester fetal echocardiogram: left to right or bidirectional ductus arteriosus flow (61% vs 0%), and/or a peak pulmonary valve velocity > 3.0 m/s (odds ratio 16.9, 95% confidence interval 3.02-94.17) with a sensitivity of 90.4% and specificity of 97.7%. Ductus arteriosus flow direction and pulmonary valve peak velocity in the 3rd trimester can successfully predict the need for newborn inpatient PBV. We speculate these findings may be useful in choosing delivery site for the pregnancy complicated by fetal IPS.

Multimodality Imaging in Ebstein Anomaly.

Ebstein anomaly is the most common form of tricuspid valve congenital anomalies. The tricuspid valve is abnormal with different degrees of displacement of the septal leaflet and abnormal rotation of the valve towards the right ventricular outflow tract. In severe forms, it results in significant tricuspid regurgitation and requires surgical repair. There is an increased interest in understanding the anatomy of the tricuspid valve in this lesion as the surgical repair has evolved with the invention and wide adoption of the cone operation. Multimodality imaging plays an important role in diagnosis, follow-up, surgical planning and post-operative care. This review provides anatomical tips for the cardiac imagers caring for patients with Ebstein anomaly and will help provide image-based personalized medicine.

Anogenital warts and relationship to child sexual abuse: Systematic review and meta-analysis.

BACKGROUND/OBJECTIVES: In children, distinguishing anogenital warts (AGW) acquired innocently from those acquired by child sexual abuse (CSA) is challenging. High-quality studies examining this relationship are sparse. Here, we sought to evaluate the association between AGW and sexual abuse in children 12 years of age and younger with respect to wart location, age, and gender. METHODS: A systematic review of Ovid MEDLINE, Embase, and Web of Science was performed for studies published on or before 2/16/2018. Studies were eligible for inclusion if they contained at least 10 patients 12 years old and younger and reported the number of patients who were sexually abused. The principal summary measures were the odds ratios (OR) of reported CSA with respect to subject age, wart location, and gender. RESULTS: Three hundred twenty-seven studies were identified through record search. Twenty five were included in a summary synthesis (791 subjects); 10 were included in the final statistical analysis (199 subjects). In our overall review, 102 of 468 (21%) females and 36 of 204 (18%) males with AGW were abused or probably abused. Overlapping HPV types were found in abused and non-abused subjects. Perianal location and gender were not significant predictors of abuse. Both age and genital wart location (penis, vulva) did significantly predict CSA (α = .05). The odds ratio for sexual abuse of children aged 3-4 years was 7.45; 6.52 for ages 5-8 years; and 6.93 for ages 9-12 years compared to those 0-2 years of age. Genital location was associated with an OR of CSA of 5.93. CONCLUSIONS: Our systematic review supports a significant association between AGW in a child greater than 2 years of age and odds of CSA. Genital wart location significantly predicts CSA as well. HPV typing is not a reliable method to ascertain CSA. Male family members and acquaintances were the most likely perpetrators of abuse.

Feasibility and Safety of Outpatient Parenteral Antimicrobial Therapy in Conjunction With Addiction Treatment for People Who Inject Drugs.

BACKGROUND: Research is limited on combining outpatient parenteral antimicrobial therapy (OPAT) with addiction treatment for people who inject drugs (PWID) with serious infections. METHODS: This is a retrospective study of PWID (n = 68) requiring intravenous antibiotics evaluated for suitability for our OPAT program with concurrent addiction treatment. RESULTS: Most common infections were bacteremia and/or endocarditis (73.5%), bone and/or joint infections (32.4%), and epidural abscess (22.1%). Of the 20 patients (29.4%) who qualified, 100.0% completed the course of antibiotics, 30.0% experienced a 30-day readmission, and 15.0% relapsed. No overdoses, deaths, or peripherally inserted central catheter-line complications were reported. CONCLUSIONS: Outpatient parenteral antimicrobial therapy with addiction treatment may be feasible and safe for PWID with serious infections.

Peripheral Nerve Microscopic Changes Related to Study Procedures: Two Nonclinical Case Studies.

Peripheral nerves are routinely examined microscopically during the nonclinical safety assessment of therapeutics. In addition to test article-related on- or off-target changes, microscopic changes in peripheral nerves may also be caused by study procedures, such as parenteral test article administration and blood or tissue sampling. We present 2 nonclinical case studies in which nonstandard peripheral nerves had study procedure-related histologic changes. The first case study describes mouse trigeminal nerve changes as a result of blood sampling via retro-orbital sinus puncture. These changes included minimal-to-mild nerve fiber (axonal) degeneration associated with macrophage infiltration. The second case study presents rat brachial plexus changes associated with animal handling and blood sampling. Brachial plexus changes included minimal-to-moderate inflammation, focal hemorrhage, and nerve fiber degeneration. In both cases, the histological changes were morphologically indistinguishable from those that might be due to test article. Therefore, careful consideration of the incidence and severity across groups and a review of study procedures to rule out handling-related nerve damage are essential before identifying a test article-related effect on peripheral nerves. Study design considerations to avoid such procedure-related changes will be discussed, as well as sampling strategies to help distinguish these from test article-related effects.

I (Dis)Like it Like That: Gender, Pornography, and Liking Sex.

Rates of pornography consumption in the U.S. are high and increasing. With exploratory aims, this study addresses the questions: What is the association between pornography consumption and liking of sexual behaviors commonly depicted in pornography, and is enjoyment moderated by gender? Sexual scripts theory suggests that increased pornography consumption is associated with increased engagement in pornographic sex acts, but it does not speak to enjoyment of the acts when engaged. The current study seeks to fill that gap. Based on data collected from a larger sample of 1,883 heterosexual men and women (predominantly, 86.6%, college or university students) in the U.S., and comparing correlations between pornography consumption (frequency of use) and reported enjoyment of a range of sexual behaviors by gender using Fisher's z transformations (α value set at <.0025), analysis revealed that pornography consumption, overall, was not significantly correlated with increased enjoyment of the sexual acts that comprise the pornographic sexual script. However, gender was a significant moderating factor in the enjoyment, specifically, of degrading and/or uncommon acts. Male respondents were significantly more likely to report enjoying these acts than their female counterparts. These findings have possible implications for consumers, educators, and mental health professionals.

The origin of the elements: a century of progress.

This review assesses the current state of knowledge of how the elements were produced in the Big Bang, in stellar lives and deaths, and by interactions in interstellar gas. We begin with statements of fact and discuss the evidence that convinced astronomers that the Sun is fusing hydrogen, that low-mass stars produce heavy elements through neutron capture, that massive stars can explode as supernovae and that supernovae of all types produce new elements. Nucleosynthesis in the Big Bang, through cosmic ray spallation, and in exploding white dwarfs is only ranked below the above facts in certainty because the evidence, while overwhelming, is so far circumstantial. Next, we highlight the flaws in our current understanding of the predictions for lithium production in the Big Bang and/or its destruction in stars and for the production of the elements with atomic number [Formula: see text]. While the theory that neutron star mergers produce elements through neutron-capture has powerful circumstantial evidence, we are unconvinced that they produce all of the elements past nickel. Also in dispute is the exact mechanism or mechanisms that cause the white dwarfs to explode. It is difficult to determine the origin of rare isotopes because signatures of their production are weak. We are uncertain about the production sites of some lithium and nitrogen isotopes and proton-rich heavy nuclei. Finally, Betelgeuse is probably not the next star to become a supernovae in the Milky Way, in part because Betelgeuse may collapse directly to a black hole instead. The accumulated evidence in this review shows that we understand the major production sites for the elements, but islands of uncertainty in the periodic table exist. Resolving these uncertainties requires in particular understanding explosive events with compact objects and understanding the nature of the first stars and is therefore primed for new discoveries in the next decades. This article is part of the theme issue 'Mendeleev and the periodic table'.

Impact of Medications for Opioid Use Disorder on Discharge Against Medical Advice Among People Who Inject Drugs Hospitalized for Infective Endocarditis.

BACKGROUND AND OBJECTIVES: The impact of medications for opioid use disorder (MOUD) on against medical advice (AMA) discharges among people who inject drugs (PWID) hospitalized for endocarditis is unknown. METHODS: A retrospective review of all PWID hospitalized for endocarditis at our institution between 2016 and 2018 (n = 84). RESULTS: PWID engaged with MOUD at admission, compared with those who were not, were less likely to be discharged AMA but this did not reach statistical significance in adjusted analysis (odds ratio [OR], 0.22; 95% confidence interval [CI], 0.033-1.41; P = .11). Among out-of-treatment individuals, newly initiating MOUD did not lead to significantly fewer AMA discharges (OR, 0.98; 95% CI, 0.26-3.7; P = .98). CONCLUSION AND SCIENTIFIC SIGNIFICANCE: PWID hospitalized for endocarditis are at high risk for discharge AMA but more research is needed to understand the impact of MOUD. (Am J Addict 2020;29:155-159).

Condom Use, Pornography Consumption, and Perceptions of Pornography as Sexual Information in a Sample of Adult U.S Males.

Using survey data from heterosexual adult men in the U.S., the present study has two objectives. The first objective is to provide an additional data point on the overall, bivariate association between frequency of pornography consumption and condom use. The second objective is to test the theoretical proposition that the association between using pornography more frequently and using condoms less frequently will be stronger when pornography is seen as functionally important and weaker when pornography is not seen as functionally important. At the bivariate level, more frequent pornography consumption was associated with using condoms less consistently. At the level of contingency, pornography use predicted condom nonuse only when men perceived that pornography was a primary source of information about sex. When men did not perceive that pornography was a primary source of sexual information, their rate of condom use was unrelated to how much or how little they consumed pornography. Collectively, these results are consistent with the public health position that pornography can be a risk-factor for condomless sex and the theoretical position that the socializing impact of sexual media depends on the pedagogical value attributed to that media.

First-in-Human Randomized, Controlled Trial of Mosaic HIV-1 Immunogens Delivered via a Modified Vaccinia Ankara Vector.

Background: Mosaic immunogens are bioinformatically engineered human immunodeficiency virus type 1 (HIV-1) sequences designed to elicit clade-independent coverage against globally circulating HIV-1 strains. Methods: This phase 1, double-blinded, randomized, placebo-controlled trial enrolled healthy HIV-uninfected adults who received 2 doses of a modified vaccinia Ankara (MVA)-vectored HIV-1 bivalent mosaic immunogen vaccine or placebo on days 0 and 84. Two groups were enrolled: those who were HIV-1 vaccine naive (n = 15) and those who had received an HIV-1 vaccine (Ad26.ENVA.01) 4-6 years earlier (n = 10). We performed prespecified blinded cellular and humoral immunogenicity analyses at days 0, 14, 28, 84, 98, 112, 168, 270, and 365. Results: All 50 planned vaccinations were administered. Vaccination was safe and generally well tolerated. No vaccine-related serious adverse events occurred. Both cellular and humoral cross-clade immune responses were elicited after 1 or 2 vaccinations in all participants in the HIV-1 vaccine-naive group. Env-specific responses were induced after a single immunization in nearly all subjects who had previously received the prototype Ad26.ENVA.01 vaccine. Conclusions: No safety concerns were identified, and multiclade HIV-1-specific immune responses were elicited. Clinical Trials Registration: NCT02218125.

Structural network topology correlates of microstructural brain dysmaturation in term infants with congenital heart disease.

Neonates with complex congenital heart disease (CHD) demonstrate microstructural brain dysmaturation, but the relationship with structural network topology is unknown. We performed diffusion tensor imaging (DTI) in term neonates with CHD preoperatively (N = 61) and postoperatively (N = 50) compared with healthy term controls (N = 91). We used network topology (graph) analyses incorporating different weighted and unweighted approaches and subject-specific white matter segmentation to investigate structural topology differences, as well as a voxel-based analysis (VBA) to confirm the presence of microstructural dysmaturation. We demonstrate cost-dependent network inefficiencies in neonatal CHD in the pre- and postoperative period compared with controls, related to microstructural differences. Controlling for cost, we show the presence of increased small-worldness (hierarchical fiber organization) in CHD infants preoperatively, that persists in the postoperative period compared with controls, suggesting the early presence of brain reorganization. Taken together, topological microstructural dysmaturation in CHD infants is accompanied by hierarchical fiber organization during a protracted critical period of early brain development. Our methodology also provides a pipeline for quantitation of network topology changes in neonates and infants with microstructural brain dysmaturation at risk for perinatal brain injury.

A potential therapeutic role for angiotensin-converting enzyme 2 in human pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a deadly disease with no cure. Alternate conversion of angiotensin II (AngII) to angiotensin-(1-7) (Ang-(1-7)) by angiotensin-converting enzyme 2 (ACE2) resulting in Mas receptor (Mas1) activation improves rodent models of PAH. Effects of recombinant human (rh) ACE2 in human PAH are unknown. Our objective was to determine the effects of rhACE2 in PAH.We defined the molecular effects of Mas1 activation using porcine pulmonary arteries, measured AngII/Ang-(1-7) levels in human PAH and conducted a phase IIa, open-label pilot study of a single infusion of rhACE2 (GSK2586881, 0.2 or 0.4 mg·kg-1 intravenously).Superoxide dismutase 2 (SOD2) and inflammatory gene expression were identified as markers of Mas1 activation. After confirming reduced plasma ACE2 activity in human PAH, five patients were enrolled in the trial. GSK2586881 was well tolerated with significant improvement in cardiac output and pulmonary vascular resistance. GSK2586881 infusion was associated with reduced plasma markers of inflammation within 2-4 h and increased SOD2 plasma protein at 2 weeks.PAH is characterised by reduced ACE2 activity. Augmentation of ACE2 in a pilot study was well tolerated, associated with improved pulmonary haemodynamics and reduced markers of oxidant and inflammatory mediators. Targeting this pathway may be beneficial in human PAH.

Personal Pornography Viewing and Sexual Satisfaction: A Quadratic Analysis.

Personal pornography viewing has been associated with lower sexual satisfaction in both experimental and observational research. The language used to hypothesize this relationship typically suggests that it is frequent viewing, rather than infrequent or only occasional viewing, that is responsible for any adverse effects. When the nature of the relationship between a predictor and a criterion depends on the levels of the predictor, a curvilinear relationship is indicated. Nevertheless, studies have assumed linearity in their analytical approach. Curvilinear relationships will go undetected unless they are specifically tested. This article presents results from a survey of approximately 1,500 U.S. adults. Quadratic analyses indicated a curvilinear relationship between personal pornography viewing and sexual satisfaction in the form of a predominately negative, concave downward curve. The nature of the curvilinearity did not differ as a function of participants' gender, relationship status, or religiosity. But the negative acceleration was slightly more pronounced for men than for women, for people not in a relationship than for people in a relationship, and for religious people than for nonreligious people. For all groups, negative simple slopes were present when viewing reached once a month or more. These results are correlational only. However, if an effects perspective were adopted, it would suggest that consuming pornography less than once a month has little or no impact on satisfaction, that reductions in satisfaction tend to initiate once viewing reaches once a month, and that additional increases in the frequency of viewing lead to disproportionately larger decrements in satisfaction.

Pornography and the Male Sexual Script: An Analysis of Consumption and Sexual Relations.

Pornography has become a primary source of sexual education. At the same time, mainstream commercial pornography has coalesced around a relatively homogenous script involving violence and female degradation. Yet, little work has been done exploring the associations between pornography and dyadic sexual encounters: What role does pornography play inside real-world sexual encounters between a man and a woman? Cognitive script theory argues media scripts create a readily accessible heuristic model for decision-making. The more a user watches a particular media script, the more embedded those codes of behavior become in their worldview and the more likely they are to use those scripts to act upon real life experiences. We argue pornography creates a sexual script that then guides sexual experiences. To test this, we surveyed 487 college men (ages 18-29 years) in the United States to compare their rate of pornography use with sexual preferences and concerns. Results showed the more pornography a man watches, the more likely he was to use it during sex, request particular pornographic sex acts of his partner, deliberately conjure images of pornography during sex to maintain arousal, and have concerns over his own sexual performance and body image. Further, higher pornography use was negatively associated with enjoying sexually intimate behaviors with a partner. We conclude that pornography provides a powerful heuristic model which is implicated in men's expectations and behaviors during sexual encounters.

Induction of HIV-1-specific mucosal immune responses following intramuscular recombinant adenovirus serotype 26 HIV-1 vaccination of humans.

BACKGROUND: Defining mucosal immune responses and inflammation to candidate human immunodeficiency virus type 1 (HIV-1) vaccines represents a current research priority for the HIV-1 vaccine field. In particular, it is unclear whether intramuscular immunization can elicit immune responses at mucosal surfaces in humans. METHODS: In this double-blind, randomized, placebo-controlled clinical trial, we evaluated systemic and mucosal immune responses to a candidate adenovirus serotype 26 (Ad26) vectored HIV-1 envelop (Env) vaccine in baseline Ad26-seronegative and Ad26-seropositive healthy volunteers. Systematic mucosal sampling with rectal Weck-Cel sponges and rectal biopsies were performed. RESULTS: Intramuscular immunization elicited both systemic and mucosal Env-specific humoral and cellular immune responses in the majority of subjects. Individuals with preexisting Ad26-specific neutralizing antibodies had vaccine-elicited immune responses comparable to those of subjects who were Ad26 seronegative. We also observed no increase in activated total or vector-specific mucosal CD4+ T lymphocytes following vaccination by either histopathology or flow cytometry. CONCLUSIONS: These data demonstrate that a single intramuscular administration of this Ad26-vectored HIV-1 Env vaccine elicited both systemic and mucosal immune responses in humans. Induction of antigen-specific humoral and cellular mucosal immunity was not accompanied by a detectable increase in mucosal inflammation. CLINICAL TRIALS REGISTRATION: NCT01103687.

Making thawed universal donor plasma available rapidly for massively bleeding trauma patients: experience from the Pragmatic, Randomized Optimal Platelets and Plasma Ratios (PROPPR) trial.

BACKGROUND: The Pragmatic, Randomized Optimal Platelets and Plasma Ratios (PROPPR) trial was a randomized clinical trial comparing survival after transfusion of two different blood component ratios for emergency resuscitation of traumatic massive hemorrhage. Transfusion services supporting the study were expected to provide thawed plasma, platelets, and red blood cells within 10 minutes of request. STUDY DESIGN AND METHODS: At the 12 Level 1 trauma centers participating in PROPPR, blood components transfused and delivery times were tabulated, with a focus on universal donor (UD) plasma management. The adequacy of site plans was assessed by comparing the bedside blood availability times to study goals and the new American College of Surgeons guidelines. RESULTS: Eleven of 12 sites were able to consistently deliver 6 units of thawed UD plasma to their trauma-receiving unit within 10 minutes and 12 units in 20 minutes. Three sites used blood group A plasma instead of AB for massive transfusion without complications. Approximately 4700 units of plasma were given to the 680 patients enrolled in the trial. No site experienced shortages of AB plasma that limited enrollment. Two of 12 sites reported wastage of thawed AB plasma approaching 25% of AB plasma prepared. CONCLUSION: Delivering UD plasma to massively hemorrhaging patients was accomplished consistently and rapidly and without excessive wastage in high-volume trauma centers. The American College of Surgeons Trauma Quality Improvement Program guidelines for massive transfusion protocol UD plasma availability are practicable in large academic trauma centers. Use of group A plasma in trauma resuscitation needs further study.

Fetuses of Mothers with Thyroid Disease May Be at Higher Risk of Developing Supraventricular Tachycardia.

OBJECTIVE: Fetal tachyarrhythmias complicate 0.5% of pregnancies, with high morbidity and mortality. We hypothesized that maternal factors may predispose to fetal supraventricular tachycardia (SVT). STUDY DESIGN: We reviewed medical records of all 124 mothers who presented to the Vanderbilt Fetal Cardiology Clinic from 2004 to 2010 for fetal arrhythmias, excluding heart block. Maternal factors were compared between 28 fetuses with SVT and a control group of 112 fetuses screened for noncardiac conditions. The proportions were analyzed using chi-square or Fisher exact test for categorical variables and Wilcoxon rank sum test for continuous variables. RESULTS: Of maternal factors, thyroid disease was statistically significant compared with controls. Among mothers whose fetuses had SVT, 21% had thyroid disease (83% hypothyroidism) compared with 3% of controls (p < 0.001). CONCLUSION: In this cohort, the maternal thyroid disease was more common in fetuses with SVT compared with controls (odds ratio = 9.8, 95% confidence interval 2.3-42.3), suggesting closer screening for fetal arrhythmias and SVT in mothers with thyroid disease. Also, routine screening of thyroid functions and thyroid autoantibodies may be warranted in mothers of fetuses with SVT.