The Study of the Epidemiology of Pediatric Hypertension Registry (SUPERHERO): Rationale and Methods.

Despite increasing prevalence of hypertension in youth and high adult cardiovascular mortality rates, the long-term consequences of youth-onset hypertension remain unknown. This is due to limitations of prior research such as small sample sizes, reliance on manual record review, and limited analytic methods that did not address major biases. The Study of the Epidemiology of Pediatric Hypertension (SUPERHERO) is a multisite retrospective Registry of youth evaluated by subspecialists for hypertension disorders. Sites obtain harmonized electronic health record data using standardized biomedical informatics scripts validated with randomized manual record review. Inclusion criteria are index visit for International Classification of Diseases Diagnostic Codes, 10th Revision (ICD-10 code)-defined hypertension disorder ≥January 1, 2015 and age <19 years. We exclude patients with ICD-10 code-defined pregnancy, kidney failure on dialysis, or kidney transplantation. Data include demographics, anthropomorphics, U.S. Census Bureau tract, histories, blood pressure, ICD-10 codes, medications, laboratory and imaging results, and ambulatory blood pressure. SUPERHERO leverages expertise in epidemiology, statistics, clinical care, and biomedical informatics to create the largest and most diverse registry of youth with newly diagnosed hypertension disorders. SUPERHERO's goals are to (i) reduce CVD burden across the life course and (ii) establish gold-standard biomedical informatics methods for youth with hypertension disorders.

Conceptus Estrogen and prostaglandins provide the maternal recognition of pregnancy signal to prevent Luteolysis during early pregnancy in the pig†.

Conceptus estrogens and prostaglandins have long been considered the primary signals for maternal recognition of pregnancy (MRP) in the pig. However, loss-of-function studies targeting conceptus aromatase genes (CYP19A1 and CYP19A2) and prostaglandin-endoperoxide synthase 2 (PTGS2) indicated that conceptuses can not only signal MRP without estrogens or prostaglandins but can maintain early pregnancy. However, complete loss of estrogen production leads to abortion after day 25 of gestation. Although neither conceptus estrogens nor prostaglandins had a significant effect on early maintenance of CL function alone, the two conceptus factors have a biological relationship. To investigate the role that both conceptus estrogens and prostaglandins have on MRP and maintenance of pregnancy, a triple loss-of function model (TKO) was generated for conceptus CYP19A1, CYP19A2 and PTGS2. In addition, a conceptus CYP19A2-/- model (A2KO) was established to determine the role of placental estrogen during later pregnancy. Estrogen and prostaglandin synthesis were greatly reduced in TKO conceptuses which resulted in a failure to inhibit luteolysis after day 15 of pregnancy despite the presence of conceptuses in the uterine lumen. However, A2KO placentae not only maintained functional CL but were able to maintain pregnancy to day 32 of gestation. Despite the loss of placental CYP19A2 expression, the allantois fluid content of estrogen was not affected as the placenta compensated by expressing CYP19A1 and CYP19A3, which are normally absent in controls. Results suggest conceptuses can signal MRP through production of conceptus PGE or stimulating PGE synthesis from the endometrium through conceptus estrogen. Failure of conceptuses to produce both factors results in failure of MRP and loss of pregnancy.

Laparoscopic treatment of fourteen cases of pelvic ring disruption: a case series.

PURPOSE: Open surgical approaches for the treatment of anterior pelvic arc lesions are associated with several complications. We present the first retrospective descriptive case series on the use of laparoscopy as an alternative. METHODS: This descriptive, retrospective, single-centre study enrolled all patients who underwent laparoscopy for the treatment of pelvic ring disruption between May 2020 and March 2022. The primary outcome was the procedure failure rate based on conversion to open surgery. Secondary outcomes were the duration of the surgical procedure, x-ray exposure, length of hospitalisation, postoperative pain assessment, and functional scores at the last follow-up. RESULTS: The study included two females and 12 males. The mean age of the study participants was 44.2 (23-67) years. In total, nine (64.3%) patients had pubic symphysis disjunction, four (28.6%) had bilateral fractures of the obturator frames, and one (7%) had both. None of the patients required conversion to open surgery. The median operating times for symphysis pubis disruption, obturator frame fracture, and patients with both injuries were 90.0 (60-120), 135 (105-180), and 240 min, respectively. The median overall operating time was 102.5 (60-240) min. The median Iowa Pelvic Score and Majeed Functional Score at the last follow-up were 87 (70-99) and 84 (70-100), respectively. CONCLUSION: Laparoscopic internal fixation is a reliable treatment for pelvic ring disruption. The clinical and radiological outcomes of our patients suggest the usefulness of this technique as an alternative to open approaches.

How parent stress and COVID-19 impact on the family are associated with parental pressure to eat during COVID-19.

This study aimed to assess how parent stress and COVID-19 impact on the family are associated with parental pressure to eat during the COVID-19 pandemic. Parents of healthy preschool-aged children completed measures including pressure to eat (Child Feeding Questionnaire), parent perception of their stress (Perceived Stress Scale), household food insecurity (Hunger Vital Sign) and effects of COVID-19 on families (COVID-19 Exposure and Family Impact). Children (N = 228) were racially, ethnically, and socioeconomically diverse (34 % Black, 15 % Hispanic, and 29 % with household income <$20,000). Bivariate analyses showed that parent stress at Year 1 (ß 0.02; 95 % CI 0.006, 0.04) was significantly associated with pressure to eat at Year 1 and that COVID-19 impact at Year 1 (ß 0.02; 95 % CI 0.001, 0.03) was also significantly associated with pressure to eat. Multivariable linear regression analyses showed that parent stress at Year 1 was significantly associated with pressure to eat at Year 1 (ß 0.39; 95 % CI 0.16, 0.61) while COVID-19 impact was not significantly associated with pressure to eat at Year 1. This study, consisting of racially and socioeconomically diverse children, found that while parent stress was significantly associated with increased parental utilization of pressure to eat feeding practice, COVID-19 impact was not significantly associated with pressure to eat in adjusted analyses. This suggests that overall perceived stress by parents could be an important factor in parent pressuring feeding practices.

Differences in maternal and paternal pressure to eat and perception of household responsibilities.

Controlling feeding practices, such as pressure to eat, are associated with a child's disinhibited eating and extremes in bodyweight. We aimed to explore which factors are associated with parent dyads' pressuring feeding practices, including how mothers and fathers perceive the sharing of household tasks such as mealtime and child feeding responsibilities. In this cross-sectional study, parent dyads (mother and father) of healthy preschool-aged children completed an identical questionnaire consisting of measures of picky eating (food fussiness subscale of Child Eating Behavior Questionnaire), parental concern for undereating, and pressure to eat (Child Feeding Questionnaire). We used separate multivariable linear regression models for mothers and fathers to assess correlates associated with pressure to eat subscale score, including slowness of eating and enjoyment of food, child BMI z-score and race/ethnicity, and household income. Separate unadjusted linear regression models for mothers and fathers were used to report the association of pressure to eat with household responsibilities. Parents (N = 88) had similar mean picky eating, concern for undereating, and pressure to eat scores; more fathers had high pressure to eat scores (36% vs 27%). Higher pressure to eat was significantly associated with lower income, non-Hispanic Black or Black race/ethnicity, slow eating, and lower enjoyment of food. Pressure was not associated with household responsibilities. While there were similar maternal and paternal perceptions of child eating behaviors, more fathers reported pressuring their child to eat. Identifying differences in parental feeding practices may assist in intervention development to improve feeding practices.

Maternal recognition of pregnancy in the pig: A servomechanism involving sex steroids, cytokines and prostaglandins.

Maternal recognition of pregnancy (MRP) is a term utilized in mammals to describe pathways in which the conceptus alters the endometrial environment to prevent regression of corpora lutea to ensure continued production of progesterone (P4) required for establishment and maintenance of pregnancy. For nearly 40 years after publication of the endocrine/exocrine theory, conceptus estrogen (E2) was considered the primary maternal recognition signal in the pig. Conceptus production of prostaglandin E2 (PGE2) was also considered to be a major factor in preventing luteolysis. An addition to E2 and PGE2, pig conceptuses produce interleukin 1B2 (IL1B2) and interferons (IFN) delta (IFND) and gamma (IFNG). The present review provides brief history of the discovery of E2, PGs and IFNS which led to research investigating the role of these conceptus secreted factors in establishing and maintaining pregnancy in the pig. The recent utilization of gene editing technology allowed a more direct approach to investigate the in vivo roles of IL1B2, E2, PGE2, AND IFNG for establishment of pregnancy. These studies revealed unknown functions for IFNG and ILB2 in addition to PGE2 and E2. Thus, pregnancy recognition signal is via a servomechanism in requiring sequential effects of P4, E2, IL1B2, PGE2 and IFNG. Results indicate that the original established dogma for the role of conceptus E2 and PGs in MRP is a far too simplified model that involves the interplay of numerous mechanisms for inhibiting luteolysis, inducing critical elongation of the conceptuses and resolution of inflammation in pigs.

Extended Survival of 9- and 10-Gene-Edited Pig Heart Xenografts with Ischemia Minimization and CD154 Costimulation Blockade-Based Immunosuppression.

BACKGROUND: Xenotransplantation has made significant advances recently using pigs genetically engineered to remove carbohydrate antigens, either alone or with addition of various human complement, coagulation, and anti-inflammatory 'transgenes'. Here we evaluated results associated with gene-edited (GE) pig hearts transplanted in baboons using an established costimulation-based immunosuppressive regimen and a cold-perfused graft preservation technique. METHODS: Eight baboons received heterotopic abdominal heart transplants from 3-GE (GalKO.ß4GalNT2KO.hCD55, n=3), 9-GE (GalKO.ß4GalNT2KO.GHRKO.hCD46.hCD55. TBM.EPCR.hCD47.HO-1, n=3) or 10-G (9-GE+CMAHKO, n=2) pigs using Steen's cold continuous perfusion for ischemia minimization. Immunosuppression (IS) included induction with anti-thymocyte globulin and αCD20, ongoing αCD154, MMF, and tapered corticosteroid. RESULTS: All three 3-GE grafts functioned well initially, but failed within 5 days. One 9-GE graft was lost intraoperatively due to a technical issue and another was lost at POD 13 due to antibody mediated rejection (AMR) in a baboon with a strongly positive pre-operative cross-match. One 10-GE heart failed at POD113 with combined cellular and antibody mediated rejection. One 9-GE and one 10-GE hearts had preserved graft function with normal myocardium on protocol biopsies, but exhibited slowly progressive graft hypertrophy until elective necropsy at POD393 and 243 respectively. Elevated levels of IL-6, MCP-1, C-reactive protein, and human thrombomodulin were variably associated with conditioning, the transplant procedure, and clinically significant postoperative events. CONCLUSION: Relative to reference genetics without thrombo-regulatory and anti-inflammatory gene expression, 9- or 10-GE pig hearts exhibit promising performance in the context of a clinically applicable regimen including ischemia minimization and αCD154-based IS, justifying further evaluation in an orthotopic model.