Pupil Size and Reactivity in Pediatric Patients With Sickle Cell Disease.

Pupil size and reactivity have been studied to objectively measure pain utilizing pupillometry measurements. Given the challenges associated with treating vaso-occlusive pain in pediatric patients with sickle cell disease, better assessment tools are needed. The objective of this study is to establish normative values for pupil size and reactivity in pediatric patients with sickle cell disease with the hope that pupillometry can be used as a tool to objectively measure pain and response to treatment with analgesic medications. Readings were performed using a NeurOptics PLR-2000 pupillometer. Forty-four males and 38 females, all black, were studied. Their median age was 11 years (range: 2 to 21). When comparing our participants with white participants in a previously published pediatric study, there was a significant difference in maximum constriction velocity ( t =3.45, P =0.009), maximum pupil size ( t =-5.57 mm, P <0.0001), and minimum pupil size ( t =-3.24, P =0.002). There was no significant difference in pupil size and reactivity between patients with sickle cell disease and black patients without the disease when compared with the previously published study. Therefore, further investigation of pupillometry within the black population during vaso-occlusive crisis and in the "well state" is warranted in pediatric patients with sickle cell disease.

Elevated Blood Pressure and Stage 1 Hypertension in Pregnancy: A Review of the Literature.

Importance: Maternal and perinatal morbidity/mortality is significantly increased in pregnancies complicated by hypertension. The definition of hypertension has recently changed with the addition of 2 categories: elevated blood pressure (BP) and stage 1 hypertension. Should these categories be considered during pregnancy? Objective: The aim of this study was to analyze the impact of the new hypertensive categories of elevated BP and stage 1 hypertension on maternal/perinatal outcomes. Methods: Literature search of PubMed, Web of Science, and CINAHL search was undertaken. Citations were limited to the past 20 years. Results: Of the 333 articles identified, 26 articles were the basis of this review. In 2017, new guidelines on the diagnosis and management of hypertension were published. Prepregnancy hypertension was replaced by elevated BP (systolic BP 120-129 mm Hg and diastolic BP <80 mm Hg) and stage 1 hypertension (systolic BP 130-139 mm Hg and diastolic BP 80-89 mm Hg). The risk factors for elevated BP and stage 1 hypertension are similar to chronic hypertension (CHTN) risk factors, diagnosed by BP readings before pregnancy or before 20 weeks' gestation. Patients with elevated BP and stage 1 hypertension are at increased risk for hypertensive disorders of pregnancies compared with normal patients. Treatment strategies for elevated BP and stage 1 hypertension are uncertain. Before 2017, these patients would not have been considered hypertensive and no guidelines existed. Conclusions: Elevated BP and stage 1 hypertension increase the number of women labeled with hypertension in pregnancy. These women are at increased risk for adverse perinatal and maternal outcomes. There are currently no firm guidelines on management during pregnancy.

Granzyme B and miR-378a Interaction in Acetaminophen Toxicity in Children.

BACKGROUND AND AIM: Hepatic phase I drug-metabolizing enzymes CYP2E1, CYP1A2 and CYP3A4 catalyze the biotransformation of Acetaminophen (APAP) and are important in the mediation of toxicity. The potential role of other hepatic and non-hepatic Phase I enzymes in APAP toxicity has not been established. METHODS: PCR array containing 84 genes involved in phase I drug metabolism was examined in subgroups of hospitalized children for APAP overdose, categorized as no toxicity (ALT ≤ 45 IU/L, n=5) and moderate toxicity (ALT ≥ 500 IU/L, n=5). RESULTS: Significant downregulation was observed for ALDH6A1, CYP4F12 and GZMB in the no toxicity subgroup and ALDH1A1, CYP27A1 and GZMB in the moderate toxicity subgroup. qRTPCR confirmed significant downregulation for ALDH1A1, CYP4F12, and GZMB. In-silico analysis identified GZMB 3'UTR to be a target of miR-378a-5p. Overexpression of miR-378a-5p reduced the luciferase activity of GZMB 3'UTR reporter plasmid reportedly by 50%. NK-92 cells transfected with the miR-378a-5p mimic extended the effect of APAP on GZMB protein expression compared to mimic controls. In addition, miR-378a-5p was significantly upregulated in blood samples of children with APAP overdose undergoing NAC treatment. CONCLUSION: Overall, our study suggests the presence of a novel signaling pathway, whereby miR- 378a-5p inhibits GZMB expression in children with APAP overdose.

Dose-response effects of tiagabine on the sleep of older adults.

STUDY OBJECTIVES: To evaluate the dose- response effects of tiagabine on sleep and safety measures in healthy older adults. DESIGN: Randomized, double-blind, Latin-square design. SETTING: Sleep laboratory. PARTICIPANTS: Twenty-four healthy older adults (11 men, 13 women; mean age 68.0 +/- 6.2 years) INTERVENTIONS: Tiagabine 2, 4, or 8 mg, or placebo, each given on two consecutive nights. MEASUREMENTS AND RESULTS: Polysomnography revealed that compared with placebo, tiagabine 4 mg increased total sleep time, reduced wake after sleep onset, and increased minutes of slow-wave sleep. Tiagabine 8 mg decreased wake after sleep onset, increased slow-wave sleep, and improved a sleep-continuity index. No differences were seen between the 2-mg dose and placebo. Subjective ratings indicated fewer awakenings with the 8-mg dose. Central nervous system adverse events were somewhat higher in the 8-mg condition only. Measures of morning performance were minimally affected. CONCLUSIONS: Research with tiagabine at dosages of 8 mg or less appears warranted in elderly clinical populations.