Investigating the association factors of acute postpartum pain: a cohort study.

BACKGROUND: Labor pain intensity is known to predict persistent postpartum pain, whereas acute postpartum pain may interfere with maternal postpartum physical, mental, and emotional well-being. Nevertheless, there is little research studying the association between labor pain intensity and acute postpartum pain. This study investigated the associations between labor pain intensity and psychological factors with acute postpartum pain. METHODS: We included women with American Society of Anesthesiologists (ASA) physical status II, having ≥ 36 gestational weeks and a singleton pregnancy. We investigated the association between labor pain intensity (primary exposure) and high acute postpartum pain at 0 to 24 h after delivery (Numeric Rating Scale (NRS) ≥ 3 of 10; primary outcome). Pre-delivery questionnaires including Angle Labor Pain Questionnaire (A-LPQ), Pain Catastrophizing Scale (PCS), Fear Avoidance Components Scale (FACS) and State Trait Anxiety Inventory (STAI) were administered. Demographic, pain, obstetric and neonatal characteristics were also collected accordingly. RESULTS: Of the 880 women studied, 121 (13.8%) had high acute postpartum pain at 0 to 24 h after delivery. A-LPQ total, PCS, FACS and STAI scores were not significantly associated with acute postpartum pain. Greater A-LPQ subscale on birthing pain (adjusted odds ratio (aOR) 1.03, 95% CI 1.01-1.05, p = 0.0008), increased blood loss during delivery (for every 10ml change; aOR 1.01, 95% CI 1.00-1.03, p = 0.0148), presence of shoulder dystocia (aOR 10.06, 95% CI 2.28-44.36, p = 0.0023), and use of pethidine for labor analgesia (aOR 1.74, 95% CI 1.07-2.84, p = 0.0271) were independently associated with high acute postpartum pain. "Sometimes" having nausea during menstruation before current pregnancy (aOR 0.34, 95% CI 0.16-0.72, p = 0.0045) was found to be independently associated with reduced risk of high acute postpartum pain. CONCLUSIONS: Pre-delivery pain factor together with obstetric complications (shoulder dystocia, blood loss during delivery) were independently associated with high acute postpartum pain. TRIAL REGISTRATION: This study was registered on clinicaltrials.gov registry (NCT03167905) on 30/05/2017.

3D-Reconstructed Retinal Pigment Epithelial Cells Provide Insights into the Anatomy of the Outer Retina.

The retinal pigment epithelium (RPE) is located between the neuroretina and the choroid, and plays a critical role in vision. RPE cells internalise outer segments (OS) from overlying photoreceptors in the daily photoreceptor renewal. Changes to RPE structure are linked with age and retinopathy, which has been described in the past by conventional 2D electron microscopy. We used serial block face scanning electron microscopy (SBF-SEM) to reconstruct RPE cells from the central mouse retina. Three-dimensional-reconstructed OS revealed the RPE to support large numbers of photoreceptors (90-216 per RPE cell). Larger bi-nucleate RPE maintained more photoreceptors, although their cytoplasmic volume was comparable to smaller mono-nucleate RPE supporting fewer photoreceptors. Scrutiny of RPE microvilli and interdigitating OS revealed the angle and surface area of contact between RPE and photoreceptors. Bi-nucleate RPE contained more mitochondria compared to mono-nucleate RPE. Furthermore, bi-nucleate cells contained larger sub-RPE spaces, supporting a likely association with disease. Use of perfusion-fixed tissues ensured the highest possible standard of preservation, providing novel insights into the 3D RPE architecture and changes linked with retinopathy. This study serves as a benchmark for comparing retinal tissues from donor eyes with age-related macular degeneration (AMD) and other retinopathies.

A novel method for examining corneal endothelial cell morphology in infants.

Previous studies have suggested that central corneal endothelial cell density (ECD) decreases from 6,100 cells/mm2 in neonates to 3,100 cells/mm2 in 10-year-olds. Currently data on ECD in young children as well as the trend for ECD decrease during childhood is sparse because of the difficulty of examination using existing clinic-based specular microscopes. We developed a novel method of imaging young children intraoperatively with the goal of beginning to establish age-specific normative data for ECD and hexagonality of cells (%HEX). Children were imaged using our novel technique under general anesthesia or awake in clinic using a child-friendly technique. A total of 58 children were recruited (mean age, 5.50; range, 0.44-10.36). Our cohort displayed a significant linear decrease in ECD with age (r = -0.56, P < 0.001). No correlation was found between %HEX and age (r = -0.10, P = 0.48).

Angiotensin II-inducible smooth muscle cell apoptosis involves the angiotensin II type 2 receptor, GATA-6 activation, and FasL-Fas engagement.

RATIONALE: Fas ligand (FasL)-mediated smooth muscle cell (SMC) apoptosis within the vulnerable plaque may lead to plaque instability and rupture, events that underlie myocardial infarction and stroke. OBJECTIVE: The molecular mechanisms underlying FasL transcription and FasL-dependent SMC apoptosis were investigated in this study in vitro and in vivo. METHODS AND RESULTS: We demonstrate that GATA-6, the predominant GATA family member expressed in SMCs, stimulates SMC apoptosis in an extracellular FasL-dependent manner. Both GATA-6 and FasL were inducibly and transiently expressed following balloon injury to rat carotid arteries. We identified two potential GATA binding in the FasL promoter and demonstrated using DNA binding and chromatin immunoprecipitation assays that GATA-6 regulates FasL through one ((-298)TTATCA(-303)) but not both these elements. Angiotensin II (Ang II) stimulated expression of both GATA-6 and FasL. Ang II increased SMC apoptosis in an Ang II type 2 receptor-, caspase 8-, and FasL-dependent fashion. GATA-6 activation was MEK-ERK1/2- and JNK-dependent, and GATA-6 small interfering RNA blocked Ang II-inducible FasL expression and SMC apoptosis. Administration of Ang II to rats increased FasL expression and apoptosis in carotid artery SMCs in an Ang II type 2 receptor- and GATA-6-dependent manner. CONCLUSIONS: This study provides new insights into the transcriptional events underpinning FasL-dependent SMC apoptosis after exposure to Ang II.

Death receptors and their ligands in atherosclerosis.

Atherosclerosis is characterized by the accumulation of a fibro-fatty plaque consisting of immune cells, vascular smooth muscle cells (VSMCs), vascular endothelial cells (ECs), and extracellular matrix, surrounding a lipid-rich core. The complexity of atherosclerosis is highlighted by the multifaceted effects that apoptosis and proliferation of specific cell types can have on vessels at different stages of the disease. Death receptors are membrane-bound protein complexes that on binding their cognate ligand, activate an intracellular signaling cascade that results in apoptosis. More recently, signaling from these receptors has been shown to activate multiple other processes, including cell proliferation. This review summarizes our current understanding of signaling events after death receptor activation and the role of death receptors and their ligands in atherosclerosis.

Angiotensin II-inducible platelet-derived growth factor-D transcription requires specific Ser/Thr residues in the second zinc finger region of Sp1.

Sp1, the first identified and cloned transcription factor, regulates gene expression via multiple mechanisms including direct protein-DNA interactions, protein-protein interactions, chromatin remodeling, and maintenance of methylation-free CpG islands. Sp1 is itself regulated at different levels, for example, by glycosylation, acetylation, and phosphorylation by kinases such as the atypical protein kinase C-zeta. Although Sp1 controls the basal and inducible regulation of many genes, the posttranslational processes regulating its function and their relevance to pathology are not well understood. Here we have used a variety of approaches to identify 3 amino acids (Thr668, Ser670, and Thr681) in the zinc finger domain of Sp1 that are modified by PKC-zeta and have generated novel anti-peptide antibodies recognizing the PKC-zeta-phosphorylated form of Sp1. Angiotensin II, which activates PKC-zeta phosphorylation (at Thr410) via the angiotensin II type 1 receptor, stimulates Sp1 phosphorylation and increases Sp1 binding to the platelet-derived growth factor-D promoter. All 3 residues in Sp1 (Thr668, Ser670, and Thr681) are required for Sp1-dependent platelet-derived growth factor-D activation in response to angiotensin II. Immunohistochemical analysis revealed that phosphorylated Sp1 is expressed in smooth muscle cells of human atherosclerotic plaques and is dynamically expressed together with platelet-derived growth factor-D in smooth muscle cells of the injured rat carotid artery wall. This study provides new insights into the regulatory mechanisms controlling the PKC-zeta-phospho-Sp1 axis and angiotensin II-inducible gene expression.