Inhibition of LTßR signalling activates WNT-induced regeneration in lung.

Lymphotoxin ß-receptor (LTßR) signalling promotes lymphoid neogenesis and the development of tertiary lymphoid structures1,2, which are associated with severe chronic inflammatory diseases that span several organ systems3-6. How LTßR signalling drives chronic tissue damage particularly in the lung, the mechanism(s) that regulate this process, and whether LTßR blockade might be of therapeutic value have remained unclear. Here we demonstrate increased expression of LTßR ligands in adaptive and innate immune cells, enhanced non-canonical NF-κB signalling, and enriched LTßR target gene expression in lung epithelial cells from patients with smoking-associated chronic obstructive pulmonary disease (COPD) and from mice chronically exposed to cigarette smoke. Therapeutic inhibition of LTßR signalling in young and aged mice disrupted smoking-related inducible bronchus-associated lymphoid tissue, induced regeneration of lung tissue, and reverted airway fibrosis and systemic muscle wasting. Mechanistically, blockade of LTßR signalling dampened epithelial non-canonical activation of NF-κB, reduced TGFß signalling in airways, and induced regeneration by preventing epithelial cell death and activating WNT/ß-catenin signalling in alveolar epithelial progenitor cells. These findings suggest that inhibition of LTßR signalling represents a viable therapeutic option that combines prevention of tertiary lymphoid structures1 and inhibition of apoptosis with tissue-regenerative strategies.

Cholesterol metabolism promotes B-cell positioning during immune pathogenesis of chronic obstructive pulmonary disease.

The development of chronic obstructive pulmonary disease (COPD) pathogenesis remains unclear, but emerging evidence supports a crucial role for inducible bronchus-associated lymphoid tissue (iBALT) in disease progression. Mechanisms underlying iBALT generation, particularly during chronic CS exposure, remain to be defined. Oxysterol metabolism of cholesterol is crucial to immune cell localization in secondary lymphoid tissue. Here, we demonstrate that oxysterols also critically regulate iBALT generation and the immune pathogenesis of COPD In both COPD patients and cigarette smoke (CS)-exposed mice, we identified significantly upregulated CH25H and CYP7B1 expression in airway epithelial cells, regulating CS-induced B-cell migration and iBALT formation. Mice deficient in CH25H or the oxysterol receptor EBI2 exhibited decreased iBALT and subsequent CS-induced emphysema. Further, inhibition of the oxysterol pathway using clotrimazole resolved iBALT formation and attenuated CS-induced emphysema in vivo therapeutically. Collectively, our studies are the first to mechanistically interrogate oxysterol-dependent iBALT formation in the pathogenesis of COPD, and identify a novel therapeutic target for the treatment of COPD and potentially other diseases driven by the generation of tertiary lymphoid organs.

Evaluating the content and quality of intrapartum care in vaginal births: An example of a state hospital.

OBJECTIVE: The purpose of the research was to assess the content and quality of the intrapartum care offered in vaginal births in Turkey, based on the example of a state hospital. MATERIALS AND METHODS: This cross-sectional study was conducted between January 1st, 2013 and December 31st, 2014 at Aydin Maternity and Children's Hospital. The study sample consisted of 303 women giving vaginal birth, who were recruited into the study using the method of convenience sampling. Research data were collected with a questionnaire created by the researchers and assessed using the Bologna score. Numbers and percentages were assessed in the data analysis. RESULTS: The mean age of the women was 25.14±5.37 years and 40.5% had given one live birth. Of the women, 45.2% were admitted to hospital in the latent phase, 76.6% were administered an enema, 3.3% had epidural anesthesia, 2.6% delivered using vacuum extraction, and 54.1% underwent an episiotomy. Some 23.8% of the women experienced spontaneous laceration that needed sutures. The babies of two women exhibited an Apgar score below 7 in the fifth minute. When the quality of the intrapartum care given to the women was assessed with the Bologna score, it was found that 92.7% went into labor spontaneously, 100% of the births were supervised by midwives and doctors, 97.7% of the women had no supporting companion, and the nonsupine position was only used in 0.3% of the women. A partogram was used to follow up on the birth process in 72.6% of the women, and 82.5% achieved contact with their babies within the first hour after birth. Induction was applied in 76.6% of the women and fundal pressure in 27.4%. CONCLUSION: The study revealed that the quality of intrapartum care in vaginal births was inadequate. Reformulating the guidelines regarding intrapartum care in accordance with World Health Organization recommendations and evidence-based practices may contribute to improving mother and infant health.

The feeling of discomfort during vaginal examination, history of abuse and sexual abuse and post-traumatic stress disorder in women.

AIMS AND OBJECTIVES: To examine the feeling of discomfort during vaginal examinations, history of abuse and sexual abuse and post-traumatic stress disorder in women to determine the correlation between these variables. BACKGROUND: Women who have experienced abuse or sexual abuse may feel more discomfort during vaginal examinations and may perceive a sensation similar to what they experienced during sexual abuse. DESIGN: Cross-sectional. METHODS: This study included 320 women receiving a vaginal examination. The data were collected using a questionnaire composed of items related to descriptive characteristics, vaginal examinations and violence, a visual analogue scale of discomfort, and the Post-Traumatic Stress Disorder Scale-civilian version. RESULTS: The mean score for the feeling of discomfort during vaginal examinations was 3·92 ± 3·34; 26·3% of the women described discomfort. Thirty-eight (12%) of the 320 women had experienced emotional violence, 25 (8%) had experienced physical violence, and 25 (8%) had been forced into sexual intercourse by their spouses. Of the women, 64·7% suffered from post-traumatic stress disorder, and physical, emotional and sexual violence were found to increase the possibility of this disorder. Exposure to emotional violence increased the possibility of discomfort during vaginal examinations by 4·5 (OR = 4·482; 95% CI = 1·421-14·134). Post-traumatic stress disorder (OR = 1·038; 95% CI = 1·009-1·066) was found to increase the possibility of discomfort during vaginal examinations; however, as the number of live births increases, women reported a reduction in their discomfort with vaginal examinations. CONCLUSION: This study revealed a positive correlation between discomfort during vaginal examinations and emotional violence and post-traumatic stress disorder but a negative correlation between discomfort during vaginal examinations and the number of live births. In addition, having a history of abuse and sexual abuse was found to increase post-traumatic stress disorder. RELEVANCE TO CLINICAL PRACTICE: Considering these findings during vaginal examinations may help change women's experiences for the positive and reduce the trauma, this procedure may cause.