Women’s, partners’ and healthcare providers’ views and experiences of assisted vaginal birth: a systematic mixed methods review

Background When certain complications arise during the second stage of labour, assisted vaginal delivery (AVD), a vaginal birth with forceps or vacuum extractor, can effectively improve outcomes by ending prolonged labour or by ensuring rapid birth in response to maternal or fetal compromise. In recent decades, the use of AVD has decreased in many settings in favour of caesarean section (CS). This review aimed to improve understanding of experiences, barriers and facilitators for AVD use. Methods Systematic searches of eight databases using predefined search terms to identify studies reporting views and experiences of maternity service users, their partners, health care providers, policymakers, and funders in relation to AVD. Relevant studies were assessed for methodological quality. Qualitative findings were synthesised using a meta-ethnographic approach. Confidence in review findings was assessed using GRADE CERQual. Findings from quantitative studies were synthesised narratively and assessed using an adaptation of CERQual. Qualitative and quantitative review findings were triangulated using a convergence coding matrix. Results Forty-two studies (published 1985–2019) were included: six qualitative, one mixed-method and 35 quantitative. Thirty-five were from high-income countries, and seven from LMIC settings. Confidence in the findings was moderate or low. Spontaneous vaginal birth was most likely to be associated with positive short and long-term outcomes, and emergency CS least likely. Views and experiences of AVD tended to fall somewhere between these two extremes. Where indicated, AVD can be an effective, acceptable alternative to caesarean section. There was agreement or partial agreement across qualitative studies and surveys that the experience of AVD is impacted by the unexpected nature of events and, particularly in high-income settings, unmet expectations. Positive relationships, good communication, involvement in decision-making, and (believing in) the reason for intervention were important mediators of birth experience. Professional attitudes and skills (development) were simultaneously barriers and facilitators of AVD in quantitative studies. Conclusions Information, positive interaction and communication with providers and respectful care are facilitators for acceptance of AVD. Barriers include lack of training and skills for decision-making and use of instruments

Gene Expression Profiling in Cells with Enhanced γ-Secretase Activity

BACKGROUND: Processing by gamma-secretase of many type-I membrane protein substrates triggers signaling cascades by releasing intracellular domains (ICDs) that, following nuclear translocation, modulate the transcription of different genes regulating a diverse array of cellular and biological processes. Because the list of gamma-secretase substrates is growing quickly and this enzyme is a cancer and Alzheimer's disease therapeutic target, the mapping of gamma-secretase activity susceptible gene transcription is important for sharpening our view of specific affected genes, molecular functions and biological pathways. METHODOLOGY/PRINCIPAL FINDINGS: To identify genes and molecular functions transcriptionally affected by gamma-secretase activity, the cellular transcriptomes of Chinese hamster ovary (CHO) cells with enhanced and inhibited gamma-secretase activity were analyzed and compared by cDNA microarray. The functional clustering by FatiGO of the 1,981 identified genes revealed over- and under-represented groups with multiple activities and functions. Single genes with the most pronounced transcriptional susceptibility to gamma-secretase activity were evaluated by real-time PCR. Among the 21 validated genes, the strikingly decreased transcription of PTPRG and AMN1 and increased transcription of UPP1 potentially support data on cell cycle disturbances relevant to cancer, stem cell and neurodegenerative diseases' research. The mapping of interactions of proteins encoded by the validated genes exclusively relied on evidence-based data and revealed broad effects on Wnt pathway members, including WNT3A and DVL3. Intriguingly, the transcription of TERA, a gene of unknown function, is affected by gamma-secretase activity and was significantly altered in the analyzed human Alzheimer's disease brain cortices. CONCLUSIONS/SIGNIFICANCE: Investigating the effects of gamma-secretase activity on gene transcription has revealed several affected clusters of molecular functions and, more specifically, 21 genes that hold significant potential for a better understanding of the biology of gamma-secretase and its roles in cancer and Alzheimer's disease pathology

Erythropoietin: a multimodal neuroprotective agent

The tissue protective functions of the hematopoietic growth factor erythropoietin (EPO) are independent of its action on erythropoiesis. EPO and its receptors (EPOR) are expressed in multiple brain cells during brain development and upregulated in the adult brain after injury. Peripherally administered EPO crosses the blood-brain barrier and activates in the brain anti-apoptotic, anti-oxidant and anti-inflammatory signaling in neurons, glial and cerebrovascular endothelial cells and stimulates angiogenesis and neurogenesis. These mechanisms underlie its potent tissue protective effects in experimental models of stroke, cerebral hemorrhage, traumatic brain injury, neuroinflammatory and neurodegenerative disease. The preclinical data in support of the use of EPO in brain disease have already been translated to first clinical pilot studies with encouraging results with the use of EPO as a neuroprotective agent

Artificial intelligence extension of the OSCAR-IB criteria

Artificial intelligence (AI)-based diagnostic algorithms have achieved ambitious aims through automated image pattern recognition. For neurological disorders, this includes neurodegeneration and inflammation. Scalable imaging technology for big data in neurology is optical coherence tomography (OCT). We highlight that OCT changes observed in the retina, as a window to the brain, are small, requiring rigorous quality control pipelines. There are existing tools for this purpose. Firstly, there are human-led validated consensus quality control criteria (OSCAR-IB) for OCT. Secondly, these criteria are embedded into OCT reporting guidelines (APOSTEL). The use of the described annotation of failed OCT scans advances machine learning. This is illustrated through the present review of the advantages and disadvantages of AI-based applications to OCT data. The neurological conditions reviewed here for the use of big data include Alzheimer disease, stroke, multiple sclerosis (MS), Parkinson disease, and epilepsy. It is noted that while big data is relevant for AI, ownership is complex. For this reason, we also reached out to involve representatives from patient organizations and the public domain in addition to clinical and research centers. The evidence reviewed can be grouped in a five-point expansion of the OSCAR-IB criteria to embrace AI (OSCAR-AI). The review concludes by specific recommendations on how this can be achieved practically and in compliance with existing guidelines

Non-small-cell lung cancer: molecular targeted therapy and personalized medicine – drug resistance, mechanisms, and strategies

Marybeth Sechler,1,2 Amber D Cizmic,3 Sreedevi Avasarala,1 Michelle Van Scoyk,1 Christine Brzezinski,1 Nicole Kelley,1 Rama Kamesh Bikkavilli,1 Robert A Winn1–3 1Division of Pulmonary Sciences and Critical Care, 2Program in Cancer Biology, University of Colorado, Aurora, CO, USA; 3Veterans Affairs Medical Center, Denver, CO, USA Abstract: Targeted therapies for cancer bring the hope of specific treatment, providing high efficacy and in some cases lower toxicity than conventional treatment. Although targeted therapeutics have helped immensely in the treatment of several cancers, like chronic myelogenous leukemia, colon cancer, and breast cancer, the benefit of these agents in the treatment of lung cancer remains limited, in part due to the development of drug resistance. In this review, we discuss the mechanisms of drug resistance and the current strategies used to treat lung cancer. A better understanding of these drug-resistance mechanisms could potentially benefit from the development of a more robust personalized medicine approach for the treatment of lung cancer. Keywords: lung cancer, drug targets, personalized medicine, NSCL

Comparison of Idiopathic Interstitial Pneumonia and Connective Tissue Disease Related Interstitial Lung Disease by Physiologic and Functional Testing Parameters

Introduction: Pulmonary function tests (PFTs) and six minute walk tests(6MWTs) in Idiopathic Interstitial Pneumonias (IIP) and Connective Tissue Disease related Interstitial Lung Disease (CTD-ILD) provide a baseline for longitudinal care and functional assessment. This retrospective, cross-sectional study was designed to characterize differences in physiologic and functional parameters among patients with IIP or CTD-ILD. Methods: Electronic medical records were used to identify patients evaluated in the Henry Ford Hospital Pulmonary Clinics for ILD (identified via International Classification of Diseases 9 code for ILD) and had undergone forced vital capacity (FVC) and diffusing capacity of carbon monoxide (DLCO) between January 1st, 2010 and August 31st, 2015. Patients who did not have a 6MWT within 90 days of a selected PFT and an echocardiogram within 180 days of a matched pair of PFT and 6MWT were excluded. Patients with echocardiographic features of pulmonary hypertension or systolic dysfunction were also excluded. Demographic variables and results from diagnostic testing (PFT and 6MWT performed according to ATS criteria) and echocardiogram were collected. Mean values and percentages were calculated for linear and categorical variables. Two-sample t-tests were performed for continuous variables comparing the IIP and CTD-ILD groups. Linear regression analysis of %predicted DLCO adjusted for hemoglobin (%pred adjDLCO) with degree of desaturation on 6MWT by group was performed. Results: Forty-two of the 438 ILD patients who underwent PFTs, 6MWT and echocardiogram met full inclusion criteria: 24 with IIP and 18 with CTD-ILD. Patients with IIP were older (mean age 63 years) than those with CTD-ILD (mean age 50 years). The majority of patients with IIP were male (75%) while only 33.3% of the CTD-ILD group were male. Despite similar mean %pred adjDLCO, more patients with IIP (45.8%) required supplemental oxygen, compared to 22.2% of CTD-ILD patients. There were no significant differences in mean %predicted FVC, baseline Borg dyspnea or fatigue scores, or degree of desaturation on 6MWT between the two groups. There was no significant correlation of %pred adjDLCO with change in oxygen saturation during 6MWT for the IIP or CTD-ILD groups, after control for amount of supplemental oxygen worn. Conclusions: In this single center cohort of IIP and CTD-ILD patients, the %pred adjDLCO did not correlate with the degree of desaturation during 6MWT, despite a higher percentage of patients with IIP requiring supplemental oxygen. Small sample size and use of supplemental oxygen during 6MWT in about 1/3 of the patients may have influenced our findings

Comparison of idiopathic interstitial pneumonia and connective tissue disease related interstitial lung disease by physiologic and functional testing parameters.

Introduction: Pulmonary function tests (PFTs) and six minute walk tests(6MWTs) in Idiopathic Interstitial Pneumonias (IIP) and Connective Tissue Disease related Interstitial Lung Disease (CTD-ILD) provide a baseline for longitudinal care and functional assessment. This retrospective, cross-sectional study was designed to characterize differences in physiologic and functional parameters among patients with IIP or CTD-ILD. Methods: Electronic medical records were used to identify patients evaluated in the Henry Ford Hospital Pulmonary Clinics for ILD (identified via International Classification of Diseases 9 code for ILD) and had undergone forced vital capacity (FVC) and diffusing capacity of carbon monoxide (DLCO) between January 1st, 2010 and August 31st, 2015. Patients who did not have a 6MWT within 90 days of a selected PFT and an echocardiogram within 180 days of a matched pair of PFT and 6MWT were excluded. Patients with echocardiographic features of pulmonary hypertension or systolic dysfunction were also excluded. Demographic variables and results from diagnostic testing (PFT and 6MWT performed according to ATS criteria) and echocardiogram were collected. Mean values and percentages were calculated for linear and categorical variables. Two-sample t-tests were performed for continuous variables comparing the IIP and CTD-ILD groups. Linear regression analysis of %predicted DLCO adjusted for hemoglobin (%pred adjDLCO) with degree of desaturation on 6MWT by group was performed. Results: Forty-two of the 438 ILD patients who underwent PFTs, 6MWT and echocardiogram met full inclusion criteria: 24 with IIP and 18 with CTD-ILD. Patients with IIP were older (mean age 63 years) than those with CTD-ILD (mean age 50 years). The majority of patients with IIP were male (75%) while only 33.3% of the CTD-ILD group were male. Despite similar mean %pred adjDLCO, more patients with IIP (45.8%) required supplemental oxygen, compared to 22.2% of CTD-ILD patients. There were no significant differences in mean %predicted FVC, baseline Borg dyspnea or fatigue scores, or degree of desaturation on 6MWT between the two groups. There was no significant correlation of %pred adjDLCO with change in oxygen saturation during 6MWT for the IIP or CTD-ILD groups, after control for amount of supplemental oxygen worn. Conclusions: In this single center cohort of IIP and CTD-ILD patients, the %pred adjDLCO did not correlate with the degree of desaturation during 6MWT, despite a higher percentage of patients with IIP requiring supplemental oxygen. Small sample size and use of supplemental oxygen during 6MWT in about 1/3 of the patients may have influenced our findings

Atomistic Investigation of the Electronic Structure, Thermal Properties and Conduction Defects in Ge-rich GexSe1-x Materials for Selector Applications

status: publishe