Membrane estrogen receptor-α levels in MCF-7 breast cancer cells predict cAMP and proliferation responses

INTRODUCTION: 17β-estradiol (E(2)) can rapidly induce cAMP production, but the conditions under which these cAMP levels are best measured and the signaling pathways responsible for the consequent proliferative effects on breast cancer cells are not fully understood. To help resolve these issues, we compared cAMP mechanistic responses in MCF-7 cell lines selected for low (mER(low)) and high (mER(high)) expression of the membrane form of estrogen receptor (mER)-α, and thus addressed the receptor subform involved in cAMP signaling. METHODS: MCF-7 cells were immunopanned and subsequently separated by fluorescence activated cell sorting into mER(high )(mER-α-enriched) and mER(low )(mER-α-depleted) populations. Unique (compared with previously reported) incubation conditions at 4°C were found to be optimal for demonstrating E(2)-induced cAMP production. Time-dependent and dose-dependent effects of E(2 )on cAMP production were determined for both cell subpopulations. The effects of forskolin, 8-CPT cAMP, protein kinase A inhibitor (H-89), and adenylyl cyclase inhibitor (SQ 22,536) on E(2)-induced cell proliferation were assessed using the crystal violet assay. RESULTS: We demonstrated a rapid and transient cAMP increase after 1 pmol/l E(2 )stimulation in mER(high )cells; at 4°C these responses were much more reliable and robust than at 37°C (the condition most often used). The loss of cAMP at 37°C was not due to export. 3-Isobutyl-1-methylxanthine (IBMX; 1 mmol/l) only partially preserved cAMP, suggesting that multiple phosphodiesterases modulate its level. The accumulated cAMP was consistently much higher in mER(high )cells than in mER(low )cells, implicating mER-α levels in the process. ICI172,780 blocked the E(2)-induced response and 17α-estradiol did not elicit the response, also suggesting activity through an estrogen receptor. E(2 )dose-dependent cAMP production, although biphasic in both cell types, was responsive to 50-fold higher E(2 )concentrations in mER(high )cells. Proliferation of mER(low )cells was stimulated over the whole range of E(2)concentrations, whereas the number of mER(high )cells was greatly decreased at concentrations above 1 nmol/l, suggesting that estrogen over-stimulation can lead to cell death, as has previously been reported, and that mER-α participates. E(2)-mediated activation of adenylyl cyclase and downstream participation of protein kinase A were shown to be involved in these responses. CONCLUSION: Rapid mER-α-mediated nongenomic signaling cascades generate cAMP and downstream signaling events, which contribute to the regulation of breast cancer cell number

The burden and risks of pediatric pneumonia in Nigeria: A desk‐based review of existing literature and data

Background: Pneumonia is a leading killer of children under‐5 years, with a high burden in Nigeria. We aimed to quantify the regional burden and risks of pediatric pneumonia in Nigeria, and specifically the states of Lagos and Jigawa. / Methods: We conducted a scoping literature search for studies of pneumonia morbidity and mortality in under‐5 children in Nigeria from 10th December 2018 to 26th April 2019, searching: Cochrane, PubMed, and Web of Science. We included grey literature from stakeholders' websites and information shared by organizations working in Nigeria. We conducted multivariable logistic regression using the 2016 to 2017 Multiple Cluster Indicators Survey data set to explore factors associated with pneumonia. Descriptive analyses of datasets from 2010 to 2019 was done to estimate trends in mortality, morbidity, and vaccination coverage. / Results: We identified 25 relevant papers (10 from Jigawa, 8 from Lagos, and 14 national data). None included data on pneumonia or acute respiratory tract infection burden in the health system, inpatient case‐fatality rates, severity, or age‐specific pneumonia mortality rates at state level. Secondary data analysis found that no household or caregiver socioeconomic indicators were consistently associated with self‐reported symptoms of cough and/or difficulty breathing, and seasonality was inconsistently associated, dependant on region. / Conclusion: There is a clear evidence gap around the burden of pediatric pneumonia in Nigeria, and challenges with the interpretation of existing household survey data. Improved survey approaches are needed to understand the risks of pediatric pneumonia in Nigeria, alongside the need for investment in reliable routine data systems to provide data on the clinical pneumonia burden in Nigeria

Health system challenges for improved childhood pneumonia case management in Lagos and Jigawa, Nigeria

Background: Case fatality rates for childhood pneumonia in Nigeria remain high. There is a clear need for improved case management of pneumonia, through the sustainable implementation of the Integrated Management of Childhood Illnesses (IMCI) diagnostic and treatment algorithms. We explored barriers and opportunities for improved case management of childhood pneumonia in Lagos and Jigawa states, Nigeria. / Methods: A mixed‐method analysis was conducted to assess the current health system capacity to deliver quality care. This was done through audits of 16 facilities in Jigawa and 14 facilities in Lagos, questionnaires (n = 164) and 13 focus group discussions with providers. Field observations provided context for data analysis and triangulation. / Results: There were more private providers in Lagos (4/8 secondary facilities) and more government providers in Jigawa (4/8 primary, 3/3 secondary, and 1/1 tertiary facilities). Oxygen and pulse oximeters were available in two of three in Jigawa and six of eight in Lagos of the sampled secondary care facilities. None of the eight primary facilities surveyed in Jigawa had oxygen or pulse oximetry available while in Lagos two of three primary facilities had oxygen and one of three had pulse oximeters. Other IMCI and emergency equipment were also lacking including respiratory rate timers, particularly in Jigawa state. Health care providers scored poorly on knowledge of IMCI, though previous IMCI training was associated with better knowledge. Key enabling factors in delivering pediatric care highlighted by health care providers included accountability procedures and feedback loops, the provision of free medication for children, and philanthropic acts. Common barriers to provide care included the burden of out‐of‐pocket payments, challenges in effective communication with caregivers, delayed presentation, and lack of clear diagnosis, and case management guidelines. / Conclusion: There is an urgent need to improve how the prevention and treatment of pediatric pneumonia is directed in both Lagos and Jigawa. Priority areas for reducing pediatric pneumonia burden are training and mentoring of health care providers, community health education, and introduction of oximeters and oxygen supply

Rapid production of large-area, transparent and stretchable electrodes using metal nanofibers as wirelessly operated wearable heaters

A rapidly growing interest in wearable electronics has led to the development of stretchable and transparent heating films that can replace the conventional brittle and opaque heaters. Herein, we describe the rapid production of large-area, stretchable and transparent electrodes using electrospun ultra-long metal nanofibers (mNFs) and demonstrate their potential use as wirelessly operated wearable heaters. These mNF networks provide excellent optoelectronic properties (sheet resistance of similar to 1.3 O per sq with an optical transmittance of similar to 90%) and mechanical reliability (90% stretchability). The optoelectronic properties can be controlled by adjusting the area fraction of the mNF networks, which also enables the modulation of the power consumption of the heater. For example, the low sheet resistance of the heater presents an outstanding power efficiency of 0.65 W cm(-2) (with the temperature reaching 250 degrees C at a low DC voltage of 4.5 V), which is similar to 10 times better than the properties of conventional indium tin oxide-based heaters. Furthermore, we demonstrate the wireless fine control of the temperature of the heating film using Bluetooth smart devices, which suggests substantial promise for the application of this heating film in next-generation wearable electronics

Correction: Management of Cardiovascular Disease Patients With Confirmed or Suspected COVID-19 in Limited Resource Settings.

[This corrects the article DOI: 10.5334/gh.823.]

Management of Cardiovascular Disease Patients With Confirmed or Suspected COVID-19 in Limited Resource Settings

In this paper, we provide recommendations on the management of cardiovascular disease (CVD) among patients with confirmed or suspected coronavirus disease (COVID-19) to facilitate the decision making of healthcare professionals in low resource settings. The emergence of novel coronavirus disease, also known as Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2), has presented an unprecedented global challenge for the healthcare community. The ability of SARS-CoV-2 to get transmitted during the asymptomatic phase and its high infectivity have led to the rapid transmission of COVID-19 beyond geographic regions, leading to a pandemic. There is concern that COVID-19 is cardiotropic, and it interacts with the cardiovascular system on multiple levels. Individuals with established CVD are more susceptible to severe COVID-19. Through a consensus approach involving an international group this WHF statement summarizes the links between cardiovascular disease and COVID-19 and present some practical recommendations for the management of hypertension and diabetes, acute coronary syndrome, heart failure, rheumatic heart disease, Chagas disease, and myocardial injury for patients with COVID-19 in low-resource settings. This document is not a clinical guideline and it is not intended to replace national clinical guidelines or recommendations. Given the rapidly growing burden posed by COVID-19 illness and the associated severe prognostic implication of CVD involvement, further research is required to understand the potential mechanisms linking COVID-19 and CVD, clinical presentation, and outcomes of various cardiovascular manifestations in COVID-19 patients

Thermoplastic lignocellulose materials: A review on recent advancement and utilities

Lignocellulosic biomass is the most abundantly available resource in nature. However, its potential as a replacement of oil in plastic production has not been fully exploited. To reduce the carbon footprint, the use of lignocellulose biomass to produce bio-based plastics is attracting increasing global interest. The aim of this review article is to systematically summarize the recent advancements of the development of lignocellulose materials that possess thermoplastic properties, meaning they can be processed/shaped by common plastic processing techniques. The approaches used for modification of lignocellulose biomass and the properties of the modified materials, as well as factors affecting the properties of these, are discussed. The regulatory aspects and policy directions of bio-based plastics, including thermoplastic lignocellulose, are also mentioned. Current challenges of producing thermoplastic lignocellulose and the way forward to solve this are also explored