IoMT-Driven eHealth: A Technological Innovation Proposal Based on Smart Speakers

Internet of Medical Things (IoMT) is a technological concept applied in healthcare contexts to achieve the digital interconnection of everyday objects with the Internet in order to make life easier for people. IoMT can help monitor, inform and notify not only caregivers, but provide healthcare providers with actual data to identify issues before they become critical or to allow for earlier invention. In this sense, this paper is contextualized in Assisted Repro duction Treatment (ART) processes to reduce the number of hospital visits, reduce healthcare costs and improve patientcare, as well as the productivity of the healthcare professional. So, we present an IoMT-based technological pro posal to manage and control the prescription of pharmacological treatments to patients who are carried out ART processes. In this context, we propose the integration of iMEDEA (modular system specialized in the management of electronic clinical records for ART unit) and smart speaker devices (specifically, Amazon’s Alexa), as well as the validation of our proposal in the real envi ronment offered by Inebir clinicMinisterio de Economía y Competitividad TIN2016-76956-C3-2-R (POLOLAS)Junta de Andalucía AT17-5904-US

Structure and Function of ABCG2-Rich Extracellular Vesicles Mediating Multidrug Resistance

Multidrug resistance (MDR) is a major impediment to curative cancer chemotherapy. The ATP-Binding Cassette transporters ABCG2, ABCB1 and ABCC2 form a unique defense network against multiple structurally and functionally distinct chemotherapeutics, thereby resulting in MDR. Thus, deciphering novel mechanisms of MDR and their overcoming is a major goal of cancer research. Recently we have shown that overexpression of ABCG2 in the membrane of novel extracellular vesicles (EVs) in breast cancer cells results in mitoxantrone resistance due to its dramatic sequestration in EVs. However, nothing is known about EVs structure, biogenesis and their ability to concentrate multiple antitumor agents. To this end, we here found that EVs are structural and functional homologues of bile canaliculi, are apically localized, sealed structures reinforced by an actin-based cytoskeleton and secluded from the extracellular milieu by the tight junction proteins occludin and ZO-1. Apart from ABCG2, ABCB1 and ABCC2 were also selectively targeted to the membrane of EVs. Moreover, Ezrin-Radixin-Moesin protein complex selectively localized to the border of the EVs membrane, suggesting a key role for the tethering of MDR pumps to the actin cytoskeleton. The ability of EVs to concentrate and sequester different antitumor drugs was also explored. Taking advantage of the endogenous fluorescence of anticancer drugs, we found that EVs-forming breast cancer cells display high level resistance to topotecan, imidazoacridinones and methotrexate via efficient intravesicular drug concentration hence sequestering them away from their cellular targets. Thus, we identified a new modality of anticancer drug compartmentalization and resistance in which multiple chemotherapeutics are actively pumped from the cytoplasm and highly concentrated within the lumen of EVs via a network of MDR transporters differentially targeted to the EVs membrane. We propose a composite model for the structure and function of MDR pump-rich EVs in cancer cells and their ability to confer multiple anticancer drug resistance

Do specialty registrars change their attitudes, intentions and behaviour towards reporting incidents following a patient safety course?

<p>Abstract</p> <p>Background</p> <p>Reporting incidents can contribute to safer health care, as an awareness of the weaknesses of a system could be considered as a starting point for improvements. It is believed that patient safety education for specialty registrars could improve their attitudes, intentions and behaviour towards incident reporting. The objective of this study was to examine the effect of a two-day patient safety course on the attitudes, intentions and behaviour concerning the voluntary reporting of incidents by specialty registrars.</p> <p>Methods</p> <p>A patient safety course was designed to increase specialty registrars' knowledge, attitudes and skills in order to recognize and cope with unintended events and unsafe situations at an early stage. Data were collected through an 11-item questionnaire before, immediately after and six months after the course was given.</p> <p>Results</p> <p>The response rate at all three points in time assessed was 100% (n = 33). There were significant changes in incident reporting attitudes and intentions immediately after the course, as well as during follow-up. However, no significant changes were found in incident reporting behaviour.</p> <p>Conclusions</p> <p>It is shown that patient safety education can have long-term positive effects on attitudes towards reporting incidents and the intentions of registrars. However, further efforts need to be undertaken to induce a real change in behaviour.</p

Air–liquid interface cultures enhance the oxygen supply and trigger the structural and functional differentiation of intestinal porcine epithelial cells (IPEC)

The specific function of the epithelium as critical barrier between the intestinal lumen and the organism’s internal microenvironment is reflected by permanent maintenance of intercellular junctions and cellular polarity. The intestinal epithelial cells are responsible for absorption of nutritional components, facing mechanical stress and a changing oxygen supplementation via blood stream. Oxygen itself can regulate the barrier and the absorptive function of the epithelium. Therefore, we compared the dish cell culture, the transwell-like membrane culture and the oxygen enriched air–liquid interface (ALI) culture. We demonstrated strong influence of the different culture conditions on morphology and function of intestinal porcine epithelial cell lines in vitro. ALI culture resulted in a significant increase in cell number, epithelial cell layer thickness and expression as well as apical localisation of the microvilli-associated protein villin. Remarkable similarities regarding the morphological parameters were observed between ALI cultures and intestinal epithelial cells in vivo. Furthermore, the functional analysis of protein uptake and degradation by the epithelial cells demonstrated the necessity of sufficient oxygen supply as achieved in ALI cultures. Our study is the first report providing marked evidence that optimised oxygen supply using ALI cultures directly affects the morphological differentiation and functional properties of intestinal epithelial cells in vitro

Does advancing male age influence the expression levels and localisation patterns of phospholipase C zeta (PLCζ) in human sperm?

Socio-economic factors have led to an increasing trend for couples to delay parenthood. However, advancing age exerts detrimental effects upon gametes which can have serious consequences upon embryo viability. While such effects are well documented for the oocyte, relatively little is known with regard to the sperm. One fundamental role of sperm is to activate the oocyte at fertilisation, a process initiated by phospholipase C zeta (PLCζ), a sperm-specific protein. While PLCζ deficiency can lead to oocyte activation deficiency and infertility, it is currently unknown whether the expression or function of PLCζ is compromised by advancing male age. Here, we evaluate sperm motility and the proportion of sperm expressing PLCζ in 71 males (22–54 years; 44 fertile controls and 27 infertile patients), along with total levels and localisation patterns of PLCζ within the sperm head. Three different statistical approaches were deployed with male age considered both as a categorical and a continuous factor. While progressive motility was negatively correlated with male age, all three statistical models concurred that no PLCζ–related parameter was associated with male age, suggesting that advancing male age is unlikely to cause problems in terms of the sperm’s fundamental ability to activate an oocyt

Effect of Cytoskeletal Disruption on Mechanotransduction of Hydrostatic Pressure by C3H10T1/2 Murine Fibroblasts

Cyclic hydrostatic pressure of physiological magnitude (< 10 MPa) stimulates chondrogenic differentiation of mesenchymal stem cells, but mechanotransduction mechanisms are not well understood. It was hypothesized that an intact cytoskeleton would be required for uninhibited mechanotransduction of hydrostatic pressure. Therefore we examined the effects of drugs which selectively interfere with actin and tubulin polymerization on pressure-induced upregulation of aggrecan and col2a1 (type II collagen) mRNA expression. C3H10T1/2 cells were cultured as pellets in either 4µM cytochalasin D or 4µM nocodazole and subjected to 3 days of cyclic hydrostatic compression (1 Hz, 5 MPa, 2 h per day). Phalloidin staining and indirect immunostaining with anti α-tubulin antibody confirmed disruption of microfilament and microtubule assemblies, respectively. Real time RT-PCR revealed that both drugs substantially lowered the basal level of aggrecan and col2a1 mRNA, but that neither drug prevented a pressure-stimulated increase in gene expression relative to the altered basal state. Thus upregulation of macromolecular gene expression by cyclic hydrostatic pressure did not require a completely intact cytoskeleton

Multi-dimensional knowledge of malaria among Nigerian caregivers: implications for insecticide-treated net use by children

Abstract Background Poor malaria knowledge can negatively impact malaria control programmes. This study evaluates knowledge distribution in the domains of causation, transmission, vulnerability, symptoms, and treatment of malaria. It assesses the association between a caregiver’s knowledge about malaria and ownership and use of insecticide-treated nets (ITNs) by children. Methods Some 1939 caregivers of young children were recruited through a school-based survey in two Nigerian states. A 20-item, multi-dimensional survey instrument was developed and used to rank each caregiver’s knowledge in five dimensions (cause, transmission, vulnerability, symptoms, treatment of malaria). Scores for each domain were used to create an aggregate knowledge score for each caregiver. The outcome measures were ITN ownership, and ITN use the night and week before the study. Regression models were used to evaluate the relationship between caregiver’s knowledge (individual domains and aggregate score) and ownership and use of ITN after controlling for likely confounders. Results The main predictor of ITN use was ITN ownership (r = 0.653; p < 0.001); however, ownership only explains 43 % of variance in net use. Total knowledge index for the study population was significantly associated with both ITN ownership (r = 0.122; p = 0.001) and use (r = 0.095; p = 0.014). The spectrum of caregiver’s knowledge of malaria and its causes captured in the various domains was, however, found to be poor. Fifty percent of the respondents knew that malaria is transmitted by female mosquitoes and 65 % still believe that too much exposure to the sun is a risk factor for malaria. Knowledge of populations most vulnerable to malaria (83 %) and knowledge of malaria transmission (32 %) were the domains with the highest and lowest average correct answers. Conclusions There is a need to improve ITN coverage in Nigeria as ITN ownership was associated with ITN use. Additionally, treating knowledge as a multi-dimensional phenomenon revealed that a lot of misperceptions about malaria still exist. Distribution of ITNs through the public/private sector may need to be augmented with tailored behavioural change communication to dispel myths and improve the multi-dimensional knowledge of malaria in the local population.http://deepblue.lib.umich.edu/bitstream/2027.42/134666/1/12936_2016_Article_1557.pd

Two Distinct Integrin-Mediated Mechanisms Contribute to Apical Lumen Formation in Epithelial Cells

Background: Formation of apical compartments underlies the morphogenesis of most epithelial organs during development. The extracellular matrix (ECM), particularly the basement membrane (BM), plays an important role in orienting the apico-basal polarity and thereby the positioning of apical lumens. Integrins have been recognized as essential mediators of matrix-derived polarity signals. The importance of b1-integrins in epithelial polarization is well established but the significance of the accompanying a-subunits have not been analyzed in detail. Principal Findings: Here we demonstrate that two distinct integrin-dependent pathways regulate formation of apical lumens to ensure robust apical membrane biogenesis under different microenvironmental conditions; 1) a2b1- and a6b4integrins were required to establish a basal cue that depends on Rac1-activity and guides apico-basal cell polarization. 2) a3b1-integrins were implicated in positioning of mitotic spindles in cysts, a process that is essential for Cdc42-driven epithelial hollowing. Significance: Identification of the separate processes driven by particular integrin receptors clarifies the functional hierarchies between the different integrins co-expressed in epithelial cells and provides valuable insight into the complexity of cell-ECM interactions thereby guiding future studies addressing the molecular basis of epithelial morphogenesis durin