Interactive exploration of population scale pharmacoepidemiology datasets

Population-scale drug prescription data linked with adverse drug reaction (ADR) data supports the fitting of models large enough to detect drug use and ADR patterns that are not detectable using traditional methods on smaller datasets. However, detecting ADR patterns in large datasets requires tools for scalable data processing, machine learning for data analysis, and interactive visualization. To our knowledge no existing pharmacoepidemiology tool supports all three requirements. We have therefore created a tool for interactive exploration of patterns in prescription datasets with millions of samples. We use Spark to preprocess the data for machine learning and for analyses using SQL queries. We have implemented models in Keras and the scikit-learn framework. The model results are visualized and interpreted using live Python coding in Jupyter. We apply our tool to explore a 384 million prescription data set from the Norwegian Prescription Database combined with a 62 million prescriptions for elders that were hospitalized. We preprocess the data in two minutes, train models in seconds, and plot the results in milliseconds. Our results show the power of combining computational power, short computation times, and ease of use for analysis of population scale pharmacoepidemiology datasets. The code is open source and available at: https://github.com/uit-hdl/norpd_prescription_analyse

Analysis and study of hospital communication via social media from the patient perspective

Currently, the online interaction between citizens and hospitals is poor, as users believe that there are shortcomings that could be improved. This study analyzes patients’ opinions of the online communication strategies of hospitals in Spain. Therefore, a mixed-method is proposed. Firstly, a qualitative analysis through a focus-group was carried out, so around twenty representatives of national, regional and local patients’ associations were brought together. Secondly, the research is supplemented with a content assessment of the Twitter activity of the most influential hospitals in Spain. The results reveal that the general public appreciate hospitals’ communication potential through social media, although they are generally unaware of how it works. The group says that, apart from the lack of interaction, they find it hard to understand certain messages, and some publications give a biased picture. In order to improve communication, patients and relatives are demanding that their perspective be taken into consideration in the messages issued to enhance the quality of life and well-being of society

Bicyclic Boronate β-Lactamase Inhibitors: The Present Hope against Deadly Bacterial Pathogens

The use of β-lactamase inhibitors in combination with β-lactam antibiotics is an emerging area in drug discovery. This strategy allows the restoration of the therapeutic efficacy of these antibiotics in clinical use against multiresistant bacteria. These pathogens are drug resistant because they express β-lactamase enzymes, which prevent the antibiotic therapeutic action by catalyzing the hydrolysis of the β-lactam ring. These enzymes are quite diverse in both their structural architecture and hydrolytic capability, as well as in the mechanism of action. The ever-increasing emergence of pathogens that are capable of coproducing different types of β-lactamases has triggered the search for ultrabroad-spectrum inhibitors capable of deactivating both serine- and metallo-β-lactamases. A recent breakthrough in this long-pursued and unmet need is the discovery of bicyclic boronate inhibitors, specifically taniborbactam, VNRX-7145, and QPX7728, which are currently under clinical development in combination with cefepime, ceftibuten, and QPX2014, respectively. The present article highlights the therapeutic potential of these inhibitors and their spectrum of efficacy is compared with those of other β-lactam/β-lactamase inhibitor combinations recently approved by the food and drug administration. The molecular basis of the ultrabroad-spectrum of activity of boron-based inhibitors is also discussed, on the basis of the available crystal structures and the results of computational studiesinancial support from the Spanish Ministry of Economy and Competiveness (SAF2016-75638-R, PID2019-105512RB-I00), the Xunta de Galicia [ED431B 2018/04 and Centro singular de investigación de Galicia accreditation 2019–2022 (ED431G 2019/03)], and the European Regional Development Fund (ERDF) is gratefully acknowledgedS

Emerging methods in therapeutics using multifunctional nanoparticles

Clinical translation of nanoparticle‐based drug delivery systems is hindered by an array of challenges including poor circulation time and limited targeting. Novel approaches including designing multifunctional particles, cell‐mediated delivery systems, and fabrications of protein‐based nanoparticles have gained attention to provide new perspectives to current drug delivery obstacles in the interdisciplinary field of nanomedicine. Collectively, these nanoparticle devices are currently being investigated for applications spanning from drug delivery and cancer therapy to medical imaging and immunotherapy. Here, we review the current state of the field, highlight opportunities, identify challenges, and present the future directions of the next generation of multifunctional nanoparticle drug delivery platforms.This article is categorized under:Biology‐Inspired Nanomaterials > Protein and Virus‐Based StructuresNanotechnology Approaches to Biology > Nanoscale Systems in BiologyNovel approaches in designing nanoparticles to overcome challenges faced by traditional nanoparticle‐based drug delivery systems.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155963/1/wnan1625.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155963/2/wnan1625_am.pd

Cerium Oxide Nanoparticles: Advances in Biodistribution, Toxicity, and Preclinical Exploration

Antioxidant nanoparticles have recently gained tremendous attention for their enormous potential in biomedicine. However, discrepant reports of either medical benefits or toxicity, and lack of reproducibility of many studies, generate uncertainties delaying their effective implementation. Herein, the case of cerium oxide is considered, a well‐known catalyst in the petrochemistry industry and one of the first antioxidant nanoparticles proposed for medicine. Like other nanoparticles, it is now described as a promising therapeutic alternative, now as threatening to health. Sources of these discrepancies and how this analysis helps to overcome contradictions found for other nanoparticles are summarized and discussed. For the context of this analysis, what has been reported in the liver is reviewed, where many diseases are related to oxidative stress. Since well‐dispersed nanoparticles passively accumulate in liver, it represents a major testing field for the study of new nanomedicines and their clinical translation. Even more, many contradictory works have reported in liver either cerium‐oxide‐associated toxicity or protection against oxidative stress and inflammation. Based on this, finally, the intention is to propose solutions to design improved nanoparticles that will work more precisely in medicine and safely in society

Functional evidence of mTORβ splice variant involvement in the pathogenesis of congenital heart defects

mTOR dysregulation has been described in pathological conditions, such as cardiovascular and overgrowth disorders. Here we report on the first case of a patient with a complex congenital heart disease and an interstitial duplication in the short arm of chromosome 1, encompassing part of the mTOR gene. Our results suggest that an intragenic mTOR microduplication might play a role in the pathogenesis of non-syndromic congenital heart defects (CHDs) due to an upregulation of mTOR/Rictor and consequently an increased phosphorylation of PI3K/AKT and MEK/ERK signaling pathways in patient-derived amniocytes. This is the first report which shows a causative role of intragenic mTOR microduplication in the etiology of an isolated complex CHD

Pseudomonas aeruginosa quorum sensing systems as drug discovery targets: current position and future perspectives

Antimicrobial resistance (AMR) is a serious threat to public health globally, manifested by the frequent emergence of multi-drug resistant pathogens that render current chemotherapy inadequate. Health organizations worldwide have recognized the severity of this crisis and implemented action plans to contain its adverse consequences and prolong the utility of conventional antibiotics. Hence, there is a pressing need for new classes of antibacterial agents with novel modes of action. Quorum sensing (QS), a communication system employed by bacterial populations to co-ordinate virulence gene expression, is a potential target that has been intensively investigated over the last decade. This Perspective will focus on recent advances in targeting the three main quorum sensing systems (las, rhl and pqs) of a major opportunistic human pathogen, Pseudomonas aeruginosa, and will specifically evaluate the medicinal chemistry strategies devised to develop QS inhibitors from a drug discovery perspective

Research findings from the Memories of Nursing oral history project.

Capturing the stories of nurses who practised in the past offers the opportunity to reflect on the changes in practice over time to determine lessons for the future. This article shares some of the memories of a group of 16 nurses who were interviewed in Bournemouth, UK, between 2009 and 2016. Thematic analysis of the interview transcripts identified a number of themes, three of which are presented: defining moments, hygiene and hierarchy. The similarities and differences between their experiences and contemporary nursing practice are discussed to highlight how it may be timely to think back in order to take practice forward positively in the future

The Impact of 3D Printing on Trade and FDI

This paper analyzes the effects of 3D printing technologies on the volume of trade and on the structure of FDI. A standard model with firm-specific heterogeneity generates three main predictions. First, 3D printers are introduced in areas with high economic activity that also face high transport costs. Second, technological progress related to 3D printing machines leads to a gradual replacement of FDI that relies on traditional production structures with FDI based on 3D printing techniques. At this stage international trade stays unaffected. Finally, at later stages, with 3D printing machines being widely used, further technological progress in 3D printing leads to a gradual replacement of international trade. Empirical evidence indicates that countries subject to higher transport costs and with high levels of economic activity are indeed among the ones that import more 3D printers. Anecdotal evidence also supports the second and third predictions of the model