Bench-to-bedside review : targeting antioxidants to mitochondria in sepsis

Peer reviewedPublisher PD

Personal Drug Selection: Problem-Based Learning in Pharmacology: Experience from a Medical School in Nepal

BACKGROUND: At the Manipal College of Medical Sciences, Pokhara, Nepal, Pharmacology is taught during the first four semesters of the undergraduate medical course. Personal or P-drug selection is an important exercise. The present study was carried out to obtain student opinion about the P-drug learning sessions, the assessment examinations, and on the small group dynamics. METHOD: The practical sessions on P-drug selection are carried out in small groups. Student feedback about the session was obtained using focus group discussions. The focus groups were selected to represent both genders and the three main nationalities, Nepalese, Indians, and Sri Lankans. There were four Nepalese, five Indians, and three Sri Lankans. Within each nationality and gender category the students were randomly selected. The respondents were explained the objectives of the study and were invited to participate. Written informed consent was obtained. The discussion lasted around two hours and was conducted in the afternoon in two groups of six students each. The first author (PRS) acted as a facilitator. The responses were recorded and analyzed qualitatively. RESULTS: The overall student opinion was positive. Around 25% (3 respondents) of respondents were confused about whether P-drugs were for a disease or a patient. Group consensus was commonly used to give numerical values for the different criteria. The large number of brands created problems in calculating cost. The students wanted more time for the exercise in the examination. Formative assessment during the learning sessions may be considered. The group members usually got along well. Absenteeism was a problem and not all members put in their full effort. The physical working environment should be improved. CONCLUSIONS: Based on what the students say, the sessions on P-drugs should be continued and strengthened. Modifications in the sessions are required. Sessions during the clinical years and internship training can be considered

A Mass Spectrometry-Based Approach for Mapping Protein Subcellular Localization Reveals the Spatial Proteome of Mouse Primary Neurons

We previously developed a mass spectrometry-based method, Dynamic Organellar Maps, for the determination of protein subcellular localisation, and the identification of translocation events in comparative experiments. The use of metabolic labelling for quantification (SILAC) renders the method best suited to cells grown in culture. Here we have adapted the workflow to both label-free quantification (LFQ) and chemical labelling/multiplexing strategies (Tandem Mass Tagging, TMT). Both new methods are highly effective for generation of organellar maps and capture of protein translocations. Furthermore, application of label-free organellar mapping to acutely isolated mouse primary neurons provided subcellular localisation and copy number information for over 8,000 proteins, allowing a detailed analysis of organellar organisation. Our study extends the scope of Dynamic Organellar Maps to any cell type or tissue, and also to high throughput screening.This work was funded by the German Research Foundation (DFG/Gottfried Wilhelm Leibniz Prize MA 1764/2-1), the Louis-Jeantet Foundation, the Max Planck Society for the Advancement of Science, a Wellcome Trust Senior Clinical Research Fellowship 108070/Z/15/Z (to M.P.W.), and a strategic award to Cambridge Institute for Medical Research from the Wellcome Trust (100140)

Urban blue space renovation and local resident and visitor well-being: A case study from Plymouth, UK

This is the final version. Available on open access from Elsevier via the DOI in this recordObservational studies have suggested that people with better access to attractive, safe, and inclusive blue spaces enjoy higher psychological well-being, with particular benefits for those living in deprived urban areas. However, intervention studies are scarce. To help bridge this gap we conducted a repeat cross-sectional study exploring local resident and visitor well-being before and after a small-scale intervention aimed at improving the quality of an urban beach area in a deprived neighbourhood in Plymouth, United Kingdom. Physical alterations were co-created with local stakeholders and residents, and accompanied by a series of on-site community events. Key outcomes were self-reported psychological well-being, satisfaction with personal safety and community belonging, and perceptions of site quality. Adjusted linear models showed that positive well-being (B = 7.42; 95% CI = 4.18–10.67) and life satisfaction (B = 0.40; 95% CI = 0.11–0.70) were both higher after the intervention compared to before, with associations for life satisfaction stronger among those who visited the site in the last four weeks. Associations with positive well-being were partially mediated by greater satisfaction with community belonging; and associations with life satisfaction were partially and independently mediated by greater satisfaction with personal safety and community belonging. Although caution needs to be taken due to the repeat cross-sectional design and the sampling of site visitors as well as local residents, the findings support the idea that environmental improvements to urban blue spaces can foster better psychological well-being, and underline the importance of community involvement in the process.European Union Horizon 2020Amsterdam Public Health Research Institut

Detection, Isolation and Confirmation of Crimean-Congo Hemorrhagic Fever Virus in Human, Ticks and Animals in Ahmadabad, India, 2010–2011

A nosocomial outbreak of CCHFV occurred in January 2011, in a tertiary care hospital in Ahmadabad, Gujarat State in western India. Out of a total five cases reported, contact transmission occurred to three treating medical professionals, all of whom succumbed to the disease. The only survivor was the husband of the index case. These results highlight the importance of considering CCHFV as a potential aetiology for Hemorrhagic fever (HF) cases in India. This also underlines the need for strict barrier nursing and patient isolation while managing these patients. During the investigation presence of CCHFV RNA in Hyalomma anatolicum ticks and livestock were detected in the village from where the primary case (case A) was reported. Further retrospective investigation confirmed two CCHF human cases in Rajkot village 20 kilometres to the west of Ahmadabad in 2010, and CCHFV presence in the livestock 200 kilometres to the north in the neighbouring State Rajasthan. This report shows the presence of CCHFV in human, ticks and animals in Gujarat, India. The fact of concern is the spread of this disease from one state to another due to trading of livestock

Unsupervised joint PoS tagging and stemming for agglutinative languages

This is an accepted manuscript of an article published by Association for Computing Machinery (ACM) in ACM Transactions on Asian and Low-Resource Language Information Processing on 25/01/2019, available online: https://doi.org/10.1145/3292398 The accepted version of the publication may differ from the final published version.The number of possible word forms is theoretically infinite in agglutinative languages. This brings up the out-of-vocabulary (OOV) issue for part-of-speech (PoS) tagging in agglutinative languages. Since inflectional morphology does not change the PoS tag of a word, we propose to learn stems along with PoS tags simultaneously. Therefore, we aim to overcome the sparsity problem by reducing word forms into their stems. We adopt a Bayesian model that is fully unsupervised. We build a Hidden Markov Model for PoS tagging where the stems are emitted through hidden states. Several versions of the model are introduced in order to observe the effects of different dependencies throughout the corpus, such as the dependency between stems and PoS tags or between PoS tags and affixes. Additionally, we use neural word embeddings to estimate the semantic similarity between the word form and stem. We use the semantic similarity as prior information to discover the actual stem of a word since inflection does not change the meaning of a word. We compare our models with other unsupervised stemming and PoS tagging models on Turkish, Hungarian, Finnish, Basque, and English. The results show that a joint model for PoS tagging and stemming improves on an independent PoS tagger and stemmer in agglutinative languages.This research is supported by the Scientific and Technological Research Council of Turkey (TUBITAK) with the project number EEEAG-115E464.Published versio

Therapeutic Potential of Phytoconstituents in Management of Alzheimer’s Disease

Since primitive times, herbs have been extensively used in conventional remedies for boosting cognitive impairment and age-associated memory loss. It is mentioned that medicinal plants have a variety of dynamic components, and they have become a prominent choice for synthetic medications for the care of cognitive and associated disorders. Herbal remedies have played a major role in the progression of medicine, and many advanced drugs have already been developed. Many studies have endorsed practicing herbal remedies with phytoconstituents, for healing Alzheimer’s disease (AD). All the information in this article was collated from selected research papers from online scientific databases, such as PubMed, Web of Science, and Scopus. The aim of this article is to convey the potential of herbal remedies for the prospect management of Alzheimer’s and related diseases. Herbal remedies may be useful in the discovery and advancement of drugs, thus extending new leads for neurodegenerative diseases such as AD. Nanocarriers play a significant role in delivering herbal medicaments to a specific target. Therefore, many drugs have been described for the management of age-linked complaints such as dementia, AD, and the like. Several phytochemicals are capable of managing AD, but their therapeutic claims are restricted due to their lower solubility and metabolism. These limitations of natural therapeutics can be overcome by using a targeted nanocarrier system. This article will provide the primitive remedies as well as the development of herbal remedies for AD management.</jats:p