Neuropathological findings processed by artificial neural networks (ANNs) can perfectly distinguish Alzheimer's patients from controls in the Nun Study

<p>Abstract</p> <p>Background</p> <p>Many reports have described that there are fewer differences in AD brain neuropathologic lesions between AD patients and control subjects aged 80 years and older, as compared with the considerable differences between younger persons with AD and controls. In fact some investigators have suggested that since neurofibrillary tangles (NFT) can be identified in the brains of non-demented elderly subjects they should be considered as a consequence of the aging process. At present, there are no universally accepted neuropathological criteria which can mathematically differentiate AD from healthy brain in the oldest old.</p> <p>The aim of this study is to discover the hidden and non-linear associations among AD pathognomonic brain lesions and the clinical diagnosis of AD in participants in the Nun Study through Artificial Neural Networks (ANNs) analysis</p> <p>Methods</p> <p>The analyses were based on 26 clinically- and pathologically-confirmed AD cases and 36 controls who had normal cognitive function. The inputs used for the analyses were just NFT and neuritic plaques counts in neocortex and hippocampus, for which, despite substantial differences in mean lesions counts between AD cases and controls, there was a substantial overlap in the range of lesion counts.</p> <p>Results</p> <p>By taking into account the above four neuropathological features, the overall predictive capability of ANNs in sorting out AD cases from normal controls reached 100%. The corresponding accuracy obtained with Linear Discriminant Analysis was 92.30%. These results were consistently obtained in ten independent experiments. The same experiments were carried out with ANNs on a subgroup of 13 non severe AD patients and on the same 36 controls. The results obtained in terms of prediction accuracy with ANNs were exactly the same.</p> <p>Input relevance analysis confirmed the relative dominance of NFT in neocortex in discriminating between AD patients and controls and indicated the lesser importance played by NP in the hippocampus.</p> <p>Conclusion</p> <p>The results of this study suggest that: a) cortical NFT represent the key variable in AD neuropathology; b) the neuropathologic profile of AD subjects is complex, however, c) ANNs can analyze neuropathologic features and differentiate AD cases from controls.</p

Portuguese honeys as antimicrobial agents against Candida species

Background and aim Honey has been recognized worldwide for its antioxidant, anti-tumor, anti-inflammatory and antimicrobial properties. Among them, the antifungal properties associated to honey make it an attractive alternative treatment for Candida-associated infections, particularly for topical application to the mucous membranes and skin. In this sense, the main purpose of this work was to evaluate physicochemical properties of five Portuguese honeys and Manuka honey (an Australian honey with well recognized medical proprieties, used as control) and to evaluate the antifungal activity in Candida species planktonic and biofilm assays. Experimental procedure Pollen analysis, pH determination, color, concentration of protein and methylglyoxal, conductivity, total phenolics and flavonoids, hydrogen peroxide concentration, and characterization by differential scanning calorimetry in honey samples were determined. Additionally, the effect of honeys on planktonic growth of Candida was initially evaluated by determination of the minimum inhibitory concentrations. Then, the same effect of those honeys was evaluated in biofilms, by Colony Forming Units enumeration. Results and conclusion It has been shown that Portuguese heather (Erica cinereal) honey presented the most similar physicochemical properties to manuka honey (specially phenolic and flavonoids contents). The five Portuguese honeys under study, presented in general a potent activity against planktonic multi-resistant yeast pathogens (several clinical isolates and reference strains of Candida species) and S. aureus and P. aeruginosa bacteria cultures. Additionally, it was also concluded that Portuguese heather honey (50% and 75% (w/v)) can also act as a good Candida species biofilm reducer, namely for C. tropicalis.This study was supported by the Portuguese Foundation for Science and Technology (FCT), Portugal, under the scope of the strategic funding of UIDBB/04469/2020020 unit and BioTecNorte operation (NORTE-01-0145-FEDER-000004) funded by the European Regional Development Fund, Portugal, under the scope of Norte 2020 - Programa Operacional Regional do Norte.info:eu-repo/semantics/publishedVersio

Hookah (Shisha, Narghile) Smoking and Environmental Tobacco Smoke (ETS). A Critical Review of the Relevant Literature and the Public Health Consequences

Hookah (narghile, shisha, “water-pipe”) smoking is now seen by public health officials as a global tobacco epidemic. Cigarette Environmental Tobacco Smoke (ETS) is classically understood as a combination of Side-Stream Smoke (SSS) and Exhaled Main-Stream Smoke (EMSS), both diluted and aged. Some of the corresponding cigarette studies have served as the scientific basis for stringent legislation on indoor smoking across the world. Interestingly, one of the distinctive traits of the hookah device is that it generates almost no SSS. Indeed, its ETS is made up almost exclusively by the smoke exhaled by the smoker (EMSS), i.e. which has been filtered by the hookah at the level of the bowl, inside the water, along the hose and then by the smoker’s respiratory tract itself. The present paper reviews the sparse and scattered scientific evidence available about hookah EMSS and the corresponding inferences that can be drawn from the composition of cigarette EMSS. The reviewed literature shows that most of hookah ETS is made up of EMSS and that the latter qualitatively differs from MSS. Keeping in mind that the first victim of passive smoking is the active smoker her/himself, the toxicity of hookah ETS for non-smokers should not be overestimated and hyped in an unscientific way

Wound contraction effects and antibacterial properties of Tualang honey on full-thickness burn wounds in rats in comparison to hydrofibre

<p>Abstract</p> <p>Background</p> <p>Full-thickness burn wounds require excision and skin grafting. Multiple surgical procedures are inevitable in managing moderate to severe full-thickness burns. Wound bed preparations prior to surgery are necessary in order to prevent wound infection and promote wound healing. Honey can be used to treat burn wounds. However, not all the honey is the same. This study aims to evaluate the wound contraction and antibacterial properties of locally-produced <it>Tualang </it>honey on managing full-thickness burn wounds <it>in vivo</it>.</p> <p>Methods</p> <p>Thirty-six female <it>Sprague Dawley </it>rats were randomly divided into three groups. Under anaesthesia, three full-thickness burn wounds were created on the dorsum of the rats. The full-thickness burn wounds were inoculated with a specific organism (10⁴), namely <it>Pseudomonas aeruginosa </it>(n = 12), <it>Klebsiella pneumoniae </it>(n = 12), or <it>Acinetobacter baumannii </it>(n = 12). The three burn wounds were dressed with <it>Tualang </it>honey, hydrofibre and hydrofibre silver respectively. Swab samples were obtained every 3 days (day 3, 6, 9, 12, 15, 18 and 21) for quantitative and semi-quantitative microbiological analyses. Clinical assessments, including observations concerning the appearance and wound size, were measured at the same time.</p> <p>Results</p> <p>There was a rapid 32.26% reduction in wound size by day 6 (<it>p </it>= 0.008) in the <it>Tualang </it>honey-treated wounds, and 49.27% by day 15 (<it>p </it>= 0.005). The wounds remained smaller by day 18 (<it>p </it>< 0.032). <it>Tualang </it>honey-treated rats demonstrated a reduction in bacterial growth in <it>Pseudomonas aeruginosa </it>inoculated wounds (<it>p </it>= 0.005). However, hydrofibre silver and hydrofibre-treated wounds are superior to honey-treated wounds with <it>Acinetobacter baumannii </it>(<it>p </it>= 0.035). There was no statistical significant of antibacterial property in <it>Klebsiella pneumonia </it>inoculated wounds.</p> <p>Conclusions</p> <p><it>Tualang </it>honey has better results with regards to its control of <it>Pseudomonas aeruginosa </it>and its wound contraction effects on full-thickness burn wound <it>in vivo</it>.</p

The twilight of the Liberal Social Contract? On the Reception of Rawlsian Political Liberalism

This chapter discusses the Rawlsian project of public reason, or public justification-based 'political' liberalism, and its reception. After a brief philosophical rather than philological reconstruction of the project, the chapter revolves around a distinction between idealist and realist responses to it. Focusing on political liberalism’s critical reception illuminates an overarching question: was Rawls’s revival of a contractualist approach to liberal legitimacy a fruitful move for liberalism and/or the social contract tradition? The last section contains a largely negative answer to that question. Nonetheless the chapter's conclusion shows that the research programme of political liberalism provided and continues to provide illuminating insights into the limitations of liberal contractualism, especially under conditions of persistent and radical diversity. The programme is, however, less receptive to challenges to do with the relative decline of the power of modern states

Constitutivism

A brief explanation and overview of constitutivism

Challenges of maintaining research protocol fidelity in a clinical care setting: A qualitative study of the experiences and views of patients and staff participating in a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Trial research has predominantly focused on patient and staff understandings of trial concepts and/or motivations for taking part, rather than why treatment recommendations may or may not be followed during trial delivery. This study sought to understand why there was limited attainment of the glycaemic target (HbA_1c≤6.5%) among patients who participated in the Treating to Target in Type 2 Diabetes Trial (4-T). The objective was to inform interpretation of trial outcomes and provide recommendations for future trial delivery.</p> <p>Methods</p> <p>In-depth interviews were conducted with 45 patients and 21 health professionals recruited from 11 of 58 trial centres in the UK. Patients were broadly representative of those in the main trial in terms of treatment allocation, demographics and glycaemic control. Both physicians and research nurses were interviewed.</p> <p>Results</p> <p>Most patients were committed to taking insulin as recommended by 4-T staff. To avoid hypoglycaemia, patients occasionally altered or skipped insulin doses, normally in consultation with staff. Patients were usually unaware of the trial's glycaemic target. Positive staff feedback could lead patients to believe they had been 'successful' trial participants even when their HbA_1cexceeded 6.5%. While some staff felt that the 4-T automated insulin dose adjustment algorithm had increased their confidence to prescribe larger insulin doses than in routine clinical practice, all described situations where they had not followed its recommendations. Staff regarded the application of a 'one size fits all' glycaemic target during the trial as contradicting routine clinical practice where they would tailor treatments to individuals. Staff also expressed concerns that 'tight' glycaemic control might impose an unacceptably high risk of hypoglycaemia, thus compromising trust and safety, especially amongst older patients. To address these concerns, staff tended to adapt the trial protocol to align it with their clinical practices and experiences.</p> <p>Conclusions</p> <p>To understand trial findings, foster attainment of endpoints, and promote protocol fidelity, it may be necessary to look beyond individual patient characteristics and experiences. Specifically, the context of trial delivery, the impact of staff involvement, and the difficulties staff may encounter in balancing competing 'clinical' and 'research' roles and responsibilities may need to be considered and addressed.</p

Act In case of Depression: The evaluation of a care program to improve the detection and treatment of depression in nursing homes. Study Protocol

Contains fulltext : 95616.pdf (publisher's version ) (Open Access)BACKGROUND: The aim of this study is evaluating the (cost-) effectiveness of a multidisciplinary, evidence based care program to improve the management of depression in nursing home residents of somatic and dementia special care units. The care program is an evidence based standardization of the management of depression, including standardized use of measurement instruments and diagnostical methods, and protocolized psychosocial, psychological and pharmacological treatment. METHODS/DESIGN: In a 19-month longitudinal controlled study using a stepped wedge design, 14 somatic and 14 dementia special care units will implement the care program. All residents who give informed consent on the participating units will be included. Primary outcomes are the frequency of depression on the units and quality of life of residents on the units. The effect of the care program will be estimated using multilevel regression analysis. Secondary outcomes include accuracy of depression-detection in usual care, prevalence of depression-diagnosis in the intervention group, and response to treatment of depressed residents. An economic evaluation from a health care perspective will also be carried out. DISCUSSION: The care program is expected to be effective in reducing the frequency of depression and in increasing the quality of life of residents. The study will further provide insight in the cost-effectiveness of the care program. TRIAL REGISTRATION: Netherlands Trial Register (NTR): NTR1477