The phosphodiesterase 5 inhibitor sildenafil decreases the proinflammatory chemokine IL-8 in diabetic cardiomyopathy: in vivo and in vitro evidence

Purpose: Interleukin (IL)-8 is a proinflammatory C-X-C chemokine involved in inflammation underling cardiac diseases, primary or in comorbid condition, such diabetic cardiomyopathy (DCM). The phosphodiesterase type 5 inhibitor sildenafil can ameliorate cardiac conditions by counteracting inflammation. The study aim is to evaluate the effect of sildenafil on serum IL-8 in DCM subjects vs. placebo, and on IL-8 release in human endothelial cells (Hfaec) and peripheral blood mononuclear cells (PBMC) under inflammatory stimuli. Methods: IL-8 was quantified: in sera of (30) DCM subjects before (baseline) and after sildenafil (100 mg/day, 3-months) vs. (16) placebo and (15) healthy subjects, by multiplatform array; in supernatants from inflammation-challenged cells after sildenafil (1 µM), by ELISA. Results: Baseline IL-8 was higher in DCM vs. healthy subjects (149.14 ± 46.89 vs. 16.17 ± 5.38 pg/ml, p < 0.01). Sildenafil, not placebo, significantly reduced serum IL-8 (23.7 ± 5.9 pg/ml, p < 0.05 vs. baseline). Receiver operating characteristic (ROC) curve for IL-8 was 0.945 (95% confidence interval of 0.772 to 1.0, p < 0.01), showing good capacity of discriminating the response in terms of drug-induced IL-8 decrease (sensitivity of 0.93, specificity of 0.90). Sildenafil significantly decreased IL-8 protein release by inflammation-induced Hfaec and PBMC and downregulated IL-8 mRNA in PBMC, without affecting cell number or PDE5 expression. Conclusion: Sildenafil might be suggested as potential novel pharmacological tool to control DCM progression through IL-8 targeting at systemic and cellular level

Valorisation of by-products from soybean (Glycine max (L.) Merr.) processing

In recent years, increased awareness of the health benefits associated with consuming soy-based foods, knowledge of milk-related allergies and a move towards more sustainable food production have led to an increase in the number of available soy-based products. The biggest producers in the world, the USA, South America and China, are from the Pacific region. This enormous production is accompanied by the accumulation of related by-products, in particular, a substance that is known as okara. Okara is a paste that is rich in fibre (50%), protein (25%), fat (10%), vitamins and trace elements. Its proper use would lead to economic advantages and a reduction in the potential for polluting the environment. Its high fibre content and low production costs mean that it could also be used as a dietary supplement to prevent diabetes, obesity and hyperlipidaemia. Chemical or enzymatic treatment, fermentation, extrusion, high pressure and micronisation can all increase the soluble fibre content, and thus improve nutritional quality and processing properties. However, the product also degrades rapidly due to its high moisture content (70–80%), which makes it difficult to handle and expensive to dry by conventional means. The aim of this paper is therefore to thoroughly study the existing literature on this subject in order to develop a general protocol for okara exploitation and valorisation. A cost/benefit analysis could drive the design of eco-friendly, sustainable protocols for the preparation of high-value nutritional products

Surgery for Port-Wine Stains: A Systematic Review

Background: Port-wine stains (PWS) are congenital low-flow vascular malformations of the skin. PWS tend to become thicker and darker with time. Laser therapy is the gold standard and the first-line therapy for treating PWS. However, some resistant PWS, or PWS that have tissue hypertrophy, do not respond to this therapy. Our aim is to evaluate the role of surgery in the treatment of PWS birthmarks. Methods: A literature search was performed in PubMed, Scopus, Web of Science (WOS) and Google Scholar for all papers dealing with surgery for port-wine stains, from January 2010 to December 2020 using the search strings: (capillary vascular malformation OR port-wine stains OR Sturge Weber Syndrome OR sws OR pws) AND (surgical OR surgery). Results: Ten articles were identified and used for analysis. They were almost all case series with a short follow up period and lacked an objective–systematic score of evaluation. Conclusions: Delay in treatment of port wine stains may result in soft tissue and bone hypertrophy or nodules with disfiguring or destructive characteristics. The correction of PWS-related facial asymmetry often requires bone surgery followed by soft tissue corrections to achieve a more harmonious, predictable result

The date mussel Lithophaga lithophaga: Biology, ecology and multiple impacts of its illegal fishery

The date mussel Lithophaga lithophaga is an edible endolithic bivalve, protected by the EU Habitats Directive and other international agreements, living inside carbonate rocks. Its illegal harvesting is carried by breaking the rocks where the bivalve grows. The impact has cascade consequences as it causes permanent changes in the substrate characteristics, the removal of benthic species, a shift from highly complex to structurally simplified habitats. As a result, the rich biodiversity of rocky reefs turns into a biological desert, named “barren”. Along with the over exploitation of fish, this practice leads to the increase of sea urchin density and grazing pressure on habitats, hampering the resilience of the associated biodiversity and functions. This paper summarizes the information on date mussel biology, ecology, ecotoxicology, fishery and the legal framework regulating its protection. Evidence indicates that illegal harvesting is still operated and widespread along the Mediterranean and has huge costs in terms of loss of natural capital and ecosystem services, and in terms of active ecological restoration. Two case study areas (the Sorrento and Salento peninsulas) were selected to assess the economic costs of this practice. Tangible economic costs in terms of ecosystems services' loss are huge (from ca. 35,000 to more than 400,000 euros/year in 6.6 km of Sorrento and ca. 1.8 million euros/year along the 69 km of Salento). These costs are, on average, ca. 30 times lower than those of ecosystem restoration. Data mining from websites indicates that date mussels are presently commercialized in hundreds of restaurants in Greece, Balkan countries, Spain and Italy, favoured also by the lack of appropriate consumer information. This practice should be controlled and contrasted at local scale, enforced by national legislations, and implemented by transnational initiatives. Social campaigns are needed to increase public awareness of the serious consequences of date-mussel fishery and consumption

Inferior Alveolar Canal Automatic Detection with Deep Learning CNNs on CBCTs: Development of a Novel Model and Release of Open-Source Dataset and Algorithm

Featured Application Convolutional neural networks can accurately identify the Inferior Alveolar Canal, rapidly generating precise 3D data. The datasets and source code used in this paper are publicly available, allowing the reproducibility of the experiments performed. Introduction: The need of accurate three-dimensional data of anatomical structures is increasing in the surgical field. The development of convolutional neural networks (CNNs) has been helping to fill this gap by trying to provide efficient tools to clinicians. Nonetheless, the lack of a fully accessible datasets and open-source algorithms is slowing the improvements in this field. In this paper, we focus on the fully automatic segmentation of the Inferior Alveolar Canal (IAC), which is of immense interest in the dental and maxillo-facial surgeries. Conventionally, only a bidimensional annotation of the IAC is used in common clinical practice. A reliable convolutional neural network (CNNs) might be timesaving in daily practice and improve the quality of assistance. Materials and methods: Cone Beam Computed Tomography (CBCT) volumes obtained from a single radiological center using the same machine were gathered and annotated. The course of the IAC was annotated on the CBCT volumes. A secondary dataset with sparse annotations and a primary dataset with both dense and sparse annotations were generated. Three separate experiments were conducted in order to evaluate the CNN. The IoU and Dice scores of every experiment were recorded as the primary endpoint, while the time needed to achieve the annotation was assessed as the secondary end-point. Results: A total of 347 CBCT volumes were collected, then divided into primary and secondary datasets. Among the three experiments, an IoU score of 0.64 and a Dice score of 0.79 were obtained thanks to the pre-training of the CNN on the secondary dataset and the creation of a novel deep label propagation model, followed by proper training on the primary dataset. To the best of our knowledge, these results are the best ever published in the segmentation of the IAC. The datasets is publicly available and algorithm is published as open-source software. On average, the CNN could produce a 3D annotation of the IAC in 6.33 s, compared to 87.3 s needed by the radiology technician to produce a bidimensional annotation. Conclusions: To resume, the following achievements have been reached. A new state of the art in terms of Dice score was achieved, overcoming the threshold commonly considered of 0.75 for the use in clinical practice. The CNN could fully automatically produce accurate three-dimensional segmentation of the IAC in a rapid setting, compared to the bidimensional annotations commonly used in the clinical practice and generated in a time-consuming manner. We introduced our innovative deep label propagation method to optimize the performance of the CNN in the segmentation of the IAC. For the first time in this field, the datasets and the source codes used were publicly released, granting reproducibility of the experiments and helping in the improvement of IAC segmentation

Multiple General Anesthesia in Children: A Systematic Review of Its Effect on Neurodevelopment

The effect of multiple general anesthesia (mGA) procedures administered in early life is a critical theme and has led the Food and Drug Administration (FDA) to issue an alert. This systematic review seeks to explore the potential effects on neurodevelopment of mGA on patients under 4 years. The Medline, Embase and Web of Science databases were searched for publications up to 31 March 2021. The databases were searched for publications regarding “children multiple general anesthesia OR pediatric multiple general anesthesia”. Case reports, animal studies and expert opinions were excluded. Systematic reviews were not included, but they were screened to identify any possible additional information. A total of 3156 studies were identified. After removing the duplicates, screening the remaining records and analyzing the systematic reviews’ bibliography, 10 studies were considered suitable for inclusion. Comprehensively, a total cohort of 264.759 unexposed children and 11.027 exposed children were assessed for neurodevelopmental outcomes. Only one paper did not find any statistically significant difference between exposed and unexposed children in terms of neurodevelopmental alterations. Controlled studies on mGA administered before 4 years of age support that there might be a greater risk of neurodevelopmental delay in children receiving mGA, warranting the need for careful risk/benefit considerations

Changes in body weight and food choice in those attempting smoking cessation: a cluster randomised controlled trial

<p><b>Background:</b> Fear of weight gain is a barrier to smoking cessation and significant cause of relapse for many people. The provision of nutritional advice as part of a smoking cessation programme may assist some in smoking cessation and perhaps limit weight gain. The aim of this study was to determine the effect of a structured programme of dietary advice on weight change and food choice, in adults attempting smoking cessation.</p> <p><b>Methods:</b> Cluster randomised controlled design. Classes randomised to intervention commenced a 24-week intervention, focussed on improving food choice and minimising weight gain. Classes randomised to control received "usual care".</p> <p><b>Results:</b> Twenty-seven classes in Greater Glasgow were randomised between January and August 2008. Analysis, including those who continued to smoke, showed that actual weight gain and percentage weight gain was similar in both groups. Examination of data for those successful at giving up smoking showed greater mean weight gain in intervention subjects (3.9 (SD 3.1) vs. 2.7 (SD 3.7) kg). Between group differences were not significant (p=0.23, 95% CI -0.9 to 3.5). In comparison to baseline improved consumption of fruit and vegetables and breakfast cereal were reported in the intervention group. A higher percentage of control participants continued smoking (74% vs. 66%).</p> <p><b>Conclusions:</b> The intervention was not successful at minimising weight gain in comparison to control but was successful in facilitating some sustained improvements in the dietary habits of intervention participants. Improved quit rates in the intervention group suggest that continued contact with advisors may have reduced anxieties regarding weight gain and encouraged cessation despite weight gain. Research should continue in this area as evidence suggests that the negative effects of obesity could outweigh the health benefits achieved through reductions in smoking prevalence.</p&gt

The Snail repressor recruits EZH2 to specific genomic sites through the enrollment of the lncRNA HOTAIR in epithelial-to-mesenchymal transition

The transcription factor Snail is a master regulator of cellular identity and epithelial-to-mesenchymal transition (EMT) directly repressing a broad repertoire of epithelial genes. How chromatin modifiers instrumental to its activity are recruited to Snail-specific binding sites is unclear. Here we report that the long non-coding RNA (lncRNA) HOTAIR (for HOX Transcript Antisense Intergenic RNA) mediates a physical interaction between Snail and enhancer of zeste homolog 2 (EZH2), an enzymatic subunit of the polycomb-repressive complex 2 and the main writer of chromatin-repressive marks. The Snail-repressive activity, here monitored on genes with a pivotal function in epithelial and hepatic morphogenesis, differentiation and cell-type identity, depends on the formation of a tripartite Snail/HOTAIR/EZH2 complex. These results demonstrate an lncRNA-mediated mechanism by which a transcriptional factor conveys a general chromatin modifier to specific genes, thereby allowing the execution of hepatocyte transdifferentiation; moreover, they highlight HOTAIR as a crucial player in the Snail-mediated EMT.Oncogene advance online publication, 25 July 2016; doi:10.1038/onc.2016.260

Understanding the UK hospital supply chain in an era of patient choice

Author Posting © Westburn Publishers Ltd, 2011. This is a post-peer-review, pre-copy-edit version of an article which has been published in its definitive form in the Journal of Marketing Management, and has been posted by permission of Westburn Publishers Ltd for personal use, not for redistribution. The article was published in Journal of Marketing Management, 27(3-4), 401 - 423, doi:10.1080/0267257X.2011.547084 http://dx.doi.org/10.1080/0267257X.2011.547084The purpose of this paper is to investigate the UK hospital supply chain in light of recent government policy reform where patients will have, inter alia, greater choice of hospital for elective surgery. Subsequently, the hospital system should become far more competitive with supply chains having to react to these changes as patient demand becomes less predictable. Using a qualitative case study methodology, hospital managers are interviewed on a range of issues. Views on the development of the hospital supply chain in different phases are derived, and are used to develop a map of the current hospital chain. The findings show hospital managers anticipating some significant changes to the hospital supply chain and its workings as Patient Choice expands. The research also maps the various aspects of the hospital supply chain as it moves through different operational phases and highlights underlying challenges and complexities. The hospital supply chain, as discussed and mapped in this research, is original work given there are no examples in the literature that provide holistic representations of hospital activity. At the end, specific recommendations are provided that will be of interest to service to managers, researchers, and policymakers