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In recent years, the importance of the gut microbiota in human health has been revealed and many publications have highlighted its role as a key component of human physiology. Owing to the use of modern sequencing approaches, the characterisation of the microbiome in healthy individuals and in disease has demonstrated a disturbance of the microbiota, or dysbiosis, associated with pathological conditions. The microbiota establishes a symbiotic crosstalk with their host: commensal microbes benefit from the nutrient-rich environment provided by the gut and the microbiota produces hundreds of proteins and metabolites that modulate key functions of the host, including nutrient processing, maintenance of energy homoeostasis and immune system development. Many bacteria-derived metabolites originate from dietary sources. Among them, an important role has been attributed to the metabolites derived from the bacterial fermentation of dietary fibres, namely SCFA linking host nutrition to intestinal homoeostasis maintenance. SCFA are important fuels for intestinal epithelial cells (IEC) and regulate IEC functions through different mechanisms to modulate their proliferation, differentiation as well as functions of subpopulations such as enteroendocrine cells, to impact gut motility and to strengthen the gut barrier functions as well as host metabolism. Recent findings show that SCFA, and in particular butyrate, also have important intestinal and immuno-modulatory functions. In this review, we discuss the mechanisms and the impact of SCFA on gut functions and host immunity and consequently on human health.
Deutetrabenazine (Austedo) is approved by the FDA for treatment of tardive dyskinesia (TD) in adults. In the 12-week ARM-TD and AIM-TD studies, deutetrabenazine showed clinically significant improvements in Abnormal Involuntary Movement Scale (AIMS) scores compared with placebo, and there were low rates of overall adverse events (AEs) and discontinuations associated with deutetrabenazine. The objective of this study was to evaluate the long-term safety and tolerability of deutetrabenazine in patients with TD at 3 years.
Patients who completed ARM-TD or AIM-TD were included in this open-label, single-arm extension study, in which all patients restarted/started deutetrabenazine 12 mg/day, titrating up to a maximum total daily dose of 48 mg/day based on dyskinesia control and tolerability. The study comprised a 6-week titration period and a long-term maintenance phase. Safety measures included incidence of AEs, serious AEs (SAEs), and AEs leading to withdrawal, dose reduction, or dose suspension. Exposure-adjusted incidence rates (EAIRs; incidence/patient-years) were used for calculating AE frequencies. This analysis reports results up to Week 158.
A total of 343 patients were enrolled (111 received placebo and 232 received deutetrabenazine in the parent studies). At the time of this analysis, 183 patients were still receiving treatment; 259 completed 1 year, 172 completed 2 years, and 41 completed 3 years. There were 623 patient-years of exposure. More than 40% of patients reached the maximum dose. EAIRs of AEs were comparable to or lower than those observed in the ARM-TD and AIM-TD short-term randomized trials of deutetrabenazine vs. placebo. The frequency of SAEs (EAIR 0.10) was similar to that observed with short-term placebo (0.33) and short-term deutetrabenazine (range 0.06–0.33) treatment. AEs leading to withdrawal (0.06), dose reduction (0.10), and dose suspension (0.05) were uncommon.
These results support the safety outcomes observed in the ARM-TD and AIM-TD parent studies and the safety of deutetrabenazine for long-term use in patients with TD.
Funding Acknowledgements: This study was funded by Teva Pharmaceuticals, Petach Tikva, Israel
In the 12-week ARM-TD and AIM-TD studies evaluating deutetrabenazine for the treatment of tardive dyskinesia (TD), the percentage of patients achieving ≥50% response was higher in the deutetrabenazine-treated group than in the placebo group. These studies also showed low rates of overall adverse events (AEs) and discontinuations associated with deutetrabenazine. The current open-label study evaluated the long-term efficacy and safety of deutetrabenazine in patients with TD.
Patients with TD who completed ARM-TD or AIM-TD could enroll in this open-label, single-arm extension study, titrating up over 6 weeks to a maximum total daily dose of deutetrabenazine 48 mg/day on the basis of dyskinesia control and tolerability. The proportion of Abnormal Involuntary Movement Scale (AIMS; items 1-7) responders was assessed based on response rates for achieving ≥50% improvement from baseline in the open-label extension study. AlMS score was assessed by local site raters for this analysis.
343 patients enrolled in the extension study. At Week 54 (n=249; total daily dose [mean ± standard error]: 38.6±0.66 mg), the mean percentage change from baseline in AIMS score was –40%; 48% of patients achieved a ≥50% response and 59% of those had already achieved a ≥50% response at Week 15. Further, 34% of those who had not achieved a ≥50% response at Week 15 achieved a ≥50% response at Week 54. At Week 106 (n=169; total daily dose: 39.6±0.77 mg), the mean percentage change from baseline in AIMS score was –45%; 55% of patients achieved a ≥50% response, 59% of those patients had already achieved a ≥50% response at Week 15, and 41% of those who had not achieved a ≥50% response at Week 15 but who reached Week 106 achieved a ≥50% response. At Week 132 (n=109; total daily dose: 39.7±0.97 mg), the mean percentage change from baseline in AIMS score was –61%; 55% of patients achieved a ≥50% response, 61% of those patients had already achieved a ≥50% response at Week 15, and 43% of those who had not achieved a ≥50% response at Week 15 but who reached Week 132 achieved a ≥50% response. Completer analysis suggests that long-term efficacy was not due to dose increases over time. Treatment with deutetrabenazine was generally well tolerated. There were 623 patient-years of exposure through Week 158, and exposure-adjusted incidence rates (incidence/patient-years) of adverse events of special interest were 0.01 for akathisia and restlessness, 0.07 for somnolence and sedation, 0.04 for parkinsonism, and 0.05 for depression.
Patients who received long-term treatment with deutetrabenazine achieved response rates that were indicative of clinically meaningful long-term benefit. Results from this open-label trial suggest the possibility of increasing benefit over time with individual dose titration of deutetrabenazine.
This study was funded by Teva Pharmaceuticals, Petach Tikva, Israel.
The ‘making’ of fashion cannot merely refer to garment production and manufacturing. It is the prerequisite for a nation to actively participate on the global stage. To establish a ‘recognisable’ fashion image, a country must go far beyond the competition of a specialised garment and textile industry. Being recognised as the ‘author countries’ for fashion creation is part of a process in which the (re)negotiation of national hierarchies and roles are constantly at play. For a country or a city, expressing an instantly recognisable aesthetic has become an important corollary of the communication of political and economic strength. More than in the past centuries, fashion has been tasked with not only reflecting and representing social or individual needs, but also constructing ex novo territories in which old stereotypes and imaginary are creatively set free. This is because, unlike most production and commercial activities, fashion expresses an elaborate culture whose composition of symbols, ideologies and lifestyles (Crane 2004) can be drawn on. On the other hand, the accelerated production relocation in past decades has irrevocably changed the geography of fashion, as well as the rhetoric of the origin of national creativity. In particular, it leads one to wonder what happens when two or more players are engaged in the making of fashion. Specifically, what happens when Italy and China collaborate in transglobal fashion-making? How does one account for the national creativity that has sprung from the Sino-Italian co-creation? Drawing on accounts of Italian fashion and Chinese fashion, this article discusses the intricacy of Sino-Italian collaboration and the implications of such a fashion co-creation; it then reflects on transglobal fashion-making and proposes a framework for its examination.
This paper focuses on the encounters between Italy and Siam at the dawn of the twentieth century, as it was the most dynamic period of Italian settlement in the modernising Siam. The paper analyses the development of Siamese modernisation as a challenging opportunity for Italian entrepreneurs and professionals, thanks to a healthy diplomatic relation between the two countries. Compared to the main characteristics of the Italian diaspora, the Italian colony in Siam stands out because of the fruits of its creative production. Siam was described as a symbol of tradition, not very different from the way China was often viewed, while the West was regarded as a source of modernity. With this perspective, the fact that Siam herself initiated the modernisation process, as well as the recruitment of Italians as part of the government's team in public works, architectural construction and civil engineering, was emphasised less than the part played by Italians in transforming the image of the Siamese capital. The paper examines how the encounters between Italy and Siam developed, attempting to do this from both Siamese and Italian perspectives, since both shared cultural memories, empirical evidence of cultural encounters and transculturality.
This article consists of three sections. The first one concentrates on the conceptualisation of the Italian concession in Tianjin (1901–1947). The second connects the past imagery of the Italian ‘aristocratic concession’ to its contemporary reinvention as the ‘New Italian-style Town’. The third section explores the rationale for the diffusion of what I define as Italianerie: a fascination for Italy, for a ‘real-unreal’ Italian-flavoured atmosphere, through the creation of multi-million-dollar luxury designer outlets known as ‘Florentia Villages’. The first Florentia Village, ‘inspired by classic Italian architecture’, opened in Wuqing, halfway between Beijing and Tianjin, in June 2011, followed by the replica of this template in eight Chinese cities. Is this the outcome of a specific patrimonialisation strategy? What is the significance of this showcase of Italian design in China? What lies behind the apparent paradox of reproducing ‘in/authentic’ Italy in miniature, and using it to sell the ‘real’ luxury products, in a country like China, which is stereotyped as the paradise of the fake? Is innovation by design reconfiguring the relationship between production and consumption of cultural images and commodities? This article intends to explore these questions with particular attention to transcultural strategies in Chinese urbanism – past and present.
As Italian society struggles to come to terms with the presence of Chinese immigrants and with changing global patterns of industrialisation and shifts in the dynamics of industrial power, the question of Sino-Italian relations is increasingly present in Italian cultural representations across media and genre. Among the themes which recur within Italian discourse on Chinese industry are Made in Italy vs Made in China, tradition vs modernity, and environmental responsibility. In this paper, I offer a reading of the complex and, at times, ambivalent treatment of these themes in Gianni Amelio's 2006 film, La stella che non c’è (The Missing Star), and Alessandro Perissinotto's 2014 novel, Coordinate d'Oriente (Oriental Coordinates). Central to my analysis of the two works is an examination of the trope of contacts between the economies and societies of the two countries being sublimated in the fictional narratives into relationships between Western men and Chinese women. Against this backdrop, I propose an interpretation of the power dynamics which underpin the narratives.
On the Italian internet, the dominant, Italian-centred – and arguably often nationalistic – discourse on Global China, and, by extension, Global Italy, emphasises economic growth and opportunities. The celebratory and homogenising rhetoric of this discourse has been challenged by a counter-discourse on subaltern China, which focuses on the many, localised social inequities and discriminations suffered by the Chinese – or, more accurately, sinophone – workers. In this counter- discourse, an important role is played by small-screen documentaries on displaced migrants both in the People's Republic of China (PRC) and in Italy. I propose that they provide meaningful evidence of an Italian-accented ‘sinologia di sinistra’ or activist sinology, which views research as a transnational practice and advocates a stronger link between academic discourse and civil society.
During the Fascist ventennio, prominent Italian writers and journalists, such as Mario Appelius, Raffaele Calzini, Arnaldo Cipolla, Arnaldo Fraccaroli, Roberto Suster and Cesco Tommaselli, reported from China, Japan and Korea for Il Popolo d'Italia, Corriere della Sera and La Stampa. Their travel narratives were crucial for the creation and diffusion in Italy of the dominant representation of China and Korea as remote, decadent and exotic societies; and of Japan as a progressive society resonant with Fascist Italy. The narrativisation of these countries in Italian travelogues from the Fascist ventennio was part of a widespread discursive practice by Italian intellectuals willing to subscribe to, and actively disseminate, the guiding principles of Fascism. When emphasising China's and Korea's irreconcilable difference from, and Japan's affinity with, Fascist Italy, these intellectuals extolled the Italian race and culture, justified Italy's position in geopolitical dynamics, and propagandised the exceptionality of the Fascist ideology.
Relations between Italy and other countries – such as China – are often imagined within a binary frame that essentialises national and ethnic communities and fails to recognise the complex transcultural ramifications of an increasingly globalising world. This is particularly problematic when studying those social and cultural spaces that Ilaria Vanni (2016) has described as transcultural edges. These are marginal spaces of transition and encounters between different cultures and societies, which have the potential to create new, innovative and productive ecosystems. We argue that one such space is Prato, an industrial town near Florence, well known for its textile district, and host to one of the largest Chinese communities in Europe. Significant academic attention has been devoted to the Chinese community in Prato, including studies of its social and economic impact on the host local community and the textile industry. Most of these studies tend to isolate the Chinese community from the ethnic complexity of the area, within a binary frame that fails to acknowledge the large presence of other migrant groups and the reciprocal permeability and transculturation between the Chinese community, the Italian community, and other ethnic groups. As part of a larger project, a group of scholars is currently digitally remapping Prato, to include quantitative and qualitative geolocalised information collected through a multidisciplinary method that includes ethnography, media analysis, translation studies, transcultural studies, and digital participatory action research. Through a brief description of the aims and characteristics of this research project, the paper will discuss the importance of rethinking the relationship between Italy and China, and between Italians and Chinese, within a more complex and nuanced transcultural frame.
For more than four decades after the introduction of cv. Italia (Vitis vinifera L.) in Brazil, several somatic mutations in the genome of cv. Italia and its somatic mutants gave rise to phenotypes which generated at least five new cultivars of fine table grapes. Since no molecular marker proved to be effective in discriminating cv. Italia (V. vinifera L.) and its coloured mutants (Rubi, Benitaka, Brasil, Black Star), primers for the long terminal repeat (LTR) sequences were developed to analyse Inter Retrotransposon Amplified Polymorphism (IRAP) and Retrotransposon-Microsatellite Amplified Polymorphism (REMAP), and investigate how the coloured cultivars derived from clonal propagations of somatic mutations are genetically structured. Primers for LTR sequences of IRAP and REMAP markers were edited from grape sequence databases available at a GenBank. Twenty-four primers, denominated DKS001–DKS024, were edited. Three hundred and forty-nine DNA segments were amplified by individual DKS primers and DKS/ISSR (Inter Simple Sequence Repeats) primer combinations, at an average of 13.96 amplicons per primer pair. High genetic divergence between the five cultivars was inferred from polymorphism in retrotransposons IRAP and REMAP. The analysis of polymorphism of IRAP and REMAP retrotransposons was crucial to show that clonal propagation of somatic mutations may lead towards the formation of genetically divergent cultivars by the formation of genetically structured vineyards and show the mixture of genomes within each cultivar.