Eustache Deschamps\u27 \u3ci\u3e L\u27art de dictier \u3c/i\u3e

L\u27Art de dictier, written in 1392 by the prolific courtier-poet Eustache Deschamps, is the first ars poetica ever written in French. It provides invaluable insights into medieval poetics as perceived by a respected medieval poet. L\u27Art de dictier is composed of two sections: a brief introductory liberal arts treatise and a prescriptive poetics devoted to the lyric. In the introduction, music is divided into two sub-categories. Deschamps calls instrumental music artificial music because he feels it can be taught to anyone. Natural music, in contrast, is poetry, for only those who are inspired to compose it can do so. Since Deschamps was the disciple of the great poet-musician Guillaume de Machaut, it is not surprising that Deschamps linked poetry with music; however, Deschamps felt strongly that natural music was superior to artificial music and might even be better performed without it. Although a long history of artes poeticae precede it, L\u27Art de dictier is related to neither the Latin nor the vernacular tradition. Since L\u27Art de dictier treats lyric poetry, it is, however, more fruitfully compared with the Old Provencal prescriptive treatises (e.g. Las Leys d\u27amor, the Razos de trobar and the Regles de trobar). Comparison with Dante\u27s De Vulgari eloquentia also yields valuable insights. L\u27Art de dictier was last edited by the Societe des Anciens Textes Francais in 1878. A new edition was therefore necessary. Textual variants have been noted and a glossary prepared, as well as extensive annotations. Since it had never been translated into any modern language, L\u27Art de dictier has been translated here

Identification of plant-derived alkaloids with therapeutic potential for myotonic dystrophy type I

Myotonic dystrophy type I (DM1) is a disabling neuromuscular disease with no causal treatment available. This disease is caused by expanded CTG trinucleotide repeats in the 3 UTR of the dystrophia myotonica protein kinase gene. On the RNA level, expanded (CUG)n repeats form hairpin structures that sequester splicing factors such as muscleblind-like 1 (MBNL1). Lack of availableMBNL1leads to misregulated alternative splicing of many target pre-mRNAs, leading to the multisystemic symptoms in DM1. Many studies aiming to identify small molecules that target the (CUG)n-MBNL1 complex focused on synthetic molecules. In an effort to identify new small molecules that liberate sequesteredMBNL1from (CUG)n RNA, we focused specifically on small molecules of natural origin. Natural products remain an important source for drugs and play a significant role in providing novel leads and pharmacophores for medicinal chemistry. In a new DM1 mechanism-based biochemical assay, we screened a collection of isolated natural compounds and a library of over 2100 extracts from plants and fungal strains. HPLC-based activity profiling in combination with spectroscopic methods were used to identify the active principles in the extracts. The bioactivity of the identified compounds was investigated in a human cell model and in a mouse model of DM1.We identified several alkaloids, including the -carboline harmine and the isoquinoline berberine, that ameliorated certain aspects of theDM1pathology in these models. Alkaloids as a compound class may have potential for drug discovery in other RNA-mediated diseases

Single-cell analysis of human MAIT cell transcriptional, functional and clonal diversity

Mucosal-associated invariant T (MAIT) cells are innate-like T cells that recognize microbial metabolites through a semi-invariant T cell receptor (TCR). Major questions remain regarding the extent of human MAIT cell functional and clonal diversity. To address these, we analyzed the single-cell transcriptome and TCR repertoire of blood and liver MAIT cells and developed functional RNA-sequencing, a method to integrate function and TCR clonotype at single-cell resolution. MAIT cell clonal diversity was comparable to conventional memory T cells, with private TCR repertoires shared across matched tissues. Baseline functional diversity was low and largely related to tissue site. MAIT cells showed stimulus-specific transcriptional responses in vitro, with cells positioned along gradients of activation. Clonal identity influenced resting and activated transcriptional profiles but intriguingly was not associated with the capacity to produce IL-17. Overall, MAIT cells show phenotypic and functional diversity according to tissue localization, stimulation environment and clonotype

Dysferlinopathy in Switzerland: clinical phenotypes and potential founder effects.

BACKGROUND: Dysferlin is reduced in patients with limb girdle muscular dystrophy type 2B, Miyoshi myopathy, distal anterior compartment myopathy, and in certain Ethnic clusters. METHODS: We evaluated clinical and genetic patient data from three different Swiss Neuromuscular Centers. RESULTS: Thirteen patients from 6 non-related families were included. Age of onset was 18.8 ± 4.3 years. In all patients, diallelic disease-causing mutations were identified in the DYSF gene. Nine patients from 3 non-related families from Central Switzerland carried the identical homozygous mutation, c.3031 + 2 T>C. A possible founder effect was confirmed by haplotype analysis. Three patients from two different families carried the heterozygous mutation, c.1064_1065delAA. Two novel mutations were identified (c.2869 C>T (p.Gln957Stop), c.5928 G>A (p.Trp1976Stop)). CONCLUSIONS: Our study confirms the phenotypic heterogeneity associated with DYSF mutations. Two mutations (c.3031 + 2 T>C, c.1064_1065delAA) appear common in Switzerland. Haplotype analysis performed on one case (c. 3031 + 2 T>C) suggested a possible founder effect

Autochthonous hepatitis E as a cause of acute-on-chronic liver failure and death: histopathology can be misleading but transaminases may provide a clue.

Acute decompensation and death have been observed in patients with acute hepatitis E virus (HEV) infection and preexisting liver cirrhosis. However, the clinical, laboratory and histological features need to be fully characterised. Some of us recently described the histological presentation of hepatitis E in a large panel of liver tissue specimens. Here, we conducted a case-control study to investigate the clinical and laboratory features of the subset of patients with HEV-related acute-on-chronic liver failure (ACLF) and death. Each patient was matched to three control patients with histologically confirmed severe alcoholic hepatitis based on sex, age, total bilirubin, INR, serum creatinine and MELD score on admission. Of 5 patients who died in a context of HEV-related ACLF, 3 (60%) were male and the median age was 66 years (range 51–76). Median alanine aminotransferase (ALT) at presentation was 2610 U/l (range 705–3134) and aspartate aminotransferase (AST) 2818 U/l (range 1176–8611). Liver function was heavily altered in all patients. Histological analyses revealed steatohepatitis on a background of cirrhosis, suggestive of an alcoholic or nonalcoholic origin. Based on histopathology, alcoholic hepatitis was initially suspected in two patients and corticosteroid treatment was initiated. Ribavirin was started in four patients. Median time from hospitalisation to death was 17 days (range 6–25 days). AST levels in patients with HEV-related ACLF were significantly higher as compared to the matched patients with severe alcoholic hepatitis. Typical histopathological features of viral hepatitis may be absent in ACLF caused by HEV infection. HEV infection should be sought in acute decompensation of cirrhosis and ACLF even in the absence of histological changes suggesting viral infection

SoundCloud and Bandcamp as alternative music platforms

We examine two ‘producer-oriented’ audio distribution platforms, SoundCloud and Bandcamp, that have been important repositories for the hopes of musicians, commentators and audiences that digital technologies and cultural platforms might promote democratisation of the cultural industries, and we compare their achievements and limitations in this respect. We show that the emancipatory elements enshrined in SoundCloud’s ‘bottom-up’ abundance are compromised by two elements that underpin the platform: the problematic ‘culture of connectivity’ of the social media systems to which it must remain integrally linked, and the systems of intellectual property that the firm has been increasingly compelled to enforce. By contrast, it seems that Bandcamp has been relatively stable in financial terms while being at odds with some key aspects of ‘platformization’, and we explore the possibility that some of the platform’s apparent success may derive from how its key features makes it attractive to indie musicians and fans drawn to an independent ethos. Nevertheless, we argue, even while in some respects Bandcamp acts more effectively as an ‘alternative’ than does SoundCloud, the former is also congruent economically and discursively with how platforms capitalise on the activity of self-managing, self-auditing, specialist, worker-users

Telomeres and the natural lifespan limit in humans

An ongoing debate in demography has focused on whether the human lifespan has a maximal natural limit. Taking a mechanistic perspective, and knowing that short telomeres are associated with diminished longevity, we examined whether telomere length dynamics during adult life could set a maximal natural lifespan limit. We define leukocyte telomere length of 5 kb as the 'telomeric brink', which denotes a high risk of imminent death. We show that a subset of adults may reach the telomeric brink within the current life expectancy and more so for a 100-year life expectancy. Thus secular trends in life expectancy should confront a biological limit due to crossing the telomeric brink

Double blind, randomized, placebo controlled clinical trial for the treatment of diabetic foot ulcers, using a nitric oxide releasing patch: PATHON

<p>Abstract</p> <p>Background</p> <p>Diabetes Mellitus constitutes one of the most important public health problems due to its high prevalence and enormous social and economic consequences. Diabetic foot ulcers are one of the chronic complications of diabetes mellitus and constitute the most important cause of non-traumatic amputation of inferior limbs. It is estimated that 15% of the diabetic population will develop an ulcer sometime in their lives. Although novel therapies have been proposed, there is no effective treatment for this pathology. Naturally produced nitric oxide participates in the wound healing process by stimulating the synthesis of collagen, triggering the release of chemotactic cytokines, increasing blood vessels permeability, promoting angiogenic activity, stimulating the release of epidermical growth factors, and by interfering with the bacterial mitochondrial respiratory chain. Topically administered nitric oxide has demonstrated to be effective and safe for the treatment of chronic ulcers secondary to cutaneous leishmaniasis. However, due to their unstable nitric oxide release, the topical donors needed to be applied frequently, diminishing the adherence to the treatment. This difficulty has led to the development of a multilayer polymeric transdermal patch produced by electrospinning technique that guarantees a constant nitric oxide release. The main objective of this study is to evaluate the effectiveness and safety of this novel nitric oxide releasing wound dressing for the treatment of diabetic foot ulcers.</p> <p>Methods and design</p> <p>A double-blind, placebo-controlled clinical trial, including 100 diabetic patients was designed. At the time of enrollment, a complete medical evaluation and laboratory tests will be performed, and those patients who meet the inclusion criteria randomly assigned to one of two groups. Over the course of 90 days group 1 will receive active patches and group 2 placebo patches. The patients will be seen by the research group at least every two weeks until the healing of the ulcer or the end of the treatment. During each visit the healing process of the ulcer, the patient's health status and the presence of adverse events will be assessed. Should the effectiveness of the patches be demonstrated an alternative treatment would then be available to patients.</p> <p>Trial registration</p> <p>NCT00428727.</p

Lifestyle physical activity among urban Palestinians and Israelis: a cross-sectional comparison in the Palestinian-Israeli Jerusalem risk factor study

<p>Abstract</p> <p>Background</p> <p>Urban Palestinians have a high incidence of coronary heart disease, and alarming prevalences of obesity (particularly among women) and diabetes. An active lifestyle can help prevent these conditions. Little is known about the physical activity (PA) behavior of Palestinians. This study aimed to determine the prevalence of insufficient PA and its socio-demographic correlates among urban Palestinians in comparison with Israelis.</p> <p>Methods</p> <p>An age-sex stratified random sample of Palestinians and Israelis aged 25-74 years living in east and west Jerusalem was drawn from the Israel National Population Registry: 970 Palestinians and 712 Israelis participated. PA in a typical week was assessed by the Multi-Ethnic Study of Atherosclerosis (MESA) questionnaire. Energy expenditure (EE), calculated in metabolic equivalents (METs), was compared between groups for moderate to vigorous-intensity physical activity (MVPA), using the Wilcoxon rank-sum test, and for domain-specific prevalence rates of meeting public health guidelines and all-domain insufficient PA. Correlates of insufficient PA were assessed by multivariable logistic modeling.</p> <p>Results</p> <p>Palestinian men had the highest median of MVPA (4740 METs-min_*wk^-1) compared to Israeli men (2,205 METs-min_*wk^-1<it>p </it>< 0.0001), or to Palestinian and Israeli women, who had similar medians (2776 METs-min_*wk^-1). Two thirds (65%) of the total MVPA reported by Palestinian women were derived from domestic chores compared to 36% in Israeli women and 25% among Palestinian and Israeli men. A high proportion (63%) of Palestinian men met the PA recommendations by occupation/domestic activity, compared to 39% of Palestinian women and 37% of the Israelis. No leisure time PA was reported by 42% and 39% of Palestinian and Israeli men (<it>p </it>= 0.337) and 53% and 28% of Palestinian and Israeli women (<it>p </it>< 0.0001). Palestinian women reported the lowest level of walking. Considering all domains, 26% of Palestinian women were classified as insufficiently active versus 13% of Palestinian men (<it>p </it>< 0.0001) who did not differ from the Israeli sample (14%). Middle-aged and elderly and less educated Palestinian women, and unemployed and pensioned Palestinian men were at particularly high risk of inactivity. Socio-economic indicators only partially explained the ethnic disparity.</p> <p>Conclusions</p> <p>Substantial proportions of Palestinian women, and subgroups of Palestinian men, are insufficiently active. Culturally appropriate intervention strategies are warranted, particularly for this vulnerable population.</p

Effects of antidepressant treatment on heart rate variability in major depression: A quantitative review

<p>Abstract</p> <p>Background</p> <p>The literature measuring effects of antidepressant and electroconvulsive therapy (ECT) for major depression on heart rate variability (HRV) in medically well individuals was reviewed.</p> <p>Methods</p> <p>Fourteen studies evaluating HRV were included. Twenty three pre-post or within group comparisons were available. Treatment impact on measures of HRV was pooled over studies. We examined different classes of antidepressants, and for short and long electrocardiogram (ECG) recordings separately.</p> <p>Results</p> <p>Tricyclic antidepressants (TCAs) were associated with declines in most measures of HRV and significant increase in heart rate (HR) in studies with short recording intervals. No significant changes were found for longer recording times.</p> <p>Treatment effects with selective serotonin reuptake inhibitors (SSRIs) were more variable. Short-recording studies revealed a significant decrease in HR and an increase in one HRV measure. In two 24-hour recording studies no significant changes were observed. No relationship between ECT and HRV has been established in the literature. The effects of other drugs are reported.</p> <p>Limitations</p> <p>Few studies measure the effects of treatment of depression on HRV. Existing studies have generally used very small samples, employing a variety of measurements and methodologies.</p> <p>Conclusion</p> <p>We confirm that TCAs are associated with a large decrease in HRV and increase HR. However, data for SSRIs is not clear. Although the effect of SSRIs on HRV is weaker than for TCAs, evidence shows that SSRIs are associated with a small decrease in HR, and an increase in one measure of HRV. The use of TCAs in depression leads to changes in HRV that are associated with increased risk of mortality.</p