Antitumour necrosis factor-α therapy for hidradenitis suppurativa: results from a national cohort study between 2000 and 2013

International audienceHidradenitis suppurativa (HS) is a frequent chronic inflammatory skin disease typically characterized by recurrent painful, deep inflammatory nodules of the axillary, breast, groin and gluteal areas. European recommendations are mainly based on expert opinion. Drug treatments are heterogenous (e.g., antibiotics, corticosteroids, retinoids) and lack consensus among expert centres. The most severe disease forms or those failing to respond to conventional drugs may be associated with worsened functional prognosis. Anti-tumor necrosis factor α (anti-TNFα) drugs have been prescribed in these cases. The results of randomized controlled trials (RCTs) are discordant. Three RCTs concluded to the efficacy of adalimumab (ADA), and two others did not detect any difference between infliximab (IFX) or etanercept (ETA) and placebo. Finally, data from the literature and reported experiences do not conclude on the efficacy of anti-TNFα drugs for HS. This article is protected by copyright. All rights reserve

Primary prevention with a defibrillator: are therapies always really optimized before implantation?

AIMS:Left ventricle ejection fraction (LVEF) ≤ 30-35% is widely accepted as a cut-off for primary prevention with an implantable cardiac defibrillator (ICD) in patients with both ischaemic and non-ischaemic cardiomyopathy supposedly on optimal medical therapy. This study reports evolutions of LVEF and treatments of patients implanted in our institution with an ICD for primary prevention of sudden death, after 2 years of follow-up. METHODS AND RESULTS: Among 84 patients with LVEF under 35% implanted between 2005 and 2007, 28 (33%) had improved their LVEF >35% after the 2 years of follow-up. During this period, even if Beta-blockers (98%) and renin-angiotensin system (RAS) blockers (95%) were already initially prescribed, treatments were significantly optimized with improvement of maximal doses of beta-blockers and RAS blockers at 2 year follow-up compared with initial prescription (62 vs. 37% and 68 vs. 45%, respectively). In patients with improved LVEF, a trend toward a better treatment optimization and revascularization procedures (in the sub-group of ischaemic patients) were observed compared with non-improved LVEF patients. CONCLUSIONS: In our study of patients with prophylactic ICD, one-third of them have improved their LVEF after a 2 year follow-up. Despite an optimal medical therapy at the time of implantation, we were able to further improve the maximal treatment doses after implantation. This study highlights the issue of what should be considered as \u27optimal\u27 therapy and the possibility of improvement of LVEF related to a real optimized treatment before implantation

Modeling of oropharyngeal articulatory adaptation to compensate for the acoustic effects of nasalization

Hypernasality is one of the most detrimental speech disturbances that lead to declines of speech intelligibility. Velopharyngeal inadequacy, which is associated with anatomic defects such as cleft palate or neuromuscular disorders that affect velopharygneal function, is the primary cause of hypernasality. A simulation study by Rong and Kuehn [J. Speech Lang. Hear. Res. 55(5), 1438–1448 (2012)] demonstrated that properly adjusted oropharyngeal articulation can reduce nasality for vowels synthesized with an articulatory model [Mermelstein, J. Acoust. Soc. Am. 53(4), 1070–1082 (1973)]. In this study, a speaker-adaptive articulatory model was developed to simulate speaker-customized oropharyngeal articulatory adaptation to compensate for the acoustic effects of nasalization on /a/, /i/, and /u/. The results demonstrated that (1) the oropharyngeal articulatory adaptation effectively counteracted the effects of nasalization on the second lowest formant frequency (F2) and partially compensated for the effects of nasalization on vowel space (e.g., shifting and constriction of vowel space) and (2) the articulatory adaptation strategies generated by the speaker-adaptive model might be more efficacious for counteracting the acoustic effects of nasalization compared to the adaptation strategies generated by the standard articulatory model in Rong and Kuehn. The findings of this study indicated the potential of using oropharyngeal articulatory adaptation as a means to correct maladaptive articulatory behaviors and to reduce nasalit

Allelopathy of Bracken Fern (Pteridium arachnoideum): New Evidence from Green Fronds, Litter, and Soil

The neotropical bracken fern Pteridium arachnoideum (Kaulf.) Maxon. (Dennstaedtiaceae) is described as an aggressive pioneer plant species. It invades abandoned or newly burned areas and represents a management challenge at these invaded sites. Native to the Atlantic Forest and Cerrado (Tropical Savanna) Brazilian biomes, P. arachnoideum has nevertheless become very problematic in these conservation hotspots. Despite some reports suggesting a possible role of allelopathy in this plant’s dominance, until now there has been little evidence of isolated and individually identified compounds with phytotoxic activities present in its tissues or in the surrounding environment. Thus, the aim of this study was to investigate the allelopathic potential of P. arachnoideum by isolating and identifying any secondary metabolites with phytotoxic activity in its tissues, litter, and soil. Bioguided phytochemical investigation led to the isolation and identification of the proanthocyanidin selligueain A as the major secondary compound in the green fronds and litter of this fern. It is produced by P. arachnoideum in its green fronds, remains unaltered during the senescence process, and is the major secondary compound present in litter. Selligueain A showed phytotoxic activity against the selected target species sesame (Sesamum indicum) early development. In particular, the compound inhibited root and stem growth, and root metaxylem cell size but did not affect chlorophyll content. This compound can be considered as an allelochemical because it is present in the soil under P. arachnoideum patches as one of the major compounds in the soil solution. This is the first report of the presence of selligueain A in any member of the Dennstaedtiaceae family and the first time an isolated and identified allelochemical produced by members of the Pteridium species complex has been described. This evidence of selligueain A as a putative allelochemical of P. arachnoideum reinforces the role of allelopathy in the dominance processes of this plant in the areas where it occurs

Glycophenotypic Alterations Induced by Pteridium aquilinum in Mice Gastric Mucosa: Synergistic Effect with Helicobacter pylori Infection

The bracken fern Pteridium aquilinum is a plant known to be carcinogenic to animals. Epidemiological studies have shown an association between bracken fern exposure and gastric cancer development in humans. The biological effects of exposure to this plant within the gastric carcinogenesis process are not fully understood. In the present work, effects in the gastric mucosa of mice treated with Pteridium aquilinum were evaluated, as well as molecular mechanisms underlying the synergistic role with Helicobacter pylori infection. Our results showed that exposure to Pteridium aquilinum induces histomorphological modifications including increased expression of acidic glycoconjugates in the gastric mucosa. The transcriptome analysis of gastric mucosa showed that upon exposure to Pteridium aquilinum several glycosyltransferase genes were differently expressed, including Galntl4, C1galt1 and St3gal2, that are mainly involved in the biosynthesis of simple mucin-type carbohydrate antigens. Concomitant treatment with Pteridium aquilinum and infection with Helicobacter pylori also resulted in differently expressed glycosyltransferase genes underlying the biosynthesis of terminal sialylated Lewis antigens, including Sialyl-Lewisx. These results disclose the molecular basis for the altered pattern of glycan structures observed in the mice gastric mucosa. The gene transcription alterations and the induced glycophenotypic changes observed in the gastric mucosa contribute for the understanding of the molecular mechanisms underlying the role of Pteridium aquilinum in the gastric carcinogenesis process

Effect of arbuscular mycorrhizal (AM) colonization on terpene emission and content of Artemisia annua L.

Plant roots interact with a wide variety of rhizospheric microorganisms, including bacteria and the symbiontic arbuscular mycorrhizal (AM) fungi. The mycorrhizal symbiosis represents a series of complex feedbacks between plant and fungus regulated by their physiology and nutrition. Despite the widespread distribution and ecological significance of AM symbiosis, little is known about the potential of AM fungi to affect plant VOC metabolism. The purpose of this study was to investigate whether colonization of plant roots by AM fungi and associated soil microorganisms affects VOC emission and content of Artemisia annua L. plants (Asteraceae). Two inoculum types were evaluated: one consisted of only an arbuscular mycorrhizal (AM) fungus species (Glomus spp.), and the other was a mixture of different Glomus species and associated soil bacteria. Inoculated plants were compared with non-inoculated plants and with plants supplemented with extra phosphorus (P) to obtain plants of the same size as mycorrhizal plants, thus excluding potentially-confounding mycorrhizal effects on shoot growth. VOC emissions of Artemisia annua plants were analyzed by leaf cuvette sampling followed by off-line measurements with pre-concentration and gas chromatography mass spectrometry (GC-MS). Measurements of CO2 and H2O exchanges were conducted simultaneously. Several volatile monoterpenes were identified and characterized from leaf emissions of Artemisia annua L. by GC-MS analysis. The main components identified belong to different monoterpene structures: alpha-pinene, beta-pinene, camphor, 1,8-cineole, limonene, and artemisia ketone. A good correlation between monoterpene leaf concentration and leaf emission was found. Leaf extracts included also several sesquiterpenes. Total terpene content and emission was not affected by AM inoculation with or without bacteria, while emission of limonene and artemisia ketone was stimulated by this treatment. No differences were found among treatments for single monoterpene content, while accumulation of specific sesquiterpenes in leaves was altered in mycorrhizal plants compared to control plants. Growth conditions seemed to have mainly contributed to the outcome of the symbiosis and influenced the magnitude of the plant response. These results highlight the importance of considering the below-ground interaction between plant and soil for estimating VOC emission rates and their ecological role at multitrophic level

De novo characterization of the gametophyte transcriptome in bracken fern, Pteridium aquilinum

<p>Abstract</p> <p>Background</p> <p>Because of their phylogenetic position and unique characteristics of their biology and life cycle, ferns represent an important lineage for studying the evolution of land plants. Large and complex genomes in ferns combined with the absence of economically important species have been a barrier to the development of genomic resources. However, high throughput sequencing technologies are now being widely applied to non-model species. We leveraged the Roche 454 GS-FLX Titanium pyrosequencing platform in sequencing the gametophyte transcriptome of bracken fern (<it>Pteridium aquilinum</it>) to develop genomic resources for evolutionary studies.</p> <p>Results</p> <p>681,722 quality and adapter trimmed reads totaling 254 Mbp were assembled <it>de novo </it>into 56,256 unique sequences (i.e. unigenes) with a mean length of 547.2 bp and a total assembly size of 30.8 Mbp with an average read-depth coverage of 7.0×. We estimate that 87% of the complete transcriptome has been sequenced and that all transcripts have been tagged. 61.8% of the unigenes had blastx hits in the NCBI nr protein database, representing 22,596 unique best hits. The longest open reading frame in 52.2% of the unigenes had positive domain matches in InterProScan searches. We assigned 46.2% of the unigenes with a GO functional annotation and 16.0% with an enzyme code annotation. Enzyme codes were used to retrieve and color KEGG pathway maps. A comparative genomics approach revealed a substantial proportion of genes expressed in bracken gametophytes to be shared across the genomes of <it>Arabidopsis</it>, <it>Selaginella </it>and <it>Physcomitrella</it>, and identified a substantial number of potentially novel fern genes. By comparing the list of <it>Arabidopsis </it>genes identified by blast with a list of gametophyte-specific <it>Arabidopsis </it>genes taken from the literature, we identified a set of potentially conserved gametophyte specific genes. We screened unigenes for repetitive sequences to identify 548 potentially-amplifiable simple sequence repeat loci and 689 expressed transposable elements.</p> <p>Conclusions</p> <p>This study is the first comprehensive transcriptome analysis for a fern and represents an important scientific resource for comparative evolutionary and functional genomics studies in land plants. We demonstrate the utility of high-throughput sequencing of a normalized cDNA library for <it>de novo </it>transcriptome characterization and gene discovery in a non-model plant.</p

Validating the predictive ability of the 2MACE score for major adverse cardiovascular events in patients with atrial fibrillation: results from phase II/III of the GLORIA-AF registry

The 2MACE score was specifically developed as a risk-stratification tool in atrial fibrillation (AF) to predict cardiovascular outcomes. We evaluated the predictive ability of the 2MACE score in the GLORIA-AF registry. All eligible patients from phase II/III of the prospective global GLORIA-AF registry were included. Major adverse cardiac events (MACEs) were defined as the composite outcome of stroke, myocardial infarction and cardiovascular death. Cox proportional hazards were used to examine the relationship between the 2MACE score and study outcomes. Predictive capability of the 2MACE score was investigated using receiver-operating characteristic curves. A total of 25,696 patients were included (mean age 71 years, female 44.9%). Over 3 years, 1583 MACEs were recorded. Patients who had MACE were older, with more cardiovascular risk factors and were less likely to be managed using a rhythm-control strategy. The median 2MACE score in the MACE and non-MACE groups were 2 (IQR 1-3) and 1 (IQR 0-2), respectively (p &lt; 0.001). The 2MACE score was positively associated with an increase in the risk of MACE, with a score of &amp; GE; 2 providing the best combination of sensitivity (69.6%) and specificity (51.6%), HR 2.47 (95% CI, 2.21-2.77). The 2MACE score had modest predictive performance for MACE in patients with AF (AUC 0.655 (95% CI, 0.641-0.669)). Our analysis in this prospective global registry demonstrates that the 2MACE score can adequately predict the risk of MACE (defined as myocardial infarction, CV death and stroke) in patients with AF. Clinical trial registration:. Unique identifiers: NCT01468701, NCT01671007 and NCT0193737