Involvement of pro-inflammatory cytokines and growth factors in the pathogenesis of Dupuytren's contracture: a novel target for a possible future therapeutic strategy?

Dupuytren's contracture (DC) is a benign fibro-proliferative disease of the hand causing fibrotic nodules and fascial cords which determine debilitating contracture and deformities of fingers and hands. The present study was designed to characterize pro-inflammatory cytokines and growth factors involved in the pathogenesis, progression and recurrence of this disease, in order to find novel targets for alternative therapies and strategies in controlling DC. The expression of pro-inflammatory cytokines and of growth factors was detected by immunohistochemistry in fibrotic nodules and normal palmar fascia resected respectively from patients affected by DC and carpal tunnel syndrome (CTS; as negative controls). Reverse transcription (RT)-PCR analysis and immunofluorescence were performed to quantify the expression of transforming growth factor (TGF)-β1, interleukin (IL)-1β and vascular endothelial growth factor (VEGF) by primary cultures of myofibroblasts and fibroblasts isolated from Dupuytren's nodules. Histological analysis showed high cellularity and high proliferation rate in Dupuytren's tissue, together with the presence of myofibroblastic isotypes; immunohistochemical staining for macrophages was completely negative. In addition, a strong expression of TGF-β1, IL-1β and VEGF was evident in the extracellular matrix and in the cytoplasm of fibroblasts and myofibroblasts in Dupuytren's nodular tissues, as compared with control tissues. These results were confirmed by RT-PCR and by immunofluorescence in pathological and normal primary cell cultures. These preliminary observations suggest that TGF-β1, IL-1β and VEGF may be considered potential therapeutic targets in the treatment of Dupuytren's disease (DD)

Neuronal dynamics of signal selective motor plan cancellation in the macaque dorsal premotor cortex

Primates adopt various strategies to interact with the environment. Yet, no study has examined the effects of behavioural strategies with regard to how movement inhibition is implemented at the neuronal level. We used a modified version of the stop-task by adding an extra signal – termed the Ignore signal – capable of influencing the inhibition of movements only within a specific strategy. We simultaneously recorded multisite neuronal activity from the dorsal premotor (PMd) cortex of macaque monkeys during the task and applied a state-space approach. As a result, we found that movement generation is characterized by neuronal dynamics that evolve between subspaces. When the movement is halted, this evolution is arrested and inverted. Conversely, when the Ignore signal is presented, inversion of the evolution is observed briefly and only when a specific behavioural strategy is adopted. Moreover, neuronal signatures during the inhibitory process were predictive of how PMd processes inhibitory signals, allowing the classification of the resulting behavioural strategy. Our data further corroborate the PMd as a critical node in movement inhibition

Simulation and Analysis of Dynamic Regimes Involving Ground and Excited State Transitions in Quantum Dot Passively Mode-Locked Lasers

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An Italian prospective multicenter survey on patients suspected of having non-celiac gluten sensitivity.

BACKGROUND: Non-celiac gluten sensitivity (NCGS) is still an undefined syndrome with several unsettled issues despite the increasing awareness of its existence. We carried out a prospective survey on NCGS in Italian centers for the diagnosis of gluten-related disorders, with the aim of defining the clinical picture of this new syndrome and to establish roughly its prevalence compared with celiac disease. METHODS: From November 2012 to October 2013, 38 Italian centers (27 adult gastroenterology, 5 internal medicine, 4 pediatrics, and 2 allergy) participated in this prospective survey. A questionnaire was used in order to allow uniform and accurate collection of clinical, biochemical, and instrumental data. RESULTS: In total, 486 patients with suspected NCGS were identified in this 1-year period. The female/male ratio was 5.4 to 1, and the mean age was 38 years (range 3–81). The clinical picture was characterized by combined gastrointestinal (abdominal pain, bloating, diarrhea and/or constipation, nausea, epigastric pain, gastroesophageal reflux, aphthous stomatitis) and systemic manifestations (tiredness, headache, fibromyalgia-like joint/muscle pain, leg or arm numbness, 'foggy mind,' dermatitis or skin rash, depression, anxiety, and anemia). In the large majority of patients, the time lapse between gluten ingestion and the appearance of symptoms varied from a few hours to 1 day. The most frequent associated disorders were irritable bowel syndrome (47%), food intolerance (35%) and IgE-mediated allergy (22%). An associated autoimmune disease was detected in 14% of cases. Regarding family history, 18% of our patients had a relative with celiac disease, but no correlation was found between NCGS and positivity for HLA-DQ2/-DQ8. IgG anti-gliadin antibodies were detected in 25% of the patients tested. Only a proportion of patients underwent duodenal biopsy; for those that did, the biopsies showed normal intestinal mucosa (69%) or mild increase in intraepithelial lymphocytes (31%). The ratio between suspected NCGS and new CD diagnoses, assessed in 28 of the participating centers, was 1.15 to 1. CONCLUSIONS: This prospective survey shows that NCGS has a strong correlation with female gender and adult age. Based on our results, the prevalence of NCGS seems to be only slightly higher than that of celiac disease. Please see related article http://www.biomedcentral.com/1741-7015/12/86

Development of high-speed directly-modulated DFB and DBR lasers with surface gratings

The conventional distributed feedback and distributed Bragg reflector edge-emitting lasers employ buried gratings, which require two or more epitaxial growth steps. By using lateral corrugations of the ridge-waveguide as surface gratings the epitaxial overgrowth is avoided, reducing the fabrication complexity, increasing the yield and reducing the fabrication cost. The surface gratings are applicable to different materials, including Al-containing ones and can be easily integrated in complex device structures and photonic circuits. Single-contact and multiple contact edge-emitting lasers with laterally-corrugated ridge waveguide gratings have been developed both on GaAs and InP substrates with the aim to exploit the photon-photon resonance in order to extend their direct modulation bandwidth. The paper reports on the characteristics of such surface-grating-based lasers emitting both at 1.3 and 1.55 μm and presents the photon-photon resonance extended small-signal modulation bandwidth (> 20 GHz) achieved with a 1.6 mm long single-contact device under direct modulation. Similarly structured devices, with shorter cavity lengths are expected to exceed 40 GHz smallsignal modulation bandwidth under direct modulatio

Spatial distribution of heterochromatin bodies in the nuclei of Triatoma infestans (Klug)

Constitutive heterochromatin typically exhibits low gene density and is commonly found adjacent or close to the nuclear periphery, in contrast to transcriptionally active genes concentrated in the innermost nuclear region. In Triatoma infestans cells, conspicuous constitutive heterochromatin forms deeply stained structures named chromocenters. However, to the best of our knowledge, no information exists regarding whether these chromocenters acquire a precise topology in the cell nuclei or whether their 18S rDNA, which is important for ribosome function, faces the nuclear center preferentially. In this work, the spatial distribution of fluorescent Feulgen-stained chromocenters and the distribution of their 18S rDNA was analyzed in Malpighian tubule cells of T. infestans using confocal microscopy. The chromocenters were shown to be spatially positioned relatively close to the nuclear periphery, though not adjacent to it. The variable distance between the chromocenters and the nuclear periphery suggests mobility of these bodies within the cell nuclei. The distribution of 18S rDNA at the edge of the chromocenters was not found to face the nuclear interior exclusively. Because the genome regions containing 18S rDNA in the chromocenters also face the nuclear periphery, the proximity of the chromocenters to this nuclear region is not assumed to be associated with overall gene silencing.133CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP304668/2014-1; 304668/2014-1Não tem2015/10356-2This research was supported by the São Paulo State Research Foundation (FAPESP, Brazil; grant no. 2015/10356-2) and the Brazilian National Council for Research and Development (CNPq, grant no. 304668/2014-1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. C.H.L.I. received a fellowship from the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES, Brazil – Finance Code 001). M.L.S.M. received a fellowship from CNPq (grant no. 304668/2014-1)

Safety of occasional ingestion of gluten in patients with celiac disease: a real-life study

Background Gluten-free diet (GFD) decreases the quality of life of celiac disease (CD) patients, who frequently ask to occasionally ingest gluten-containing food. We evaluated CD patients reporting voluntary and occasional transgressions to their GFD. Methods From October 2017 to September 2018, the patients reporting occasional and voluntary gluten ingestion (GFD-noncompliant) were prospectively enrolled. These patients underwent clinical examination, blood tests, duodenal biopsy, capsule enteroscopy (CE), and a validated food-frequency questionnaire (FFQ) assessing the frequency and quantity of gluten intake. Mortality was calculated and compared to the general population. A group of patients on strict GFD (GFD-adherent) acted as controls. Results One thousand three hundred seventy-eight CD patients were evaluated during the study period. One hundred nine (8%) reported occasional (weekly or monthly) voluntary ingestion of gluten. The mean gluten intake was 185.2 +/- 336.9 g/year, and the duration of their incorrect GFD was 8.6 +/- 6.9 years. Among the noncompliant patients, 57% did not present any histological alteration; furthermore, the Marsh score profile was not different between compliant and noncompliant patients. Seventy percent did not present any alteration at CE. Seventy-five percent of patients reported no gastrointestinal symptoms after gluten ingestion. Twenty-three percent of patients in the GFD-noncompliant group presented positive tTG-IgA. No association was found between gluten intake, clinical symptoms, and biomarkers. Mortality was not different between the groups and the general population. Conclusions Our results are that in a real-life scenario, a group of CD patients on long-term gluten intake showed no significant clinical symptoms or small bowel damage, thus suggesting that a degree of tolerance towards gluten consumption can be reached

Reverse ground-state excited-state emission transition dynamics in two-section quantum dot semiconductor lasers: Simultaneous two-state mode-locking and state-switching via a resistor self-electro-optic effect device (SEED)

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