Allergen sensitization stratifies IL-31 production by memory T cells in atopic dermatitis patients

Background:The role of allergen sensitization in IL-31 production by T cells and specifically in the clinical context of atopic dermatitis (AD) has not been characterized. MethodsThe response to house dust mite (HDM) in purified memory T cells cocultured with epidermal cells from AD patients (n=58) and control subjects (n=11) was evaluated. AD-associated cytokines from culture supernatants, plasma proteins and mRNA expression from cutaneous lesions were assessed and related with the clinical features of the patients. ResultsHDM-induced IL-31 production by memory T cells defined two subsets of AD patients according to the presence or absence of IL-31 response. Patients in the IL-31 producing group showed a more inflammatory profile, and increased HDM-specific (sp) and total IgE levels compared to the IL-31 non-producing group. A correlation between IL-31 production and patient's pruritus intensity, plasma CCL27 and periostin was detected. When the same patients were analyzed based on sp IgE and total IgE levels, an increased IL-31 in vitro response, as well as type 2 markers in plasma and cutaneous lesions, was found in patients with sp IgE levels > 100 kUA/L and total IgE levels > 1000 kU/L. The IL-31 response by memory T cells was restricted to the cutaneous lymphocyte-associated antigen (CLA)(+) T-cell subset. ConclusionIgE sensitization to HDM allows stratifying IL-31 production by memory T cells in AD patients and relating it to particular clinical phenotypes of the disease

Metabolic Syndrome as a Cardiovascular Disease Risk Factor: Patients Evaluated in Primary Care

To estimate the prevalence of metabolic syndrome (MS) in a population receiving attention in primary care centers (PCC) we selected a random cohort of ostensibly normal subjects from the registers of 5 basic-health area (BHA) PCC. Diagnosis of MS was with the WHO, NCEP and IDF criteria. Variables recorded were: socio-demographic data, CVD risk factors including lipids, obesity, diabetes, blood pressure and smoking habit and a glucose tolerance test outcome. Of the 720 individuals selected (age 60.3 ± 11.5 years), 431 were female, 352 hypertensive, 142 diabetic, 233 pre-diabetic, 285 obese, 209 dyslipemic and 106 smokers. CVD risk according to the Framingham and REGICOR calculation was 13.8 ± 10% and 8.8 ± 9.8%, respectively. Using the WHO, NCEP and IDF criteria, MS was diagnosed in 166, 210 and 252 subjects, respectively and the relative risk of CVD complications in MS subjects was 2.56. Logistic regression analysis indicated that the MS components (WHO set), the MS components (IDF set) and the female gender had an increased odds ratio for CVD of 3.48 (95CI%: 2.26–5.37), 2.28 (95%CI: 1.84–4.90) and 2.26 (95%CI: 1.48–3.47), respectively. We conclude that MS and concomitant CVD risk is high in ostensibly normal population attending primary care clinics, and this would necessarily impinge on resource allocation in primary care

Acyl-CoA synthetase 3 promotes lipid droplet biogenesis in ER microdomains

Control of lipid droplet (LD) nucleation and copy number are critical, yet poorly understood, processes. We use model peptides that shift from the endoplasmic reticulum (ER) to LDs in response to fatty acids to characterize the initial steps of LD formation occurring in lipid-starved cells. Initially, arriving lipids are rapidly packed in LDs that are resistant to starvation (pre-LDs). Pre-LDs are restricted ER microdomains with a stable core of neutral lipids. Subsequently, a first round of “emerging” LDs is nucleated, providing additional lipid storage capacity. Finally, in proportion to lipid concentration, new rounds of LDs progressively assemble. Confocal microscopy and electron tomography suggest that emerging LDs are nucleated in a limited number of ER microdomains after a synchronized stepwise process of protein gathering, lipid packaging, and recognition by Plin3 and Plin2. A comparative analysis demonstrates that the acyl-CoA synthetase 3 is recruited early to the assembly sites, where it is required for efficient LD nucleation and lipid storag

Dinophysis Ehrenberg (Dinophyceae) in Southern Chile harbours red cryptophyte plastids from Rhodomonas/Storeatula clade

Photosynthetic species of the dinoflagellate genus Dinophysis are known to retain temporary cryptophyte plastids of the Teleaulax/Plagioselmis/Geminigera clade after feeding the ciliate Mesodinium rubrum. In the present study, partial plastid 23S rDNA sequences were retrieved in Southern Chilean waters from oceanic (Los Lagos region), and fjord systems (Aysén region), in single cells of Dinophysis and accompanying organisms (the heliozoan Actinophrys cf. sol and tintinnid ciliates), identified by means of morphological discrimination under the light microscope. All plastid 23S rDNA sequences (n = 23) from Dinophysis spp. (Dinophysis acuta, D. caudata, D. tripos and D. subcircularis) belonged to cryptophytes from clade V (Rhinomonas, Rhodomonas and Storeatula), although they could not be identified at genus level. Moreover, five plastid sequences obtained from heliozoans (Actinophryida, tentatively identified as Actinophrys cf. sol), and tintinnid ciliates, grouped together with those cryptophyte sequences. In contrast, two additional sequences from tintinnids belonged to other taxa (chlorophytes and cyanobacteria). Overall, the present study represents the first time that red cryptophyte plastids outside of the Teleaulax/Plagioselmis/Geminigera clade dominate in wild photosynthetic Dinophysis spp. These findings suggest that either Dinophysis spp. are able to feed on other ciliate prey than Mesodinium and/or that cryptophyte plastids from clade V prevail in members of the M. rubrum species complex in the studied area

Itch and Sleep Improvements with Baricitinib in Patients with Atopic Dermatitis : A Post Hoc Analysis of 3 Phase 3 Studies

Altres ajuts: Eli Lilly and Company.Introduction: Burdensome symptoms of atopic dermatitis include itch and sleep disturbance. This post hoc analysis reports the effect of baricitinib on itch and sleep disturbance during the first week of treatment in 3 phase 3 studies. Methods: Patients were randomized 2:1:1:1 to once-daily placebo or baricitinib 1 mg, 2 mg, or 4 mg in the BREEZE-AD1 and -AD2 studies and 1:1:1 to once-daily placebo or baricitinib 2 mg or 4 mg in the BREEZE-AD7 study. Topical corticosteroids were only allowed in BREEZE-AD7. Patients completed the itch numerical rating scale and atopic dermatitis sleep scale (ADSS) items 1-3 using an electronic daily diary. Data were analyzed by study as least squares mean percent change from baseline in daily scores for the randomized patients. Mixed model repeated measures analysis was used to analyze change from baseline values. Results: A total of 624, 615, and 329 patients were randomized in BREEZE-AD1, -AD2, and -AD7, respectively. Itch severity significantly improved with baricitinib 2 mg and 4 mg versus placebo starting at day 2 (1 day after first dose) in BREEZE-AD1 and -AD7 and at day 1 in BREEZE-AD2. Patients' ability to fall asleep (ADSS item 1) significantly improved with baricitinib 2 mg and 4 mg versus placebo starting at day 2 in all three studies. There were significant improvements in patients waking due to itch (ADSS item 2) with baricitinib 4 mg versus placebo starting at day 2 in all three studies. Patients' ability to return to sleep after being woken by itch (ADSS item 3) was significantly improved with baricitinib 4 mg versus placebo starting at day 2 in BREEZE-AD1 and -AD2 and at day 4 in BREEZE-AD7. Conclusion: Rapid onset of action, typically 1 day after taking the first dose of baricitinib, was observed consistently for the burdensome symptoms of itch and sleep disturbance. ClinicalTrials.gov identifiers: BREEZE-AD1, NCT03334396; BREEZE-AD2, NCT03334422; BREEZE-AD7, NCT03733301

Acyl-CoA synthetase 3 promotes lipid droplet biogenesis in ER microdomains.

Control of lipid droplet (LD) nucleation and copy number are critical, yet poorly understood, processes. We use model peptides that shift from the endoplasmic reticulum (ER) to LDs in response to fatty acids to characterize the initial steps of LD formation occurring in lipid-starved cells. Initially, arriving lipids are rapidly packed in LDs that are resistant to starvation (pre-LDs). Pre-LDs are restricted ER microdomains with a stable core of neutral lipids. Subsequently, a first round of "emerging" LDs is nucleated, providing additional lipid storage capacity. Finally, in proportion to lipid concentration, new rounds of LDs progressively assemble. Confocal microscopy and electron tomography suggest that emerging LDs are nucleated in a limited number of ER microdomains after a synchronized stepwise process of protein gathering, lipid packaging, and recognition by Plin3 and Plin2. A comparative analysis demonstrates that the acyl-CoA synthetase 3 is recruited early to the assembly sites, where it is required for efficient LD nucleation and lipid storage

Alexandrium catenella cyst accumulation by passive and active dispersal agents: Implications for the potential spreading risk in Chilean Patagonian fjords

The dinoflagellate Alexandrium catenella is responsible for paralytic shellfish poisoning and negative socioeconomic impacts on the fishing industry and aquaculture. In Chilean Patagonia, the reasons underlying the significant increase in the geographical extension (from south to north) of A. catenella blooms during the last five decades are not well understood. To assess the potential spreading risk of A. catenella during an intense austral summer bloom, we conducted an in situ experiment in a "hotspot" of this dinoflagellate in southern Chile. The objective was to assess the accumulation of A. catenella resting cysts in passive (fishing nets) and active (mussels) dispersal agents during the phase of bloom decline. Large numbers of resting cysts were detected in fishing nets (maximum of 5334 cysts net−1 per month) at 5 m depth and in mussels (maximum of 16 cysts g−1 of digestive gland) near Vergara Island. The potential of these vectors to serve as inoculum sources and the implications of our findings for A. catenella population dynamics are discussed

Acyl-CoA synthetase 3 promotes lipid droplet biogenesis in ER microdomains.

Control of lipid droplet (LD) nucleation and copy number are critical, yet poorly understood, processes. We use model peptides that shift from the endoplasmic reticulum (ER) to LDs in response to fatty acids to characterize the initial steps of LD formation occurring in lipid-starved cells. Initially, arriving lipids are rapidly packed in LDs that are resistant to starvation (pre-LDs). Pre-LDs are restricted ER microdomains with a stable core of neutral lipids. Subsequently, a first round of"emerging" LDs is nucleated, providing additional lipid storage capacity. Finally, in proportion to lipid concentration, new rounds of LDs progressively assemble. Confocal microscopy and electron tomography suggest that emerging LDs are nucleated in a limited number of ER microdomains after a synchronized stepwise process of protein gathering, lipid packaging, and recognition by Plin3 and Plin2. A comparative analysis demonstrates that the acyl-CoA synthetase 3 is recruited early to the assembly sites, where it is required for efficient LD nucleation and lipid storage