Stick-slip instability for viscous fingering in a gel

The growth dynamics of an air finger injected in a visco-elastic gel (a PVA/borax aqueous solution) is studied in a linear Hele-Shaw cell. Besides the standard Saffmann-Taylor instability, we observe - with increasing finger velocities - the existence of two new regimes: (a) a stick-slip regime for which the finger tip velocity oscillates between 2 different values, producing local pinching of the finger at regular intervals, (b) a ``tadpole'' regime where a fracture-type propagation is observed. A scaling argument is proposed to interpret the dependence of the stick-slip frequency with the measured rheological properties of the gel.Comment: 7 pages, 4 figures. Submitted to Europhysics Letter

Refractory vasculitic ulcer of the toe in adolescent suffering from Systemic Lupus Erythematosus treated successfully with hyperbaric oxygen therapy

Skin ulcers are a dangerous and uncommon complication of vasculitis. We describe the case of a teenager suffering from Systemic Lupus Erythematosus with digital ulcer resistant to conventional therapy, treated successfully with Hyperbaric Oxygen Therapy. The application of hyperbaric oxygen, which is used for the treatment of ischemic ulcers, is an effective and safe therapeutic option in patients with ischemic vasculitic ulcers in combination with immunosuppressive drugs. Further studies are needed to evaluate its role as primary therapy for this group of patients

Perioperative chemotherapy in poorly differentiated neuroendocrine neoplasia of the bladder: A multicenter analysis

There is scant evidence about optimal management of poorly differentiated neuroendocrine carcinoma of the bladder (BNEC). We performed a multicenter retrospective study on BNEC patients from 13 Italian neuroendocrine-dedicated centers to analyze strategies associated with better outcomes. Mixed adeno-neuroendocrine carcinomas (MANEC) were included. We analyzed overall survival (OS) in the overall cohort, relapse-free survival (RFS) in radically operated patients and progression-free survival (PFS) in patients who received chemotherapy for metastatic disease. Fifty-one BNEC patients were included (male: 46, median age: 70 years). Overall, median OS was 16.0 months, radical tumor resection was performed in 37 patients (72.5%) and 11 of these (29.7%) also received peri-operative platinum-etoposide chemotherapy. Median OS was longer in patients with better performance status (PS) and in those with stage I–III disease at diagnosis compared to stage IV. Among patients who underwent radical tumor resection (N = 37), RFS was longer in patients with better PS and showed a trend towards a longer RFS in those treated with peri-operative chemotherapy than with surgery alone (11 vs. 6 months; p = 0.078). Among 28 patients receiving chemotherapy for metastatic disease, PFS was 5.0 months and there was a trend towards improved PFS in patients receiving carboplatin-etoposide chemotherapy compared to other regimens. A multivariate model unmasked a significant association between carboplatin-etoposide chemotherapy and risk for disease progression or death (HR: 0.39 (95%CI: 0.16–0.96) p = 0.040). Performance status might be associated with improved RFS in radically operated patients, while type of chemotherapy might affect PFS in patients receiving chemotherapy for metastatic BNEC

Biodiversity and ecology of lichens of Katmai and Lake Clark National Parks and Preserves, Alaska

We inventoried lichens in Lake Clark (LACL) and Katmai (KATM) National Parks and Preserves. We assembled the known information on lichens in these parks by combining field, herbarium, and literature studies. Our results provide baseline data on lichen occurrence that may be used in resource condition assessments, vulnerability assessments, long-term ecological monitoring, and resource management. We report a total of 896 taxa of lichenized fungi from the Parks, adding 889 taxa to the total of seven taxa reported for the Parks by the National Park Service database and including ten new species first published elsewhere. An additional 15 lichenicolous fungi are reported here. Seven non-lichenized fungi associated with young living twigs of particular host species are also included. Sixteen species are new to Alaska, and six species new to North America (Caloplaca fuscorufa, Lecanora leucococca s.l., Ochrolechia brodoi, Protoparmelia memnonia, and Rhizocarpon leptolepis). Four new combinations are made, Cetraria minuscula, Enchylium millegranum var. bachmanianum, Lathagrium undulatum var. granulosum, and Protomicarea alpestris. Additional new species based on collections from the Parks have been described in separate publications

NLRP3 inflammasome assembly in neutrophils is supported by PAD4 and promotes NETosis under sterile conditions

© The Author(s), 2021. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Muenzer, P., Negro, R., Fukui, S., di Meglio, L., Aymonnier, K., Chu, L., Cherpokova, D., Gutch, S., Sorvillo, N., Shi, L., Magupalli, V. G., Weber, A. N. R., Scharf, R. E., Waterman, C. M., Wu, H., & Wagner, D. D. NLRP3 inflammasome assembly in neutrophils is supported by PAD4 and promotes NETosis under sterile conditions. Frontiers in Immunology, 12, (2021): 683803, https://doi.org/10.3389/fimmu.2021.683803.Neutrophil extracellular trap formation (NETosis) and the NLR family pyrin domain containing 3 (NLRP3) inflammasome assembly are associated with a similar spectrum of human disorders. While NETosis is known to be regulated by peptidylarginine deiminase 4 (PAD4), the role of the NLRP3 inflammasome in NETosis was not addressed. Here, we establish that under sterile conditions the cannonical NLRP3 inflammasome participates in NETosis. We show apoptosis-associated speck-like protein containing a CARD (ASC) speck assembly and caspase-1 cleavage in stimulated mouse neutrophils without LPS priming. PAD4 was needed for optimal NLRP3 inflammasome assembly by regulating NLRP3 and ASC protein levels post-transcriptionally. Genetic ablation of NLRP3 signaling resulted in impaired NET formation, because NLRP3 supported both nuclear envelope and plasma membrane rupture. Pharmacological inhibition of NLRP3 in either mouse or human neutrophils also diminished NETosis. Finally, NLRP3 deficiency resulted in a lower density of NETs in thrombi produced by a stenosis-induced mouse model of deep vein thrombosis. Altogether, our results indicate a PAD4-dependent formation of the NLRP3 inflammasome in neutrophils and implicate NLRP3 in NETosis under noninfectious conditions in vitro and in vivo.This work was supported by a grant from National Heart, Lung, and Blood Institute of the National Institutes of Health (grant R35 HL135765) and a Steven Berzin family support to DDW, an Individual Erwin Deutsch fellowship by the German, Austrian and Swiss Society of Thrombosis and Hemostasis Research to RES, a Whitman fellowship (MBL) to DDW, and an Individual Marie Skłodowska-Curie Actions fellowship by the European Commission (796365 - COAGULANT) to PM. ANRW was funded by the Deutsche Forschungsgemeinschaft (TRR156/2 –246807620) and a research grant (We-4195/15-19). CMW was supported by the Division of Intramural Research, NHLBI, NIH

captem or folfiri as second line therapy in neuroendocrine carcinomas and exploratory analysis of predictive role of pet imaging and biological markers seneca study

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Author Correction: Enhanced NF-κB signaling in type-2 dendritic cells at baseline predicts non-response to adalimumab in psoriasis.

Funder: Department of HealthBiologic therapies have transformed the management of psoriasis, but clinical outcome is variable leaving an unmet clinical need for predictive biomarkers of response. Here we perform in-depth immunomonitoring of blood immune cells of 67 patients with psoriasis, before and during therapy with the anti-TNF drug adalimumab, to identify immune mediators of clinical response and evaluate their predictive value. Enhanced NF-κBp65 phosphorylation, induced by TNF and LPS in type-2 dendritic cells (DC) before therapy, significantly correlates with lack of clinical response after 12 weeks of treatment. The heightened NF-κB activation is linked to increased DC maturation in vitro and frequency of IL-17+ T cells in the blood of non-responders before therapy. Moreover, lesional skin of non-responders contains higher numbers of dermal DC expressing the maturation marker CD83 and producing IL-23, and increased numbers of IL-17+ T cells. Finally, we identify and clinically validate LPS-induced NF-κBp65 phosphorylation before therapy as a predictive biomarker of non-response to adalimumab, with 100% sensitivity and 90.1% specificity in an independent cohort. Our study uncovers important molecular and cellular mediators underpinning adalimumab mechanisms of action in psoriasis and we propose a blood biomarker for predicting clinical outcome

Defining trajectories of response in patients with psoriasis treated with biologic therapies

From Wiley via Jisc Publications RouterHistory: accepted 2021-04-03, pub-electronic 2021-06-04Article version: VoRPublication status: PublishedFunder: Medical Research Council; Id: http://dx.doi.org/10.13039/501100000265; Grant(s): MR/K006665/1, MR/L011808/1, MR/N00583X/1Summary: Background: The effectiveness and cost‐effectiveness of biologic therapies for psoriasis are significantly compromised by variable treatment responses. Thus, more precise management of psoriasis is needed. Objectives: To identify subgroups of patients with psoriasis treated with biologic therapies, based on changes in their disease activity over time, that may better inform patient management. Methods: We applied latent class mixed modelling to identify trajectory‐based patient subgroups from longitudinal, routine clinical data on disease severity, as measured by the Psoriasis Area and Severity Index (PASI), from 3546 patients in the British Association of Dermatologists Biologics and Immunomodulators Register, as well as in an independent cohort of 2889 patients pooled across four clinical trials. Results: We discovered four discrete classes of global response trajectories, each characterized in terms of time to response, size of effect and relapse. Each class was associated with differing clinical characteristics, e.g. body mass index, baseline PASI and prevalence of different manifestations. The results were verified in a second cohort of clinical trial participants, where similar trajectories following the initiation of biologic therapy were identified. Further, we found differential associations of the genetic marker HLA‐C*06:02 between our registry‐identified trajectories. Conclusions: These subgroups, defined by change in disease over time, may be indicative of distinct endotypes driven by different biological mechanisms and may help inform the management of patients with psoriasis. Future work will aim to further delineate these mechanisms by extensively characterizing the subgroups with additional molecular and pharmacological data