Clustering based on clinicophysiologic parameters yielded 4 stable and reproducible clusters that associate with different pathobiological pathways.

Objective To investigate the molecular mechanisms of CCL13/monocyte chemoattractant protein 4 (MCP‐4) chemokine expression through proinflammatory cytokines in different primary human fibroblasts and the contribution of CCL13 to monocyte migration. Methods Using RNase protection assays and enzyme‐linked immunosorbent assays, we quantified the expression of CCL13 compared with that of CCL2/MCP‐1 in primary human fibroblasts. Boyden chamber assays were performed to determine the importance of CCL13 for migration of primary monocytes. Pharmacologic inhibitors as well as small interfering RNA knockdown approaches were used to investigate the signaling pathways regulating CCL13 expression. Results The interleukin‐6 (IL‐6)–type cytokine oncostatin M (OSM) was a powerful inducer of CCL13 expression in primary synovial fibroblasts from patients with rheumatoid arthritis (RA) as well as those from healthy control subjects but not in other types of fibroblasts. Neither IL‐6 nor tumor necrosis factor α could stimulate the expression of CCL13 in synovial fibroblasts; IL‐1β was a very weak inducer. Synovial fibroblasts from patients with RA constitutively produced low amounts of CCL13, which was partially dependent on constitutive production of OSM. By investigating the underlying molecular mechanism, we identified STAT‐5, ERK‐1/2, and p38 as critical factors involved in OSM‐dependent transcription and messenger RNA stabilization of CCL13. Conclusion In contrast to other prominent cytokines involved in the pathogenesis of RA, OSM can strongly up‐regulate the expression of CCL13, a chemokine recently identified in the synovial fluid of patients with RA. Despite potent OSM‐induced signal transduction in all types of fibroblasts analyzed, only synovial fibroblasts secreted CCL13, which might be indicative of tissue‐specific imprinting of different fibroblasts during development.

Background Radiotherapy may lead to side-effects undermining patients’ quality of life (QOL). While mind-body practices such as qigong appear to improve QOL in cancer survivors, little is known about benefits for patients undergoing radiotherapy. Thus, this RCT examined the efficacy of a qigong intervention on QOL in women with breast cancer during and after treatment. Methods Ninety-six women with breast cancer were recruited from a cancer center in Shanghai, China, and randomized to the qigong (N=49) or waitlist control (N=47) group. Women in the qigong group attended 5 weekly classes over 5–6 weeks of radiotherapy. QOL outcomes (i.e., depressive symptoms, fatigue, sleep disturbance, and overall QOL) and cortisol slopes were assessed at baseline, during and at the end of treatment, and 1 and 3 months later. Results The mean age of the women was 46 years (range 25–64); stage 0 (7%) stage I (25%), stage II (40%) and stage III (28%); with over half (54%) having undergone mastectomy surgery. Multilevel analyses revealed that women in the qigong group reported less depressive symptoms over time than in the control group (P=.05). Women with elevated depressive symptoms at radiotherapy onset reported less fatigue (P<.01) and better overall QOL (P<.05) in the qigong compared to the control group. Findings were clinically significant. No significant differences were found for sleep disturbance and cortisol slopes. Conclusion Qigong may have therapeutic effects in the management of QOL in women receiving radiotherapy for breast cancer. Benefits were particularly evident for patients with pre-intervention elevated levels of depressive symptoms.

A microdose cocktail containing midazolam, dabigatran etexilate, pitavastatin, rosuvastatin, and atorvastatin has been established to allow simultaneous assessment of a perpetrator impact on the most common drug metabolizing enzyme, cytochrome P450 (CYP)3A, and the major transporters organic anion-transporting polypeptides (OATP)1B, breast cancer resistance protein (BCRP), and MDR1 P-glycoprotein (P-gp). The clinical utility of these microdose cocktail probe substrates was qualified by conducting clinical drug interaction studies with three inhibitors with different in vitro inhibitory profiles (rifampin, itraconazole, and clarithromycin). Generally, the pharmacokinetic profiles of the probe substrates, in the absence and presence of the inhibitors, were comparable to their reported corresponding pharmacological doses, and/or in agreement with theoretical expectations. The exception was dabigatran, which resulted in an approximately twofold higher magnitude for microdose compared to conventional dosing, and, thus, can be used to flag a worst-case scenario for P-gp. Broader application of the microdose cocktail will facilitate a more comprehensive understanding of the roles of drug transporters in drug disposition and drug interactions.

U-BIOPRED cohort n=91 epithelial brushings or biopsies IL-17 High Clinical phenotype Nasal polyps Smoking Antibiotic use Epithelial Gene Expression Profile Clinical phenotype FeNO Exacerbations Gene expression shared with psoriasis IDO1 IL1B DEFB4B S100A8, S100A9 PI3 CXCL3, CXCL8 CXCL10, CCL20 Gene signature SERPINB2 POSTN CLCA1 IL-13 High T cell infiltration Neutrophilia Eosinophilia IL-17-high asthma with features of a psoriasis immunophenotype From a the Respiratory,