Frequency of wrist pain and its associated risk factors in students using mobile phones.

OBJECTIVE: To assess the frequency of wrist pain in students due to mobile phone usage, and impact of usage hours and screen size of mobile phones on pain and disability at wrist joint. METHODS: A cross-sectional survey was conducted among students studying in different universities of Islamabad and Rawalpindi belonging to both public and private sectors. The study was conducted between May 2018 and March 2019. Sample size was 360 students which were selected through convenience sampling. Data was collected through self-formulated closed ended questionnaire. Patient Rated Wrist Evaluation questionnaire was used to assess pain and disability at wrist joint. Data entry and analysis were done using SPSS 21. Results were analyzed using descriptive statistics. Spearman's and point-biserial correlation coefficients were applied to determine association between different variables. RESULTS: Point, last month, last 3 months, last 6 months, last year and lifetime frequency were found to be 9%, 18.6%, 29%, 33.3%, 42% and 45.3% respectively. Duration of mobile phone usage was found to be of significant association factor that could lead to wrist pain and disability (p=0.004). Wrist pain was not significantly related to mobile phone screen size (p=0.488). CONCLUSION: It appears that wrist pain is common among mobile phone users and an increase in use of mobile phones increased pain and disability of wrist joint. In addition, it seems that screen size of mobile phone has no significant effect on pain and disability of wrist joint.

Human Bronchial Epithelial Cell-derived Factors from Severe Asthmatic Subjects Stimulate Eosinophil Differentiation.

Activated bronchial epithelial cells (BEC) release various alarmins, including thymic stromal lymphopoietin (TSLP), that drive type 2 inflammation. We hypothesize that BEC-derived factors promote in situ eosinophil differentiation and maturation, a process that is driven by an IL-5-rich microenvironment in asthmatic airways. To assess the eosinophilopoietic potential of epithelial-derived factors, eosinophil/basophil colony forming units (Eo/B-CFU) were enumerated in 14-day methylcellulose cultures of blood-derived nonadherent mononuclear cells incubated with BEC supernatants (BECSN) from healthy nonatopic controls (n = 8), mild atopic asthmatics (n = 9), and severe asthmatics (n = 5). Receptor-blocking antibodies were used to evaluate the contribution of alarmins. Modulation of the mRNA expression of transcription factors that are crucial for eosinophil differentiation was evaluated. BECSN stimulated the clonogenic expansion of eosinophil progenitors in vitro. In the presence of IL-5, Eo/B-CFU numbers were significantly greater in cocultures of BESCN from severe asthmatics compared with other groups. This was attenuated in the presence of a TSLP (but not an IL-33) receptor-blocking antibody. Recombinant human TSLP (optimal at 100 pg/ml) stimulated Eo/B-CFU growth, which was significantly enhanced in the presence of IL-5 (1 ng/ml). Overnight culture of CD34+ cells with IL-5 and TSLP synergistically increased GATA-binding factor 2 and CCAAT/enhancer-binding protein α mRNA expression. The eosinophilopoietic potential of factors derived from BEC is increased in severe asthma. Our data suggest that TSLP is a key alarmin that is produced by BECs and promotes in situ eosinophilopoiesis in a type 2-rich microenvironment.

Thymic stromal lymphopoietin and IL-33 modulate migration of hematopoietic progenitor cells in patients with allergic asthma.

BACKGROUND: Thymic stromal lymphopoietin (TSLP) and IL-33 are considered important initiators of type 2 immunity. In asthmatic patients allergic inflammatory responses are associated with increased lung homing of bone marrow-derived CD34(+) hematopoietic progenitor cells (HPCs), which include eosinophil lineage-committed progenitor cells. In this study we investigated the role of TSLP and IL-33 in the recruitment of progenitor cells to the airways in asthmatic subjects. OBJECTIVES: We sought (i) to examine the effect of allergen inhalation challenge on expression levels of receptors for TSLP (thymic stromal lymphopoietin receptor [TSLPR] and CD127) and IL-33 (ST2) and (ii) investigate the functional effects of these cytokines on HPCs. METHODS: Consenting patients with mild atopic asthma (n = 19) with an FEV1 of 70% or greater and methacholine PC20 of 16 mg/mL or less were recruited. Blood- and sputum-extracted progenitors were phenotyped by flow cytometry before and 24 hours after allergen challenge. Functional responses, including cytokine production and migration to TSLP and IL-33, were assessed in vitro. RESULTS: Significant increases in mature eosinophil, HPC, and eosinophil lineage-committed progenitor cell counts in sputum were observed 24 hours after allergen and were associated with a significant allergen-induced increase in HPCs expressing TSLPR, CD127, and ST2. Pre-exposure to TSLP and IL-33 primed the migration of HPCs to a potent progenitor cell chemoattractant, stromal cell-derived factor 1α (CXCL12). Incubation with TSLP and IL-33 stimulated significant production of IL-5 and IL-13, but not IL-4, by HPCs. This priming effect was inhibited by blocking antibodies to TSLPR and ST2, respectively, and IL-13 receptor α1 in both scenarios. CONCLUSIONS: In allergic asthmatic responses increased lung homing of HPCs may be orchestrated by TSLP and IL-33 through an IL-13-dependent axis.

Lung homing of endothelial progenitor cells in humans with asthma after allergen challenge.

RATIONALE: Increased bronchial vascularity is a feature of asthma that can contribute to airflow obstruction and progressive decline in lung function. Angiogenesis is associated with the lung homing and in situ differentiation of endothelial progenitor cells (EPC) in mouse models of asthma. We have previously shown that inhibiting allergen (Ag)-induced recruitment of EPC in sensitized mice attenuated increased bronchial vascularity and development of airway hyperresponsiveness. OBJECTIVES: We investigated the accumulation of EPC and formation of new blood vessels in the lungs of human subjects with asthma after Ag inhalation challenge. METHODS: Consenting patients with mild atopic asthma (n = 13) with FEV1 ≥ 70%, methacholine PC20 ≤ 16 mg/ml, and a dual response to Ag were recruited. Sputum levels of EPC were determined by multigating flow cytometry, and lung vascularity was enumerated by immunostaining with von Willebrand factor. MEASUREMENTS AND MAIN RESULTS: Sputum levels of EPC were determined by multigating flow cytometry and lung vascularity was enumerated by immunostaining with von Willebrand factor. There was a significant increase in sputum EPC levels 24 hours post Ag but not diluent challenge. Similarly, a significant increase in the number and diameter of blood vessels in lung biopsy tissue 24 hours post Ag was observed. In vitro culture of EPC demonstrated the capacity of these cells to differentiate into mature endothelial cells and form tubelike vessel structures. In sputum supernatants, there was a significant increase in CXCR2 agonists, IL-8, and Gro-α 24 hours post Ag. Only Gro-α stimulated a significant EPC migrational response in vitro. CONCLUSIONS: Our data suggest that increased lung homing of EPC may promote bronchial vascularity in allergic asthmatic responses and that the recruitment of these progenitors maybe orchestrated by CXCR2 chemokines.

In vitro inhibition of cytochrome P450-mediated reactions by gemfibrozil, erythromycin, ciprofloxacin and fluoxetine in fish liver microsomes.

Inhibition of mammalian cytochrome P450 enzymes (CYPs) is well characterized; major hepatic CYPs can be inhibited by drugs and other environmental contaminants. CYP function and inhibition has not yet been well established in fish yet these studies are important for several reasons. First, such studies will provide functional information for non-mammalian CYPs. Second, specific inhibitors can be used as a diagnostic tool for studying CYP-mediated reactions. Lastly, pharmaceutical mixtures are found in the aquatic environment and adverse effects associated with drug-drug interactions, including CYP inhibition by pharmaceuticals may be of concern. Using liver microsomes from untreated and ß-naphthoflavone (BNF)-treated rainbow trout, eight fluorescent CYP-mediated catalytic assays were used to assess in vitro CYP inhibition by four pharmaceuticals: fluoxetine, ciprofloxacin, gemfibrozil and erythromycin. Expressed zebrafish CYP1 proteins (CYP1A, CYP1B1, CYP1C1 and CYP1C2) were assessed for inhibition with selected substrates. All pharmaceuticals decreased the metabolism of a number of substrates. Fluoxetine was the strongest and most broad inhibitor of CYP-mediated reactions in liver microsomes. Zebrafish CYP1s were strongly inhibited by erythromycin and fluoxetine. Although the pharmaceuticals are selective CYP inhibitors in mammals, inhibition across a number of substrates suggests they are broad inhibitors in fish. These data demonstrate that in vitro hepatic CYP inhibition by pharmaceuticals is possible in fish and the patterns seen here are different than what would be expected based on CYP inhibition in mammals.

The Effect of PPAR Agonists on the Migration of Mature and Immature Eosinophils.

PPARγ agonists can either enhance or inhibit eosinophil migration, which is a sum of directional migration (chemotaxis) and random cell movement (chemokinesis). To date, the effects of PPAR agonists on chemokinesis have not been examined. This study investigates the effects of PPARα, δ, and γ agonists on eosinophil migration and chemokinesis. Eosinophils purified from blood of atopic donors were preincubated with rosiglitazone (PPARγ agonist), GW9578 (PPARα agonist), GW501516 (PPARδ agonist), or diluent. The effects of PPAR agonists were examined on eosinophil chemokinesis, eotaxin-induced migration of eosinophils, and migration of IL-5Rα+ CD34+ cells. Expressions of CCR3, phospho-p38, phospho-ERK, and calcium release were also measured in eosinophils after rosiglitazone treatment. Low concentrations of rosiglitazone, but not GW9578 or GW501516, increased chemokinesis of eosinophils (P = 0.0038), and SDF-1α-induced migration of immature eosinophils (P = 0.0538). Rosiglitazone had an effect on eosinophil calcium flux but had no effect on expression of CCR3 or phosphorylation of p38 or ERK. In contrast, high concentrations of rosiglitazone inhibited eosinophil migration (P = 0.0042). The effect of rosiglitazone on eosinophil migration and chemokinesis appears to be through modification of calcium signaling, which alludes to a novel PPAR-mediated mechanism to modulate eosinophil function.