Protein synthesis must rapidly and repeatedly discriminate between a single correct and many incorrect aminoacyl-tRNAs. We have attempted to measure the frequencies of all possible missense errors by tRNA

BackgroundThymic stromal lymphoproetin (TSLP) is a cytokine secreted by the airway epithelium in response to respiratory viruses and it is known to promote allergic Th2 responses in asthma. This study investigated whether virally-induced secretion of TSLP is directional in nature (apical vs. basolateral) and/or if there are TSLP-mediated effects occurring at both sides of the bronchial epithelial barrier in the asthmatic state.MethodsPrimary human bronchial epithelial cells (HBEC) from control (n = 3) and asthmatic (n = 3) donors were differentiated into polarized respiratory tract epithelium under air-liquid interface (ALI) conditions and treated apically with dsRNA (viral surrogate) or TSLP. Sub-epithelial effects of TSLP were examined in human airway smooth muscle cells (HASMC) from normal (n = 3) and asthmatic (n = 3) donors. Clinical experiments examined nasal airway secretions obtained from asthmatic children during naturally occurring rhinovirus-induced exacerbations (n = 20) vs. non-asthmatic uninfected controls (n = 20). Protein levels of TSLP, CCL11/eotaxin-1, CCL17/TARC, CCL22/MDC, TNF-α and CXCL8 were determined with a multiplex magnetic bead assay.ResultsOur data demonstrate that: 1) Asthmatic HBEC exhibit an exaggerated apical, but not basal, secretion of TSLP after dsRNA exposure; 2) TSLP exposure induces unidirectional (apical) secretion of CCL11/eotaxin-1 in asthmatic HBEC and enhanced CCL11/eotaxin-1 secretion in asthmatic HASMC; 3) Rhinovirus-induced asthma exacerbations in children are associated with in vivo airway secretion of TSLP and CCL11/eotaxin-1.ConclusionsThere are virally-induced TSLP-driven secretory immune responses at both sides of the bronchial epithelial barrier characterized by enhanced CCL11/eotaxin-1 secretion in asthmatic airways. These results suggest a new model of TSLP-mediated eosinophilic responses in the asthmatic airway during viral-induced exacerbations.

BackgroundEarly detection of lung cancer using low-dose computed tomography (LDCT) can potentially reduce morbidity and mortality. However, LDCT for lung cancer screening, especially in low income countries, has been underutilized. The objective of this study was to evaluate the prevalence and the potential personal, social, and economic barriers of lung cancer screening using LDCT.MethodsA total sample of 156 smokers and 200 general physicians was collected during December 2016-February 2017 from community settings in Karachi, Pakistan. Two separate questionnaires were constructed to characterize participants’ knowledge, attitudes, and practices regarding lung cancer screening. Screening-eligible smokers and physicians were asked to identify patient barriers to screening and were asked their opinion regarding most effective approach for increasing awareness of screening guidelines.ResultsThe majority of smokers' (n=91, 58.3%) and physicians' (n=131, 65.7%) beliefs about the US Preventive Services Task Force (USPSTF) eligibility criteria were inconsistent with the actual recommendations. Major barriers to screening included financial cost, lack of patient counseling and health anxiety related to screening. Over two-thirds (n=105, 67.3%) of smokers were receptive to further information about LDCT screening, and half (n=78, 50.0%) favored one-on-one counseling by their physician, compared to other media. Only one-third (n=65, 33.3%) of physicians reported use of LDCT screening, although 54.5% (n=108) felt that screening implementation would be very effective in their practice.ConclusionLDCT screening is currently an uncommon practice in Pakistan. Financial cost, inadequate doctor-patient communication, and lack of awareness of guidelines among both patients and physicians are the major barriers in the utilization of LDCT screening.

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