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Objective: Some of the most common causes of chronic cough include cough variant asthma (CVA), bronchial asthma (BA), and asthma–COPD overlap (ACO). Although there is some overlap in the etiology of these diseases, it is clinically important to attempt an early differential diagnosis due to treatment strategies and prognoses. Methods: Spirometry and impulse oscillometry (IOS) before and after bronchodilator inhalation were analyzed for clinically diagnosed CVA (cCVA, n = 203), BA (cBA, n = 222), and ACO (cACO, n = 61). Results: A significant difference in ΔFEV1 was observed between cBA and cCVA (ΔFEV1 improvement of 122.5 mL/5.4% and 65.7 mL/2.2%, respectively), but no difference was observed in ΔPEF, ΔV50, or ΔV25. Except for R20 (resistance at 20 Hz), significant differences between the three groups were observed in IOS. In IOS, cCVA and cBA showed comparable peripheral airway response to bronchodilator which was thought to be commensurate with changes in V50 and V25. cACO improved ΔFEV1 improvement of 81.0 mL/6.2% and was distinguished by a downward respiratory system reactance (Xrs) waveform with a limited bronchodilator response. FEV1/FVC, %FEV1, and %V25 had relatively strong correlations with the three IOS parameters, X5 (reactance at 5 Hz), resonant frequency (Fres), and low-frequency reactance area (ALX), in the correlation between IOS and spirometers. Conclusion: Changes in IOS parameters were more sensitive in this study than changes in FEV1 or the flow-volume curve. Considering the benefits and relevance of the two different tests, simultaneous IOS and spirometry testing were useful in the diagnosis of asthmatic cough. [ABSTRACT FROM AUTHOR]

Background: Osimertinib is a third‐generation epidermal growth factor receptor‐tyrosine kinase inhibitor (EGFR‐TKI) approved for the treatment of patients with EGFR‐mutant non‐small cell lung cancer (NSCLC). However, the mechanisms of acquired drug resistance to osimertinib have not as yet been clarified. Exosomes and microRNAs (miRNAs) are involved in carcinogenesis and drug resistance in human cancers. Methods: We used previously established osimertinib‐resistant HCC827 (HCC827‐OR) and PC‐9 (PC‐9‐OR) cells. We evaluated the profiles of exosomal miRNA associated with resistance to osimertinib in EGFR‐mutant NSCLC cells. Results: Epithelial–mesenchymal transition (EMT) phenomenon was observed in HCC827‐OR and PC‐9‐OR cells. Microarray and quantitative reverse transcription‐polymerase chain reaction analysis revealed that miR‐210‐3p was co‐upregulated in exosomes isolated from HCC827‐OR and PC‐9‐OR cells compared with those isolated from parental HCC827 and PC‐9 cells. HCC827‐OR cell‐derived exosomes induced EMT changes and resistance to osimertinib in HCC827 cells. Subsequently, the induction of miR‐210‐3p directly promoted the EMT phenomenon and resistance to osimertinib in HCC827 cells. Conclusions: Exosomal miR‐210‐3p may play a crucial role in resistance to osimertinib in the tumor microenvironment of EGFR‐mutant NSCLC. [ABSTRACT FROM AUTHOR]

Previous studies have demonstrated the transmission of rotavirus vaccine strains from vaccinated children to nonvaccinated siblings. We sought to fully elucidate the safety of rotavirus (RV) vaccination in closed contact circumstance, such as the foster home for future assessment of the vaccine safety in an neonatal intensive care unit. Stool samples were collected from 4 RV vaccinated (160 samples) and 23 unvaccinated (766 samples) infants. RV viral RNA loads were measured using real-time reverse transcription polymerase chain reaction (RT-PCR). RV vaccine strain RNA was persistently detected in stool samples collected from the four vaccine recipients and one unvaccinated infant, but not in the stool samples collected from the 22 other unvaccinated infants. The unvaccinated infant who tested positive for the RV vaccine strain was vaccinated prior to enrollment in this study. The quantitative real-time RT-PCR data revealed a peak viral RNA load 1 week after vaccination followed by a gradual decrease. The current study suggests that RV vaccination may be safe in a close contact environment because there was limited transmission from RV vaccinated to unvaccinated infants. J. Med. Virol. 89:79-84, 2017. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

(1) Background: Acquired resistance to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) is an intractable problem for many clinical oncologists. The mechanisms of resistance to EGFR-TKIs are complex. Long non-coding RNAs (lncRNAs) may play an important role in cancer development and metastasis. However, the biological process between lncRNAs and drug resistance to EGFR-mutated lung cancer remains largely unknown. (2) Methods: Osimertinib- and afatinib-resistant EGFR-mutated lung cancer cells were established using a stepwise method. A microarray analysis of non-coding and coding RNAs was performed using parental and resistant EGFR-mutant non-small cell lung cancer (NSCLC) cells and evaluated by bioinformatics analysis through medical-industrial collaboration. (3) Results: Colorectal neoplasia differentially expressed (CRNDE) and DiGeorge syndrome critical region gene 5 (DGCR5) lncRNAs were highly expressed in EGFR-TKI-resistant cells by microarray analysis. RNA-protein binding analysis revealed eukaryotic translation initiation factor 4A3 (eIF4A3) bound in an overlapping manner to CRNDE and DGCR5. The CRNDE downregulates the expression of eIF4A3, mucin 1 (MUC1), and phospho-EGFR. Inhibition of CRNDE activated the eIF4A3/MUC1/EGFR signaling pathway and apoptotic activity, and restored sensitivity to EGFR-TKIs. (4) Conclusions: The results showed that CRNDE is associated with the development of resistance to EGFR-TKIs. CRNDE may be a novel therapeutic target to conquer EGFR-mutant NSCLC. [ABSTRACT FROM AUTHOR]

• Childhood varicella patients has declined after implementation of universal two-dose varicella vaccination in Japan. • Sporadic varicella outbreaks in Japan mainly occur in non–universal vaccination targets. • Catch-up immunization for non-universal vaccination targets is needed to control varicella in Japan. To elucidate the trend and clinical spectrum of virologically diagnosed varicella patients after implementation of universal vaccination as a national immunization program in Japan. Study subjects were patients suspected of varicella, less than 15 years of age, who visited 14 pediatric clinics in the Nagoya VZV Study Group from September 2015 to August 2019. Practitioners collected patient samples and information such as backgrounds, clinical symptoms, and previous immunization status. All patients were confirmed as having varicella based on molecular diagnostic assays. Varicella zoster virus (VZV) DNA was detected in swab samples from 506 (83.1%) of the 609 suspected patients. The 455 varicella patients for whom vaccination status was available were divided into two groups: 180 universal vaccination targets and 275 non-targets. Numbers of monthly varicella patients decreased gradually during the observation period. In the 2016/17 season, the seasonal epidemic of varicella became undetectable in the universal vaccination target group, and starting in the 2017/18 season, it was obscured even in the non-target group. The median age of patients was significantly lower in the universal vaccination target group (3 years) than the non-target group (7 years) (P < 0.001). Vaccination status differed significantly between the two groups (P < 0.001). Most varicella patients were in the non-target group, especially those who had been vaccinated once (60.4%). Frequency of fever (P < 0.001) and number of skin rashes at the time of the first hospital visit (P = 0.001) were significantly higher in the non-target group. Although the number of childhood varicella patients declined after implementation of national immunization with two doses of varicella vaccination, sporadic outbreaks still occurred, mainly in the non–universal vaccination target group. Insufficient vaccination of members of this group is likely to be a major reason for small local outbreaks. [ABSTRACT FROM AUTHOR]

Objective Matched case control study was conducted to elucidate the effectiveness of the Oka/Biken vaccine immediately after implementation of the universal immunization program in Japan. Methods Cases were laboratory confirmed varicella patient under 15 years of age diagnosed at 14 designated pediatric clinics between September 2015 and September 2016. Controls were selected from patients who visited the same practice for different reasons as the varicella case within 2 weeks. Swab samples were collected from varicella suspected patients and molecular diagnostic assays were used to confirm varicella cases. Matched odds ratio were used to calculate vaccine effectiveness (VE). Results Varicella zoster virus DNA was detected in 183 (81.3%) of 225 suspected cases. One sample was excluded because it was positive for the Oka vaccine strain (182/225, 80.9%). Three hundred twenty-three control subjects were enrolled. The effectiveness of 1 dose of the Oka/Biken vaccine compared with no vaccine was 76.7% (95% confidence interval [CI]: 58.6–86.9%; P < 0.001). The effectiveness of 2 doses of the Oka/Biken vaccine was 94.2% (95% CI: 85.7–97.6%; P < 0.001). After adjusting for potential confounding effects, the adjusted VE of 1 and 2 doses of varicella vaccine were 76.9% (95% CI: 58.1–87.3%; P < 0.001) and 94.7% (95% CI: 86.0–98.0%; P < 0.001), respectively. Conclusions VE of one dose of Oka/Biken varicella vaccine was insufficient to control varicella. Therefore, two doses of Oka/Biken varicella vaccine is significant for controlling varicella in Japan. [ABSTRACT FROM AUTHOR]