Respiratory viral infections in exacerbation of chronic airway inflammatory diseases: novel mechanisms and insights from the upper airway epithelium.

Respiratory virus infection is one of the major sources of exacerbation of chronic airway inflammatory diseases. These exacerbations are associated with high morbidity and even mortality worldwide. The current understanding on viral-induced exacerbations is that viral infection increases airway inflammation which aggravates disease symptoms. Recent advances in in vitro air-liquid interface 3D cultures, organoid cultures and the use of novel human and animal challenge models have evoked new understandings as to the mechanisms of viral exacerbations. In this review, we will focus on recent novel findings that elucidate how respiratory viral infections alter the epithelial barrier in the airways, the upper airway microbial environment, epigenetic modifications including miRNA modulation, and other changes in immune responses throughout the upper and lower airways. First, we reviewed the prevalence of different respiratory viral infections in causing exacerbations in chronic airway inflammatory diseases. Subsequently we also summarized how recent models have expanded our appreciation of the mechanisms of viral-induced exacerbations. Further we highlighted the importance of the virome within the airway microbiome environment and its impact on subsequent bacterial infection. This review consolidates the understanding of viral induced exacerbation in chronic airway inflammatory diseases and indicates pathways that may be targeted for more effective management of chronic inflammatory diseases

Tahap penglibatan komuniti kejiranan FRIM dalam program pemuliharaan FRIM sebagai tapak warisan dunia UNESCO.

Kajian ini dijalankan bagi menilai tahap penglibatan komuniti setempat dalam program pemuliharaan Tapak Warisan Kebangsaan FRIM dalam penglibatan umum serta empat peringkat penglibatan iaitu perancangan, pelaksanaan, pemantauan dan perkongsian faedah.Seramai 600 responden wakil isi rumah telah dipilih secara rawak dari kalangan penempatan komuniti yang berhampiran dengan persekitaran Tapak Warisan Kebangsaan FRIM. Maklumat kajian dikumpul melalui temu bual dari rumah ke rumah menggunakan borang soal selidik dan dianalisis melalui aplikasi perisian SPSS. Skor min bagi tahap penglibatan komuniti ditentukan dengan menggunakan Kaedah Skala Likert.Hasil kajian menunjukkan penglibatan umum komuniti setempat dalam aktiviti yang dianjurkan FRIM berada pada tahap yang rendah dengan nilai skor min iaitu 1.18. Manakala penglibatan komuniti dalam empat peringkat penglibatan yang lain turut menunjukkan keputusan julat skor min antara 1- 2.33 iaitu tahap penglibatan yang rendah. Antara faktor yang telah dikenalpasti mempengaruhi penglibatan komuniti adalah kesedaran tentang faedah program, keinginan melihat sumber alam, peranan individu dalam program, sikap dan personaliti individu tersebut.Kertas kerja ini diharap dapat memberikan maklumat asas kepada FRIM bagi merangka program untuk meningkatkan penyertaan komuniti dalam pemuliharaan FRIM kearah pengiktirafan UNESCO sebagai Tapak Warisan Dunia

Driving the green vehicles shift: an evaluation of Malaysian consumers’ acceptance

With the current drastic changes in global weather, more countries are worried about the sustainability of the ecosystem. Global leaders are more concerned about the drastic climate change, and various initiatives are being taken to prevent further damage to the ecosystem. In Malaysia, the transportation sector, mainly motor vehicles, emitted approximately 97% of carbon monoxide to the environment, causing harmful air pollution. Because of this, green vehicles were introduced to overcome this problem. However, there remain various challenges that may impede or trigger the interest of Malaysian consumers in accepting green vehicles. Thus, this study applies the cognitive-affection model to predict the consumers’ intention to accept green vehicles. Using a purposive sampling among current vehicle drivers, a face-to-face survey was conducted and gathered a total of 606 responses. Data were analysed using statistical measurements such as descriptive analysis, exploratory factor analysis and structural equation modelling. Five latent factors such as consumers’ acceptance, perceived quality, perceived value (environmental concern, acquisition and maintenance cost), and government policies were identified. The results indicated that perceived value (environmental concern), perceived quality, and government policies have a strong positive relationship with consumers’ acceptance. The perceived value showed a negative relationship with consumer acceptance, indicating that consumers would only consider accepting green vehicles if they were cheaper and had a low maintenance cost

Immediate implant placement in conjunction with guided bone regeneration and/or connective tissue grafts: an experimental study in canines

PURPOSE This study was conducted to assess the effect of hard and/or soft tissue grafting on immediate implants in a preclinical model. METHODS In 5 mongrel dogs, the distal roots of P2 and P3 were extracted from the maxilla (4 sites in each animal), and immediate implant placement was performed. Each site was randomly assigned to 1 of the following 4 groups: i) gap filling with guided bone regeneration (the GBR group), ii) subepithelial connective tissue grafting (the SCTG group), iii) GBR and SCTG (the GBR/SCTG group), and iv) no further treatment (control). Non-submerged healing was provided for 4 months. Histological and histomorphometric analyses were performed. RESULTS Peri-implant tissue height and thickness favored the SCTG group (height of peri-implant mucosa: 1.14 mm; tissue thickness at the implant shoulder and ±1 mm from the shoulder: 1.14 mm, 0.78 mm, and 1.57 mm, respectively; median value) over the other groups. Bone grafting was not effective at the level of the implant shoulder and on the coronal level of the shoulder. In addition, simultaneous soft and hard tissue augmentation (the GBR/SCTG group) led to a less favorable tissue contour compared to GBR or SCTG alone (height of peri-implant mucosa: 3.06 mm; thickness of peri-implant mucosa at the implant shoulder and ±1 mm from the shoulder: 0.72 mm, 0.3 mm, and 1.09 mm, respectively). CONCLUSION SCTG tended to have positive effects on the thickness and height of the peri-implant mucosa in immediate implant placement. However, simultaneous soft and hard tissue augmentation might not allow a satisfactory tissue contour in cases where the relationship between implant position and neighboring bone housing is unfavorable

Validation of the Thai version of the family reported outcome measure (FROM-16)© to assess the impact of disease on the partner or family members of patients with cancer

© The Author(s). 2019Background: Cancer not only impairs a patient's physical and psychosocial functional behaviour, but also contributes to negative impact on family members' health related quality of life. Currently, there is an absence of a relevant tool in Thai with which to measure such impact. The aim of this study was to translate and validate the Family Reported Outcome Measure (FROM-16) in Thai cancer patients' family members. Methods: Thai version of FROM-16 was generated by interactive forward-backward translation process following standard guidelines. This was tested for psychometric properties including reliability and validity, namely content validity, concurrent validity, known group validity, internal consistency, exploratory and confirmatory factor analysis. Construct validity was examined by comparing the Thai FROM-16 version with the WHOQOL-BREF-THAI. Results: The internal consistency reliability was strong (Cronbach's alpha = 0.86). A Negative moderate correlation between the Thai FROM-16 and WHOQOL-BREF-THAI was observed (r = - 0.4545, p < 0.00), and known group validity was proved by a statistically significant higher score in family members with high burden of care and insufficient income. The factor analysis supported both 3-factor and 2-factor loading model with slight difference when compared with the original version. Conclusions: The Thai FROM-16 showed good reliability and validity in Thai family members of patients with cancer. A slight difference in factor analysis results compared to the original version could be due to cross-culture application.Peer reviewedFinal Published versio

Genome-wide association study with 1000 genomes imputation identifies signals for nine sex hormone-related phenotypes.

PublishedJournal ArticleResearch Support, Non-U.S. Gov'tThis is the final version of the article. Available from Nature Publishing Group via the DOI in this record.Genetic factors contribute strongly to sex hormone levels, yet knowledge of the regulatory mechanisms remains incomplete. Genome-wide association studies (GWAS) have identified only a small number of loci associated with sex hormone levels, with several reproductive hormones yet to be assessed. The aim of the study was to identify novel genetic variants contributing to the regulation of sex hormones. We performed GWAS using genotypes imputed from the 1000 Genomes reference panel. The study used genotype and phenotype data from a UK twin register. We included 2913 individuals (up to 294 males) from the Twins UK study, excluding individuals receiving hormone treatment. Phenotypes were standardised for age, sex, BMI, stage of menstrual cycle and menopausal status. We tested 7,879,351 autosomal SNPs for association with levels of dehydroepiandrosterone sulphate (DHEAS), oestradiol, free androgen index (FAI), follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin, progesterone, sex hormone-binding globulin and testosterone. Eight independent genetic variants reached genome-wide significance (P<5 × 10(-8)), with minor allele frequencies of 1.3-23.9%. Novel signals included variants for progesterone (P=7.68 × 10(-12)), oestradiol (P=1.63 × 10(-8)) and FAI (P=1.50 × 10(-8)). A genetic variant near the FSHB gene was identified which influenced both FSH (P=1.74 × 10(-8)) and LH (P=3.94 × 10(-9)) levels. A separate locus on chromosome 7 was associated with both DHEAS (P=1.82 × 10(-14)) and progesterone (P=6.09 × 10(-14)). This study highlights loci that are relevant to reproductive function and suggests overlap in the genetic basis of hormone regulation.We thank Roche Diagnostics Australia Pty Limited, Castle Hill, Australia, who provided support for the analysis of the hormones. We thank the volunteer twins for their participation in the study. Twins UK received funding support from NIHR Biomedical Research Centre (grant to Guys’ and St Thomas’ Hospitals and King’s College London); the Chronic Disease Research Foundation; Canadian Institutes of Health Research, the Canadian Foundation for Innovation, the Fonds de la Recherche en Santé Québec, The Lady Davis Institute, the Jewish General Hospital and Ministère du Développement économique, de l'Innovation et de l'Exportation du Quebec. The Australian National Health and Medical Research Council (NHMRC project grants 1010494, 1048216), and Sir Charles Gairdner Hospital Research (grant PP2009/028). This work was supported by funding from the Wellcome Trust (092447/Z/10/Z) and Medical Research Council (MC_U106179472)

Analysis of T cell receptor clonotypes in tumor microenvironment identifies shared cancer-type-specific signatures.

Despite the conventional view that a truly random V(D)J recombination process should generate a highly diverse immune repertoire, emerging reports suggest that there is a certain bias toward the generation of shared/public immune receptor chains. These studies were performed in viral diseases where public T cell receptors (TCR) appear to confer better protective responses. Selective pressures generating common TCR clonotypes are currently not well understood, but it is believed that they confer a growth advantage. As very little is known about public TCR clonotypes in cancer, here we set out to determine the extent of shared TCR clonotypes in the intra-tumor microenvironments of virus- and non-virus-driven head and neck cancers using TCR sequencing. We report that tumor-infiltrating T cell clonotypes were indeed shared across individuals with the same cancer type, where the majority of shared sequences were specific to the cancer type (i.e., viral versus non-viral). These shared clonotypes were not particularly enriched in EBV-associated nasopharynx cancer but, in both cancers, exhibited distinct characteristics, namely shorter CDR3 lengths, restricted V- and J-gene usages, and also demonstrated convergent V(D)J recombination. Many of these shared TCRs were expressed in patients with a shared HLA background. Pattern recognition of CDR3 amino acid sequences revealed strong convergence to specific pattern motifs, and these motifs were uniquely found to each cancer type. This suggests that they may be enriched for specificity to common antigens found in the tumor microenvironment of different cancers. The identification of shared TCRs in infiltrating tumor T cells not only adds to our understanding of the tumor-adaptive immune recognition but could also serve as disease-specific biomarkers and guide the development of future immunotherapies

Socioeconomic differentials in the immediate mortality effects of the national Irish smoking ban

This article has been made available through the Brunel Open Access Publishing Fund.Background: Consistent evidence has demonstrated that smoking ban policies save lives, but impacts on health inequalities are uncertain as few studies have assessed post-ban effects by socioeconomic status (SES) and findings have been inconsistent. The aim of this study was to assess the effects of the national Irish smoking ban on ischemic heart disease (IHD), stroke, and chronic obstructive pulmonary disease (COPD) mortality by discrete and composite SES indicators to determine impacts on inequalities. Methods: Census data were used to assign frequencies of structural and material SES indicators to 34 local authorities across Ireland with a 2000–2010 study period. Discrete indicators were jointly analysed through principal component analysis to generate a composite index, with sensitivity analyses conducted by varying the included indicators. Poisson regression with interrupted time-series analysis was conducted to examine monthly age and gender-standardised mortality rates in the Irish population, ages ≥35 years, stratified by tertiles of SES indicators. All models were adjusted for time trend, season, influenza, and smoking prevalence. Results: Post-ban mortality reductions by structural SES indicators were concentrated in the most deprived tertile for all causes of death, while reductions by material SES indicators were more equitable across SES tertiles. The composite indices mirrored the results of the discrete indicators, demonstrating that post-ban mortality decreases were either greater or similar in the most deprived when compared to the least deprived for all causes of death. Conclusions: Overall findings indicated that the national Irish smoking ban reduced inequalities in smoking-related mortality. Due to the higher rates of smoking-related mortality in the most deprived group, even equitable reductions across SES tertiles resulted in decreases in inequalities. The choice of SES indicator was influential in the measurement of effects, underscoring that a differentiated analytical approach aided in understanding the complexities in which structural and material factors influence mortality

Jet production in charged current deep inelastic e⁺p scatteringat HERA

The production rates and substructure of jets have been studied in charged current deep inelastic e⁺p scattering for Q² > 200 GeV² with the ZEUS detector at HERA using an integrated luminosity of 110.5 pb⁻¹. Inclusive jet cross sections are presented for jets with transverse energies E_{T}^{jet} > 5 GeV. Measurements of the mean subjet multiplicity, 〈n_{sbj}〉, of the inclusive jet sample are presented. Predictions based on parton-shower Monte Carlo models and next-to-leading-order QCD calculations are compared to the measurements. The value of α_{s} (M_{z}), determined from 〈n_{sbj}〉 at y_{cut} = 10⁻² for jets with 25 < E_{T}^{jet} < 119 GeV, is α_{s} (M_{z}) = 0.1202 ± 0.0052 (stat.)_{-0.0019}^{+0.0060} (syst.)_{-0.0053}^{+0.0065} (th.). The mean subjet multiplicity as a function of Q² is found to be consistent with that measured in NC DIS