Smoking and non-neoplastic lung disease in Canadian men and women

MAIN OBJECTIVE: To document and assess the current health impact of non-neoplastic lung disease (NNLD) in Canadian men and women that is attributable to smoking. DESIGN: Comparison of three recent studies providing estimates of smoking-attributable deaths, potential years of life lost, hospital separations and hospital days due to NNLD in Canada. Review of recent epidemiological studies providing relative risk estimates of smoking-attributable mortality and morbidity for chronic obstructive pulmonary disease and pneumonia, including a meta-analysis. MAIN RESULTS: Each year at least 6700 Canadian men and women die from NNLD attributable to smoking. Smoking-attributable NNLD deaths in men outnumber those in women by about 2 to 1. The majority of these deaths are due to chronic obstructive pulmonary disease, which is exceeded in importance as a smoking-attributable cause of death only by lung cancer and ischemic heart disease. NNLD accounts for about 20% of all smokingattributable deaths in Canada, 14% of the potential years of life lost due to smoking, and 22% and 25% of all smokingattributable hospital separations and hospital days, respectively. Long term follow-up assessments of large cohorts suggest that the impact of smoking on health has been underestimated. Recent studies also suggest that women may be more susceptible than men to the adverse effects of smoking on lung function. CONCLUSION: NNLD caused by smoking has an important health impact in Canada. Tobacco control strategies must be enhanced. Key Words: Lung diseases, Morbidity, Mortality, Smoking Le tabagisme et la maladie pulmonaire non cancéreuse chez les Canadiens et Canadiennes OBJECTIF PRINCIPAL : Documenter et évaluer les influences actuelles sur la santé de la maladie pulmonaire non cancéreuse chez des Canadiens et Canadiennes, et qui sont imputables au tabagisme. MODÈLE : Comparaison de trois études récentes fournissant des estimés des décès attribuables au tabagisme, des années potentielles de vie perdues, des congés donnés aux patients hospitalisés et des journées d'hospitalisation dus à la maladie pulmonaire non cancéreuse au Canada. Revue des études épidémiologiques récen-tes fournissant des estimés du risque relatif de la mortalité attribuable au tabagisme et de la morbidité liée à la maladie pulmonaire obstructive chronique et à la pneumonie, incluant une méta-analyse. voir page suivante I t is now well established that smoking is the most important preventable cause of premature mortality and morbidity in Canadian men and women (1,2), as it is in the populations of other developed countries (3,4). At least 33,000 Canadians die each year as a result of tobacco use, which also accounts for more than 200,000 hospital separations, three million hospital days and some $9.5 billion in costs from lost productivity and direct health care expenditures (2). Despite this enormous health toll, smoking remains prevalent. Estimates from the National Population Health Survey conducted in 1994 indicate that 6.9 million Canadians, 31% of the population aged 15 years and over, smoke (5). Further, rates of smoking among young Canadians, after some years of decline, have now plateaued (6) and may actually be increasing in some provinces, notably in Ontario The primary purpose of this paper is to document and assess current estimates of the health impact of smoking in Canada with regard to non-neoplastic lung disease (NNLD) and to point out some limitations of these data. As well, recent reports concerning long term epidemiological studies of the relationship of smoking to NNLD are reviewed, including a meta-analysis of relative risk estimates. Attention is drawn to recent studies that indicate the possibility that the lungs of women may be particularly susceptible to the adverse effects of tobacco smoke. HEALTH IMPACT OF SMOKING DUE TO NNLD Smoking-attributable mortality: Three studies provide estimates of the current mortality impact of tobacco use in Canadian men and women Makomaski Illing and Kaiserman (1), using risk estimates from the same source, concluded that in 1991 there were more than 8100 NNLD deaths among Canadians attributable to smoking, out of a total of 41,408 smoking-attributable deaths. Most recently, Single et al (2) used mortality estimates derived from a meta-analysis of epidemiological studies conducted by English et al (10), discussed further below. They concluded that in 1992 NNLD deaths in Canadians attributable to smoking exceeded 6700, out of a total estimate of more than 33,000 smoking-attributable deaths. In all three estimates shown in Comparability of the mortality estimates: Because the RISKS OF NNLD MORTALITY AND MORBIDITY ASSOCIATED WITH SMOKING Mortality: A study by Canadian investigators was among the first to document the excess risk of mortality from NNLD in smokers compared with nonsmokers (11,12). In the final six-year follow-up study of some 78,000 male veterans, initiated in 1955 by the Department of National Health and Welfare (12), it was found that veterans with a lifetime history of smoking cigarettes had about 11 and eight times the risk of mortality from chronic bronchitis and emphysema, respectively, compared with nonsmokers. A dose-response relationship between the amount smoked daily and the risk of mortality was also observed. For pneumonia and influenza there was a small increase in relative risk (1.4). Since then, a host of epidemiological studies from many countries have confirmed the causal relationship between smoking and COPD in both men and women, as well as a small increase in the risk of mortality from pneumonia (13-17). Doll et al Doll et al Recently, Gold et al (27), in a study of the effects of cigarette smoking on the level and rate of growth of pulmonary function in large cohorts of adolescent boys and girls, demonstrated that the growth of lung function in association with smoking was more severely affected in the girls. This finding is particularly worrisome in the context of the ages at which adolescent girls and boys begin to smoke. In the 1994 Canadian Youth Smoking Survey (6) it was found that although the rates of beginning to smoke were similar in boys and girls ages 10 to 12 years (4% in each), by ages 13 to 14 years this rate was significantly higher than girls (15%) compared with boys (9%). Girls may not only be more susceptible to the adverse effects of smoking, but they appear to be getting a 'head start' on this addiction. While sex differences in susceptibility to the smokinginduced changes in lung function require more study, particularly with regard to underlying biological mechanisms, the primal importance of smoking cessation in reducing the age-related decline in FEV 1 in smokers with mild obstructive pulmonary disease is beyond disput

Associations between childhood maltreatment and psychiatric disorders: analysis from electronic health records in Hong Kong

There has been a lack of high-quality evidence concerning the association between childhood maltreatment and psychiatric diagnoses particularly for Axis II disorders. This study aimed to examine the association between childhood maltreatment exposure and Axis I and Axis II psychiatry disorders using electronic health records. In this study, the exposed group (n = 7473) comprised patients aged 0 to 19 years with a first-time record of maltreatment episode between January 1, 2001 and December 31, 2010, whereas the unexposed group (n = 26,834) comprised individuals of the same gender and age who were admitted into the same hospital in the same calendar year and month but had no records of maltreatment in the Hong Kong Clinical Data Analysis and Reporting System (CDARS). Data on their psychiatric diagnoses recorded from the date of admission to January 31, 2019 were extracted. A Cox proportional hazard regression model was fitted to estimate the hazard ratio (HR, plus 95% CIs) between childhood maltreatment exposure and psychiatric diagnoses, adjusting for age at index visit, sex, and government welfare recipient status. Results showed that childhood maltreatment exposure was significantly associated with subsequent diagnosis of conduct disorder/ oppositional defiant disorder (adjusted HR, 10.99 [95% CI 6.36, 19.01]), attention deficit hyperactivity disorder (ADHD) (7.28 [5.49, 9.65]), and personality disorders (5.36 [3.78, 7.59]). The risk of psychiatric disorders following childhood maltreatment did not vary by history of childhood sexual abuse, age at maltreatment exposure, and gender. Individuals with a history of childhood maltreatment are vulnerable to psychiatric disorders. Findings support the provision of integrated care within the primary health care setting to address the long-term medical and psychosocial needs of individuals with a history of childhood maltreatment

Cognitive skills and literacy performance of Chinese adolescents with and without dyslexia

The present study sought to identify cognitive abilities that might distinguish Hong Kong Chinese adolescents with dyslexia and to assess how these abilities were associated with Chinese word reading, word dictation, and reading comprehension. The cognitive skills of interest were morphological awareness, visual-orthographic knowledge, rapid naming, and verbal working memory. A total of 90 junior secondary school students, 30 dyslexic, 30 chronological age controls, and 30 reading level controls was tested on a range of cognitive and literacy tasks. Dyslexic students were less competent than the control students in all cognitive and literacy measures. The regression analyses also showed that verbal working memory, rapid naming, morphological awareness, and visual-orthographic knowledge were significantly associated with literacy performance. Findings underscore the importance of these cognitive skills for Chinese literacy acquisition. Overall, this study highlights the persistent difficulties of Chinese dyslexic adolescents who seem to have multiple causes for reading and spelling difficulties

Propofol-related urine discoloration in a patient with fatal atypical intracerebral hemorrhage treated with hypothermia

Case description We report the case of a 77-year old woman with atypical intracerebral hemorrhage that was treated with mild hypothermia in addition to osmotic therapy. The patient’s urine subsequently showed a green discoloration. Urine discoloration was completely reversible upon discontinuation of propofol. Discussion and evaluation Propofol-related urine discoloration may have been provoked by hypothermia. Due to the benign nature of this side effect, propofol should be stopped and gastrointestinal function should be supported. Conclusion More studies are needed to show a causal role of hypothermia and related decreased enzymatic function

Genome-Wide Association Study in Asian Populations Identifies Variants in ETS1 and WDFY4 Associated with Systemic Lupus Erythematosus

Systemic lupus erythematosus is a complex and potentially fatal autoimmune disease, characterized by autoantibody production and multi-organ damage. By a genome-wide association study (320 patients and 1,500 controls) and subsequent replication altogether involving a total of 3,300 Asian SLE patients from Hong Kong, Mainland China, and Thailand, as well as 4,200 ethnically and geographically matched controls, genetic variants in ETS1 and WDFY4 were found to be associated with SLE (ETS1: rs1128334, P = 2.33×10−11, OR = 1.29; WDFY4: rs7097397, P = 8.15×10−12, OR = 1.30). ETS1 encodes for a transcription factor known to be involved in a wide range of immune functions, including Th17 cell development and terminal differentiation of B lymphocytes. SNP rs1128334 is located in the 3′-UTR of ETS1, and allelic expression analysis from peripheral blood mononuclear cells showed significantly lower expression level from the risk allele. WDFY4 is a conserved protein with unknown function, but is predominantly expressed in primary and secondary immune tissues, and rs7097397 in WDFY4 changes an arginine residue to glutamine (R1816Q) in this protein. Our study also confirmed association of the HLA locus, STAT4, TNFSF4, BLK, BANK1, IRF5, and TNFAIP3 with SLE in Asians. These new genetic findings may help us to gain a better understanding of the disease and the functions of the genes involved

Intervening with Urinary Tract Infections Using Anti-Adhesives Based on the Crystal Structure of the FimH–Oligomannose-3 Complex

Escherichia coli strains adhere to the normally sterile human uroepithelium using type 1 pili, that are long, hairy surface organelles exposing a mannose-binding FimH adhesin at the tip. A small percentage of adhered bacteria can successfully invade bladder cells, presumably via pathways mediated by the high-mannosylated uroplakin-Ia and alpha3beta1 integrins found throughout the uroepithelium. Invaded bacteria replicate and mature into dense, biofilm-like inclusions in preparation of fluxing and of infection of neighbouring cells, being the major cause of the troublesome recurrent urinary tract infections.We demonstrate that alpha-D-mannose based inhibitors of FimH not only block bacterial adhesion on uroepithelial cells but also antagonize invasion and biofilm formation. Heptyl alpha-D-mannose prevents binding of type 1-piliated E. coli to the human bladder cell line 5637 and reduces both adhesion and invasion of the UTI89 cystitis isolate instilled in mouse bladder via catheterization. Heptyl alpha-D-mannose also specifically inhibited biofilm formation at micromolar concentrations. The structural basis of the great inhibitory potential of alkyl and aryl alpha-D-mannosides was elucidated in the crystal structure of the FimH receptor-binding domain in complex with oligomannose-3. FimH interacts with Man alpha1,3Man beta1,4GlcNAc beta1,4GlcNAc in an extended binding site. The interactions along the alpha1,3 glycosidic bond and the first beta1,4 linkage to the chitobiose unit are conserved with those of FimH with butyl alpha-D-mannose. The strong stacking of the central mannose with the aromatic ring of Tyr48 is congruent with the high affinity found for synthetic inhibitors in which this mannose is substituted for by an aromatic group.The potential of ligand-based design of antagonists of urinary tract infections is ruled by the structural mimicry of natural epitopes and extends into blocking of bacterial invasion, intracellular growth and capacity to fluxing and of recurrence of the infection

The use of mesenchymal stem cells for cartilage repair and regeneration: a systematic review.

BACKGROUND: The management of articular cartilage defects presents many clinical challenges due to its avascular, aneural and alymphatic nature. Bone marrow stimulation techniques, such as microfracture, are the most frequently used method in clinical practice however the resulting mixed fibrocartilage tissue which is inferior to native hyaline cartilage. Other methods have shown promise but are far from perfect. There is an unmet need and growing interest in regenerative medicine and tissue engineering to improve the outcome for patients requiring cartilage repair. Many published reviews on cartilage repair only list human clinical trials, underestimating the wealth of basic sciences and animal studies that are precursors to future research. We therefore set out to perform a systematic review of the literature to assess the translation of stem cell therapy to explore what research had been carried out at each of the stages of translation from bench-top (in vitro), animal (pre-clinical) and human studies (clinical) and assemble an evidence-based cascade for the responsible introduction of stem cell therapy for cartilage defects. This review was conducted in accordance to PRISMA guidelines using CINHAL, MEDLINE, EMBASE, Scopus and Web of Knowledge databases from 1st January 1900 to 30th June 2015. In total, there were 2880 studies identified of which 252 studies were included for analysis (100 articles for in vitro studies, 111 studies for animal studies; and 31 studies for human studies). There was a huge variance in cell source in pre-clinical studies both of terms of animal used, location of harvest (fat, marrow, blood or synovium) and allogeneicity. The use of scaffolds, growth factors, number of cell passages and number of cells used was hugely heterogeneous. SHORT CONCLUSIONS: This review offers a comprehensive assessment of the evidence behind the translation of basic science to the clinical practice of cartilage repair. It has revealed a lack of connectivity between the in vitro, pre-clinical and human data and a patchwork quilt of synergistic evidence. Drivers for progress in this space are largely driven by patient demand, surgeon inquisition and a regulatory framework that is learning at the same pace as new developments take place

Investments in the digital silk road

This chapter discusses opportunities for the new digital economy, a strategically important factor of the economic growth for contributing to the Central Asia Digital Silk Road concept. Focusing on new opportunities for international cooperation, including the development of digital technologies, the chapter also draws attention to the fact that technology advancement causes changes in the economic system which may result in digital inequality. It argues that the O&G industry can become a key driver of growth and development and could potentially boost competitiveness across all sectors. The authors consider a set of public policies in ICT-related sectors in Kazakhstan. These policies are focusing on diversification from the O&G sector, supporting domestic companies and research, encouraging export-oriented projects, and pushing companies to join international initiatives

Mapping genomic loci implicates genes and synaptic biology in schizophrenia

Schizophrenia has a heritability of 60-80%1, much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are expressed in excitatory and inhibitory neurons of the central nervous system, but not in other tissues or cell types. Using fine-mapping and functional genomic data, we identify 120 genes (106 protein-coding) that are likely to underpin associations at some of these loci, including 16 genes with credible causal non-synonymous or untranslated region variation. We also implicate fundamental processes related to neuronal function, including synaptic organization, differentiation and transmission. Fine-mapped candidates were enriched for genes associated with rare disruptive coding variants in people with schizophrenia, including the glutamate receptor subunit GRIN2A and transcription factor SP4, and were also enriched for genes implicated by such variants in neurodevelopmental disorders. We identify biological processes relevant to schizophrenia pathophysiology; show convergence of common and rare variant associations in schizophrenia and neurodevelopmental disorders; and provide a resource of prioritized genes and variants to advance mechanistic studies