This third edition of what has now become a well-established textbook in cardiovascular medicine is again edited by Dr Eugene Braunwald with the assistance of 65 other authors who read like a Who's Who of American Cardiology. Since the second edition, 12 new chapters have been added or substituted and others have been significantly revised. The first volume includes Part I on "Examination of the Patient" and Part II on "Normal and Abnormal Circulatory Function." The second volume deals with specific diseases. Part III, "Diseases of the Heart, Pericardium and Vascular System," includes new sections on "Risk Factors for Coronary Artery Disease," "The Pathogenesis of Atherosclerosis," and "Interventional Catheterization Techniques." Part IV, "Broader Perspectives on Heart Disease and Cardiologic Practice," includes new chapters on "Genetics and Cardiovascular Disease," "Aging in Cardiac Disease," and "Cost Effective Strategies in Cardiology." The last 200 pages of the book (Part V) are devoted to

Heart Disease: A Textbook of Cardiovascular Medicine

Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and similar to 2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 x 10(-8)), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.

Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index

The worldwide obesity epidemic has been mainly attributed to lifestyle changes. However, who becomes obese in an obesity-prone environment is largely determined by genetic factors. In the last 20 years, important progress has been made in the elucidation of the genetic architecture of obesity. In parallel with successful gene identifications, the number of gene–environment interaction (GEI) studies has grown rapidly. This paper reviews the growing body of evidence supporting gene–environment interactions in the field of obesity. Heritability, monogenic and polygenic obesity studies provide converging evidence that obesity-predisposing genes interact with a variety of environmental, lifestyle and treatment exposures. However, some skepticism remains regarding the validity of these studies based on several issues, which include statistical modelling, confounding, low replication rate, underpowered analyses, biological assumptions and measurement precision. What follows in this review includes (1) an introduction to the study of GEI, (2) the evidence of GEI in the field of obesity, (3) an outline of the biological mechanisms that may explain these interaction effects, (4) methodological challenges associated with GEI studies and potential solutions, and (5) future directions of GEI research. Thus far, this growing body of evidence has provided a deeper understanding of GEI influencing obesity and may have tremendous applications in the emerging field of personalized medicine and individualized lifestyle recommendations.

The importance of gene–environment interactions in human obesity

Liquid biopsy: miRNA as a potential biomarker in oral cancer.

KG Tantisira, J Lasky-Su, M Harada. N Engl J Med. 2011;365(13):1173–1183

To determine the genetic basis for the individual variability response to inhaled glucocorticoid (ICS) therapy.

The primary study population was the Childhood Asthma Management Program cohort of 1041 children with asthma who were 5 to 12 years old at enrollment. Additional subjects were selected from 3 other National Institutes of Health–sponsored clinical …

https://pediatrics.aappublications.org/content/pediatrics/130/Supplement_1/S41.1.full.pdf

Genomewide Association Between GLCCI1 and Response to Glucocorticoid Therapy in Asthma

Circulating microRNAs (miRNAs) have been detected in various types of cancer and have been proposed as novel biomarkers for diagnosis and treatment. Until recently, however, no studies had comprehensively examined circulating miRNAs in oral cancer. The current study used an ultra-sensitive genome-wide miRNA array to investigate changes in circulating miRNAs in plasma from five patients with oral cancer and ten healthy individuals. Results indicated that there were only a few circulating miRNAs, including miR-223, miR-26a, miR-126, and miR-21, that were up-regulated in patients with oral cancer. A subsequent validation test indicated that circulating miR-223 levels were significantly higher (~2-fold, P< 0.05) in patients with oral cancer (n = 31) than in those without cancer (n = 31). Moreover, miR-223 was found to be up-regulated in tumor-adjacent normal tissue compared to tumor tissue from patients with oral cancer. A gain-of-function assay was performed to explore the potential roles of circulating miR-223 in the development of oral cancer. Results revealed that miR-223 functions as a tumor suppressor by inhibiting cell proliferation and inducing apoptosis. In conclusion, this study suggested that circulating miR-223 may serve as a potential biomarker for diagnosis and that it may represent a novel therapeutic target for treatment of oral cancer.

/pdf/circulating-mir-223-in-oral-cancer-its-potential-as-a-novel-20kp77r3db.pdf

Circulating miR-223 in Oral Cancer: Its Potential as a Novel Diagnostic Biomarker and Therapeutic Target.

Learning curve for port-access thoracoscopic anatomic lung segmentectomy.

Obesity is associated with environmental factors; however, information about gene-environment interactions is lacking. We aimed to elucidate the effects of gene-environment interactions on obesity, specifically between genetic predisposition and various obesity-related lifestyle factors, using data from a population-based prospective cohort study. The genetic risk score (GRS) calculated from East Asian ancestry single-nucleotide polymorphisms was significantly associated with the body mass index (BMI) at baseline (P<0.001). Significant gene-environment interactions were observed for six nutritional factors, alcohol intake, metabolic equivalents-hour per day and the homeostasis model assessment ratio. The GRS altered the effects of lifestyle factors on BMI. Increases in the BMI at baseline per unit intake for each nutritional factor differed depending on the GRS. However, we did not observe significant correlations between the GRS and annual changes in BMI during the follow-up period. This study suggests that the effects of lifestyle factors on obesity differ depending on the genetic risk factors. The approach used to evaluate gene-environment interaction in this study may be applicable to the practice of preventive medicine.

Gene–environment interactions in obesity: implication for future applications in preventive medicine

CM2 is the second membrane protein of influenza C virus. Although its biochemical characteristics, coding strategy, and properties as an ion channel have been extensively studied, the role(s) of CM2 in the virus replication cycle remains to be clarified. In order to elucidate this role, in the present study we generated CM2-deficient influenza C virus-like particles (VLPs) and examined the VLP-producing 293T cells, VLPs, and VLP-infected HMV-II cells. Quantification of viral RNA (vRNA) in the VLPs by real-time PCR revealed that the CM2-deficient VLPs contain approximately one-third of the vRNA found in wild-type VLPs although no significant differences were detected in the expression levels of viral components in VLP-producing cells or in the number and morphology of the generated VLPs. This finding suggests that CM2 is involved in the genome packaging process into VLPs. Furthermore, HMV-II cells infected with CM2-deficient VLPs exhibited significantly reduced reporter gene expression. Although CM2-deficient VLPs could be internalized into HMV-II cells as efficiently as wild-type VLPs, a smaller amount of vRNA was detected in the nuclear fraction of CM2-deficient VLP-infected cells than in that of wild-type VLP-infected cells, suggesting that the uncoating process of the CM2-deficient VLPs in the infected cells did not proceed in an appropriate manner. Taken together, the data obtained in the present study indicate that CM2 has a potential role in the genome packaging and uncoating processes of the virus replication cycle.

Role of the CM2 Protein in the Influenza C Virus Replication Cycle

China and Japan share numerous similarities other than their geographical proximity. Facing the great challenges of non-communicable diseases (NCDs), China and Japan have developed different preventive strategies and systems. While Japan has made great progress in primary prevention of NCDs through strong legislation, the ‘Specific Health Check and Guidance System’ and a unique licensed health professional system, China is attempting to catch up by changing its strategies in NCDs control. In this manuscript, we compared disease burden of NCDs, health care systems and preventive strategies against NCDs between China and Japan. In this light, we summarized the points that the two countries can learn from each other, and proposed recommendations for the two countries in NCDs control.

/pdf/non-communicable-diseases-control-in-china-and-japan-523etc3j2g.pdf

Ri Sho

Papers

Circulating miR-223 in Oral Cancer: Its Potential as a Novel Diagnostic Biomarker and Therapeutic Target.

Learning curve for port-access thoracoscopic anatomic lung segmentectomy.

Gene–environment interactions in obesity: implication for future applications in preventive medicine

Role of the CM2 Protein in the Influenza C Virus Replication Cycle

Non-communicable diseases control in China and Japan