From evidence-based medicine to genomic medicine

The concept of ‘evidence-based medicine’ dates back to mid-19th century or even earlier. It remains pivotal in planning, funding and in delivering the health care. Clinicians, public health practitioners, health commissioners/purchasers, health planners, politicians and public seek formal ‘evidence’ in approving any form of health care provision. Essentially ‘evidence-based medicine’ aims at the conscientious, explicit and judicious use of the current best evidence in making decisions about the care of individual patients. It is in fact the ‘personalised medicine’ in practice. Since the completion of the human genome project and the rapid accumulation of huge amount of data, scientists and physicians alike are excited on the prospect of ‘personalised health care’ based on individual’s genotype and phenotype. The first decade of the new millennium now witnesses the transition from ‘evidence-based medicine’ to the ‘genomic medicine’. The practice of medicine, including health promotion and prevention of disease, stands now at a wide-open road as the scientific and medical community embraces itself with the rapidly expanding and revolutionising field of genomic medicine. This article reviews the rapid transformation of modern medicine from the ‘evidence-based medicine’ to ‘genomic medicine’.     

INDUSTRY CALLING!—Is There a Doctor in the House?

Medical service is needed in industry by both management and labor as never before. Industry is just beginning to awaken to this need. The medical profession is largely unaware of it. Unless physicians are prepared to heed this call, there is danger that management and labor will come to a bipartisan agreement over the bargaining table which will specify the amount, quality, and price of medical service irrespective of the effects of such an agreement on the practice of medicine. Such agreements should invariably be tripartite—between management, labor and medicine—if we are to continue to strive for medicine''s traditional ideals: The best of medical care for all alike.This situation imposes at least two important obligations on organized medicine at the national level and especially at state and local levels where there is industrial concentration:1. Provision of a strong and competent committee or council whose members are especially interested in occupational medicine and who will make their presence known to management and labor alike, offering to advise with them on all medical problems, to mediate their disagreements or medical questions, and to help them attain a common goal.2. Assisting the members of organized medicine who are interested, to learn more about the medical problems peculiar to occupational health.     

Focus: The Aging Brain: Neural stem/progenitor cells in Alzheimer’s disease

Alzheimer’s disease (AD) is the most prevalent neurodegenerative disease and a worldwide health challenge. Different therapeutic approaches are being developed to reverse or slow the loss of affected neurons. Another plausible therapeutic way that may complement the studies is to increase the survival of existing neurons by mobilizing the existing neural stem/progenitor cells (NSPCs) — i.e. “induce their plasticity” — to regenerate lost neurons despite the existing pathology and unfavorable environment. However, there is controversy about how NSPCs are affected by the unfavorable toxic environment during AD. In this review, we will discuss the use of stem cells in neurodegenerative diseases and in particular how NSPCs affect the AD pathology and how neurodegeneration affects NSPCs. In the end of this review, we will discuss how zebrafish as a useful model organism with extensive regenerative ability in the brain might help to address the molecular programs needed for NSPCs to respond to neurodegeneration by enhanced neurogenesis.     

The Role of the Practising Physician in Medical Student Recruitment

The role that the practitioner of medicine can play in assisting recruitment to medical schools is examined. Although the total enrolment in universities has increased sharply in the past decade, the group applying to enter medicine has decreased. The output of Canada''s 12 schools of medicine—850 graduates per year-falls significantly short of the number of new physicians required to maintain the present physician:population ratio. With the expanded output of physicians required in future, an active program of recruitment will be necessary. The recruitment program organized by the practising physicians of British Columbia and the Faculty of Medicine at the University of British Columbia is outlined.     

The indigenization of neurasthenia in Hong Kong

Despite its origin in Western psychiatry, neurasthenia has become a popular concept in Chinese folk medicine, referring to a variety of somatic and psychological symptoms. Review of Chinese medicinal materials and patent medicines shows that neurasthenia is associated more often with somatic symptoms in tonic type medicine and with psychological and psychosomatic symptoms in sedative and tranquilizer type medicine. Popular Chinese books on neurasthenia suggest that causes might be attributed to lifestyle, psychological factors, and health problems. Recommendations on treatment emphasize self-help approaches through changing lifestyle, examining attitudes, tonic care, and relaxation. As a broad term used loosely by professionals and the lay public in Hong Kong, neurasthenia serves the important function of destigmatizing psychiatric disorders. Psychosexual problems may also be conveyed discreetly through somatic presentation. The indigenization of neurasthenia exemplifies how an originally Western concept acquires cultural meaning. Implications of illness conceptualization and the medical paradigm are discussed.     

Health in China. Traditional Chinese medicine: one country,two systems.

China is the only country in the world where Western medicine and traditional medicine are practised alongside each other at every level of the healthcare system. Traditional Chinese medicine has a unique theoretical and practical approach to the treatment of disease, which has developed over thousands of years. Traditional treatments include herbal remedies, acupuncture, acupressure and massage, and moxibustion. They account for around 40% of all health care delivered in China. The current government policy of expansion of traditional facilities and manpower is being questioned because many hospitals using traditional Chinese medicine are already underutilized and depend on government subsidies for survival. Research priorities include randomised controlled trials of common treatments and analysis of the active agents in herbal remedies. As more studies show the clinical effectiveness of traditional Chinese medicine, an integrated approach to disease using a combination of Western medicine and traditional approaches becomes a possibility for the future.     

PUBLIC HEALTH IN THE SPACE AGE

Medicine and public health in the space age will work in closer partnership. Both will draw more widely from the behavioral sciences. More spectacular conquests in space will come before man learns much more about man himself and his interrelationships with his fellow man. The past century has been the era of the biological and physical scientist; we are now entering the century of the psychological man. There is a fusion of the sciences—biological, physical and social—in medical research, teaching and service.One is apt to think of public health as a specialty of medicine. Equally valid is the concept that medicine is a specialty of public health, which draws from more of the basic sciences.Epidemiology is concerned with noninfectious conditions and is moving into the epidemiology of health. The spectacular gains in life-saving in this country during the past half century are unrepeatable phenomena. The major gains in the future must come in the older ages.     

Genomic medicine and neurological disease

“Genomic medicine” refers to the diagnosis, optimized management, and treatment of disease—as well as screening, counseling, and disease gene identification—in the context of information provided by an individual patient’s personal genome. Genomic medicine, to some extent synonymous with “personalized medicine,” has been made possible by recent advances in genome technologies. Genomic medicine represents a new approach to health care and disease management that attempts to optimize the care of a patient based upon information gleaned from his or her personal genome sequence. In this review, we describe recent progress in genomic medicine as it relates to neurological disease. Many neurological disorders either segregate as Mendelian phenotypes or occur sporadically in association with a new mutation in a single gene. Heritability also contributes to other neurological conditions that appear to exhibit more complex genetics. In addition to discussing current knowledge in this field, we offer suggestions for maximizing the utility of genomic information in clinical practice as the field of genomic medicine unfolds.     

Phenotypic flexibility as key factor in the human nutrition and health relationship

Metabolic adaptation to a disturbance of homeostasis is determined by a series of interconnected physiological processes and molecular mechanisms that can be followed in space (i.e., different organs or organelles) and in time. The amplitudes of these responses of this “systems flexibility network” determine to what extent the individual can adequately react to external challenges of varying nature and thus determine the individual’s health status and disease predisposition. Connected pathways and regulatory networks act as “adaptive response systems” with metabolic and inflammatory processes as a core—but embedded into psycho-neuro-endocrine control mechanisms that in their totality define the phenotypic flexibility in an individual. Optimal metabolic health is thus the orchestration of all mechanisms and processes that maintain this flexibility in an organism as a phenotype. Consequently, onset of many chronic metabolic diseases results from impairment or even loss of flexibility in parts of the system. This also means that metabolic diseases need to be diagnosed and treated from a systems perspective referring to a “systems medicine” approach. This requires a far better understanding of the mechanisms involved in maintaining, optimizing and restoring phenotypic flexibility. Although a loss of flexibility in a specific part of the network may promote pathologies, this not necessarily takes place in the same part because the system compensates. Diagnosis at systems level therefore needs the quantification of the response reactions of all relevant parts of the phenotypic flexibility system. This can be achieved by disturbing the homeostatic system by any challenge from extended fasting, to intensive exercise or a caloric overload.     

Issues in Health Care of Middle Eastern Patients

Relationships between Middle Eastern patients and Western health care professionals are often troubled by mutual misunderstanding of culturally influenced values and communication styles. Although Middle Easterners vary ethnically, they do share a core of common values and behavior that include the importance of affiliation and family, time and space orientations, interactional style and attitudes toward health and illness. Problems in providing health care involve obtaining adequate information, “demanding behavior” by a patient''s family, conflicting beliefs about planning ahead and differing patterns of communicating grave diagnoses or “bad news.” There are guidelines that will provide an understanding of the cultural characteristics of Middle Easterners and, therefore, will improve rather than impede their health care. A personal approach and continuity of care by the same health care professional help to bridge the gap between Middle Eastern cultures and Western medical culture. In addition, periodic use of cultural interpreters helps ameliorate the intensity of some cultural issues.     

Circumpolar Genetic Structure and Recent Gene Flow of Polar Bears: A Reanalysis

Recently, an extensive study of 2,748 polar bears (Ursus maritimus) from across their circumpolar range was published in PLOS ONE, which used microsatellites and mitochondrial haplotypes to apparently show altered population structure and a dramatic change in directional gene flow towards the Canadian Archipelago—an area believed to be a future refugium for polar bears as their southernmost habitats decline under climate change. Although this study represents a major international collaborative effort and promised to be a baseline for future genetics work, methodological shortcomings and errors of interpretation undermine some of the study’s main conclusions. Here, we present a reanalysis of this data in which we address some of these issues, including: (1) highly unbalanced sample sizes and large amounts of systematically missing data; (2) incorrect calculation of F_ST and of significance levels; (3) misleading estimates of recent gene flow resulting from non-convergence of the program BayesAss. In contrast to the original findings, in our reanalysis we find six genetic clusters of polar bears worldwide: the Hudson Bay Complex, the Western and Eastern Canadian Arctic Archipelago, the Western and Eastern Polar Basin, and—importantly—we reconfirm the presence of a unique and possibly endangered cluster of bears in Norwegian Bay near Canada’s expected last sea-ice refugium. Although polar bears’ abundance, distribution, and population structure will certainly be negatively affected by ongoing—and increasingly rapid—loss of Arctic sea ice, these genetic data provide no evidence of strong directional gene flow in response to recent climate change.     

Evolutionary Dynamics of Human Toll-Like Receptors and Their Different Contributions to Host Defense

Infectious diseases have been paramount among the threats to health and survival throughout human evolutionary history. Natural selection is therefore expected to act strongly on host defense genes, particularly on innate immunity genes whose products mediate the direct interaction between the host and the microbial environment. In insects and mammals, the Toll-like receptors (TLRs) appear to play a major role in initiating innate immune responses against microbes. In humans, however, it has been speculated that the set of TLRs could be redundant for protective immunity. We investigated how natural selection has acted upon human TLRs, as an approach to assess their level of biological redundancy. We sequenced the ten human TLRs in a panel of 158 individuals from various populations worldwide and found that the intracellular TLRs—activated by nucleic acids and particularly specialized in viral recognition—have evolved under strong purifying selection, indicating their essential non-redundant role in host survival. Conversely, the selective constraints on the TLRs expressed on the cell surface—activated by compounds other than nucleic acids—have been much more relaxed, with higher rates of damaging nonsynonymous and stop mutations tolerated, suggesting their higher redundancy. Finally, we tested whether TLRs have experienced spatially-varying selection in human populations and found that the region encompassing TLR10-TLR1-TLR6 has been the target of recent positive selection among non-Africans. Our findings indicate that the different TLRs differ in their immunological redundancy, reflecting their distinct contributions to host defense. The insights gained in this study foster new hypotheses to be tested in clinical and epidemiological genetics of infectious disease.     

Intercellular communication, NO and the biology of Chinese medicine

New multiple categories of health disciplines have become popular in the west and integration between the medicinal approaches has become essential. The hypothesis presented here suggests a novel integrative view that combines Western biochemistry with the Chinese medicinal concept of qi. The core for this hypothesis is that transmission of qi along the meridians is based on informational molecules that travel via an intercellular communication system. Acupuncture at specific points enhances the flow of the signaling molecules through this communication system. Nitric oxide is suggested as a prime candidate for such a signaling molecule in the meridian system. The biochemistry of nitric oxide can shed light on the biology underlying Chinese medicine while Chinese medicinal data can provide a clue to the sought after framework for nitric oxide.     

Healthy Bodies,Toxic Medicines: College Students and the Rhetorics of Flu Vaccination

This article examines flu vaccination beliefs and practices produced during a survey of undergraduate students in Spring 2012 (IRB#10-732). This research uses the methods of rhetorical analysis — or the study of persuasive features and arguments used in language — to examine statements respondents made regarding flu and flu vaccine. In these responses, students generated unique categories of arguments about the perceived dangers of flu vaccination, including the assertion that vaccines cause disease (including illnesses and conditions other than flu), that vaccines are toxic medicines, and that vaccines carry unknown, population-wide risks that are inadequately acknowledged. This study provides insight into vaccination beliefs and rationales among a population at risk of flu (college students) and suggests that further study of this population may yield important keys to addressing flu vaccine concerns as expressed by college students. Rhetorical analysis also offers a useful set of methods to understanding vaccination beliefs and practices, adding to existing methods of study and analysis of vaccination practices and beliefs in medicine and public health.     

Regenerative and stem cell-based techniques for facial rejuvenation

This review discusses the most novel ideas and modalities being incorporated into facial rejuvenation. Recent innovative techniques include the use of regenerative stem cell techniques and regeneration supportive modalities such as nano-technology or gene therapies. This review aims to investigate approaches that are less well known and lacking established evidence in order to proactively study these techniques prior to them becoming popularized. These applications and relevant research were reviewed in the context of both surgical and non-surgical modalities in clinical practice. Future directions include the concept of “precision cosmetic medicine” utilizing gene editing and cellular therapies to tailor rejuvenation techniques based on each individual’s genetic make-up and therefore needs.     

The Need for Continuing Medical Education

Continuing medical education is an essential feature of the practice of modern medicine since it furnishes the means to maintain the doctor''s ability to provide quality patient care.To ensure that continuing medical education is provided efficiently and in the best quality, and utilized fully, it is necessary that: (1) the medical faculty inculcate in the student the concept of lifelong learning; (2) the practitioner adopt less time-consuming patterns of practice, to free more of his time for learning; (3) community hospital-based clinical teaching be provided universally; and (4) research be conducted to determine the best of current teaching methods and develop better ones. Conflicting efforts to meet these needs by practitioners (whose primary responsibility it is) and by organized medicine, specialty societies, voluntary health agencies and others have led to inefficient use of medical faculty teachers. The key parties in continuing medical education—practitioner and teacher—can learn best in medical school-administered programs, which need be supported by all other interested organizations.     

Pluripotency and Epigenetic Factors in Mouse Embryonic Stem Cell Fate Regulation

Embryonic stem cells (ESCs) are characterized by their ability to self-renew and to differentiate into all cell types of a given organism. Understanding the molecular mechanisms that govern the ESC state is of great interest not only for basic research—for instance, ESCs represent a perfect system to study cellular differentiation in vitro—but also for their potential implications in human health, as these mechanisms are likewise involved in cancer progression and could be exploited in regenerative medicine. In this minireview, we focus on the latest insights into the molecular mechanisms mediated by the pluripotency factors as well as their roles during differentiation. We also discuss recent advances in understanding the function of the epigenetic regulators, Polycomb and MLL complexes, in ESC biology.