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Opinion. Discusses the linking of the two `thinking' tools, biology and computer sciences, and the ability of physicians to become innovative utilizing these tools in relation to deoxyribonucleic acid (DNA), the genetic storage medium, experiments. Introduction to the diagnostics of DNA; How biology and computer sciences caused the existence of DNA technologies; Examining the computation of DNA. INSET: Exploding complexities..

The article discusses the use of pain medications and the fear of opioid abuse in terminally ill patients. Therapeutic effects of analgesics; Opiophobia; Myth of addiction; Stress caused by unrelieved pain; Ethical problems; Attitudes and beliefs of physicians about pain. INSET: Buy your cocaine at the corner drugstore..

Discusses the process of aging and dying in living matters. Mechanisms of cells; DNA polymerase; Relationship between the cell division phenomena and death, cancer, AIDS and aging; Strings of nucleotides called `Telomerese'; Discussion on apoptosis; Limits of human lifespan. INSET: Fountain of youth or disaster in the making?..

Probes issues on human reproduction. Discussion of mifepristone (RU-486) and other drugs; Reports of scientific discoveries and proceedings on termination of pregnancies; Discovery of `xeno-estrogens'; Use of intracytoplasmic sperm injection (ICSI) in `in vivo' fertility clinics; Paternity testing problems in DNA identification. INSETS: Fragments from the files.;Emergency contraception..

Focuses on the impact of gene therapy on medical care. Application of laboratory findings to actual cases and patients; Advances in gene therapy; Reliability of gene therapy. INSET: A dreadful history, a promising future..

Looks at information on the emergence of a domain of healthcare and ecological medicine. Parallels between human and planetary health and illnesses; Difference of the emergence of conception of ecological medicine; Report issued in 1988 by the Institute of Medicine (IOM); Outlines of six objectives of IOM report for physicians training in enviromental medicine. INSET: Little warning..

Discusses the problem of multi-drug resistance and the emergence of tuberculosis (TB). Statistics on TB; DNA transformation and gene transfers in nature; Resistance in bacteria, viruses and fungi; lessons from TB; Advances in assay techniques; Proposed answers to multidrug resistance. INSETS: Criminalizing TB.;Multi-drug resistance: A therapy in disguise?..

Features various transplantation therapies. Encapsulated cures; Bone marrow transplants; Cord blood cells; Gene transfer therapies; Genetic vaccines; Tissue engineering; Expectations. INSETS: Potatoes and bananas: Tomorrow's high-tech medicines.;Untitled (Hoechst Marion Roussel)..

Focuses on paradigms involved in molecular medicine. Significance of apoptosis to health; Importance of the molecule known as p53; Mutations of p53 and the cancer resulting from each mutation; Implications of advancements in molecular technology for the treatment of different diseases including cancer; Impact on society of the emergence of molecular technologies. INSETS: The prostate story.;The nature of nature..

Examines the birth and impending death of some of the current extensive medical mythologies ushered in by the emergence of molecular biology. Ancient medical myths; History of the origins and subsequent demythifications of past medical myths; Understanding how future medical paradigms will arise from the demise of past extensive body of medical lore. INSET: Do-it-yourself genetic engineering..

Part 5. Discusses the challenges that physicians have to cope with in order to deal with new scientific information of critical relevance to their daily practice. Neurology; Two-faced propensity of nitric oxide; Applications of chaos theory to biological science; Blurring of boundaries between traditional subspecialties; Patient as the quintessential complexity of medicine. INSET: The theory-to-practice time warp, by Stuart N. Davidson..

Part IV. Discusses the causes and treatment of technological cancer. Failure to excise outdated and inappropriate technologies from the practice of medicine; Unchecked growth of new technologies; Effect on the healthcare system if left untreated; Decrease in the ability of hospitals to offer patients the most appropriate technologies available at the lowest feasible cost. INSET: Will surgery become obsolete?..

Part III. Focuses on research studies dealing with the therapeutic use of gene transfer therapy. Mechanism of gene transfer therapy; Function of cancer genes; Therapeutic pathways as possibilities for the manipulation of suppressor genes; Innovations in genetic vaccines; Barrier presented by the human immune system in targeting drugs to the locus of their need; Approaches to drug discovery. INSETS: Untitled.;Evolution in a test tube, by Stuart N. Davidson..

Part II. Discusses some biomolecular therapeutics that will impact large numbers of diseases. Ability of therapeutics to alter or redesign existing drugs and redefine disease categories or treatments; Approval of antisense drugs; Progress in the use of monoclonal antibodies.

Discusses the development of the different types of therapeutics for the year 2000 and the next two decades. Explanation on the cell cycle and the process of cell death; Development of vaccines and therapeutics for cancer and for drug resistance in tuberculosis, syphilis and other infectious diseases; Recommendation for an oral vaccination of chickens to prevent the spread of Salmonella. INSET: Apoptosis: complex & chaaotic.

Provides information on the regeneration of cells, tissues and organs. Overview of the discovery of liver regeneration; Progress in skin and bone regeneration; Research on the regeneration of central nervous systems neurons of the brain and the spinal cord; Findings of studies on heart transplants. INSET: Restored hearing.

Discusses the increasing importance of chaos theory to medicine. Link between chaos, fractal geometry and human physiology; Application of chaos theory to medicine; Gap between available technologies and the patients that need them.

Opinion. Questions whether Dolly, the mammalian cloned lamb is a clone, with emphasis on the issue of human cloning. Reference to the daughter cells; Information on the process of brain development of a human; Information on the role of mitochondrial DNA in the process of reproduction.

Provides information on the rise and fall and medical paradigms. What are some of the things listed as medical paradigms; Reference to Thomas S. Kuhn; Definition of pardigm given; Background information on the disease tuberculosis.

Discusses the lost art of using placebos in medicine and forecasts the role of psychoneuroimmunology in medicine. Articles pertaining to mind-body connections; Potentials of the mind as healer and cure for allergies; Implications to disease prevention.

The article offers news briefs related to the European Academy of Craniomandibular Disorders (EACD). The annual meeting of EACD, reported be a young academy, was held in Zurich, Switzerland. There was over 400 registrants and the meeting ended with a round table discussion on treatment planning. The University of Detroit Mercy, School of Dentistry, Detroit, Michigan has now begun a temporomandibular joint teaching program under the auspices of the Department of Orthodontics.

Focuses on technological advances in medicine. How magnetic resonance imaging evolved; Advances in therapeutics; How physician can prepare for further advances in medicine.

S-acylation is a major posttranslational modification, catalyzed by the zinc finger DHHC domain containing (zDHHC) enzyme family. S-acylated proteins can be modified by different fatty acids; however, very little is known about how zDHHC enzymes contribute to acyl chain heterogeneity. Here, we used fatty acid-azide/alkyne labeling of mammalian cells, showing their transformation into acyl-CoAs and subsequent click chemistry-based detection, to demonstrate that zDHHC enzymes have marked differences in their fatty acid selectivity. This difference in selectivity was apparent even for highly related enzymes, such as zDHHC3 and zDHHC7, which displayed a marked difference in their ability to use C18:0 acyl-CoA as a substrate. Furthermore, we identified isoleucine-182 in transmembrane domain 3 of zDHHC3 as a key determinant in limiting the use of longer chain acyl-CoAs by this enzyme. This study uncovered differences in the fatty acid selectivity profiles of cellular zDHHC enzymes and mapped molecular determinants governing this selectivity. [ABSTRACT FROM AUTHOR]

Commercially available compression garments (CGs) demonstrate the enhanced recovery from exercise in some, but not all studies. It is possible that in some cases the degree of compression pressure (ComP) exerted is not sufficient to produce any physiological benefit. The aim of this investigation was to identify the levels of ComP exerted by commercially available CGs. This study was composed of two parts. In part A 50 healthy, physically active individuals ( n = 26 male, n = 24 female) were fitted with CGs according to manufacturer's guidelines. ComP was measured in participants standing in the anatomical position with a pressure measurement device inserted between the skin and the garment. Data were compared to 'ideal' pressure values proposed in the literature. In part B, ComP in three different brands of CG was compared in a population of 29 men who all wore a medium-sized garment. A one-way ANOVA indicated that there was a significant difference ( P < 0.05) between observed pressure and ideal pressure at the quadriceps for males and females and in the calf for the female population. There was no significant difference ( P > 0.05) between observed and ideal pressures in the calf of the male population. No significant differences in pressure ( P > 0.05) were observed between CG brands at the quadriceps or calf. In conclusion, a large number of individuals may not be experiencing an adequate ComP from CG, and this is true for all the three major brands of CGs tested in this investigation. [ABSTRACT FROM AUTHOR]

NPL is currently carrying out acoustic resonator experiments with the aim of determining the Boltzmann constant k with an uncertainty below 1 part in 10. In this article, the progress in our efforts to assess the uncertainty in our determination is described. The uncertainty contributions arising from dimensional, chemical, isotopic, thermal, and acoustical considerations are assessed, and it is concluded that a measurement with an uncertainty below 1 part in 10 is achievable. [ABSTRACT FROM AUTHOR]

Background: Exploiting synteny between mouse and human disease loci has been proposed as a cost-effective method for the identification of human susceptibility genes. Here we explore its utility in an analysis of a human personality trait, neuroticism, which can be modeled in mice by tests of emotionality. We investigated a mouse emotionality locus on chromosome 1 that contains no annotated genes but abuts four regulators of G protein signaling, one of which (rgs2) has been previously identified as a quantitative trait gene for emotionality. This locus is syntenic with a human region that has been consistently implicated in the genetic aetiology of neuroticism. Methods: The functional candidacy of 29 murine sequence variants was tested by a combination of gel shift and transient transfection assays. Murine sequences that contained functional variants and exhibited significant cross-species conservation were prioritized for investigation in humans. Genetic association with neuroticism was tested in 1869 high and 2032 low unrelated individuals scored for neuroticism, selected from the extremes of 88,141 people from southwest England. Results: Fifteen sequence variants contributed to variation in the expression of rgs18, the gene lying at the edge of the quantitative trait loci (QTL) interval. There was no evidence of association between neuroticism and single nucleotide polymorphisms (SNPs) lying in the human regions homologous to those of mouse functional variants. One SNP, rs6428058, in a region of sequence conservation 644 kb upstream of RGS18, showed significant association (p = .000631). Conclusions: It is unlikely that a single variant is responsible for the mouse emotionality locus on chromosome 1. This level of underlying genetic complexity means that although cross-species QTL concordance may be invaluable for the identification of human disease loci, it is unlikely to be as informative in the identification of human disease-causing variants. [Copyright &y& Elsevier]

Whole-genome genetic association studies in outbred mouse populations represent a novel approach to identifying the molecular basis of naturally occurring genetic variants, the major source of quantitative variation between inbred strains of mice. Measuring multiple phenotypes in parallel on each mouse would make the approach cost effective, but protocols for phenotyping on a large enough scale have not been developed. In this article we describe the development and deployment of a protocol to collect measures on three models of human disease (anxiety, type II diabetes, and asthma) as well as measures of mouse blood biochemistry, immunology, and hematology. We report that the protocol delivers highly significant differences among the eight inbred strains (A/J, AKR/J, BALBc/J, CBA/J, C3H/HeJ, C57BL/6 J, DBA/2 J, and LP/J), the progenitors of a genetically heterogeneous stock (HS) of mice. We report the successful collection of multiple phenotypes from 2000 outbred HS animals. The phenotypes measured in the protocol form the basis of a large-scale investigation into the genetic basis of complex traits in mice designed to examine interactions between genes and between genes and environment, as well as the main effects of genetic variants on phenotypes. [ABSTRACT FROM AUTHOR]

Highlights genetic linkage scan that uses extremely discordant and concordant sibling pairs to study quantitative trait loci on chromosomes which influence variation in the personality traits of neuroticism. Use of quantitative genetic analysis of personality to explore relationship between sex and neuroticism; Debatable issues generated by the findings of the research.

This study compared the surface properties and rising velocities of pristine and weathered plastic production pellets, to evaluate impacts of environmental conditions. Rising velocities were measured for 140 weathered pellets collected from a Spanish beach and compared with pristine low-density polyethylene, high-density polyethylene and polypropylene pellets. A subset of 49 weathered pellets were analysed by Fourier-transform infrared spectroscopy (FTIR), with all found to be polyethylene. Experimental rising velocities for the weathered pellets varied widely, from (2.36 ± 0.01) cm s -1 to (10.56 ± 0.26) cm s -1 , with a mean value of (5.79 ± 0.06) cm s -1 . Theoretical rising velocities were consistently higher than experimental velocities for all pellet types: on average 136% of experimental values for weathered pellets. This discrepancy was more distinct for less spherical pellets, which were often more weathered. Flatter pellets often oscillated as they rose, which explains at least some of this finding. Atomic force microscopy (AFM) analysis revealed that the roughness of the pristine and weathered pellets was (59 ± 11) nm, and (74 ± 26) nm respectively. X-ray photoelectron spectroscopy (XPS) analysis showed that the proportion of surface oxidised carbon species were 2.3% and 4.0% of the total carbon signal for a pristine and a weathered pellet, respectively; consistent with photochemical reactions changing the surface chemistry of weathered pellets. As determined by density column, weathered pellets had slightly lower experimental densities than pristine pellets. Overall, this study illustrates why it is important that modelling studies on the environmental fate and/or movements of microplastics validate or correct predictions using experimental data.

The rapid adoption of online technologies to deliver postsecondary education amid the COVID-19 pandemic has highlighted the potential for online learning, as well as important equity gaps to be addressed. For over ten years, McMaster University has delivered graduate global health education through a blended-learning approach. In partnership with universities in the Netherlands, India, Thailand, Norway, Colombia, and Sudan, experts from across the Consortium deliver lectures online to students around the world. In 2020, two courses were piloted with small groups of students from Canada and Colombia using machine translation supported by bilingual tutors. Students met weekly via video conferencing software, speaking in English and Spanish and relying on machine translation software to transcribe and translate for group members. Qualitative semi-structured interviews were conducted with students, tutors, and instructors to explore how artificial intelligence can be harnessed to integrate multilingual group work into course offerings, challenging the dominant use of English as the principal language of instruction in global health education. Findings highlight the potential for machine translation to bridge language divides, while also underscoring several key limitations of currently available technology. Further research is needed to investigate the potential for machine translation in facilitating multilingual online education as a pathway to more equitable and inclusive online learning environments., Competing Interests: Competing interestsNo conflicts of interest declared., (© The Author(s) 2022.)

Background: District advisors in five allied health disciplines were introduced in a local health district in rural Australia in 2013. These strategic leadership roles provide support to clinicians and managers. As there is little research exploring allied health leadership models from a strategic and operational perspective, the coordinated commencement of these roles provided opportunity to study the creation of this leadership structure., Methods: Four advisors participated in this action research study which used focus groups and program logic processes to explore the inputs, outputs, barriers, outcomes to date, and preferred future outcomes of the leadership model. A purpose-built questionnaire was sent to 134 allied health clinicians or managers with questionnaire responses used by advisors to visualise the leadership model., Results: Advisors prioritised policy development, representing the profession outside the organisation, and supporting department managers, whilst clinicians prioritised communication and connection-building within the organisation. Outcomes of the leadership model included connection, coordination, and advocacy for clinicians. Future preferred outcomes included increased strategic and workforce planning. Barriers included limited time, a widespread workforce and limited resourcing., Conclusions: Instituting a leadership model improved communication, cohesion, and coordination within the organisation. Future increases in workforce planning and coordination are limited by advisor capacity and competing workloads.

Objective: Ankylosing spondylitis (AS) is a highly heritable common inflammatory arthritis that targets the spine and sacroiliac joints of the pelvis, causing pain and stiffness and leading eventually to joint fusion. Although previous studies have shown a strong association of IL23R with AS in white Europeans, similar studies in East Asian populations have shown no association with common variants of IL23R, suggesting either that IL23R variants have no role or that rare genetic variants contribute. The present study was undertaken to screen IL23R to identify rare variants associated with AS in Han Chinese., Methods: A 170-kb region containing IL23R and its flanking regions was sequenced in 50 patients with AS and 50 ethnically matched healthy control subjects from a Han Chinese population. In addition, the 30-kb region of peak association in white Europeans was sequenced in 650 patients with AS and 1,300 healthy controls. Validation genotyping was undertaken in 846 patients with AS and 1,308 healthy controls., Results: We identified 1,047 variants, of which 729 were not found in the dbSNP genomic build 130. Several potentially functional rare variants in IL23R were identified, including one nonsynonomous single-nucleotide polymorphism (nsSNP), Gly(149) Arg (position 67421184 GA on chromosome 1). Validation genotyping showed that the Gly(149) Arg variant was associated with AS (odds ratio 0.61, P = 0.0054)., Conclusion: This is the first study to implicate rare IL23R variants in the pathogenesis of AS. The results identified a low-frequency nsSNP with predicted loss-of-function effects that was protectively associated with AS in Han Chinese, suggesting that decreased function of the interleukin-23 (IL-23) receptor protects against AS. These findings further support the notion that IL-23 signaling has an important role in the pathogenesis of AS., (Copyright © 2013 by the American College of Rheumatology.)

Objective: Ankylosing spondylitis (AS) is a common inflammatory arthritis affecting primarily the axial skeleton. IL23R is genetically associated with AS. This study was undertaken to investigate and characterize the role of interleukin-23 (IL-23) signaling in AS pathogenesis., Methods: The study population consisted of patients with active AS (n = 17), patients with psoriatic arthritis (n = 8), patients with rheumatoid arthritis, (n = 9), and healthy subjects (n = 20). IL-23 receptor (IL-23R) expression in T cells was determined in each subject group, and expression levels were compared., Results: The proportion of IL-23R-expressing T cells in the periphery was 2-fold higher in AS patients than in healthy controls, specifically driven by a 3-fold increase in IL-23R-positive γ/δ T cells in AS patients. The proportions of CD4+ and CD8+ cells that were positive for IL-17 were unchanged. This increased IL-23R expression on γ/δ T cells was also associated with enhanced IL-17 secretion, with no observable IL-17 production from IL-23R-negative γ/δ T cells in AS patients. Furthermore, γ/δ T cells from AS patients were heavily skewed toward IL-17 production in response to stimulation with IL-23 and/or anti-CD3/CD28., Conclusion: Recently, mouse models have shown IL-17-secreting γ/δ T cells to be pathogenic in infection and autoimmunity. Our data provide the first description of a potentially pathogenic role of these cells in a human autoimmune disease. Since IL-23 is a maturation and growth factor for IL-17-producing cells, increased IL-23R expression may regulate the function of this putative pathogenic γ/δ T cell population., (Copyright © 2012 by the American College of Rheumatology.)

Objectives: Recent association studies by the Australo-Anglo-American Spondyloarthritis Consortium (TASC) in Caucasian European populations from Australia, North America and the UK have identified a number of genes as being associated with ankylosing spondylitis (AS). A candidate gene study in a Han Chinese population was performed based on these findings to identify associated genes in this population., Methods: A case-control study was performed in a Han Chinese population of patients with AS (n = 775) and controls (n = 1587) from Shanghai and Nanjing. All patients met the modified New York criteria for AS. The cases and controls were genotyped for 115 single nucleotide polymorphisms (SNPs) tagging IL23R, ERAP1, STAT3, JAK2, TNFRSF1A and TRADD, as well as other confirmation SNPs from the TASC study, using the Sequenom iPlex and the ABI OpenArray platforms. Statistical analysis of genotyped SNPs was performed using the Cochran-Armitage test for trend and meta-analysis was performed using METAL. SNPs in AS-associated genes in this study were then imputed using MaCH, and association with AS tested by logistic regression., Results: SNPs in TNFRSF1A (rs4149577, p = 8.2 × 10⁻⁴), STAT3 (rs2293152, p = 0.0015; rs1053005, p = 0.017) and ERAP1 (rs27038, p = 0.0091; rs27037, p = 0.0092) were significantly associated with AS in Han Chinese. Association was also observed between AS and the intergenic region 2p15 (rs10865331, p = 0.023). The lack of association between AS and IL23R in Han Chinese was confirmed (all SNPs p > 0.1)., Conclusions: The study results demonstrate for the first time that genetic polymorphisms in STAT3, TNFRSF1A and 2p15 are associated with AS in Han Chinese, suggesting common pathogenic mechanisms for the disease in Chinese and Caucasian European populations. Furthermore, previous findings demonstrating that ERAP1, but not IL23R, is associated with AS in Chinese patients were confirmed.