Bach1: Function, Regulation, and Involvement in Disease

The transcription factor BTB and CNC homology 1 (Bach1) is widely expressed in most mammalian tissues and functions primarily as a transcriptional suppressor by heterodimerizing with small Maf proteins and binding to Maf recognition elements in the promoters of targeted genes. It has a key regulatory role in the production of reactive oxygen species, cell cycle, heme homeostasis, hematopoiesis, and immunity and has been shown to suppress ischemic angiogenesis and promote breast cancer metastasis. This review summarizes how Bach1 controls these and other cellular and physiological and pathological processes. Bach1 expression and function differ between different cell types. Thus, therapies designed to manipulate Bach1 expression will need to be tightly controlled and tailored for each specific disease state or cell type.

On the promotion of human flourishing

Many empirical studies throughout the social and biomedical sciences focus only on very narrow outcomes such as income, or a single specific disease state, or a measure of positive affect. Human well-being or flourishing, however, consists in a much broader range of states and outcomes, certainly including mental and physical health, but also encompassing happiness and life satisfaction, meaning and purpose, character and virtue, and close social relationships. The empirical literature from longitudinal, experimental, and quasiexperimental studies is reviewed in attempt to identify major determinants of human flourishing, broadly conceived. Measures of human flourishing are proposed. Discussion is given to the implications of a broader conception of human flourishing, and of the research reviewed, for policy, and for future research in the biomedical and social sciences.

Microbial Signatures of Oral Dysbiosis, Periodontitis and Edentulism Revealed by Gene Meter Methodology

ABSTRACTConceptual models suggest certain microorganisms (e.g., the red complex) are indicative of a specific disease state (e.g., periodontitis); however, recent studies have questioned the validity of these models. Here, the abundances of 500+ microbial species were determined in 16 patients with clinical signs of one of the following oral conditions: periodontitis, established caries, edentulism, and oral health. Our goal was to determine if the abundances of certain microorganisms reflect dysbiosis or a specific clinical condition that could be used as a signature for dental research. Microbial abundances were determined by the analysis of 138,718 calibrated probes using Gene Meter methodology. Each 16S rRNA gene was targeted by an average of 194 unique probes (n=25 nt). The calibration involved diluting pooled gene target samples, hybridizing each dilution to a DNA microarray, and fitting the probe intensities to adsorption models. The fit of the model to the experimental data was used to assess individual and aggregate probe behavior; good fits (R2>0.90) were retained for back-calculating microbial abundances from patient samples. The abundance of a gene was determined from the median of all calibrated individual probes or from the calibrated abundance of all aggregated probes. With the exception of genes with low abundances (< 2 arbitrary units), the abundances determined by the different calibrations were highly correlated (r ∼1.0). Seventeen genera were classified as signatures of dysbiosis because they had significantly higher abundances in patients with periodontitis and edentulism when contrasted with health. Similarly, 13 genera were classified as signatures of periodontitis, and 14 genera were classified as signatures of edentulism. The signatures could be used, individually or in combination, to assess the clinical status of a patient (e.g., evaluating treatments such as antibiotic therapies). Comparisons of the same patient samples revealed high false negatives (45%) for next-generation-sequencing results and low false positives (7%) for Gene Meter results.

The Athlete and Medication

The Committee on Drugs unites with the Joint Committee on Physical Fitness, Recreation, and Sports Medicine in condemning the use of drugs to improve athletic performance, However, the Committee on Drugs would like to clearly distinguish between the promiscuous use of drugs and their pharmacologic use to control a specific disease state enabling the adolescent to participate in sports, for example, the use of insulin for diabetes, anticonvulsants for epilepsy, digitalis for heart disease, or bronchodilators for asthma. Children and adolescents with handicaps should be given the same advantages as other children, including participation in athletic activities. Athletes with medical conditions controlled by drugs should not be placed in the same category as youths taking drugs for other purposes, and there should be minimal, if any, restrictions imposed on them. One recent example of the type of restrictions which should not be imposed is the athlete with exercise-induced bronchoconstriction who was disqualified in the 1972 Olympics in Munich because he used a bronchodilator prescribed by his physician. Exercise-induced bronchospasm is a common handicap of allergic youth, and may occur in between 60% and 80% of individuals with allergic respiratory distress.1 Such bronchoconstriction can be modified by the administration of theopylline, theophylline epherdrine combinations,3 or cromolyn sodium,4, 5 The Committee on Children with Handicaps also recommends that children with asthma participate in sports and physical education and that every effort be made to minimize restrictions.6 At the annual meeting of the American Academy of Allergy in Washington, D.C., February 14, 1973, the following resolution was approved unanimously: "Participants in competitive athletics with asthma and other allergic conditions should not be disqualified because of the use, with medical supervision, of therapeutic doses of ephednine before and during athletic competition."7

THE ATHLETE AND MEDICATION

The Committee on Drugs unites with the Joint Committee on Physical Fitness, Recreation, and Sports Medicine in condemning the use of drugs to improve athletic performance. However, the Committee on Drugs would like to clearly distinguish between the promiscuous use of drugs and their pharmacologic use to control a specific disease state enabling the adolescent to participate in sports, for example, the use of insulin for diabetes, anticonvulsants for epilepsy, digitalis for heart disease, or bronchodilators for asthma. Children and adolescents with handicaps should be given the same advantages as other children, including participation in athletic activities. Athletes with medical conditions controlled by drugs should not be placed in the same category as youths taking drugs for other purposes, and there should be minimal, if any, restrictions imposed on them. One recent example of the type of restrictions which should not be imposed is the athlete with exercise-induced bronchoconstriction who was disqualified in the 1972 Olympics in Munich because he used a bronchodilator prescribed by his physician. Exercise-induced bronchospasm is a common handicap of allergic youth, and may occur in between 60% and 80% of individuals with allergic respiratory distress.1 Such bronchoconstriction can be modified by the administration of theopylline,2 theophylline ephedrine combinations,3 or cromolyn sodium.4,5 The Committee on Children with Handicaps also recommends that children with asthma participate in sports and physical education and that every effort be made to minimize restrictions.6 At the annual meeting of the American Academy of Allergy in Washington, D.C., February 14, 1973, the following resolution was approved unanimously: "Participants in competitive athletics with asthma and other allergic conditions should not be disqualified because of the use, with medical supervision, of therapeutic doses of ephedrine before and during athletic competition."7