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2.
Spec Care Dentist ; 38(6): 345-355, 2018 Nov.
Article En | MEDLINE | ID: mdl-30194737

PURPOSE/AIM: The aim of this pilot study was to evaluate feasibility and gather initial data for a definitive study to test the clinical and microbiological effectiveness of a nursing facility (NF) customized oral hygiene protocol, intended to be delivered by dental hygienists and NF personnel. MATERIALS AND METHODS: A convenience sample of 8 Eastern Iowa NFs was recruited, and each NF was assigned to one of three intervention groups: (1) control (current oral hygiene practice), (2) educational program only, and (3) educational program plus 1% chlorhexidine varnish monthly application. Demographic information, systemic health data, patient centered data, oral health data, and microbiology samples were collected at baseline and after 6 months. RESULTS: Recruitment response rates were 21% for NFs and 23% for residents. A total of 81 residents were examined at baseline and of those, 49 were examined at 6 months (39.5% attrition). There were no statistically or clinically significant differences among the intervention groups at 6 months for any of the recorded clinical or microbiological outcomes. CONCLUSIONS: Recruitment and retention posed a significant challenge to this trial, even with a relatively short observation period. Results from this pilot study did not encourage further investigation of this customized oral hygiene protocol.


Nursing Homes , Oral Hygiene/education , Oral Hygiene/nursing , Aged , Aged, 80 and over , Dental Hygienists , Feasibility Studies , Female , Humans , Iowa , Male , Patient Education as Topic , Pilot Projects , Treatment Outcome
3.
Clin Exp Dent Res ; 3(6): 235-243, 2017 12.
Article En | MEDLINE | ID: mdl-29416899

Early childhood caries is a complex health care issue that has a multifactorial etiology. One aspect of this etiology is the colonization and propagation of acidogenic bacteria at an early age. There have been several bacterial species associated with caries but 1 common species is Streptococcus mutans. Here, we describe genotypic diversity and commonality of Streptococcus mutans recovered from children representing 2 groups with similar socioeconomic demographics: a Northern Plains American Indian Tribe and a Southeast Iowa population. Forty 36-month-old American Indian children were selected from a cohort of 239 mothers and children, and forty 2- to 5-year-old children from Southeast Iowa were selected to compare the genotypic profiles of Streptococcus mutans recovered from each child's plaque. S. mutans isolates were selected from whole mouth plaque samples; DNA was extracted and amplified via AP-PCR to show specific genotype patterns. These patterns were compared with GelComparIIv6.5 gel analysis software. We found 18 distinct genotypes from 524 isolates; 13 of which were common between the 2 communities. Five genotypes were unique to only the American Indian children while the Southeast Iowa children harbored no unique genotypes. Although the American Indian children had some genotypes that were not present in the Southeast Iowa children, these were not widely distributed among the community. Furthermore, the levels of genotypic diversity and commonality were similar between the 2 populations. This study sets the groundwork for a comprehensive comparison of genotypes and caries among larger subsections of both populations.

4.
J Oral Microbiol ; 8: 32940, 2016.
Article En | MEDLINE | ID: mdl-27790973

BACKGROUND: Non-mutans low pH oral streptococci are postulated to contribute to caries etiology. OBJECTIVE: This study was undertaken to investigate whether the acidogenicity and acid tolerance of clinical strains of Streptococcus oralis and Streptococcus mitis correlate with health or early-stage enamel caries. DESIGN: S. oralis and S. mitis were isolated from plaque samples taken from the occlusal surfaces of second molars sampled at two different visits 4 years apart. All sites were sound at Visit 1; subjects were segregated into one of three groups based on the status of the site at Visit 2 and caries elsewhere in the dentition. Strains of S. oralis and S. mitis were evaluated for acidogenicity and acid tolerance, and the results correlated with the clinical status of the sites from which they were isolated. Mutans streptococci (MS) isolated from the plaque samples were also quantified, and the presence or absence of growth on pH 5.5 media or on media selective for bifidobacteria was recorded. RESULTS: No significant positive correlations were found between the acidogenicity properties of the S. oralis and S. mitis clones and caries at either visit. Similar results were obtained for acid tolerance of S. oralis clones but were inconclusive for S. mitis clones. A statistically significant positive correlation between MS levels and caries (or future caries) was evident at both visits, but there were no statistical correlations with the growth on pH 5.5 media or media selective for bifidobacteria. CONCLUSIONS: The low pH potential likely varies considerably among oral streptococcal species and is least likely to be found among strains of S. mitis. Accordingly, the concept and constitution of 'low pH streptococci' may need to be re-evaluated.

5.
J Dent Educ ; 80(4): 430-8, 2016 Apr.
Article En | MEDLINE | ID: mdl-27037451

The aim of this study was to help inform faculty and curriculum leaders in academic dental institutions about the knowledge, skills, perceptions, and behavior of an institutionally diverse population of dental students with respect to evidence-based practice (EBP). A survey utilizing the validated Knowledge, Attitudes, Access, and Confidence Evaluation instrument developed by Hendricson et al. was conducted in 2012 with fourth-year dental students at seven geographically dispersed U.S. dental schools. The survey addressed elements of EBP knowledge, attitudes toward EBP, behavior in accessing evidence, and perceptions of competence in statistical analysis. A total of 138 students from the seven schools participated. A slight majority of these students correctly responded to the knowledge of critical appraisal questions. While the students demonstrated positive attitudes about EBP, they did not report high levels of confidence in their critical appraisal skills. The findings also showed that the students accessed various sources of evidence with differing frequencies. The most frequently accessed resources were colleagues, the Internet (excluding Cochrane Database of Systematic Reviews), and textbooks. The results of this study help to identify areas for improvement in EBP education in order to advance dental students' preparation to become evidence-based practitioners.


Attitude of Health Personnel , Behavior , Clinical Competence , Education, Dental , Evidence-Based Dentistry/education , Students, Dental/psychology , Access to Information , Comprehension , Cross-Sectional Studies , Databases as Topic , Humans , Internet , Interprofessional Relations , Meta-Analysis as Topic , Research Design , Self Concept , Statistics as Topic , Thinking , United States
6.
J Public Health Dent ; 76(4): 259-262, 2016 09.
Article En | MEDLINE | ID: mdl-26992441

OBJECTIVES: To compare timing of tooth emergence among groups of American Indian (AI), Black and White children in the United States at 12 months of age. METHODS: Data were from two sources - a longitudinal study of a Northern Plains tribal community and a study with sites in Indiana, Iowa and North Carolina. For the Northern Plains study, all children (n = 223) were American Indian, while for the multisite study, children (n = 320) were from diverse racial groups. Analyses were limited to data from examinations conducted within 30 days of the child's first birthday. RESULTS: AI children had significantly more teeth present (Mean: 7.8, Median: 8.0) than did Whites (4.4, 4.0, P < 0.001) or Blacks (4.5, 4.0, P < 0.001). No significant differences were detected between Black and White children (P = 0.58). There was no significant sex difference overall or within any of the racial groups. CONCLUSIONS: Tooth emergence occurs at a younger age for AI children than it does for contemporary White or Black children in the United States.


Ethnicity , Tooth Eruption/physiology , Tooth, Deciduous , Female , Humans , Infant , Longitudinal Studies , Male , United States
7.
J Bacteriol ; 198(1): 157-67, 2016 01 01.
Article En | MEDLINE | ID: mdl-26483519

UNLABELLED: Lipids endogenous to skin and mucosal surfaces exhibit potent antimicrobial activity against Porphyromonas gingivalis, an important colonizer of the oral cavity implicated in periodontitis. Our previous work demonstrated the antimicrobial activity of the fatty acid sapienic acid (C(16:1Δ6)) against P. gingivalis and found that sapienic acid treatment alters both protein and lipid composition from those in controls. In this study, we further examined whole-cell protein differences between sapienic acid-treated bacteria and untreated controls, and we utilized open-source functional association and annotation programs to explore potential mechanisms for the antimicrobial activity of sapienic acid. Our analyses indicated that sapienic acid treatment induces a unique stress response in P. gingivalis resulting in differential expression of proteins involved in a variety of metabolic pathways. This network of differentially regulated proteins was enriched in protein-protein interactions (P = 2.98 × 10(-8)), including six KEGG pathways (P value ranges, 2.30 × 10(-5) to 0.05) and four Gene Ontology (GO) molecular functions (P value ranges, 0.02 to 0.04), with multiple suggestive enriched relationships in KEGG pathways and GO molecular functions. Upregulated metabolic pathways suggest increases in energy production, lipid metabolism, iron acquisition and processing, and respiration. Combined with a suggested preferential metabolism of serine, which is necessary for fatty acid biosynthesis, these data support our previous findings that the site of sapienic acid antimicrobial activity is likely at the bacterial membrane. IMPORTANCE: P. gingivalis is an important opportunistic pathogen implicated in periodontitis. Affecting nearly 50% of the population, periodontitis is treatable, but the resulting damage is irreversible and eventually progresses to tooth loss. There is a great need for natural products that can be used to treat and/or prevent the overgrowth of periodontal pathogens and increase oral health. Sapienic acid is endogenous to the oral cavity and is a potent antimicrobial agent, suggesting a potential therapeutic or prophylactic use for this fatty acid. This study examines the effects of sapienic acid treatment on P. gingivalis and highlights the membrane as the likely site of antimicrobial activity.


Bacterial Proteins/metabolism , Gene Expression Regulation, Bacterial/physiology , Palmitic Acids/pharmacology , Porphyromonas gingivalis/drug effects , Porphyromonas gingivalis/metabolism , Protein Interaction Maps/physiology , Amino Acids/metabolism , Bacterial Proteins/genetics , Energy Metabolism , Oxygen Consumption/drug effects , Oxygen Consumption/physiology , Protein Interaction Maps/drug effects
8.
J Am Dent Assoc ; 147(4): 264-70, 2016 Apr.
Article En | MEDLINE | ID: mdl-26705602

BACKGROUND: Meta-analysis refers to statistical methodology used to combine data from many studies to obtain an overall assessment of disease risk or treatment outcomes. In this article, the authors review basic methods, interpretation, and limitations of meta-analysis. METHODS: Investigators use meta-analysis approaches to combine data from available studies to obtain an answer to a specific question. An investigator uses a fixed model if there is homogeneity among the combined studies and a random-effects model if there is heterogeneity. The random-effects model results in wider confidence limits and more conservative estimates of overall results. A meta-analysis can be biased because studies with negative results (no differences in treatment outcomes) are less likely to be published (publication bias). RESULTS: A meta-analysis should include a well-specified and reproducible set of procedures, including description of data abstraction procedures, attempts to include unpublished studies, and appropriate statistical analysis that includes thorough consideration of heterogeneity and potential bias. CONCLUSIONS: Meta-analysis cannot correct shortcomings of existing studies or data. However, if potential pitfalls are recognized, meta-analysis can be a useful tool for summarizing existing studies, providing a means to address conflicting reports. Meta-analysis can lead to increased precision, providing greater power to detect existing relationships or treatment effects. Furthermore, meta-analysis may make it possible to address questions that cannot be answered by means of individual studies. PRACTICAL IMPLICATIONS: Meta-analysis provides an objective, quantitative synthesis of available studies but needs to be understood and assessed critically by those who use it to assess risk or make treatment decisions.


Meta-Analysis as Topic , Bias , Data Interpretation, Statistical , Humans , Statistics as Topic , Treatment Outcome
9.
J Dent Educ ; 79(9): 1093-100, 2015 Sep.
Article En | MEDLINE | ID: mdl-26329034

The aim of this study was to evaluate the impact of computer-assisted learning on first-year dental students' waxing abilities and self-evaluation skills. Additionally, this study sought to determine how well digital evaluation software performed compared to faculty grading with respect to students' technical scores on a practical competency examination. First-year students at one U.S. dental school were assigned to one of three groups: control (n=40), E4D Compare (n=20), and Sirona prepCheck (n=19). Students in the control group were taught by traditional teaching methodologies, and the technology-assisted groups received both traditional training and supplementary feedback from the corresponding digital system. Five outcomes were measured: visual assessment score, self-evaluation score, and digital assessment scores at 0.25 mm, 0.30 mm, and 0.35 mm tolerance. The scores from visual assessment and self-evaluation were examined for differences among groups using the Kruskal-Wallis test. Correlation between the visual assessment and digital scores was measured using Pearson and Spearman rank correlation coefficients. At completion of the course, students were asked to complete a survey on the use of these digital technologies. All 79 students in the first-year class participated in the study, for a 100% response rate. The results showed that the visual assessment and self-evaluation scores did not differ among groups (p>0.05). Overall correlations between visual and digital assessment scores were modest though statistically significant (5% level of significance). Analysis of survey responses completed by students in the technology groups showed that profiles for the two groups were similar and not favorable towards digital technology. The study concluded that technology-assisted training did not affect these students' waxing performance or self-evaluation skills and that visual scores given by faculty and digital assessment scores correlated moderately.


Anatomy/education , Computer-Assisted Instruction , Education, Dental , Learning , Models, Anatomic , Adult , Educational Measurement/methods , Educational Technology , Faculty, Dental , Feedback , Female , Humans , Male , Motor Skills , Self-Evaluation Programs , Software , Teaching/methods , Young Adult
10.
J Oral Microbiol ; 7: 27182, 2015.
Article En | MEDLINE | ID: mdl-25840611

BACKGROUND: Severe-early childhood caries (S-ECC) is one of the most common infectious diseases in children and is prevalent in lower socio-economic populations. American Indian children suffer from the highest levels of S-ECC in the United States. Members of the mutans streptococci, Streptococcus mutans, in particular, are key etiologic agents in the development of caries. Children typically acquire S. mutans from their mothers and early acquisition is often associated with higher levels of tooth decay. METHODS: We have conducted a 5-year birth cohort study with a Northern Plains Tribe to determine the temporality and fidelity of S. mutans transmission from mother to child in addition to the genotypic diversity of S. mutans in this community. Plaque samples were collected from 239 mother/child dyads at regular intervals from birth to 36 months and S. mutans were isolated and genotyped by arbitrarily primed-polymerase chain reaction (AP-PCR). RESULTS: Here we present preliminary findings from a subset of the cohort. The focus for this paper is on initial acquisition events in the children. We identified 17 unique genotypes in 711 S. mutans isolates in our subset of 40 children, 40 mothers and 14 primary caregivers. Twelve of these genotypes were identified in more than one individual. S. mutans colonization occurred by 16 months in 57.5% of the children and early colonization was associated with higher decayed, missing and filled surface (DMFS) scores (p=0.0007). Children colonized by S. mutans shared a common genotype with their mothers 47.8% of the time. While multiple genotypes were common in adults, only 10% of children harbored multiple genotypes. CONCLUSION: These children acquire S. mutans at an earlier age than the originally described 'window of infectivity' and often, but not exclusively, from their mothers. Early acquisition is associated with both the caries status of the children and the mothers.

11.
Neurology ; 83(5): 413-25, 2014 Jul 29.
Article En | MEDLINE | ID: mdl-24991037

OBJECTIVES: To (1) investigate effects of aerobic walking on motor function, cognition, and quality of life in Parkinson disease (PD), and (2) compare safety, tolerability, and fitness benefits of different forms of exercise intervention: continuous/moderate intensity vs interval/alternating between low and vigorous intensity, and individual/neighborhood vs group/facility setting. METHODS: Initial design was a 6-month, 2 × 2 randomized trial of different exercise regimens in independently ambulatory patients with PD. All arms were required to exercise 3 times per week, 45 minutes per session. RESULTS: Randomization to group/facility setting was not feasible because of logistical factors. Over the first 2 years, we randomized 43 participants to continuous or interval training. Because preliminary analyses suggested higher musculoskeletal adverse events in the interval group and lack of difference between training methods in improving fitness, the next 17 participants were allocated only to continuous training. Eighty-one percent of 60 participants completed the study with a mean attendance of 83.3% (95% confidence interval: 77.5%-89.0%), exercising at 46.8% (44.0%-49.7%) of their heart rate reserve. There were no serious adverse events. Across all completers, we observed improvements in maximum oxygen consumption, gait speed, Unified Parkinson's Disease Rating Scale sections I and III scores (particularly axial functions and rigidity), fatigue, depression, quality of life (e.g., psychological outlook), and flanker task scores (p < 0.05 to p < 0.001). Increase in maximum oxygen consumption correlated with improvements on the flanker task and quality of life (p < 0.05). CONCLUSIONS: Our preliminary study suggests that aerobic walking in a community setting is safe, well tolerated, and improves aerobic fitness, motor function, fatigue, mood, executive control, and quality of life in mild to moderate PD. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that in patients with PD, an aerobic exercise program improves aerobic fitness, motor function, fatigue, mood, and cognition.


Exercise/physiology , Parkinson Disease/physiopathology , Parkinson Disease/therapy , Quality of Life , Residence Characteristics , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Parkinson Disease/diagnosis , Treatment Outcome
12.
Biochim Biophys Acta ; 1841(3): 319-22, 2014 Mar.
Article En | MEDLINE | ID: mdl-23994607

Lauric acid (C12:0) and sapienic acid (C16:1Δ6) derived from human sebaceous triglycerides are potent antimicrobials found at the human skin surface. Long-chain bases (sphingosine, dihydrosphingosine and 6-hydroxysphingosine) are also potent and broad-acting antimicrobials normally present at the skin surface. These antimicrobials are generated through the action of ceramidases on ceramides from the stratum corneum. These natural antimicrobials are thought to be part of the innate immune system of the skin. Exogenously providing these lipids to the skin may provide a new therapeutic option, or could potentially provide prophylaxis in people at risk of infection. This article is part of a Special Issue entitled The Important Role of Lipids in the Epidermis and their Role in the Formation and Maintenance of the Cutaneous Barrier. Guest Editors: Kenneth R. Feingold and Peter Elias.


Anti-Infective Agents/metabolism , Infections/metabolism , Lipid Metabolism , Lipids , Skin/metabolism , Animals , Ceramidases/metabolism , Humans , Infection Control
13.
Int J Oral Sci ; 5(3): 130-40, 2013 Sep.
Article En | MEDLINE | ID: mdl-23867843

Oral mucosal and salivary lipids exhibit potent antimicrobial activity for a variety of Gram-positive and Gram-negative bacteria; however, little is known about their spectrum of antimicrobial activity or mechanisms of action against oral bacteria. In this study, we examine the activity of two fatty acids and three sphingoid bases against Porphyromonas gingivalis, an important colonizer of the oral cavity implicated in periodontitis. Minimal inhibitory concentrations, minimal bactericidal concentrations, and kill kinetics revealed variable, but potent, activity of oral mucosal and salivary lipids against P. gingivalis, indicating that lipid structure may be an important determinant in lipid mechanisms of activity against bacteria, although specific components of bacterial membranes are also likely important. Electron micrographs showed ultrastructural damage induced by sapienic acid and phytosphingosine and confirmed disruption of the bacterial plasma membrane. This information, coupled with the association of treatment lipids with P. gingivalis lipids revealed via thin layer chromatography, suggests that the plasma membrane is a likely target of lipid antibacterial activity. Utilizing a combination of two-dimensional in-gel electrophoresis and Western blot followed by mass spectroscopy and N-terminus degradation sequencing we also show that treatment with sapienic acid induces upregulation of a set of proteins comprising a unique P. gingivalis stress response, including proteins important in fatty acid biosynthesis, metabolism and energy production, protein processing, cell adhesion and virulence. Prophylactic or therapeutic lipid treatments may be beneficial for intervention of infection by supplementing the natural immune function of endogenous lipids on mucosal surfaces.


Anti-Bacterial Agents/pharmacology , Bacterial Proteins/drug effects , Lipids/pharmacology , Mouth Mucosa/chemistry , Mouth Mucosa/immunology , Porphyromonas gingivalis/drug effects , Colony Count, Microbial , Fatty Acids/pharmacology , Humans , Microscopy, Electron , Mouth Mucosa/microbiology , Porphyromonas gingivalis/chemistry , Porphyromonas gingivalis/ultrastructure , Saliva/chemistry , Saliva/microbiology , Sphingolipids/pharmacology , Virulence/drug effects
14.
Antimicrob Agents Chemother ; 56(3): 1157-61, 2012 Mar.
Article En | MEDLINE | ID: mdl-22155833

There is growing evidence that the role of lipids in innate immunity is more important than previously realized. How lipids interact with bacteria to achieve a level of protection, however, is still poorly understood. To begin to address the mechanisms of antibacterial activity, we determined MICs and minimum bactericidal concentrations (MBCs) of lipids common to the skin and oral cavity--the sphingoid bases D-sphingosine, phytosphingosine, and dihydrosphingosine and the fatty acids sapienic acid and lauric acid--against four Gram-negative bacteria and seven Gram-positive bacteria. Exact Kruskal-Wallis tests of these values showed differences among lipid treatments (P < 0.0001) for each bacterial species except Serratia marcescens and Pseudomonas aeruginosa. D-sphingosine (MBC range, 0.3 to 19.6 µg/ml), dihydrosphingosine (MBC range, 0.6 to 39.1 µg/ml), and phytosphingosine (MBC range, 3.3 to 62.5 µg/ml) were active against all bacteria except S. marcescens and P. aeruginosa (MBC > 500 µg/ml). Sapienic acid (MBC range, 31.3 to 375.0 µg/ml) was active against Streptococcus sanguinis, Streptococcus mitis, and Fusobacterium nucleatum but not active against Escherichia coli, Staphylococcus aureus, S. marcescens, P. aeruginosa, Corynebacterium bovis, Corynebacterium striatum, and Corynebacterium jeikeium (MBC > 500 µg/ml). Lauric acid (MBC range, 6.8 to 375.0 µg/ml) was active against all bacteria except E. coli, S. marcescens, and P. aeruginosa (MBC > 500 µg/ml). Complete killing was achieved as early as 0.5 h for some lipids but took as long as 24 h for others. Hence, sphingoid bases and fatty acids have different antibacterial activities and may have potential for prophylactic or therapeutic intervention in infection.


Anti-Bacterial Agents/pharmacology , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Immunity, Innate , Mouth/immunology , Skin/immunology , Anti-Bacterial Agents/immunology , Gram-Negative Bacteria/growth & development , Gram-Negative Bacterial Infections/immunology , Gram-Negative Bacterial Infections/prevention & control , Gram-Positive Bacteria/growth & development , Gram-Positive Bacterial Infections/immunology , Gram-Positive Bacterial Infections/prevention & control , Humans , Lauric Acids/immunology , Lauric Acids/metabolism , Lauric Acids/pharmacology , Microbial Sensitivity Tests , Mouth/microbiology , Palmitic Acids/immunology , Palmitic Acids/metabolism , Palmitic Acids/pharmacology , Skin/microbiology , Species Specificity , Sphingosine/analogs & derivatives , Sphingosine/immunology , Sphingosine/metabolism , Sphingosine/pharmacology
15.
Brain Res ; 1396: 54-9, 2011 Jun 17.
Article En | MEDLINE | ID: mdl-21561601

The false-suffocation hypothesis of panic disorder (Klein, 1993) suggested δ-opioid receptors as a possible source of the respiratory dysfunction manifested in panic attacks occurring in panic disorder (Preter and Klein, 2008). This study sought to determine if a lack of δ-opioid receptors in a mouse model affects respiratory response to elevated CO2, and whether the response is modulated by benzodiazepines, which are widely used to treat panic disorder. In a whole-body plethysmograph, respiratory responses to 5% CO2 were compared between δ-opioid receptor knockout mice and wild-type mice after saline, diazepam (1mg/kg), and alprazolam (0.3mg/kg) injections. The results show that lack of δ-opioid receptors does not affect normal response to elevated CO2, but does prevent benzodiazepines from modulating that response. Thus, in the presence of benzodiazepine agonists, respiratory responses to elevated CO2 were enhanced in δ-opioid receptor knockout mice compared to wild-type mice. This suggests an interplay between benzodiazepine receptors and δ-opioid receptors in regulating the respiratory effects of elevated CO2, which might be related to CO2 induced panic.


Carbon Dioxide/toxicity , Panic Disorder/physiopathology , Receptors, GABA-A/physiology , Receptors, Opioid, delta/physiology , Respiratory Insufficiency/physiopathology , Animals , Benzodiazepines/pharmacology , Brain/drug effects , Brain/metabolism , Brain/physiopathology , Carbon Dioxide/blood , Disease Models, Animal , Hypercapnia/chemically induced , Hypercapnia/physiopathology , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Panic Disorder/drug therapy , Panic Disorder/metabolism , Plethysmography, Whole Body/methods , Receptors, GABA-A/drug effects , Receptors, Opioid, delta/deficiency , Receptors, Opioid, delta/genetics , Respiratory Insufficiency/drug therapy , Respiratory Insufficiency/genetics , Tidal Volume/physiology
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