New perspectives from genomic analyses of bacterial infectious agents.

Recent advances in the technologies for genomic sequencing and systems for handling and processing sequencing data have transformed bacterial genomics into a near-routine approach for both small- and large-scale investigations of infectious agents. Nonetheless, the application of genomics - especially largerscale studies - to animal infectious agents lags behind its application to human pathogens, despite the growing importance of many animal species as food sources. Assiduously conducted genomic studies offer major benefits, not merely by providing a detailed understanding of infectious agents but also through the exploitation of such findings to enable more accurate diagnosis, high-resolution typing and the development of improved interventions. The use of genomics for these and other purposes is likely to grow in future years and it must be anticipated that investigation and characterisation of important animal infectious agents will also gain considerable benefits. Using mainly animal pathogens as examples - including several infectious agents listed by the World Organisation for Animal Health - this paper provides a concise summary of some recent purposes and developments in bacterial genomics analysis.

Les récentes avancées technologiques réalisées dans le domaine du séquençage du génome et la mise au point de systèmes permettant de manipuler et de traiter les données de séquençage ont transformé la génomique bactérienne en une méthode utilisée quasiment au quotidien dans le cadre d'études à grande ou à petite échelle sur les agents infectieux. Néanmoins, s'agissant d'agents pathogènes affectant les animaux, les applications de la génomique sont bien moins avancées que dans le domaine des agents pathogènes humains, en particulier dans le cadre d'études à grande échelle et ce, malgré l'utilisation croissante de nombreuses espèces animales dans l'alimentation. Les études génomiques réalisées en continu offrent des avantages considérables, non seulement parce qu'elles apportent des informations précises pour mieux comprendre les agents de maladies infectieuses mais aussi par leurs applications concrètes, qui permettent d'obtenir une meilleure justesse de diagnostic, de procéder à un typage de haute résolution et de concevoir des interventions plus efficaces. De telles applications et d'autres encore à venir vont probablement se développer considérablement dans un futur proche et nous pouvons nous attendre à ce qu'elles soient enfin utilisées pour étudier et caractériser les principaux agents pathogènes affectant les animaux. Les auteurs résument les objectifs de l'analyse des génomes bactériens et ses accomplissements les plus récents, en illustrant leur propos d'exemples portant essentiellement sur des pathogènes affectant les animaux, dont plusieurs figurent sur la liste de l'Organisation mondiale de la santé animale.

Gracias a los últimos adelantos de las técnicas de secuenciación genómica y de los sistemas para procesar y explotar los datos resultantes, la genómica bacteriana se utiliza ahora de modo casi sistemático en el estudio (a pequeña o a gran escala) de agentes infecciosos. Sin embargo, pese a la creciente importancia que están cobrando muchas especies animales como fuente de productos alimentarios, la aplicación de la genómica a los agentes infecciosos animales (especialmente en los estudios a gran escala) aún va rezagada con respecto a su aplicación a los patógenos humanos. La realización asidua de estudios genómicos depara grandes beneficios, no solo porque procura un detallado conocimiento de los agentes infecciosos, sino también porque este saber sirve después para efectuar diagnósticos más exactos, hacer tipificaciones de alta resolución y definir intervenciones terapéuticas más eficaces. Es muy probable que el uso de la genómica con estos y otros fines vaya en aumento en los próximos años, y cabe augurar que también se extenderá al estudio y la caracterización de importantes agentes infecciosos animales. Tomando básicamente como ejemplo una serie de patógenos animales (entre ellos varios agentes infecciosos incluidos en la lista de la Organización Mundial de Sanidad Animal), los autores resumen con concisión los objetivos y avances de una serie de recientes trabajos de análisis del genoma bacteriano.

The genetic composition of populations of cynomolgus macaques (Macaca fascicularis) used in biomedical research.

BACKGROUND: The genetic composition of cynomolgus macaques used in biomedical research is not as well-characterized as that of rhesus macaques. METHODS: Populations of cynomolgus macaques from Sumatra, Corregidor, Mauritius, Singapore, Cambodia, and Zamboanga were analyzed using 24 STRs. RESULTS: The Sumatran and Cambodian populations exhibited the highest allelic diversity, while the Mauritian population exhibited the lowest. Sumatran cynomolgus macaques were the most genetically similar to all others, consistent with an Indonesian origin of the species. The high diversity among Cambodian animals may result from interbreeding with rhesus macaques. The Philippine and Mauritian samples were the most divergent from other populations, the former due to separation from the Sunda Shelf by deepwater and the latter due to anthropogenic translocation and extreme founder effects. CONCLUSIONS: Investigators should verify their research subjects' origin, ancestry, and pedigree to minimize risks to biomedical experimentation from genetic variance stemming from close kinship and mixed ancestry as these can obscure treatment effects.

Comparative molecular analysis of ovine and bovine Streptococcus uberis isolates.

Streptococcus uberis causes clinical and subclinical mastitis in cattle and sheep, but it is unknown whether the composition of Strep. uberis populations differs between host species. To address this, we characterized a collection of bovine and ovine Strep. uberis isolates with shared geographical and temporal origins by means of an expanded multilocus sequence typing scheme. Among 14 ovine and 35 bovine isolates, 35 allelic profiles were detected. Each allelic profile was associated with a single host species and all but one were new to the multilocus sequence typing database. The median number of new alleles per isolate was higher for ovine isolates than for bovine isolates. None of the ovine isolates belonged to the global clonal complexes 5 or 143, which are commonly associated with bovine mastitis and which have a wide geographical distribution. Ovine isolates also differed from bovine isolates in carriage of plasminogen activator genes, with significantly higher prevalence of pauB in ovine isolates. Isolates that were negative for yqiL, one of the targets of multilocus sequence typing, were found among ovine and bovine isolates and were not associated with a specific sequence type or global clonal complex. One bovine isolate carried a gapC allele that was probably acquired through lateral gene transfer, most likely from Streptococcus salivarius. We conclude that ovine isolates are distinct from bovine isolates of Strep. uberis, and that recombination between isolates from different host species or bacterial species could contribute to changes in virulence gene profiles with relevance for vaccine development.

Validation of a suite of ERP and QEEG biomarkers in a pre-competitive, industry-led study in subjects with schizophrenia and healthy volunteers.

OBJECTIVE: Complexity and lack of standardization have mostly limited the use of event-related potentials (ERPs) and quantitative EEG (QEEG) biomarkers in drug development to small early phase trials. We present results from a clinical study on healthy volunteers (HV) and patients with schizophrenia (SZ) that assessed test-retest, group differences, variance, and correlation with functional assessments for ERP and QEEG measures collected at clinical and commercial trial sites with standardized instrumentation and methods, and analyzed through an automated data analysis pipeline. METHODS: 81 HV and 80 SZ were tested at one of four study sites. Subjects were administered two ERP/EEG testing sessions on separate visits. Sessions included a mismatch negativity paradigm, a 40 Hz auditory steady-state response paradigm, an eyes-closed resting state EEG, and an active auditory oddball paradigm. SZ subjects were also tested on the Brief Assessment of Cognition (BAC), Positive and Negative Syndrome Scale (PANSS), and Virtual Reality Functional Capacity Assessment Tool (VRFCAT). RESULTS: Standardized ERP/EEG instrumentation and methods ensured few test failures. The automated data analysis pipeline allowed for near real-time analysis with no human intervention. Test-retest reliability was fair-to-excellent for most of the outcome measures. SZ subjects showed significant deficits in ERP and QEEG measures consistent with published academic literature. A subset of ERP and QEEG measures correlated with functional assessments administered to the SZ subjects. CONCLUSIONS: With standardized instrumentation and methods, complex ERP/EEG testing sessions can be reliably performed at clinical and commercial trial sites to produce high-quality data in near real-time.

Molecular ABO phenotyping in cynomolgus macaques using real-time quantitative PCR.

Macaques are commonly used in biomedical research as animal models of human disease. The ABO phenotype of donors and recipients plays an important role in the success of transplantation and stem cell research of both human and macaque tissue. Traditional serological methods for ABO phenotyping can be time consuming, provide ambiguous results and/or require tissue that is unavailable or unsuitable. We developed a novel method to detect the A, B, and AB phenotypes of macaques using real-time quantitative polymerase chain reaction. This method enables the simple and rapid screening of these phenotypes in macaques without the need for fresh blood or saliva. This study reports the distribution of the A, B, and AB phenotypes of captive cynomolgus macaques that, while regionally variable, closely resembles that of rhesus macaques. Blood group B, as in rhesus macaques, predominates in cynomolgus macaques and its frequency distribution leads to a probability of major incompatibility of 41%. No silencing mutations have been identified in exon 6 or 7 in macaques that could be responsible for the O phenotype, that, although rare, have been reported. The excess homozygosity of rhesus and cynomolgus macaque genotypes in this study, that assumes the absence of the O allele, suggests the possibility of some mechanism preventing the expression of the A and B transferases.

4040 SNPs for genomic analysis in the rhesus macaque (Macaca mulatta).

Although the rhesus macaque (Macaca mulatta) is commonly used for biomedical research and becoming a preferred model for translational medicine, quantification of genome-wide variation has been slow to follow the publication of the genome in 2007. Here we report the properties of 4040 single nucleotide polymorphisms discovered and validated in Chinese and Indian rhesus macaques from captive breeding colonies in the United States. Frequency-matched measures of linkage disequilibrium were much greater in the Indian sample. Although the majority of polymorphisms were shared between the two populations, rare alleles were over twice as common in the Chinese sample. Indian rhesus had higher rates of heterozygosity, as well as previously undetected substructure, potentially due to admixture from Burma in wild populations and demographic events post-captivity.

A simple multiplex polymerase chain reaction to determine ABO blood types of rhesus macaques (Macaca mulatta).

Rhesus macaques are the most common nonhuman primate model organism used in biomedical research. Their increasingly frequent use as subjects in studies involving transplantation requires that blood and other tissue antigens of donors and recipients be compatible. We report here an easy and rapid multiplex polymerase chain reaction (PCR) to determine the ABO blood group phenotypes of rhesus macaques that can be performed with only small amounts of DNA. We phenotyped 78 individuals and found this species to exhibit the A, B and AB phenotypes in frequencies that vary by geographic region. The probability of randomly pairing rhesus macaque donors and recipients that exhibit major ABO phenotype incompatibility is approximately 0.35 and 0.45 for Indian and Chinese rhesus macaques, respectively.

High-throughput single-nucleotide polymorphism discovery and the search for candidate genes for long-term SIVmac nonprogression in Chinese rhesus macaques (Macaca mulatta).

BACKGROUND: Genetic differences between Indian and Chinese rhesus macaques contribute to the phenotypic variance of clinical trials, including infection with SIVmac. The completion of the rhesus genome has facilitated the discovery of several thousand markers. METHODS: We developed a genome-wide SNP map for rhesus macaques containing 3869 validated markers with an average distance of 0.88 Mb and used the program VarLD to identify genomic areas with significant differences in linkage disequilibrium (LD) between Indian-derived and Chinese rhesus macaques. RESULTS: Forty-one statistically significant differences in LD between Chinese and Indian-origin rhesus were detected on chromosomes 1, 4, 5 and 11. The region of greatest LD difference was located on the proximal end of chromosome one, which also contained the genes ELAVL4, MAST2 and HIVEP3. CONCLUSION: These genomic areas provide entry to more detailed studies of gene function. This method is also applicable to the study of differences in biomarkers between regional populations of other species.

A rapid quantitative real-time PCR-based DNA quantification assay coupled with species--assignment capabilities for two hybridizing Macaca species.

Regional populations of rhesus and long-tailed macaques exhibit fundamental differences in mitochondrial DNA, short tandem repeat and single nucleotide polymorphism variation between mainland and insular Southeast Asian populations. Some studies have revealed genetic admixture between these species due to natural hybridization and human-assisted intercrosses. A quantitative real-time PCR (qPCR) assay was developed to efficiently determine the species of origin of a macaque biological sample, and to quantify the species-specific template DNA. Prior knowledge of species identity and DNA concentrations are crucial for maintaining cost-effective methods and accurate DNA analysis. DNA from 109 regionally representative rhesus and long-tailed macaques was qPCR amplified to determine the species and template quantities. Of the 19 Vietnamese long-tailed macaques, 3 samples were discovered to be hybrids.

Contemplating Health Economics, Coding and Reimbursement in Orthotics, Prosthetics and Pedorthics.

Reimbursement to U.S. healthcare service providers is largely transitioning from fee for service to fee for value for those clinicians who code using current procedural terminology and through their coding, describe their professional services. The Orthotic, Prosthetic and Pedorthic profession (O&P), currently codes using a system that describes the devices they evaluate for, fabricate, fit and maintain and their professional services are incorporated into their codes. These O&P codes, in contrast to those for other healthcare disciplines, are predominantly product based rather than service based, focusing on product features and function more than clinical service. This editorial manuscript provides a brief overview of the system the US O&P profession uses currently, particularly in the context of other healthcare professions transitioning to value based coding and reimbursement and culminates in a call to action for the profession to academically consider the strengths and weaknesses of the current system relative to alternative systems.

Development of a Chinese-Indian hybrid (Chindian) rhesus macaque colony at the California National Primate Research Center by introgression.

BACKGROUND: Fullbred Chinese and Indian rhesus macaques represent genetically distinct populations. The California National Primate Research Center introduced Chinese founders into its Indian-derived rhesus colony in response to the 1978 Indian embargo on exportation of animals for research and the concern that loss of genetic variation in the closed colony would hamper research efforts. The resulting hybrid rhesus now number well over a thousand animals and represent a growing proportion of the animals in the colony. METHODS: We characterized the population genetic structure of the hybrid colony and compared it with that of their pure Indian and Chinese progenitors. RESULTS: The hybrid population contains higher genetic diversity and linkage disequilibrium than their full Indian progenitors and represents a resource with unique research applications. CONCLUSIONS: The genetic diversity of the hybrids indicates that the strategy to introduce novel genes into the colony by hybridizing Chinese founders and their hybrid offspring with Indian-derived animals was successful.

Resources for genetic management and genomics research on non-human primates at the National Primate Research Centers (NPRCs).

The National Primate Research Centers (NPRCs) established Working Groups (WGs) for developing resources and mechanisms to facilitate collaborations among non-human primate (NHP) researchers. Here we report the progress of the Genome Banking and the Genetics and Genomics WGs in developing resources to advance the exchange, analysis and comparison of NHP genetic and genomic data across the NPRCs. The Genome Banking WG has established a National NHP DNA bank comprising 1250 DNA samples from unrelated animals and family trios from the 10 NHP species housed within the NPRC system. The Genetics and Genomics WG is developing SNP arrays that will provide a uniform, highly informative, efficient and low-cost method for rhesus and long-tailed macaque genotyping across the eight NPRCs. This WG is also establishing a Biomedical Informatics Research Network-based portal for shared bioinformatics resources including vital statistics, genotype and population data and information on the National NHP DNA bank.

Effects of chronic caffeine exposure during adolescence and subsequent acute caffeine challenge during adulthood on rat brain serotonergic systems.

Caffeine is the most commonly used drug in the world. However, animal studies suggest that chronic consumption of caffeine during adolescence can result in enhanced anxiety-like behavioral responses during adulthood. One mechanism through which chronic caffeine administration may influence subsequent anxiety-like responses is through actions on brainstem serotonergic systems. In order to explore potential effects of chronic caffeine consumption on brainstem serotonergic systems, we evaluated the effects of a 28-day exposure to chronic caffeine (0.3 g/L; postnatal day 28-56) or vehicle administration in the drinking water, followed by 24 h caffeine withdrawal, and subsequent challenge with caffeine (30 mg/kg; s.c.) or vehicle in adolescent male rats. In Experiment 1, acute caffeine challenge induced a widespread activation of serotonergic neurons throughout the dorsal raphe nucleus (DR); this effect was attenuated in rats that had been exposed to chronic caffeine consumption. In Experiment 2, acute caffeine administration profoundly decreased tph2 and slc22a3 mRNA expression throughout the DR, with no effects on htr1a or slc6a4 mRNA expression. Chronic caffeine exposure for four weeks during adolescence was sufficient to decrease tph2 mRNA expression in the DR measured 28 h after caffeine withdrawal. Chronic caffeine administration during adolescence did not impact the ability of acute caffeine to decrease tph2 or slc22a3 mRNA expression. Together, these data suggest that both chronic caffeine administration during adolescence and acute caffeine challenge during adulthood are important determinants of serotonergic function and serotonergic gene expression, effects that may contribute to chronic effects of caffeine on anxiety-like responses.

Prediction of clinical response based on pharmacokinetic/pharmacodynamic models of 5-hydroxytryptamine reuptake inhibitors in mice.

BACKGROUND AND PURPOSE: Bridging the gap between preclinical research and clinical trials is vital for drug development. Predicting clinically relevant steady-state drug concentrations (Css) in serum from preclinical animal models may facilitate this transition. Here we used a pharmacokinetic/pharmacodynamic (PK/PD) modelling approach to evaluate the predictive validity of 5-hydroxytryptamine (5-HT; serotonin) transporter (SERT) occupancy and 5-hydroxytryptophan (5-HTP)-potentiated behavioral syndrome induced by 5-HT reuptake inhibitor (SRI) antidepressants in mice. EXPERIMENTAL APPROACH: Serum and whole brain drug concentrations, cortical SERT occupancy and 5-HTP-potentiated behavioral syndrome were measured over 6 h after a single subcutaneous injection of escitalopram, paroxetine or sertraline. [(3)H]2-(2-dimethylaminomethylphenylsulphanyl)-5-methyl-phenylamine ([(3)H]MADAM) was used to assess SERT occupancy. For PK/PD modelling, an effect-compartment model was applied to collapse the hysteresis and predict the steady-state relationship between drug exposure and PD response. KEY RESULTS: The predicted Css for escitalopram, paroxetine and sertraline at 80% SERT occupancy in mice are 18 ng mL(-1), 18 ng mL(-1) and 24 ng mL(-1), respectively, with corresponding responses in the 5-HTP behavioral model being between 20-40% of the maximum. CONCLUSIONS AND IMPLICATIONS: Therapeutically effective SERT occupancy for SRIs in depressed patients is approximately 80%, and the corresponding plasma Css are 6-21 ng mL(-1), 21-95 ng mL(-1) and 20-48 ng mL(-1) for escitalopram, paroxetine and sertraline, respectively. Thus, PK/PD modelling using SERT occupancy and 5-HTP-potentiated behavioral syndrome as response markers in mice may be a useful tool to predict clinically relevant plasma Css values.

A randomized-controlled trial of food choices made by edentulous adults.

AIM: The aim of this study was to conduct a randomized-controlled trial to compare food choices of edentulous adults provided with implant-supported mandibular overdentures and conventional dentures. METHODS: Edentulous patients were randomly allocated to an implant group (IG) or a denture group (DG). IG subjects (n=49) were provided with conventional maxillary dentures and implant-retained mandibular overdentures. Subjects in this group refusing implants were retained using the 'intention-to-treat principle' and provided with conventional dentures. DG subjects (n=48) were provided with conventional dentures. Subjects indicated whether they consumed any of seven test foods and the level of chewing difficulty experienced. Data were collected pre-treatment and 3 months post treatment. RESULTS: IG subjects reported increased consumption of carrots, apples and nuts post-treatment (P<0.05) and decreased post-treatment difficulty in chewing apples and nuts. DG subjects reported decreased post-treatment difficulty in chewing carrots, bacon and nuts (P<0.05). Between group differences for chewing difficulty were detected for nuts that DG subjects found easier to chew than IG subjects (P=0.002). CONCLUSION: Food selection and perceived chewing difficulty improved in both groups, with no significant differences between groups. Successful rehabilitation may not result in different food selection, which may require concurrent tailored dietary interventions, but may increase available food choices.

Case report of multiple implant failure in a patient with ankylosing spondylitis.

This report details a case of multiple implant failure (so-called 'cluster phenomenon') in a patient with ankylosing spondylitis and considers some factors for implant failure including reduced bone density. It highlights the relationship between ankylosing spondylitis and osteoporosis although no direct link is made between these conditions and the implant failures in this case.

Abnormal regulation of adenosine 3',5'-monophosphate and corticosterone formation in an adrenocortical carcinoma.

A spontaneously occurring rat adrenocortical carcinoma which produces corticosterone was maintained by transplantation. The carcinoma appeared to utilize corticosterone biosynthetic steps similar to those of the normal adrenal, but the tumor produced only about 1-10% as much corticosterone per unit tissue weight as nontumorous adrenal glands. The tumor demonstrated little or no increase in corticosterone production in response to adrenocorticotropic hormone (ACTH) either in vivo or in vitro. In normal adrenals, ACTH increases the activity of adenyl cyclase which catalyzes the conversion of adenosine triphosphate (ATP) to adenosine-3',5'-monophosphate (cyclic AMP), the latter then serving as an intracellular regulator of steroidogenesis. ACTH failed to increase cyclic AMP levels in the tumor in vivo or in slices in vitro, conditions under which there were 50- and 20-fold increases in nontumorous adrenals. However, in homogenates fortified with exogenous ATP, adenyl cyclase activity was comparable in the tumor and adrenals, and cyclic AMP formation was increased 3-fold by ACTH in each. As measured in homogenates, the tumor did not possess a greater ability to destroy cyclic AMP than did normal adrenals. Although ATP levels in the carcinoma were found to be considerably lower than those in normal adrenals, it was not clear that this finding can explain the inability of ACTH to increase cyclic AMP levels in intact tumor cells. While the failure to normally influence cyclic AMP levels in the carcinoma cells could be an important factor in the lack of a steroid response to ACTH, several lines of evidence suggest that the tumor possesses one or more additional abnormalities in the regulation of steroidogenesis. First, in the absence of ACTH stimulation, the tissue concentrations of cyclic AMP were comparable in the tumor and in nontumorous adrenals, but these cyclic AMP levels were associated with a lower level of steroidogenesis in the tumor. Second, tumor slices failed to increase corticosterone production when incubated with cyclic AMP, in contrast to 5-fold increases observed with nontumorous adrenals.

ABO blood group phenotype frequency estimation using molecular phenotyping in rhesus and cynomolgus macaques.

A much larger sample (N = 2369) was used to evaluate a previously reported distribution of the A, AB and B blood group phenotypes in rhesus and cynomolgus macaques from six different regional populations. These samples, acquired from 15 different breeding and research facilities in the United States, were analyzed using a real-time quantitative polymerase chain reaction (qPCR) assay that targets single nucleotide polymorphisms (SNPs) responsible for the macaque A, B and AB phenotypes. The frequency distributions of blood group phenotypes of the two species differ significantly from each other and significant regional differentiation within the geographic ranges of each species was also observed. The B blood group phenotype was prevalent in rhesus macaques, especially those from India, while the frequencies of the A, B and AB phenotypes varied significantly among cynomolgus macaques from different geographic regions. The Mauritian cynomolgus macaques, despite having originated in Indonesia, showed significant (P ≪ .01) divergence from the Indonesian animals at the ABO blood group locus. Most Mauritian animals belonged to the B blood group while the Indonesian animals were mostly A. The close similarity in blood group frequency distributions between the Chinese rhesus and Indochinese cynomolgus macaques demonstrates that the introgression between these two species extends beyond the zone of intergradation in Indochina. This study underscores the importance of ABO blood group phenotyping of the domestic supply of macaques and their biospecimens.

Effects of naltrexone are influenced by childhood adversity during negative emotional processing in addiction recovery.

Naltrexone is an opioid receptor antagonist used in the management of alcohol dependence. Although the endogenous opioid system has been implicated in emotion regulation, the effects of mu-opioid receptor blockade on brain systems underlying negative emotional processing are not clear in addiction. Individuals meeting criteria for alcohol dependence alone (n=18, alcohol) and in combination with cocaine and/or opioid dependence (n=21, alcohol/drugs) and healthy individuals without a history of alcohol or drug dependence (n=21) were recruited. Participants were alcohol and drug abstinent before entered into this double-blind, placebo-controlled, randomized, crossover study. Functional magnetic resonance imaging was used to investigate brain response while viewing aversive and neutral images relative to baseline on 50 mg of naltrexone and placebo. We found that naltrexone modulated task-related activation in the medial prefrontal cortex and functional connectivity between the anterior cingulate cortex and the hippocampus as a function of childhood adversity (for aversive versus neutral images) in all groups. Furthermore, there was a group-by-treatment-by-condition interaction in the right amygdala, which was mainly driven by a normalization of response for aversive relative to neutral images under naltrexone in the alcohol/drugs group. We conclude that early childhood adversity is one environmental factor that influences pharmacological response to naltrexone. Pharmacotherapy with naltrexone may also have some ameliorative effects on negative emotional processing in combined alcohol and drug dependence, possibly due to alterations in endogenous opioid transmission or the kappa-opioid receptor antagonist actions of naltrexone.

A randomized controlled trial of implant-retained mandibular overdentures.

Evidence from randomized clinical trials of implant-retained overdentures is very limited at the present time. The aim of this study was to compare implant-retained mandibular overdentures and conventional complete dentures in a randomized controlled trial (RCT). Our a priori hypothesis was that implant-retained mandibular overdentures would be significantly better than conventional complete dentures. Edentulous patients (n = 118) were randomly allocated to either an Implant Group (n = 62) or a Denture Group (n = 56). Patients completed the Oral Health Impact Profile (OHIP) and a denture satisfaction scale pre-treatment and three months post-treatment. Upon completion of treatment, both groups reported improvement (p < 0.001, Wilcoxon Ranks Sum test) in oral-health-related quality of life and denture satisfaction. There were no significant post-treatment differences between the groups, but a treatment effect may be masked by application of "intention to treat" analysis. The OHIP change scores were significantly greater for patients receiving implants than for those who refused them.