Radiotherapy May Offer a Recurrence and Survival Benefit in Rectal Cancers Treated Surgically with Transanal Endoscopic Microsurgery: A Systematic Review and Meta-analysis.

BACKGROUND/AIM: Several studies report outcomes of Transanal Endoscopic Microsurgery (TEMS) surgery in combination with radiotherapy, however the combination of those treatments is provided mostly on an adhoc individual basis and the role of radiotherapy remains unclear. The aim of this study was to identify the effect of neo-adjuvant or adjuvant radiotherapy in the oncological outcomes of rectal cancer treated surgically with TEMS. MATERIALS AND METHODS: We performed a systematic review of the literature on MEDLINE and Pubmed databases. Data were extracted by two independent reviewers and meta-analyzed using an inverse variance heterogeneity model to calculate overall (pooled) effect sizes for survival or recurrence of disease against neo+/-adjuvant treatment. RESULTS: A total of 48 studies were included in the qualitative meta-analysis which included 3,285 patients with rectal cancer. The overall survival odds ratio (OR), was 9.39 (95% CI=6.1-14.4) with a Cochran's Q variable of 151.7 on 47 degrees of freedom (d.f.) (p=0.000). Recurrence-free OR was 8.7 (95%CI=6.58-11.44) with a Cochran's Q variable of Q=145.2 on 44 d.f. (p=0.000). Studies which contained more than 10% of pT3 tumours, and provided neo+/-adjuvant treatment in more than 35% of cases, were associated with survival benefit, as demonstrated by an overall odds of survival of 32.2 (95%CI=16.3-63.5, p=0.001, Q=8.4, p=0.21). Studies that contained more than 10% of pT3 tumours and provided neo+/-adjuvant treatment in more than 20% of the cases had an overall effect size of recurrence-free odds of 20.23 (95%CI=13.84-29.57, p=0.000, Q=2.18, p=0.54). CONCLUSION: There seems to be a benefit from radiotherapy on overall survival and recurrence-free odds, which is more apparent in cohorts with more than 10% of pT3 tumours. Our results suggest that neo-adjuvant or adjuvant radiotherapy should be considered for inclusion in formal treatment protocols for rectal cancers treated with TEMS as they offer a recurrence and survival benefit.

On-line preparatory information for children and their families undergoing dental extractions under general anesthesia: A phase III randomized controlled trial.

BACKGROUND: Family-centered interactive on-line games are increasingly popular in healthcare, but their effectiveness for preoperative preparation needs further research. www.scottga.org is the new on-line version of a proven nonweb-based game for children and parents/caregivers. AIMS: The aim of this study was to evaluate if www.scottga.org improved children's anxiety and families' satisfaction compared with controls. METHODS: In this phase III double-blind randomized controlled trial, children/parents/caregivers received (i) www.scottga.org, (ii) standard care, or (iii) a placebo hand-washing game. The intervention and placebo games were available online for home usage and provided again on the ward before surgery. All children were accompanied by parent/caregivers at induction and observed and scored using validated measures. Stratified randomization and generalized linear models were used. An intention-to-treat approach was adopted. RESULTS: Overall, 52/176 children had baseline "psychological disturbance." Children's anxiety increased preinduction, but there were no differences between groups (Facial Image Scale: video-standard OR = 1.08, P = .82, 95% CI [0.56, 2.1]; video-placebo OR = 0.9, P = .77 95% CI [0.46, 1.8]). There were no differences in induction behavior (visual analog scale: video mean = 3.5; standard care mean = 3.5; placebo mean = 3.7: video-standard OR = 2.0, P = .42, 95% CI [-0.6, 1.3]; video-placebo OR = 1.53, P = .65, 95% CI [-0.8, 1.1]) or induction anxiety (modified Yale Preoperative Anxiety Scale: video-standard OR 1.02, P = .97, 95% CI [0.61, 2.6]; video-placebo OR 1.38, P = .49, 95% CI [0.87, 3.81]). Families favored the intervention regarding the "child handling the visit better" (Treatment Evaluation Inventory: video-standard OR = 12; 95% CI 4.7-32; P < .001; video-placebo OR = 8.2; 95% CI 3-22; P < .001) and "improving the child's ability to cope" (Treatment Evaluation Inventory: video-standard OR = 21; 95% CI 8-56; P < .001 and video-placebo OR = 13; 95% CI 5-34; P < .001). CONCLUSION: Families believed that a video-game preparation helped their child's perioperative anxiety, but there were no objective measures of behavioral improvement associated with this intervention.

A randomized double-blind placebo-controlled trial of a multi-strain probiotic in treatment of symptomatic uncomplicated diverticular disease.

BACKGROUND: Diverticular disease is a significant burden on healthcare systems that is managed, surgically or medically, mainly as an emergency or acute condition. There are no standardized treatment recommendations for symptomatic uncomplicated disease. We hypothesized that a probiotic would reduce abdominal pain in such patients. METHODS: We conducted a single-center, double-blind, placebo-controlled trial of probiotic treatment (Symprove) in adult patients with moderate-to-severe chronic, non-acute symptomatic diverticular disease. 143 patients were randomized to receive 1 mL/kg/day of probiotic liquid (N = 72) or placebo (N = 71) daily for 3 months. The primary endpoint was abdominal pain severity. Secondary endpoints consisted of the change in the frequency of eight abdominal symptoms and the level of intestinal inflammation (fecal calprotectin). RESULTS: 120 patients completed the trial. Abdominal pain score, the primary end point, decreased in both groups, but no significant difference between the groups was found (P = 0.11). In relation to placebo, the probiotic significantly decreased the frequency of four of the eight secondary endpoints: constipation, diarrhea, mucorrhea, and back pain (P < 0.04). No significant differences were found in frequency of abdominal pain, PR bleeding, dysuria, and bloating. CONCLUSIONS: Multi-strain liquid probiotic did not improve abdominal pain scores significantly, but significantly improved the frequency of four other symptoms associated with chronic, non-acute symptomatic diverticular disease.

Malocclusion, orthodontic treatment, and the Oral Health Impact Profile (OHIP-14): Systematic review and meta-analysis.

OBJECTIVE: To synthesize evidence on the impact of malocclusion and its associated treatment on people's quality of life across studies that used the Oral Health Impact Profile (OHIP-14) questionnaire in the adult population. MATERIALS AND METHODS: A systematic search of the English literature using Medline, PubMed, and EMBASE yielded 98 unique citations. Studies using OHIP-14 with individuals 15 years of age and older were included. After initial screening, 64 citations were excluded and another 9 were excluded after reading full text reports; the remaining 25 were included in the review. All studies were observational and used one of three study designs: 11 compared the same group before and after treatment (pre-post design), 10 compared groups with and without malocclusion (independent groups design) and four compared an orthodontically treated group with an independent group requiring treatment (treated-untreated groups design). Only three studies using the pre-post design and four using the independent groups design reported comparable OHIP-14 data and were combined in separate meta-analyses. Meta-analysis was carried out using metan command in Stata. RESULTS: The standardized mean difference (SMD) in OHIP-14 total score was 1.29 (95% CI: 0.67 to 1.92) for the three studies using the pre-post design. Similarly, the SMD score was 0.84 (95% CI: 0.25 to 1.43) for the four studies using the independent groups design. There was evidence of high heterogeneity and publication bias among the studies included. CONCLUSIONS: This meta-analysis revealed that OHIP-14 scores were significantly lower after receiving treatment for malocclusion and in individuals without malocclusion/orthodontic treatment need compared to those with such condition (independent groups).

Improving access to preparatory information for children undergoing general anaesthesia for tooth extraction and their families: study protocol for a Phase III randomized controlled trial.

BACKGROUND: Children can find anaesthesia induction especially distressing and postoperative psychological and physical morbidity are common. Preparation programmes for general anaesthesia (GA) are highly effective in reducing this distress. A Phase II study has already verified the effectiveness of a prototype preoperative GA-coping computer game to help children cope with induction in a dental GA setting. The biggest patient users of pediatric GA services in the UK are children who need to have teeth removed (estimated to be 100,000 yearly). Tooth decay is the most common disease in children worldwide. This study is a Phase III randomized controlled trial (RCT) and will evaluate the effectiveness of the new internet version of this game. METHODS/DESIGN: The Phase III RCT will use a double-blind three-armed design. The clinical trial will recruit up to 210 children and will compare the web-based game against standard care and another non-medical game. At least 53 patients in each group will be required for 90% statistical power. Distress will be assessed through an evaluation of the child's behaviour during the visit and later parental reports of physical and psychological morbidity. The satisfaction of parents and children will be measured; the mode of usage of the web-based game will be automatically recorded and the impact on the service (for example, recovery time and throughput) will be reported.The Phase III study primary outcome will measure: (1) patient experience: acceptance of anaesthetic induction, child cooperation and distress, reduction of peri- and postoperative morbidity, child and family satisfaction, and (2) service improvement: anaesthetic time and improvement in throughput. Measures will be administered at baseline, at the time of the GA treatment visit, and at 48 hours and one week postoperatively. DISCUSSION: This study aims to determine the effectiveness of an online GA-coping game for children and families undergoing tooth extraction under GA. TRIAL REGISTRATION: ISRCTN18265148 (registered 24 November 2013).

How does variation in lower anterior face height influence perceived attractiveness? A quantitative investigation.

OBJECTIVE: The purpose of this investigation was to undertake an objective and quantitative evaluation of how severity of lower anterior face height (LAFH) variations influences perceived attractiveness. DESIGN: Cross-sectional study SETTING: St George's Hospital, London, UK PARTICIPANTS AND METHODS: The LAFH of an idealized male and female frontal facial image were altered in 2·5 mm increments from -20 to 20 mm (male images) and from -10 to 20 mm (female images), in order to represent reduction and increase in height of this region. These images were rated by a pre-selected group of pre-treatment orthognathic patients (n = 75), clinicians (n = 35) and laypersons (n = 75). OUTCOME MEASURES: Ratings on a seven-point Likert scale. RESULTS: With an increase in LAFH, desire for surgery became significant at 15-16 mm for male faces and 13-14 mm for female faces. With a reduction in LAFH, desire for surgery became significant at -14 to -17 mm for male faces; a smaller reduction of -6 to -8 mm led to a significant desire for surgery for female faces. CONCLUSIONS: The classical vertical facial trisection canon of upper face height as one-third (33·3%), midface height as one-third (33·3%) and LAFH as one-third (33·3%) of total anterior face height may be used as an 'ideal' proportional ratio. Mild LAFH variations were largely acceptable. In terms of the percentage LAFH to total anterior face height (TAFH) and anterior face height (AFH), observers did not desire surgery for LAFH variations of 25-42% of TAFH (40-66% of AFH) for male faces, and 28-42% of TAFH (45-66% of AFH) for female faces.

An in vitro comparison of the accuracy of measurements obtained from high- and low-resolution cone-beam computed tomography scans.

INTRODUCTION: This study aimed to investigate in an ex vivo model the reduction in patient radiation dose while maintaining accurate linear measurements by comparing cone-beam computed tomography (CBCT) scans taken at 360° versus 180° rotation, with porcine jaw specimens as a reference standard. METHODS: CBCT scans of 12 sectioned porcine hemimandibles at 360° and 180° rotations were taken with standardized clinical exposure parameters. To assess interobserver variability, 6 assessors who were blinded to the degree of rotation took linear measurements of anatomic structures on each scan. The measurements were repeated after 2 weeks to assess intraobserver variability. Accuracy of measurement was judged against the corresponding measurements taken from the porcine jaw specimens. RESULTS: Intraclass correlations signaled good-to-excellent intraobserver and interobserver agreement (0.65-0.98 and 0.79-0.98), respectively. Mixed regression analysis found no significant difference between the measurements from 180° or 360° rotations and no difference between the 2 rotations and porcine jaw specimens. CONCLUSIONS: A CBCT image sufficient to make accurate clinical measurements with a reduced radiation exposure may be obtained by using 180° rotation of the CBCT tube head.

The influence of combined orthodontic-orthognathic surgical treatment on perceptions of attractiveness: a longitudinal study.

The purpose of this investigation was to quantitatively evaluate the influence of completing the orthognathic treatment process on patients' perceptions of attractiveness and their desire for surgical correction. The mandibular prominence of an idealized profile image was altered in 2 mm increments from -16 to 12 mm, in order to represent retrusion and protrusion of the mandible, respectively. These images were rated on a seven-point Likert scale by 50 patients at T1 (pre-treatment) and T2 (6 months following orthodontic appliance removal). At T1, mandibular retrusion became noticeable at -4 mm and protrusion at 2 mm. The results remained unchanged at T2. Surgery was desired from -9 mm at T1 and -10 mm at T2. For mandibular protrusion, surgery was desired from 3 mm at T1 and 4 mm at T2. The odds of desire for surgery were reduced by 85 per cent for those patients who had undergone bimaxillary surgery in relation to those with single jaw surgery. The lowest rated images demonstrated severe degrees of mandibular protrusion and retrusion. The highest rated images represented the idealized facial profile and minor variations thereof; there was little change in perception between T1 and T2. Going through the process of orthognathic treatment does not appear to have any significant effect on patients' perceptions of facial profile attractiveness or the limits of mandibular sagittal deviation at which they would desire surgery. The clinician's information provision during treatment does not seem to unduly influence orthognathic patients and does not make them more critical of jaw deformities.

Assessing the influence of lower facial profile convexity on perceived attractiveness in the orthognathic patient, clinician, and layperson.

OBJECTIVE: The aim was a quantitative evaluation of how the severity of lower facial profile convexity influences perceived attractiveness. STUDY DESIGN: The lower facial profile of an idealized image was altered incrementally between 14° to -16°. Images were rated on a Likert scale by orthognathic patients, laypeople, and clinicians. RESULTS: Attractiveness ratings were greater for straight profiles in relation to convex/concave, with no significant difference between convex and concave profiles. Ratings decreased by 0.23 of a level for every degree increase in the convexity angle. Class II/III patients gave significantly reduced ratings of attractiveness and had greater desire for surgery than class I. CONCLUSIONS: A straight profile is perceived as most attractive and greater degrees of convexity or concavity deemed progressively less attractive, but a range of 10° to -12° may be deemed acceptable; beyond these values surgical correction is desired. Patients are most critical, and clinicians are more critical than laypeople.

Cost-effectiveness of counselling, graded-exercise and usual care for chronic fatigue: evidence from a randomised trial in primary care.

BACKGROUND: Fatigue is common and has been shown to result in high economic costs to society. The aim of this study is to compare the cost-effectiveness of two active therapies, graded-exercise (GET) and counselling (COUN) with usual care plus a self-help booklet (BUC) for people presenting with chronic fatigue. METHODS: A randomised controlled trial was conducted with participants consulting for fatigue of over three months' duration recruited from 31 general practices in South East England and allocated to one of three arms. Outcomes and use of services were assessed at 6-month follow-up. The main outcome measure used in the economic evaluation was clinically significant improvements in fatigue, measured using the Chalder fatigue scale. Cost-effectiveness was assessed using the net-benefit approach and cost-effectiveness acceptability curves. RESULTS: Full economic and outcome data at six months were available for 163 participants; GET = 51, COUN = 58 and BUC = 54. Those receiving the active therapies (GET and COUN) had more contacts with care professionals and therefore higher costs, these differences being statistically significant. COUN was more expensive and less effective than the other two therapies. The incremental cost-effectiveness ratio of GET compared to BUC was equal to £987 per unit of clinically significant improvement. However, there was much uncertainty around this result. CONCLUSION: This study does not provide a clear recommendation about which therapeutic option to adopt, based on efficiency, for patients with chronic fatigue. It suggests that COUN is not cost-effective, but it is unclear whether GET represents value for money compared to BUC. Clinical Trial Registration number at ISRCTN register: 72136156.

Assessing the influence of asymmeftry affecting the mandible and chin point on perceived attractiveness in the orthognathic patient, clinician, and layperson.

PURPOSE: The purpose of this investigation was to undertake an objective and quantitative evaluation of how severity of asymmetries affecting the mandible and chin point influence perceived attractiveness. MATERIALS AND METHODS: The mandible and chin point of idealized male and female frontal facial images were altered in 5-mm increments from 0 to 25 mm and to the left and right, to represent horizontal, vertical, and combined asymmetry affecting these regions. These images were rated on a 7-point Likert scale by a preselected group of orthognathic patients before treatment, clinicians, and laypeople. RESULTS: In relation to a 5-mm asymmetry, observers progressively decreased attractiveness ratings and increased the desire for surgery for greater asymmetries. Clinicians and patients were found to be more critical than laypeople. The desire for surgery decreased by 3% for each year increase in age, was 53% less for men, and 45% greater for white observers. CONCLUSIONS: Asymmetry of 10 mm is perceived as being significant; at 5 mm and below, it is largely unnoticed. The greater the degree of asymmetry greater than 10 mm, the more noticeable and the greater the desire was for correction. Clinician and patient ratings were similar and more critical than ratings of laypeople. A desire for surgery was negligible for 5 mm of asymmetry but increased considerably at 10 mm and continued to increase with greater degrees of asymmetry. The highest-rated images showed perfect bilateral symmetry, whereas the lowest-rated images showed significant degrees of mandibular and chin asymmetry.

Influence of chin height on perceived attractiveness in the orthognathic patient, layperson, and clinician.

OBJECTIVE: To determine an objective and quantitative evaluation of how severity of chin height variations influence perceived attractiveness. MATERIALS AND METHODS: The chin height of an idealized male and female frontal facial image was altered in 2.5-mm increments from -12.5 to 22.5 mm (male images) and from -10 to 20 mm (female images). These images were rated on a seven-point Likert scale by a preselected group of pretreatment orthognathic patients, clinicians, and laypeople. RESULTS: The classical lower facial proportional canon of upper lip height as one third (33.3%), lower lip height as one third (33.3%) and chin height as one third (33.3%) of lower anterior face height (LAFH) may be used as an "ideal" proportional ratio. However, chin height variations within a given proportional range are largely unnoticed, ie, from approximately 30% chin height in relation to LAFH (male and female) up to approximately 40% (males) and 50% (females) chin height in relation to LAFH. Additionally, surgery is only desired with greater variations in chin height: greater than 50% and less than 20%-23% of LAFH in males, and greater than 58% and less than 20%-22% of LAFH in females. Patients and clinicians are more critical than laypeople, but no significant differences were found between clinicians and patients. CONCLUSIONS: In relation to the classical canon, surgical correction of chin height deformities are desired with chin height greater than 50% and less than 20%-23% of LAFH in males, and greater than 58% and less than 20%-22% of LAFH in females.

Canine substitution for missing maxillary lateral incisors: the influence of canine morphology, size, and shade on perceptions of smile attractiveness.

INTRODUCTION: This study was conducted to determine whether variations in the morphology, size, or shade of maxillary canines would influence perceptions of smile attractiveness in patients with canines substituted for missing maxillary lateral incisors. METHODS: A smiling photograph of a hypodontia patient who had had orthodontic space closure with maxillary canines replacing the lateral incisors was digitally modified to create a bilaterally symmetrical image. Four groups of images were created, digitally altering canine gingival height, crown tip height, canine width, and canine shade. Three groups of judges (40 orthodontists, 40 dentists, and 40 laypeople) ranked the images for smile attractiveness, also scoring the most and the least attractive of each of the 4 groups, and the most and least attractive of all images. RESULTS: Canine gingival height was the most attractive 0.5 mm below the gingival margin of the maxillary central incisor and progressively less attractive with increasing gingival height. Increasing canine width, increased canine tip height, and pointed canines were perceived to be unattractive. Brighter than normal shades of canines were preferred to darker shades. Narrow canine crowns were most frequently ranked as the most attractive overall, 1.5 mm narrower was preferred by the orthodontists and dentists, and 3.0 mm narrower was preferred by the laypeople. All 3 groups ranked the darkest image, 20 times darker than the original, most frequently as the least attractive image overall. There was good general agreement between orthodontists, dentists, and laypeople for all 4 parameters of smile attractiveness, although laypeople demonstrated greater intragroup variations. CONCLUSIONS: The morphology, size, and shade of the maxillary canine in patients having orthodontic space closure and lateral incisor substitution can have a marked effect on perceived smile attractiveness.

The hidden cost of chronic fatigue to patients and their families.

BACKGROUND: Nearly 1 in 10 in the population experience fatigue of more than six months at any one time. Chronic fatigue is a common reason for consulting a general practitioner, and some patients report their symptoms are not taken seriously enough. A gap in perceptions may occur because doctors underestimate the impact of fatigue on patients' lives. The main aim of the study is to explore the economic impact of chronic fatigue in patients seeking help from general practitioners and to identify characteristics that explain variations in costs. METHODS: The design of study was a survey of patients presenting to general practitioners with unexplained chronic fatigue. The setting were 29 general practice surgeries located in the London and South Thames regions of the English National Health Service. Use of services over a six month period was measured and lost employment recorded. Regression models were used to identify factors that explained variations in these costs. RESULTS: The mean total cost of services and lost employment across the sample of 222 patients was 3878 pounds for the six-month period. Formal services accounted for 13% of this figure, while lost employment accounted for 61% and informal care for 26%. The variation in the total costs was significantly related to factors linked to the severity of the condition and social functioning. CONCLUSIONS: The economic costs generated by chronic fatigue are high and mostly borne by patients and their families. Enquiry about the functional consequences of fatigue on the social and occupational lives of patients may help doctors understand the impact of fatigue, and make patients feel better understood.

Reliability and cross-cultural validity of a Japanese version of the Dental Fear Survey.

BACKGROUND: This study established the reliability and cross-cultural validity of a Japanese version of the Dental Fear Survey (DFS). METHODS: Two studies were carried out in separate populations. The first involved 166 Japanese dental and nursing students and assessed internal consistency and test-retest reliability. The second involved 2,095 Japanese parents or guardians of school children and tested the hypothesis that the conceptual structure of the Japanese translation was consistent with the U.S. version using Structural Equation Modeling (SEM). RESULTS: In the first study Cronbach alpha ranged from .94 to .96 and test-retest reliability (Spearman correlation) ranged from .89 to .92. The intra-class correlation coefficients (ICC) was 0.919 (95%CI: 0.892 - 0.940). In the second study SEM was used on the covariance matrix of the 20 questions in a random sample of 600 questionnaires to evaluate the goodness of fit of the theoretical model; and then, in an exploratory manner corrected for specification errors until a model that fit the data well was achieved. CONCLUSION: The Japanese version of the DFS appears reliable and demonstrates cross-cultural validity. The modeling confirms the three factors on which the English language version was based.

Dental age assessment (DAA): reference data for British caucasians at the 16 year threshold.

UNLABELLED: The purpose of this study was to determine reference data for dental age assessment (DAA) for the 16 year threshold in British caucasians. PATIENTS, MATERIALS AND METHODS: One thousand seven hundred and twenty-two Dental Panoramic Radiographs of individuals aged between 4 and 24 years were re-used to establish reference intervals using the tooth development stages (TDSs) previously described [A. Demirjian, H. Goldstein, J.M. Tanner, A new system of dental age, assessment, Human Biology 45 (1973) 221-227]. All teeth present in the left maxilla and mandible, and the third permanent molars were assessed. In addition, to test the accuracy of DAA, the radiographs of a study sample of 50 children of known chronological age (CA) were assessed in the same manner as the reference population. These were aged between 15 and 17 years and separate from the database. For each subject in the study sample a new method of mathematical manipulation based on meta-analysis was applied to all teeth that were still developing [G.J. Roberts, S. Parekh, A. Petrie, V.S. Lucas, Dental age assessment (DAA): a simple method for children and emerging adults, British Dental Journal 204(4) (2008) 192-193]. The estimated calculated average of all the teeth present on the radiograph of each individual generated by the meta-analysis was assigned to each individual as the dental age. For each test subject this was then compared to the gold standard of chronological age. RESULTS: The average difference between dental age and chronological age for individuals in the test sample was 0.27 years (3.24 months) in females and 0.23 years (2.76 months) in males. CONCLUSION: Dental age assessment obtained by calculation of tooth development stages using meta-analysis provides estimates of age around the 16 year threshold.

A biomarker-based mathematical model to predict bone-forming potency of human synovial and periosteal mesenchymal stem cells.

OBJECTIVE: To develop a biomarker-based model to predict osteogenic potency of human mesenchymal stem cells (MSCs) from synovial membrane and periosteum. METHODS: MSC populations were derived from adult synovium and periosteum. Phenotype analysis was performed by fluorescence-activated cell sorting and real-time reverse transcriptase-polymerase chain reaction (RT-PCR). Telomere lengths were determined by Southern blot analysis. In vitro osteogenesis was assessed quantitatively by measurements of alkaline phosphatase activity and calcium deposits. To investigate bone formation in vivo, MSCs were seeded onto osteoinductive scaffolds and implanted subcutaneously in nude mice. Bone was assessed by histology, and the human origin investigated by in situ hybridization for human Alu genomic repeats. Quantitation was achieved by histomorphometry and real-time RT-PCR for human osteocalcin. Analysis at the single-cell level was performed with clonal populations obtained by limiting dilution. Multiple regressions were used to explore the incremental predictive value of the markers. RESULTS: Periosteal MSCs had significantly greater osteogenic potency than did synovial MSCs inherent to the single cell. Bone was largely of human origin in vivo. Within the same tissue type, there was variability between different donors. To identify predictors of osteogenic potency, we measured the expression levels of osteoblast lineage genes in synovial and periosteal clonal MSCs prior to osteogenic treatment. We identified biomarkers that correlated with osteogenic outcome and developed a mathematical model based on type I collagen and osteoprotegerin expression that predicts the bone-forming potency of MSC preparations, independent of donor-related variables and tissue source. CONCLUSION: Our findings indicate that our quality-control mathematical model estimates the bone-forming potency of MSC preparations for bone repair.