***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: The split-mouth design is a popular design in oral health research . In the most common split-mouth study , each of two treatments are r and omly assigned to either the right or left halves of the dentition . The attractiveness of the design is that it removes a lot of inter-individual variability from the estimates of the treatment effect . However , already about 20 years ago the pitfalls of the design have been reported in the oral health literature . Yet , many clinicians are not aware of the potential problems with the split-mouth design . Further , it is our experience that most statisticians are not even aware of the existence of this design . Since most of the critical remarks appeared in the oral health literature , we argue that it is necessary to introduce the split-mouth design to a statistical audience , so that both clinicians and statisticians clearly underst and the advantages , limitations , statistical considerations , and implication s of its use in clinical trials and advise them on its use in practice Das Ziel der hier vorgestellten Untersuchung war es , die Auswirkung von Intrusion sowie Extrusion auf die Blutversorgung der Pulpa am Menschen zu ermitteln . Die Unterschiede der Durchblutungsänderungen wurden an zehn lateralen Inzisiven ( sechs Prob and en ) durch Laser Doppler Flowmetry ( Perimed , Sweden ) mittels an den bukkalen Flächen der Zähne befestigter Metallröhrchen gemessen . Die Brackets wurden an den Zähnen 13 und 23 befestigt , und intrusive bzw . extrusive Kräfte von 2 N wurden an den zu untersuchenden Zähnen über einen Zeitraum von fünf Minuten appliziert . Der jeweilige kontralaterale Zahn diente als Kontrolle . Die Extrusion bewirkte keine signifikante Veränderung des Pulpablutdurchflusses weder während noch nach der Aufhebung der extrusiven Kräfte . Intrusive Kräfte reduzierten jedoch während der ersten Minute der Kraftapplikation den Pulpablutdurchfluß um 20 % . Während der nächsten vier Minuten kam es zu einer kontinuierlichen Zunahme des Pulpablutdurchflusses in Richtung des Ausgangswertes , und drei Minuten nach Aufhebung der Kraft erreichte er wieder den normalen Wert . Zusammenfassend kann festgestellt werden , daß die orthodontische Intrusion mit einer Kraft von 2 N eine temporäre Reaktion des Pulpablutdurchflusses hervorrief , die Extrusion hingegen keine Auswirkung auf den Pulpablutdurchfluß hatte . The purpose of the present investigation was to measure the effect of tooth intrusion and extrusion on pulpal blood flow in man . The flow changes were measured in 10 lateral incisors ( 6 subjects ) by means of laser Doppler flowmetry ( Perimed , Sweden ) applied on the buccal surface through metal tubes bonded to the teeth . Brackets were bonded onto teeth 13 and 23 , and intrusive and extrusive forces of 2 N were applied in r and om order to the experimental tooth for 5 min before unloading . The contralateral tooth served as a control . Extrusion of the teeth gave no significant changes in pulpal blood flow during loading or unloading , However , intrusion of the teeth reduced the pulpal blood flow by 20 % during the first minute after force application . The pulpal blood flow gradually increased towards the preloading flow values for the next 4 min , and was returned to the prestimulus level 3 min after unloading . In conclusion orthodontic intrusion of teeth with a 2 N force evoked a temporary reduction in the pulpal blood flow , whereas extrusion had no effect on the pulpal blood flow A careful review of the literature reveals an absence of studies about the reactions of dental pulp to orthodontic extrusion . The purpose of the present research investigation is to study the pulpal reactions and the sequence of histologic events in human dental pulp after orthodontic extrusion . The sample consisted of 36 intact maxillary first premolars of young adult orthodontic subjects . The mean age of the subjects was 18 years . Eighteen maxillary first premolars were extruded , under controlled conditions with the aid of fixed edgewise orthodontic appliances , for either 1 , 2 , or 4 weeks . The contralateral maxillary first premolars were not extruded and were used as controls . Immediately after removal of the appliances , all the maxillary first premolars were extracted . The pulps were histologically examined in a double-blind experiment . The results obtained from this study indicate that certain characteristic pulpal reactions arise from orthodontic extrusion . These reactions involve circulatory disturbances with congested and dilated blood vessels , odontoblastic degeneration , vacuolization and edema of the pulp tissues , and ( by the fourth week ) manifestation of fibrotic changes . It is speculated that the vacuolization of the pulp tissues ( which occurred after the application of extrusive orthodontic forces in young adult subjects ) result ed from a prolapse of the pulp , made possible by the relatively wide apical foramina . However , the odontoblastic degeneration is most probably the result of a compromised blood supply . The authors believe that this study constitutes a building block for establishing a more complete biologic foundation for orthodontic tooth movement . Further studies are suggested to reach more definitive conclusions This study examines the aspartate aminotransferase activity in the pulp of orthodontically treated teeth . Seventeen healthy male and female subjects ( ages : 14.5 - 19.6 ; mean 16.8 + /- 1.6 years ) who needed extraction of the maxillary first premolars for orthodontic reasons were enrolled in the study . One r and omly chosen maxillary first premolar , included in a straight-wire fixed orthodontic appliance and supporting orthodontic force , was considered as the test tooth . The contralateral first premolar , included in the orthodontic appliance but not subjected to mechanical stress , was used as the control tooth . After a week of treatment , the dental pulp tissues were extracted from both experimental teeth . Aspartate aminotransferase activity was significantly elevated in the test teeth as compared with the control teeth . These results demonstrate that in the early phases of treatment , orthodontic force application to the teeth can lead to significant metabolic changes in the pulp of these teeth OBJECTIVES To study a possible dose-response relation between force magnitude and rate of orthodontic tooth movement by altering forces during bodily orthodontic tooth movement . SETTING AND SAMPLE POPULATION Eight young adult beagle dogs were used . The experiments were carried out in the Central Animal Facility , and all analyses were conducted in the Department of Orthodontics and Oral Biology , Radboud University Nijmegen Medical Centre . MATERIAL S AND METHODS Orthodontic appliances were placed exerting a reciprocal force on the m and ibular second premolars and first molars . A force of 10 or 300 cN was r and omly assigned to each side of the dogs . After 22 weeks , all forces were changed to 600 cN. Based on intra-oral measurements , tooth movement rates were calculated . RESULTS The premolars showed no difference in the rates of tooth movement with 10 or 300 cN. Replacing 10 for 600 cN increased the rate , but replacing 300 for 600 cN did not . Molars moved faster with 300 than with 10 cN , and changing both forces to 600 cN increased the rate of tooth movement . Data from all teeth were pooled considering their relative root surfaces , and a logarithmic relation was found between force and rate of tooth movement . CONCLUSIONS Only in the very low force range , a positive dose-response relation exists , while in higher force ranges , no such relation could be established This study investigates the effect of an orthodontic force on pulpal respiration in the human premolar . The participants in this study required the removal of four first premolars for orthodontic treatment .  After written consent was obtained , these teeth were used in the following manner . R and omly , the premolars on one side of the mouth were design ated as experimental and the premolars on the opposing side served as controls . The four teeth were removed following a 3-day application of an orthodontic force . The pulp tissue was then extirpated and used for the investigation . A radioactively labeled carbon dioxide production system was used to evaluate the effect on pulpal respiration of the orthodontic force . It is thought that this method has been proved to provide a viable and sensitive biochemical analysis of tissue respiration on very small sample s over short observation periods . The data were collected and prepared for statistical analysis . This investigation demonstrated that the pulp tissue respiration in seventeen subjects was depressed an average of 27 % as a result of orthodontic force application . A positive correlation between the age of the participant and the amount of tissue respiratory depression was also demonstrated . It was therefore concluded that orthodontic forces of very short duration do cause biochemical and biologic pulpal tissue alterations and that orthodontic forces may be less biologically safe as the age of the patient increases INTRODUCTION The aim of this study was to examine alkaline phosphatase ( ALP ) activity in the dental pulp of orthodontically treated teeth . METHODS Sixteen healthy subjects ( mean age 17.0 + /-1.6 years ) who required extraction of 4 first premolars for orthodontic reasons participated . One maxillary first premolar subjected to orthodontic force was the test tooth . The contralateral first premolar , bracketed but not subjected to mechanical stress , was the control tooth . After a week of treatment , the first premolars were extracted and the dental pulp removed from the teeth . ALP activity was determined spectrophotometrically and the results expressed as units/liter per milligram of pulp tissue [ U/(L x mg ) ] . RESULTS ALP activity was 89 + /- 26 U/(L x mg ) in the test teeth and 142 + /- 33 U/(L x mg ) in the control teeth . The difference between the groups was statistically significant ( P < .01 ) . CONCLUSIONS Orthodontic treatment can lead to significant early-phase reduction in ALP activity in human dental pulp tissue 
    Output:
    
Because of a lack of high- quality studies there is no conclusive scientific evidence for a relation between force level and dental pulp tissue reaction in humans .
There is contradictory scientific support for a force-dependent reduction of blood flow