human
***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: INTRODUCTION : The purpose of this study was to compare the subcutaneous tissue responses of freshly mixed or set endodontic root canal sealers ( i.e. RoekoSeal , AH26 , AH Plus ) in Wistar Albino rats . MATERIAL S AND METHODS : Seventy-two male albino rats weighing 200 - 250 g were used . The animals were r and omly divided into six groups of 12 rats each . Root canal sealers were implanted in subcutaneous tissue in both freshly mixed and set conditions . The animals were sacrificed after 7 , 14 , and , 60 days . After histological preparation and Hematoxylin and Eosin ( H&E ) staining , the specimens were evaluated for capsule thickness , severity and extent of inflammation , and necrosis . Results were statistically analyzed using Multivariate ANOVA test . RESULTS : Differences between set and freshly mixed root canal sealers were significant ( P=0.014 ) , but not significant between test material s and controls , except for capsule thickness and extent of inflammation between control and AH26 ( P=0.019 and P=0.006 respectively ) . The interaction between the type of material and setting condition was significant for capsule thickness and severity of inflammation in AH26 specimens at 14 and 60 days ( P=0.001 ) . CONCLUSION : Based on the results of this study assessing the biocompatibility , both set and freshly mixed states can be used . [ Iranian Endodontic Journal 2009;4(4):152 - 7 The purpose of this study was to compare ISO st and ards versus a new technique for in vitro evaluation of cytotoxicity of root canal sealers . The cytotoxicity of AH Plus , Cortisomol , and Sealapex was first recorded according to ISO st and ards on L 929 fibroblasts by the MTT assay . In parallel , 30 single-rooted teeth were cut at the cementum enamel junction ( CEJ ) , and the roots were prepared and sterilized before filling with the lateral condensation using one of three sealers ( n = 10 ) . The apexes of the roots were dipped into 1 ml of minimum essential medium for 1 , 2 , and 30 days renewing the medium every other day . After 24-h contact between the medium and the filled roots , the medium was used to measure the cytotoxicity on L 929 with the MTT assay . ISO st and ards always gave a statistically higher cytotoxicity than the root-dipping technique ( p < 0.0001 ) , whatever the sealer and the exposure time . The ISO st and ards showed statistically significant differences among the sealers ( p < 0.0001 ) . AH Plus was noncytotoxic , Cortisomol showed a high cytotoxicity decreasing over time ( p < 0.001 ) , and Sealapex displayed a high cytotoxicity that did not decrease over time ( NS ) . The new technique showed statistically significant differences among the sealers ( p = 0.001 ) , but the differences were so small that they were likely not clinical ly relevant . The high cytotoxicity of Sealapex decreased over time but the cytotoxicity of AH Plus and Cortisomol did not . The results show that the ISO st and ards may strongly over-evaluate the cytotoxicity of the endodontic sealers , emphasize the difference among the sealers , and may clinical ly correspond to a large overfilling . The new technique reduces the discrimination of the test and may clinical ly correspond to a classical filling . Therefore , both methods might be considered as clinical ly relevant , corresponding to classical and overfilling conditions In vitro pre- clinical research is an important aspect of the development of new dental material s and techniques , because it can provide essential information for further testing of therapeutic approaches in clinical trials . These pre- clinical experiments should therefore be reported with the same rigor as studies involving humans . The objectives of this paper were twofold : ( a ) to search and assess existing guidelines for reporting in vitro studies in dentistry , and ( b ) to present a methodology for reporting these studies , based on the CONSORT checklist for reporting r and omized clinical trials . After a comprehensive search in PubMed data base , no guidelines for reporting in vitro studies in dentistry were found . The proposed methodology is presented and the rationale for the choice of fourteen guidelines for producing the different sections of such papers is described in detail . The assessment of a sample of in vitro studies using the proposed guidelines showed that the st and ards of reporting should be improved . Good st and ards of reporting of studies are necessary for improvement of efficiency in dental research . The guidelines presented are the first st and ards for reporting in vitro studies in dentistry . As with the original CONSORT document , the modified checklist is evolving . It should , therefore , be further tested by research ers and the results of these assessment s should be used for further improvement of this tool INTRODUCTION This study analyzed bone tissue reactions to MTA Fillapex ( Ângelus Industria de Produtos Odontológicos Ltda , Londrina , Brazil ) compared with an epoxy resin-based material in the femur of Wistar rats . METHODS Bone tissue reactions were evaluated in 15 animals after 7 , 30 , and 90 days ( n = 5 per period ) . Three surgical cavities were prepared on the femur and filled with 0.2 mL MTA Fillapex , AH Plus ( Dentsply DeTrey GmbH , Konstanz , Germany ) , or no sealer ( negative control ) . By the end of each experimental period , 5 animals were r and omly euthanized . The sample s were histologically processed and analyzed using a light microscope . The presence of inflammatory cells , fibers , and hard tissue barrier formation was evaluated . Differences among the groups and between the 3 experimental periods were evaluated by using 2-way analysis of variance followed by the Bonferroni post hoc test ( P ≤ .05 ) . RESULTS MTA Fillapex scored significantly higher for neutrophils at 7 days than at 90 . At 7 days , the same occurred when comparing MTA Fillapex with AH Plus . The presence of lymphocytes/plasmocytes significantly decreased over time in all groups . Macrophages , giant cells , eosinophils , and fiber condensation presented no differences among groups and periods . Within 90 days , all groups presented complete hard tissue barrier formation . CONCLUSIONS The presence of mineral trioxide aggregate in MTA Fillapex composition did not improve the bone tissue repair . The presence of sealers provided the re-establishment of the original bone tissue structure and the inflammatory response decreased over time , so they can be considered biocompatible Clinicians often witness impressive treatment results in practice and may wish to pursue research to formally explore their anecdotal experiences . The potential to further new knowledge both within the profession and to the greater healthcare system is compelling . An obvious next step for a practitioner considering research is to connect with experienced research ers to convey their idea for a study , who may in turn ask , “ What is your research question ? ” With limited underst and ing of how to respond , this interaction may result in the first and last experience these clinicians will have with the research community . It has been estimated that between 1 % and 7 % of the chiropractic profession in Canada is engaged in research . 1,2 Arguably , this low engagement could be the result of practitioners ’ perceived importance of research and levels of research literacy and capacity . However , increasing dem and s for evidence -based approaches across the health system puts pressure on all clinicians to base their decisions on the best available scientific evidence . Lack of clinician representation in research has the probable effect of limiting growth and new developments for the profession . Furthermore , lack of clinician involvement in research complicates the transfer of study findings into practical setting s. The Canadian Institutes of Health Research describes integrated knowledge translation as a process that involves collaboration between research ers and knowledge users at all stages of a research project.3 This necessitates involvement of clinicians to help in forming a research question , interpreting the results , and moving research findings into practice . This shared effort between clinicians and research ers increases the likelihood that research initiatives will be relevant to practice .3 Conversely , it has been reported that there is a growing communication gap between clinicians and academics in chiropractic . 4 Clinicians have important practice -related questions to ask , but many may lack the ability to map out their research strategy , specifically in communicating their question in a manner required to develop a research protocol . David L. Sackett , Officer of the Order of Canada and the founding Chair of Canada ’s first Department of Clinical Epidemiology & Biostatistics at McMaster University , highlights the importance of mapping one ’s research strategy in exploration of the research question : “ one-third of a trial ’s time between the germ of your idea and its publication in the New Engl and Journal of Medicine should be spent fighting about the research question . ” ( personal communication , November 30 , 2011 ) We describe a r and omized controlled trial ( RCT ) example to highlight how clinicians may use existing literature and the PICOT format to formulate a research question on treatment efficacy AIM The aim of this study was to evaluate pigmentation and tissue response to four endodontic sealers placed in the oral mucosa of rabbits by either submucous injection or implant in polyethylene tubes . METHODOLOGY Thirty white New Zeal and rabbits were divided r and omly into two groups of eight for N-Rickert and AH-26 , and two groups of seven for Fillcanal and Sealer 2 6 . On the right side of the filter , corresponding to the gingivo-labial sulcus in humans , the sealer was injected ; on the left side the sealer was placed within a polyethylene tube and implanted . Direct clinical observations were made at 30 , 60 and 90 days . The animals were then sacrificed for histological analysis . RESULTS After 60 days of observation N-Rickert and AH-26 produced tattoos that became larger by 90 days . Submucous injection produced larger and more numerous pigmentation , when compared to implant in polyethylene tubes . N-Rickert sealer displayed larger and more numerous tattoos when compared to AH-26 . Histological analysis showed no differences between the two methods of implantation . All sealers elicited some kind of inflammatory response ; the most irritant was Fillcanal , followed by N-Rickert and AH-26 . Sealer 26 elicited a mild reaction only . CONCLUSIONS Under the conditions of this study there was no relationship between the method of implantation and the tissue response ; the silver-containing sealers produced pigmentation , and the concentration of silver influenced the quantity and size of the tattoos . The sealers elicited various responses when in direct contact with the surrounding tissues : the calcium hydroxide-containing sealer had enhanced healing when compared to the other sealers In regard to biological properties of  endodontic sealers  , there are many characteristics that should be considered . The aim of this study was to examine the biological effects of new calcium phosphate-based root canal sealers , CAPSEAL I and CAPSEAL II ( CPS ) , on human periodontal fibroblast cells by examining the expression levels of inflammatory mediators and to compare the effects of CPS on the viability and osteogenic potential of human osteoblast MG63 cells compared to those of other commercially available calcium phosphate sealers [ Apatite Root Sealer type I ( ARS I ) and Apatite Root Sealer III ( ARS III ) ; Sankin Kogyo , Tokyo , Japan ] and a zinc oxide eugenol-based sealer ( Pulp Canal Sealer EWT [ PCS EWT ] ; Kerr , Detroit , MI ) . The levels of IL-6 in the new CPS group ( CAPSEAL I , II ) were higher than those in the control and all experimental groups at all time points after 2 h. TGF-β1 and FGF-1 levels decreased at 72 h compared to the levels in the control , in cells treated with every sealers except ARS I. The new CPS sealers showed low cytotoxicity . Reverse transcription polymerase chain reaction showed that CAPSEAL I , II , and Apatite Root Sealer type III induced expression of early stage markers of differentiation ( alkaline phosphatase and osteopontin ) at 7 days . Also , new CPS showed higher mineralized nodule formation at 28 days . These results suggest that CAPSEAL I and II facilitate the periapical dentoalveolar and alveolar healing by controlling cellular mediators from PDL cells and osteoblast differentiation of precursor cells Background Systematic Review s ( SRs ) of experimental animal studies are not yet common practice , but awareness of the merits of conducting such SRs is steadily increasing . As animal intervention studies differ from r and omized clinical trials ( RCT ) in many aspects , the methodology for SRs of clinical trials needs to be adapted and optimized for animal intervention studies . The Cochrane Collaboration developed a Risk of Bias ( RoB ) tool to establish consistency and avoid discrepancies in assessing the method ological quality of RCTs . A similar initiative is warranted in the field of animal experimentation . Methods We provide an RoB tool for animal intervention studies ( SYRCLE ’s RoB tool ) . This tool is based on the Cochrane RoB tool and has been adjusted for aspects of bias that play a specific role in animal intervention studies . To enhance transparency and applicability , we formulated signalling questions to facilitate judgment . Results The result ing RoB tool  for animal studies contains 10 entries . These entries are related to selection bias , performance bias , detection bias , attrition bias , reporting bias and other biases . Half these items are in agreement with the items in the Cochrane RoB tool . Most of the variations between the two tools are due to differences in design between RCTs and animal studies . Shortcomings in , or unfamiliarity with , specific aspects of experimental design of animal studies compared to clinical studies also play a role . Conclusions SYRCLE ’s RoB tool is an 
    Output:
    
agent
In general , studies suggest that root canal sealers elicit mild to severe toxic effects and that several factors may influence biocompatibility , e.g. , material setting condition and time , material concentration , and type of exposure .
4 ) Conclusions : The available evidence shows that root canal sealers exhibit variable toxic potential at the cellular and tissue level .
However , the method ological heterogeneity among studies included in this systematic review and the somewhat conflicting results do not allow a conclusion on which type of sealer presents higher biocompatibility .
***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: INTRODUCTION : The purpose of this study was to compare the subcutaneous tissue responses of freshly mixed or set endodontic root canal sealers ( i.e. RoekoSeal , AH26 , AH Plus ) in Wistar Albino rats . MATERIAL S AND METHODS : Seventy-two male albino rats weighing 200 - 250 g were used . The animals were r and omly divided into six groups of 12 rats each . Root canal sealers were implanted in subcutaneous tissue in both freshly mixed and set conditions . The animals were sacrificed after 7 , 14 , and , 60 days . After histological preparation and Hematoxylin and Eosin ( H&E ) staining , the specimens were evaluated for capsule thickness , severity and extent of inflammation , and necrosis . Results were statistically analyzed using Multivariate ANOVA test . RESULTS : Differences between set and freshly mixed root canal sealers were significant ( P=0.014 ) , but not significant between test material s and controls , except for capsule thickness and extent of inflammation between control and AH26 ( P=0.019 and P=0.006 respectively ) . The interaction between the type of material and setting condition was significant for capsule thickness and severity of inflammation in AH26 specimens at 14 and 60 days ( P=0.001 ) . CONCLUSION : Based on the results of this study assessing the biocompatibility , both set and freshly mixed states can be used . [ Iranian Endodontic Journal 2009;4(4):152 - 7 The purpose of this study was to compare ISO st and ards versus a new technique for in vitro evaluation of cytotoxicity of root canal sealers . The cytotoxicity of AH Plus , Cortisomol , and Sealapex was first recorded according to ISO st and ards on L 929 fibroblasts by the MTT assay . In parallel , 30 single-rooted teeth were cut at the cementum enamel junction ( CEJ ) , and the roots were prepared and sterilized before filling with the lateral condensation using one of three sealers ( n = 10 ) . The apexes of the roots were dipped into 1 ml of minimum essential medium for 1 , 2 , and 30 days renewing the medium every other day . After 24-h contact between the medium and the filled roots , the medium was used to measure the cytotoxicity on L 929 with the MTT assay . ISO st and ards always gave a statistically higher cytotoxicity than the root-dipping technique ( p < 0.0001 ) , whatever the sealer and the exposure time . The ISO st and ards showed statistically significant differences among the sealers ( p < 0.0001 ) . AH Plus was noncytotoxic , Cortisomol showed a high cytotoxicity decreasing over time ( p < 0.001 ) , and Sealapex displayed a high cytotoxicity that did not decrease over time ( NS ) . The new technique showed statistically significant differences among the sealers ( p = 0.001 ) , but the differences were so small that they were likely not clinical ly relevant . The high cytotoxicity of Sealapex decreased over time but the cytotoxicity of AH Plus and Cortisomol did not . The results show that the ISO st and ards may strongly over-evaluate the cytotoxicity of the endodontic sealers , emphasize the difference among the sealers , and may clinical ly correspond to a large overfilling . The new technique reduces the discrimination of the test and may clinical ly correspond to a classical filling . Therefore , both methods might be considered as clinical ly relevant , corresponding to classical and overfilling conditions In vitro pre- clinical research is an important aspect of the development of new dental material s and techniques , because it can provide essential information for further testing of therapeutic approaches in clinical trials . These pre- clinical experiments should therefore be reported with the same rigor as studies involving humans . The objectives of this paper were twofold : ( a ) to search and assess existing guidelines for reporting in vitro studies in dentistry , and ( b ) to present a methodology for reporting these studies , based on the CONSORT checklist for reporting r and omized clinical trials . After a comprehensive search in PubMed data base , no guidelines for reporting in vitro studies in dentistry were found . The proposed methodology is presented and the rationale for the choice of fourteen guidelines for producing the different sections of such papers is described in detail . The assessment of a sample of in vitro studies using the proposed guidelines showed that the st and ards of reporting should be improved . Good st and ards of reporting of studies are necessary for improvement of efficiency in dental research . The guidelines presented are the first st and ards for reporting in vitro studies in dentistry . As with the original CONSORT document , the modified checklist is evolving . It should , therefore , be further tested by research ers and the results of these assessment s should be used for further improvement of this tool INTRODUCTION This study analyzed bone tissue reactions to MTA Fillapex ( Ângelus Industria de Produtos Odontológicos Ltda , Londrina , Brazil ) compared with an epoxy resin-based material in the femur of Wistar rats . METHODS Bone tissue reactions were evaluated in 15 animals after 7 , 30 , and 90 days ( n = 5 per period ) . Three surgical cavities were prepared on the femur and filled with 0.2 mL MTA Fillapex , AH Plus ( Dentsply DeTrey GmbH , Konstanz , Germany ) , or no sealer ( negative control ) . By the end of each experimental period , 5 animals were r and omly euthanized . The sample s were histologically processed and analyzed using a light microscope . The presence of inflammatory cells , fibers , and hard tissue barrier formation was evaluated . Differences among the groups and between the 3 experimental periods were evaluated by using 2-way analysis of variance followed by the Bonferroni post hoc test ( P ≤ .05 ) . RESULTS MTA Fillapex scored significantly higher for neutrophils at 7 days than at 90 . At 7 days , the same occurred when comparing MTA Fillapex with AH Plus . The presence of lymphocytes/plasmocytes significantly decreased over time in all groups . Macrophages , giant cells , eosinophils , and fiber condensation presented no differences among groups and periods . Within 90 days , all groups presented complete hard tissue barrier formation . CONCLUSIONS The presence of mineral trioxide aggregate in MTA Fillapex composition did not improve the bone tissue repair . The presence of sealers provided the re-establishment of the original bone tissue structure and the inflammatory response decreased over time , so they can be considered biocompatible Clinicians often witness impressive treatment results in practice and may wish to pursue research to formally explore their anecdotal experiences . The potential to further new knowledge both within the profession and to the greater healthcare system is compelling . An obvious next step for a practitioner considering research is to connect with experienced research ers to convey their idea for a study , who may in turn ask , “ What is your research question ? ” With limited underst and ing of how to respond , this interaction may result in the first and last experience these clinicians will have with the research community . It has been estimated that between 1 % and 7 % of the chiropractic profession in Canada is engaged in research . 1,2 Arguably , this low engagement could be the result of practitioners ’ perceived importance of research and levels of research literacy and capacity . However , increasing dem and s for evidence -based approaches across the health system puts pressure on all clinicians to base their decisions on the best available scientific evidence . Lack of clinician representation in research has the probable effect of limiting growth and new developments for the profession . Furthermore , lack of clinician involvement in research complicates the transfer of study findings into practical setting s. The Canadian Institutes of Health Research describes integrated knowledge translation as a process that involves collaboration between research ers and knowledge users at all stages of a research project.3 This necessitates involvement of clinicians to help in forming a research question , interpreting the results , and moving research findings into practice . This shared effort between clinicians and research ers increases the likelihood that research initiatives will be relevant to practice .3 Conversely , it has been reported that there is a growing communication gap between clinicians and academics in chiropractic . 4 Clinicians have important practice -related questions to ask , but many may lack the ability to map out their research strategy , specifically in communicating their question in a manner required to develop a research protocol . David L. Sackett , Officer of the Order of Canada and the founding Chair of Canada ’s first Department of Clinical Epidemiology & Biostatistics at McMaster University , highlights the importance of mapping one ’s research strategy in exploration of the research question : “ one-third of a trial ’s time between the germ of your idea and its publication in the New Engl and Journal of Medicine should be spent fighting about the research question . ” ( personal communication , November 30 , 2011 ) We describe a r and omized controlled trial ( RCT ) example to highlight how clinicians may use existing literature and the PICOT format to formulate a research question on treatment efficacy AIM The aim of this study was to evaluate pigmentation and tissue response to four endodontic sealers placed in the oral mucosa of rabbits by either submucous injection or implant in polyethylene tubes . METHODOLOGY Thirty white New Zeal and rabbits were divided r and omly into two groups of eight for N-Rickert and AH-26 , and two groups of seven for Fillcanal and Sealer 2 6 . On the right side of the filter , corresponding to the gingivo-labial sulcus in humans , the sealer was injected ; on the left side the sealer was placed within a polyethylene tube and implanted . Direct clinical observations were made at 30 , 60 and 90 days . The animals were then sacrificed for histological analysis . RESULTS After 60 days of observation N-Rickert and AH-26 produced tattoos that became larger by 90 days . Submucous injection produced larger and more numerous pigmentation , when compared to implant in polyethylene tubes . N-Rickert sealer displayed larger and more numerous tattoos when compared to AH-26 . Histological analysis showed no differences between the two methods of implantation . All sealers elicited some kind of inflammatory response ; the most irritant was Fillcanal , followed by N-Rickert and AH-26 . Sealer 26 elicited a mild reaction only . CONCLUSIONS Under the conditions of this study there was no relationship between the method of implantation and the tissue response ; the silver-containing sealers produced pigmentation , and the concentration of silver influenced the quantity and size of the tattoos . The sealers elicited various responses when in direct contact with the surrounding tissues : the calcium hydroxide-containing sealer had enhanced healing when compared to the other sealers In regard to biological properties of  endodontic sealers  , there are many characteristics that should be considered . The aim of this study was to examine the biological effects of new calcium phosphate-based root canal sealers , CAPSEAL I and CAPSEAL II ( CPS ) , on human periodontal fibroblast cells by examining the expression levels of inflammatory mediators and to compare the effects of CPS on the viability and osteogenic potential of human osteoblast MG63 cells compared to those of other commercially available calcium phosphate sealers [ Apatite Root Sealer type I ( ARS I ) and Apatite Root Sealer III ( ARS III ) ; Sankin Kogyo , Tokyo , Japan ] and a zinc oxide eugenol-based sealer ( Pulp Canal Sealer EWT [ PCS EWT ] ; Kerr , Detroit , MI ) . The levels of IL-6 in the new CPS group ( CAPSEAL I , II ) were higher than those in the control and all experimental groups at all time points after 2 h. TGF-β1 and FGF-1 levels decreased at 72 h compared to the levels in the control , in cells treated with every sealers except ARS I. The new CPS sealers showed low cytotoxicity . Reverse transcription polymerase chain reaction showed that CAPSEAL I , II , and Apatite Root Sealer type III induced expression of early stage markers of differentiation ( alkaline phosphatase and osteopontin ) at 7 days . Also , new CPS showed higher mineralized nodule formation at 28 days . These results suggest that CAPSEAL I and II facilitate the periapical dentoalveolar and alveolar healing by controlling cellular mediators from PDL cells and osteoblast differentiation of precursor cells Background Systematic Review s ( SRs ) of experimental animal studies are not yet common practice , but awareness of the merits of conducting such SRs is steadily increasing . As animal intervention studies differ from r and omized clinical trials ( RCT ) in many aspects , the methodology for SRs of clinical trials needs to be adapted and optimized for animal intervention studies . The Cochrane Collaboration developed a Risk of Bias ( RoB ) tool to establish consistency and avoid discrepancies in assessing the method ological quality of RCTs . A similar initiative is warranted in the field of animal experimentation . Methods We provide an RoB tool for animal intervention studies ( SYRCLE ’s RoB tool ) . This tool is based on the Cochrane RoB tool and has been adjusted for aspects of bias that play a specific role in animal intervention studies . To enhance transparency and applicability , we formulated signalling questions to facilitate judgment . Results The result ing RoB tool  for animal studies contains 10 entries . These entries are related to selection bias , performance bias , detection bias , attrition bias , reporting bias and other biases . Half these items are in agreement with the items in the Cochrane RoB tool . Most of the variations between the two tools are due to differences in design between RCTs and animal studies . Shortcomings in , or unfamiliarity with , specific aspects of experimental design of animal studies compared to clinical studies also play a role . Conclusions SYRCLE ’s RoB tool is an 
    Output:
    