Question:
You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:
dental materials contain a great variety of different monomers and additives.1 because of the complex chemical composition and the incomplete monomer
polymer conversion , several components are leached out from each resin - based restorative material into the oral environment.2,3 this in turn may cause some adverse effects.4 previous studies have used in vitro cytotoxicity tests to evaluate the biological risks of resin composites used in dentistry.1,5 cytotoxicity tests have primarily focused on restorative materials such as glass ionomers , dental adhesives and composite resins.68 however , fewer studies on prosthodontic materials have been published , and investigations regarding the cytotoxicity of provisional prosthodontic materials are even more limited.5,9 provisional restorations are used in the interim between tooth preparation and fitting a definitive restoration . the length of time between preparation of teeth and cementation of final restorations can vary from a few days for straightforward cases , to several weeks or even , in the case of complex reconstruction , several months .
provisional restorations are generally essential to cover freshly cut dentine , stabilize the position of the prepared tooth , regain chewing function and phonation , maintain esthetic appearance and evaluate the minimal thickness of the definitive restoration .
they can also help stabilize the periodontal condition prior to definitive restoration.10 provisional materials can be classified by the type of resin .
acrylic polymethyl or polyethyl methacrylates belong to the oldest group of provisional materials . the latest class of materials is formed by bis - acryl composite resins , which are comparable to composite resins used for direct restoration therapy.10 they consist of an organic matrix and inorganic fillers .
bis - acryl composites produce less heat and shrinkage during polymerization than other resins , resulting in a better marginal fit.11 aesthetically they are reasonable and are more color stable than polymethyl or polyethyl methacrylates.12 most recently , visible light cured resins have been introduced based on urethane dimethacrylate .
these resins have good mechanical properties , being light cured , the operator has some control over the material s working time and colour is relatively stable but marginal fit can be poor.10,13 acrylates and mainly methacrylates were found to cause cytotoxic effects.14 evaluation of the cytotoxicity of dental resin materials showed a relationship between their composition and the degree of cytotoxicity.15 continuous cell lines , like l929 mouse fibroblasts are being routinely used for the testing of cytotoxic properties of dental materials because of their reproducible growth rates and biological responses.1 the purpose of this in vitro study was to evaluate the effect of current bis - acryl and urethane dimethacrylate based provisional materials on the fibroblast cell viability .
two of the tested materials were bis - acryl based ( tempofit duomix , detax , germany & protemp 3 garant , 3 m espe , germany ) and one was urethane dimethacrylate based ( revotek lc , gc corporation , japan ) provisional restoration materials .
test specimens were prepared according to the manufacturers instructions in standard teflon discs , 5 mm in diameter and 2 mm of height .
all specimens were prepared and handled under aseptic conditions to limit the influence of biological contamination on the cell culture tests .
specimens were prepared between mylor and glass slabs to minimize the oxygen inhibition and maximize the surface smoothness .
tempofit duomix is a two - part base / catalyst , hand - mix , self - curing and bis - acrylic composite based provisional restoration material .
base and catalyst were extruded equal amounts by pressing onto piston in the dispenser onto mixing pad .
protemp 3 garant is a two - part base / catalyst , auto - mix , self - curing and bis - acrylic composite based provisional restoration material . using the garant dispenser ,
the base and catalyst were extruded directly into the teflon disc and after 2 min 30 sec curing completed .
revotek lc is a light cure single component sculptable composite resin for temporary restorations . using a spatula required amount of material dispensed and applied into the teflon disc .
the specimen was light - cured for 6 sec by led light curing unit ( led , bluephase , ivoclar vivadent , liechtenstein , austria ) .
the samples immersed in 7 ml culture medium for 24 hours at 37c to extract residual monomer or cytotoxic substances .
the culture medium containing material extracts were sterile filtered to use on the cell cultures .
l929 fibroblast cell line ( atcc ccl 1 ) cultured in basal medium eagle ( bme ) , biological industries , israel ) containing 10% new born calf serum ( biochrom ag , berlin , germany ) and 100 mg / ml penicilin / streptomysin ( biological industries , israel ) at 37c in a humidified atmosphere of 95% air/5% co2 .
confluent cells were detached with 0.25% trypsin and seeded at a density of 510 well in 96-well plate at 37c under 5% co2 for 24h and .
after 24 hours incubation , culture medium was replaced with 200 l of culture medium containing material extracts of provisional restoration materials .
the succinic dehydrogenase activity has been shown to be reasonably representative of mitochondrial activity in the cells and reflects both cell number and activity.16 the old medium removed and cell cultures were rinsed with phosphate buffer saline ( pbs ) and 200 l aliquots of freshly prepared mtt [ 3-(4,5-dimethyl - thiazol-2-yl)-2,5-diphenyl - tetrazolium bromide , sigma aldrich , germany ] solution ( 0.5 mg / ml in bme ) were added to each well . after a 2h incubation period ( 37c , 5% co2 )
the supernatant was removed and the intracellulary stored mtt formazan was solubilized in 200 l dimethyl sulfoxide for 30 min at room temperature .
twelve replicate cell cultures were exposed to a constant concentration of a single material in at least two independent experiments .
l929 fibroblast cell line ( atcc ccl 1 ) cultured in basal medium eagle ( bme ) , biological industries , israel ) containing 10% new born calf serum ( biochrom ag , berlin , germany ) and 100 mg / ml penicilin / streptomysin ( biological industries , israel ) at 37c in a humidified atmosphere of 95% air/5% co2 .
confluent cells were detached with 0.25% trypsin and seeded at a density of 510 well in 96-well plate at 37c under 5% co2 for 24h and .
after 24 hours incubation , culture medium was replaced with 200 l of culture medium containing material extracts of provisional restoration materials .
the succinic dehydrogenase activity has been shown to be reasonably representative of mitochondrial activity in the cells and reflects both cell number and activity.16 the old medium removed and cell cultures were rinsed with phosphate buffer saline ( pbs ) and 200 l aliquots of freshly prepared mtt [ 3-(4,5-dimethyl - thiazol-2-yl)-2,5-diphenyl - tetrazolium bromide , sigma aldrich , germany ] solution ( 0.5 mg / ml in bme ) were added to each well . after a 2h incubation period ( 37c , 5% co2 ) the supernatant was removed and the intracellulary stored mtt formazan was solubilized in 200 l dimethyl sulfoxide for 30 min at room temperature .
twelve replicate cell cultures were exposed to a constant concentration of a single material in at least two independent experiments .
in contrast , protemp 3 garant group demonstrate full cell density in figure 2(c ) .
the results showed that , eluates of the revotek lc and protemp 3 garant lead to 99% and 101% cell survival . statistically revotek lc and protemp 3 garant were not cytotoxic for cells when compared to control group ( p>.05 ) .
tempofit duomix was cytotoxic for cells when compared to control group and other tested materials ( p<.05 ) .
the literature contains descriptions of cell - culture tests with various cell types to establish cell damage caused by dental materials.17 in the present study the effect of two bis - acryl and one urethane dimethacrylate based commercially available provisional restoration materials on fibroblast cells were investigated by mtt test .
fibroblasts are the targets of any chemical components that may be released from the dental restorative materials .
l929 fibroblast cells were selected due to its availability , popularity and efficiency to grow in vitro.18 mtt assay is a well - established method for analyzing cell viability.16 the viability and proliferation of the cells are assessed by means of the functional state of the cell mitochondria.19 mitochondrial dehydrogenases in living cells reduce the yellow tetrazolium salt , mtt ( 3-(4,5-dimethyl ) thiazol-2-yl ) 2,5 diphenyltetrazolium bromide ) to blue mtt formazan , which is then retained in the cell .
formation of the formazan product has been found to correlate well with number of viable cells.8,19,20 today , bis - acryl composites possess considerable amount of the market share for tooth colored provisional material .
main advantages of bis - acryl provisional materials include a lower curing temperature , reduced polymerization shrinkage ( 5% ) with improved marginal fit , and minimal odour and taste.13,21 the low setting temperature of these materials allows them to be used directly with decreased risk of pulpal injury.22 in addition , bis - acryls are gaining in popularity , in part because of their cartridge delivery system .
this dispensary method not only is convenient but also may allow for a more accurate and consistent mix.21 dental practitioners have clearly welcomed these products and very limited data can be available about their cytotoxicity and biocompatibility . in present study , two of the tested provisional restoration material was bis - acryl based which are chemically very similar to bisphenol - a - glycidyl methacrylate ( bis - gma ) composites . according to our results , eluates from tempofit duomix lead to 88% cell survival and when compared to control group and other tested materials it was cytotoxic for cells ( figure 2a  b ) . on the hand protemp
3 garant , the other bis - acryl based provisional material , was not cytotoxic for l929 fibroblast cells ( figure 2c ) .
the modifications include a newly developed monomer system , not with the rigid intermediate chain characteristic of some bis - gma homologues , but with a somewhat flexible chain in comparison to other synthetic resins ( espe technical product profile ) .
however , manufacturer of tempofit duomix do not state any difference in monomer formulation . probably as most other bis - acryl
based provisional materials , the organic polymer matrix of tempofit duomix is composed of traditional monomers such as bis - gma , triethylene glycol dimethacrylate ( tegdma ) or similar monomer systems .
patents may also hinder objective research.23 only available composition of the resin cements tested in this study .
current investigations reported the cytotoxic effects of some resin monomers , such as bis - gma , tegdma and urethane dimethacrylate ( udma).24,25 these resin monomers are able to deplete intracellular glutathione as well as interfere with the expression of some proteins , such as collagen i , osteonectin , and dentin sialoprotein , which play a fundamental role in the pulp repair.26,27 among the tested materials , revotek lc is the only udma based and light cure provisional material .
geurtsen et al1 reported that udma is as cytotoxic as bis - gma and tegdma .
elution of residual monomers from resin materials related to degree of their polymerization , properties of resin composition , and chemistry of organic solvents in vitro situation.28 altntas et al29 demonstrated that leaching of udma was lower than bis - gma and tegdma from a resin cement .
consequently , in present study , eluates of the revotek lc showed similar cytotoxicity with control group .
the results of this study demonstrated that cytotoxic potential may vary among provisional materials . taking into consideration the limitations of this in vitro study
, provisional restoration materials may have cytotoxic effects and should be selected carefully for clinical applications .

Answer:
objectives : the aim of the present study was to evaluate the cytotoxic effects of three different provisional restoration materials on fibroblasts . two bis - acrylic based [ tempofit duomix ( detax ) , protemp 3 garant ( 3 m espe ) ] and one urethan dimethacrylate [ revotek lc ( gc corporation ) ] based provisional restoration materials used.methods:materials were prepared according to the manufacturers instructions in standard teflon disks ( 25 mm ) and four samples were extracted in 7 ml of basal medium eagle with 10% new born calf serum and 100 mg / ml penicillin / streptomycin for 24 hours .
 the l929 fibroblast cells were plated ( 25.000 cells / ml ) in well plates , and maintained in a co2 incubator at 37c for 24h . after 24 hours
 , the incubation medium was replaced by the immersed medium in which the samples were stored and the l929 fibroblasts were incubated in contact with eluates for 24 hours at 37c for 24h .
 the fibroblast cell viability was analyzed by measuring the mitochondrial activity with the methyltetrazolium test ( mtt ) .
 twelve well used for each specimen and experiment repeated for two times .
 the data was statistically analyzed by mann - whitney u tests.results:the results showed that , revotek lc and protemp 3 garant were not cytotoxic for fibroblast cells when compared to control group ( p>.05 ) .
 however , tempofit duomix was cytotoxic for l929 fibroblasts when compared to control group and other tested materials ( p<.05).conclusions : taking into consideration the limitations of an in vitro study , our study indicate that provisional restoration materials might have cytotoxic effects on fibroblasts and should be selected carefully for clinical applications .


Question:
You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:
zonisamide ( zns ) is an antiepileptic drug that has recently been approved in many countries .
it is also effective for the management of migraine , neuropathic pain , essential tremor , anxiety , and other conditions .
recently , zns has been approved as a new adjunctive therapy for motor complications of parkinson 's disease ( pd ) in japan .
more recently , zns was reported to be effective for the management of impulse control behavior in pd , suggesting potential effects on non - motor pd symptoms .
dream enactment associated with aggressive , violent behavior can carry a serious risk of injury to patients , as well as to spouses or caretakers .
we describe a patient with pd who had vivid nightmares and dream - enacting behavior that resolved after treatment with zns .
in 2009 , a 71-year - old man with a history of pulmonary surgery noticed tremor of the left hand and akinesia . in march 2010 , he showed features of moderate parkinsonism , including masked face , stooped posture , bradykinesia , left - side - dominant rigidity , and resting tremor .
bradykinesia , rigidity , and resting tremor responded to treatment with pramipexole ( 0.5 mg / day ) . since july 2010 ,
his wife was awakened nearly every night because of the patient 's aggressive or violent behavior during the middle of the night .
for example , he suddenly flew up or walked , collided with furniture or walls , cried out , or exercised his limbs noisily .
he was often injured . on the nights he presented with this behavior , he remembered having vivid nightmares , such as being chased by a cat , bear , or his wife or of fighting with a thief or grandchild .
interviews with the patient 's wife indicated that this aggressive , violent behavior during the night occurred sometimes in 2009 . in april 2011 , stooped posture and lumbar pain developed , which were attributed to pramipexole .
we switched from pramipexole ( 1.0 mg / day , once before sleep ) to zns ( 25 mg / day , once before sleep ) .
before switching to zns , motor and non - motor symptoms were as follows : the scores on parts i , ii , iii , and iv of the unified parkinson 's disease rating scale ( updrs ) were 3 , 5 , 17 , and 0 , respectively .
the scores on the mini - mental state examination ( 29/30 ) and frontal assessment battery ( 18/18 ) were normal .
the heart - mediastinum 123i - metaiodobenzylguanidine uptake ratio was significantly decreased . because he noticed reduced olfactory sensitivity
, we assessed olfactory recognition ability by using the odor stick identification test for japanese ( osit - j ) , as described previously .
briefly , the osit - j tests for 13 kinds of odors familiar to japanese people ( curry , cooking gas , perfume , japanese cypress , india ink , menthol , nattou [ fermented soybeans]/sweaty socks , rose , putrid smell , wood , roasted garlic , condensed milk , japanese orange ) .
we asked the patient to choose an answer among four possible odor names , one of which was correct , plus
detectable but not recognizable and  odorless. he could identify four odors ( perfume , curry , cooking gas , and condensed milk ) .
the identification rate was 33% , consistent with that of patients with olfactory disturbances ( 36  34% ) .
the score on the pittsburgh sleep quality index ( ranging from 14 for normal to 56 for unsleeping ) was 16 , and the 2-point increase above normal was ascribed to difficulty in sleeping caused by nightmares .
his wife was no longer awakened since the patient 's aggressive and violent behavior had resolved .
we obtained informed consent from the patient and tested whether pramipexole elicited nightmares or violent behavior .
first , he was given pramipexole ( 0.5 mg / day ) in the context of stable doses of zns ( 25 mg / day ) for 2 weeks .
our patient showed aggressive and violent behavior associated with vivid nightmares , which probably preceded such behavior , during the middle of the night .
this disorder strongly suggested a rapid - eye - movement sleep behavior disorder ( rbd ) . in our patient , who had rbd
dopamine agonists can lead to vivid dreams , nightmares , and parasomnia - like motor activity , but rbd in our patient was not induced by rechallenge with pramipexole . in patients with pd ,
pramipexole was reported to be effective for rbd , but to worsen rem sleep electromyographic abnormalities on video - polysomnography .
one study showed that pramipexole did not improve rbd in pd , and the authors mentioned that rbd in pd may be either 2 different stages of the same condition or 2 completely different conditions .
this can explain our observations during treatment with pramipexole , but we believe that pramipexole did not alter rbd in our patient since the wife 's interviews indicated that rbd was evident before starting pramipexole .
this notion is supported by the results of a previous study   showing that the frequency and severity of rbd were unaffected by pramipexole therapy .
however , our finding raises an open question whether zns is useful for treating rbd in patients with early pd .
dream generators are suppressed by inhibition of brainstem locomotor pattern generators , which can modify dream content in rbd .
dopaminergic dysfunction may play a role in the pathophysiology of rbd   and dopamine modulates the expression of locomotion and other rhythmic motor patterns in neural circuits known as central pattern generators . a zns - induced effect on the dopaminergic system
might have modulated or inhibited brainstem locomotor pattern generators , consequently suppressing vivid nightmares , leading to the resolution of dream - enacting behavior .
our experience suggests that zns potentially might be effective for the management of vivid nightmares or dream - enacting behavior in patients with early pd .
the authors report no conflicts of interest . there was no financial disclosure related with this work .

Answer:
recently , zonisamide ( zns ) has been approved as a new adjunctive therapy for motor complications of parkinson 's disease ( pd ) .
 more recently , zns was reported to be effective for the management of impulse control behavior in pd , suggesting potential effects on non - motor pd symptoms .
 dream enactment associated with aggressive , violent behavior can carry a serious risk of injury to patients , as well as to spouses or caretakers .
 this report describes a patient with pd who had vivid nightmares and dream - enacting behavior that resolved after treatment with zns .
 the present case raises the question whether zns might potentially be effective for the management of vivid nightmares or dream - enacting behavior .


Question:
You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:
the occurrence of screw loosening is reported to be 12.7% in single tooth restoration and 6.7% in partial fixed prostheses .
23 jemt et al.4 observed that most of the screw loosening occurred within a year and the frequency of screw loosening was reduced over time .
henry et al.5 and khraisat et al.6 stated that screw loosening is more frequent in external type implants .
in internal type connections , the stability of the prosthesis is obtained from the clamping force of the screw joint and the frictional force created by contact between the conical mating parts of the implant - abutment assembly .
because of this connection , internal type implants have more favourable stress distribution , better stability , and superior resistance to lateral load.7 however , tsuge and hagiwara8 presented no significant difference between internal and external implant - abutment connections concerning their effect on the abutment screw loosening .
theoharidou et al.9 also reported that the frequency of screw loosening in single tooth restoration was 2.7% in external type implants and 2.4% in internal type implants ; this difference was not statistically significant .
the frequency of screw loosening is reduced over time , but still occurs in spite of recent advances in the design and screw materials .
screw loosening produces discomfort for patients ; therefore , methods to prevent screw loosening are needed .
one method for preventing screw loosening that is easily applicable to clinical practice is retightening .
gradual functional loading causes sliding of the screw thread and relief of screw extension induced by preload .
gradual reduction of preload below a critical point causes screw turning . applying a greater preload on the screw in the first phase of screw loosening
siamos et al.11 reported that in order to minimize the loss of preload , it is necessary to retighten the screw 10 minutes after the first screw tightening .
however , the retightening procedure may change the shape of the abutment screw and the inner screw thread of the implant ; hence , stability during function may be affected.12 in addition , conflicting results on the effect of retightening have been reported . according to tzenakis et al.,13
if the abutment screw is repeatedly retightened , a higher preload can be obtained because of surface wear that can lower the coefficient of friction .
however , weiss et al.14 reported that repeated tightening / removal procedures decreased the reverse torque value ( rtv ) of screws .
riccardi - copped et al.15 reported that repeated tightening and removal of titanium screws caused the rtv to decrease gradually .
the effect of screw retightening remains controversial and on the timing and frequency of retightening are lacking .
the aim of this study was to assess the effect of dynamic loading and screw retightening on rtv in external and internal connection type implants .
twenty external type implants ( diameter , 4 mm ; length , 10 mm ; sola , shinhung , seoul , korea ) and 20 internal type implants ( diameter , 4 mm ; length , 10 mm ; luna , shinhung , seoul , korea ) were used ( fig .
1 ) . abutments for cementretained prostheses ( diameter , 5 mm ; gingival height , 5.5 mm ; esthetic abutment for external implant and duo abutment for internal implant , shinhung , seoul , korea ) were connected to each implant ( fig .
each implant and abutment assembly was held in a customized jig in all testing procedures . using a digital torque controller ( mgt 12 , mark-10 co. , new york , ny , usa )
after 10 minutes , the assemblies were retightened with 30 ncm torque to compensate for embedment relaxation.11 after tightening the screws twice , an initial measurement of rtv was made .
the implant / abutment assemblies were divided into 4 groups ( 10 assemblies per group ) in order to evaluate the effect of intermittent retightening : 1 ) ext - n , external type implant with no retightening ; 2 ) ext - rt , external type implant with retightening ; 3 ) int - n , internal type implant with no retightening ; 4 ) int - rt , internal type implant with retightening .
the implant / abutment assemblies were fitted to the mounting base of a universal testing machine ( electroplus e 3000 , instron , washington dc , wa , usa ) with the long axis of the implant fixed at 30 degrees relative to the vertical axis ( fig .
the testing device delivered sine curved cyclic loading between 20 and 250 n at 14 hz for 100,000 cycles . in the groups with no retightening ( ext - n and int - n ) , the rtv was measured after 100,000 cycles of loading , while rtv was measured after 3 , 10 , and 100 cycles as well as every 20,000 cycles in the retightening groups ( fig .
3 ) . for all statistical evaluations , spss version 20.0 , spss inc . ,
one - way analysis of variance ( anova ) was used for comparing rtv depending on the implant system and retightening . when the rtv was measured repeatedly after various loading cycles ,
tukey 's test was used for post hoc comparisons , and the significance level was set at =0.05 .
the initial rtvs were 27.8  1.3 ncm in external implants and 25.1  1.9 ncm in internal implants .
both implant systems showed decreased rtvs when compared with the tightening torque value of 30 ncm .
the initial rtv of external implants was significantly higher than that of internal implants ( p<.05 ) .
the rtvs of all implant / abutment assemblies were significantly reduced after cyclic loading ( p<.05 , table 1 , table 2 ) .
the rtvs of the groups without retightening were 25.4  1.2 ncm in the ext - n group and 15.8  1.8 ncm in the int - n group .
the ext - n group showed a significantly higher rtv when compared with the int - n group ( p<.05 ) .
the rtvs of the groups with retightening were 23.8  1.8 ncm in the ext - rt group and 19.9  3.3 ncm in the int - rt group .
the ext - rn group showed a significantly higher rtv than the int - rn group ( p<.05 ) . in external implants
on the other hand , retightened internal implant / abutment assemblies showed superior rtvs when compared to internal implants with no retightening ( table 1 , table 2 ) .
screw loosening is the most frequently occurring mechanical complication of implant restorations.516 abutment screw loosening has been reported in a large number of studies with an incidence ranging from 2% to 15% of abutments .
2359 screw loosening is caused by inadequate tightening torque , settling of implant components , inappropriate implant position , inadequate occlusal scheme or crown anatomy , poorly fitting frameworks , improper screw design / material , and heavy occlusal forces.171819 to overcome screw loosening and joint instability , many technical solutions have been suggested .
for example , new abutment screw designs and materials for maximizing preload,120 mechanical torque - applying instruments for optimizing tightening torque,21 precise implant components for antirotation , and internal conical connection implants with no micromotion or microgaps have been proposed . in the current study ,
the initial rtv was always smaller than the tightening torque ( 30 ncm ) in external and internal type implants .
haack et al.22 reported that most of the tightening torque is used to overcome the friction of the surface and only 10% of the tightening torque is used to generate preload .
they suggested that 75 - 80% of tightening torque remained in titanium or gold screws.22 kim et al.23 reported that the amount of remaining torque was affected by the screw material ( 77% remained in titanium alloy and 66% remained in gold alloy ) . for standardization of the results ,
the same titanium alloy was used for both internal and external abutment screws in the present study .
the results showed that the remaining torque was 90.9% in external implants and 83.3% in internal implants .
these relatively high remaining initial rtvs might have been caused by advanced milling technique and/or the screw design / material .
in the current experiments , initial rtvs and post - cyclic loading rtvs were higher in external implants than in internal implants .
this is a result of the difference in connection type between the implants . in external implants ,
joint stability is obtained by the tension of the screw , while it is achieved mainly by friction between the abutment and the implant in internal type implants.24 most of the tightening torque is used to produce preload in external implants,25 while in internal implants , tightening torque is distributed between friction with the abutment and preload on the screw .
moreover , internal implants are susceptible to the wedge effect , which arises when tightening torque and mechanical load are applied , leading to axial displacement of the abutment , so that the tensile force of the screw is lost and preload is decreased.232425 according to lee et al.24 and kim et al.,25 axial displacement of the abutment is greater in internal implants , while rtv is greater in external implants .
although screws from the same manufacturer were used for standardisation , the screws for external implants have longer threads than those of the screws used for internal implants ( fig .
1 ) . the thread - engaging surface may affect the preload in screw - tightening procedures .
to our knowledge , no internal / external implant system manufactured by the same manufacturer offers either similar or identical screw shapes owing to the different inner structures of internal / external implants .
although the 2 implant systems had different screw sizes and dimensions , the lengths of the engaging or the mating threads were similar in both.24 the upper part of the thread in the screw of the external implant was not in contact and just passed through the inner surface of the implant .
comparison of the groups with and without retightening after cyclic loading revealed no significant differences in rtvs in external implants .
however , in internal implants , retightening resulted in higher rtvs than those found in implants without retightening .
these results can be explained by the difference in connection type between the implants and the number of times the implants were retightened . in internal type implants , less settling effect occurs during tightening and loosening procedures , because tightening torque generates less preload due to dissipation of force via friction between the abutment and the implant .
therefore , a greater number of retightening procedures allows more settling effect and making an adequate surface of the screw .
cardoso et al.26 found that rtvs decreased as the number of insertion / removal cycles increased in external type implants .
in contrast , tzenakis et al.13 reported an increase of preload in internal type implants .
therefore , retightening of screws is strongly recommended for joint stability , especially in internal type implants .
the appropriate number of retightening procedures is not clear from the results of previous studies .
tzenakis et al.13 reported a gradual increase in gold screw preload from tightening for the first time to retightening 5 and 10 times in internal type implants . in the current study
it should be noted that retightening more than 5 times is not recommended for the maintenance of preload . in the present study ,
this phenomenon was observed in both external and internal type implants . according to delben et al.,27 rtvs
were maintained constantly by retightening after every 100,000 cycles of loading in external type implants . according to binon and
mchugh,28 the average daily number of mastication is about 2,700 and so 100,000 cycles corresponds to around one month . in the current study ,
the load cycle was decreased to 20,000 cycles ( corresponding to one week ) in order to infer the timing of retightening , because previous studies found no significant differences with 100,000 load cycles . in the current experiments ,
rtvs decreased only 10 rounds of cyclic loading in external and internal type implants . in our previous study,24
thus , axial displacement of the abutment screw can affect joint stability , especially in internal implants . to increase preload and secure joint stability ,
it is recommended that retightening be performed after 10 loading cycles for both external and internal implants . moreover , retightening after 1 week is also profitable for internal type implants .
this study evaluated rtv according to retightening and cyclic loading in external and internal type implants .
initial rtv and postcyclic loading rtv were higher in external implants than in internal implants . in external type implants ,
retightening did not produce a significant difference in rtv when compared with the non - retightening group after 100,000 rounds of cyclic loading . in internal type implants ,
the retightening group showed significantly increased rtvs when compared with the non - retightening group after cyclic loading .
a decrease in rtv occurred after only 10 rounds of cyclic loading , which represents the early stage of cyclic loading .
after 20,000 cycles of loading , rtvs were maintained constantly in both external and internal type implants .

Answer:
purposethe aim of this study was to evaluate the effect of cyclic loading and screw retightening on reverse torque value ( rtv ) in external and internal type implants.materials and methodscement - retained abutments were connected with 30 ncm torque to external and internal type implants .
 experimental groups were classified according to implant connection type and retightening / loading protocol . in groups with no retightening
 , rtv was evaluated after cyclic loading for 100,000 cycles . in groups with retightening ,
 rtv was measured after 3 , 10 , 100 cycles as well as every 20,000 cycles until 100,000 cycles of loading.resultsevery group showed decreased rtv after cyclic loading . before and after cyclic loading , external type implants had significantly higher rtvs than internal type implants . in external type implants , retightening did not affect the decrease in rtv .
 in contrast , retightening 5 times and retightening after 10 cycles of dynamic loading was effective for maintaining rtv in internal type implants.conclusionretightening of screws is more effective in internal type implants than external type implants .
 retightening of screws is recommended in the early stage of functional loading .


Question:
You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:
pelvic fractures and in particular crescent fracture dislocations , which are characterised by disruption of the sacroiliac joint with extension proximally as a fracture of the posterior iliac wing , usually occur as a result of high velocity trauma ( 1,2 ) .
osteopenia and the associated loss of bone trabeculae decreases the elastic resistance of the osseous elements of the pelvis , thus making the pelvis a common location for insufficiency fractures ( 3 ) . as the general population ages , the number of osteopenic specific pelvic fracture patterns are likely to increase . in cases where surgical fixation is required ,
less invasive techniques are beneficial in this older population ( 3 ) . the unique fracture pattern described in this report occurred as a result of the patient falling in such a way as to result in simultaneous sudden flexion of one hip with extension of the contra - lateral hip , into a position known in athletic terms as the front splits . the combination of the torque force produced by the fall and the patients reduced bone mineral density resulted in a unique , unstable pelvic fracture . to our knowledge
this is the first reported case of bilateral crescent fractures , and the first reported case of pelvic fracture as a result of this mechanism of injury .
the authors have obtained the patient 's informed written consent for print and electronic publication of this case report .
a 57 year old woman slipped while shopping resulting in a fall , where - upon her right hip flexed to 90 degrees and her left hip extended to 90 degrees , to a point where her perineum came to rest on the floor .
this particular fall resulted in a twisting or torque like force being transmitted through her pelvis as she fell .
she attributed the increased pain that she was experiencing to aggravation of her long standing back complaint . prior to her fall
she had attended the spinal clinic for her back pain and was scheduled for a bone scan with a view to progressing to facet joint blocks .
on attendance at the spinal clinic following her scan it was noted that her low back pain had become more pronounced and she required walking aides in the form of crutches to mobilise . on reviewing the bone scan ,
further imaging , both plain film and computed tomography ( ct ) ( fig.1 & fig .
2 ) revealed extensive pelvic fractures with displaced bilateral superior and inferior pubic rami fractures and bilateral posterior ring crescent fractures .
she had no previous fractures and prior to her fall worked as a care assistant .
coronal computerised tomography ( ct ) image demonstrating bilateral posterior iliac wing fractures and sacro - iliac joint disruption three - dimensional ct reconstruction showing both the bilateral crescent and superior and inferior pubic rami fractures following admission , routine blood parameters ( including bone profile ) were all normal and a pelvic mri scan out - ruled any intra - pelvic soft tissue lesions . open reduction and internal fixation of her anterior pelvic ring was undertaken through a stoppa approach , both rami fractures were reduced and plated anteriorly and superiorly . at this time bone and soft tissue samples from the anterior ring were sent for analysis . following reduction and fixation of her anterior pelvis , intra - operative fluoroscopy revealed that her posterior injuries were in an acceptable position .
a 3 cm long vertical incision was made over both anterior inferior iliac spines and supra - acetabular screws were placed from the anterior inferior iliac spines to the posterior inferior iliac spines to fix the bilateral iliac wing fractures .
inlet radiograph at 16 months post surgery demonstrating solid fixation and bony healing post - operative recovery was uneventful .
subsequent dual energy x - ray absorptiometry scanning revealed mild osteopenia for which she is being managed medically .
final follow - up at 16 months demonstrated that the fractures had healed , and the patient was pain free and mobilising unaided ( fig .
these injuries are rotationally unstable , there may also be some vertical displacement but this is limited by the sacrotuberous and sacrospinous ligaments , which typically remain intact ( 1,2 ) .
our patient sustained bilateral crescent fractures and complete bony disruption of her anterior pelvic ring through inadvertently and suddenly performing what is known in athletic terms as the front splits , where one hip is flexed and the other extended to 90 degrees in neutral adduction / abduction .
although this does not fit with the classic description of high energy trauma , the force imparted to the untrained individual s pelvis in performing such an act would be considerable .
another contributing factor is our patients post - operative diagnosis of osteopenia , the associated loss of bone trabeculae decreases the pelvic elastic resistance making it a common location for insufficiency fractures in post - menopausal women ( 4 ) .
day et al ( 5 ) have classified crescent fractures according to the extent of sacroiliac joint involvement , with type i fractures entering the anterior third of the sacroiliac joint , type ii fractures involving the middle third and type iii fractures limited to the posterior third of the sacroiliac joint .
operative stabilisation of these injuries is recommended and aims to achieve accurate reduction of the sacroiliac joint and stabilisation of the associated pelvic ring fracture , thus facilitating early mobilisation and minimising disability due to post - traumatic malunion and osteoarthritis or instability of the sacroiliac joint ( 2,3,6 - 9 )
. however both reduced function and ongoing pain are commonly reported even after technically satisfactory surgery ( 2,7 ) .
pelvic insufficiency fractures are relatively common and should be suspected in older female patients with unexplained hip , groin , buttock , low back pain and/or difficulty with ambulation , particularly if there is any recent history of trauma ( 10 ) . while the majority of these insufficiency fractures may be treated conservatively our patient required surgical fixation due to the unstable nature of her injury . to our knowledge this is the first reported case of bilateral crescent fractures and also of a pelvic fracture occurring as a result of this unique mechanism of injury .

Answer:
a case is presented of a healthy 57 year old female who slipped and fell awkwardly into what is known in athletic terms as the front splits . as a result of her fall she sustained bilateral crescent and superior and inferior rami pelvic fractures .
 successful operative fixation was undertaken by a combination of open and percutaneous techniques . to our knowledge
 this is the first reported case of bilateral crescent fractures , and of a pelvic fracture as a result of this mechanism of injury .


Question:
You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:
supravalvar mitral ring is a circumferential ridge or membrane arising from the left atrial wall overlying the mitral valve and frequently attached to the mitral valve.1 variable in thickness and extent , the ring ranges from a thin membrane to a thick discrete fibrous ridge.2 the membranous variety may be difficult to detect because the membrane often adheres to the anterior mitral valve leaflet while remaining just proximal to the posterior mitral leaflet .
adhesion to the valve may impair the opening of the leaflets , and this impairment may be the main mechanism of mitral valve inflow obstruction in some patients .
in other patients , the ring may be large enough to protrude into the mitral valve inflow and cause obstruction .
the supramitral ring may initially be incomplete and eccentric , allowing for an unobstructed flow through the mitral valve .
however , turbulence can cause a progressive increase in the supravalvar membrane or ridge thickness , worsening mitral inflow obstruction.3 the same mechanism is responsible for the acquired variety of supravalvar mitral stenosis , which occurs after mitral annuloplasty for the repair of mitral regurgitation .
we herein present a case of a supraventricular ring in a 17-year - old male , who presented with syncope .
about 15 years ago , he had undergone a cardiac operation for ventricular septal defect ( vsd ) closure and mitral valve repair . in chest x - ray
both lungs were clear , and the electrocardiogram result showed normal sinus rhythm , had undergone right bundle branch block , and right ventricular hypertrophy .
transthoracic echocardiography , transesophageal echocardiography , and finally cardiac catheterization revealed ejection fraction of 5055% , pulmonary hypertension with pulmonary artery pressure ( pap ) of 80/40 mm hg , pulmonary capillary wedge pressure of 23 mm hg , gradient in the mitral valve plane of 40 mm hg , no residual vsd , no patent ductus arteriosus ( pda ) , bicuspid aortic valve , no aortic insufficiency , no aortic stenosis , no sub - aortic web , normal coronary arteries , mild mitral regurgitation , moderate to severe mitral stenosis , supra mitral valve ring , normal left ventricle size , moderate right ventricle enlargement , and moderate systolic dysfunction .
there was a free floating high redundant obstructive membrane in the left atrium that was attached to the mid portion of the anterior mitral valve leaflet and also in the medial and base of the posterior mitral valve leaflet and large papillary muscles in the left ventricle ( figure 1 ) .
it also extended just adjacent to the lower limb of the left atrium appendage mouth with a small orifice ( 6 mm ) in the lateral side and also multiple small fenestrations ( by 2 dimensional echocardiography ) , resulting in a severely restricted diastolic flow ( mean peak gradient = 9.3 mm hg ) .
this web was not found in mri cine turbo - flash images acquired on a 1.5 t scanner ( magnetom vision - siemens ) in the four - chamber view ( 3a ) and the transverse plane , short - axis view ( figure 2 ) . the patient s ascending aorta , descending aorta , and aortic arch were tortuous with moderate narrowing of the descending aorta distal to the subclavian artery with a systolic gradient of about 30 mm hg , which was suggestive of insignificant coarctation of the aorta .
after heparinization , extracorporeal circulation was established between the venae cava and the ascending aorta . following a median sternotomy ,
there was a long supravalvar muscular band , which was resected ( figure 3 ) .
supravalvar mitral ring rarely occurs as an isolated defect ; other congenital heart defects coexist in 90% of patients .
the mitral valve itself is often abnormal and stenotic at the valvar or subvalvar level ; fusion of leaflets , a small valve orifice , and abnormal papillary muscles are common abnormalities .
shone s complex is a combination of four congenital heart defects : supravalvar mitral ring , parachute mitral valve , subvalvar aortic stenosis , and aortic coarctation .
other common associated lesions in patients with supravalvar mitral ring are ventricular septal defect ( vsd ) , pda , atrioventricular ( av ) canal defect , and tetralogy of fallout.4 uncommonly associated defects include atrial septal defect , cor triatriatum , left superior vena cava , unroofed coronary sinus , partial anomalous pulmonary venous drainage , pulmonary venous obstruction , double - orifice mitral valve , and wolff - parkinson - white syndrome.5 lesions such as transposition of the great arteries , atrioventricular discordance , and double - outlet right ventricle are occasionally complicated by a supravalvar left atrioventricular valvular ring .
obstruction to the mitral inflow results from the reduced area of the mitral valve orifice .
when clinically significant , a diastolic pressure difference occurs between the left atrium and the left ventricle . left atrial and pulmonary venous pressures increase , leading to exudation of fluid into the pulmonary interstitial , which increases lung stiffness .
breathlessness and tachypnea are secondary to the interstitial edema and diminished pulmonary compliance.6 in severe cases , frank pulmonary edema can occur.7 an associated atrial septal defect may decompress the left atrium , reducing or masking the severity of the mitral valve obstruction .
associated lesions such as vsd or pda , which increase the left ventricle output , exacerbate the manifestations of mitral inflow obstruction.8 conversely , a supravalvar mitral ring may be difficult to detect in conditions with a diminished pulmonary blood flow such as tetralogy of fallot.9 persistently elevated pulmonary venous hypertension leads to pulmonary arterial hypertension , rise in pulmonary vascular resistance , and eventual failure of the right ventricle and tricuspid regurgitation .
it also deserves of note that predilection for race , age , and sex has not been found yet .
treatment is the surgical resection of the web , but balloon dilatation is reported to have been successfully performed under fluoroscopic and transesophageal echocardiographic guidance by some authors.10
preoperative identification of a supravalvular mitral ring is the target for obtaining good surgical results . for the identification of this congenital heart disease ,

Answer:
supravalvar mitral ring is a rare congenital heart defect of surgical importance .
 the condition is characterized by an abnormal ridge of the connective tissue on the atrial side of the mitral valve .
 it often substantially obstructs the mitral valve inflow .
 we herein introduce a case of a supravalvar mitral ring in a 17-year - old male , who was admitted to our hospital with cardiac syncope .
 he had undergone a cardiac operation for ventricular septal defect ( vsd ) closure and mitral valve repair 15 years before .
 transthoracic echocardiography , transesophageal echocardiography , and finally cardiac catheterization revealed a neglected supravalvular mitral ring .
 the ring was resected in a second operation , and the patient was discharged from the hospital symptom free .


Question:
You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:
more recently , they have been used in autotransplantation procedures to replace non - restorable teeth .
the transplantation of third molars may help to maintain alveolar bone and enable endosseous implantation without requiring bone regeneration , fulfilling functional and aesthetic demands .
information regarding morphology and number of roots may be especially beneficial for careful extraction and subsequent endodontic procedures in autotransplantation .
relatively few studies have been conducted on the root and canal morphology of mandibular third molars , and there is no available report that specifically examines the use of cone - beam computed tomography ( cbct ) .
cbct was introduced for head and neck applications and consists of a conical radiographic source and a high - performance digital panel detector .
cbct has been used in various applications , including measurements for gingival and dentogingival units , as a preoperative tool in decision making for furcation involvement , evaluation of the facial bony wall , estimation of cancellous bone density , clinical assessment of bone grafting , assessment of root length , and resorption of the root .
it has been suggested that cbct data may provide a better basis for treatment plans .
the main purpose of this study was to investigate the root morphology of korean mandibular third molars , and to evaluate the prevalence of c - shaped ( gutter - shaped ) , two - rooted , and three - rooted mandibular third molars with distolingual roots .
evaluations were performed on 60 male and 77 female patients whose mean age was 35.3  15.3 [ table 1 ] .
descriptive statistics of study population according to the age and gender an i - cat scanner ( imaging sciences international , hatfield , pa , usa ) with a spatial resolution of 10 line pairs per centimeter and an isotropic 0.4-mm voxel size was used for this study .
serial axial cbct images were evaluated continuously by moving the toolbar from the floor of pulp chamber to the apex to determine the number of roots and their morphology , using commercially available software ( m - view , seoul , korea ) .
the incidences of mandibular third molars with one - root , c - shaped roots , two roots , or three roots were evaluated by age group , gender , and topology [ figures 14 ] . to evaluate the bilateral occurrence of one - rooted , c - shaped , and three - rooted mandibular third molars ,
evaluations were performed only on the patients who had bilateral mandibular third molars ( patient n = 77 ) .
cone - beam computed tomography images showing mandibular third molars with one root ( arrow ) mandibular third molars with one root with c - shaped canal ( arrow ) mandibular third molars with two roots ( arrow ) mandibular third molars with three roots having distolingual root ( arrow ) statistical analyses of the occurrences , according the contributing factors , were performed using the chi - square test .
data analysis was done with commercially available software ( pasw statistics 18 , spss inc . ,
the number and percentage of mandibular third molars evaluated in the study group are listed in table 1 .
one hundred and twenty - one teeth ( 56.5% ) were detected to have two roots .
only 3.7% of mandibular third molars had c - shaped roots , and 1.9% had three roots with distolingual roots . calculating the incidence of each type by using the total number of teeth in each age group as the denominator ,
the occurrence of three - rooted teeth in each affected age group ( 20 - 29 , 30 - 39 , 40 - 49 ) increased to a respective 1.0% ( 1/99 ) , 4.2% ( 2/48 ) , and 6.7% ( 1/15 ) .
the percentage of c - shaped roots for the age groups 20 - 29 , 30 - 39 , 50 - 59 , 60 - 69 was a respective 4.0% ( 4/99 ) , 2.1% ( 1/48 ) , 5.6% ( 1/18 ) , and 14.3% ( 2/14 ) .
the overall occurrence of the number of roots in each age group was reported to show significant difference [ p < 0.05 , table 2 ] , and the incidence of multi - rooted third molars tended to increase with patient age .
analysis of incidence of mandibular third molars with one - root , c - shaped root , two roots , or three roots according to age groups the classification of mandibular third molars by root number and gender is seen in table 3 .
using the total number of mandibular molars in male and female patients as the denominator , the incidences of one root ( 31.5% ( 29/92 ) for male versus 42.6% ( 52/122 ) for female ) , c - shaped root ( 4.3% ( 4/92 ) for male versus 3.3% ( 4/122 ) for female ) , two roots ( 63.0% ( 58/92 ) for male versus 51.6% ( 63/122 ) for female ) , three roots ( 1.1% ( 1/192 ) for male versus 2.5% ( 2/112 for female ) were similar between males and females ( p = 0.144 ) .
classification of mandibular third molars by root number and gender classification of mandibular third molars by number of roots and topology is done in table 4 .
the incidences of one root ( 37.3% ( 42/110 ) for right side versus 38.5% ( 40/104 ) for left side ) , c - shaped root ( 3.6% ( 4/110 ) for right side versus 3.8% ( 4/104 ) for left side ) , two roots ( 57.3% ( 63/110 ) for right side versus 55.8% ( 58/104 ) for left side ) , three roots ( 1.8% ( 2/110 ) for right side versus 1.9% ( 2/104 ) for left side ) appeared to be very similar between the right and left sides ( p = 0.919 ) .
classification of permanent mandibular third molars by root number and topology ( right and left side ) an analysis of bilateral and unilateral distribution of mandibular third molars with c - shaped roots , two roots , or three roots having distolingual roots is listed in table 5 . to evaluate the bilateral occurrence of one - rooted , c - shaped , two - rooted , and three - rooted mandibular third molars , only patients who had bilateral mandibular third molars
the incidence rate of each of these types was calculated using the total number of mandibular molars in each group ( the one - rooted , c - shaped , two - rooted , and three - rooted groups ) as the denominator .
bilateral occurrence was more evident for all groups except for the three - rooted group .
calculated bilateral and unilateral distributions for each group are as follows : one - rooted group ( 79.4% ( 50/63 ) for bilateral distribution versus 20.6% ( 13/63 ) for unilateral distribution ) , c - shaped group ( 66.7% ( 4/6 ) for bilateral distribution versus 33.3% ( 2/6 ) for unilateral distribution ) , two - rooted group ( 85.4% ( 70/82 ) for bilateral distribution versus 14.6% ( 12/82 ) for unilateral distribution ) , and three - rooted group ( 0.0% ( 0/3 ) for bilateral distribution versus 100.0% ( 3/3 ) for unilateral distribution ) .
analysis of bilateral and unilateral distribution of mandibular third molars with c - shaped root , two roots or three roots having distolingual root
this study used cbct images to evaluate the number of roots and the morphology of 214 mandibular third molars in 137 korean individuals .
the mandibular third molar , the last tooth in the molar series , is reported to be associated with greater variation in root pattern and canal systems . it is widely accepted that mandibular molars usually have two roots : one located mesially and one distally .
this study showed that highest percentage of mandibular third molars ( 56.5% ) had two roots , which is consistent with previous reports that showed respective results of 53.0% and 53.4% .
the incidence of three roots found for this report was rare ( 1.9% ) , and the additional roots were found in the distolingual area .
an additional root that is located distolingually is called radix entomolaris , and this is a morphological variant identified as an mongolian trait . an additional root located in the lingual area
we found that the overall occurrence of the number of roots according to age groups was significantly different ; specifically , the younger the group , the lower the incidence rate of multi - rooted teeth .
further study with a larger number of patients may be needed to draw conclusions about this apparent trend .
gender predilection for the presence of distolingual roots and c - shaped roots in mandibular third molars was also evaluated in this study .
previous reports have already found no significant differences in third molar development between males and females , and no significant relationship between the gender of the patient and the presence or absence of third molars has been found either .
topological predilection for the presence of either the distolingual root or c - shaped root in mandibular third molars is rarely reported in the literature .
this study observed very similar occurrences between the right and left sides of the same patient 's jaw .
no significant side differences of mandibular third molar mineralization have been reported previously , and prior study found that left - right symmetry in the root development of the mandibular third molar was very high , with a correlation coefficient of 0.93 for males and 0.95 for females .
analysis was performed to evaluate the unilateral or bilateral occurrence of one - rooted , c - shaped , two - rooted , and three - rooted teeth in the mandibular third molars .
most patients ( 80.5% ) exhibited similar morphology on both their right and left mandibular sides .
a previous report indicated that 78.2% of the individuals studied possessed both mandibular third molars , while 11.3% had one and 10.5% had none .
extraction of mandibular third molars is a common operation in oral and maxillofacial surgery , and many reports have been published related to this issue .
various aspects such as the prevalence of caries experience , carious lesions , or restorations on the occlusal surface have been determined in asymptomatic third molars that have erupted to the occlusal plane .
the prevalence of caries in third molars is considered to be high as well as associated with patients caries experiences in first and second molars .
the morphology of mandibular third molars may be of interest to the operator for many procedures including surgical removal , autotransplantation for atraumatic procedures , and endodontic treatment .
tooth autotransplantation using mandibular third molars is reported be a useful surgical method to replace non - restorable teeth , with a high long - term survival rate .
recently , phase - contrast radiography was used to assess the root morphology of mandibular third molars , and it was suggested that phase - contrast radiography may be more useful than conventional radiography for this purpose .
there was a high prevalence of two - rooted and one - rooted mandibular third molars from a korean population , and it was found that the incidence of multi - rooted third molars tended to increase with patient age .
these data regarding the occurrence and morphology of teeth roots will provide useful information to dentists for various dental procedures .

Answer:
objective : the purpose of this study was to investigate the morphology and number of roots of korean mandibular third molars , and to evaluate the prevalence of c - shaped , two - rooted , and three - rooted mandibular third molars using cone - beam computed tomography ( cbct).materials and methods : serial axial cbct images of the mandibles were gathered from 137 korean patients .
 the total number of roots in the mandibular third molars of these patients was measured , and both the incidence and the correlations between left- and right - side occurrences , as well as between males and females , were analyzed.results:most of the mandibular third molars either had two roots ( 56.5% ) or one root ( 37.9% ) .
 there was no significant difference regarding the incidence of the different types of roots according to gender ( female versus male ) or topology ( right versus left side ) . a higher percentage ( 80.5% ) of the patients had similar root morphology on both sides.conclusion:the morphology and number of 214 mandibular third molars were examined using cbct .
 there was a high prevalence of two - rooted mandibular and one - rooted mandibular third molars from this korean population .
 even though the anatomical variations in the mandibular third molars may not be high , these data regarding the occurrence and morphology of the roots will provide useful information to dentists performing these procedures .


Question:
You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:
the main attributes of biological identity are sex , age , stature , and ethnic background of the individual , which are also called the  big four in forensic context .
human identification is of paramount importance , for both legal as well as humanitarian purpose .
albeit there have been tremendous advancements in forensic medicine , this remains a practical problem .
the use of dental identification has long been considered a reliable method , especially when other methods ( fingerprints ) fail because body conditions are not available , and over time , forensic odontology has emerged as a complete branch .
teeth can survive and remain virtually unaffected long after other soft tissue and skeletal tissues have been destroyed .
the recognition of teeth as a tissue that withstands great variation in environment ( temperature upto 1600 c , humidity , and ph ) has lead to its application in personal identification .
it has been observed in past time that dental tissues have witnessed its importance worldwide where it has contributed enormously in identification of victims in disaster , 80% of non - thai in tsunami in thailand and 20% in 26/11 incidence where 12 coordinated shooting and bombing attacks were carried by terrorists in mumbai , india 's most populous city on 26 november , 2010 were identified using teeth .
other than this , it has been reported that renowned people like adolf hitler and indian prime minister rajiv gandhi were identified using tooth .
several parameters have been proposed for sex determination to identify an individual from teeth , but none of them have proved its reliability .
recently , dna analysis in forensic have gained attraction , but it is expensive and time - consuming .
this prompted us to look for other methods of dental identification , which will be cost - effective yet reliable .
tooth pulp is encased in a hard tissue casting , where it may be protected from detrimental effects of impact , trauma , and heat .
developed a technique using pulpal tissue stained with quinacrine mustard , specific for y chromosome to determine sex of an individual . in literature , there is scarcity of relevant studies that analyzed the effect of caries on viability of pulpal tissue in sex determination .
so , keeping in mind this fact , present study was conducted to analyze the effect of caries on pulpal tissue stained with quinacrine hydrochloride with the application of fluorescent microscope .
this study was carried out in the department of oral pathology and microbiology , swami devi dyal hospital and dental college barwala , panchkula .
the study protocol was approved by the ethical committee of college before commencement of the procedure .
fifty maxillary and mandibular permanent teeth that were indicated for extraction for periodontal and endodontic reasons were included in the study .
study sample consisted of 25 male and 25 female teeth , which were further categorized into 5 groups of 10 each ( 10 from males and 10 from females ) based on the extent of caries progression .
group a includes freshly extracted tooth specimens with no caries , group b consisted of tooth specimens with caries in enamel , group c comprised of tooth specimens with caries less than half way of dentin , group d consisted of freshly extracted teeth with caries more than half way of dentin , and group e includes freshly extracted tooth specimen with caries involving pulp . the teeth were examined radiographically and clinically for analyzing the various stages of caries progression [ figure 1 ] .
( a ) sound teeth , ( b ) enamel , ( c ) less than half way of dentin , ( d ) more than half way of dentin , ( e ) pulp modeling wax was folded and made into a block .
the tooth was embedded on the modeling block . to remove the pulp , the crown
it was adequately washed in normal saline to remove any calcified bone or dentine particles .
the pulp tissue was then transferred to the dry and clean conical centrifuge tubes containing 5 ml of fixative ( 3 methanol:1 glacial acetic acid ) and left as such for about half an hour to 2 hours for the fixation of the pulp cells .
it was then crushed with the glass rod sufficiently to isolate the pulp cells . a suspension
five ml of fresh fixative was then added to re - suspend the pellet , and the process was repeated thrice till a clear suspension of the pulp cells was obtained .
thin smears were prepared on chilled microscope slides of 1 mm thickness by the air - drying method i.e. , by dropping 2 - 3 drops of the above suspension on the slide from a distance of inches to get a homogenous population of cells .
the slide was mounted in buffer of ph 5.5 and was observed under leica dmr fluorescent microscope ( oil immersion in dark field at 40 ) by bv exciting method ( emitting a blue - violet color , mainly at 4.047a0 and 4.038a0 ) . only those cells which contained the characteristic y chromatin i.e. , a brightly fluorescent spot attached to the nuclear membrane were counted as positive cells while those which did not show any such fluorescent spot were labeled as negative .
results obtained were subjected to statistical analysis by using independent t - test using spss ( version 9.0 ) software .
the tooth was embedded on the modeling block . to remove the pulp , the crown
it was adequately washed in normal saline to remove any calcified bone or dentine particles .
the pulp tissue was then transferred to the dry and clean conical centrifuge tubes containing 5 ml of fixative ( 3 methanol:1 glacial acetic acid ) and left as such for about half an hour to 2 hours for the fixation of the pulp cells .
it was then crushed with the glass rod sufficiently to isolate the pulp cells . a suspension
five ml of fresh fixative was then added to re - suspend the pellet , and the process was repeated thrice till a clear suspension of the pulp cells was obtained .
thin smears were prepared on chilled microscope slides of 1 mm thickness by the air - drying method i.e. , by dropping 2 - 3 drops of the above suspension on the slide from a distance of inches to get a homogenous population of cells .
the slide was mounted in buffer of ph 5.5 and was observed under leica dmr fluorescent microscope ( oil immersion in dark field at 40 ) by bv exciting method ( emitting a blue - violet color , mainly at 4.047a0 and 4.038a0 ) . only those cells which contained the characteristic y chromatin i.e. , a brightly fluorescent spot attached to the nuclear membrane were counted as positive cells while those which did not show any such fluorescent spot were labeled as negative .
results obtained were subjected to statistical analysis by using independent t - test using spss ( version 9.0 ) software .
this study was done to evaluate the use of the fluorescent body test as a diagnostic test for sex determination .
table 1 showed sensitivity , specificity , positive predictive value , negative predictive value , and efficiency of each of the five groups .
the values obtained were highest for sound teeth with caries in enamel and value decreases with the progression of the caries .
table 2 depicted that fluorescent bodies were found to be more in sound teeth in males as the caries increase , the mean percentage of fluorescent bodies observed decreases in males .
we also observed the fluorescent spots in females , and the value of the spot increases in female as the caries progresses , thereby giving false positive results in females [ figure 3 ] .
the p value were found to be significant for sound teeth and teeth with caries in enamel and involving less than half the way of dentin , whereas it was non - significant for teeth involved with further caries involvement .
diagnostic utility of fluorescent body in identifying gender percentage of fluorescent bodies ( in % ) in different groups fluorescent photomicrograph showing bright fluorescent cell in males representing y chromosome fluorescent photomicrograph representing faint fluorescence in females
despite the fact that tremendous research work is carried out to determine a reliable method , but none have proven its efficacy .
the most reliable means of identification include fingerprints , dental comparisons , and biologic methods such as dna profiling . in some cases
, however , fingerprints are not available from the deceased , or ante - mortem prints can not be obtained . sex determination from skull
is highly unreliable although number of workers have described differences in the size of male and female teeth , such measurements seem unlikely to be used to determine the sex of an individual .
so , a technique has been developed , which may offer a solution whenever soft tissue remains can be recovered .
casperson et al . showed that chromosome stained with quinacrine mustard fluoresced differentially along their length when viewed in ultraviolet light and the human y chromosome fluoresced more brightly than other chromosomes .
he suggested that alkylating agents like quinacrine acts on the dna portion rich in guanine and accumulate there .
this technique has been used in forensic science for sex determination from dried blood stains , saliva , and hair .
thus , it might be applicable to sex determination from tooth pulp some time after death , because the teeth are a stable part of the skeleton and the pulp tissue is well - protected .
seno and ishizu carried out the detection of y chromosome in the nuclei of dental pulp .
they found that f- body positive rate in the nucleated cells of male dental pulp was over 30% , even with the male teeth as old as 5 months , after the extraction . with female teeth ,
typical f - body can not be detected , and f - body like spot has been observed in 0.4% of cells , indicating that there can be no error in the identification of male tooth from that of female one , even such an f - body like spot is taken as an f - body itself .
present study revealed that in males , 60 - 75% fluorescent y bodies [ figure 2 ] were observed in sound teeth ( mean 69.4% bodies ) , 59 - 70% bodies in tooth with caries in enamel ( mean 64.2% bodies ) , 19 - 53% in teeth with caries in half way of dentin ( mean 39.8% bodies ) , teeth with caries involving more than half way of dentin and involving pulp showed 13 - 29% , 1 - 19% ( mean 21.8% , 6.37% bodies ) off bodies respectively as shown in table 2 .
seno and ishizu showed a range of 56 - 72% fluorescent y bodies in freshly extracted sound teeth , which are in accordance to sound teeth in this study .
pseudo y body in the present study [ figure 4 ] in females were found to be in the range of 0 - 12% ( mean 5.2% ) , 0 - 12% ( mean 5.2% ) , 14 - 22% ( mean 17.8)% , 12 - 22 ( mean 16.8% ) , and 7 - 15% ( mean 11.6% ) for sound teeth , teeth with caries in enamel , caries in half way of dentin , caries involving more than half way of dentin caries , and caries involving pulp , respectively , as shown in table 2 .
fluorescent photomicrograph representing artifacts or pseudo f - bodies in females discrepancy between various studies could be attributed to random inclusion of carious and non - carious teeth .
so , the present study considered the effect of caries on fluorescent body test as literature ( when searched via pubmed and medline ) revealed lack of studies analyzing this fact . from present study , it can be inferred that as the caries progresses from enamel to dentin and further to pulp tissue , the sensitivity and specificity of determining y chromosome decreases [ table 1 ] .
when the caries have involved only enamel or half the way of dentin , it has shown significant difference in fluorescent body test determining males and females , unlike when it involved more than half way of dentin and pulp where the difference is non - significant [ table 2 ] .
the decrease in  y body could be attributed to the fact that cariogenic bacteria alter the microenvironment of pulp , resulting in alteration in fluorescent staining . as the caries progresses , the inflammatory processes in the pulp are initiated , as the inflammation progresses the internal architecture of the cell is lost , and is also characterized by necrotic poorly stained cellular debris .
many workers attributed the appearance of fluorescent bodies in females to artifacts , whereas others ascribed it to the presence of fluorescent debris .
it was necessary to smear pulp cells thinly to prevent masking the fluorescent y chromosomes by fluorescent debris .
sex determination by fluorescent staining of the y chromosome is a reliable technique in teeth with healthy pulp tissue or caries with enamel or upto half way of dentin .

Answer:
aims : to determine and compare the reliability of pulp tissue in determination of sex and to analyze whether caries have any effect on fluorescent body test.materials and methods : this study was carried on 50 maxillary and mandibular teeth ( 25 male teeth and 25 female teeth ) , which were indicated for extraction .
 the teeth are categorized into 5 groups , 10 each ( 5 from males and 5 from females ) on the basis of caries progression .
 the pulp cells are stained with quinacrine hydrochloride and observed with fluorescent microscope for fluorescent body .
 gender is determined by identification of y chromosome fluorescence in dental pulp.results:fluorescent bodies were found to be more in sound teeth in males as the caries increase the mean percentage of fluorescent bodies observed decreases in males .
 we also observed the fluorescent spots in females , and the value of the spot increases in female as the caries progresses , thereby giving false positive results in females.conclusion:sex determination by fluorescent staining of the y chromosome is a reliable technique in teeth with healthy pulps or caries with enamel or up to half way of dentin .
 teeth with caries involving pulp can not be used for sex determination .


Question:
You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:
a 16-month old , baby girl , weighing 9.5 kg and measuring 74 cm , visited the hospital because of a cough . in a chest radiograph
done under the suspicion of an upper respiratory infection , a round foreign object with a diameter of 21 mm was detected in the upper esophagus ( fig .
1 ) . in a sleep endoscopy , it was confirmed to be a circular battery ( fig .
2 ) , and ingestion was estimated to occur three days prior to the hospital visit , and it was determined that endoscopic removal would not be easy .
the infant had no underlying disease , and glycopyrrolate 0.05 mg was i m injected 30 minutes before arriving at the operating room as premedication for the anesthesia .
the infant was monitored by ecg , non - invasive blood pressure ( nibp ) , and a pulse oximetry , and before anesthesia , her blood pressure was 85/61 mmhg ; her heart rate was 160 beats / min with 100% oxygen saturation .
10 mg of ketamine was iv injected and after loss of consciousness , 5 mg of rocunium was iv injected .
when the muscles were sufficiently relaxed , an uncuffed endotracheal tube with a 4 mm inside diameter was intubated .
after intubation , both lungs were checked through a stethoscope and found to be normal , and the endotracheal tube was set to 11 cm in accordance with the top front teeth .
anesthesia was maintained by 2 l / min of air , 2 l / min of o2 , and 2.0 - 3.5 vol% of sevoflurane .
the tidal volume was 90 ml ; respiratory rate was 18/min through volume - controlled mechanical ventilation to maintain an end - tidal co2 ( etco2 ) pressure of 35 - 40 mmhg and the peak inspiratory pressure ( pip ) at this point was 19 cmh2o .
an adult endoscope with a 9 mm outer diameter was used for the removal procedure because the hospital did not have a pediatric endoscope with forceps .
2 minutes after inserting the endoscope , severe abdominal inflation was observed , and pip increased up to 28 - 30 cmh2o with the tidal volume decreasing to less than 50 ml .
the battery had caused an inflammatory change and conglutinated onto surrounding tissue in the esophagus , and 3 minutes after inserting the endoscope , oxygen saturation decreased to 80% , and etco2 pressure rose to 70 mmhg therefore the surgery was stopped and the endoscope was removed . by manual ventilation using 100% oxygen , oxygen saturation was recovered to 100% and etco2 pressure to 40 mmhg , and thereafter , the endoscope was reinserted . in the second attempt of the procedure ,
manual ventilation was done instead of mechanical ventilation . however , 1 minute after the insertion of the endoscope , a sudden strong resistance was felt in the reservoir bag , and the tidal volume was less than 20 ml despite applying more than 35 cmh2o for the pip .
oxygen saturation dropped below 60% so the procedure could not be continued ; therefore , the endoscope was removed again . here , a pip of 25 - 30 cmh2o and a tidal volume of 50 ml were maintained .
the endoscope was reinserted after recovering oxygen saturation to 100% , but due to the increased airway pressure , ventilation was not possible , and oxygen saturation dropped back down to less than 40% .
the authors suspected the possibility of tef considering the period of intake and the excessive air volume seen in the stomach in the chest radiograph taken before the surgery .
hence , the endotracheal tube was inserted until one lung ventilation was possible and then retreated while auscultating to secure onto the location where the pulmonary sound from both lungs became equal .
the adjusted position of the endotracheal tube was 15 cm based on the top front teeth .
a pip of 25 - 30 cmh2o and a tidal volume of 80 - 100 ml were maintained . in the next insertion of the endoscope ,
a pip of 30 cmh2o and a tidal volume of 50 ml were maintained but abdominal inflation was excessive so air in the stomach was partially removed with the endoscope , and the operating doctor was required to use the minimal amount of air for the surgery to proceed .
a pip of 25 - 30 cmh2o , a tidal volume of 50 - 80 ml , and oxygen saturation of 100% were maintained during the procedure , and the battery was removed . after the removal of the battery , the vital signs were blood pressure 96/69 mmhg , heart rate 152 beats / min , and 100% oxygen saturation .
the patient was not extubated but moved to postoperative intensive care , and after pediatrics observed vital signs for about 3 hours to verify that there were no abnormalities , extubation was done .
subsequent vital sign checks and physical exam were normal , and there were no abnormalities found in the blood test .
moreover , the right main bronchus appeared on the screen in the postoperative esophagography ( fig .
3 ) , and the chest ct scan found tef at 1.4 cm in the upper carina ( fig .
4 ) . the guardian wanted to have surgery for tef at another hospital ; therefore , 3 days after the surgery , she was transferred .
ingested batteries usually pass through the gastrointestinal tract and are defecated in a few days , but when it is caught in the esophagus , the moist environment of the esophagus allows for the discharge of substances inside the battery together with electrical discharges , which can cause tissue damage of the esophagus .
in addition , necrosis can develop in the mucus membrane of the esophagus due to the pressure from the battery , and these can trigger complications such as esophageal burns , perforation , and tef .
more severe complications arose in cases where the diameter of the battery was larger than 20 mm and the infant was younger than 4 years old .
the main factors that cause severe complications in battery ingestion were the size ( larger than 20 - 30 mm ) and components of the battery .
especially if the negative terminal of the battery is attached to the tissue , it can lead to more severe results .
in addition , lithium batteries cause the most severe damages , and it was reported that in a dog 's esophagus , necrosis developed in the trachea within an hour . in this case study , the corroded battery and inflamed mucous membrane of the esophagus were confirmed in endoscopy before the surgery , but tef could not be tested and confirmed due to the urgency of the surgery .
it is reported that esophageal burns start 4 hours after battery ingestion and perforations that form fistulas start in 6 hours . since the estimated ingestion period for this case was 3 days , it is enough time for tef to develop .
the infant in this case study did not have respiratory difficulties before of the surgery , but ventilation failure during the surgery was because the endotracheal tube was fixed at 11 cm at first .
the tef located approximately 2.6 cm under the end of the endotracheal tube allowed the inhalation gas for the anesthesia to flow into the stomach leading to abdominal inflation , and consecutively , the air injected for the endoscopic surgery flowed over to the respiratory tract to greatly increase the airway pressure .
afterwards , when the endotracheal tube was inserted deeply into the carina , the tube was located past the tef so the influence of tef was eliminated for the decrease in airway pressure . when there is tef , it is important to position the endotracheal tube above the carina and below the tef to maintain anesthesia .
this is because effective ventilation would not happen due to a loss of the tidal volume through the fistulous openings in the tef , the contents of the stomach being aspirated into the lungs , and excessive positive pressure ventilation when inducing anesthesia can cause abdominal inflation and cardiovascular suppression .
however , in our case , ventilation was not completely recovered even when the endotracheal tube was inserted deeply to eliminate the influence of tef , and this is thought to be from accompanying ventilation failure from the endoscope .
this ventilation failure can be caused by pressure on the pharynx and the trachea from the weight of the endoscope , or motor abnormality of the diaphragm due to abdominal inflation from the injected air .
wengrower et al .   reported that approximately 7% of infants who had endoscopic procedures under sedation or anesthesia exhibited temporary desaturation .
there are reports that an infant with a similar height and weight developed ventilation failure from a tee probe with outer diameter of 10  8 mm . in our case , the fact that direct pressure on the respiratory tract was applied by using an adult endoscope with a 9 mm diameter and that air had to be injected continually since the battery had attached itself to the esophagus and was hard to remove could have been some other causes for the excessive airway pressure , ventilation failure , and hypoxemia .
when upper gastrointestinal endoscopic procedures were done on 99 infants of 0.9 - 10.1 kg using an endoscope with a 5.2 mm outer diameter , only 1 infant with global developmental delay exhibited hypoxemia , and gryboski recommended using endoscopes with a 5 mm outer diameter on infants with esophageal diseases .
it is important to use pediatric endoscopes with the smallest possible outer diameters to prevent hypoxemia during endoscopic procedures on infants . since the removal of foreign objects in the esophagus of infants
are usually done under general anesthesia , anesthesiologists need to anticipate ventilation failure and hypoxemia from the physical pressure from the procedural equipment and the excessive injection of air and proceed with anesthesia under close cooperation with the operating surgeon .
especially when a battery has been ingested , it is necessary to be aware that there could be complications such as tef in the location where the battery is depending on the battery 's components , size , and ingestion period .
in addition , to more effectively block the mutual flow of air and anesthetic gas towards either the esophagus or the trachea in the case of a potential tef , a cuffed endotracheal tube should be chosen preferentially and special caution should be taken to fix the position of the tube and in selecting a suitable size for the endoscope used in the procedure .

Answer:
ingestion of disk batteries may have serious complications such as esophageal burn , perforation , and tracheoesophageal fistula , particularly when the battery is caught in the esophagus .
 proper placement of the tracheal tube is critical when tracheoesophageal fistula was occurred from esophageal impaction the battery .
 endoscopy of upper gastrointestinal tract in infants and children is an important and effective tool for the diagnosis and treatment of foreign body ingestion . but
 upper gastrointestinal endoscopy in infant and children has very high risk of tracheal compression and airway compromise .
 we present a case of ventilatory compromise during insertion of the upper gastrointestinal endoscopy in 16-month - old child with tracheoesophageal fistula secondary to disk battery ingestion .


Question:
You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:
a total of 30 mabs that were either developed or in - licensed by companies are currently undergoing evaluation in late - stage studies ( tables 1 and 2 ) .
five of these ( brodalumab , mabp1 , moxetumomab pasudotox , tildrakizumab , rilotumumab ) transitioned into phase 3 studies during the period from late 2012 to april 2013 .
brodalumab ( amg827 , amgen ; khk4827 , kyowa hakko kirin ) , a human igg2 targeting the interleukin ( il)-17 receptor , is undergoing evaluation in three phase 3 studies ( amagine-1 , -2 , and -3 ) of patients with psoriasis .
the amagine-1 study ( nct01708590 ) is evaluating the efficacy , safety , and effect of withdrawal and retreatment with brodalumab in patients with moderate - to - severe plaque psoriasis . in this study , either of two doses ( 140 mg or 210 mg ) or placebo is administered subcutaneously ( sc ) every two weeks until week 12 , when patients are rerandomized to placebo or continued treatment .
the estimated primary completion date for the study is march 2014 . in the amagine-2 ( nct01708603 ) and amagine-3 ( nct01708603 ) studies ,
the efficacy and safety of induction and four maintenance regimens of brodalumab compared with placebo and ustekinumab in patients with moderate - to - severe plaque psoriasis is being evaluated .
these studies have estimated primary completion dates of august and september 2014 , respectively . note : table compiled from information available as of april 25 , 2013 .
abbreviations : cd , cluster of differentiation ; il , interleukin ; pcsk9 , proprotein convertase subtilisin / kexin type ; sle , systemic lupus erythematosus . note : table compiled from information available as of april 25 , 2013 . * in - licensed
; national cancer institute is sponsoring the phase 3 study in hairy cell leukemia patients .
abbreviations : all , acute lymphoblastic leukemia ; cll , chronic lymphocytic leukemia ; hgf / sf , hepatocyte growth factor/ scatter factor ; nhl , non - hodgkin lymphoma ; nscl , non - small cell lung ; vegfr2 , vascular endothelial growth factor receptor 2 . a first phase 3 study ( nct01767857 ) of mabp1 ( xilonix , xbiotech , inc . ) , a human mab targeting il-1 , was recruiting patients as of march 2013
. the study will evaluate overall survival of metastatic colorectal cancer patients with cachexia who are administered the mab as a monotherapy .
the effects of mabp1 administered intravenously ( iv ) every two weeks , plus best supportive care will be compared with those of megestrol acetate administered daily plus best supportive care .
the difference between the study arms in median overall survival from baseline to 18 mo will be compared .
the recombinant immunotoxin moxetumomab pasudotox ( cat-8015 , astrazeneca ) is undergoing evaluation in a phase 3 study ( nct01829711 ) of patients with relapsed / refractory hairy cell leukemia .
the study is sponsored by the national cancer institute ( nci ) ; the mab is currently licensed to astrazeneca . in 2004 , nci licensed moxetumomab pasudotox to genencor , inc .
the mab was then acquired in 2005 by cambridge antibody technology , which was itself acquired by astrazeneca in 2006 .
moxetumomab pasudotox comprises a mouse disulfide stabilized variable fragment with the variable heavy domain fused with a 7-mer linker and the pseudomonas aeruginosa exotoxin a pe38 fragment . in the phase 3 study
, patients will receive 40 g / kg of the immunotoxin administered iv over 30 min on days 1 , 3 , 5 of each 28 d cycle until complete response , progressive disease , initiation of alternate therapy or unacceptable toxicity is observed .
initiated in march 2013 , the study s estimated primary completion date is december 2014 .
two phase 3 studies of tildrakizumab ( sch900222/mk-3222 , merck ) , a humanized mab targeting the p19 subunit of il-23 , are recruiting patients .
initiated in december 2012 , nct01722331 is a 64-week study to evaluate the efficacy and safety / tolerability of sc administration of tildrakizumab in patients with moderate - to - severe chronic plaque psoriasis .
patients receive 100 mg or 200 mg tildrakizumab at week 0 and week 4 , and then every 12 weeks until study end or participant discontinuation .
patients receive the same doses of tildrakizumab , but the study includes 50 mg etanercept as well as placebo as comparators .
the two phase 3 studies have estimated primary completion dates of june and july 2015 , respectively .
rilotumumab ( amgen ) is a human igg2 targeting human hepatocyte growth factor / scatter factor ( hgf / sf ) that blocks binding of hgf / sf to its receptor met , thereby inhibiting the met signaling pathways .
the mab is undergoing evaluation in a phase 3 study ( nct01697072 ) of chemotherapy ( epirubicin , cisplatin and capecitabine ) with rilotumumab or placebo for untreated advanced met - positive gastric or gastresophageal junction adenocarcinoma .
rilotumumab or placebo is administered iv at doses of 15 mg / kg every 21 d. the primary outcome measure is overall survival in a time - frame of three years .
initiated in october 2012 , the estimated primary completion date for the study is december 2015 .
recently announced results for three late - stage studies of two mabs for cancer ( farletuzumab , naptumomab estafenatox ) and tabalumab , a mab treatment for autoimmune disorders , indicate that clinical endpoints were not met .
farletuzumab ( morab-003 , morphotek / eisai ) is a humanized igg1 mab that targets human folate receptor  , which is overexpressed in most epithelial ovarian cancers , as well as some forms of endometrial , breast , renal , lung and colorectal cancers .
the primary endpoint of progression - free survival ( pfs ) was not met in the phase 3 far-131 study ( nct00849667 ) of farletuzumab in combination with carboplatin and a taxane in patients with platinum - sensitive epithelial ovarian cancer in first relapse .
patients received placebo or farletuzumab at either 1.25 mg / kg or 2.5 mg / kg weekly for ~six cycles .
although the primary endpoint was not met , a trend toward improved pfs was observed in some patient subsets in a post - hoc analysis .
the safety and efficacy of farletuzumab in combination with a platinum containing doublet in chemotherapy - nave subjects with stage iv adenocarcinoma of the lung are being evaluated in a phase 2 study ( nct01218516 ) . as announced in january 2013 by active biotech ab , initial results of a phase 2/3 study ( nct00420888 ) of naptumomab estafenatox ( abr-217620 , anyara ) in combination with interferon  as a treatment for advanced renal cell carcinoma indicated that the study did not achieve its primary clinical endpoint of overall survival in the intention - to - treat cohort .
a confounding factor was the presence of high levels of pre - formed anti - drug antibodies found in a majority of patients in this , but not previous , studies .
a doubling of pfs and overall survival occurred in the 25% of patients who had low or normal levels of base - line il-6 and expected levels of anti - drug antibodies .
naptumomab estafenatox is composed of an antigen - binding fragment ( fab ) that targets metastasis - associated 5t4 fused to a mutated form of staphylococcal enterotoxin a ( sea / e-120 ) .
phase 3 studies of tabalumab ( ly2127399 , eli lilly and co. ) as a treatment for ra have been discontinued due to lack of efficacy .
tabalumab , a human igg4 targeting b - lymphocyte stimulator , was being evaluated in five phase 3 studies of ra patients .
tabalumab in combination with bortezomib and dexamethasone is also being evaluated in a phase 2/3 study ( nct01602224 ) of patients with previously treated multiple myeloma .
historically , ~50% of mabs in the commercial clinical pipeline have been studied as cancer agents ; however , ~67% of the current cohort of mabs at phase 3 is in studies for non - cancer indications ( table 1 ) .
these 20 mabs are human or humanized , with more than half ( 55% ) targeting an interleukin or an interleukin receptor .
the mabs are being developed as treatments for immunological disorders such as ra , sle , ms and psoriasis , but also for hypercholesterolemia , cachexia and alzheimer disease . reflecting the overall greater challenge of demonstrating safety and efficacy in cancers ,
the molecular types of the 10 mabs in late - stage studies of cancer ( table 2 ) are more diverse than those for non - cancer indications .
of particular note is the inclusion of a toxin in three molecules ( naptumomab estafenatox , moxetumomab pasudotox , inotuzumab ozogamicin ) and use of less than a full - length sequence for three molecules ( naptumomab estafenatox , moxetumomab pasudotox , onartuzumab ) . the majority ( 70% ) of the 10 product candidates
are in studies of solid tumors , with the remainder undergoing evaluation as treatments for hematological cancers .
the number of anti - cancer mabs at phase 3 is likely to increase in the next 35 y as more adcs move into and through the clinical pipeline .

mabs will continue to track the progress of antibody therapeutics in clinical study throughout 2013 , and we look forward to reporting on results that may be released during the year in  which are the antibodies to watch in 2014 ?

Answer:
the transitions of antibody therapeutics to late - stage clinical development , regulatory review and the market are proceeding at a rapid pace in 2013 . since late 2012 , two monoclonal antibody ( mab ) therapeutics ( itolizumab , trastuzumab emtansine ) received their first approvals , first marketing applications for three mabs ( vedolizumab , ramucirumab , obinutuzumab ) were submitted to regulatory agencies , and five mabs ( brodalumab , mabp1 , moxetumomab pasudotox , tildrakizumab , rilotumumab ) entered their first phase 3 studies . the current total of commercially - sponsored antibody therapeutics undergoing evaluation in late - stage studies is 30 .
 recently announced study results for farletuzumab , naptumomab estafenatox , and tabalumab indicate that clinical endpoints were not met in some phase 3 studies of these product candidates .