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:
obesity is a leading risk factor for many adverse health outcomes including type 2 diabetes , hypertension , dyslipidemia , coronary heart disease , and certain types of cancer .
the prevalence of adult obesity in the us had doubled from 19761980 to 1999 - 2000 . in 2009
us ranked the highest in adult obesity prevalence among all countries in the organization for economic cooperation and development .
the estimated annual medical cost of obesity in the us totaled 147 billion us dollars in 2008 .
more recent data indicated a slowing down of the trend in adult obesity and even some leveling off in childhood obesity .
small but significant declines in the prevalence of obesity among low - income preschoolers aged 25 years were reported in 19 of 43 us states examined in the pediatric nutrition surveillance system from 2008 to 2011 .
no significant change in the prevalence of adult obesity was found between 20032008 and 2009 - 2010 in the national health and nutrition examination survey ( nhanes ) .
the prevalence of morbid ( i.e. , grades 2 and 3 ) obesity was still increasing from 2005 to 2010 , but its growth rate had slowed down as indicated in the behavioral risk factor surveillance system ( brfss ) . given the large disease burden of obesity and its high prevalence , it is crucial to continuously monitor the prevalence of obesity in the us .
this study provides national estimates of obesity among us adults aged 20 years and older in 2011 - 2012 and tracks its trends from 1999 to 2012 .
study sample came from nhanes 1999 - 2000 , 2001 - 2002 , 2003 - 2004 , 2005 - 2006 , 2007 - 2008 , 2009 - 2010 , and 2011 - 2012 waves .
nhanes is a program of studies designed to assess the health and nutritional status of adults and children and represents a multistage probability sample of the us civilian , noninstitutionalized population .
participants ' body weight and stature height were measured by digital scale and stadiometer in the nhanes mobile examination center .
body mass index ( bmi ) is defined by weight in kilograms divided by height in meters squared .
four prevalence measures were examined : overweight and obesity combined ( bmi  25 ) , obesity ( bmi  30 ) , grades 2 and 3 obesity combined ( bmi  35 ) , and grade 3 obesity ( bmi  40 ) .
age was adjusted by direct standardization to the year 2000 census population using the age groups 2039 years old , 4059 years old , and 60 years and older .
nhanes wave - specific sampling weight , sampling stratum , and primary sampling unit were taken into account in estimating prevalence in the population .
prevalence was estimated for both the overall population and subpopulations stratified by gender and race / ethnicity ( i.e. , non - hispanic white , non - hispanic african american , and hispanic ) .
piecewise logistic regressions were used to test the differential trends in adult obesity before and after 2010 .
the model has the following setup :
 ( 1)logit(yi)=0+1xi+2(xi2010)di+i , di=1{xi2010}. in ( 1 ) , yi is an indicator variable for overweight and obesity combined ( bmi  25 ) , obesity ( bmi  30 ) , grades 2 and 3 obesity combined ( bmi  35 ) , or grade 3 obesity ( bmi  40 ) ; xi a continuous variable taking the values of 2000 , 2002 , 2004 , 2006 , 2008 , 2010 , and 2012 for the nhanes waves 1999 - 2000 , 2001 - 2002 , 2003 - 2004 , 2005 - 2006 , 2007 - 2008 , 2009 - 2010 , and 2011 - 2012 , respectively ; di an indicator variable for xi  2010 ; and i the error term . if the estimated coefficient 2 is significantly different from zero ( equivalent to the estimated odds ratio e to be significantly different from one ) ,
piecewise logistic regressions were performed on the overall sample and on each gender and race / ethnicity group , controlling for age group ( i.e. , 2039 years old , 4059 years old , and 60 years and older ) and accounting for survey design .
in total , 5,560 adults aged 20 years and older participated in the nhanes 2011 - 2012 wave . among them , 57 pregnant women and 322 individuals with missing values in body weight / height measures were excluded from the analyses .
nhanes oversamples minorities : 1,364 non - hispanic african americans and 1,037 hispanic were included besides non - hispanic white .

table 2 reports the estimated bmi and prevalence measures among us adults aged 20 years and older in 2011 - 2012 .
the age - adjusted mean bmi was 28.5 ( 95% ci : 28.029.0 ) among men and 28.8 ( 28.329.3 ) among women .
non - hispanic african american women had the highest mean bmi of 32.3 ( 31.633.0 ) among all gender and race / ethnicity subgroups .
the age - adjusted prevalence of overweight and obesity combined ( bmi  25 ) was 71.1% ( 68.0%74.2% ) among men and 65.5% ( 61.8%69.3% ) among women , and the age - adjusted prevalence of obesity ( bmi  30 ) was 33.3% ( 30.5%36.2% ) among men and 35.8% ( 32.3%39.4% ) among women . among men , 11.8% ( 9.7%13.9% ) and 4.3% ( 2.2%6.3% )
were classified in grades 2 and 3 obesity combined ( bmi  35 ) and grade 3 obesity ( bmi  40 ) , respectively , whereas among women , 16.7% ( 14.5%8.9% ) and 8.0% ( 6.6%9.5% ) were classified in grades 2 and 3 obesity combined and grade 3 obesity , respectively .
women had higher prevalence of obesity , grades 2 and 3 obesity combined , and grade 3 obesity than men ( although the differences were not always statistically significant ) among all race / ethnicity groups .
non - hispanic african american women had the highest prevalence of overweight and obesity combined ( 81.5% ) , obesity ( 56.4% ) , grades 2 and 3 obesity combined ( 28.7% ) , and grade 3 obesity ( 15.8% ) among all gender and race / ethnicity groups , which were 29% , 73% , 92% , and 122% higher than among non - hispanic white women , respectively .

figure 1 shows the percentage change in prevalence measures among us adults of 20 years and older from 1999 - 2000 to 2011 - 2012 with 1999 - 2000 as the baseline .
the age - adjusted prevalence of overweight and obesity combined ( bmi  25 ) , obesity ( bmi  30 ) , grades 2 and 3 obesity combined ( bmi  35 ) , and grade 3 obesity ( bmi  40 ) in 2009 - 2010 were 7.2% , 17.8% , 17.6% , and 33.0% higher than in 1999 - 2000 . compared to 2009 - 2010 ,
the prevalence measures slightly decreased in 2011 - 2012 , but the reductions were not statistically significant at p < 0.05 .

figure 2 shows the gender- and race / ethnicity - specific trend in the age - adjusted prevalence of overweight and obesity combined ( bmi  25 ) , obesity ( bmi  30 ) , grades 2 and 3 obesity combined ( bmi  35 ) , and grade 3 obesity ( bmi  40 ) among us adults aged 20 years and older from 1999 - 2000 to 2011 - 2012 .
compared to 2009 - 2010 , most gender- and race / ethnicity - specific prevalence measures remained unchanged or slightly decreased in 2011 - 2012 , except for the prevalence of overweight and obesity combined among non - hispanic white women , the prevalence of obesity among hispanic men , and all 4 prevalence measures among hispanic women which increased by 1.3 to 3.3 percentage points .
none of the changes in gender- and race / ethnicity - specific prevalence measures ( 24 of them in total ) between 2009 - 2010 and 2011 - 2012 were statistically significant at p < 0.05 .

table 3 reports the statistical tests for trends in obesity over the 14 years of survey cycles from 1999 to 2012 using piecewise logistic regressions .
the coefficients are expressed as annualized odds ratios ( ors ) , denoting the estimated increase per year in the odds of a prevalence measure .
a majority of the gender- and race / ethnicity - specific prevalence measures seemed to slightly increase over time ( as indicated by the estimated e > 1 ) .
for example , the estimated or for the prevalence of obesity ( bmi  30 ) among hispanic women is 1.03 ( 1.011.04 ) , approximately equivalent to a yearly increase in obesity prevalence of 0.6 percentage points .
nearly all gender- and race / ethnicity - specific prevalence measures appeared to deviate downwards from the increasing trend ( as indicated by the estimated e < 1 ) during 20102012 , but those changes in trends were not statistically significant at p < 0.05 .
the rate of increase appeared to slow down since the 2000s and most recent data on childhood obesity even indicated some leveling off . using a nationally representative sample ,
this study estimates the obesity prevalence among us adults aged 20 years and older in 2011 - 2012 and tracks its trends from 1999 to 2012 . the main advantage of nhanes relative to other national health surveillance systems such as the brfss and the national health interview survey ( nhis ) is the objectively measured body weight and height , which eliminates self - report bias .
however , the relatively small sample size of nhanes ( about 5,000 in every two - year survey cycle , compared to about 0.4 million a year in brfss ) limits the precision for population estimates . unlike brfss or nhis , nhanes
moreover , nhanes is a probability sample of the us civilian , noninstitutionalized population , excluding inmates of institutions ( e.g. , people in penal / mental facilities or homes for the aged , or on active duty in the armed forces ) .
the prevalence measures are based on bmi , a function of weight and height , rather than on body fatness .
although bmi has been found to be closely associated with percentage body fat measured by dual x - ray absorptiometry in the nhanes , these two measures are fundamentally different and their levels of agreement could be a function of gender , age , and race / ethnicity .
for instance , percentage body fat was found to be more correlated with bmi in women than men .
the relation between percentage body fat and bmi in hispanic american women differed from that of african american and european american women . a thorough investigation on the differential relationship between bmi and body fatness across population groups and the long - term trend of obesity prevalence measured by percentage body fat is beyond the scope of this study but warranted in future research .
the growth rate of the obesity epidemic among us adults appears to have slowed down in 2000s , but it is still too early to conclude that it has already reached the plateau and begun to level off . both figures 1 and 2 showed some decline in the obesity prevalence measures in 2011 - 2012 compared to in 2009 - 2010 , but none of the changes were statistically significant .
this has also been indicated in the results of piecewise logistic regressions where the null hypotheses on the similarity in trends for prevalence measures before and after 2010 were not rejected . in conclusion ,
concurrent evidence on the leveling off of the obesity epidemic in the us is thin and the trend is unclear and inconclusive at this time . given the high prevalence of obesity and its profound socioeconomic consequences , close monitoring of the trend is warranted .

Answer:
aim . to provide national estimates of obesity among us
 adults aged 20 years and older in 2011 - 2012 and track its trends from 1999 to 2012 .
 methods . measured weight / height from national health and nutrition examination survey 19992012 waves was used to calculate body mass index ( bmi ) and prevalence measures .
 piecewise logistic regressions were conducted to test the differential trends before and after 2010 .
 results . in 2011 - 2012 , the age - adjusted prevalence of overweight and obesity combined ( bmi  25 ) was 71.1% ( 95% ci : 68.0%74.2% ) among men and 65.5% ( 61.8%69.3% ) among women , and the prevalence of obesity ( bmi  30 ) was 33.3% ( 30.5%36.2% ) among men and 35.8% ( 32.3%39.4% ) among women . from 19902000 to 2009 - 2010 , the prevalence of overweight and obesity combined , obesity , grades 2 and 3 obesity combined ( bmi  35 ) , and grade 3 obesity ( bmi  40 ) increased by 7.2% , 17.8% , 17.6% , and 33.0% , respectively . compared to 2009 - 2010 , most gender- and race / ethnicity - specific prevalence measures remained unchanged or slightly decreased in 2011 - 2012 .
 no significant difference in trends among prevalence measures was found before and after 2010 .
 conclusions
 . concurrent evidence on the leveling off of obesity in the us is thin .
 given its high prevalence and profound socioeconomic consequences , close monitoring of the trend is warranted .


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:
tiam1 is involved in a number of cellular processes including migration and the regulation of cell - cell adhesions and survival .
althoughtiam1 has been implicated in cellular proliferation , its role during the cell cycle is unknown . in mdck
ii cells expressing either gfp - tagged tiam1 or ha - tagged tiam1 , we were intrigued to observe a signal not only at cell - cell adhesions ( as previously described ) but also at the two microtubule ( mt ) asters surrounding the centrosomes .
this localization was apparent both before nuclear envelope breakdown ( nebd ) in prophase cells ( figure  1a and figure  s1a ,  available online ) and after nebd in prometaphase cells ( figure  1b and figure  s1b ) and was dependent on mts because it was lost after nocodazole treatment ( data not shown ) .
however , in metaphase cells , tiam1 localization to centrosomal regions was no longer detected ( right - hand cell , figure  1b ) . to investigate the potential function of tiam1 at centrosomes , we generated mdck ii cells expressing doxycycline - inducible short hairpin interfering rnas ( shrnas ) to tiam1 ( two independent targets : rnai # 1 and rnai # 2 ) or control scrambled shrna ( scr ) . upon doxycycline addition , endogenous
tiam1 protein was depleted from cells containing either tiam1 shrna target ( figure  1c ) . in subcellular fractions enriched for centrosomes ,
endogenous tiam1 cosedimented with the centrosomal marker -tubulin and was depleted from these fractions after tiam1 shrna expression ( figures s1c and s1d ) .
moreover , immunofluorescence analysis confirmed that endogenous tiam1 localized to centrosomal regions in early mitosis ( figures 1d and s1e ) ; this signal was depleted after tiam1 shrna expression ( figure  1d ) . because tiam1 is a rac - specific activator
gfp - tagged rac was detected at cell - cell adhesions as shown previously ; however , it also colocalized with the two mt asters in prophase ( figure  1e ) and prometaphase cells ( figure  s1f ) .
endogenous rac showed a similar localization ( figure  1f and figure  s1 g ) .
hence , tiam1 and rac localize to centrosomal regions in early mitosis . during prophase ,
duplicated centrosomes begin to separate around the nuclear envelope before nebd ( prophase pathway ) , in preparation to form a bipolar spindle in prometaphase  .
hence , we measured centrosome separation in control and tiam1-depleted prophase cells . strikingly , the intercentrosomal distance increased by over 40% in tiam1-depleted cells ( figure  2a ) .
this defect was efficiently rescued by expressing rnai - resistant wild - type tiam1 ( figure  2a ) but not the gef mutant tiam1 ( q1191a , k1195a ) , which is unable to activate rac ( figure  2a ) .
treatment with a specific rac inhibitor ( nsc-23766 ) also increased centrosome separation in prophase cells ( figure  s2a ) .
after tiam1 depletion , a similar increase in centrosome separation was seen in mouse p1 cells ( figures s2b and s2c ) . thus , tiam1 functions via rac to oppose centrosome separation in prophase .
relatively little is known about centrosome separation during prophase , with conflicting evidence for the involvement of eg5 [ 13 , 14 ] .
treatment with the eg5-specific inhibitor monastrol   led to a significant decrease in the intercentrosomal distance of prophase mdck ii cells ( figure  2b ) ; similar results were obtained with a second eg5-specific inhibitor s - trityl - l - cysteine   ( stlc , data not shown ) .
tiam1 also localizes to the cortex in prophase cells ( figure  1a and figure  s1a ) , and cortical movements driven by myosin - ii activity ( regulated by rho kinase [ rock ] ) are required after nebd for centrosome separation via astral mt connections . to gain mechanistic insight into the regulation of centrosome separation in prophase
, we treated cells with inhibitory concentrations of blebbistatin ( myosin - ii inhibitor ) or y-27632 ( rock inhibitor ) ( figures s2d and s2e ) .
however , neither treatment affected centrosome separation in control prophase cells ( figure  2b ) or the increased intercentrosomal distance in tiam1-depleted prophase cells ( figure  2c ) .
in contrast , low concentrations of taxol , a mt - stabilizing agent , although not effecting centrosome separation in control cells , prevented the increased centrosomal separation of tiam1-depleted prophase cells ( figure  2c ) .
these data suggest that in prophase , centrosome separation is driven by eg5 but is unlikely to involve cortical movements .
further , the effects of tiam1 depletion on centrosome separation , although probably independent of the cortex , may be mediated through microtubule stabilization , although how is currently unclear . a role for tiam1 in stabilizing mts during front - rear polarization in cell migration
we detected no change in the localization of eg5 in tiam1-depleted cells ( data not shown ) , suggesting that this is independent of tiam1 . using time - lapse fluorescence microscopy of cells expressing -tubulin - gfp
after tiam1 depletion , there was no significant difference in the period between the onset of centrosome separation and nebd compared with controls ( figure  2d ) .
however , the centrosome separation rate in prophase was significantly increased in tiam1-depleted cells compared to controls ( figures 2d and 2e ) .
further , tiam1-depleted cells maintained their increased centrosome separation after nebd ( figure  s2f ) .
consistent with this , the intercentrosomal distance in prometaphase from fixed samples was also significantly increased after tiam1 depletion ( figure  s2 g ) or rac inhibition ( figure  s2h ) . however , the rate of centrosome separation during prometaphase was markedly reduced compared to prophase and was unaffected by tiam1 depletion ( figure  2e ) . to investigate further the role of tiam1 in centrosome separation in prometaphase , we arrested cells in  a monopolar prometaphase state with monastrol , then released them to allow mitosis to proceed .
we found that centrosomes in tiam1-depleted cells separate significantly further 10 min after washout compared to controls ; however , at 20 min the increase was not significant ( figure  s2i ) .
thus , tiam1-rac affects centrosome separation apparently independently of the nuclear envelope and seemingly more potently when centrosomes are in close proximity .
this property may account for the greater influence that inhibition of this pathway exerts during prophase compared to prometaphase . to examine whether tiam1 antagonizes eg5 during bipolar spindle formation , we treated control and tiam1-depleted cells for 18 hr with stlc or monastrol at concentrations that reduce but do not abolish eg5 activity . in controls ,
eg5 suppression resulted in mainly monopolar mitotic spindles ( figure  3a ) : 60% in stlc - treated cells ( figure  3b ) and 70% in monastrol - treated cells ( figure  s3a ) .
however , after tiam1 depletion , mitotic spindles were mainly bipolar ( figure  3a ) , with significantly fewer monopolar spindles : 15% in stlc - treated ( figure  3b ) and 30% in monastrol - treated cells ( figure  s3a ) .
we next confirmed that the bipolar spindles formed in tiam1-depleted cells , under conditions of eg5 suppression , were functional and able to segregate chromosomes later in mitosis .
in control cells , the proportion of mitotic cells in anaphase or telophase significantly reduced from over 32% to 20% after stlc ( figure  3c ) and 12% after monastrol treatment ( figure  s3b ) .
conversely , in tiam1-depleted cells , eg5 suppression had little effect on the proportion of mitotic cells in anaphase or telophase : 32% after stlc ( figure  3c ) and over 25% after monastrol treatment ( figure  s3b ) .
consistent with this , in controls the mitotic index increased by over 4.5-fold after eg5 suppression ( figure  3d and figure  s3c ) as  a result of the monopolar spindles activating the spindle assembly checkpoint ( sac ) , thereby delaying mitosis .
however , tiam1 depletion prevented the accumulation of mitotic cells after eg5 suppression ( figure  3d and figure  s3c ) . to determine whether eg5 function is antagonized by rac signaling in  vivo , we utilized conditional rac1 knockout mice , focusing on the intestinal epithelium .
epithelial cells within intestinal crypts are highly proliferative and arrest rapidly after administration of various drugs ; this arrest is visualized via an accumulation of mitotic figures within the intestinal crypt .
we first conditionally deleted rac1 within the intestinal epithelium ( as described in the supplemental experimental procedures ) .
three days after cre induction , the intestinal epithelium from ahcre rac1 mice showed loss of rac1 ( figures s3d and s3e ) .
deletion of rac1 at this stage did not affect proliferation ( data not shown ) or cellularity ( figure  s3f ) .
we next treated mice with 25 mg / kg stlc and  investigated mitotic arrest after 3 hr . in wild - type mice , stlc treatment induced a significant mitotic arrest ( figures 3e and 3f ; rac1 control versus rac1 stlc - treated ) . remarkably , rac1 deletion completely rescued the induction of mitotic arrest ( figures 3e and 3f ; rac1 stlc - treated versus rac1 stlc - treated ) .
moreover , in wild - type mice the proportion of mitotic cells in anaphase was significantly reduced after stlc treatment , indicating an arrest prior to this stage ( figure  3 g ) .
taken together , these data indicate that tiam1-rac signaling antagonizes eg5 function , both in  vitro and in  vivo ; in their absence mitotic cells can assemble bipolar spindles and complete mitosis under conditions of reduced eg5 activity .
we tested whether tiam1 depletion induced further mitotic defects by using time - lapse fluorescence microscopy of cells  expressing histone-2b - gfp . in controls ,
chromosomes efficiently congressed to the metaphase plate after nebd and  rapidly entered anaphase ( figure  4a ) . in over 60% of tiam1-depleted cells , however , chromosomes spent over 15  min aligning on the metaphase plate ( compared to less than 5% of controls ) , before eventually aligning and entering  anaphase ( figure  4a ) .
the duration of early mitotic stages ,  calculated from numerous movies , indicated that tiam1 depletion specifically increased prometaphase duration ( figure  4b ) .
analysis of fixed mitotic cells revealed that after tiam1 depletion , congression errors were over 2.5-fold higher than controls ( figure  4c ; see figure  s4a for example images ) .
similar results were obtained after tiam1 depletion in p1 cells ( data not shown ) .
importantly , this chromosome congression defect was efficiently rescued by expressing rnai - resistant wild - type tiam1 , but not gef mutant tiam1 ( figure  4c ) .
moreover , cells treated with rac inhibitor also displayed significantly increased congression errors compared to controls ( figure  4d ; see figure  s4b for example images ) , consistent with a role for rac downstream of tiam1 .
we confirmed that these congression errors observed in tiam1-depleted cells were due to an increased prometaphase duration ( figure  s4c ) .
hence , cells with compromised tiam1-rac signaling fail to efficiently align chromosomes to the metaphase plate , resulting in a prolonged prometaphase .
this is probably due to maintained activation of the sac , which delays mitosis until all chromosome kinetochores are captured .
subsequently , we determined whether the increased centrosome separation of tiam1-depleted cells leads to the congression errors . using time - lapse fluorescence microscopy of individual mitotic cells expressing -tubulin - gfp
, we confirmed that in the presence of stlc , the majority of tiam1-depleted mitotic cells formed bipolar spindles ( figure  s4d ) ; furthermore , the intercentrosomal distance in prometaphase was now similar to that found in untreated controls ( figure  4e ) .
significantly , correcting the balance of forces during bipolar spindle formation completely rescued the chromosome congression errors resulting from tiam1 depletion ( figures 4f and 4 g ) and restored normal mitotic progression ( figures s4e and s4f ) .
together , these data indicate that the defects in chromosome congression induced by tiam1 depletion are due to the increased centrosome separation . in conclusion
, we have shown that tiam1 , acting through rac , is a critical mediator of forces during bipolar spindle assembly .
tiam1-rac signaling counteracts eg5 during bipolar spindle formation in  vitro and in  vivo .
to our knowledge , this is the first signaling module that retards centrosome separation during prophase in mammalian cells and the first demonstration of an increased rate of centrosome separation in prophase leading to chromosome congression defects .
importantly , we show that correcting the balance of forces , by attenuating eg5 activity in tiam1-depleted cells , completely rescues the defects in chromosome congression , allowing cells to satisfy the sac and progress through mitosis normally ( for a model see figure  4h ) .
there are numerous other pathways that promote [ 1 , 3 , 20 ] and oppose [ 13 , 21 ] centrosome separation during bipolar spindle formation .
this considerable overlap is not surprising given the importance of the bipolar mitotic spindle to the survival of eukaryotic cells , providing a number of fail - safes that decrease the risk of chromosome segregation errors during cell division .

Answer:
summarycentrosome separation , critical for bipolar spindle formation and subsequent chromosome segregation during mitosis , occurs via distinct prophase and prometaphase pathways [ 13 ] .
 kinesin-5 ( eg5 ) , a microtubule ( mt ) motor , pushes centrosomes apart during bipolar spindle assembly [ 4 ] ; its suppression results in monopolar spindles and mitotic arrest [ 5 , 6 ] .
 forces that antagonize eg5 in prophase are unknown . here
 we identify a new force generating mechanism mediated by the guanine nucleotide exchange factor ( gef ) tiam1 , dependent on its ability to activate the gtpase rac .
 we reveal that tiam1 and rac localize to centrosomes during prophase and prometaphase , and tiam1 , acting through rac , ordinarily retards centrosome separation .
 importantly , both tiam1-depleted cells in culture and rac1-deficient epithelial cells in  vivo escape the mitotic arrest induced by eg5 suppression .
 moreover , tiam1-depleted cells transit more slowly through prometaphase and display increased chromosome congression errors .
 significantly , eg5 suppression in tiam1-depleted cells rectifies not only their increased centrosome separation but also their chromosome congression errors and mitotic delay .
 these findings identify tiam1-rac signaling as the first antagonist of centrosome separation during prophase , demonstrate its requirement in balancing eg5-induced forces during bipolar spindle assembly in  vitro and in  vivo , and show that proper centrosome separation in prophase facilitates subsequent chromosome congression .


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:
three types of calibrated microspheres have recently been approved in japan as embolic agents for hypervascular tumors and arteriovenous malformations . to date , two types of embolic microspheres capable of being loaded with drug have been introduced : dc bead ( biocompatibles , farnham , uk ) and hepasphere ( biosphere medical , roissy cdg cedex , france ) . in a phase
ii randomized controlled study of transarterial chemoembolization ( tace ) using a drug - eluting bead ( deb - tace ) for hepatocellular carcinoma ( hcc ) , the precision - v study , the response rate after 6 months was 52% in the deb - tace group and 44% in the tace group using a lipiodol ( laboratoire guerbet , aulnay - sous - bois , france)/anticancer drug mixture solution ( lip - tace ) , showing no significant difference or superiority of deb - tace .
however , complication by postembolization syndrome , such as abdominal pain , fever , nausea , vomiting and liver enzyme elevation , developed in 2080% after lip - tace [ 3 , 4 ] , whereas symptoms developed in only 1837% after deb - tace [ 5 , 6 ] , showing that the complications were milder than those after lip - tace . on the other hand , deb - tace induced liver abscesses at a relatively high frequency , which could be fatal [ 5 , 7 , 8 , 9 ] .
adverse events after deb - tace have been reported occasionally [ 5 , 7 , 8 , 9 , 10 , 11 ] , but as it has just been introduced in japan , many points regarding adverse events are unclear with respect to the developmental mechanism and risk factors .
we encountered a hcc patient who underwent deb - tace and experienced delayed intratumoral hemorrhage .
an 81-year - old male regularly visited his physician for treatment of hepatitis c virus - related cirrhosis . on routine abdominal ultrasonography ( us ) ,
on esophagogastroduodenoscopy , a type 0-iia early gastric carcinoma with a diameter of 25 mm was detected in the lesser curvature of the middle body .
the patient was referred to our hospital for further examination and treatment . during the first examination ,
the liver function was classified as child - pugh class a , and the tumor markers were normal ( afp level : 3.4 ng / ml , afp - l3 fraction level < 0.5% ) , but the pivka ii had a level of 118 mau / ml , showing a mild elevation .
it was capsulated and enhanced in the arterial phase on dynamic computed tomography ( ct ) ( fig .
1 ) , and showed a mosaic pattern accompanied by a marginal hypoechoic zone on gray - scale us .
the mass was enhanced in the vascular phase ( 040 s ) on contrast - enhanced us ( ceus ) using sonazoid ( daiichi sankyo , tokyo , japan ) , and showed a hypoechoic area in the postvascular phase ( 10 min after an intravenous injection of sonazoid ) .
based on the tumor marker and imaging findings , the patient was diagnosed with hcc .
deb - tace was performed because the patient declined to undergo surgical resection of hcc .
access for tace was performed under sterile conditions and under local anesthesia , via the right femoral artery using a 3-fr sheath ( medikit , tokyo , japan ) and in a retrograde fashion .
when a microcatheter was advanced to the anterior segmental artery of the right hepatic artery and contrast imaging was applied , an intensely stained tumor was observed , with a5 as the feeding artery . a solution impregnated with 100300 m dc bead and 50 mg epirubicin hydrochloride , with a dc bead volume of 0.35 ml , was administered via the feeding artery to perform deb - tace .
disappearance of the intensely stained tumor image was confirmed by right hepatic arterial angiography , and the treatment was completed .
the course after deb - tace was favorable , and no adverse events above grade 3 according to the common terminology criteria for adverse events ( ctcae ) version 4.0 were observed .
endoscopic submucosal dissection ( esd ) of the early gastric carcinoma was performed about 1 month after deb - tace .
right hypochondriac pain suddenly developed 3 days after esd , but no adverse events were assumed to be caused by esd ( i.e. , free air , noted on dynamic ct ) .
however , the tumor diameter had increased from that before deb - tace , and the tumor showed a high - intensity area on unenhanced ct ( fig .
2a ) , which was not enhanced in the arterial phase on dynamic ct , suggesting intratumoral hemorrhage .
the hemodynamics of the tumor were followed using ceus over the time before and after deb - tace .
on ceus carried out on the day after deb - tace , the whole intratumoral enhancement decreased , and nonenhanced patchy regions , assumed to be necrosis , were noted in the tumor in the vascular phase . on ceus
performed 4 weeks after deb - tace , i.e. , immediately before esd , the tumor size was 33  31 mm , and the enhancement area was increased in the vascular phase ( fig .
however , the tumor had enlarged to 41  36 mm on ceus when the right hypochondriac pain developed ( 5 weeks after deb - tace ) , and changes in the echogenicity on gray - scale us and nonenhancement of almost the entire tumor in the vascular phase on ceus were noted ( fig .
based on the above findings , the cause of right hypochondriac pain may have been deb - tace - associated intratumoral hemorrhage .
since the hemorrhage was limited to inside the tumor , it stopped spontaneously with rest .
the advantages of deb - tace are as follows : the infusion dose of the chemotherapeutic agent can be modified by adjusting the chemotherapeutic agent carrier , while altering the depth of embolization with beads , the duration of tumor exposure to chemotherapeutic agent can be fine - tuned through sustained release of the chemotherapeutic agent , and systemic adverse reactions of chemotherapeutic agent can be attenuated by continuous release of high - dose chemotherapeutic agents into the tumors .
deb has proven to be extremely potent and safe by allowing large amounts of the chemotherapeutic agent to concentrate within the tumor over time , thereby maximizing the cytotoxic effect , which also makes it attractive as an effective treatment for large lesions .
favorable therapeutic effects have been reported occasionally [ 8 , 9 ] and have increased the expectations of hcc treatment with deb - tace ; however , the beads exhibit characteristic physical properties and behavior that are different from those of gelatin particles .
it is important to fully investigate these characteristics to avoid inadequacy of the therapeutic effect and to prevent the onset of adverse events .
previous studies have reported that the incidence of mild adverse events , such as postembolization syndrome , is lower in the deb - tace group compared with the lip - tace group [ 3 , 4 , 5 , 6 ] .
meanwhile , liver abscesses were induced at a relatively high frequency ( about 1.67.4% ) [ 5 , 7 , 8 , 9 ] .
malagari et al .   reported that the 30-day mortality was 1.26% among 237 hcc patients treated with deb - tace with dc bead loaded with doxorubicin , and that the cause was liver abscess in all cases .
regarding other adverse events , acute pancreatitis and cholecystitis developed with incidences of 15 and 16.3% , respectively .
previous studies have shown that rare adverse events included liver failure and infection , bile duct injury , upper gastrointestinal bleeding , pulmonary embolism , splenic infarction , or spinal embolization [ 1 , 7 , 10 , 11 ] .
unlike lip - tace , many adverse events occurred due to ischemic changes induced by the inflow of beads into organs other than the hcc lesion , which is characteristic of deb - tace .
tumor hemorrhage has also been reported after deb - tace [ 1 , 7 , 10 , 11 , 13 ] with large tumors , with a diameter of 516 cm , and the tumor locations were subcapsular in all previous reports . to our knowledge , there has been no case of a tumor with a diameter < 5 cm distinct from the subcapsular , as was observed in our patient .
there has been no report of a mechanism underlying the deb - tace - specific tumor hemorrhage . in general
, the mechanism of tumor rupture after tace might be related to increased intratumoral pressure as a result of rapid edematic expansion due to tumor necrosis or vascular injury , secondary to embolization .
the risk is particularly high in subcapsular lesions , and we must be careful because the spread of hemorrhage in the abdominal cavity can not only lead to hemorrhagic shock , but also peritoneal metastasis .
unlike the reported cases of tumor hemorrhage after deb - tace , in the present case , the tumor diameter was not large and the tumor was distinct from the subcapsular region .
however , intratumoral hemorrhage occurred about 1 month after deb - tace . local pooling of the contrast agent within the target tumor could occur during deb - tace , and seki et al .
reported that it occurred in 25.2% of 135 hcc patients treated with deb - tace ( epirubicin - loaded hepasphere ) .
while the cause of this local pooling remains unclear , it is similar to extravasation or blood sinus , suggesting that it was a local hemorrhage due to intratumor vascular collapse as a consequence of the treatment .
when local pooling of the contrast agent was noted , seki et al .   added a small amount of gelatin sponge particles , with a diameter ranging from 1 to 2 mm , to the feeding artery until the pooling disappeared .
based on the above findings , the observation of local pooling of the contrast agent within the target tumor during treatment suggests that intratumoral pressure has already increased , which was unlikely in our patient .
treatment - induced intratumoral hemorrhage continued immediately after deb - tace because no pooling was noted during treatment or on confirmation angiography following treatment .
however , it is possible that the amount of dc bead was insufficient and embolization was incomplete .
it was assumed that incomplete embolization subsequently caused intratumoral vascular collapse , i.e. , a phenomenon similar to pooling , and that the hemorrhage expanded to the necrotic intratumoral area by sustained release of the chemotherapeutic agent and embolization , leading to complication of intratumoral hemorrhage despite the low risk of tumor hemorrhage .
many points remain unclear , i.e. , the appropriate bead sizes for each case and the level of embolization , but it may be important to apply sufficient embolization because insufficient embolization is likely to lead to tumor hemorrhage .
deb - tace is considered to rarely cause adverse events , but fatal complications have been reported [ 5 , 7 , 8 , 9 ] , and reports of adverse events may increase with augmentation of the numbers of deb - tace - treated patients . if reports of tumor hemorrhage after deb - tace increase , the mechanism of intratumoral hemorrhage in cases similar to our patient may be elucidated .
intratumoral hemorrhage was suspected due to the presence of a high - intensity area in the tumor on unenhanced ct and a rapid increase in the tumor diameter and accompanying enlargement of the unenhanced area on ceus performed before and after deb - tace . based on these findings
it was difficult to assess the therapeutic effect of deb - tace by ct , based on lipiodol accumulation , unlike that after conventional lip - tace , and evaluation of the intratumoral hemodynamics could be important .
ceus is superior in evaluating intratumoral hemodynamics in real time , and the utility of ceus to evaluate the therapeutic effect after deb - tace was suggested .
we encountered a patient who experienced intratumoral hemorrhage about 1 month after deb - tace .
deb - tace for hcc is a new treatment method in japan , and reports of adverse events may increase in the future . to obtain the therapeutic effect of deb - tace while preventing the adverse events , it may be important to understand the characteristics of the beads themselves and to apply the appropriate embolization to each individual case .
it was also suggested that ceus is useful to evaluate the therapeutic effect after deb - tace .

Answer:
transarterial chemoembolization ( tace ) using a drug - eluting bead ( deb - tace ) for hepatocellular carcinoma ( hcc ) is a new treatment method .
 we report on a case of delayed intratumoral hemorrhage after deb - tace .
 an 81-year - old male with hepatitis c virus - related cirrhosis was diagnosed with a hcc of 35 mm in diameter in s5 detected by dynamic computed tomography ( ct ) and contrast - enhanced ultrasonography ( ceus ) .
 deb - tace with dc bead and epirubicin hydrochloride was performed because the patient declined to undergo surgical resection .
 the treatment was completed , and the course after deb - tace was favorable . however , right hypochondriac pain suddenly developed about 1 month after deb - tace .
 unenhanced ct showed an increase of the tumor diameter and intratumoral high - intensity area , which was not enhanced in the arterial phase .
 ceus performed at the time of right hypochondriac pain ( 5 weeks after deb - tace ) showed nonenhancement of almost the entire tumor in the vascular phase .
 the cause of the symptom may have been deb - tace - associated intratumoral hemorrhage .
 tumor hemorrhage has been reported after deb - tace with tumors > 5 cm in diameter , and the tumor locations were subcapsular in all previous reports . there has been no case of a tumor with a diameter < 5 cm distinct from the subcapsular , as was observed in our patient .
 incomplete embolization might be the cause of the intratumoral hemorrhage experienced by this case presenting a few risks . to obtain the therapeutic effect of deb - tace while preventing the adverse events
 , it may be important to understand the characteristics of the beads and to apply the appropriate embolization to each individual case .


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:
these include evolution from fiberoptic imaging to generation of images using a charge - coupled device and high definition digital imaging .
enhanced endoluminal imaging techniques have included chromoendoscopy and modalities that aspire to optical biopsy . among techniques for enhanced optical diagnosis , narrow band imaging ( nbi )
is a proprietary imaging modality in which the endoscope processor filters standard white light to specific wavelengths in the blue    green spectrum ( 415  nm and 540  nm ) .
nbi thereby capitalizes on the peak absorption of hemoglobin and has the ability to accentuate visualization of the mucosal vasculature 1 .
proposed clinical applications of nbi include endoscopic evaluation of barrett s esophagus and endoscopic diagnosis of colorectal polyps .
studies of nbi in endoscopic inspection of barrett s esophagus have demonstrated high sensitivity of nbi in detection of barrett - associated high grade dysplasia 2 , and the ability of nbi to detect dysplasia in a higher proportion of patients with fewer biopsy samples compared with standard white light endoscopy 3 . with respect to colorectal polyps ,
an nbi - based classification scheme has been developed which may accurately distinguish adenomatous from hyperplastic polyps 4 , although it is not certain that use of nbi improves polyp detection rates 5
 6
 7 . despite data regarding potential gastrointestinal endoscopic applications of nbi , the degree to which nbi use has been adopted into clinical practice
legitimate questions exist regarding the degree to which efficacy of nbi as demonstrated in clinical studies will translate into effective use of nbi in actual practice 8 .
the aim of this study , therefore , was to prospectively define the rate of nbi use among patients referred to a large group endoscopy practice for diagnostic endoscopy ( esophagogastroduodenoscopy and colonoscopy ) , and to identify procedural factors associated with nbi use .
approval to conduct this study as a quality assurance protocol was granted by the institutional review board at the study institution .
this study was conducted at the endoscopy center of a tertiary care academic center , where both inpatient and outpatient procedures are performed in a hospital - based suite .
each procedure room is equipped with nbi capability ( 180 series gastroscope or colonoscope , cv-180 evis exera ii video processor , and clv-180 light source ; olympus medical systems , tokyo , japan ) .
each consecutive esophagogastroduodenoscopy ( egd ) and colonoscopy was directly observed by in - room endoscopy technicians , who assist the endoscopist with equipment setup and when endoscopic accessory use ( i.  e. biopsy forceps , polypectomy snare , endoscopic hemostatic device , etc . )
a technician is present in each procedure room for the entire duration of each procedure . for each eligible procedure , the technician documented whether or not nbi was used .
procedures performed by the study author were not included ; otherwise all faculty endoscopists were eligible for observation .
the following endoscopic procedures were excluded from the analysis : egd or colonoscopy with therapeutic intent , specifically endoscopic dilation , endoluminal stent maneuvers , or delivery of endoscopic hemostatic therapy ; egd for nasoenteral or percutaneous feeding tube placement ; balloon- or spiral - assisted small - bowel enteroscopy ; endoscopic retrograde cholangiopancreatography ; egd with endoscopic ultrasound ; ileoscopy and pouchoscopy .
following completion of the 2-week observational study period , operative reports including reports generated by olympus endoworks software and dictated operative notes were manually reviewed by the study author , who was not blinded to study design or intent .
the following data were extracted : procedure type , procedure indication , identification of attending endoscopist , trainee involvement , patient type ( inpatient versus outpatient ) , procedure start time ( a.m. vs. p.m. ) , sedation - type ( endoscopist - directed conscious or deep sedation vs. monitored anesthesia care with anesthesia staff support ) ; performance of endoscopic polypectomy , either by snare or forceps biopsy ; performance of endoscopic tissue biopsy for intent other than polypectomy .
extracted data were stored in a microsoft excel spreadsheet , and statistical analyses were performed using jmp 10.0.0 software ( sas institute , cary , nc , usa ) .
the chi - squared or fisher s exact test was used for comparison of categorical variables . two - sided p values of  <  0.05 were considered statistically significant .
during the two - week observational study period in july    august 2013 , data regarding nbi use were recorded for 318 elective endoscopic procedures , consisting of 106 egds and 212 colonoscopies .
the most common indications for egd were evaluation of abdominal pain / dyspepsia ( 22  % ) and evaluation of gastroesophageal reflux disease ( 19  % ) .
additional indications included evaluation of weight loss , anemia or suspected gastrointestinal bleeding , and diarrhea . the most common indication for colonoscopy was screening / surveillance for colorectal cancer ( 56  % ) .
additional indications included evaluation of suspected or established inflammatory bowel disease , anemia or suspected gastrointestinal bleeding , and diarrhea .
this included use of nbi in 4.7  % ( 5/106 ) of egds and 7.5  % ( 16/212 ) of colonoscopies ( p  =  0.47 for comparison ) .
no difference in rate of nbi use was found when comparing egd with or without biopsy ( 5.5  % [ 3/55 ] vs. 3.9  % [ 2/51 ] ; p  =  1 ) , or when comparing colonoscopy with or without biopsy ( 10.5  % [ 8/76 ] vs. 5.9  % [ 8/136 ] ; p  =  0.28 ) .
nbi use was significantly higher in colonoscopy with polypectomy when compared with colonoscopy without polypectomy ( 13  % [ 10/77 ] vs. 4.4  % [ 6/135 ] ; p  =  0.03 ) ( fig .  1 ) .

rates of narrow band imaging ( nbi ) use for all study procedures , esophagoduodenoscopy ( egd ) with and without biopsy , colonoscopy with and without polypectomy .
, there was no association between patient type ( outpatient vs. inpatient ) , procedure start time , sedation type , or trainee involvement and use / non - use of nbi . for both egd and colonoscopy ,
there was no association between procedure indication and use / non - use of nbi .
nbi use was observed in zero of seven egds with a documented primary procedural indication of screening for or surveillance of barrett s esophagus .
nbi use was observed in 2 of 9 ( 22  % ) colonoscopies with a documented primary indication of surveillance in the setting of chronic ulcerative colitis .
no use of an alternative imagine modality , such as methylene blue chromoendoscopy or high magnification endoscopy was described in any operative report .
observed endoscopic procedures were performed by 23 faculty endoscopists , with a procedure volume ranging from 1 to 58 per endoscopist during the 2-week study period .
the rate of nbi use ranged from 0 to 100  % of procedures per endoscopist .
after excludsion of endoscopists who performed fewer than five endoscopies during the study period , the rate of nbi use for the remaining 15 endoscopists ranged from 0 to 23  % . there was a significant difference in rate of nbi use ( p  <  0.01 for overall comparison ) amongst these 15 endoscopists .
nbi use among the 5 highest volume endoscopists ranged from 0 to 16  % . among cases with
observed nbi use , photodocumentation of nbi use was present in 24  % ( 5/21 ) of operative reports .
this observational study detected use of nbi in 6.6  % of elective endoscopic procedures .
the highest rate of nbi use was observed in colonoscopies with polypectomy ( 13  % ) , and this rate was significantly higher than that observed in colonoscopies without polypectomy .
this study also detected a significant difference in the rate of nbi use in global comparison of individual endoscopists .
specific factors that influence the adoption of nbi use into routine practice by individual endoscopists were not examined in this study .
endoscopists were not asked to self - report nbi use and were not informed of the study .
the study was designed in this fashion to avoid the potential of a hawthorne effect , wherein performance may be influenced in subjects who are aware that they are being observed .
the endoscopists were blinded to the study , making the study design and findings unique .
a survey of european university hospitals reported use of nbi or alternative commercial enhanced - imaging technology in 67  % of institutions in the evaluation of barrett s neoplasia 9 , but did not report a per - case use rate . in the current study , there was no a priori hypothesis regarding the rate of nbi use expected in this observational study , as there are limited standard recommendations or guidelines for routine nbi use in diagnostic endoscopy , and existing guidelines are open to flexible interpretation .
for instance , the american gastroenterological association medical position statement on barrett s esophagus suggests that chromoendoscopy or electronic chromoendoscopy is not necessary in the routine endoscopic surveillance of barrett s esophagus , but may be helpful in guiding biopsies for patients with dysplasia or visible mucosal abnormalities 10 .
the rate of nbi use in this study can therefore not be subjectively designated as high or low , but instead serves as a baseline metric in this study setting against which future nbi use can be measured .
adoption of nbi use in routine diagnostic endoscopy may have implications for application of future enhanced - imaging technologies . in the hands of the endoscopist
no additional equipment is required other than an existing video monitor and nbi - equipped scope and processor .
an endoscopist can toggle between nbi and standard white light literally in seconds , without use of additional endoscopic devices , accessories , or medications . and while there may be a learning curve for interpretation of nbi images 11
 12 , endoscopist interpretation of endoluminal nbi images would seem less a departure from white light endoluminal images than interpretation of images generated by other optical techniques , such as endomicroscopy , that focus on cellular structures . based on these criteria , one would speculate that adoption and use of imaging technologies requiring additional equipment or capital investment , additional time with respect to procedure duration , and/or increasingly complex image analysis would be lower than that for nbi . finally , it is worthwhile to note that documentation of nbi use was uncommon .
photodocumentation of nbi use was provided in 24  % ( 5/21 ) of operative reports from cases in which nbi use was observed .
future consideration may be warranted as to whether documentation guidelines should exist for procedural use of nbi or other adjunct imaging modalities .
an american society of gastrointestinal endoscopy preservation and incorporation of valuable endoscopic innovations ( pivi ) statement on real - time endoscopic assessment of histology of colon polyps suggests that lesion photocumentation is necessary if a resect - and - discard strategy is to be implemented 13 . while extending the study duration to increase sample size would increase statistical power and eliminate the possibility of type ii error in examining factors associated with nbi use , the study as completed is likely to have strong internal validity , in that the observed range of endoscopic procedures during the 2-week time period is likely to offer an accurate representation of the range of endoscopic practice in this setting
. it may not be possible , however , to generalize the study findings to other institutions or endoscopy settings which may have differing practice patterns .
instances of nbi use may not have been documented if not observed or not recognized by the endoscopy technician .
an alternative would have been to video record the entire procedure for subsequent review ; however maintenance of adequate blinding with this approach would be challenging .
documented cases of nbi use can not distinguish between intentional and unintentional nbi use    for instance , if the endoscopist had inadvertently pressed the button on the scope handle for application of nbi when he / she had intended instead to press the button for image capture . in addition , there was limited heterogeneity in some of the procedural variables ( e.  g. trainee involvement ) to adequately assess for potential association with nbi use / non - use .
a post hoc survey of participating endoscopists might offer insight as to whether their opinions on the role of nbi match their actual practice , but has no bearing on the aim of this study , which was to objectively document rate of nbi use . in summary ,
additional large - scale prospective data are needed to assess the magnitude of impact of nbi on routine endoscopic practice .

Answer:
background and study aim : narrowband imaging ( nbi ) is an enhanced endoscopic optical technique which filters white light and accentuates imaging of the mucosal vasculature .
 potential clinical applications of nbi include endoscopic inspection of barrett s esophagus and endoscopic diagnosis of colorectal polyps .
 the degree to which nbi use has been adopted into clinical practice is unknown . the study objective was to identify the rate of nbi use in patients undergoing elective esophagoduodenoscopy ( egd ) and colonoscopy , and to identify procedural factors associated with nbi use .

 methods : elective endoscopic procedures were prospectively observed over a 2-week study period .
 nbi use during diagnostic egd or colonoscopy was recorded in blinded fashion .

 results : nbi use was observed in 6.6  % ( 21/318 ) of procedures , including 4.7  % ( 5/106 ) of egds and 7.5  % ( 16/212 ) of colonoscopies .
 there was no difference in rate of nbi use when comparing egd with or without biopsy , or when comparing colonoscopy with or without biopsy .
 nbi use was significantly higher in colonoscopy with polypectomy compared with colonoscopy without polypectomy ( 13  % [ 10/77 ] vs. 4.4  % [ 6/135 ] , p  =  0.03 ) .
 nbi use varied significantly among endoscopists .
 there was no association between patient type ( outpatient vs. inpatient ) , procedure start time , sedation type , or trainee involvement and use / non - use of nbi . procedural documentation of nbi use was limited .

 conclusions nbi use was observed in 6.6  % of elective endoscopic procedures and was highest in colonoscopies with polypectomy .
 rate of nbi use varied significantly among endoscopists .
 additional studies are needed to assess the magnitude of impact of nbi on routine endoscopic practice .


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:
in 1978 , primary health care was seen as the solution to the inadequate illness management systems that had developed throughout the world .
it was hoped that phc would address some of the major inequalities in health that were observed by a balanced system of treatment and disease prevention . the world health organization ( who ) envisaged that phc would take place as close as possible to where people live and work and be the first element of a continuing health care process .
additionally , health service collaboration and multi - professional partnerships were expected to replace professional boundaries and competition . to sum up
, phc used family physician as the most important ways to increase equitable access and utilization of public health services . in any case , family physician , with the key elements of first contact , comprehensiveness , continuity , and coordination of patient care , is central to the health of any health care system .
recent government initiatives are supporting general practice to deliver health care through a variety of means and personnel .
these initiatives have included expanding the roles of nurses in general practice and enabling better access to allied health services through general practitioners ( gps ) .
evidence clearly indicates the effectiveness of teams in improving the outcomes , especially in chronic disease .
now , people in most of the countries use professional and educated nurses [ called nurse practitioner ( np ) ] besides family physician or are under their supervision for diagnosis , treatment , and specifically health education of the family . in accordance with the international council of nurses definition ,
 a nurse practitioner is a registered nurse who has acquired the expert knowledge base , complex decision - making skills , and clinical competencies for expanded practice , the characteristics of which are shaped by the context and/or country in which s / he is credentialed to practice .
 the royal college of nursing ( rcn ) defines an np as a registered nurse who has undertaken a specific course of study of at least first - degree ( honors ) level and who :
 makes professionally autonomous decision , for which he or she is accountable;works collaboratively with other health care professionals;provides counseling and health education;screens patient for disease risk factors and early signs of illness ; andhas the authority to admit or discharge patients from their caseload , and refers patients to other health care providers as appropriate .

makes professionally autonomous decision , for which he or she is accountable ; works collaboratively with other health care professionals ; provides counseling and health education ; screens patient for disease risk factors and early signs of illness ; and has the authority to admit or discharge patients from their caseload , and refers patients to other health care providers as appropriate . in new reform toward family physician in iran ,
there is not enough attention toward nurses , their services , and specifically their role in education and counseling .
according to the health - for - all goals , the central concern of nurses in primary care should be the prevention of the disease by educating individuals and families on healthy lifestyles , and teaching community health workers and traditional birth practitioners to carry out many of the functions that nurses themselves have normally performed .
whereas a big part of the family physician program has not been realized in iran yet ( especially in big cities with a population of over 20,000 ) , most graduate nurses are now working in the school of nursing and midwifery , hospitals , and ambulatory clinics with limited responsibilities .
in addition , most graduate nurses in our community can play an important role in preventing medicine and family physician team . consequently , in spite of their ability and capacity , they have a brief role in our family physician team & their job description .
the main goal of this study was to review the role and situation of nps in the new reform for better use of their capabilities in health care services .
this is a qualitative , comparative ( role of nurses in family physicians team ) , and cross - sectional study that was carried out with triangulation method in three stages in 2011 . in the first stage , we conducted a literature review to design a conceptual framework .
the second stage was a comparative study on four countries that had great experiences in these two fields ( family physician reform and nps ) and included usa , uk , austria , and canada , based on purposive sampling . in the third stage ,
all experts were completely familiar with the health system and had academic and research experiences in nursing education system in iran .
the survey on health systems in different countries indicates that many of the health sectors have begun their reforms with two main goals , including quality improvement and cost limiting .
family physician and referral system are among the few options that can maintain and even upgrade the quality of services , reducing the costs simultaneously . as each health system in each country
has its specific referral system , iran is now on the verge of implementing a  best fit  referral system reform .
so , it is crucial to well define the roles of each component , such as nurses , in this system . in the united states ,
nps are licensed by the state in which they practice , and have a national board certification ( usually through the american nurses credentialing center or american academy of nurse practitioner ) .
most nps specialize in a particular field of medical care , and there are as many types of nps as there are medical specialties .
nps provide high - quality , cost - effective individualized care that is comparable to the health care provided by the physicians , and np services are often covered by insurance providers .
role of nurses in some organizations in canada , the nurses involved in clinics should participate in specific training course of diagnosis and management of health care after registration .
then , they are allowed to prescribe drugs , and lab and other diagnostic tests .
having access to patient medical record , nps can reduce unnecessary visits . according to the standards of practice for nps , the college of nurses of ontario states that they offer  the full scope of primary health care practice , including consultation with physicians or other health care professionals when the client requires care beyond the nps scope of practice .
further , they are accountable for establishing a consultative relationship with a physician and consultation occurs with a family physician ; however , nps may consult with a specialist physician , if appropriate to the situation and practice setting .
no legislative or regulatory deterrent related to the scope of practice exists for the nps to refer to specialist physicians . in austria , nurses in nursing home and maternity do some of the medical procedures under the supervision of physicians .
these nurses are educated , and can treat , inject drugs , and request for some diagnostic tests for their patients . in the united kingdom ,
the gps monopoly on primary care has been broken by nurse - led services , including nhs direct , which provides 24-h health advice by telephone , and nhs walk - in centers , which treat minor illness and injury .
practice nurses and nps increasingly substitute for gps in the care of minor illness and routine management of chronic diseases such as asthma , diabetes , and coronary heart disease . in england and wales ,
the role of the nps had evolved from that of undertaking traditional , medically prescribed nursing tasks in a treatment room to undertaking screening activities and health assessments of new patients , with over 50% of the nps managing chronic disease clinics .
six experts in two panels were asked to confirm the role of nurses in family physician reform .
they suggested that special courses are needed to empower our graduated nurses for their new rules .
meanwhile , using nps as substitution of gps does not seem to be logically correct due to the gps workload and the social and cultural background in iran .
the survey on health systems in different countries indicates that many of the health sectors have begun their reforms with two main goals , including quality improvement and cost limiting .
family physician and referral system are among the few options that can maintain and even upgrade the quality of services , reducing the costs simultaneously . as each health system in each country
has its specific referral system , iran is now on the verge of implementing a  best fit  referral system reform .
so , it is crucial to well define the roles of each component , such as nurses , in this system .
in the united states , nps are licensed by the state in which they practice , and have a national board certification ( usually through the american nurses credentialing center or american academy of nurse practitioner ) .
most nps specialize in a particular field of medical care , and there are as many types of nps as there are medical specialties .
nps provide high - quality , cost - effective individualized care that is comparable to the health care provided by the physicians , and np services are often covered by insurance providers .
role of nurses in some organizations in canada , the nurses involved in clinics should participate in specific training course of diagnosis and management of health care after registration .
then , they are allowed to prescribe drugs , and lab and other diagnostic tests .
having access to patient medical record , nps can reduce unnecessary visits . according to the standards of practice for nps , the college of nurses of ontario states that they offer  the full scope of primary health care practice , including consultation with physicians or other health care professionals when the client requires care beyond the nps scope of practice .
further , they are accountable for establishing a consultative relationship with a physician and consultation occurs with a family physician ; however , nps may consult with a specialist physician , if appropriate to the situation and practice setting .
no legislative or regulatory deterrent related to the scope of practice exists for the nps to refer to specialist physicians . in austria , nurses in nursing home and maternity do some of the medical procedures under the supervision of physicians .
these nurses are educated , and can treat , inject drugs , and request for some diagnostic tests for their patients . in the united kingdom ,
the gps monopoly on primary care has been broken by nurse - led services , including nhs direct , which provides 24-h health advice by telephone , and nhs walk - in centers , which treat minor illness and injury .
practice nurses and nps increasingly substitute for gps in the care of minor illness and routine management of chronic diseases such as asthma , diabetes , and coronary heart disease . in england and wales ,
the role of the nps had evolved from that of undertaking traditional , medically prescribed nursing tasks in a treatment room to undertaking screening activities and health assessments of new patients , with over 50% of the nps managing chronic disease clinics .
six experts in two panels were asked to confirm the role of nurses in family physician reform .
they suggested that special courses are needed to empower our graduated nurses for their new rules .
meanwhile , using nps as substitution of gps does not seem to be logically correct due to the gps workload and the social and cultural background in iran .
according to the who , in most countries , nurses are the most important group of health workers in terms of numbers , closeness to people and their health problems , and understanding of community needs . there is still debate in nursing and medical circles about what the focus of their role should be .
for example , lauder , sharkey , and reel suggest that nps and gps in rural and remote areas should be interchangeable and that the focus should be on the competency of the person delivering care rather than the right of one discipline ( medicine ) to perform a particular role .
in contrast , campbell believes that public acceptance of nurses as gp substitutes would be poor , and therefore suggests that a better role for nurses in primary care would be health education and illness prevention . on the other hand , in our country ( iran ) until now , nurses have not got a competent role in health sector reform .
given that consumers have limited understanding of phc , it is not surprising they do not articulate confidence in nps acting autonomously but rather as complementary to gps , perhaps undertaking initial assessment for triage purposes and providing ongoing management , education , and support under the gps delegation .
they would also like them to be family oriented and holistic in their practice , supporting their emotional and social needs in the context of their family lives .
it means that any effort to change nurses roles in health care services should accompany with some social and cultural changes toward their competencies . in iran , whereas a noticeable reform toward  family physician  is going on , redefining nurses role is essential .
they can perform more active roles in associating with gps in the clinics of family physicians , both in urban and rural areas , even with higher degrees of autonomy .
their competencies for case management , education , treatment , and follow - up may repair many of the pitfalls we are confronting in health care services .
of course , if it has to be done , special courses are needed to empower graduated nurses for their new rules .
meanwhile , substitution of gps with nps does not seem to be a good suggestion due to gp workload and social and cultural background in iran .
thus , it can be concluded that in order to achieve the goals of family physicians reform and also utilize the maximum capacity of trained nurses , a fixed and definite place must be considered for them in the gp team to provide their services under the supervision of family physicians .
their active role not only enriches the family physician team , but also might be crucial in patients training , which is currently one of our weaknesses .

Answer:
background : most countries use educated nurses called  nurse practitioners  ( nps ) besides the family physicians for diagnosis , treatment , and specifically health education of the family .
 the main goal of this study was to redefine the role of nps for better use of their capabilities in the so - called  family physician reform  in iran.materials and methods : this is a qualitative and comparative study carried out in three stages ( triangulation method ) in 2011 . in the first stage
 , we conducted a literature review to design a conceptual framework .
 the second stage was a comparative study on four countries . in this study , we focused on the role of nps , which in turn helped to redefine this role in the health sector reform of iran . in the third stage ,
 two expert panels were involved and the suggested roles were confirmed.results:in the united states , nps are licensed by the state in which they practice and have a national board certification . in canada , nurses involved in clinics should participate in specific training course of diagnosis and management of health care after registration . in austria ,
 nurses in nursing homes and maternity do some of the medical procedures under the supervision of the physicians . in the united kingdom ,
 nps increasingly substitute for gps in the care of minor illness and routine management of chronic diseases.conclusions:there is still debate in nursing and medical circles about what the focus of the np roles should be . in iran , whereas a noticeable reform toward  family physician
 is ongoing , redefining the nurses role is essential .
 they can perform more active roles in associating with gps in the clinics of family physicians , both in urban and rural areas , even with higher degrees of autonomy .


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:
neonatal intestinal perforation ( nip ) is an extremely rare complication of intestinal hemangioma ( ih ) .
neonates younger than 30 days and having perforation include more common etiologies such as necrotizing enterocolitis , meconium ileus , and spontaneous idiopathic as well as gastric perforation.1 nip has been associated with mortality rates of 40% to 70%.2 this report presents a rare case of nip resulting from ih .
a 27-day - old male neonate was admitted with low - grade fever , abdominal distension , and bilious vomiting associated with bouts of diarrhea of 2 days duration .
baby was a product of full - term spontaneous vaginal delivery with normal prenatal follow - up . before coming to our hospital ,
the patient weighed 4.1  kg and was febrile , irritable , and moderately dehydrated .
plain abdominal radiographs suggested bowel obstruction versus ileus , therefore a barium meal follow through was obtained , which showed persistently dilated jejunal and proximal ileal loops but normal flow of contrast .
computed tomographic scan with intravenous contrast was not done because of family history of allergic reaction to the dye . on the basis of the diagnosis of intestinal obstruction , a decision for exploratory laparotomy was made .
laparotomy revealed dense inflammatory adhesions surrounding a solitary hemangioma located at the antimesenteric border 30 cm from the ileocaecal valve and on close inspection a small perforation was seen on one side of the hemangioma , which was sealed by extensive adhesions ( fig .
other areas of the bowels inspected were normal and resection with primary anastomosis was done .

dilated capillary spaces lined by single layer of endothelium with proliferation of endothelial cells in between .
hemangiomas of the gastrointestinal tract are rare and account for only 0.05% of all intestinal neoplasms.3 they are commonly found within the small bowel , jejunum being the commonest site and compose 7 to 10% of all benign tumors.3

4 they have a tendency toward multiplicity , with solitary tumors being extremely rare.3
 5 microscopically , ih may be classified as cavernous , capillary , or mixed types , commonest being the cavernous.6 the usual presentation is intestinal bleeding usually insidious presenting as anemia7 or sometimes acute and potentially life threatening.4 other forms of rare presentation include intussusception , obstruction , and perforation.8
 9
 10
  ileal perforation is a rare complication of ih in neonates , and so far , only one case has been reported in the literature , by mcgaughey et al,11 who discovered evidence of ileal perforation due to ih while operating on a neonate with intestinal obstruction .
ours is the second reported case of nip due to ih , and what makes it unique is the fact that the hemangioma belonged to the rare capillary type whereas the previously reported case was of the commoner cavernous type .
diagnosis in both reported cases , including ours , were made only at surgery for presumed acute intestinal obstruction .
although various causes of nip including the rare ih have been reported , diagnosis can be difficult and exploratory laparotomy has often proved to be the final diagnostic tool .
although a rare cause of intestinal perforation in neonates , ih should be considered in the differential diagnosis .

Answer:
intestinal perforation is an extremely rare complication of hemangioma of the small intestine in the neonatal period .
 this is a case report of a 27-days - old male infant who presented with signs and symptoms of acute intestinal obstruction .
 exploratory laparotomy findings revealed intestinal perforation due to solitary hemangioma in the ileum , which led to obstruction from peritoneal reaction and adhesions .
 there are two reported cases in the literature presenting with ileal perforation in the pediatric age group , but only one previous report mentioned in the neonatal period . because there are other more common causes of perforation in the neonatal period , intestinal hemangioma in spite of its rarity
 should be included in the differential diagnosis .


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 36-year - old japanese man was referred to us for the evaluation of bilateral retinal hemorrhages .
he developed an acute vision decrease in his left eye , pain in his right chest area , and headache after he had trekked at an altitude of 4600 m in tibet for 1 week .
because of the illness , he descended 3 days later , and he felt better at that time but the visual impairment remained .
our examination showed that his visual acuity was 20/20 od and 20/200 os with refractive errors of  0.25 diopters ( d ) od and  0.50 d os measured 3 weeks after the onset of the visual decrease .
funduscopic examination revealed multiple intraretinal hemorrhages bilaterally and a macular hemorrhage in the left eye [ fig . 1 ] .
sd - oct ( spectralis , heidelberg engineering , heidelberg , germany ) showed that the macular hemorrhage was in the superficial layer of the retina beneath the inner limiting membrane of the left eye [ fig
the thickness of the choroidal layer at the fovea was 530 m od and 490 m os which was thicker than the mean subfoveal choroidal thickness in normal subjects of approximately 300 m in the enhanced depth images obtained by spectralis sd - oct .
most recent studies report that the average subfoveal choroidal thickness is 287 m in caucasians of an average age of 50.4 years and 272.6 m in the japanese of an average age of 30.5 years obtained by the enhanced depth imaging of the spectralis sd - oct .
fundus photograph of the right eye ( a ) and the left eye ( b ) showing multiple intraretinal hemorrhages and a macular hemorrhage in the left eye optical coherence tomographic images at the first visit .
the choroidal layers ( white arrowheads ) are thick in both eyes ( a : right eye , b : left eye ) .
a macular hemorrhage located in the superficial retina beneath the inner limiting membrane of the left eye ( white arrow ) can be seen
individuals with acute mountain sickness present with lethargy , nausea , headache , insomnia , anorexia , and disorientation .
the proposed mechanism for the symptoms of acute mountain sickness is respiratory alkalosis from hyperventilation and increased cerebral blood flow . in hace , there is a breakdown of the blood
however , hace can lead to long - lasting severe neurological and psychiatric disorders and even death in some cases .
wiedman and tabin examined 40 climbers who had ascended to altitudes of over 4870 m whether they developed signs of har , symptoms of acute mountain sickness , and clinically signs of hace .
thus , they concluded that when advanced har is recognized , treatment should be initiated for hace with oxygen , steroids , or diuretics , and immediate descent to prevent further progression of hace . a pronounced increase in retinal blood flow in mountaineers with retinal hemorrhage and
dilated epipapillary network has been detected with heidelberg retina flowmeter after acute hypoxic stress at high altitudes .
the increase in retinal blood blow and cerebral blood flow under hypoxic conditions may also be associated with an increase in choroidal blood flow resulting in an increase in choroidal thickness .
the pathogenesis of the increased choroidal thickness may be similar to that of hace , namely a breakdown of the blood
it is difficult to draw strong conclusions from a single case ; however , we suggest that measurements of the choroidal thickness may be useful in evaluating the status of hace
. currently , data are not available from population - based studies on the normal values for the choroidal thickness of a large number of caucasians or asians .
further studies are needed to evaluate the choroidal thickness in mountaineers with acute mountain sickness .

Answer:
we report a case of high - altitude retinopathy with increased choroidal thickness detected by spectral - domain optical coherence tomography ( sd - oct ) . a 36-year - old japanese man developed an acute vision decrease in his left eye after he had trekked at an altitude of 4600 m in tibet for 1 week .
 his visual acuity was 20/20 od and 20/200 os with refractive errors of  0.25 diopters ( d ) od and  0.50 d os 3 weeks after the onset of the visual decrease .
 funduscopic examinations revealed multiple intraretinal hemorrhages bilaterally and a macular hemorrhage in the left eye .
 sd - oct showed that the thickness of choroidal layer at the fovea was 530 m od and 490 m os which is thicker than that in normal subjects of approximately 300 m .
 we suggest that the increase in the retinal blood flow under hypoxic conditions may be associated with an increase in the choroidal blood flow resulting in an increase in choroidal thickness .


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:
( itbl ) are
 often used as synonyms for hilar or intrahepatic diffuse bile duct strictures ,
 necrosis , ecstasies , or dilatations ( see figure 1 ) [ 1 , 2 ] .
the reported
 incidence of itbl after olt varies between 1.4% and 20% [ 35 ] .
this complication encounters for major morbidity and mortality , creates high
 costs , and aggravates organ shortage [ 7 , 8 ] .
a recent study on 1113 liver transplant patients showed
 no relevant donor or recipient risk factor of itbl .
there are only
 two studies evaluating the impact of chemokine receptors ( ccr ) on the
 development of itbl [ 6 , 9 ] . in moench 's study on 146 olt patients ccr-532 mutation
was evaluated and correlated
 with a significant increased incidence of itbl . a recent study on
 137 pediatric liver transplants failed to show an association between ccr-532 and biliary complications .

ccr-532 is a single base - pair deletion of ccr-5 that
 leads to a nonfunctional receptor .
the clinical impact of this
 mutation was first described for homozygous ccr-532 caucasians being highly resistant to hiv-1
 infection .
if there was an immunological cause for itbl , a
 nonfunctional ccr might be relevant for this complication .
experimental studies correlated a
 nonfunctional ccr-5 with less acute rejection episodes in lung , heart   and islet cell transplantation .
the aim of this study was to re - examine a
 correlation of ccr-532 genotype with the susceptibility of itbl
 within our patients .
all patients were transplanted at the transplant center of the
 humboldt university of berlin between 03/2002 and 03/2005 and were included
 during routine follow - up examination .
11 patients with the established diagnosis of itbl , that were transplanted
 earlier than 03/2001 , were selectively included into this study due to the low
 incidence of itbl of only 4.0% within our patients .
the diagnosis of itbl was
 made within the first year after transplantation in 82% of the patients .
the
 following demographic data were extracted from the hospital records and
 evaluated : age , gender , underlying liver disease , blood group , child - pugh score
 ( cps ) , model for end stage liver disease score ( meld score ) , initial
 immunosuppression , cytomegalovirus infection ( cmv ) , hla match , donor age and
 gender , donor serum sodium , cause of brain death and length of stay on
 intensive care unit ( icu ) prior to organ harvesting .
154 patients received a
 cadaver graft , 15 patients received a graft from a living donor .
itbl was defined as nonanastomotic intra- or
 extrahepatic biliary strictures without any history of hepatic artery
 complications , abo , incompatibility or other known causes of bile duct damages .
 in all cases patency of the hepatic artery
recurrence
 of primary biliary cirrhosis ( pbc ) or primary sclerosing cholangitis ( psc ) and
 vanishing bile duct syndrome were ruled out in all cases by liver biopsy .

diagnosis of itbl was always established with endoscopic retrograde
 cholangiography or percutaneous transhepatic cholangiography .
all
 genotype analyses were performed at the johannes gutenberg university of mainz ,
 department of transplantation surgery . for analysis of the ccr-5 genotype ,

genomic dna was prepared from 200 l peripheral blood using the qiaamp dna blood
 kit ( qiagen , cologne , germany ) .
2.5 l of dna were amplified by pcr using the
 following ccr-5 specific primers : ccr - sense , 5-caaaaagaaggtcttcattacacc-3
 and ccr-5-antisense , 5-cctgtgcctcttcttctcatttcg-3. the pcr mixture was
 composed of 2.5 l 10 x pcr buffer ( roche molecular systems ,
 mannheim , germany ) , 0.5 l of 12.5 mmol / l dntp ( peqlab , erlangen ,
 germany ) , 2.5 l of each sense and antisense primer ( 10 mol / l ) , and 1.25 u amplitag dna polymerase
 ( roche molecular systems ) in a total volume of 25 l .
forty pcr cycles were run on a genius
 thermocycler ( techne , cambridge , uk ) , using the following temperature profile :
 initial denaturation , 94c 3 minutes ; amplification , 94c 1 minute , 64c 1
 minute , and , 72c 1 minute ( 40 cycles ) ; terminal elongation , 72c 9 minutes .
the size
 of the wild - type product was 189 base pairs ( bp ) , and the ccr-532 allele yielded a product of 157 bp .
descriptive statistics
 were used to summarize the donor and recipients characteristics . for
 independent variables , cross tabulations and chi - square tests were performed .

nonparametric variables were evaluated with fisher 's exact test ,   and asymptotic
 significance was calculated .
all
 calculations were performed in association with the department of biometrical
 medicine of the humboldt university of berlin .
a total
 number of 169 liver transplant recipients were available for genotyping and
 complete data analysis .
gender and age were equally distributed between
 wild - type group ( wt / wt ) and heterozygous ccr-532 group ( wt/32 ) .
the observed genotype
 frequency was as expected assessed by hardy - weinberg equilibrium in the study
 population .
there were no differences between wt / wt group and wt/32 group regarding to cps score , meld score or
 blood group ( table 1 ) .
there were
 no statistical significant differences in the composition of underlying liver
 disease of group wt / wt and wt/32 .
initial
 immunosuppression was tacrolimus based in 82.6% in the wt / wt group compared to
 84.8% in the wt/32 group .
cmv infection
 that demanded ganciclovir treatment was present in approximately 30% in the
 wt / wt and wt/32 group and in both homozygous patients .
donors of group 32/32 were younger ( 35.7 years versus 46.5 years and
 48.5 years ) .
mmol / l in the wt/32 group and 155.5 mmol / l in the 32/32 group .
data of causes of brain death and
 length of stay on the icu prior to organ harvesting are shown in table 2 .
incidence
 of itbl was 11.2% in this study due to the selection of patients with itbl that
 were additionally included into this evaluation .
homozygous 32 patients developed no itbl compared to 11.2%
 and 12.1% of homozygous wild - type patients and heterozygous patients ,
 respectively .
the rate of retransplantation was 3.0% in both wt / wt and wt/32 group ( see table 3 ) .
retransplantation of
 the heterozygous patient was indicated due to chronic ductopenic rejection
 following olt for psc . in the wt / wt group ,
the
 problem of genetic association studies and complex clinical syndromes or
 diseases must be addressed .
one can always question the usefulness of these
 studies that    are often    even small in sample size .
, it seems important to undertake
 replication studies for reported associations between genetic polymorphisms and
 diseases , especially in diseases of major clinical importance . in this
 study ,
the distribution of heterozygous 32 and homozygous 32 mutation was very consistent with   the
 published data of the global distribution of this gene polymorphism [ 10 , 16 ] .
heterozygous and homozygous genotypes occur
 in caucasian population in 15%20% and 1% , respectively .
this seems
 important due to the small number of patients included in this study and the
 possible bias by including selected patients with the diagnosis of itbl into
 the study cohort . despite
 increasing success rates in clinical olt over the past decades
, itbl remains a
 major cause for recipient morbidity and mortality [ 15 ] .
up till
 today , only risk factors for itbl could be identified in various clinical
 studies .
the length of cold ischemic time was correlated with the development
 of itbl [ 14 ] .
immunological causes seem to play only a minor role in the pathogenesis of
 itbl .
described a single base - pair deletion in the coding region
 of the chemokine receptor-532 , ccr-532 , to be a significant risk factor for the
 development of itbl . in moench 's study on 146 olt patients ccr-532 was a significant risk factor for itbl
 ( incidence of itbl in ccr-532 patients was 30% versus 11.7% in ccr-5
 wild - type patients ) and was correlated with a decreased survival rate after
 olt .
the different incidence of itbl of the study by
 moench and this study may be a reason for the different findings , even though
 both investigators used the same definition of itbl .
donors were younger in
 this study with 38.2  16
 ( non - itbl patients ) and 42.9  17 ( itbl )
 versus 46  14
 ( non - itbl ) and 52  14 ( itbl )
 in moench 's study . however , cold ischemic time was shorter in moench 's
 investigation ( 564 minutes   ( itbl ) and 538   minutes ( non - itbl ) versus 637   minutes ( itbl ) and
 558   minutes ( non - itbl ) ) .
the use of arterial back table perfusion was also
 routinely done for all organs that were harvested by a team of our own .

analyzed ccr-532 polymorphism in 137 pediatric patients but
 showed no correlation with biliary complications .
the incidence of
 itbl varies between 1.4% and 20% according to the literature , which might be a
 problem of different definition of this disease [ 35 ] .
the rate of itbl in our olt
 patients ( 2100 patients between 1988 and 2004 ) is 4.0% . in the presented study
 on 169 olt patients
the overall incidence of itbl was 11.7% , but only due to a
 selective inclusion of patients with the established diagnosis of itbl .
this
 practice of patient recruitment may be criticized , but we think it is justified
 according to our low incidence of itbl .
itbl rate in ccr-532 patients was virtually equal to the one in
 ccr-5 wild - type patients .
no statistically significant differences regarding
 itbl or retransplantation were observed . why would
 ccr-532 mutation promote the development of itbl ?
ccr-532 is a 32-base - pair deletion within the
 coding region of ccr-5 , which results in a frame shift and generates a
 nonfunctional receptor .

homozygous expression of ccr-532 is associated with a reduced risk of
 asthma and with a reduced severity of rheumatoid arthritis [ 17 , 18 ] ,
 multiple sclerosis [ 19 , 20 ] , and primary biliary cirrhosis ( pbc ) . in other words ,
the nonfunctional nature of
 ccr-532 protects the individual from autoimmune
 diseases where ccr-5 seems to play a central pathophysiological role .
these
 data do not backup the theory , that immunological risk factors are dominant in
 the development of itbl .
likewise , a correlation of a reduced survival rate
 with ccr-532 would not be consistent to the literature ,
 where ccr-532 mutation is associated with an increased
 survival in renal , lung , heart   and islet
 cell transplantation .
in contrast
 to those findings , ccr-532 is strongly associated with an increased
 severity of psc .
patients suffering from psc have been
 described as carrying a higher risk for itbl , with a reported significantly
 increased incidence of 15.8% to 25% [ 1 , 8 , 23 ] .
another study reported psc as the only
 independent risk factor for itbl with an incidence of 31% compared with 9%   of the
 control group .
however ,
 the problem of differentiation between itbl and recurrence of psc must be addressed .

recurrence rates of 8.6% to 25% were described for psc after olt [ 2527 ] .
the diagnose of recurrence
 of psc is based on cholangiographic findings of intrahepatic , hilar and/or
 exrahepatic strictures , duct irregularities and on the histopathological picture
 of fibrous cholangitis and/or fibro - obliterative lesions with or without
 ductopenia , biliary fibrosis , or biliary cirrhosis .
most of these findings are neither
 pathognomonic for either recurrence of psc nor itbl .
all patients with itbl in this study
 underwent percutaneous liver biopsy , and our pathologists ruled out psc
 recurrence .
since two
 of three studies failed to show an association between itbl and ccr-532 gene polymorphism , a general recommendation
 for screening of olt patients for ccr-532 does not seem to be justified .

Answer:
it has been shown that certain chemokine receptor polymorphisms may correspond to certain complications after organ transplantation .
 ischemic - type biliary lesion ( itbl ) encounters for major morbidity and mortality in liver transplant recipients .
 so far , the exact cause for itbl remains unclear .
 certain risk factors for the development of itbl like donor age and cold ischemic time
                   are well described . in a previous study , a 32-nucleotide deletion of the chemokine receptor-532 ( ccr-532 )
 was strongly associated with the incidence of itbl in adult liver transplantation .
 this study re - evaluates the association of ccr-532 gene polymorphism and the incidence of itbl .
 169 patients were included into this retrospective
                   analysis .
 134 patients were homozygous for wild - type ccr-5 , 33 patients heterozygous , and 2 patients were homozygous for ccr-532 mutation .
 there were no major differences in donor or recipients demographics .
 no association was found between ccr-532 mutation and the development of itbl .
 we conclude that ccr-532 is no risk factor for the development of itbl in our patient cohort .