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:
fructose is a monosaccharide that is widely available in natural food sources such as fruits and honey .
however , in most countries the main source of fructose is from sucrose , a disaccharide composed of equal portions of fructose and glucose . in the united states another major source of fructose is high - fructose corn syrup ( hfcs ) , which is a commercial liquid product consisting of fructose and glucose in varying proportions , but which in soft drinks is usually 55% fructose and 45% glucose .
fructose intake has increased markedly over the last 2 centuries , primarily due to the increasing intake of sucrose and hfcs [ 13 ] . in particular ,
the introduction of hfcs in the 1970s resulted in an accelerated intake of added sugars in the usa , in part because hfcs was inexpensive and could be easily mixed in with processed foods .
it has been suggested that the increase in added sugars worldwide may partially explain the marked increase in frequency of overweight and obese humans and may explain the rising frequency of metabolic syndrome , diabetes , hypertension , and cardiovascular diseases ( coronary artery disease , congestive heart failure , stroke , and chronic kidney disease ) [ 13 ] .
fructose is absorbed into the intestine enterocyte by the glut-5 specific transporter . while some fructose is metabolized in the small intestinal wall , much of it
is passed via the portal vein to the liver , with perhaps 20 to 30% escaping into the systemic circulation [ 5 , 6 ] . within the hepatocyte ,
fructose is phosphorylated to fructose-1-phosphate by fructokinase . because this reaction has no negative feedback system ,
this results in the generation of amp which is metabolized by amp deaminase to inosine monophosphate and eventually to uric acid .
the transient atp depletion has some similarities to ischemia and can result in arrest of protein synthesis with the induction of oxidative stress and inflammation [ 79 ] .
circulating fructose is taken up by a variety of cell types , including endothelial cells , but also is excreted into the urine where it is absorbed via the glut-5 transporter into the s3 segment of the proximal tubule .
this cell also expresses fructokinase ; as such , the metabolism of fructose by this proximal tubular cell can also lead to local oxidative stress and inflammation [ 8 , 10 ] .
fructose is known to stimulate fat accumulation in the liver by both increasing synthesis and blocking fat oxidation [ 11 , 12 ] .
perhaps not surprisingly , clinical studies have linked the intake of excessive fructose with the development of nonalcoholic fatty liver disease in humans , and the amount of fructose ingested correlates with the risk for progression to cirrhosis [ 15 , 16 ] .
fructose is also known to stimulate glycogen accumulation in the liver [ 17 , 18 ] , which primarily appears to be due to inhibiting glycogenolysis due to inhibition of glycogen phosphorylase .
fructose intake has been shown to induce insulin resistance in rats [ 20 , 21 ] ; fructose can also induce insulin resistance in humans .
the proposed mechanisms are complex but may include a consequence of hepatic lipid deposition , with diacylglycerol accumulation leading to activation of protein kinase [ 22 , 23 ] or via the hepatic stimulation of pgc-1 . some of the effects may also be due to fructose - induced hyperuricemia with effects on endothelial and adipocyte function [ 14 , 25 ] .
however , the lowering of uric acid with allopurinol did not prevent the development of insulin resistance in subjects administered large doses ( 200  g / d for two weeks ) of fructose
. fructose intake may also accelerate the development of type 2 diabetes in rats , possibly by accelerating islet dysfunction via induction of mild islet inflammation and oxidative stress [ 12 , 27 ] .
one study suggests that this might be due in part to the effects of systemic uric acid that increase in response to fructose ( or sucrose ) ingestion .
fructose may also stimulate the production of advanced glycation end products ( ages ) that have been shown to be toxic in diabetes .
indeed , chronic fructose ingestion has been associated with the accelerated formation of cataracts in diabetic rats .
intake of sugary soft drinks has also been associated with the development of obesity and diabetes . [ 30 , 31 ] indeed , a recent meta - analysis by malik et al . found a strong independent relationship between the intake of sugar - containing soft drinks with the subsequent development of diabetes .
fructose does not acutely stimulate leptin or insulin release and hence may not trigger normal satiety responses .
in addition , added sugars such as sucrose have been found to trigger dopamine responses in the ventral and dorsal striatum , which chronically may lead to downregulation of the d2 receptors and sugar bingeing .
fructose intake can also induce a central leptin resistance in rats , leading to increased food intake and the development of visceral obesity .
interestingly , rats on a high - fructose diet may not show an increase in overall body weight unless it is associated with diets high in fat .
fructose intake from added sugars is also associated with elevated blood pressure in humans , and diets low in added sugar have been reported to lower blood pressure .
furthermore , the acute ingestion of fructose ( 60  g ) can increase systolic blood pressure in humans , and this is not seen in subjects given the same dose as glucose .
in addition , in one study , overweight men were administered 200  g fructose daily for two weeks and sustained a significant increase in ambulatory blood pressure .
interestingly , the increase in blood pressure in response to fructose is better observed by tail cuff measurement as opposed to intra - aortic telemetry [ 40 , 41 ] .
however , blood pressure rises in response to sucrose or fructose diet by telemetry during the first hours of feeding [ 12 , 42 ] .
the mechanism of hypertension in response to fructose is complex but appears to be mediated by increased sodium absorption in the intestine , by inhibition of systemic endothelial function , and by stimulation of the sympathetic nervous system [ 14 , 43 , 44 ] ( figure 1 ) .
in addition , some of the effect of fructose to increase blood pressure may be the consequence of fructose - induced increases in intracellular and serum uric acid .
first , fructose - induced hypertension in rats is largely ameliorated by lowering uric acid levels .
second , in one study in overweight men , the rise in ambulatory blood pressure in response to 200  g of oral fructose per day for two weeks was blocked in those subjects concomitantly administered allopurinol .
fructose and sucrose are also known to induce renal hypertrophy and tubulointerstitial disease in rats [ 10 , 45 , 46 ] .
first , the rise in uric acid in response to uric acid may cause an afferent arteriolopathy resulting in glomerular hypertension .
second , fructose may also be filtered into the urine where it is taken up in the s3 segment of the proximal tubule , leading to local intracellular generation of uric acid with oxidative stress and local inflammation .
the administration of fructose to rats with reduced renal function ( the remnant kidney model ) can accelerate the progression of renal disease , resulting in worse proteinuria , glomerulosclerosis , and tubulointerstitial fibrosis . fructose intake also impairs calcium absorption and reduces 25-oh vitamin d and 1,25-dihydroxy vitamin d levels in this model . furthermore , the intake of sugary soft drinks in humans is associated with increased prevalence of albuminuria .
our group has also recently administered a low - fructose diet to subjects with stable chronic kidney disease for a period of 6 weeks . while we observed no effect on renal function during the period of the study
, we did observe a reduction in inflammatory markers and a fall in blood pressure in subjects with the  dipper  physiology ( i.e. , those subjects whose blood pressure spontaneously falls at night during sleep ) .
clearly further studies are needed to determine if limiting added sugars may benefit subjects with kidney disease .
while much work has focused on fructose as driving obesity , insulin resistance , and cardiorenal disease , not all fructose sources may be the same .
thus , natural fruits also are rich in antioxidants , ascorbate , polyphenols , potassium , and fiber that may counter the effects of fructose [ 13 , 50 ] . indeed , forman et al .
reported that fructose intake did not correlate with elevated blood pressure in a population in which much of the fructose intake was from fruit , whereas jalal et al .   found a strong association of fructose intake with blood pressure when the fructose content from natural fruits was excluded .
while there is increasing evidence for a role for fructose as a contributory factor to obesity and metabolic syndrome , most of the data has relied on epidemiological studies , experimental models , and cell culture .
in contrast , studies in which fructose or sucrose is administered to subjects have shown variable effects on metabolic parameters .
in general , few metabolic effects are observed with fructose when it is given to young , healthy , and lean subjects [ 5254 ] .
this contrasts with studies in overweight / obese or insulin - resistant subjects in which metabolic effects from fructose or sucrose are commonly observed [ 22 , 26 , 5558 ] .
one potential explanation may relate to the absorption of fructose , which is known to increase with fructose exposure [ 59 , 60 ] .
fructose effects are also potentiated by glucose [ 61 , 62 ] , and most studies have only examined fructose alone .
most studies also show , both in animals and humans , that the effects of fructose are greater on postprandial lipids , fatty liver , and insulin resistance rather than on weight gain per se . indeed , the effects of fructose may be more on inducing leptin resistance , and it may require the addition of high - fat diet to show the weight gain .
nevertheless , the evidence that excessive intake of fructose may have multiple adverse effects on human health seems to be mounting .
there are likely multiple mechanisms driving the current epidemic of obesity , diabetes , and cardiorenal disease .
future studies should investigate the effect of reducing fructose intake or blocking the metabolic effects of fructose as a means for preventing or treating these important diseases .

Answer:
fructose is a sugar present in sucrose , high - fructose corn syrup , honey , and fruits .
 fructose intake has increased markedly in the last two centuries , primarily due to increased intake of added sugars .
 increasing evidence suggests that the excessive intake of fructose may induce fatty liver , insulin resistance , dyslipidemia , hypertension , and kidney disease .
 these studies suggest that excessive intake of fructose might have an etiologic role in the epidemic of obesity , diabetes , and cardiorenal disease .


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 response to the changing needs of the community , dental practice is subject to constant changes .
these changes , in turn , influence patient expectations from dentists . to successfully serve the community as a health care professional
, dentists must be competent not only in their clinical practice , but also in some non - clinical aspects of their practice .
previous studies in the united states , france , the netherlands , and mexico   have shown some deficiencies in non - clinical competencies including legal and financial performance , time and quality management , occupational health and practice organization among dentists and dental students . in order to improve non - clinical competencies of dentists , various approaches have been implemented such as holding educational courses for dental students , revision of dental curricula [ 810 ] and holding continuing education programs for dentists .
dentists in iran are trained based on a national dental curriculum focusing mainly on clinical competencies , with no specific course on non - clinical domains such as professional health , communication skills , practice management or evidence - based dentistry .
moreover , the discipline - based nature of the curriculum acts as a barrier against integrated and comprehensive education .
although the revised national curriculum debuted in 2012 attempts to cover some of the above - mentioned deficiencies , some problems still remain among the practicing dentists .
this calls for specific courses in the form of continuing education programs in order to make dentists competent in non - clinical domains of dental practice . in the current study
, we designed , implemented and evaluated the efficacy of a comprehensive course on non - clinical competencies that dentists must possess for a successful dental practice .
this interventional study with a before - after design was performed in the school of dentistry , tehran university of medical sciences in 2010 .
first , in an expert panel of five academic staff members and five general practitioners , the topics for a course on successful dental practice were derived through a nominal group technique .
based on the consensus of the participants , 12 topics were chosen that are not covered by the national dental curriculum either partially or completely and there was a need for complementary or continuing education courses on them .
the course plans for the 12 topics ( table 1 ) were designed by the expert panel members in the form of a two - day course .
the derived topics and the subheadings of the two - day educational course on successful dental practice for dentists in order to acquire an adequate sample , three different sampling approaches were implemented .
first , a short message introducing the program was sent to 1000 randomly selected cellphone numbers of dentists practicing in tehran province .
third , the chief dental officers of tehran city informed the dentists working in health centers about this course .
they were invited to participate in the program , which was conducted in january 2010 , at the school of dentistry , tehran university of medical sciences .
based on the derived course topics , a questionnaire was designed to assess the participants opinion about the necessity of attending the program on each topic for dentists , their self - assessed awareness of each topic and their knowledge of the course contents .
age , sex and work experience ( in months ) were asked as demographic information of subjects .
some questions regarding the quality and efficacy of the course were also included in the post - test questionnaire .
the participants were asked to express their level of agreement with the necessity to receive training on each topic covered in the course using a five - point likert scale from 1 meaning no necessity to 5 meaning maximum necessity .
the dentists were asked to report their knowledge of the course ( separately for each topic ) using a five - point likert scale from 1 meaning no knowledge to 5 meaning maximum knowledge .
an anonymous questionnaire was administered among the participating dentists on the first day before commencement of the program as pre - test . the same questionnaire , with additional questions about the quality and efficacy of the course ,
was completed by the dentists at the end of the course on the second day .
each participant assigned a three - digit code to the pre - test questionnaire to be re - entered in post - test questionnaire .
first , in an expert panel of five academic staff members and five general practitioners , the topics for a course on successful dental practice were derived through a nominal group technique .
based on the consensus of the participants , 12 topics were chosen that are not covered by the national dental curriculum either partially or completely and there was a need for complementary or continuing education courses on them .
the course plans for the 12 topics ( table 1 ) were designed by the expert panel members in the form of a two - day course . the derived topics and the subheadings of the two - day educational course on successful dental practice for dentists
first , a short message introducing the program was sent to 1000 randomly selected cellphone numbers of dentists practicing in tehran province .
third , the chief dental officers of tehran city informed the dentists working in health centers about this course .
the program was explained to the volunteer dentists . they were invited to participate in the program , which was conducted in january 2010 , at the school of dentistry , tehran university of medical sciences .
based on the derived course topics , a questionnaire was designed to assess the participants opinion about the necessity of attending the program on each topic for dentists , their self - assessed awareness of each topic and their knowledge of the course contents .
age , sex and work experience ( in months ) were asked as demographic information of subjects .
some questions regarding the quality and efficacy of the course were also included in the post - test questionnaire .
the participants were asked to express their level of agreement with the necessity to receive training on each topic covered in the course using a five - point likert scale from 1 meaning no necessity to 5 meaning maximum necessity .
the dentists were asked to report their knowledge of the course ( separately for each topic ) using a five - point likert scale from 1 meaning no knowledge to 5 meaning maximum knowledge .
an anonymous questionnaire was administered among the participating dentists on the first day before commencement of the program as pre - test . the same questionnaire , with additional questions about the quality and efficacy of the course ,
was completed by the dentists at the end of the course on the second day .
each participant assigned a three - digit code to the pre - test questionnaire to be re - entered in post - test questionnaire .
forty - six dentists with a mean age of 40.8 years ( range 25 to 58 years ) participated in this study .
the mean work experience of the participants was 163.3 months ( range 10 to 480 months).table 2 shows the distribution of responses regarding the necessity for training on each specified topic before and after participation in the course . as seen in table 2 , at least two - thirds of the participants in both pre- and post - tests stated that they believed training on all topics was necessary ( a score of 4 or 5 ) . in terms of necessity of receiving training on each topic before the course , the highest priority was given to ergonomics and occupational health as 93.4% of the respondents gave a score of 4 or 5 to this topic .
the topic with the least priority before the course was workplace design since 67.4% of the participants gave a score of 4 or 5 to this topic .
after the course , the most necessary topic was reported to be management of medical emergencies ( 95.6% gave a score of 4 or 5 ) , and the least necessary topic covered by the training course was documentation principles and it applications in dentistry ( 68.9% gave a score of 4 or 5 ) . before attending the course , less than 40% of the participants assessed their level of knowledge to be high ( a score of 4 or 5 ) about 10 of the 12 topics .
however , this value decreased to two topics after the course ( table 3 ) .
distribution of the responses by a group of dentists ( n=46 * ) regarding the necessity of training on each specified topic using a five - point likert scale from 1 ( the least ) to 5 ( the most ) before and after participation in a course on successful dental practice the maximum number of unanswered questions was 2 .
distribution of the responses by a group of dentists ( n=46 * ) regarding the self - assessed knowledge about each specified topic using a five - point likert scale from 1 ( the least ) to 5 ( the most ) before and after participation in a course on successful dental practice the maximum unanswered questions was 2 in pre - test and 7 in post - test .
the opinion of the participants regarding the necessity of receiving training on two topics significantly changed after the course and they gave a higher priority to ergonomics and professional health and communication skills in post - test compared to the pre - test ( p<0.05 ) ( table 4 ) .
the self - assessed knowledge of the dentists improved significantly after attending the course on seven topics including the ergonomics and occupational health , workplace design , documentation principles and it application in dentistry , national rules and regulations of dental practice , medical emergencies , dental ethics and communication skills ( p<0.05 ) ( table 4 ) .
comparison of pre- and post - teat scores of self - perceived need for education and self - assessed knowledge about each specified topic among a group of dentists ( n=46 ) attending a course on successful dental practice wilcoxon signed - rank test regarding the quality and efficacy of the course , more than 70% of the participants were completely satisfied or satisfied with practical implication of the course , conformity of course contents with the title and course settings .
moreover , 87% of the participants completely agreed or agreed that more training in this field was required .
in the present study , a course on successful dental practice was designed and its effect on self - assessed need for training and self - assessed knowledge in this regard was investigated through a before - after design .
the course mainly focused on non - clinical competencies that a general dentist should possess .
designing a comprehensive course covering a wide range of topics related to successful dental practice , focusing on weaknesses of the national dental curriculum and implementing the views of the dentists as the main stakeholders in designing the course   can be considered as the strengths of our study . on the other hand , lack of a control group ,
short - term evaluation and using a questionnaire for the course evaluation were weaknesses of our study .
however , with regard to the fact that no similar course in iran or elsewhere was found , designing such a course per se was one of the main goals , which was achieved .
a study aiming to explore important aspects of practice and patient management among dental residents and their views on the level of undergraduate training regarding these subjects was done in the united states .
the results showed that the most important topics included time management , multidisciplinary coordination and total quality management .
respondents considered dealing with health care payers to be important to their future practices while this topic received low priority in their curriculum . another study in france on senior dental students who had the experience of working as associates in dental offices as a part of their undergraduate training showed that the two most reported problems included time management ( 90% ) and administrative matters ( 85% ) .
a study in the netherlands on newly qualified dentists showed that the most frequently reported factors responsible for being unprepared for practice were law and insurance matters ( 61.2% ) , practice organization ( 56.6% ) and staff management ( 55.2% ) . in our study , ergonomics and professional health received the highest priority in self - perceived educational needs expressed by dentists .
this finding confirms the studies reporting the high prevalence of musculoskeletal disorders among dentists [ 1416 ] and emphasizes on providing the dentists with sufficient training in this regard , similar to previous studies [ 17 , 18 ] .
the second important topic according to the dentists perspectives was management of medical emergencies in the dental office .
this is in line with previous studies in iran [ 1921 ] and other countries [ 2224 ] calling for more emphasis on this topic in undergraduate dental curricula and continuing education programs .
moreover , only 19.6% of the participants reported to have sufficient knowledge on this topic .
more than 80% of the dentists reported insufficient knowledge about this topic and also workplace design .
this shows that although the dentists rated their self - assessed knowledge as low on this topic , they gave a lower priority to further education on this topic compared to other topics .
however , it should be noted that more than two - thirds of the dentists felt that there was a need for more training even on this topic . in general , these findings show the deficiency of the national dental curriculum and continuing education programs in non - clinical aspects of dental practice . in seven out of 12 topics ,
this increase was significant in ergonomics and professional health and communication skills , showing that the course successfully revealed the need for further education among the participants .
this increase was significant for seven of the 12 topics , showing that the course in general was successful in enhancing the self - assessed knowledge of the dentists in short - term .
the respondents also believed that the course was successful as most of them were satisfied with the course content and conduction . since no similar course has been reported in previous studies , it was impossible to compare our results with those of other studies .
studies on educational interventions covering some of our topics for dental students [ 6,7 , 25 ] have reported positive results in increasing the knowledge and improving the attitudes of the participants .
in conclusion , a need for more training on non - clinical domains of dental practice was evident among the dentists .
the designed course seemed to be successful in revealing the participants need for further education . with regard to the satisfaction rate of the attendants

Answer:
objectives : we aimed to design , implement and evaluate the efficacy of a comprehensive course on non - clinical competencies that dentists must possess for a successful dental practice.materials and methods : in this interventional before - after study an expert panel of five academic staff members and five general practitioners derived the topics for a course on successful dental practice , and aggregated them in the form of a two - day course .
 it was held for 46 randomly selected dentists in january 2010 , at the school of dentistry , tehran university of medical sciences .
 the participants completed an anonymous questionnaire asking about their self - perceived need to receive training in each of the proposed topics and their self - assessed knowledge about each topic before and after attending the course.results:participants gave a higher priority to the necessity of training on  ergonomics and professional health  and communication skills in post - test compared to pre - test ( p<0.05 ) .
 the self - assessed knowledge of dentists improved significantly after attending the course in seven domains : ergonomics and occupational health , workplace design , documentation principles and it applications in dentistry , national rules and regulations of dental practice , medical emergencies , dental ethics and communication skills ( p<0.05 ) .
 more than 70% of the participants were completely satisfied or satisfied with practical implication of the course , conformity of the contents with the title and course settings.conclusion:the designed course seemed to be successful in revealing the need of participants for further education .
 considering the high satisfaction rate of the attendants , this course can serve as a model for continuing education purposes .


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:
trigeminal neuralgia ( tn ) is a debilitating pain syndrome that is characterized by agonizing , paroxysmal , and lancinating pain .
the recommended first - line treatment for tn is medical therapy , but this often fails to provide pain relief .
thus , second - line treatment modalities are given to patients whose symptoms are intractable or who can not tolerate medication .
these treatment modalities include invasive procedures such as microvascular decompression ( mvd ) , and ablative procedures such as gamma knife radiosurgery ( gkrs ) , percutaneous balloon microcompression , radiofrequency rhizotomy , and glycerol rhizolysis .
recently , gkrs has been used as a treatment modality in several centers for patients with concurrent medical illness who are poor candidates for mvd or who refuse more invasive surgery17,20 ) .
other treatment modalities provide short - term pain relief at a rate of 80 - 90% ; gkrs also produces short - term alleviation of pain at similar rates , usually within 6 - 12 months after the operation2,3,7,9,11,15,18,23,29 - 31 ) . pain relief after mvd and radiofrequency rhizotomy for long - term periods has been well reported . in previous studies ,
patients who underwent mvd and radiofrequency reported favorable long - term pain relief of for more than 5 years1,5,10,25,28,32 ) .
however , long - term outcomes of gkrs for tn have been published in only a few reports12,22,29 ) .
thus , we conducted the present study to analyze the long - term outcomes in a series of patients with tn who underwent single gkrs treatment and were followed up for a minimum of 60 months .
between march 1995 and march 2009 , 40 patients with typical tn underwent gkrs at our clinic .
indications for gkrs included medically intractable pain , > 65 years of age , refusal of invasive procedures , or failure of previous invasive procedures . among them , we retrospectively reviewed the medical records of patients with tn undergoing gkrs treatment that had a minimum follow - up of 60 months .
patient demographic characteristics , clinical presentation , treatment history , and the radiosurgical modality were reviewed in 22 patients whose median follow - up was 92.2 months ( range : 60 - 144 months ) .
all patients were treated with leksell gamma knife ( eleckta instruments , stockholm , sweden ) under local anesthesia . as a planning tool ,
the kula system was used until 2001 , and the leksell gamma plan system ( eleckta ab , stockholm , sweden ) has been used since 2001 .
all patients were treated using a single isocenter through a 4-mm collimator helmet targeting the root entry zone of the trigeminal nerve ( fig .
the mean maximal dose to the target was 77.1 gy ( range , 65.2 - 83.6 gy ) .
long - term outcomes were established by face to face interview with a written questionnaire after the treatment in the outpatient clinic .
the questionnaire was devised based on the barrow neurological institute ( bni ) pain scale24 ) but modified at our institution to better incorporate the use of adjuvant medications .
facial pain outcomes were categorized into one of the following classes : grade i , no pain , no medication ; grade ii , no pain with medication ; grade iii , > 50% improved pain with medication ; grade iv , 50% improved pain with medication ; and grade v , no pain relief .
patients with grade i - ii on the pain scale ( equivalent to bni grades i and iiia ) were considered to have a good treatment outcome .
patients with grade iv - v on the pain scale ( equivalent to bni grades iv and v ) were considered to have a poor treatment outcome ( table 1 ) .
statistical verification was determined using spss statistic software , version 13.0 ( spss , inc .
the mean age was 61.5 years ( range 25 - 84 years ) , and the mean symptom duration from onset to treatment was 46.8 months ( range 1 - 84 months ) .
the most common distribution of pain involved the second and third divisions of the trigeminal nerve , observed in a total of 40.9% of patients ( 9 out of 22 patients ) .
thirteen patients had right - sided pain , and 9 had left - sided pain . during the last follow - up period ,
6 patients ( 27.3% ) had good treatment outcomes ( represented by grades i and ii ) , and 7 patients ( 31.8% ) had poor treatment outcomes ( represented by grades iv and v ) during a median follow - up period of 92.2 months ( range 60 - 144 months )
. of the 6 patients with good outcomes , 4 patients ( 18.2% ) experienced complete pain relief without medication , and 2 ( 9.1% ) had complete pain relief with medications .
of the 7 patients with poor outcomes , 5 patients ( 22.7% ) experienced 50% improved pain with medication , and 2 ( 9.1% ) had no pain relief ( table 3 ) . subgroup analysis of excellent , good , and poor outcomes found 2 statistically significant factors related to achieving and maintaining complete pain relief : symptomatic periods before treatment ( p=0.035 ) and previous surgery ( p=0.008 ) .
however , sex , age , pain distribution , and laterality of pain did not correlate with facial pain improvement ( table 4 ) . out of a total of 22 patients ,
16 patients had been treated with medication only before gkrs ( primary group ) , and 6 had gone through mvd prior to gkrs ( secondary group ) . during the final follow - up period ,
patients with good outcomes were 37.5% and 0% in the primary and secondary group , respectively ; patients with poor outcomes , on the other hand , were 12.5% and 83.3% in the primary and secondary group , respectively ( table 5 ) .
of the 22 patients , only one patient ( 4.54% ) experienced facial numbness after gkrs , with grade iii pain on the pain scale .
none of the patients had neuropathic pain , dry eye , keratitis , or jaw weakness after gkrs .
tn patients in whom medical therapy fails are recommended to undergo several treatment modalities , including mvd , radiofrequency rhizotomy , percutaneous balloon microcompression and gkrs . in general ,
the most effective surgical treatment is considered to be mvd in healthy patients because it has a demonstrated effective initial pain - free rate and good long - term outcomes .
barker et al.1 ) reported that the pain - free rate was maintained at 70% of 1185 patients for a median of 6.2 years after mvd .
severe complications that developed include 2 deaths ( 0.2% ) and 16 patients ( 1% ) with ipsilateral hearing loss .
tronnier et al.27 ) reported that 65% of patients had excellent outcomes at 10 years , and 63% at 20 years after mvd . in this study ,
broggi et al.4 ) reported that 53 - 94% of mvd patients were pain - free after a long - term follow - up .
they also reported that the mortality of mvd was 0.3% and that cranial nerve dysfunction rates ranged from 0.1 - 3% .
additionally , radiofrequency rhizotomy also demonstrated an effective long - term outcome for tn patients .
taha et al.26 ) found that 75% were pain - free at 10 years , and 23% experienced facial dysesthesia . in previous studies ,
patients who underwent mvd reported long - term pain relief at rates of 62 - 89% , and patients who underwent radiofrequency reported long - term pain relief at rates of 20 - 82% for > 5 years after achieving a short - term pain relief rate of > 90%1,4,5,10,25 - 28,32 ) .
however , severe complications have occurred in tn patients who underwent mvd or radiofrequency rhizotomy at rates of approximately 2 - 19%1,4,5,10,25 - 28,32 ) . in previous reports with long - term follow - up , gkrs for tn patients
has long term outcomes slightly inferior to mvd and radiofrequency rhizotomy , but with lower complication rates .
urgosik et al.29 ) reported that 80% of 107 patients had good outcomes ( patients with 60% < residual pain ) at a median of 5 years .
little et al.12 ) reported that 83% of 136 patients had good outcomes ( bni pain score of class i , ii , or iii ) at a median of 6.3 years .
riesenburger et al.22 ) reported that 58.5% achieved good outcomes ( bni pain score of class i , ii , or iii ) at a follow - up period of 48 months .
these reports have demonstrated that gkrs is a safe technique for the management of tn , as trigeminal sensory disturbance , the main complication of radiosurgery for tn , only developed in approximately 10% of the patients .
in addition , gkrs patients did not develop any of the severe complications which patients that had undergone mvd or radiofrequency rhizotomy experienced14 ) .
however , most of the other reports on gkrs and tn combined the longer - term follow - up patients with more recently treated patients , thus making it more difficult to identify long - term results . in the present study ,
we strictly evaluated long - term outcomes at a follow - up period of a minimum of 5 years .
thus , our data demonstrate that patients experience lasting pain relief with few complications after gkrs , although patients with good outcomes are fewer than in the previous long - term follow - up studies of outcomes after gkrs .
this seems to be due to the fact that only patients with no pain regardless of medication were included in the " good outcome " patient group in our study , whereas published reports on long - term follow - up studies on gkrs included patients with medication - controlled pain in the " good outcome " group .
because pain negatively impacts upon the quality of life of chronic tn patients , we think that the goal of treatment in tn should be complete pain relief . therefore , we believe it is better to grade patient outcome by the reporting of pain - free outcomes that clearly separates effective pain relief from continued pain . in the current study , patients with pain that had decreased by 50% or more with the use of medication were classified separately as patients with fair outcomes . as a result
, our data demonstrated that patients with good and fair outcomes comprise 72.7% of all treated patients , which is a similar outcome to that in previous reports .
therefore , from the results of this 5-year long - term follow - up study , we suggest that the proportion of patients with good outcomes , consisting purely of pain - free patients with or without medication , after gkrs was 27.3% .
published reports have used radiation dose protocols ranging from 70 - 100 gy7,8,21,31 ) . in general , higher doses of radiation are related to better outcomes , but complications , including facial sensory loss and paresthesia , increase at doses greater than 90 gy19,21 ) . generally , maximal radiation doses between 70 - 90 gy are used to treat tn . in previous long - term follow - up studies ,
the mean maximal radiation dose was approximately 80 gy , and complications included facial numbness , which affected approximately 10% of the treated patients12,22,29 ) .
in the present study , the mean maximal dose was 77.7 gy , which is lower than that utilized in other recent studies ; this is partly due to the long follow - up period which started from 1995 , and partly because the dose was slightly lowered to avoid the development of lasting complications . in our study , only one patient ( 4.54% ) experienced facial dysesthesia . thus , we believe that lower radiation doses are associated with lower complication rates .
the presence of previous surgery is regarded as a predictive factor significantly associated with a poor short - term outcome6,13,16,20 ) .
however , long - term pain relief factors have not been well studied until recently .
little et al.12 ) recently reported that at long term follow - up , 75% of patients who were treated with primary
gkrs achieved long - term pain relief at 7 years , but only 10% of patients in whom previous surgery had achieved a similar outcome .
similarly , our study found that good outcomes in primary gkrs group ( 37.5% ) was better than in secondary gkrs group ( 0% ) , respectively .
also , the presence of previous surgery was observed to be a statistically significant factor related to achieving and maintaining complete pain relief according to our subgroup analysis of good and poor outcomes . based upon these findings
, we have come to believe that there is significant correlation between previous surgery and poor long - term outcomes .
first , although the pain intensity scale is validated tools for the quantification of pain , they are subjective outcome measures because they are dependent on personal interpretations and variation .
second , the small sample size and retrospective study design limit the power of our outcome observations .
gkrs performed at lower radiation doses not only decreased complication rates , but also lessened the development of more severe complications in the long run
. however , the long - term results of gkrs for tn are not as satisfactory as those of mvd and other conventional modalities .
although gkrs achieves relatively good outcomes of initial pain relief , our results suggest a steady rate of late failure , particularly among patients who performed secondary gkrs following prior surgery .
gkrs is a safe , effective and minimally invasive treatment modality for only limited group of patients who are not suited to more invasive treatment .

Answer:
objectivegamma knife radiosurgery ( gkrs ) is the least invasive surgical option for patients with trigeminal neuralgia ( tn ) .
 however , the indications and long term outcomes of gkrs are still controversial .
 additionally , a series with uniform long - term follow - up data for all patients has been lacking . in the present study ,
 the authors analyzed long - term outcomes in a series of patients with tn who underwent a single gkrs treatment followed by a minimum follow - up of 60 months.methodsfrom 1994 to 2009 , 40 consecutive patients with typical , intractable tn received gkrs . among these
 , 22 patients were followed for > 60 months .
 the mean maximum radiation dose was 77.1 gy ( 65.2 - 83.6 gy ) , and the 4 mm collimator was used to target the radiation to the root entry zone.resultsthe mean age was 61.5 years ( 25 - 84 years ) .
 the mean follow - up period was 92.2 months ( 60 - 144 months ) . according to the pain intensity scale in the last follow - up , 6 cases were grades i -
 ii ( pain - free with or without medication ; 27.3% ) and 7 cases were grade iv - v ( < 50% pain relief with medication or no pain relief ; 31.8% ) .
 there was 1 case ( facial dysesthesia ) with post - operative complications ( 4.54%).conclusionthe long - term results of gkrs for tn are not as satisfactory as those of microvascular decompression and other conventional modalities , but gkrs is a safe , effective and minimally invasive technique which might be considered a first - line therapy for a limited group of patients for whom a more invasive kind of treatment is unsuitable .


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 open , laparoscopic , or endoscopic approaches . however , there are disadvantages and limitations with each of these techniques .
the open method requires a large incision with its associated morbidity , and the laparoscopic techniques described so far are technically challenging in the pediatric population .
the endoscopic approach has poor results as the cystenteric opening is small and tends to occlude leading to recurrence and infection .
we describe our combined technique of laparoscopic and gastroscopic transgastric cystogastrostomy for pseudopancreatic cysts in children .
she had high amylase and lipase levels and a computed tomographic ( ct ) scan showed necrotizing pancreatitis .
subsequently , an abdominal ct scan revealed a well - formed wall enhancing pseudopancreatic cyst ( fig .
axial cut of computed tomographic scan demonstrating pseudocyst posterolateral to stomach . under anesthesia a pediatric pentax gastroscope ( pentax medical company , montvale , new jersey , united states )
three more 5-mm step ports were placed under direct vision : 2 ports on either side of the umbilicus and 1 port just under the costal arch to retract the gall bladder . using these ports ,
the stomach was insufflated with air from the gastroscope and two sutures of 30 vicryl were placed to pexy the stomach to the abdominal wall using a granee needle ( r - med , oregon , ohio , united states ) ( fig .
a 12-mm port was then directly introduced into the stomach under vision of the gastroscope as well as the laparoscope ( fig .
it is very important to have the visualization through the gastroscope while placing the initial transgastric port as the cyst protruding from the posterior gastric wall compromises the gastric lumen severely .
if performed without the visualization of the gastroscope there is a risk injury to the posterior gastric wall during the transgastric port placement .
one of the other ports used for gallbladder removal was then also introduced into the stomach under vision .
the 5-mm 30-degree telescope was then introduced into the stomach and the stomach was continuously insufflated with low flow .
a laparoscopic needle was introduced through the laparoscopy port into the cyst to confirm the position of the cyst ( fig .
a harmonic scalpel was then introduced into the stomach through the same port and an opening was made into the posterior wall of the stomach in to the cyst ( fig .
once this was achieved a 30-mm endo gia ( covidien , mansfield , massachusetts , united states ) stapler was introduced through the 12-mm umbilical port and a stapled cystogastrostomy was achieved ( fig .
( a ) laparoscopic needle inserted in the posterior gastric wall to confirm the presence of pseudocyst .
( b ) harmonic scalpel used to incise the posterior wall of stomach and the pseudocyst after needle aspiration of the pseudocyst .
( c ) endo gia stapler being applied to the posterior gastric wall and the pseudocyst .
( d ) endo gia stapler applied to the posterior gastric wall and the pseudocyst .
under anesthesia a pediatric pentax gastroscope ( pentax medical company , montvale , new jersey , united states ) was introduced into the stomach .
three more 5-mm step ports were placed under direct vision : 2 ports on either side of the umbilicus and 1 port just under the costal arch to retract the gall bladder . using these ports ,
the stomach was insufflated with air from the gastroscope and two sutures of 30 vicryl were placed to pexy the stomach to the abdominal wall using a granee needle ( r - med , oregon , ohio , united states ) ( fig .
a 12-mm port was then directly introduced into the stomach under vision of the gastroscope as well as the laparoscope ( fig .
it is very important to have the visualization through the gastroscope while placing the initial transgastric port as the cyst protruding from the posterior gastric wall compromises the gastric lumen severely .
if performed without the visualization of the gastroscope there is a risk injury to the posterior gastric wall during the transgastric port placement .
one of the other ports used for gallbladder removal was then also introduced into the stomach under vision .
the 5-mm 30-degree telescope was then introduced into the stomach and the stomach was continuously insufflated with low flow .
a laparoscopic needle was introduced through the laparoscopy port into the cyst to confirm the position of the cyst ( fig .
a harmonic scalpel was then introduced into the stomach through the same port and an opening was made into the posterior wall of the stomach in to the cyst ( fig .
once this was achieved a 30-mm endo gia ( covidien , mansfield , massachusetts , united states ) stapler was introduced through the 12-mm umbilical port and a stapled cystogastrostomy was achieved ( fig .
( a ) laparoscopic needle inserted in the posterior gastric wall to confirm the presence of pseudocyst .
( b ) harmonic scalpel used to incise the posterior wall of stomach and the pseudocyst after needle aspiration of the pseudocyst .
( c ) endo gia stapler being applied to the posterior gastric wall and the pseudocyst .
( d ) endo gia stapler applied to the posterior gastric wall and the pseudocyst .
the patient tolerated the procedure well with no intraoperative complications and was started on a regular diet on the fourth postoperative day .
she had well - healed scars and was tolerating a regular diet with no other problems .
pancreatic pseudocysts , because of pancreatitis , trauma , or ductal obstruction , are uncommon in children.1 however , they may require treatment if symptomatic or persist after 4 to 6 weeks
. internal drainage of pancreatic pseudocysts has traditionally been accomplished by laparotomy , although laparoscopic and endoscopic modalities have recently been described .
the open technique has been shown to have mortality rates of 1 to 6% , complication rates of 10 to 40% , and recurrence rates of 5 to
20%.2
  the laparoscopic technique consists of either creation of an anterior gastrotomy to create a psuedocyst gastrostomy or identification of the cyst stomach interface through the lesser sac.3 both modalities have been shown to be safe and effective in the adult literature but both can be technically challenging and cumbersome in the smaller working space in children .
endoscopic therapy alone involves identifying the region of the cyst bulge with the endoscope , needle localization of the tract , and stent placement for internal drainage .
however , the cystenteric opening is limited in size which can lead to occlusion , infection , or recurrence.4
 5 beckingham et al performed endoscopic drainage in 34 adults with a success rate of 71% .
the failures were found to be associated with pseudocysts complicated by acute necrotizing pancreatitis and cyst wall thickness greater than 1 cm.6 repeated procedures due to catheter - related complications requiring additional anesthetics are not ideal in the pediatric population .
melman et al compared the three techniques for drainage of pancreatic pseudoscyts in adults and found lower primary success rates for endoscopic drainage as compared with laparoscopic and open cystgastrostomies as well as the need for repeat procedures.5
  the approach of combined laparoscopic and endoscopic / gastroscopic pseudocyst gastrostomy using intraperitoneal and as well as intragastric visualization has been described in the adult literature but has not been previously reported in children.4
 7 the use of the laparoscopy during cystgastrostomy allows for pseudocyst debridement , fashioning a large communication between the cyst and stomach , as well as minimizes the risk of complications such as gastric perforation .
in addition , laparoscopy adds the ability to add other procedures if needed such as cholecystectomy as was done in this case .
gastroscopy helps in visualization of the primary transgastric port placement preventing injury to the posterior gastric wall and gastric insufflation during the procedure .
finally , the decreased need for additional port sites leads to an improved cosmetic result which is of particular interest in the pediatric population .
laparoscopic gastroscopic transgastric cystogastrostomy is a safe technique for the treatment of pancreatic pseudocysts in children .

Answer:
a 15-year - old girl presented with gallstone pancreatitis .
 subsequently , a pseudopancreatic cyst developed that was diagnosed on computed tomographic scan .
 she underwent a laparoscopic and gastroscopic transgastric cystogastrostomy . in the following report
 , we describe our novel approach and technique for the above condition .


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 the last decade , preimplantation genetic diagnosis ( pgd ) has become an important alternative to prenatal diagnosis for couples at high risk of transmitting inherited disorders to their children .
fluorescence in situ hybridization ( fish ) has been offered for gender selection in x - linked diseases ( 1 , 2 ) , chromosomal translocations ( 3 - 5 ) , aneuploidy , and recurrent implantation failure ( 6 , 7 ) .
procedures using polymerase chain reaction ( pcr ) has been applied for single gene defects including x - linked diseases ( 8 - 11 ) .
ornithine transcarbamylase ( otc ; ec 2.1.3.3 ) is placed in the mitochondrial matrix where it contributes to the detoxification of nitrogenous wastes through the urea cycle , and catalyzes the synthesis of citruline from carbamyl phosphate and ornithine .
the otc gene is located on the short arm of the x chromosome within band xp21.1 ( 12 ) .
it spans 73 kb , has an open reading frame of 1,062 nucleotides , and contains 10 exons and 9 introns ( 13 , 14 ) .
otc deficiency ( mim-#311250 ) is an x - linked and co - dominant metabolic disorder with partial penetrance in females ( 15 ) .
the phenotype of otc deficiency is extremely heterogeneous , ranging from asymptomatic adult hemizygous males to acute neonatal hyperammonemic coma in the first week of affected male babies .
approximately 80% of heterozygous females are asymptomatic and remaining 20% show clinical severity similar to males with partial deficiencies ( 16 , 17 ) .
there are more than 341 mutations known to cause otc deficiency , all of which are specific for the individual families .
mutations have been found in all exons and introns with a relative paucity of mutations in the sequence encoding the leader peptide ( exon 1 and a part of exon 2 ) and in exon 7 ( 17 , 18 ) . to our knowledge , only two cases have been reported where specific pgd for otc deficiency were carried out using multiplex or duplex - nested pcr assay and healthy babies devoid of the otc mutation were born ( 19 , 20 ) . in this study
, we describe the successful pregnancy and birth after pgd for otc deficiency with simultaneous analyses of fish and duplex - nested pcr in korea .
we have applied a duplex - nested pcr for the amplification of both the causative mutation and the y chromosome specific sry gene , and fish for aneuploidy screening of chromosome x , y and 18 .
a couple was referred to our center after therapeutic termination of the second pregnancy following prenatal diagnosis for otc deficiency . in the first pregnancy ,
a male baby was born but died at 10 days after birth due to liver dysfunction accompanying hyperammonemia .
molecular genetic analysis of the couple 's otc gene was performed by pcr and direct sequencing at seoul asan hospital and revealed a single base substitution ( r320x ) in the exon 9 of the female partner . in the second pregnancy , the fetus
was identified to be an affected boy by pcr and direct sequencing on a chorionic villus sample , and the pregnancy was therapeutically terminated . in order to avoid a pregnancy with an affected baby , the couple was counseled for pgd in cheil general hospital . in order to determine the efficiency of single cell pcr and allele drop - out ( ado ) rate , primers used for the detection of the causative mutation and y chromosome specific sry gene were tested using single lymphocytes ( table 1 ) .
ovarian stimulation , in vitro fertilization , and blastomere biopsy were done as previously described ( 4 , 5 ) .
after the blastomere biopsy procedure , the embryos were washed several times and transferred to the g2.2 medium ( vitrolife sweden ab , kungsbacka , sweden ) .
each blastomere was washed twice through two drops of g2.2 medium and transferred into sterile 0.2 ml pcr tubes containing 5 l of alkaline lysis buffer .
the nested - duplex pcr analysis was performed by previously described protocol ( 6 ) .
mutation analysis by restriction fragment length polynorphism ( rflp ) with bcli restriction enzyme was carried out only for positively amplified pcr products of blastomeres .
the fish analysis for chromosome x , y and 18 was done as previously described and the manufacture 's protocol ( 4 , 5 ) .
the embryos with the normal genotype were selected and transferred on day 4 after fertilization .
all 10 exons and exon - intron boundaries of the otc gene were screened by pcr followed by direct dna sequencing analysis .
the heterozygous otc gene with r320x nonsense mutation ( cgatga ) and wild type was detected in the exon 9 of the female partner by rflp ( fig . 1 ) and direct sequencing ( data not shown ) .
this r320x nonsense mutation was associated with acute neonatal hyperammonemia in their first pregnancy and reduced enzyme activity by 10 - 15% ( 21 ) .
the efficiency and accuracy of the duplex - nested pcr analysis were tested on single lymphocytes from the heterozygous female partner and normal male partner .
pcr on single lymphocytes resulted in 90.6% ( 58/64 ) amplification rate , whereas none of the negative controls showed a positive band .
after ovarian hyperstimulation , a total of 18 oocytes were retrieved and 17 oocytes were injected using intracytoplasmic sperm injection in order to prevent dna contamination from inseminated sperm . among a total of 11 embryos ,
two blastomeres per embryo from 9 embryos were biopsied and simultaneously analyzed by duplex - nested pcr and fish , and one blastomere per embryo from 2 embryos by only duplex - nested pcr . as a result of duplex - nested pcr and rflp analysis with the bcli restriction enzyme ,
ten showed successful amplification for the exon 9 of the otc gene , and the amplification rate was 90.9% , almost same as that of the single lymphocyte test .
there were two unaffected males , five affected males , two unaffected females , and one heterozygous female ( fig . 2 and table 2 ) .
on the other hand , out of nine blastomeres analyzed by fish , only six blastomeres were identified as chromosomally normal embryos ( fig .
however , among total four unaffected embryos ( embryo 1 , 2 , 3 , and 8) diagnosed by pcr , only two embryos ( embryo 3 and 8) were identified as chromosomally normal by fish .
the other two embryos ( embryo 1 and 2 ) were shown to have trisomy 18 and monosomy 18 , respectively . only one male embryo ( embryo 8) was transferred , and another female unaffected embryo ( embryo 3 ) was cryopreserved at blastocyst stage on day 5 after fertilization .
this pgd cycle resulted in a singleton pregnancy and the genotype of the fetus was confirmed to be a normal male by amniocentesis at 16 weeks of gestation .
the genotype of the baby for the exon 9 of otc gene and level of ammonia were confirmed as normal .
most pgd cycles for x - linked disorders such as duchenne muscular dystrophy and fragile x syndrome involved the selection of female embryos which were diagnosed as normal or heterozygous . these gender selections were supported by couples at risk of x - linked recessive conditions .
ado for affected allele could lead to yielding an affected heterozygous baby , even if the female embryo was diagnosed as normal by pgd for otc deficiency .
gender selection with fish for y chromosome - specific loci is more reliable because amplification failure could occasionally occur in single cell pcr .
thus , our protocol with pcr and fish in this study provides higher accuracy for the selection of genetically and chromosomally normal embryos in the pgd for x - linked co - dominant defects .
we applied duplex - nested pcr and fish analysis in two blastomeres from each embryo , which were more than 6-cell stage .
biopsy of more than a quarter of blastomeres from each embryo could interfere with developmental potential of embryos .
thus , single blastomere biopsy was applied to less than 6-cell stage embryos in this study .
sequential pcr and fish analysis in one blastomere ( cell recycling ) was reported and could be used to detect the aneuploidy , but the rate of ado after pcr seems to be higher using this method ( 22 , 23 ) .
a duplex - nested pcr analysis was developed for the simultaneous diagnosis of a r320x mutation and a gender selection , and fish analysis was used to detect aneuploidy for chromosome x , y and 18 . as a result of duplex nested pcr and fish analysis ,
concordant results have been obtained from two blastomeres at the sex locus , and the amplification efficiency was 100% ( 9/9 except two blastomeres , that were not analyzed by fish analysis ) for sry .
and the amplification rate was 90.9% ( 10/11 ) for exon 9 of the otc gene .
several strategies have been developed to decrease amplification failure and ado in single cell analysis of pgd .
these included the development of sequential first and second polar body analysis ( 24 ) , improvement of the pcr condition by increasing the denaturation temperature and time ( 19 ) , using a more powerful lysis method ( 25 - 28 ) and the use of fluorescent pcr for mutations or linked markers and multiplex pcr ( 29 - 32 ) .
as mentioned above , we have also endeavored to optimize single cell pcr conditions , which included longer initial denaturation time , higher denaturation temperature , and the selection of taq polymerase , the concentration of mgcl2 , and lysis methods .
the incidence of ado was 5 - 15% in many pgd laboratories ( 27 , 28 ) . at a preliminary experiment on single lymphocytes in this study ,
the ado rate for exon 9 of the otc gene was about 13.0% when using duplex - nested pcr .
we could not absolutely exclude the possibility of ado in the diagnosis of unaffected female embryo owing to the relatively higher ado .
thus , fish was simultaneously applied for the aneuploidy screening and sex selection to prevent the pregnancy of heterozygous female . in this study
, we report the successful pgd and delivery of a healthy boy in a couple at risk of transmitting the otc deficiency .
this was carried out by the simultaneous analysis of the duplex - nested pcr for a r320x mutation in the otc gene underlying the otc deficiency and y chromosome - specific loci , and fish for aneuploidy screening of chromosome x , y and 18 .
this strategy could provide higher accuracy for the selection of genetically and chromosomally normal embryos in pgd for single gene defects .

Answer:
ornithine transcarbamylase ( otc ) deficiency is an x - linked co - dominant disorder .
 a couple , with a previous history of a neonatal death and a therapeutical termination due to otc deficiency , was referred to our center for preimplantation genetic diagnosis ( pgd ) .
 the female partner has a nonsense mutation in the exon 9 of the otc gene ( r320x ) .
 we carried out nested polymerase chain reaction ( pcr ) for r320x mutation and fluorescence in situ hybridization ( fish ) for aneuploidy screening . among a total of 11 embryos , two blastomeres per embryo from 9 embryos were biopsied and analyzed by duplex - nested pcr and fish , and one blastomere per embryo from 2 embryos by only duplex - nested pcr . as a result of pcr and restriction fragment length polymorphism analysis , four embryos were diagnosed as unaffected embryos having the normal otc gene . among these embryos , only one embryo was confirmed as euploidy for chromosome x , y and 18 by fish analysis . a single normal embryo was transferred to the mother , yielding an unaffected pregnancy and birth of a healthy boy .
 based on our results , pcr for mutation loci and fish for aneuploidy screening with two blastomeres from an embryo could provide higher accuracy for the selection of genetically and chromosomally normal embryos in the pgd for single gene defects .


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:
bridging integrator-1 breast cancer 1 and 2 cyclin - dependent kinase cyclin - dependent kinase inhibitor human homolog of double minute 2 poly(adp - ribosyl)ation poly(adpribose ) polymerase 1 retinoblastoma 1 protein
the discovery of gleevec ( sti-571 ) , a tyrosine kinase inhibitor , was a milestone achievement in clinical oncology and this inhibitor has demonstrated remarkable efficacy in philadelphia chromosome - positive ( ph ) chronic myeloid leukemia . since then , mechanism - based approaches have been used to specifically target various kinases and/or downstream oncogenic pathways that are critically involved in cell cycle progression and tumorigenesis . however , in addition to this approach , a more recent and novel use of small - molecule inhibitors has emerged as a promising endeavor in the field of cancer chemotherapy . here , we briefly review the mechanistic basis of restoration of a tumor suppressor and its potential complications for cancer therapy .
the tumor suppressor function mediated by the retinoblastoma 1 protein ( rb1 ) is principally attributed to its interaction with the e2f transcription factor 1 ( e2f1 ) .
the rb1/e2f1 complex represses a number of e2f1-dependent transcriptional target genes that are required for the transition from g1 to s phase in the cell cycle .
because rb1 is inactivated by phosphorylation mediated by the g1 cyclin - dependent kinases 4 and 6 ( cdk4 and cdk6 ) , restoring rb1 function by inactivating cdk4/6 is theoretically an obvious approach .
although structural similarities among a number of cdk family members hampered the development of a cdk4/6-specific inhibitor for many years , some agents , including palbociclib ( pd-0332991 ) , have recently demonstrated promising results in phase i / ii clinical trials for human malignancies , including breast cancer . above and beyond rb1 , another tumor suppressor that is critical for numerous growth inhibitory pathways
the abundance of wild - type p53 protein is massively reduced as a result of ubiquitin - dependent and human homolog of double minute 2 ( hdm2)-mediated degradation of p53 .
therefore , dissociation of p53 from the p53/hdm2 complex is a reasonable strategy for rescuing p53 function .
based on the crystallographic structure of the p53/hdm2 peptide complex , small p53 peptides that mimic the region of p53 sufficient for hdm2 binding and small - molecule hdm2 antagonists have been shown to disrupt the p53/hdm2 interaction in vitro and in vivo .
some of these , including mi-219 , nutlin-3 , and rg7112 , have been found to be effective preclinically and have consequently moved into phase i / ii clinical trials   although proteasome inhibitors such as bortezomib ( ps-341 ) may not be as specific for stabilizing p53 as these hdm2 inhibitors , other growth - inhibitory gene products , including the cyclin - dependent kinase inhibitor 1b ( cdkn1b or p27 , kip1 ) protein , can also be degraded in an ubiquitin - dependent manner .
therefore , it may be advantageous to re - establish a broad spectrum of growth - inhibitory functions by blocking the proteasome pathway .
although the approach of re - establishing tumor suppressor function in tumors as a therapeutic option is mechanistically intriguing , there are potential dilemmas associated with the systemic restoration of tumor suppressor function .
tumor suppressor genes are frequently mutated or deleted in cancer patients , and given that some of the mutant genes acquire oncogenic potential , this approach may simply reboot a mutant ( i.e. , oncogenic ) tumor suppressor .
even if a tumor suppressor gene is intact , its function should not depend on other cancer - susceptible proteins .
for example , the cyclin - dependent kinase inhibitor 2a ( cdkn2a ) gene is not frequently deleted in cancer cells , but is inactivated by dna methylation . however , epigenetic reactivation of the cdkn2a gene may not be an effective approach if rb1 and/or p53 are deficient , because the tumor suppressor functions of the products of the 2 alternative reading frames of cdkn2a  p16 and p14 proteins  largely depend on rb1 and p53 , respectively .
therefore , for the tumor suppression approach to be fully effective , it will be important to identify a non - mutated ( or non - deleted ) tumor suppressor whose function does not rely on other tumor suppressors that might be already mutated or deleted .
bridging integrator-1 ( bin1 ) was originally identified as a c - myc oncoprotein - interacting tumor suppressor . the bin1 gene itself is rarely mutated or deleted , but is frequently silenced in human cancer cells
moreover , bin1 acts as a tumor suppressor in vitro and in vivo in the absence of rb1 and p53 .
we recently demonstrated that bin1 , whose gene promoter is activated by e2f1 , directly interacts with e2f1 and represses its transcription , implying that a negative - feedback loop regulates bin1 gene expression .
interestingly , we found that e2f1 is poly(adp - ribosyl)ated by poly(adp - ribose ) polymerase 1 ( parp1 ) and that parp1 inhibition unlocks the e2f1bin1 negative - feedback loop to vigorously activate the bin1 gene , which induces g2/m arrest in the cell cycle and/or apoptosis .
synthetic lethality, parp inhibitors have been actively used for clinical trials in breast cancer 1 and 2 ( brca1/2)-deficient breast and ovarian cancers . however , it was unclear why parp inhibitors alone also show therapeutic efficacy , even in cancer cells expressing wild - type brca1/2 . based on our recent data ,
the restoration of bin1 by parp inhibitors may offer a mechanistic rationale for expanding the clinical usage of parp inhibitors over a wider range of tumor types , regardless of the status of rb1 , tp53 , and brca1/2  genes ( fig .
1 ) .
 figure 1.small-molecule inhibitors used in cancer therapy restore the functions of various tumor suppressors in malignant cells .
the tumor suppressor functions of retinoblastoma 1 protein ( rb1 ) , tumor protein p53 ( tp53 , known as p53 ) , and bridging integrator-1 ( bin1 ) can be pharmacologically restored by small - molecule inhibitors , such as palbociclib ( pd-0332991 ) , mi-219 , and olaparib , respectively . in the case of p53 restoration , a human homolog of double minute 2 ( hdm2 ) , named hdm4 ( also known as hdmx ) , might interfere with the effectiveness of hdm2 antagonists , probably because of overlapping functions between hdmx and hdm2 .
p , phosphorylation ; par , poly(adp - ribosyl)ation ; dp1 ( or tfdp1 ) , transcription factor dp1 ; e2f1 , e2f transcription factor 1 ; cdk4/6 , cyclin - dependent kinase 4 and 6 ; g1/s : transition between g1 ( growth1/gap1 ) phase to s ( dna synthesis ) phase in the cell cycle ; g2/m , transition between g2 ( growth2/gap2 ) phase to m ( mitosis ) phase in the cell cycle .

small - molecule inhibitors used in cancer therapy restore the functions of various tumor suppressors in malignant cells .
the tumor suppressor functions of retinoblastoma 1 protein ( rb1 ) , tumor protein p53 ( tp53 , known as p53 ) , and bridging integrator-1 ( bin1 ) can be pharmacologically restored by small - molecule inhibitors , such as palbociclib ( pd-0332991 ) , mi-219 , and olaparib , respectively . in the case of p53 restoration , a human homolog of double minute 2 ( hdm2 ) , named hdm4 ( also known as hdmx ) ,
might interfere with the effectiveness of hdm2 antagonists , probably because of overlapping functions between hdmx and hdm2 .
p , phosphorylation ; par , poly(adp - ribosyl)ation ; dp1 ( or tfdp1 ) , transcription factor dp1 ; e2f1 , e2f transcription factor 1 ; cdk4/6 , cyclin - dependent kinase 4 and 6 ; g1/s : transition between g1 ( growth1/gap1 ) phase to s ( dna synthesis ) phase in the cell cycle ; g2/m , transition between g2 ( growth2/gap2 ) phase to m ( mitosis ) phase in the cell cycle .
chemotherapy and radiotherapy are conventional treatments for eradicating tumors , but cancer often develops therapeutic resistance over time . given that many tumor suppressors are proapoptotic in response to dna damaging agents , it would be clinically pertinent to increase the chemo- and radiosensitivities of cancer by combining standard treatments with agents that can restore the activity of silenced tumor suppressors , provided they are not mutated or deleted , in human malignancies .
this work was partially supported by a grant from the us national institutes of health ( nih ) ( r01ca140379 ) ( to d.s . ) .

Answer:
over the last decades , accumulating data have advanced our understanding of the mechanism of action of tumor suppressor proteins and therapeutic strategies to restore tumor suppressor pathways have emerged as a promising approach for cancer therapy . based on our recent findings on bridging integrator-1 ( bin1 ) ,
 we outline potential advantages and disadvantages of chemical activation of tumor suppressors .


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:
x - linked dominant chondrodysplasia punctata ( cdpx2 , omim 302960 ) is an inheritable systemic disease and is characterized by skeletal , ophthalmologic , and cutaneous manifestations . in the late seventies , rudolph happle reported a female and brilliantly recognized a group of published patients with chondrodysplasia punctata whose mosaic phenotype and sex rate corresponded with an x - linked dominant pattern of inheritance . in 1999 , the gene emopamil binding protein ( ebp ) was identified and associated with cdpx2 , so called conradi - hnermann - happle syndrome .
the ebp gene is located on the short arm of the x chromosome ( xp11.22-p11.23 ) and spans 7 kb of genomic dna , containing five exons coding a mature transcript of 1 kb which is ubiquitously expressed .
this protein consists of 230 amino acids and four transmembrane domains , it has a molecular weight of 27 kda and it is implicated in cholesterol biosynthesis .
cutaneous lesions in cdpx2 usually start as erythematous scaly plaques following the lines of blaschko that fade over time , and some patients may be born with congenital erythroderma .
while cdpx2 may exhibit variable phenotypes , psoriasiform skin lesions are exceptional and histopathologic investigations of psoriasiform skin lesions show epidermal hyperproliferation in addition to ichthyotic retention hyperkeratosis . in this report , a case of a 12-year - old girl diagnosed with x - linked dominant chondrodysplasia punctata with a psoriasiform phenotype is reported with genetical confirmation .
we discuss here a rare clinical presentation which helps in better depict this rare genodermatosis and on the lack of correlation between phenotype and genotype in this disease .
a 12-year - old girl , who had been born with congenital erythroderma , had a 4-month history of linear and whorled inflammatory cutaneous lesions on her trunk , leg , and arms .
extensively distributed thickly adherent scaling had been developed at the age of one , and continued since then .
the patient had been born at term following a normal pregnancy and delivery and family history was unremarkable .
she displayed growth retardation , bilateral conductive hearing , and unilateral congenital cataract in her right eye .
she exhibited short stature with asymmetric shortening of her limbs , being her right arm shorter than her left .
dysmorphic facial features with frontal bossing , flat nasal bridge , and a depressed tip of the nose were observed .
dermatological examination revealed brown streaky hyperkeratotic plaques with thickly adherent scaling located along blaschko 's lines .
also , erythematous scaling and guttate lesions were observed on her trunk , arms , and legs .
there were patchy areas of scarring alopecia on frontal and temporal regions of the scalp and lateral regions of eyebrows .
dorsal and lumbosacral magnetic resonance imaging showed scoliosis deformity , height losses of the t8 vertebrae left half and l3 , l4 vertebral the right halves ( tethered cord ) .
clinical features of the patient with conradi  hnermann  happle syndrome ( x - linked dominant chondrodysplasia punctata ) genomic dna of the patient was extracted from peripheral blood leukocytes via a conventional phenol - chloroform method .
exons 1 - 5 and the intronic splicing regions from the ebp gene were amplified by polymerase chain reaction ( pcr ) as previously described .
the reaction was conducted in a 2720 thermal cycler ( applied biosystems , foster city , ca , u.s.a . ) .
automatic sequencing was performed with the abi prism 310 genetic analyzer ( applied biosystems ) .
we identified a previously reported ebp mutation , c. 440 g > a ( p.r147h ) in the patient , but not in her parents [ figure 2 ] . according to the clinical and laboratory findings
, the diagnosis of conradi - hnermann - happle syndrome was established . a skin biopsy of one of the guttate , erythematous , and scaling plaques revealed retention hyperkeratosis , parakeratosis , acanthosis with regular elongation of rete ridges , capillary proliferation , and mononuclear cell infiltration in papillary dermis , being this consistent with a psoriasiform pattern .
the pedigree and dna sequencing showed a heterozygous mutation c. 440 g > a resulting in p.r147h in ebp gene
in conradi - hnermann - happle syndrome , cutaneous findings are remarkable and characterized by hyperkeratotic lesions on an erythematous background following the blaschko 's lines .
bruch et al . described a unique adult patient presenting both with ichthyotic and pustular psoriasiform lesions together .
later , in a large spanish series , a patient with ichthyosis in a psoriasiform pattern was reported with the genetic analysis showed c. 187c > t ( p.arg63x ) de novo mutation .
we here present an exceptional case of cdpx2 with psoriasiform and ichthyotic skin lesions together in an adolescent , the first case from tunisia .
histopathological features of guttate , erythematous , and scaling plaques followed a psoriasiform pattern . in 1999 , the gene ebp was identified and associated with the conradi - hnermann - happle syndrome ( xp11.22-p11.23 ) . to date , about 70 different mutations in the ebp gene have been described related with this disease .
we found a c.(440 g > a ) missense de novo mutation in the ebp gene ( p.arg147his ) , placed in the second endoplasmic reticulum domain ( er2 ) of the protein .
the unique case of cdpx2 with a similar phenotype to ours displayed a c.(187c > t ) , p.arg63x nonsense mutation , which had also been described in two patients with typical skin phenotype of cdpx2 .
the c. 440 g seems to be a nucleotide with particularly high mutational susceptibility within the ebp gene , a hot spot .
on the other hand , the clinical phenotype associated with this mutation has been variable , which subscribes the lack of correlation between genotype and phenotype in this disease .
although the relationship between the various genotypes and phenotypes in conradi - hnermann - happle syndrome has not been fully elucidated , detailed clinical and molecular analyses are helpful for providing data to be used in genetic counseling .
our case expands the clinical phenotypic variation in cdpx2 and further demonstrates the lack of correlation between genotype and phenotype in this disease .
unique additional clinical manifestations like plaque - type psoriasis may present with different mutations . conradi - hunermann - happle may represent extensive plaque - type psoriasis in adolescent patients .

Answer:
conradi - hnermann - happle syndrome ( cdpx2 , omim 302960 ) is an inherited x - linked dominant variant of chondrodysplasia punctata which primarily affects the skin , bones , and eyes .
 cdpx2 patients display skin defects , including ichthyotic lesions , follicular atrophoderma , cicatricial alopecia , and less frequently ichthyosiform erythroderma , cataracts , and skeletal abnormalities consisting of short stature , asymmetric shortening of the limbs , epiphyseal stippling , and craniofacial defects .
 cdpx2 results from mutations in emopamil binding protein ( ebp ) gene .
 the aim of our study is to identify ebp mutation in a unique case of conradi - hnermann - happle syndrome with rare psoriasiform lesions .


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:
laparoscopic surgery has enjoyed increasing success since its modest beginning in 1983 and has become the standard of care for cholecystectomy .
evaluation and application of new technologies has allowed for the rapid advancement of laparoscopic surgical techniques .
what remains ill - defined is the application and safety of laparoscopic surgery to complex solid - organ procedures such as liver resection .
the difficulties in approaching laparoscopic liver surgery require continued improvements in technology , such as video imaging , electrosurgical instruments , laparoscopic duplex ultrasound , and greater success with bloodless surgery .
one possible application of advancements in laparoscopic liver surgery is the performance of partial nonanatomic hepatectomy . using open surgical techniques ,
partial nonanatomic hepatectomy has gained acceptance as a procedure that may be used to treat patients with hepatocellular carcinoma , as well as other diagnoses .
nonanatomic liver resection is technically demanding due to hepatic anatomic variability and can be associated with considerable morbidity .
this study evaluated a new technique for liver resection using the ligasure electrosurgical vessel - sealing device ( valleylab - tyco healthcare , boulder , co ) .
it does so by combining energy control with physical compression , including a brief cool down that produces a distinctive , translucent seal of partially denatured protein ; thereby , fusing the collagen in the vessel walls and occluding the lumen entirely .
these seals have bursting strengths comparable to those of ligatures and , unlike clips , resist dislodgment because they are intrinsic to the vessel wall structure .
thermal spread is minimal and the autologous seals formed by the ligasure device can withstand 3x systolic pressure . the ligasure device may be used for sealing vessels up to 7 mm in diameter .
the effectiveness of this device for liver resection is not known , but we hypothesize that it has excellent potential for use in laparoscopic nonanatomic liver resection .
this series is our initial experience with the ligasure device in the performance of laparoscopic nonanatomic resections of the liver using a sus scrofa pig model .
the animal experiments were performed in accordance with the 1996 national research council guide for the care and use of laboratory animals and applicable federal regulations .
preoperatively , the animals were fasted 12 hours and medicated with hydromorphone ( 0.1 mg/ kg ) , acepromazine ( 0.1 mg / kg ) , and glycopyrrolate ( 0.01 mg / kg intramuscularly ) .
anesthesia was induced with tiletamine / zolazepam ( telazol ) ( 6 mg / kg intramuscularly ) .
the animals were then intubated and given xylazine ( 2 mg / kg intravenously ) , and anesthesia was maintained using isoflurane ( 1.53% ) .
monitoring of the anesthetized animals was conducted using pulse oximetry for oxygen saturation , end - tidal carbon dioxide sensors , and cardiac sensors .
the 9 domestic swine used in the experiments weighed 29 kg to 36 kg and were divided equally into 3 groups . in all of the experiments ,
60% to 80% of the left lobe was removed . before concluding each operation , all groups of animals ( i , ii , and iii )
were visually inspected for bleeding and biliary leakage at the site of resection . in laparoscopic cases ,
pneumoperitoneum was released for 10 minutes prior to the final visual inspection . in all cases , adequate hemostasis and biliary control
postoperative analgesia for groups i and ii consisted of morphine epidural ( 2 mg ) placed between vertebrae l6 and s1 in addition to a transdermal fentanyl patch ( 75 g ) stapled to the animals ' posterior neck .
postoperative analgesia for group iii consisted of buprenorphine ( 0.01 mg / kg q 12 hours ) and a transdermal fentanyl patch ( 75 g ) stapled to the animals ' posterior neck .
surgical details of liver resections were as follows : the control animals underwent a nonanatomic left hepatic lobectomy through a scalpel incision in the abdominal midline by using the finger - fracture method .
blood vessels and bile ducts were clipped or suture ligated as appropriate and electrocautery ( bovie ) was used where indicated .
the animals in group ii underwent a nonanatomic left hepatic lobectomy through a scalpel incision in the abdominal midline .
the animals in group iii underwent a laparoscopic , non - anatomic , left hepatic lobectomy with the ligasure device for dividing the liver parenchyma and sealing and dividing all blood vessels and bile ducts .
the pneumoperitoneum was insufflated by veress needle and maintained at a constant abdominal pressure of 12 mm hg .
the laparoscopic atlas version of the ligasure was used to divide the parenchyma as well as any vessels or bile ducts in continuity without isolating them first .
this was accomplished by opening the jaws of the device and then gently applying pressure to the parenchymal surface .
the device was activated by depressing a foot pedal , and increasing pressure applied to the handle , slowly approximating ( closing ) the jaws .
the rate of compression of the parenchyma was guided by the surgeon , who maintained a 1-mm blanched area of parenchyma around the jaws .
when the jaws of the device were approximated , indicated by the handle locking , the device was  recycled ,
the excised segment of the liver was placed in an endocatch bag , morselated , and removed through one of the port - site incisions .
animals from all groups ( i , ii , and iii ) were assessed for biliary leakage on postoperative day 2 by cholescintigraphy .
animals were anesthetized with telazol ( 6 mg / kg intramuscularly ) to allow administration of the radiopharmaceutical , hepatolite ( 10 millicuries ) , given via a jelco 22 gauge needle in the animals ' left lateral ear vein .
one hour later , a hida scan was performed using the adac forte camera , allowing evaluation of hepatocellular function and patency of the hepatobiliary system by tracking the production and flow of radiolabeled bile from the liver through the bile ducts and into the intestine . following the hida scan
, all animals underwent a midline abdominal incision for gross inspection of the cut surface of the liver and the surrounding area for any evidence of hemorrhage or biliary leakage .
upon visual inspection , no apparent evidence was present of biliary leakage , resolving hematoma , or abscess formation .
samples of the cut surface were taken for histological examination , and the animals were euthanized with a barbiturate overdose ( beuthanasia , 1 ml plus 1 ml/5 kg , intravenously ) .
the control animals underwent a nonanatomic left hepatic lobectomy through a scalpel incision in the abdominal midline by using the finger - fracture method .
blood vessels and bile ducts were clipped or suture ligated as appropriate and electrocautery ( bovie ) was used where indicated .
the animals in group ii underwent a nonanatomic left hepatic lobectomy through a scalpel incision in the abdominal midline .
the animals in group iii underwent a laparoscopic , non - anatomic , left hepatic lobectomy with the ligasure device for dividing the liver parenchyma and sealing and dividing all blood vessels and bile ducts .
the pneumoperitoneum was insufflated by veress needle and maintained at a constant abdominal pressure of 12 mm hg .
the ligasure device was introduced through a 10-mm trocar . the laparoscopic atlas version of the ligasure was used to divide the parenchyma as well as any vessels or bile ducts in continuity without isolating them first .
this was accomplished by opening the jaws of the device and then gently applying pressure to the parenchymal surface .
the device was activated by depressing a foot pedal , and increasing pressure applied to the handle , slowly approximating ( closing ) the jaws .
the rate of compression of the parenchyma was guided by the surgeon , who maintained a 1-mm blanched area of parenchyma around the jaws .
when the jaws of the device were approximated , indicated by the handle locking , the device was  recycled ,
the excised segment of the liver was placed in an endocatch bag , morselated , and removed through one of the port - site incisions .
animals from all groups ( i , ii , and iii ) were assessed for biliary leakage on postoperative day 2 by cholescintigraphy .
animals were anesthetized with telazol ( 6 mg / kg intramuscularly ) to allow administration of the radiopharmaceutical , hepatolite ( 10 millicuries ) , given via a jelco 22 gauge needle in the animals ' left lateral ear vein .
one hour later , a hida scan was performed using the adac forte camera , allowing evaluation of hepatocellular function and patency of the hepatobiliary system by tracking the production and flow of radiolabeled bile from the liver through the bile ducts and into the intestine . following the hida scan
, all animals underwent a midline abdominal incision for gross inspection of the cut surface of the liver and the surrounding area for any evidence of hemorrhage or biliary leakage . upon visual inspection ,
no apparent evidence was present of biliary leakage , resolving hematoma , or abscess formation .
samples of the cut surface were taken for histological examination , and the animals were euthanized with a barbiturate overdose ( beuthanasia , 1 ml plus 1 ml/5 kg , intravenously ) .
intraoperative blood loss and operative times were significantly lower using the ligasure device and are shown in table 1 .
open resection animals ( groups i and ii ) were depressed postoperatively , had decreased appetite , and required analgesia . in contrast , laparoscopic animals ( group iii ) were alert , responsive , and feeding ad libitum 1 hour after recovery from anesthesia .
histological examination of excised liver and remaining liver at sacrifice showed secure sealing of all biliary and vascular structures in the ligasure groups .
not unexpectedly , thermal injury from standard electrocautery was 4 times greater than that observed in tissue examined where the ligasure device was used , as measured on histological specimens .
one animal in group i had a bile leak detected on hida scan . however , this leak was not discernible upon subsequent visual inspection and was considered clinically insignificant .
additionally , postoperative bleeding was absent in all animals as confirmed by gross inspection on postoperative day 2 .
laparoscopic surgery provides benefits to the patients , such as shorter recovery time , less pain , and more cosmetically acceptable incisions .
however , solid visceral organs such as the liver pose a significant challenge to the laparoscopic surgeon because they have a soft parenchyma richly interspersed with vasculature .
realization of the potential advantages of laparoscopic liver resection requires the technical ability to ensure hemostasis during division of the parenchyma .
the effectiveness of laparoscopic instrumentation in maintaining a hemostatic , clear operative field has not been well documented to date . due to this fact ,
the application of laparoscopic surgery to procedures on the liver has been delayed by the lack of appropriate instrumentation , and the testing of laparoscopic surgical techniques .
greater acceptance of laparoscopic liver resection requires careful evaluation of the safety and efficiency of available technology and techniques . to date
, laparoscopic liver resection has been evaluated in several case studies demonstrating the expected benefits to patients : decreased postoperative pain , reduced trauma to the abdominal wall , smaller incisions , shorter hospital stay , and earlier ambulation and return to normal activities compared with conventional liver surgery . in this study
, we evaluated the application of vesselsealing technology to liver resection in both open and laparoscopic approaches .
our findings demonstrate effective sealing of intrahepatic blood vessels and bile ducts without requiring isolation .
little to no blood loss occurred using the ligasure device as compared with that with the standard finger - fracture method of partial hepatectomy .
our specimens did not contain any veins greater than 7 mm , and we believe that other methods , such as endovascular staplers , would be required for larger portal or hepatic vein branches .
a significant limitation of laparoscopic surgery , which has prevented application to liver resection , is the difficulty in controlling blood vessels .
laparoscopic suturing is difficult in the best circumstances ; trying to control a bleeding hepatic vein using laparoscopic suturing would be a formidable undertaking .
the ability of the ligasure device to effectively seal intraparenchymal blood vessels is a significant advancement that increases the feasibility of laparoscopic liver resection .
the additional finding that bile ducts were effectively sealed further strengthens the applicability of the device to liver resection .
the effectiveness of the ligasure in nonanatomic liver resection in this study emphasizes the importance of new surgical technology in extending the range of laparoscopic procedures available to the surgeon .
there is no question that liver resection , especially nonanatomic , is a technically challenging operation .
the application of laparoscopic techniques to these procedures should be considered only where full support for advanced laparoscopic procedures is available , and by surgical teams experienced in all aspects of liver surgery .

Answer:
background : advancements in technology have allowed laparoscopic surgery to expand into advanced procedures such as liver resection ; however , the value and safety of laparoscopic liver surgery is still a topic for debate .
 this study was designed to evaluate the feasibility and outcome of laparoscopic nonanatomic hepatectomy using the ligasure device in a swine model.methods:nonanatomic hepatic lobe resection was performed in 3 groups comparing the open finger - fracture method , the open method with the ligasure device , and the laparoscopic method with the ligasure device .
 the cut surfaces of the liver were evaluated for bleeding and biliary leakage at the time of the operation .
 the animals were inspected 48 hours later for hemorrhage and evaluated with cholescintigraphy ( hepatobiliary iminodiacetic acid [ hida ] scan ) for biliary leakage , in addition to histo - logical evaluation of liver specimens.results:no hemorrhage or biliary leakage was noted in the groups where the ligasure device was used , whereas 1 animal from the open finger - fracture method sustained a bile leak observed on hida scan .
 the operative blood loss was considerably less in the groups where the liga - sure device was used , and the shortest operative time was observed in the laparoscopic group.conclusions:the ligasure device can be safely and effectively used to perform a laparoscopic nonanatomic hepatectomy .