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:
video laryngoscopes ( vl ) which work on the principles of indirect laryngoscopy have become popular in clinical practice .
they provide a significantly better view of the larynx , which may be useful in difficult tracheal intubation scenarios . the key novel feature of these
indirect laryngoscopes is that they facilitate visualisation of the vocal cords without the need to align the oropharyngeal and tracheal axes .
kaplan and berci introduced c - mac vl ( karl storz , tuttligen , germany ) in 2003 .
it has been found to improve cormack - lehane ( c - l ) grading by 2 to 1 grade and possibly aid easier intubation .
it provides both a direct laryngoscopic view and a small digital camera view that is displayed on the video screen , in contrast to many previous vls .
recognition of the anatomical structures and anomalies is easier , and manipulation of airway devices is facilitated .
nasotracheal intubation ( nti ) is often required for head and neck surgeries like tonsillectomies .
direct laryngoscopy with the macintosh blade , with the use of magill 's forceps to direct endotracheal tube ( ett ) into glottic opening , is time - consuming and may lead to trauma to surrounding structures and damage ett cuff .
hence , this study was conducted to assess the intubating conditions , using the conventional macintosh laryngoscope and the storz c - mac vl during nti in paediatric patients posted for tonsillectomy surgeries .
this prospective randomised study was conducted after obtaining approval from the institutional review board ( iec no .
patients of either sex , aged between 8 and 18 years , belonging to american society of anesthesiologists physical status i , ii and mallampati grade i , ii were included and study was conducted between january 2013 and june 2014 . parents who refused to give consent , patients with significant systemic disease and patients having contraindications for nti were excluded from the study .
the procedure was explained to the patients and written informed consent from parent / guardian was obtained .
patients in group 1 underwent conventional laryngoscopy using macintosh direct laryngoscope and group 2 underwent videolaryngoscopy using c - mac vl for nasal intubation .
the sample size was estimated based on a pilot study carried out in 10 patients where it was found that mean intubation times for the macintosh group , and the c - mac group were 55 s and 45 s respectively with standard deviation ( sd ) of 5 s. based on these figures and using alpha error = 0.05 and 0.85 power of the study , we got the required sample size of 25 each . hence , we recruited 30 into each group by increasing the sample size by 5 .
the investigator who performed the intubation in this study had previously performed about 100 nti using c - mac vl .
after connecting the routine pre - induction monitors , baseline values of systolic blood pressure ( sbp ) , diastolic blood pressure ( dbp ) , mean blood pressure ( mbp ) , heart rate ( hr ) and oxygen saturation ( spo2 ) were recorded .
all patients were pre - medicated with injection glycopyrrolate 10 g / kg , injection fentanyl 2 g / kg and injection midazolam 10 g / kg intravenous ( iv ) .
anaesthesia was induced with injection propofol 2 mg / kg iv and neuromuscular blockade achieved with injection vecuronium 0.1 mg / kg .
patients were ventilated with oxygen , nitrous oxide ( 33:67 ratio ) and end - tidal concentration of isoflurane 0.81.2 as observed on the gas monitor for initial 4 min , followed by ventilation with 100% oxygen for 1 min before intubation .
preservative free injection lignocaine 1.5 mg / kg iv was administered 90 s before intubation .
five minutes after giving injection vecuronium , ensuring adequate muscle relaxation , lubricated appropriate sized nasotracheal ett was inserted through the most patent nostril until its tip lay in the oropharynx .
laryngoscopy was then performed using either macintosh laryngoscope ( blade size 2 or 3 ) or storz c - mac vl ( macintosh blade size 2 or 3 ) as per the group and a view of laryngeal opening was obtained .
initially , attempt was made to pass the ett through the vocal cords without the aid of manoeuvres ( m0 ) .
if difficulty was encountered , additional external manipulations ( m1 ) such as head flexion , rotation of tube and backwards , upwards , rightwards pressure ( burp ) were used . in case of failure to intubate using above manoeuvres , cuff of the ett
was inflated with approximately 10 ml of air and the ett brought into view ( m2 ) ( as per study done by baddoo hk et al . ) .
once the tip of ett was in the glottic opening , cuff was deflated ; the ett was then advanced into the trachea and then cuff was reinflated .
if this technique failed then , cuff was deflated , and magill 's forceps alone ( m4 ) or in combination with burp ( m5 ) was used to position and guide the tube .
the manuoevres were followed in the sequence described in table 1 . if there was failure to intubate with all the above - said manoeuvres , oral intubation was performed .
correct placement of ett was confirmed by auscultation over the chest for bilateral equal air entry and using capnograph .
sequence of additional manoeuvres used in the study during this procedure , hr , sbp , dbp , mbp and spo2 were recorded every minute for the initial 5 min after induction of anaesthesia , and thereafter at 5 min intervals for next 15 min .
if a decrease in saturation to 90% or lower was observed during nasal intubation then oral intubation was performed .
parameters noted during the study were : c - l grading , time required for intubation , intubation without any manoeuvre ( m0 ) , need for the manoeuvres , type of manoeuvre ( m1m5 ) used , haemodynamic changes , lowest recorded spo2 during or immediately after intubation attempt and occurrence of any other complications .
duration of nti was defined as the time taken from the insertion of the ett through the nostril , till passage of tube through vocal cords by visual confirmation by the intubating anaesthesiologist .
duration of nti more than 120 s , fall in spo2 below 90% during the procedure were considered as failed nti .
data collected were coded , tabulated , and then analysed using statistical package for the social sciences ( spss 20 , ibm , armonk , ny , united states of america ) computer package .
mann - whitney u - test was used for analysing age , sex , c - l grading and for comparing the duration of intubation between both groups .
independent - t - test was used to compare haemodynamics with respect to hr , sbp , dbp , mbp in both groups . a difference with the adjusted p
demographic profiles were evenly distributed between both groups . in group 1 , 86.7% of patients and in group 2 , 96.6% had c - l grading of 1 and remaining patients had c - l grading of 2 , which was not statistically significant ( p = 0.35 ) .
duration of intubation was significantly shorter in group 2 compared to group 1 patients . in group 1 , 36.6% of patients and in group 2 , 93.3% of patients were intubated within 2 min which was statistically significant p = 0.001 [ figure 1 ] . comparison of intubation time between the groups in group 1 , 3.3% of patients and in group 2 , 23.3% of patients were intubated successfully without the application of manoeuvres ( m0 ) .
application of optimisation manoeuvres ( m1m5 ) was needed more in group 1 compared to group 2 ( c - mac ) ( 97% vs. 77% ) and was statistically significant p = 0.001 [ figure 2 ] . in group 1 , 30% of patients and in group 2 , 53.3% patients needed additional external manipulation ( m1 ) .
only 6.7% patients of either the groups were intubated using cuff inflation technique alone ( m2 ) . combined use of cuff inflation with external laryngeal manipulation ( m3 ) was not useful in both groups .
use of magill 's forceps alone ( m4 ) and m4 with external manipulation ( m5 ) were required more in group 1 compared to group 2 ( m4 - 37% vs. 13% ) ( m5 - 23% vs. 3% ) .
( m3 = combined use of cuff inflation with external laryngeal manipulation was not useful in both the groups ) after induction , haemodynamic parameters ( hr , sbp , dbp and mbp ) decreased in both groups when compared to pre - induction values . at the 1 min after intubation ,
the values increased in both groups , but there were no intergroup differences and both the parameters returned to baseline after 5 min after nti [ table 2 ] .
no complications ( drop in spo2 , dental trauma , etc ) were observed during the procedure in both groups .
c - mac vl allows adequate glottic view , without the need for aligning oropharyngeal and laryngeal axes .
we found no significant difference in airway assessment using c - l grading in both groups .
this can be explained by the fact that both groups of patients were of similar demography and patients with airway difficulties were excluded from the study .
duration of nti was significantly decreased in group 2 in comparison with group 1 patients .
c - mac vl has slim blade profile and edges are inclined , thus reducing the potential contact area of the blade with the upper incisors .
it magnifies airway view and allows supporting staff to optimise their assistance such as applying adequate external manipulation as necessary .
the anterior angulation of the blade and placement of the video camera allow the operator to see structures that would be difficult or even impossible to see under direct vision .
the majority of patients in group 1 required different manoeuvres as per study protocol . external laryngeal manipulation ( m1 )
this can be explained by the fact that there was requirement of more hand - eye coordination while viewing the glottis on vl monitor and intubating the patient even with experienced anaesthesiologists .
a previous study showed that cuff inflation technique ( m2 ) helps to lift ett from the posterior pharyngeal wall , thus helping to bring it into view and also directs it towards the glottis .
this technique of cuff inflation has been described for blind nasal intubation in spontaneously breathing patients .
however , the technique was found to be less useful for successful intubation in this study .
combined use of cuff inflation with external laryngeal manipulation ( m3 ) was not useful in this study .
direct laryngoscopy requires elevation of the laryngoscope blade , moves the larynx upwards and elevates the glottis .
thus , lengthens the distance between the glottic orifice and the posterior pharyngeal wall and also makes the nasally introduced tube slide upwards and then downwards in sequence .
thus , it often requires the use of magill 's forceps to align this ett tip with the glottic inlet and its use may sometimes lead to trauma to surrounding structures , damage to ett cuff .
magill 's forceps alone ( m4 ) and m4 with additional external manipulation ( m5 ) were needed more in group 1 as compared to group 2 .
similar studies conducted by kaki et al . and hirabayashi and seo concluded that vls needed lesser use of magill 's forceps for nti .
c - mac vl helped the supporting staff to assist intubation , using less invasive manoeuvres and thus may prevent trauma to oral cavity , damage to ett cuff .
it was also observed that there was a positive correlation between the number of manoeuvres used and the intubation time required in both groups .
patients in group 1 required longer time ( 2 min ) to intubate than group 2 ( 1.5 min ) when the use of additional manoeuvres of the highest level ( m5 ) was required . for good glottic view
, videolaryngoscopy requires the application of lesser force as compared to direct laryngoscopy to the base of the tongue .
therefore , videolaryngoscopy is less likely to stimulate pressor - response and induce local tissue injury .
in contrast , both groups in our study had similar intubation responses which returned to baseline after 5 min .
the difference between both groups preoperatively , before induction and after intubation was statistically insignificant .
further studies are required to know its utility in paediatric patients with difficult airways as well as in adult patients posted for nasal tracheal intubation .
limitation of this study was that anaesthesiologist could not be blinded to the type of device being used for nti .
the study was limited to only sixty patients considering intubation time as the primary outcome parameter .
larger number of enrolled cases are required to assess other parameters of the nasotracheal intubating conditions .
storz c - mac vl provided better glottis visualisation as compared to conventional macintosh direct laryngoscope .
lesser time was required for intubation and there was lesser need for magill 's forceps during nti .
however , requirement of additional external manipulations ( m1 ) was more with the c - mac vl group .
thus , c - mac vl improves the nasotracheal intubating conditions and can be superior alternative to macintosh laryngoscope in clinical practice in paediatric patients .

Answer:
background and aims : c - mac video laryngoscope ( vl ) with macintosh blade has been found to improve cormack - lehane ( c - l ) laryngoscopic view as well as intubating conditions for orotracheal intubation .
 however , studies done on the performance of c - mac vl for nasotracheal intubation ( nti ) are very few in number . hence , we compared laryngoscopy and intubating conditions between macintosh direct laryngoscope and c - mac vl for nti.methods:sixty american society of anesthesiologists physical status i , ii patients , aged 818 years , posted for tonsillectomy surgeries under general anaesthesia with nti were randomised , into two groups .
 patients in group 1 were intubated using macintosh direct laryngoscope and group 2 with c - mac vl .
 c - l grading , time required for intubation , need for additional manoeuvres and haemodynamic changes during and after intubation were compared between the groups.results:c-l grade 1 views were obtained in 26 and 29 patients in group 1 and group 2 , respectively ( 86.7% vs. 96.7% ) .
 remaining patients were having c - l grade 2 ( 13.3% vs. 3.3% ) .
 duration of intubation was less than a minute in group 2 ( 93.3% ) .
 need for additional manoeuvres ( m1m5 ) were more in group 1 ( 97% vs. 77% ) .
 m1 ( external manipulation ) was needed more in group 2 compared to group 1 ( 53.3% vs. 30% ) .
 magill 's forceps alone ( m4 ) and m4 with additional external manipulation ( m5 ) were needed more in group 1 compared to group 2 ( 60% vs. 16%).conclusion : the overall performance of c - mac vl was better when compared to conventional direct macintosh laryngoscope during nti in terms of glottis visualisation , intubation time and need for additional manoeuvres .


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:
nephrotic syndrome in the first year of life in two thirds of cases is caused by mutations in four genes ( nphs1 , nphs2 , wt1 , and lamb2 ) .
the wilms tumor suppressor gene 1 ( wt1 ) encodes a transcription factor involved in kidney and gonadal development .
drash syndrome ( dds ) and frasier syndrome ( fs ) , two syndromes characterized by nephrotic syndrome ( ns ) with either diffuse mesangial sclerosis ( dms ) in dds or focal segmental glomerulosclerosis ( fsgs ) in fs , genitourinary defects and a higher risk of developing wilms tumor in dds , or gonadal dysgerminoma in both dds and fs .
.   recently published three children with fsgs on renal biopsy and wt1 mutations , who responded to intensified therapy consisting of oral cyclosporine a ( csa ) in combination with oral or intravenous glucocorticoids .
the mechanism of csa action in minimal change disease was the inhibition of nuclear factor of activated t cell ( nfat ) signaling in t lymphocytes .
however , the therapeutic effect of csa in genetic nephrotic syndrome is probably related to a direct influence of csa on podocytes .   in this report
, we present a patient with denys  drash syndrome , in whom the calcineurin inhibitors were found to induce total remission .
our patient is the first child of non - consanguineous young parents ( mother 32 , father 34  years ) without any past medical history of kidney diseases .
the infant was born at 41  weeks gestation ( birth weight 3,450  g , length 55  cm ) .
the delivery and neonatal period were normal . at the age of 7  months , she was hospitalized for the first time in the pediatric nephrology department because of proteinuria and hematuria , which was found in routine urinalysis performed before the vaccination . on admission ,
physical examination revealed no edema , normal female external genitalia , and normal body weight and height for chronological age .
initial laboratory investigations revealed variable non - selective proteinuria 200960  mg / dl in morning sample , protein / creatinine ratio 27  g / g , hypoproteinemia ( 4.79  g / dl ) , hypoalbuminemia ( 3.0  g / dl ) , hypercholesterolemia ( 299  mg / dl ) , thrombocytosis ( 567    10/l ) , and reduced levels of igg and iga .
the serum creatinine level was 0.23  mg / dl , urea was 8  mg / dl , and the glomerular filtration rate was 133  ml / min/1.73  m by the schwartz formula .
antinuclear antibodies were negative , and the level of c3 and c4 were within normal limits .
chromosomal analysis demonstrated karyotype 46 , xx , and the biopsy of the kidney demonstrated diffuse mesangial proliferation and diffuse fibrillar increase , what may represent early stage of diffuse mesangial sclerosis .
the glomerular lesions contained high amount of fibrils in the mesangial matrix with diffuse mesangial proliferation .
immunofluorescence on frozen sections using rabbit polyclonal antisera against human igg , iga , igm , and c3 revealed only weak segmental igm staining .
the molecular genetic analysis was performed in the laboratory at the university of michigan in the usa .
mutation analysis of exons 8 to 9 of wt1 was performed , and the mutation r394w ( c. 1180 c  >  t ) was found in our patient .
the treatment with enalapril ( 1.25  mg / day ) , which was started after the admission and was continued for 11  months , did not change the proteinuria significantly .
there was no reduction in proteinuria after 4-week oral prednisone treatment ( 60  mg / m / day ) .
seven months later , we started the therapy with csa ( 6  mg / kg/24  h in two divided doses ) .
the pre - dose / trough ( c0 ) csa level was 104.4  ng / ml .
the serum total protein was ( 6.47  mg / dl ) , albumin ( 4.26  mg / dl ) , cholesterol 197  mg / dl , and platelet count 385    10/ql .
creatinine level was 0.32  mg / dl and the glomerular filtration rate was 147  ml / min/1.73  m. the pre - dose / trough ( c0 ) csa level was 95.03  ng / ml .
at the 6  month of the treatment , we decided for csa dose reduction to 4.5  mg / kg , but a month later , slight proteinuria was observed .
now csa treatment is continued with the higher dose ( 6  mg / kg/24  h ) .
the ultrasonography examination , performed every 3  months , has not revealed any signs of tumor .
we report the benefits of csa treatment of the patient with glomerulopathy associated with wt1 mutation as seen in denys  drash syndrome .
the girl in this report had early - onset srns secondary to dms , what was confirmed in kidney biopsy .
genetic studies showed mutations in intron 9 of wt1 gene c. 1180 c  >  t. this is the most common mutation found in dds .
mutations in exons 8 and 9 of the wt1 gene have been found in patients with isolated srns and in srns associated with wilms tumor or urogenital malformations .
.   indicated that screening of wt1 exons 8 and 9 in patients with sporadic srns is sufficient to detect pathogenic wt1 mutations .
it is possible that our patients have an incomplete form of dds ; however , it corresponds to the observation of ismaili et al . , who reported the presence of wilms tumor in only one of two patients with dds .
chernin et al .   in the recent publication suggested that missense mutations can occur with and without wilms tumor . in our patient ,
in this situation , csa therapy was started with a significant reduction of proteinuria and remission of nephrotic syndrome .
three months later , complete remission of proteinuria was found . whereas genetic forms of nephrotic syndrome do not respond to therapy with immunosuppressive drugs ,
partial remission has been reported following therapy with calcineurin inhibitors in patients with nphs2 , frasier syndrome , mutations of the phospholipase c epsilon gene ( plce1 ) , and alport syndrome [ 3 , 4 ] .
reported three children with fsgs associated with wt1 mutation treated with combined csa and prednisone therapy given for 6 and 12  months .
in long - term observation , the authors observed remission of ns and significant reduction of proteinuria .
the therapy does not seem to be accompanied by a significant loss of renal function on the short term .
we plan to continue the treatment with the lowest possible dose which controls the proteinuria .
it was considered that the main effect of csa treatment in nephrotic syndrome caused by t cell dysfunction was the inhibition of nfat signaling in t cells .
however , it was found that csa can also reduce proteinuria in non - immunological diseases , raising doubts about the above hypothesis . in genetic diseases , mechanisms
similarly , the afferent arteriole vasoconstriction , which is induced by csa , does not seem to play the main role in the reduction of proteinuria .
this fact was suggested by zietse et al . , who studied the influence of csa on proteinuria in different glomerulopathies and found the reduction of protein excretion in minimal change disease , but not in membranoproliferative glomerulonephritis or fsgs .
the possible mechanism in genetic ns may be that proposed by faul et al . .
the authors suggested the influence of csa on synaptopodin , an actin binding protein that was highly expressed in podocytes .
it was shown that calcineurin caused the dephosphorylation of synaptopodin and caused proteinuria via its degradation .
this mechanism seems to be possible because significant reduction ( 30% ) of csa dose caused the slight proteinuria in our patient , so we increased the dose to initial one .
our observation seems to confirm the theory of mundel and reiser , who suggested that proteinuria is due to an enzymatic disease of the podocytes .
it is likely that podocytes are a direct target of csa , which preserves the phosphorylation - dependent synaptopodin-14 - 3 - 3beta interaction , protects synaptopodin from degradation , and preserves a stable filtration barrier [ 7 , 17 ] .
the fact that the antiproteinuric effect of csa results from a direct effect on podocytes explains not only its beneficial role in most steroid - resistant and steroid - dependent nephrotic syndromes but also the fact of cyclosporine dependency .
our observation and observations of other authors [ 3 , 4 , 9 , 12 , 15 ] confirm the beneficial effect of csa treatment in genetic ns ; however , the potential nephrotoxicity of this drug will probably not allow the long - term use .

Answer:
denys  drash syndrome ( dds ) is characterized by progressive glomerulopathy caused by diffuse mesangial sclerosis ( dms ) , genitourinary defects , and a higher risk of developing wilms tumor .
 it is commonly assumed that the dms is unresponsive to any medications . in this report , we present a patient with denys  drash syndrome , in whom the cyclosporine a ( csa ) was found to induce total remission .
 this observation and observations of other authors confirm that in genetic forms of nephrotic syndrome , the proteinuric effect of csa may be due to a non - immunologic mechanism .
 we confirm the beneficial effect of csa treatment in dds ; however , the potential nephrotoxicity of this drug will probably not allow long - term use .


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:
hirsutism is an abnormal growth of terminal hairs in areas dependent on androgen in women and is referred as an increase of unwanted hairs more than what is acceptable in a race or society .
hirsutism is a cultural attitude and what is considered hirsutism in one culture may be considered typical in another .
for example , a woman who is regarded hirsute in a culture may be completely normal in another culture . in the conducted studies ,
the difference in iran from the foreign studies is probably due to racial difference and difference of age groups of the studies .
hirsutism is a symptom of hyperandrogenism and different causes such as polycystic ovary syndrome ( pcos ) , congenital adrenal hyperplasia , androgen - secreting ovarian and adrenal tumors , cushing syndrome , pregnancy , hyperprolactinemia , gonads disorders , drug intake , and idiopathic causes can induce it .
its prevalent symptoms include obesity , acne , menstrual disorders , and alopecia which can cause affliction of the person with pcos .
about half of the hirsute people are obese , and there is a significant relationship between obesity and hirsutism in different studies .
hyperprolactinemia is observed in about 510% of the patients with amenorrhoea which is almost accompanied by galactorrhoea and one of its important complications is infertility .
considering frequency of hirsutism and failure to study prolactin ( prl ) level in patients , the performance of this study about hirsutism causes can help confront with the hirsute patients to find the main cause and determine a suitable solution for patients .
in this cross - sectional study , all patients with hirsutism referring to the dermatology clinic of babol city , northern iran , were included in the study . after giving necessary explanations about this study and receiving a letter of consent , a questionnaire including a history of the disease and physical examination
history of disease included age , marital status , term of affliction with hirsutism , menstrual disorder ( < 21 days and more than 35 days ) , history of galactorrhoea , history of androgenic alopecia , history of hirsutism , history of thyroid disease , pcos , and treatment for infertility ( bromocriptine , clomiphene , and metformin ) .
morning venous blood samples were obtained after a 12 h overnight fasting from the subjects at days 2 to 3 of a menstrual cycle , and immediately centrifuged , and the serum was frozen and stored until all the samples from all the cases had been collected .
follicle stimulating hormone ( fsh ) , luteinizing hormone ( lh ) , prl , dehydroepiandrosterone sulfate ( dhea - s ) , 17-oh progesterone , testosterone , sex hormone - binding globulin ( shbg ) , thyroid - stimulating hormone ( tsh ) , t3 , and t4 tests were performed for all patients . in case ,
there was suspicion about pcos syndrome , pelvic ultrasonography was requested for the patients . according to the definition , the cases with more than ten cysts with dimensions of 28 mm in ovary were called pcos . in the case of confirming the diagnosis ,
a chemiluminescence immunoassay system was used for the determination of sex hormones ( diasorin , germany ) .
testosterone of more than 1.2 ng / ml , dhea - s of more than 340 g / ml , prl of more than 27 ng / ml , lh of more than 27
iu / l , and fsh of more than 15 iu / l , 17-hydroxy progesterone of more than 300 ng / ml , shbg of more than 20 nmol / l , tsh of more than 5.1 miu / ml , t3 of more than 3.1
data were collected and coded . after being recorded in the designed tables , it was entered in version 21 of spss version 21 for windows ( ibm corp , armonk , ny , usa ) and then statistically analyzed .
the obtained information was described by presenting tables of frequency and the related figures . to describe
qualitative characteristics , frequency and percent were used and for quantitative characteristics , mean and range of variations were used . to compare qualitative variables , chi - square test was used and to determine the relationship between quantitative variables , a t - test was used in case of normal distribution .
during the study period , 200 patients were included . the mean age of the studied people was 26.17  6.05 years .
the minimum age of patients was 16 years , and the maximum age was 45 years .
eighty - five patients ( 42.5% ) were single , 115 ( 57.5% ) were married , and 23 married patients ( 20% ) underwent pharmacotherapy due to infertility .
half of the patients ( 100 patients ) had regular menses , whereas the remaining 100 patients had irregular menses .
sixty percent found to have a first - degree family history of hirsutism . in studied patients , 18 patients ( 9% ) had galactorrhoea , 45 patients ( 22.5% ) had androgenic alopecia , and 29 patients ( 14.5% ) had the history of ovary cyst .
out of the 200 patients in the study , 25 patients ( 12.5% ) had hyperprolactinemia .
the mean level of prl in the studied people was 16.69  7.24 ng / ml . table 1 shows the comparison of the patients complaint with hyperprolactinemia . comparing the studied variables with hyperprolactinemia in the studied patients the mean age of the people with hyperprolactinemia was 26.16  5.51 years , and the mean age of the people without hyperprolactinemia was 26.17  6.13 years .
the mean age between the people with hyperprolactinemia and the people without hyperprolactinemia did not show a significant difference ( p = 0.914 ) .
hyperprolactinemia was found in two patients with galactorrhoea ( 8% ) , three patients with androgenic alopecia ( 12% ) , five patients with androgenic alopecia ( 12% ) , five patients with the history of ovary cyst ( 20% ) , one patient receiving drug for infertility ( among 115 married women ) , and 15 patients with positive family history of hirsutism .
there was no significant difference between these cases and hyperprolactinemia , but there was a significant difference between regular menses and hyperprolactinemia [ table 1 ] . in general ,
measurement of dhea - s level showed that 18 patients ( 9% ) had a serum level more than 340 g / ml , and there was hyperprolactinemia in two patients .
twenty - two patients ( 11% ) had hypothyroidism , and all of them underwent treatment .
thyroid serum tests were normal in all treated cases , but three cases of these patients had hyperprolactinemia .
after measuring lh and fsh and calculating the ratio of lh to fsh , lh / fsh ratio was more than 3 in four patients who did not have hyperprolactinemia , and ovary lesions were not found in these four patients after performing ultrasonography .
testosterone level was abnormal in 62 patients ( 31% ) among whom 19 patients had hyperprolactinemia in 11 patients with high testosterone , dhea - s was high but they did not have hyperprolactinemia .
hirsutism makes different problems for women due to the creation of hairs in some parts of the body which are visible . for this reason ,
many patients who refer to treat hirsutism are young women so that mean age of the studied people was 26.18  6.05 in this study , and most patients were in age group of 2125 years .
the mean term of affliction with hirsutism in the studied people was 4.96  3.75 years .
similar to our study , the patients with hirsutism are young women in similar studies . in a study by farnaghi et al . , which investigated 110 patients with hyperprolactinemia in the razi hospital of tehran , mean age of the patients was 29.7  3.2 years with an age range of 1638 years .
the term of affliction with hirsutism was 8 months to 7 years with the mean age of 4.2  1.2 years .
in the study by tirgar - tabari et al . , most patients ( 70.1% ) were in age group of 2023 years . in the study by rahimnejad et al . in southern iran ,
which 81 patients with hirsutism were studied , mean age was 22.5  0.5 years ( between 13 and 41 years ) .
considering that one of the symptoms of endogenous glands diseases particularly ovary diseases is irregular menses , irregular menses was also investigated in this study . in our study ,
, 38% in study by tirgar - tabari , 23.4% in study by yazdanfar et al . , 19.8% in study by ghaderi et al . ,
and 52% in study by rahimnejad et al . difference in the reported percent can be attributed to other diseases and racial and hereditary causes . in our study , 60% of the patients had a positive family record in the first degree relatives in terms of affliction with hirsutism .
in different studies , different percent have been reported in terms of positive family record among people with hirsutism .
a positive family record of hirsutism was found in 29% of patients in study by farnaghi et al .
, 28% of patients in study by tirgar - tabari , 72.8% in study by rahimnejad et al . , 40.7% in study by yazdanfar et al . , and
considering high positive family record in our study , it can be said that genetic has played an effective role in hirsutism .
it should be considered that there is a strong family relation in some endogenous glands such as pcos or adrenal congenital hyperplasia one of which is hirsutism . in this study , 9% of the patients had galactorrhoea , 22.5% had androgenic alopecia , and 14.5% had ovary cyst record . moreover
, 23 out of 115 married patients ( 20% ) underwent pharmacotherapy due to infertility . in a study by tirgar - tabari et al .
low rate of androgenic alopecia in our study can be due to the exclusion of the patients with pco because androgenic alopecia is one of the manifestations of pcos syndrome . in our study , 25 patients ( 12.5% ) had hyperprolactinemia .
hyperprolactinemia was found in two patients ( 8% ) with galactorrhoea , three patients ( 12% ) with androgenic alopecia , five patients ( 20% ) with a history of ovary cyst , one patient receiving the drug for infertility ( 115 married women ) and 15 patients with a positive family record of hirsutism . there was a significant difference between menstrual disorder and hyperprolactinemia .
comparison of mean age between the people with hyperprolactinemia and the people without hyperprolactinemia and comparison of the mean term of affliction with hirsutism between the people with hyperprolactinemia and the people without hyperprolactinemia did not show a significant difference .
hyperprolactinemia was 12.5% in our study , 22.8% in the study by ahmad et al .
, 0.3% in the study by azziz et al . , 0% in the study by carmina et al . , and
the important point of our study is that the patients with pcos , which may be accompanied by hyperprolactinemia , were excluded from the study unlike other studies so that high prl level is not be a confounding factor due to affliction with pco .
prolactinoma is the most prevalent pituitary gland tumor which secrets high amount of prl and can cause hirsutism , infertility , galactorrhoea , acne , and headache .
pituitary gland tumors should be considered in the people with high prl . although increase in the concentration of blood prl can be due to pregnancy , primary hypothyroidism , intake of some drugs ( chlorpromazine , perphenazine , haloperidol , metoclopramide , alpha methyldopa , resertin , opioids , amitriptyline , fluoxetine , verapamil , estrogen , and antiandrogen ) and pcos .
in our study , despite the exclusion of patients with pco , the prevalence of hyperprolactinemia was high .
therefore , high serum prl level should be considered in the referring people with hirsutism .
considering the importance of hyperprolactinemia as one of the causes of infertility and unawareness of patients with hirsutism , the hirsute patients particularly those with a positive family record of hirsutism are recommended to inform the physician and necessary studies should be conducted in this regard .
the present work was supported by a grant from the babol university of medical sciences . no additional external funding received for this study .
the present work was supported by a grant from the babol university of medical sciences . no additional external funding received for this study .

Answer:
background : hirsutism is one of the most important diseases that lead women to refer to dermatology clinic .
 hyperprolactinemia is one of the causes of hirsutism .
 the aim of this study was to determine prolactin ( prl ) levels in hirsute women.materials and methods : in this cross - sectional study , hirsute patients were evaluated .
 for all of the patients , 2 or 3 days after mense starting , hormone level tests were performed , and 200 patients that had not polycystic ovary syndrome enrolled to the study .
 a questionnaire of history and physical examination were performed .
 data have been analyzed with spss version 21.results:hyperprolactinemia were seen in 25 patients ( 12.5% ) .
 there was no significant relation between marital statuses , galactorrhoea , positive family history , and infertility with hyperprolactinemia .
 but significant relation was seen between irregular mense and hyperprolactinemia.conclusion:although hyperprolactinemia is the rare cause of hirsutism , the prevalence of hyperprolactinemia was high in our study .
 thus , prl level in hirsute patients should be evaluate .


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:
bulking agent injection is now a standard treatment for patients with grade 1 - 3 primary vesicoureteral reflux ( vur ) .
patients with higher grades and secondary types of vur show an unacceptably high failure rate when treated with injections of a bulking agent .
collagen has been used for many years as a bulking agent in ureterovesical orifice and bladder neck to treat vur and incontinence .
collagen , however , can get calcified in the tissue , a process that can cause a series of problems for patients .
we present a case of a patient in whom calcified injected collagen showed imaging features mimicking ureteral stone .
a 15-year - old girl presented with moderate degree of right flank pain for 2 weeks .
pain was localized on the right side , altered with change in position , and did not relate to any particular organ .
the patient had been treated successfully for bilateral grade 2 vur when she was 3 years old .
a kidney ureter bladder ( kub ) radiography was requested and the report indicated presence of bilateral ureteral stone [ figure 1 ] .
ultrasonography showed bilateral ureterovesical junction ( uvj ) stone and mild stasis in both kidneys , which was compatible with the findings of the non - enhanced spiral abdomino - pelvic computed tomography ( ct ) scan [ figure 2 ] .
however , diethylene triamine pentaacaetic acid ( dtpa ) scan with furosemide injection and radionuclide cystography ( rnc ) scan ruled out obstruction and relapse of vur .
calcification of bilateral intravesical collagen injected to treat her vur 12 years earlier was responsible for the positive findings on kub , ultrasonography , and spiral ct .
15-year - old female with bilateral flank pain , which was suspected to be due to stones in bilateral ureterovesical junction , later diagnosed as due to calcification of collagen used 12 years earlier to treat vesicoureteral reflux .
15-year - old female with bilateral flank pain , which was suspected to be due to stones in bilateral ureterovesical junction , later diagnosed as due to calcification of collagen used 12 years earlier to treat vesicoureteral reflux .
spiral ct scan of pelvis without intravenous and oral contrast shows bilateral uvj calcifications ( arrows ) .
endoscopic therapy for vur has gained popularity because of elimination of invasive surgical procedures in children .
in addition , it has an acceptable success rate and a low level of complications . although a transition has occurred in the material of choice from teflon to collagen and now to hyaluronic acid copolymers .
however , we do find patients who were treated with collagen now in the second decade of their life .
the injected material , being a foreign body , can induce inflammatory response that leads to tissue calcification .
this calcification has been reported to be symptomatic with some patients reporting episodes of stone passing , hematuria , and even obstruction .
this is the second case report of ureterovesical injection calcification presenting as a ureteral stone during differential diagnosis and the first report of its imaging .
unlike the first case report where the patient presented with renal colic and passing of stone , our patient was completely asymptomatic , except for positional non - related flank pain .
there is no difference between a ureteral stone and calcification of injected collagen , when viewed by different imaging modalities like kub [ figure 1 ] , ct scanning [ figure 2 ] , and also ultrasound examination .
this similarity is because of the place where the bulking agent is injected . in doubtful cases , as in our case , uvj obstruction can be ruled out by dtpa nuclear scan in which glomerular filtration of injected nuclear radioisotope reveals any obstruction in the upper urinary tract .
the diagnosis of uvj stone in the presence of uvj calcification , possibility of ureteral stone passing ( in a patient with renal colic ) after uvj injection therapy , and the probability of recurrent vur after ureteral intervention ( in which calcified ureteral orifice will tolerate dilatation to pass the ureteroscope ) remain to be studied .
vur can be assessed by rnc in which a radioisotope passing to the bladder via the urethral catheter reveals presence of vur .
the standard treatment for grade 1 and 3 primary vur is injection of a bulking agent into the uvj .
clinicians should be aware that calcification of bulking agent like collagen can occur and they need to differentiate this from ureterovesical stones on imaging findings .

Answer:
primary vesicoureteral reflux can be treated by injection of a bulking agent into the wall of the ureterovesical junction . over time , the bulking agent can get calcified .
 radiological images of the area show findings that mimic those seen in ureterovesical junction calculi . in this report
 , we present the imaging findings of this phenomenon and discuss its challenging aspects .


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

Paper text:
a 53-year - old asian woman with a history of lupus erythematosus was initially treated with hydroxychloroquine ( plaquenil , unknown dose ) for 5 years .
approximately 3 years ago , the patient 's medication was changed to chloroquine ( 400 mg daily ) . within a few years of taking chloroquine
, she noticed a circular shadow in her central vision , which she described as an arch surrounding her central vision . at first
, she only noticed a superiorly oriented half - moon shadow that lasted for a few seconds during reading .
the shadow was seen while both eyes were open and disappeared after a few seconds . because of these symptoms and the presence of bull 's eye maculopathy on fundus examination , chloroquine was discontinued and the patient 's medication was changed to dapsone ( unknown dose ) .
the best - corrected visual acuity ( corrected with current spectacles ) of the highly myopic patient during her most recent examination was 20 / 25 in both eyes , with no evidence of an afferent pupillary defect .
slit - lamp examination indicated that the anterior segment was unremarkable and goldmann applanation intraocular pressure was normal ( 16 mmhg ) in both eyes .
however , a significant central defect was noted on humphrey visual field ( hvf ) examination ( humphrey visual field analyzer 10 - 2 ; humphrey instruments , san leandro , ca , usa ) in both eyes . dilated fundoscopy revealed tilting of the optic nerves in both eyes , consistent with myopia , and a ring - shaped area of rpe depigmentation in the parafoveal area of the left eye ( fig .
fundus autofluorescence ( faf ) imaging revealed a hypofluorescent lesion in the foveal and perifoveal areas correspond with the bull 's eye retinopathy . in the left eye ,
a prominent hypofluorescent lesion was also noticed on faf imaging , reflecting marked atrophy of the rpe layer ( fig .
cross - sectional retinal scans , obtained with sd - oct ( spectralis hra+oct ; heidelberg engineering , heidelberg , germany ) showed obvious thinning of the macula and disruptions in the outer retina .
more specifically , loss of the photoreceptor inner / outer segment ( is / os ) junction corresponded to the location of the maculopathy as identified on fundus photography , faf , and hvf 10 - 2 .
the outer retinal layer had a moth - eaten appearance at the is / os junction , but the thickness and appearance of the inner retina were within normal limits .
additionally , a downward displacement of the overlying retina was seen in perifoveal areas and corresponded to the hypofluorescent lesion in faf images . unlike the anatomically disrupted areas , which corresponded to the bull 's eye lesion , the central fovea had normal thickness and structure on sd - oct in both eyes ( fig .
the ao system used in the current study utilized a dual liquid crystal on silicon spatial light modulators ( lcos - slms ; x10468 - 02 , hamamatsu photonics , morimoto , japan ) first introduced by hirose et al . .
although deformable mirrors have been widely used , their performance is limited with respect to compensating large amounts of aberration of human eyes . meanwhile , although lcos - slm is able to compensate large amounts of aberration by the phase wrapping method utilizing a continuity of the wavefront of a laser beam , it is only capable of compensating a particular polarization component .
this system is very efficient at following changes in aberration of a subject according to change in imaging location , but is not suitable for obtaining high contrast images because the power of the lights used for simultaneous imaging and measurement / compensation of time is limited for safety . in this study
, we overcame these problems by adopting dual lcos - slm to compensate the two orthogonal polarization components and sequential processing of slo imaging and measurement / compensation of aberrations .
ao - slo images were obtained and cone density was measured 0.5 , 1.0 , and 1.5 mm from the center of the fovea in each of the 4 major directions ( superior , inferior , nasal , and temporal ) .
a montage was then created and verified by checking the correspondence between the ao - slo and wide - field images .
cone density was calculated using photoreceptor analysis software ( canon , tokyo , japan ) . to obtain an accurate cone density ,
the axial length , anterior chamber depth , and keratometry values were all considered when counting cone cells , which were represented in images as bright spots 2 to 5 m in size .
we manually selected areas of interest , and excluded retinal vessels and artifacts that obscured the underlying cone mosaic .
ao - slo images showed patch cone mosaic lesions , indicating abnormal regions of missing or lost cones .
in addition , the observed cones were asymmetrical in shape and size and varied in brightness ( fig .
cone densities in the right eye were 14,927 , 10,377 , and 11,853 cones / mm at 0.5 , 1.0 , and 1.5 mm from the center of the fovea , respectively .
the corresponding cone densities in the left eye were 16,692 , 12,564 , and 13,100 cones / mm , respectively .
the cone density at 1.5 mm from the center of the fovea was closer to normal than the other distances ; however , the photoreceptors located 1.5 mm from the foveal center exhibited asymmetrical shapes and sizes , and varied in brightness in ao - slo images .
additionally , sd - oct images showed an abnormal is / os cytoarchitecture 1.5 mm from the foveal center .
when we matched the disrupted areas on the ao - slo images with the visual field test , the areas with abnormal cone mosaic patterns and low cone density corresponded with the location of visual field defects on hvf ( fig .
ocular side effects associated with chloroquine can be primarily divided into keratopathy , ciliary body changes , and retinopathy .
bull 's eye maculopathy , a type of retinopathy , is associated with the use of antimalarial agents and is relatively rare . however , bull 's eye maculopathy is the most serious of the ocular adverse effects and is of serious pathologic concern , as the associated visual changes can be severe and there is little chance of visual recovery .
in addition , visual loss associated with bull 's eye maculopathy can progress even after the drug treatment is terminated .
patients with retinopathy usually present with central visual loss , visual field defect , color vision deficiency , photoaversion , night blindness , and entopic phenomenon .
easterbrook reported that patients with minimal paracentral scotomas do not complain of symptoms and have normal color vision . in these patients ,
however , in nearly 70% of patients with ocular symptoms , abnormal color vision , and fundus changes , retinopathy progresses even after termination of drug use . together
, these studies illustrate the importance of early detection , ideally before the onset of visual symptoms .
fluorescein angiography ( fa ) can reveal the bull 's eye pattern of granular hyperfluorescence , but is not useful for the diagnosis of early retinopathy .
in full - field electroretinography ( erg ) , there may be a deepening of the a - wave   or an amplitude reduction in the scotopic b - wave .
however , in most cases , erg findings are normal with minimal macular damage and decrease only after diffuse retinal damage has occurred .
it was also reported that sd - oct images are able to show the perifoveal interruption of the photoreceptor is / os junction in eyes with chloroquine retinopathy . however , despite this new information , there is currently no established criteria for diagnosing chloroquine retinal toxicity prior to the development of irreversible visual loss .
studies performed in mice have shown that photoreceptors are the primary targets affected by chloroquine maculopathy , and that further degeneration occurs despite cessation of medication .
additionally , rosenthal et al .   showed that use of chloroquine in rhesus monkeys causes significant changes in both the inner and outer retinal layers .
exposure to ultraviolet radiation causes chloroquine to fluoresce , and based on this property , clinical studies have shown that a widespread , severe reduction of rod and cone processes occur in the outer nuclear and plexiform layers . still , because of aberrations of ocular optics , none of the currently available imaging methods are capable of observing cells with disrupted photoreceptors in living human eyes . recently
, ao technology has been developed that allows for individual cones to be clearly visualized in vivo by compensating for aberrations in ocular optics [ 6 - 8 ] . using ao - slo technology ,
several studies have shown that successful visualization of photoreceptor microstructure is possible in both normal eyes and eyes with various retinal diseases .
consistent with previous ao studies , our ao - slo images from normal eyes showed a regular cone mosaic pattern , in which the cone density decreased with increasing distance from the center of the fovea . in the patient with bull 's eye maculopathy , we observed a disrupted cone mosaic pattern with individual cones having irregular shapes and sizes .
additionally , compared with normal patients , patients with bull 's eye maculopathy can exhibit irregular cone brightness as well as dark and patchy lesions where cones are either missing or lost . in the present study , along with the disrupted cone mosaic pattern , measured cone densities were diminished in all areas . to better interpret the findings in our study , comparative data was obtained from both previous studies and historical controls . in normal eyes
the average cone densities 0.5 and 1.0 mm away from the foveal center are approximately 30,000 and 15,000 cones / mm , respectively .
these values were in agreement with histological studies reporting cone densities of 37,000 , 16,000 , and 14,000 cones / mm at 0.5 , 1.0 , and 1.5 mm away from the foveal center , respectively .
stepien et al .   previously reported an ao image of bull 's eye maculopathy associated with antimalarial agent use .
although similar abnormal images of cones have been obtained using their ao system , they were not as high quality as the images obtained in the present study .
specifically , we were able to achieve improved image quality and contrast because our ao - slo utilized a dual liquid crystal on lcos - slms to correct for wavefront aberrations , while the system used by stepien et al .
moreover , creating a montage of ao - slo images made it possible to compare each ao - slo image to visual field test results . using this technique , we were able to demonstrate that areas with visual defects could be matched with cone pattern and density abnormalities .
because ao - slo can image the retina with such high resolution , it is more sensitive to photoreceptor abnormalities than sd - oct . in our study
, sd - oct images revealed equal disruption of the outer retinal layer at 1.0 and 1.5 mm away from the fovea .
however , ao - slo images revealed a higher level of cone pattern disruption and a lower cone density at 1.0 mm away from the fovea , compared with 1.5 mm away from the fovea .
there were several limitations of the present study that should be mentioned . because the central foveal structure was conserved , our patient had a visual acuity of 20 / 25 .
however , we could not obtain images of the central fovea for reasons described in previous studies [ 6 - 8 ] .
unfortunately , the inability to obtain these images made it impossible to compare cellular images of the fovea with those obtained from the bull 's eye lesion .
another limitation of our study was that the ao - slo system could not acquire images from the central fovea or the peripheral retina .
therefore , we only investigated cone properties at 0.5 , 1.0 , and 1.5 mm away from the center of the fovea .
because of this limitation , we were unable to compare preserved areas adjacent to the bull 's eye lesion , which may possibly have contained cones in the preclinical stage of the disease . as described above , the visual acuity of the patient was 20 / 25 , and we hypothesized that the reason for the relatively mild visual decrease was because the structure of the central fovea remained relatively preserved .
however , we could not confirm this possibility because the center of the fovea could not be precisely imaged by ao - slo .
similarly , because the ao - slo can not obtain images from the peripheral retina , it was not possible to compare the disrupted macula to the relatively preserved peripheral retina .
depending on the specific disease , patients may be treated with either a chronic maintenance or acute high - level dose of chloroquine . a daily dose of chloroquine > 3 mg / kg and a treatment duration of > 5 years
therefore , patients who are taking chloroquine or hydroxychloroquine should have regular ophthalmic examinations to detect retinal changes as early as possible in order to minimize retinal toxicity . in the present study
, we showed that ao - slo can image cellular structures of the retina in living eyes in order to detect preclinical stages of chloroquine associated retinal damage that may not be apparent on standard clinical tests ( e.g. , fundus photography , fa , hvf , and electrophysiological testing ) .
importantly , the ability to identify photoreceptor disruptions in the preclinical stages of toxicity should allow for chloroquine withdrawal during the reversible stages of maculopathy . despite the limitations of our ao system
, our results suggest that ao - slo should provide a non - invasive , quantitative , high - resolution modality for imaging chloroquine retinopathy patients .
likewise , the abilities of ao - slo have the potential to provide a new approach for the diagnosis and monitoring of chloroquine toxicity .

Answer:
a 53-year - old asian woman was treated with hydroxychloroquine and chloroquine for lupus erythematosus . within a few years
 , she noticed circle - shaped shadows in her central vision . upon examination ,
 the patient 's visual acuity was 20 / 25 in both eyes .
 humphrey visual field ( hvf ) testing revealed a central visual defect , and fundoscopy showed a ring - shaped area of parafoveal retinal pigment epithelium depigmentation .
 fundus autofluorescence imaging showed a hypofluorescent lesion consistent with bull 's eye retinopathy .
 adaptive optics scanning laser ophthalmoscope ( ao - slo ) revealed patch cone mosaic lesions , in which cones were missing or lost .
 in addition , the remaining cones consisted of asymmetrical shapes and sizes that varied in brightness . unlike previous studies employing deformable mirrors for wavefront aberration correction , our ao - slo approach utilized dual liquid crystal on silicon spatial light modulators .
 thus , by using ao - slo , we were able to create a photographic montage consisting of high quality images .
 disrupted cone ao - slo images were matched with visual field test results and functional deficits were associated with a precise location on the montage , which allowed correlation of histological findings with functional changes determined by hvf .
 we also investigated whether adaptive optics imaging was more sensitive to anatomical changes compared with spectral - domain optical coherence tomography .


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:
ventral hernias are the second most common type of abdominal wall hernias , after inguinal hernias .
the majority of ventral hernias are incisional , occurring in 3% to 13% of laparotomy incisions , necessitating approximately 90 000 ventral hernia operations per year .
the use of prosthetic material , such as polypropylene mesh , polytetrafluoroethylene , and marlex mesh has decreased rates of recurrence . however , wound complications with the use of mesh in open ventral hernia repair are significant . since 1992
, the laparoscopic technique has been applied to the repair of ventral hernias because of its many advantages including the absence of large subcutaneous flaps , a lower incidence of wound infection , and a reduction in postoperative pain and hospital stay .
the lower recurrence rates are most likely due to the tension - free and intraperitoneal placement of the mesh .
laparoscopy offers a clear view of the entire fascial defect , which is not always possible with the open technique , especially if a
thus , the entire defect is completely circumscribed with the laparoscopic technique . the surgical technique described for laparoscopic ventral hernia repair varies by surgeon
. however , all techniques reported use at least 3 port sites , with one or more being 10 mm . using this technique , either the primary surgeon or the first assistant is working in mirror - image .
between july 2002 and january of 2003 , 3 patients underwent laparoscopic ventral hernia repair with mesh in which only two 5-mm ports were used for small incisional or ventral hernias .
follow - up surveillance for complications and hernia recurrence was performed in the immediate postoperative period , 1 week to 2 weeks after surgery .
additional follow - up was obtained by telephone interview 6 months to 12 months postoperatively .
after the abdomen was prepped , an iodine impregnated adhesive drape dressing was placed on the patients ' abdomen .
access to the abdomen was obtained in an area lateral to the hernia by using a veress needle .
after exploration of the abdomen , a second 5-mm trocar was introduced under direct visualization on the opposite side of the fascial defect .
adhesiolysis was performed to free the anterior abdominal wall , and the margins of the hernia defect were circumferentially cleared to a distance of at least 4 cm .
a dual , expanded polytetrafluoroethylene ( eptfe ) mesh ( dualmesh , wl gore , flagstaff , az ) was used , ranging in size from 8.5 cm to 10 cm .
once the mesh was place intracorporeally , the sutures were retrieved through the abdominal wall by using a laparoscopic suture passer .
the sutures were tied extracorporeally , and the knots were buried in the subcutaneous tissues .
the circumference of the mesh was then affixed , by using a 5-mm spiral tacking device , to the posterior abdominal wall at intervals of approximately 1 cm .
after the abdomen was prepped , an iodine impregnated adhesive drape dressing was placed on the patients ' abdomen .
access to the abdomen was obtained in an area lateral to the hernia by using a veress needle .
after exploration of the abdomen , a second 5-mm trocar was introduced under direct visualization on the opposite side of the fascial defect .
adhesiolysis was performed to free the anterior abdominal wall , and the margins of the hernia defect were circumferentially cleared to a distance of at least 4 cm .
a dual , expanded polytetrafluoroethylene ( eptfe ) mesh ( dualmesh , wl gore , flagstaff , az ) was used , ranging in size from 8.5 cm to 10 cm .
once the mesh was place intracorporeally , the sutures were retrieved through the abdominal wall by using a laparoscopic suture passer .
the sutures were tied extracorporeally , and the knots were buried in the subcutaneous tissues .
the circumference of the mesh was then affixed , by using a 5-mm spiral tacking device , to the posterior abdominal wall at intervals of approximately 1 cm .
the size of the mesh used varied , based on the size of the original defect .
additionally , no recurrences were noted after a mean follow - up of 9 months ( range , 6 to 12 ) .
laparoscopic ventral hernia repair is a procedure that has gained acceptance among surgeons and patients over the last 5 years to 10 years
. the documented advantages of laparoscopic surgery in general include faster recovery and return to normal activity , less postoperative pain , fewer wound - related complications , and a better cosmetic result .
in addition , the intraperitoneal repair performed laparoscopically poses a significant mechanical advantage and is associated with less recurrence .
we present 3 patients who underwent laparoscopic repair of a ventral hernia in which two 5-mm ports were used .
these patients had no surgical complications , and the mean operating room times were acceptable .
this technique offers all the advantages inherent to laparoscopic surgery , with the added benefit of the use of only two 5-mm ports .
laparoscopic repair of ventral or incisional hernias can be performed using only two 5-mm ports .
this technique can be done on an outpatient basis in a safe , timely fashion .

Answer:
objective : high recurrence rates have been documented after primary repair of incisional hernias .
 laparoscopic ventral and incisional hernia repairs have been performed with very low rates of recurrence .
 we have modified the standard technique of laparoscopic repair in patients with small incisional and ventral hernias .
 the purpose of this study was to document the technique utilizing only two 5-mm ports and demonstrate that it is safe , effective , and feasible.methods:three patients with small incisional or ventral hernias were examined .
 the standard laparoscopic ventral hernia repair technique was modified as follows : two 5-mm ports were inserted on opposite sides of the defect .
 the defects ranged from 2.5 cm to 4 cm in size .
 expanded polytetrafluoroethylene mesh ( dualmesh , wl gore , flagstaff , az ) was used to cover the hernia defect , overlapping the defect margins circumferentially by 3 cm .
 the mesh diameter ranged from 8.5 cm to 10 cm .
 the mesh was inserted through a 5-mm skin incision site and affixed into position with transfascial sutures and spiral tacks.results:the operative time ranged from 53 minutes to 57 minutes .
 all patients were discharged home the day of surgery and reported minimal postoperative pain .
 follow - up ranged from 6 months to 1 year ; all patients were doing well without recurrence.conclusion:laparoscopic repair of ventral or incisional hernias can be performed using only two 5-mm ports .
 this technique can be done on an outpatient basis in a safe , timely fashion .


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:
pharmaceutical companies and many academic centers have thousands of high - quality compounds that represent potential new drugs .
these high - quality compound collections contain thoroughly studied development candidates and , in many cases ,  old  drugs that were generated for non - cns disorders but that might be useful therapies for one or more psychiatric diseases . however , testing these compounds for activity relevant to treating psychiatric diseases is challenging . whereas some disease areas , such as cancer or infectious disease , are relatively amenable to high - throughput in vitro testing of hundreds of thousands of compounds , psychiatric diseases are not . because psychiatric diseases generally result from disorders of cell  cell communication or circuitry , intact systems are required to detect improvement in disease - relevant endpoints .
the need for observers to be blinded to the treatment group of each animal increases the resources required to appropriately dose and randomize animals in a way that is invisible to the observer .
furthermore , multiple complementary behavioral assays are required to determine whether observed effects are robust and are not due to undesired effects , such as sedation ( crawley and paylor , 1997 ) .
thus , the discovery of new neuropharmacological drugs with novel mechanisms of action is impeded by the absence of high - throughput , robust , and objective behavioral assays . very recently a 96-well behavioral assay measuring the photomotor response of zebrafish embryos demonstrated that different classes of neuropharmacological compounds cause distinct patterns of responses ( kokel et al . , 2010 ) .
such an assay is relatively inexpensive and is well suited to screening high numbers of compounds about which little is known . for high - quality compounds , particularly compounds that have entered human testing , a rodent system offers advantages .
for advanced compounds , rodent pharmacokinetics and safety are often known , and sufficient quantities of these compounds generally exist to support rodent studies . to enable testing of many compounds for behavioral effects relevant to psychiatric disease
, psychogenics developed smartcube , an automated system in which behaviors of compound - treated mice are captured by digital video and analyzed with computer algorithms ( brunner et al . , 2002 ) .
pgi analytical systems uses data from smartcube to compare the behavioral signature of a test compound to a database of behavioral signatures obtained using a large set of diverse reference compounds . in this way ,
the neuropharmacological effects of a test compound can be predicted by similarity to major classes of compounds , such as antipsychotics , anxiolytics , and antidepressants .
this approach is ideally suited to screening collections of existing drugs or drug candidates for previously unknown neuropharmacology , which could expedite the development of new and unexpected treatments for psychiatric disorders . in this paper , we demonstrate that this system can detect relevant cns activity of compounds representing mechanisms beyond those used clinically to treat psychiatric disorders .
an overview of pgi analytical systems , a rapid , computer vision - enabled murine screening system for neuropharmacological activity , is shown in figure 1 . the pgi analytical systems training set consisted of hundreds of doses of clinically approved reference drugs , grouped per indication ( e.g. , anxiolytics , antidepressants , etc . ) .
drugs were injected 15  min before the test , and multiple challenges were presented over the course of the test session .
digital videos of the subjects were processed with computer vision algorithms to extract over 2,000 dependent measures including frequency and duration of behavioral states such as grooming , rearing , etc . , and many other features obtained during the test session .
pgi analytical systems combine proprietary hardware , robotics , computer vision , and data mining techniques to collect thousands of behavioral features in a single test session and extract unique signatures for each compound .
these signatures are compared with the signatures obtained from reference compounds ( shown to have clinical efficacy ) in different therapeutic classes and subclasses to predict clinical utility .
a proprietary machine learning algorithm was developed to train a probabilistic classifier that mapped the extracted computer vision feature values from the training set to their corresponding cns indications .
this tool was used to establish a reference database of therapeutic class signatures and provided a mechanism to determine the cns probabilistic profile of an arbitrary test sample .
our reference database comprises 14 classes of drugs with some of the major classes , such as the antidepressant class , comprising several subclasses with representatives of most of the drugs in the market .
test set  assessment were chosen from our evaluation tests and two separate types of classifiers were built that make independent predictions : one at the therapeutic class level and one at the level of highly performing subclasses .
the behavioral signatures of the test drugs were scored by these classifiers to predict potential therapeutic utility . to evaluate the ability of the pgi analytical system to detect relevant behavioral responses to novel compounds ,
we tested two compounds that represent mechanisms not yet used clinically to treat psychiatric disorders but that impact relevant behavioral endpoints in rodents .
the two test compounds , tp-10 and pf-670462 , had not been included in the computer algorithm training set .
tp-10 is a sub - nanomolar inhibitor of pde10a , a dual - substrate phosphodiesterase expressed in medium spiny neurons of the striatum that regulates striatal output by regulating both camp and cgmp hydrolysis ( strick et al . , 2007 ) .
tp-10 demonstrates multiple behavioral effects in rodents that are consistent with clinically effective antipsychotics , including decreased locomotor activity , inhibition of conditioned avoidance response , and improvement of amphetamine - induced deficits in auditory gating ( schmidt et al . , 2008 ) .
pf-670462 is a casein kinase i ( ck1 ) inhibitor ( badura et al . , 2007 ) .
all compounds were dissolved in a pharmasolve , peg , pg mixture , and were injected i.p .
13  h before the behavioral test because of its known effects on circadian rhythm at 50  mg / kg s.c .
( badura et al . , 2007 ) ; this procedure was done both in the morning and evening . as a follow - up test to confirm the anxiolytic signature of pf-670462 we use the marble burying test .
pf-670462 was dissolved in 40% cyclodextrin and injected at 10 and 30  mg / kg , s.c .
experimenters were blind to the mechanisms of action of both compounds and to the dose being used . the institutional animal care and use committee of psychogenics reviewed and approved the animal use in these studies . the animal care and use program is fully accredited by the association for assessment and accreditation of laboratory animal care , international .
in the pgi analytical system , tp-10 produced a dose - dependent signature of activity most similar to that of known antipsychotics , particularly at the 1-mg / kg dose ( figure 2 ) .
response curve in this system , consistent with its steep dose  response curve in other rodent models ( schmidt et al . , 2008 ) . at the lower 0.5  mg / kg  dose , tp-10 s activity is more similar to that of the vehicle than to any class of drugs in the reference database . at the higher dose of 2
mg / kg , tp-10 produced a behavioral pattern that is quite different from that of the vehicle yet not specific to any one class .
notably , tp-10 activity at the 2-mg / kg dose has a large behavioral component similar to that of high - dose antidepressants but not medium - dose antidepressants .
interestingly , three of the four reference antipsychotic signatures shown in figure 3 also have a larger high - dose antidepressant - like component at their highest doses .
overall , the profile of tp-10 in this computer - aided screening system is similar to that of clinically used antipsychotic drugs ( gleason and shannon , 1997 ; powell et al . , 2008 ;
this observation is consistent with tp-10 s activity in multiple rodent models ( schmidt et al . , 2008 ) , suggesting that the pgi analytical systems can identify antipsychotic - like activity of compounds acting through novel mechanisms . the pde10a inhibitor tp-10 produced a signature of activity suggesting potential antipsychotic activity .
the size of a given colored region on each bar indicates the probability that the activity of tp-10 at that dose matches a given class of neuropharmacological agents .
the size of the white area represents that probability that the activity is more similar to that of the vehicle rather than to that of any compounds in the reference database .
drug signatures of four of the antipsychotic drugs included in the reference dataset : aripiprazole , clozapine , haloperidol , and olanzapine .
in contrast to pde10a , for which considerable literature data support its role as an antipsychotic target , the potential usefulness of altering ck1 s effects on circadian rhythm for treating psychiatric disorders is unknown .
ck1 is an important regulator of period proteins ( per ) that regulate the clock mechanism in cells ( lee et al . , 2001 ) . clearly , improved regulation of circadian rhythm could improve functioning in patients with sleep disorders .
furthermore , disruptions of the sleep  wake cycle can affect cognition , memory , and mood ( benca et al .
ck1 is also involved in darp32 phosphorylation and thus participates in dopamine - dependent behavioral activation ( bryant et al . ,
thus , the ck1 mechanism is a good candidate for screening in a system that may identify behavioral signatures relevant to a wide variety of psychiatric disorders . in the pgi analytical system at intermediate doses of 30 and 50
mg / kg , the ck1 inhibitor pf-670462 ( badura et al . , 2007 ) demonstrated a signature consistent with anxiolytic , but not sedative / hypnotic , activity ( figure 4 ) . because pf-670462 produces changes in circadian rhythm ( badura et al . , 2007 ) , we tested whether administering pf-670462 to mice 13  h prior to testing might produce a more relevant behavioral signature .
interestingly , the compound had almost no detectable behavioral effects in this system when dosed 13  h before testing , either in the morning ( 5:30 am ) or the afternoon ( 7 pm ) . the anxiolytic signature of pf-670462 seen at the 30 , but not 10 , mg / kg dose was confirmed in the marble burying test , in which the higher dose decreased marbles buried without a decrease in locomotion ( figure 5 ) .
the ck1 inhibitor pf-670462 demonstrated a signature consistent with anxiolytic activity ( yellow ) and , at the highest dose tested , behavioral effects similar to that of opiate analgesics ( pink ) , although this dose is higher that doses tested previously in rodents and may reflect non - specific effects .
15  min before the test in studies represented by the five left - most bars of the chart . to assess
potentially delayed behavioral effects due to its effects on circadian rhythm , pf-670462 was injected s.c .
13  h before testing in the morning ( am ) or in the afternoon ( pm ) .
the ck1 inhibitor pf-670462 shows anxiolytic activity in the marble burying test with a strong yet non - significant trend at 10  mg / kg and a significant effect at 30  mg / kg , consistent with the dose
response anxiolytic signature uncovered by the high - throughput screen [ anova f(4,43 )  >  8.8 ,
p  <  0.0001 ; fisher plsd p  <  0.02 ] . the drug was injected s.c .
our work demonstrates the usefulness of a computer vision - based system for identifying behavioral effects of novel compounds and mechanisms in a relatively high - throughput in vivo assay .
as one example , the pde10a inhibitor tp-10 demonstrated a behavioral signature in the pgi analytical system that was more similar to that of known antipsychotics than to that of other classes of neuropharmacological agents .
although the efficacy of pde10a inhibition in humans has not been tested , the activity of tp-10 here is consistent with effects of clinically used antipsychotics in multiple rat in vivo assays ( schmidt et al . , 2008 ) .
importantly , the steep dose  response curve of tp-10 was also consistent between the computer vision - based system and traditional rodent assays .
interestingly , tp-10 was ineffective in two mouse pre - pulse inhibition models ( schmidt et al . , 2008 ) , although it showed an antipsychotic - like signature in mice in the present study .
the computer vision - based system , which measures hundreds of small behavioral events , may reveal more relationships because of its ability to assess compound effects more broadly than a model designed to test one specific functional hypothesis .
the tp-10 behavioral signature at the highest dose tested suggested a small degree of activity similar to that of high - dose antidepressants .
this feature was observed with the higher doses of most of the four reference antipsychotics in figure 3 , as well , suggesting that the similarity is due to side effects caused by high doses of all such compounds .
the computer vision - based system also suggested new hypotheses regarding the behavioral effects of ck1 inhibition .
we found that moderate doses of pf-670462 produced activity similar to that of anxiolytic agents , but not sedative / hypnotics .
we followed up this result in the marble burying test , an assay predictive of anxiolytic therapeutic potential , and confirmed that a dose of 30  mg / kg has anxiolytic activity ( figure 5 ) . in summary ,
our data demonstrate that the pgi analytics computer vision - based system rapidly detects relevant behavioral effects of compounds acting through new mechanisms .
because the assay and data analysis are highly automated , use of the system eliminates the need for subjective human observation and evaluation of behavior , thus eliminating significant resource requirements along with much of the potential for bias inherent in subjective measurements .
this approach is ideally suited to screening libraries of existing drugs or drug candidates for previously unknown neuropharmacology , which could expedite the development of new and unexpected treatments for psychiatric disorders .

Answer:
the lack of predictive in vitro models for behavioral phenotypes impedes rapid advancement in neuropharmacology and psychopharmacology . in vivo
 behavioral assays are more predictive of activity in human disorders , but such assays are often highly resource - intensive . here
 we describe the successful application of a computer vision - enabled system to identify potential neuropharmacological activity of two new mechanisms .
 the analytical system was trained using multiple drugs that are used clinically to treat depression , schizophrenia , anxiety , and other psychiatric or behavioral disorders . during blinded testing the pde10 inhibitor tp-10 produced a signature of activity suggesting potential antipsychotic activity .
 this finding is consistent with tp-10 s activity in multiple rodent models that is similar to that of clinically used antipsychotic drugs .
 the ck1 inhibitor pf-670462 produced a signature consistent with anxiolytic activity and , at the highest dose tested , behavioral effects similar to that of opiate analgesics .
 neither tp-10 nor pf-670462 was included in the training set .
 thus , computer vision - based behavioral analysis can facilitate drug discovery by identifying neuropharmacological effects of compounds acting through new mechanisms .


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:
who has estimated that there were 171 million people worldwide with diabetes mellitus ( dm ) in 2000 and predicted that 366 million people will have dm by 2030 .
the united states centers for disease control and prevention have estimated that 13 million persons in the united states have diagnosed dm , and an additional 5,2 million have the disease but it is not yet being diagnosed .
diabetes mellitus is a severe metabolic disease associated with a number of complications including retinopathy , nephropathy and neuropathy .
mortality related to dm and its complications result in 3.8 million deaths annually , accounting for 6% of the total worldwide mortality [ 2 , 3 ] .
the mortality risk in the diabetic population in the age of 4049  years is about 67  years and for the age category of 6069 it is about 3 - 4  years higher , compared to mortality risk , at the same age healthy population .
the stage of nephropathy , including the severity of proteinuria is a predictable factor for the mortality risk .
approximately 2.5% to 15% of annual healthcare budgets is spent on care of patients with diabetes and associated complications .
it has been estimated that programs to identify and treat diabetic retinopathy ( dr ) would have saved the united states health care budget nearly 400 million dollars annually in the early 1990s , ] a figure that would probably be substantially higher today .
a lot of studies in dm type 2 between which is the ukpds - study , have underlined the beneficial effect of having the hba1c , not < 6% . a diverse array of micro- and macrovascular changes ,
are induced trough  bad metabolic memory  and increase , as well as decrease of hba1c ( fig .  1 ) .

increase of glycated hemoglobin in diabetic population at baseline , and in 6  years follow - up period , has the same impact on the cardiovascular complications , as the decrease of hba1c < 6.0% accord
increase of glycated hemoglobin in diabetic population at baseline , and in 6  years follow - up period , has the same impact on the cardiovascular complications , as the decrease of hba1c < 6.0% retinal vascular changes in diabetic population are the most common cause of blindness among eye diseases .
impairment of retinal circulation results in blood flow alternations that affect the delivery of oxygen and metabolic substrates to the tissue .
release of oxygen derived free radicals , nitric oxide - mediated neurotoxicity , and delayed cell death lead to neuronal damage . poor glycemic control sets the stage for initiation of the microvascular changes .
the molecular basis of dr and maculopathy takes into consideration the role of growth factors and cytokines in the development of diabetic vascular alterations , their specific influence on the cellular interaction between retinal endothelial cells and pericytes , and the role of intravascular blood components .
the earliest histological features of dr include neuroretinal damage , capillary basement membrane thickening , loss of pericytes and loss of endothelial cells .
the hallmark of proliferative diabetic retinopathy ( pdr ) is neovascularization ( nv ) which occurs at the latter stages of the disease and can result in blindness ; nv is the consequence of abnormal fibrovascular proliferations with subsequent bleeding and retinal detachment .
numerous studies have underlined the role of the angiogenic factors in the progression of dr and include vascular endothelial growth factor ( vegf ) , insuline - like growth factor ( igf-1 ) , hepatocyte growth factor ( hgf ) , basic fibroblast growth factor ( b - fgf ) , platelet - derived growth factor ( pdgf ) , pro / inflammatory cytokines and angiopoetins . on the other hand ,
the major antiangiogenic factors are : pigment epithelium derived factor ( pedf ) , transforming growth factor beta ( tgf - beta ) , thrombospondin ( tsp ) and somatostatin [ 57 ] .
the balance among angiogenic and antiangiogenic factors has a determining role in the progression of dr .
the early diabetic retinopathy study ( edrs ) demonstrates the ability of panretinal photocoagulation to reduce the rate of severe visual loss by 50% for eyes with high risk characteristics , defined as nv originating from optic disc ( > 1/3 disc diameter ) , any nv originating from the optic disc with hemorrhage , and nv originating from the retina with vitreous hemorrhage .
the edrs showed that patients with ( type 2 ) dm who were older than 40  years of age , with severe nonproliferative dr ( defined as hemorrhages in four quadrants , or intraretinal microvascular abnormalities in one quadrant ) , have benefited from early panretinal photocoagulation . the early vitrectomy diabetic study ( evds ) showed that early vitrectomy ( within 6  months of onset of vitreous haemorrhage ) was associated with better results in type 1 diabetes mellitus patients [ 79 ] .
where are we now in relation to our knowledge in prevention and early treatment of dr ? did we follow our investigations in a direction that can give us solution of the main problems , or our investigations do not have a real clinical impact ?
can we expect better predictive strategies for early diagnosis and treatment ? to answer these questions we will summarize our results achieved with currently available diagnostic and therapeutic approaches .
a number of advances in science have been translated into real and measurable advances in patient care .
the emerging investigations are concentrated on different secretory proteins and their role in the development on pdr . for example
secreted acidic proteins rich in cystein ( sparc ) are isolated from the vitreus fluid and are increased in patients with pdr .
furthermore , subretinal injections of recombinant sparc adenovirus , induce pdr - like changes in the rat , thereby providing a relevant animal model for the investigation of pdr .
robo4 , a member of roundabout ( rabo ) family , acts as a neuronal guidance receptor and plays some role in vasculogenesis and angiogenesis .
several studies have shown its effect on the formation of fibrovascular membranes in patients with pdr , and its role in choroids - retina endothelial ( rf/6a ) and human retinal pigment epithelial cells .
silencing the expression of robo4 in rf 6a and rpe cells inhibited their proliferation and reduced the hypoxic condition tolerance .
a number of studies have estimated increased levels of interleukin 8 in vitreous samples from patients with pdr and in patients with more severe large - vessel gliotic obliteration .
cystein - rich 61 ( cyr61 ) induces are reported to mediate angiogenesis , and they have been shown to cause proliferation , migration , and synthetic matrix tube formation of rf/6a cells .
recent reports indicate that cyr61 acts as an angogenic mediator of ocular nv in vitro and in vivo . it may interact in synergy with vegf in the pathogenesis of pdr . on the other hand , rosiglitazone maleate , an oral peroxsisome - proliferating activated receptor gamma agonist and oral insulin sensitising agent with potential antiangiogenic activity , delays onset of pdr .
the  golden standard  of therapy in dm is insulin , and previous studies have emphasized its inhibitory effect on the progression of the dr .
however , recent information suggests this to be controversial because insulin can stimulate vegf and hypoxia - inducible factor-1 ( hif-1 ) expression in retinal pigment epithelial cells .
vegf is considered as a main factor for the development of the pdr , but recently , a 634c / g polymorphisms in the vegf gene was shown to be associated with pdr .
the expression of vegf , vegfr1 and vegfr2 levels is much higher in patients with pdr and dm , than in diabetics with pdr and dm type 2 .
studies that have analyzed the expression of integrins and their localization within the endothelium ( in membranes from proliferative dr isolated during the vitreoretinal surgery ) may provide new possibilities for the future treatment of the proliferative dr .
the results suggest an essential role of integrins alfa and beta3 in the pathogenesis of pdr .
a number of studies have shown the beneficial effect of intravitreal anti - vegf therapy .
the results were achieved between 13  weeks in the patients with retinal neovascularization elsewhere and neovascularization of the disc .
assessment of the short - term safety and efficacy of inravitreally administrated bevacizumab ( an anti - vegf agent ) as an adjunctive treatment for pdr , especially in the severe cases with iris nv , has been estimated in a number of studies [ 1720 ] .
these studies confirmed regression of the nv , but the main disadvantage of the anti / vegf drug administration is the need of repeated injections in order to prevent recurrences of the nv .
glucocortcoids ( e.g. , triamcinolon acetonide ) that are among the drugs used for intravitreal application can influence diabetic macular edema ( dme ) .
the pathogenesis of pdr is multifactorial involving both angiogenic and inflammatory processes . when administrated together with anti - vegf drugs ( bevacizumab , ranibizumab ) can induce nv and dme regression .
the results achieved from the studies may make this procedure an important adjunctive treatment in the management of selected cases with severe pdr .
the long - term results of intravitreal bevacizumab ( avastin ) , alone , in patients with pdr do not reveal any safety concerns [ 22 , 23 ] .
for instance , laser photocoagulation , while superior to intravitreal triamcinolone ( ivt ) or anti - vegf drugs , reduces but does not eliminate the risk of continued visual loss and is destructive to the retina .
focal / grid laser is more effective than ivt with fewer side effects within the initial 2  years .
laser or ivt are both more likely to improve the va over three years compared to the expected untreated course .
clinical investigations include those which evaluated the efficacy of intravitreal injection of bevacizumab in preventing panretinal photocoagulation , macular thickening and visual dysfunction in eyes with severe pdr .
the results showed that the best corrected visual acuity increased after the combined antivegf - laser treatment while the central foveal thickness decreased .
intravitreal injection of bevacizumab can also be used in patients with pdr , that are undergoing pars plana plana vitrectomy ( ppv ) .
the intravitreal administration of bevacizumab ( before ppv for pdr ) facilitates surgery and may decrease the rate of postoperative vitreous hemorrhage and improve visual acuity [ 24 , 25 ] .
ranibizumab ( lucentis ) is an affinity - matured recombinant humanized immunoglobulin monoclonal antibody fragment with a molecular weight of 48 kd that binds to and inhibits the biologic activity of all isoforms of human vegf by preventing interaction with its receptors .
the fragment is one third the size of a full - length antibody and readily penetrates all layers of the retina after intravitreal injection , consequently decreasing cell proliferation and vascular permeability .
the latest studies have also shown the positive effect of the drug , applied intravitreal in cases of dme .
the funding was through national eye institute that sponsored cooperative agreement that was initiated in september 2002 .
at the moment there are eleven  on - going  protocols that should estimate the results of different therapeutic approaches in cases of dr .
the objective is to develop a collaborative network to facilitate multicenter clinical research on dr , dme and associated conditions ( fig .  2 ) .

2searching for the results of different treatment modalities in cases of diabetic macular edema , according to the drcr network protocols searching for the results of different treatment modalities in cases of diabetic macular edema , according to the drcr network protocols the goals of the drcr are :
  involvement of community based practices as well as academic or university - based centres. collaborate with industry to facilitate investigations and pursue opportunities otherwise not possible and to do so in a manner consistent with the networks dedication to academic integrity and optimal clinical performance .
 involvement of community based practices as well as academic or university - based centres .
 collaborate with industry to facilitate investigations and pursue opportunities otherwise not possible and to do so in a manner consistent with the networks dedication to academic integrity and optimal clinical performance .
this will include the effects of cataract surgery upon dme and the effects of intravitreal plasmin to cause a posterior vitreous detachment upon dme . with the advent of new sophisticated techniques and diagnostic tools , the latest classification of the dr seems to be insufficient .
triggered on the molecular level , the non - responders to the standard therapy should be provided a strategy of personalized patient treatment .
although individualized therapy planning seems to be expensive , we should consider the fact that the diabetic complications lead to economic and psycho - social problems .
the complicated treatment phase , including the sophisticated and expensive techniques of ppv , using different kind of drug substitutes do not always provide us satisfactory results .
the main problem at this point is not only the associated complications of the treatment , but the chronicity of the disease .
the long - term results of the surgery are not always stabile over time , and a lot of late complications can not be avoided .
thus there is a need for new diagnostic and therapeutic approaches to be instituted much earlier at a time when there is no evidence of retinal damage .
hypertension , insulin resistance , dyslipidemia and obesity , are commonly found in a combination with this stage of pdr .
new diagnostic images , that can discover early diabetic changes , can provide useful informations for the novel dr treatment .
pathology specific biomarkers , dna analysis in conditions of chronic diseases diagnostic and treatment , do not deliver us only information about the general concept of treatment , but also help us in the individual - treatment , individual drug response and benefits according to this strategy of individual healthcare .
there is a need of collaborative network , to facilitate multicenter clinical activities , and thereby development of advanced treatment algorithms for dr and dme .
the multidisciplinary approach to chronic diseases , such as dr can initiate research activities in different fields that could create the model of personal - based - patient - care .
this means , we should gain new strategies to the optimal concept that includes :
 recognize the population at risk of the diseasefollow - up before the initial changes become manifestedsearch for new approaches that can prevent the development of the diseaseearly treatmentoptimal follow - up recognize the population at risk of the disease follow - up before the initial changes become manifested search for new approaches that can prevent the development of the disease

Answer:
retinal vasculature changes in diabetic patients are most common cause of blindness among eye diseases .
 numerous studies have explored the role of the agiogenic factors in the progression of diabetic retinopathy ( dr ) .
 the balance between angiogenic and antiangiogenic factors has a determining role in the dr progression .
 current treatment modalities include laser photocoagulation , intravitreal drug application , and pars plana vitrectomy ( ppv ) .
 these maneuvers are employed with occurrence of advanced retinal changes .
 new diagnostic approaches can provide better information for the initial retinal changes thereby requiring a new dr classification and treatment guidelines .
 the results that are expected from diabetic retinopathy clinical research network ( drcr ) are at the level where prediction and prevention can not be made .
 innovative molecular - imaging technology , can pave the way for application of novel clinical approaches .
 identification of pathology - specific biomarkers and their application to diagnosis and treatment , support the individualized treatment algorithms .