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:
however studies have failed to establish a cause and effect relationship between barium retention in the appendix and subsequent development of the appendicitis .
it is still not advisable to perform appendectomy in such circumstances without the evidence of an acute episode .
we present one such patient who had features suggestive of right ureteric colic and presented with retained barium in the appendix .
a 28 years old male attended our outdoor with an 8 days old x - ray film showing tubular radio - opacity in the right iliac fossa region .
he had two episodes of severe pain right lower abdomen in past 2 months for which he underwent barium meal follow through .
although the report came out to be normal but again he had an episode of pain .
this time x - ray abdomen was not completely normal and the patient came to our opd for advice .
daysevents0barium meal follow through study4x - ray abdomen for repeat episode of pain abdomen12presented to our opd with x - ray filmroutine blood investigations , repeat x - ray abdomen ( fig .
2 ) done60x - ray abdomen - normal5 monthslost in follow up routine blood investigation were sent and found to be normal .
repeat x - ray abdomen confirmed that the findings were not an artifact ( fig .
1 ) . ultrasound abdomen was advised to rule out abnormalities in right urinary system or some obvious bowel pathology .
a contrast enhanced ct scan of the abdomen was then performed to rule out any bowel pathology especially in the appendix or near ileocaecal region .
it concluded that the bowel was normal but there was a tiny right renal calculi . an x - ray of abdomen performed 7 days later , showed persistence of the radiographic opacity ( fig .
we concluded that this is a case of retained barium in appendix with recurrent right ureteric colic because of passage of renal calculi .
symptoms got relieved on conservative therapy and subsequent usg showed no calculi in renal system .
the radio - opacity was not noticeable on x - ray abdomen , 2 months after barium study .
prophylactic appendectomy was not done in our case , and the patient did not developed signs of acute appendicitis till 5 months when he was lost in follow up .
daysevents0barium meal follow through study4x - ray abdomen for repeat episode of pain abdomen12presented to our opd with x - ray filmroutine blood investigations , repeat x - ray abdomen ( fig .
repeat x - ray abdomen confirmed that the findings were not an artifact ( fig .
ultrasound abdomen was advised to rule out abnormalities in right urinary system or some obvious bowel pathology .
a contrast enhanced ct scan of the abdomen was then performed to rule out any bowel pathology especially in the appendix or near ileocaecal region .
it concluded that the bowel was normal but there was a tiny right renal calculi .
an x - ray of abdomen performed 7 days later , showed persistence of the radiographic opacity ( fig .
based on above findings and investigation we concluded that this is a case of retained barium in appendix with recurrent right ureteric colic because of passage of renal calculi .
symptoms got relieved on conservative therapy and subsequent usg showed no calculi in renal system .
the radio - opacity was not noticeable on x - ray abdomen , 2 months after barium study .
prophylactic appendectomy was not done in our case , and the patient did not developed signs of acute appendicitis till 5 months when he was lost in follow up .
the appendix is visualized in 8090% of barium swallow or enema studies , and this is accepted as a reliable sign of a non - diseased appendix but post - examination only 10% of the patients retain barium in the appendix beyond 72  h. its prolonged retention in the appendix has been viewed as altered physiology or pathological .
although barium sulphate is inert and not harmful to the mucosa , cases have been reported where appendicitis developed long after barium studies and were tagged as barium induced appendicitis .
baroliths have been conclusively retrieved from appendectomy specimen , even after 3 months following barium study in patients with acute appendicitis . despite these case
reports studies have failed to prove the cause and effect relationship between barium study and acute appendicitis .
important in this regard is the work of maglinte et al . who studied thirty - one patients with retained barium in the appendix for longer than 72  h and followed them for over 1 year .
based on above we conclude that the decision to perform appendectomy should be based on the diagnosis of acute appendicitis and that the prolonged retention of barium in the appendix is not an indication for surgery . in our case since no signs or symptoms were suggestive of acute appendicitis , the active search for other causes were made .
finding of small renal calculi in right kidney suggested that the etiology could be ureteric colic .
if a person presents with retained barium in the appendix , no appendectomy should be performed in absence of findings suggestive of acute appendicitis .
if atypical presentation is found , then they should be appropriately further investigated . some unusual things like right ureteric colic ( as in our case ) ,
written informed consent was obtained from the patient for publication of this case report and accompanying images .
a copy of the written consent is available for review by the editor - in - chief of this journal on request .
dr mithilesh kumar sinha : data collections , data analysis and writing , dr rajan kumar sinha : writing .

Answer:
introductionretention of barium in the vermiform appendix for more than 72  h following barium meal study is uncommon
 . it may produce undue concern for increased risk for appendicitis and even prophylactic appendectomies have been performed for this.presentation of casewe encountered one such patient who presented with x - ray plate suggestive of tubular radio - opacity in the right iliac fossa region .
 the patient had episodes of severe pain in the right lower abdomen for which he underwent barium meal study .
 further evaluation and investigations established the diagnosis as , a case of recurrent right ureteric colic with retained barium in the appendix.discussionreview of the literature suggests that , in absence of acute appendicitis there is no role of appendectomy , even in a case of retained barium in the appendix.conclusionif atypical presentation is there , they should be appropriately further investigated .


Question:
You will be shown the title of a chemistry paper, together with sections excerpted from the body of the paper. The paper sections may include HTML tags like `<p>` and `</p>`; please ignore these. Your task is to write an abstract for the paper. Your response should include the abstract and no other text.

Title:
Rhodium-catalyzed asymmetric hydrogenation of β-cyanocinnamic esters with the assistance of a single hydrogen bond in a precise position

Paper sections:

Hydrogen bonding, an important noncovalent interaction, plays a crucial role in biosystem and enzyme catalysis. Inspired by enzyme catalysis, the strategy of hydrogen bonding has been elaborated and successfully applied in numerous cases of organocatalysis in the past two decades, which provides the synthetic community with many solutions for organic synthesis. 1 Among the successful catalysts, thiourea is a special motif for hydrogen bonding. As a double hydrogen donor, thiourea could activate carbonyl compounds by lowering their LUMO energy. 2 Their effective bonding with neutral functional groups, potent binding affinity, and high tunability make thiourea catalysts versatile for many types of organic reactions. 3 Herein, using ferrocene-thiourea chiral bisphosphine ligands (ZhaoPhos series) and a combination of transition metal catalysis and organocatalysis, we focus on whether two hydrogen bonds from the thiourea group are essential in the transformation of b-cyanocinnamic esters, which are very challenging substrates. When the asymmetric hydrogenation of b-cyanocinnamic esters was carried out, the catalyst (L1) with only one H-bond donor in a precise position performed better than ZhaoPhos (possesses two H-bond donors) in both reactivity and enantioselectivity. This novel discovery provides new insight for the design of catalysts in the areas of organocatalysis and metalorganocatalysis.

Chiral g-aminobutyric acids (GABA) are an essential class of compounds in neuroscience, 4 and many of them are drugs or have potential biological activities in the area of neurotransmitters and brain science, 5 such as Pregabalin, 6 Phenibut 7 and Baclofen 8 (Fig. 1). In addition, many chiral GABA derivatives are common motifs in numerous drugs, such as Rolipram, 9 Brivaracetam, 10 Vernakalant 11 and Enablex 12 (Fig. 1). Thus, the synthesis of chiral GABA and their derivatives has attracted a great deal of interest; however, very limited approaches have been developed. The methods for their synthesis include the following: enzymatic kinetic resolution, 13 biocatalytic asymmetric reduction, 14 asymmetric conjugate reduction with polymethylhydrosiloxane (PMHS) 15 and asymmetric Michael addition. 16 However, asymmetric hydrogenation of b-cyanocinnamic esters, the most straightforward access to synthesize chiral GABA derivatives, has never been reported.

Over the past decades, the transition metal catalyzed asymmetric hydrogenation of functionalized olens has emerged as a powerful and environmentally friendly approach to generate chiral compounds. 17 With the rapid development of catalytic systems, many types of olens bearing functional groups such as carbonyl, 18 sulfonyl, 19 cyano group 20 and nitryl, 21 were hydrogenated in high ee and activities. However, the asymmetric hydrogenation of b-cyanocinnamic esters has not been reported, which is due to two reasons: (1) the electronwithdrawing ester group and nitrile group, which can sharply reduce the electron density of the C]C bond, are disadvantageous for the C]C bond coordination to the metal center, which leads to the low reactivity of these substrates and (2) the linearity of the nitrile group, which is not suitable for assisting the coordination between the C]C bond and metal catalyst, makes it very difficult to achieve high enantioselectivities. 20a,b As a result, it is a very difficult task to achieve satisfactory results from the asymmetric hydrogenation of b-cyanocinnamic esters with the classical bidentate diphosphine/Rh system, as summarized in Table 1.

Methyl (Z)-3-cyano-3-phenylacrylate as a model substrate, a series of bidentate diphosphine ligands including P-chiral diphosphine ligands (entries 1-4), ligands having axial chirality (entries 5-7) and ferrocenyl chiral bisphosphorus ligands (entries 8-10) were tested, which gave low to even trace conversions and almost racemic products. This disclosed that the classical catalyst systems cannot complete this task. Recently, substrate orientation by hydrogen bonds as a strategy in asymmetric hydrogenation has been studied and some progress has been made. 22 Therefore, we tried to utilize the ester group whose carbonyl is a very good H-bond acceptor to improve the reactivity of the electron-decient substrate by employing ZhaoPhos-bearing H-bond donors. Although the preliminary result was moderate (entry 11, 28% conversion with 84% ee), it inspired us for further exploration.

In order to obtain the optimal reaction conditions, a serious of solvents were screened (summarized in the ESI †). When the reaction was carried out with 50 atm H 2 gas at 35 C in CF 3 CH 2 OH, full conversion was attained with 95% ee.

To obtain insight into this catalytic system, three other chiral ligands L1-L3 were employed and the results are summarized in Table 2. To our surprise, the N methylation of ZhaoPhos led to an increase in enantioselectivity (entry 2, 98% ee), which is quite different from the previous results we reported. 18f,23 In comparison, when both N-H groups were replaced, almost no conversion was detected (entry 3), which indicated the importance of hydrogen bonds in this reaction. In addition, the ligand L3 without the thiourea group showed very low activity and enantioselectivity (entry 4). These results show that the thiourea motif efficiently activates the carbonyl group through hydrogenbonding interaction and works as an excellent directing agent. Moreover, L1 is superior to ZhaoPhos, which indicates that one hydrogen bond in a precise position is better than two in this asymmetric transformation.

With an optimized set of conditions in hand, we explored the substrate scope and generality of this catalytic reaction. To conrm the universality of the phenomenon that L1 is superior to ZhaoPhos, almost each substrate was compared (Scheme 1). We thought that enhancement of the steric hindrance of the ester would inuence this transformation; however, the results indicate that the changes in the substrate have a slight impact on the reaction (2a-2c). Many functional groups, such as methyl   (2d), methoxy (2e), phenyl (2f), triuoromethyl (2g), and halides (2h, 2i and 2j), at the para position of the phenyl group are compatible with this transformation. Using L1, substrates with meta-or ortho-substitution on the phenyl group are also tolerated and 97% ee and 99% ee values were obtained (2k and 2l, respectively). Generally, polyuorinated compounds exist in drug molecules, 24 thus a series of polyuorinated substrates were examined. Substrates with 3,4-diuoro and 3,5-diuoro on the phenyl group were tested, and good yields with excellent enantioselectivities were achieved (2m and 2n, respectively). In comparison, when the 3,4,5-triuoro compound 1o was employed, the adduct 2o was produced with slightly compromised ee values, which may be due to the electron-poor property of 1o, as discussed above. Other disubstituted substrates could also be accommodated, as exemplied by 2p and 2q. Moreover, good yields and excellent enantioselectivities were obtained with substrates containing other aromatic fragments, including naphthalenes and thiophenes (2r and 2s, respectively). To our delight, when the aryl substituent was changed to an alkyl group, such as isobutyl, the product 2t, which can be readily converted to (S)-Pregabalin, was produced with 98% ee. All the results reect the fact that L1 bearing a single H-bond donor is more suitable than ZhaoPhos for this reaction. Moreover, when (E)-1a was employed, much lower reactivity and enantioselectivity were obtained, but the conguration of 2u supports our assumption that the enantioselectivity is inducted by the ester group of the substrates.

To gain a better understanding of the performance of ZhaoPhos and L1, the free energies (kcal mol À1 ) of the hydrogen bonds between different ligands with 2a (DG HB ) were evaluated using the B3LYP-GD3BJ/6-31G** method, 25 as summarized in Table 3. To our surprise, the free energy of the hydrogen bond between 1a and ZhaoPhos is smaller than that between 1a and L1, even at different temperature, which can explain the experimental results very well. These results indicate that one H-bond can perform better than two H-bonds in this reaction, thus we proposed that the stronger hydrogen bond is important in making L1 a more selective catalyst. Both the L1 and Zhao-Phos systems are sensitive to the reaction temperature due to their weaker hydrogen-bonding interaction with substrates at higher temperature.

To verify the accuracy of the catalytic model, the reduction of 1a was performed using L1 of varying ee. As shown in Fig. 2a, a linear correlation between the ee of the ligand and that of the product was observed, which indicates that a 1 : 1 ratio of  ligand to metal is present in the catalytic complex. 26 Moreover, a Job plot was drawn and the curve suggests a 1 : 1 binding pattern between L1 and 1a (Fig. 2b), and a 1 : 1 binding pattern between ZhaoPhos and 1a was also suggested (summarized in the ESI †). These experimental data validate our hypothesis, and the catalytic model was illustrated, as shown in Fig. 2c.

In order to further demonstrate the synthetic utility of this methodology, several gram-scale transformations were achieved, as summarized in Scheme 2. First, upon decreasing the catalyst loading to 0.05 mol%, the asymmetric reaction was conducted on a gram scale, and 97% conversion (TON ¼ 1940) with unchanged enantioselectivity was obtained (Scheme 2a). Then, a high-efficiency synthetic route for (S)-Pregabalin, 13b (R)-Phenibut and (R)-Baclofen 14a was developed. As shown in Scheme 2b, with a 0.1-0.125 mol% catalyst loading, three key intermediates were obtained on a gram scale with high yields (97-98% yield) and excellent ee values (97-98% ee). Thus far, this may be the most concise way to synthesize chiral Pregabalin, Phenibut and Baclofen. Next, gram-scale 2p, which can be readily converted to a chiral d-amino alcohol whose enantiomer can be used in the synthesis of NK1 antagonists directly, 27 was produced (Scheme 2c). Scheme 2d exhibits an efficient approach for the establishment of chiral pyrrolidines. The asymmetric hydrogenation product 2a was reduced by NiCl 2 /NaBH 4 in MeOH and afforded the corresponding lactam 3 in high yield without any loss in enantioselectivity. By treating the lactam with lithium aluminium hydride (LAH) in THF, the chiral pyrrolidine can be readily obtained. 28

Conclusions

In conclusion, the rst asymmetric hydrogenation of b-cyanocinnamic esters has been reported, which provides an efficient approach for the synthesis of chiral GABA derivatives. This transformation exhibits excellent enantioselectivities (up to 99% ee) under mild reaction conditions with low catalyst loadings. Furthermore, this method provides a concise route for the synthesis of (S)-Pregabalin, (R)-Phenibut, (R)-Baclofen, chiral d-amino alcohols, chiral g-lactam and chiral pyrrolidines, which demonstrates the high synthetic utility of the current methodology. Notably, in our ferrocene-thiourea chiral bisphosphine ligand (ZhaoPhos series) system, the catalyst with a single H-bond donor in a precise position performed better than that with double H-bond donors, which is a novel discovery in the metalorganocatalysis area. This novel discovery provides a new way to design catalysts. Further investigations on the detailed mechanisms of the proposed key hydrogen bonds and the applications of the asymmetric hydrogenation strategy in organic synthesis are in progress in our lab.

Conflicts of interest

There are no conicts to declare.

Answer: With the assistance of hydrogen bonds, the first asymmetric hydrogenation of b-cyanocinnamic esters is developed, affording chiral b-cyano esters with excellent enantioselectivities (up to 99% ee). This novel methodology provides an efficient and concise synthetic route to chiral GABA-derivatives such as (S)-Pregabalin, (R)-Phenibut, (R)-Baclofen. Interestingly, in this system, the catalyst with a single H-bond donor performs better than that with double H-bond donors, which is a novel discovery in the metalorganocatalysis area.


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

Paper text:
neonatal diabetes mellitus ( ndm ) presenting within the first 6 months of life includes permanent neonatal diabetes mellitus ( pndm ) , which require lifelong therapy , and transient neonatal diabetes mellitus ( tndm ) where the condition shows remission during infancy but relapses in adolescence .
almost all cases of neonatal diabetes have monogenic etiology in contrast to the autoimmune diabetes presenting in children beyond 6 months of age .
pndm is associated with defects in pancreatic beta cell development and function . activating mutations in the kcnj11 gene , encoding the subunit kir6.2 , and abcc8 gene ,
encoding the sulfonylurea receptor 1 ( sur1 ) of atp - sensitive potassium ( katp ) channel , which has a key role in insulin secretion in glucose metabolism , are the most common causes and account for approximately 40% of all cases of pndm12 ) .
mutations in the glucokinase ( gck ) and insulin ( ins ) genes have also been reported in patients with pndm .
sulfonylureas close the katp channel by an atp - independent route , leading to increase insulin secretion4 ) .
therefore , in many patients with pndm with kir6.2 and sur1 mutations , insulin therapy can be replaced by oral sulfonylureas which offer more improvement in glycemic control and better quality of life35 ) .
we report a case of pndm caused by a novel p.h186d heterozygous mutation in the kcnj11 gene whose treatment was successfully transitioned from insulin to oral sulfonylurea .
her parents were unrelated , and her family was healthy and had no history of diabetes .
laboratory results at diagnosis were : blood glucose , 1,041 mg / dl ; ph , 7.025 ; hco3 , 5.1
mmol / l ; pco2 , 19.8 mmhg ; sodium , 147 mmol / l ; potassium , 5.6 mmol / l ; chloride , 113 mmol / l ; blood urea nitrogen , 31 mg / dl ; creatinine , 1.2 mg / dl ; urine ketone , + + + ; glycosylated hemoglobin ( hba1c ) , 7.7% ; and c - peptide , 0.2 ng / ml . after recovery from diabetic ketoacidosis , she had injections of neutral protamine hagedorn ( nph ) insulin two times a day and regular insulin ( ri ) four times a day .
her maximal daily insulin dose was at 1.5 u / kg . her insulin requirement was gradually decreased to 0.44 u / kg / day by 4 months of age .
although there were several hypoglycemic events , insulin injection for glucose control after the infancy period could not be stopped .
genetic study for neonatal diabetes using genomic dna extracted from peripheral lymphocyte was done at 4.5 years of age , and a novel heterozygous mutation of the kcnj11 gene located on chromosome 11p15.1 and encoding kir6.2 , c.556c > g ( p.his186asp ) , was found ( fig .
transition of treatment from insulin to sulfonylurea was attempted at the age of 4.8 . before the trial ,
laboratory findings were as follows : hba1c , 6.9% ; fasting glucose , 205 mg / dl ; c - peptide , 0.84 ng / ml ; 24-hour urine c - peptide , 2.2 g ; negative for islet cell antibody ; anti - insulin antibody ; and anti - gad antibody .
she was 103.2 cm in height ( 25th-50th percentile ) , 17 kg in weight ( 50th-75th percentile ) and did not have any specific neurological deficit .
oral sulfonylurea ( glibenclamide ) was initiated at a dose of 0.1 mg / kg / day divided into two equal doses .
the glibenclamide dose was gradually increased to 0.4 mg / kg / day over 1 week and the insulin was stopped .
oral glucose tolerance test ( glucose , 1.75 g / kg ) was done at 6 months and 1 year after completion of the sulfonylurea transition .
insulinogenic index [ insulin ( 30 min-0 min)/glucose ( 30 min-0 min ) ] , a marker of beta cell function , became increased from 0.10 to 0.18 , and acute c - peptide response [ c - peptide ( 30 min-0 min)1,000/glucose ( 30 min-0 min ) ] became increased from 6.48 to 8.29 ( table 1 ) .
the patient is now 7.5 years of age with a height of 121.4 cm ( 50th percentile ) and weight of 23.4 kg ( 50th percentile ) .
blood glucose was well controlled without episodes of hypoglycemia and the hba1c has been lower than during insulin injection ( fig .
ndm is a monogenic form of diabetes that presents within the first 6 months of life .
heterozygous activating mutations in the kcnj11 and abcc8 gene encoding the subunits kir6.2 and sur1 of katp channel in pancreatic beta cells are the most common and account for nearly half of all cases of pndm12 ) .
mutations in the glucokinase ( gck ) , insulin ( ins ) genes have also been reported in patients with pndm .
the causes of rare syndromic pndm includes recessive mutations in several genes , such as pdx1 , eif2ak3 , gck , ptf1a , foxp3 , neurog3 , neurod1 , rfx6 , ier3ip1 , hnf1b , glis3 , pax6 , slc19a2 , slc2a2 , and wfs167 ) . in tndm
, imprinted locus at chromosome 6q24 seen in more than half of cases8 ) , and kcnj11 and abcc8 gene mutations are also found in some cases .
glucose increases intracellular atp level and it induces the closure of katp channels that lead to insulin secretion by pancreatic beta cells . activating mutations in the kcnj11 or abcc8 gene of katp channel lead to katp channels remaining open despite the presence of glucose , thus , insulin secretion can not be increased1 ) . on the contrary , loss of function mutations cause congenital hyperinsulinemia due to the closure of the katp channel and lead to increased insulin secretion
. sulfonylureas ( su ) can close the katp channel and increase insulin secretion4 ) .
treatment response is not expected in patients with mutations in other genes , such as glucokinase gene , foxp3 , and ipf1 .
therefore , molecular diagnosis in neonatal diabetes may help identify patients that are likely to respond to oral sulfonylureas .
pearson et al.3 ) reported the responses to sulfonylurea according to mutation types in diabetic patients caused by kcnj11 mutation .
there were no differences in blood insulin , c - peptide level , and insulin injection dose between the successful group and unsuccessful group .
v59 m , r201c , f35v , h46y , r50q , g53r , r201l , e322k , y330s , f333i mutations also belong to the successful group .
switching to su was unsuccessful in patients with q52r , i296l , and l164p mutations .
in addition , failure of switching to su was more related with the presence of neurologic features ( 14% in successful group and 80% in unsuccessful group ) and older age at initiation of su .
median age was 6 years old ( intraquartile range , 3 - 12 years ) in the successful group and 18 years old ( intraquartile range , 6 - 35 years ) in the unsuccessful group3 ) .
the report about a mother and daughter carrying the same kcnj11 mutation showed that the daughter could be switched from insulin to su at age 8.5 years , but her mother had an imcomplete response9 ) .
the trial of su switching in a poorly controlled diabetic 19 years old patient with r201h mutation , a mutation type expected to respond successfully , failed10 ) .
these observations suggest that factors that can affect the success of switching to su include ; mutation type , severity of mutation , and duration of the diabetes .
a long - standing diabetes may lead to islet beta cell exhaustion resulting in nonresponse to su9 ) .
ndm caused by kcnj11 gene mutations is inherited in autosomal dominant pattern , but most of these cases result from new mutations without family history . the patient in this case has a novel mutation ( p.h186d ) in the kcnj11 gene and presented with a mild form of pndm .
switching to su with an initial dose 0.4 mg / kg / day was successful at 4.8 years of age .
oral glucose tolerance test in index patient showed improvement in insulin secretion during the treatment at 6 months and 12 months after the use of su .
although she had hypoglycemia every 2 or 3 weeks and experienced a few episodes of hypoglycemia with mental change during insulin treatment , there was no more hypoglycemia after changing to su treatment . oral sulfonylurea therapy is both safe and better than insulin for metabolic control .
reported side effects of oral su are transitory diarrhea and tooth discoloration in a few patients311 ) .
mean hba1c was 8.1% in patients with insulin injection and 6.4% in patients with su therapy312 ) .
chronic su treatment seems to develop no beta cell desensitisation in pndm patients with kcnj11 mutation13 ) .
early su therapy at disease onset can permit insulin hypersensitivity and maintained basal insulin secretion , then provide long - term remission in animal subset14 ) . allowing for the potential beneficial effect on neurodevelopmental outcome and glycemic control , empiric tiral of su before genetic testing in neonatal diabetes patients can be considered15 ) . in conclusion , as the mutation type , severity of mutation , and duration of the diabetes are the major factors affecting the success of switching to su , early genetic analysis and trial of sulfonylurea is important in the management of neonatal diabetes .
further studies looking at the result of su treatment and long term follow in pndm patients are needed .

Answer:
permanent neonatal diabetes mellitus refers to diabetes that occurs before the age of 6 months and persists through life .
 it is a rare disorder affecting one in 0.2 - 0.5 million live births .
 mutations in the gene kcnj11 , encoding the subunit kir6.2 , and abcc8 , encoding sur1 of the atp - sensitive potassium ( katp ) channel , are the most common causes of permanent neonatal diabetes mellitus .
 sulfonylureas close the katp channel and increase insulin secretion . kcnj11 and abcc8 mutations have important therapeutic implications because sulfonylurea therapy can be effective in treating patients with mutations in the potassium channel subunits .
 the mutation type , the presence of neurological features , and the duration of diabetes are known to be the major factors affecting the treatment outcome after switching to sulfonylurea therapy .
 more than 30 mutations in the kcnj11 gene have been identified . here ,
 we present our experience with a patient carrying a novel p.h186d heterozygous mutation in the kcnj11 gene who was successfully treated with oral sulfonylurea .


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

Paper text:
in vivo , the biologically active form of dna in prokaryotes is negatively supercoiled . the amount of superhelical stress imposed on the dna is determined by the levels of competing dna topoisomerase enzyme activities , and by local events such as protein binding or dna transcription ( 13 ) .
transient changes in the level of global dna supercoiling have been observed with several types of environmental stress , including heat shock , cold shock , ph changes , osmotic shifts , transitions from aerobiosis to anaerobiosis and starvation ( 1,2 ) . along with these changes in stress level ,
the expression patterns of the bacteria involved were observed to be dramatically altered ( 46 ) .
reactions occurring on the dna template , including transcription and replication , also affect the local level of supercoiling .
when rna polymerase threads through the dna template , it pushes a wave of positive supercoils ahead , and leaves a trail of negative supercoils behind ( 3,7 ) .
one way in which negative superhelicity can influence regulation is through the destabilizing effect it has on the double helix at susceptible locations within the sequence .
destabilization by even a few kilocalories , far less than would be required to open the duplex , can have a profound effect on the ability of a regulatory molecule to unpair the dna , as is required for the initiation of transcription or replication . in this manner
experiments have shown that stress - induced duplex destabilization plays essential roles in the transcriptional regulation of several genes ( 810 ) .
we have developed computational methods that evaluate the patterns of stress - induced dna duplex destabilization ( sidd ) in dna sequences ( 11,12 ) .
these analyses predict the locations where the dna duplex becomes susceptible to separation when under superhelical stress .
all conformational and thermodynamic parameters are given their experimentally measured values , so there are no free parameters in these analyses . despite this , their results are in quantitative agreement with experiments in all cases where experimental information is available . when the entire escherichia coli genome is analyzed in this way , the sites that are predicted to be easily stress - destabilized are found not to be distributed at random . instead , these sidd sites are highly enriched in those intergenic regions that are known or inferred to contain promoters , and occur infrequently in coding regions ( 13 ) .
both components of this pattern have very high statistical significances . the frequency of sidd sites in intergenic regions separating convergent open reading frames ( orfs ) , which are inferred not to contain promoters , are consistent with random .
a similar pattern of sidd sites avoiding coding regions and being enriched in intergenic regions was noted in yeast , although there the strongest sidd sites were in the terminal flanks of genes , not in their promoters ( 14 ) .
our most recent studies also indicate that those genes in e.coli whose promoters have strong sidd sites are clustered in certain functional groups such as transcription regulators , transport and membrane proteins .
it is interesting that many known supercoil - responsive genes and environmental stress - responsive genes have highly destabilized sites in their upstream 5 flanks .
sidd sites have been shown to be important functional elements in regulating transcriptional initiation , transcriptional termination and other biological activities . in e.coli ,
activation of both the ilvpg and leuv promoters are mediated by similar mechanisms involving a binding - induced translocation of superhelical tension from a sidd site to the promoter ( 8,9 ) .
this translocated superhelical tension facilitates the formation of the open initiation complex by unwinding the dna duplex in the promoter region . in humans ,
the initiation of transcription of the c - myc gene is regulated by the binding of fbp to a highly destabilized sidd site ( 15 ) .
sidd sites also have been implicated in transcriptional termination and chromosomal matrix attachment in yeast ( 16 ) . these and other results show that sidd is an essential component of regulatory mechanisms for a variety of biological activities .
it is important to understand that sidd properties are not simply reflections of the underlying thermal stability of the sequences involved . stresses couple together the destabilization behaviors of all base pairs that experience them
this leads to much more complex , interactive behaviors than that occur with thermal melting .
[ see figures 1 and 2 of ref ( 17 ) . ] here we describe the database we are compiling of the sidd profiles of microbial genomes .
accessible over the web at , it gives users an overview of the sidd sites in their selected genome , and their positions relative to the annotated genes .
this information will facilitate the identification of regulatory elements , such as promoter - containing regions , in the genomic sequence .
in addition , the original sidd profiles ( raw data and graphs ) can be visualized and made available for downloading .
the refseq sequences of the analyzed microbial genomes were downloaded from the nih microbial website . in all cases
the protein gene products are classified into functional categories according to the information in the clusters of orthologous groups ( cog ) database ( 18 ) .
our research group has developed three algorithmic strategies to evaluate the equilibrium distribution of states of destabilization of a short dna sequence in response to negative superhelicity ( 12,19,20 ) .
these methods can calculate the probability of opening of each base pair in the sequence .
one algorithm also calculates the incremental free energy g(x ) needed to guarantee opening of the base pair at position x. this can be done for each base pair in the sequence .
strongly destabilized sites require little or no extra free energy to open , so their values of g(x ) are near zero .
sites that remain virtually as stable as they would be in relaxed conditions ( which is the majority of the genome ) have g(x ) near 10 kcal / mol . partially destabilized sites
these methods have been extended recently to enable the analysis of long dna sequences , and successfully applied to the complete genome of e.coli ( 13,17 ) .
( for detailed information on the algorithms and the methods for analyzing their results , please refer to the cited publications . )
the sidd analysis of complete microbial genomes has been semi - automated on a 38 node apple cluster .
all sidd profiles were calculated at superhelical density  = lk / lk0 = 0.06 , a moderate physiological value .
the results from the calculations were manually reviewed for integrity , then their global characteristics were analyzed by a set of perl scripts and c++ programs .
the results were directly channeled to a postgres database for storage , visualization and further analysis .
as of the present ( september 8 , 2005 ) there are 134 analyzed microbial genomes in this database , 118 from bacteria and 16 from archaea .
we update the database whenever the sidd analysis of another fully sequenced genome is completed , so the number of analyzed genomes will rise in the future . for each analyzed genome
each sidd site in the graph is a set of contiguous base pairs for all of which g(x ) < 8 kcal / mol .
these sidd sites were binned into disjoint sets according to the minimum value gm that g(x ) attains within them .
the lowest bin is determined by gm  0 , and the other bins contain the sidd sites satisfying i1 <
gm  i for i = 1 ,  , 6 . a color map scheme is used to represent these binned sidd sites .
the sidd sites in all the fully analyzed bacterial genomes have a similar pattern of distribution to that reported previously for the e.coli genome ( 13 ) .
strong destabilization preferentially occurs in the intergenic regions separating divergently ( div ) or tandemly ( tan ) transcribed orfs , while avoiding coding regions .
destabilization in intergenic regions separating convergently transcribing orfs ( con ) , which may be inferred not to contain promoters , is consistent with random .
this trend is clearly demonstrated in figure 2 , which summarizes data from the analysis of sidd locations in 42 bacterial genomes . for each genome in the siddbase database
we provide a table summarizing the number of sidd sites at each level of destabilization , and the number of these that occur in the three types of intergenic regions div , tan and con .
systematic analysis is underway to compare the sidd properties of different strains of the same species , between different phylogenetic groups of the same kingdom and between different kingdoms .
one also can display detailed sidd information for any specific region of interest , as shown in figure 3 .
these requests can be made by clicking on a region of the circular map , or by specifying the site either by identifying an annotated gene it contains or by its chromosomal location .
the figure displayed is a plot of the oriented genes in a 10 kb window centered on the requested position , together with the locations of the sidd sites in the region .
the genes are labeled , their orientations are shown by arrowheads , and they are color coded according to their cog classification .
x. ) the end of an arrowhead corresponds to the stop codon position of a gene .
the sidd sites are shown as colored bars , coded according to their gm values , and displayed below the line showing the annotated genes .
the graph of the sidd profile of a 5 kb long region centered on a sidd site can be viewed by clicking on the color bar corresponding to that site .
while the sidd calculation for an entire bacterial genome is time consuming , calculations for short dna sequences ( viz 5 kb ) can be executed efficiently . we have provided a website where users can calculate sidd profiles of short sequences of interest to them .
there one can set some of the calculation parameters , including the assumed superhelix density .
it should be noted that the results calculated from the web server may not necessarily be identical as the ones displayed on this database , even when the sequences and the parameters are the same .
the sidd profile of a dna segment in this database was calculated in its native global genomic context , while the results from the web server calculation were not .
the current database only contains sidd profiles of complete genomes from prokaryotes and archaea . in the future we also will deposit the results of sidd analyses for eukaryotic genomes .
initially this will be yeast , at least one complete chromosome from each fully sequenced eukaryote , and the encode regions of the human genome .
we intend eventually to include the sidd profiles of the complete genomes of all fully sequenced model organisms
. we will also provide sidd profiles of specific prokaryotic genomes at several superhelical densities .
we will add further functionalities to the database as these are developed , including sidd - based ( or sidd - assisted ) promoter predictions .
we will continue to analyze more microbial genomes as their sequences are completed , and we will periodically update our analyses in response to significant changes in ncbi refseq sequences .
the genes are plotted in the inner circle , color coded according to their cog classifications as shown in the gene color map .
the sidd sites are shown in the outer circle , color coded according to their minimum sidd energy as shown in the sidd color map .
the ratio of the observed number of sidd sites to the number expected if they were located at random . this ratio has been calculated for sidd sites that overlap intergenic regions whose flanking orfs are in any of three orientations ( div , divergent ; con , convergent ; and tan , tandem ) , and also for those that occur within coding regions .
these results were calculated from the sidd profiles of 42 bacterial genomes that were chosen to represent the phylogenetic diversity of sequenced genomes and the range of at / gc ratios .
the x - axis is the sidd level ; the y - axis is the ratio of predicted sidd sites found in the regions to the expected number of such sites if they were located at random .
this shows that the pattern reported previously in e.coli k12 occurs throughout the sequenced prokaryotes .
this view is obtained from the window of figure 1 by clicking on a gene , or by entering a gene name or chromosomal location into the appropriate field .
the genes are annotated , and the sidd sites are displayed as colored bars belowthe line .
clicking on a sidd color bar gives an annotated sidd profile centered on that region , as shown .

Answer:
prokaryotic genomic dna is generally negatively supercoiled in vivo .
 many regulatory processes , including the initiation of transcription , are known to depend on the superhelical state of the dna substrate .
 the stresses induced within dna by negative superhelicity can destabilize the dna duplex at specific sites .
 various experiments have either shown or suggested that stress - induced dna duplex destabilization ( sidd ) is involved in specific regulatory mechanisms governing a variety of biological processes .
 we have developed methods to evaluate the sidd properties of dna sequences , including complete chromosomes .
 this analysis predicts the locations where the duplex becomes destabilized under superhelical stress .
 previous studies have shown that the sidd - susceptible sites predicted in this way occur at rates much higher than expected at random in transcriptional regulatory regions , and much lower than expected in coding regions .
 analysis of the sidd profiles of 42 bacterial genomes chosen for their diversity confirms this pattern .
 predictions of sidd sites have been used to identify potential genomic regulatory regions , and suggest both possible regulatory mechanisms involving stress - induced destabilization and experimental tests of these mechanisms .
 here we describe the siddbase database which enables users to retrieve and visualize the results of sidd analyses of completely sequenced prokaryotic and archaeal genomes , together with their annotations .
 siddbase is available at .


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:
amblyopia is the leading cause of decreased vision among children , with refractive errors as the most important cause of this condition . because of the importance of early diagnosis and treatment of amblyopia ,
however , this method is limited because it requires an experienced examiner and an excessive amount of time . to overcome these limitations ,
several photorefractors were developed . among these was the plusoptix s09 photorefractor ( plusoptix gmbh , nuernberg , germany ) , developed for children and the disabled , and is a noninvasive tool for the rapid assessment of both eyes for refractive errors , pupil size , and inter - pupillary distance .
in total 77 eyes in 40 children aged 2 to 10 years were evaluated in uijeongbu st .
this study was conducted according to the guidelines of the association for research in vision and ophthalmology and the 1975 declaration of helsinki .
children were excluded when they had eccentric fixation , optical media opacity , or exceeded the plusoptix s09 manufacturer 's recommendations of a refractive error of a maximum spherical range of 7.00 to + 5.00 d and a pupil size range of 3 to 8  mm .
the patients were categorized according to 2 methods : ( i ) 11 eyes with hyperopia +3.0 d and 66 eyes with hyperopia < + 3.0 d , emmetropia , and myopia ; ( ii ) 12 eyes with cycloplegic and noncycloplegic refraction of spherical power +2.0 d and 65 eyes with cyclopegic and noncycloplegic refraction of spherical power
< + 2.0 d. all refractive errors ( spherical power , cylinder power , and spherical equivalent ) were determined in the following order : ( 1 ) photorefraction without cycloplegia using the plusoptix s09 ; ( 2 ) autorefraction without cycloplegia ( noncycloplegic ) using the cannon autorefractometer ( rk - f1 , canon , tokyo , japan ) ; ( 3 ) cycloplegic autorefractometer using 1% cyclopentolate ( 1% cyclogyl ) .
all cycloplegic autorefractomery was performed within 30  minutes of the use of 1% cyclopentolate 3 times per 5  minutes .
comparisons between the measurements were performed using paired t - tests and pearson 's correlation analysis .
all statistical analyses were performed using the spss statistical package 19 ( spss for windows , chicago , il ) . a value of p  <  0.05 was taken to indicate statistical significance .
there was no statistical difference between the 11 eyes with hyperopia of +3.0 d and the 66 eyes with hyperopia of < + 3.0 d , emmetropia and myopia for age and sex .
in addition , there was no statistical difference between the 12 eyes with cycloplegic and noncycloplegic refraction of spherical power +2.0 d and the 65 eyes with cyclopegic and noncycloplegic refraction of spherical power < + 2.0 d ( table 1 ) .
there was no difference between the plusoptix s09 and cycloplegic autorefractometer for both spherical power and equivalent in all of the children .
in contrast , there was a statistical difference between the plusoptix s09 and noncycloplegic autorefractometer ( p  <  0.001 ) ( table 2 ) .
pearson 's correlations between the plusoptix s09 and cycloplegic autorefractometer for spherical power , cylinder power , and spherical equivalent were 0.748 , 0.893 , and 0.782 , respectively , whereas between the plusoptix s09 and noncycloplegic autorefractometer these were 0.559 , 0.870 , and 0.580 , respectively .
these results indicate that the spherical power and spherical equivalent determined using the plusoptix s09 correlated more closely with those determined using the cycloplegic autorefractometer than using the noncycloplegic autorefractometer ( table 3 ) .
although there was no statistical difference between the plusoptix s09 and cycloplegic autorefractometer in the spherical power and spherical equivalent in all of the patients ( table 2 ) , the mean spherical power and equivalent recorded using the plusoptix s09 was 2.91    0.90 d and 2.22    0.93 d , respectively , whereas these recorded using the cycloplegic autorefractometer were 4.66    0.93 d and 4.25    0.80 d in hyperopia of +3.0 d , respectively .
there was a statistical difference between the plusoptix s09 and cycloplegic autorefractometer for the spherical power and spherical equivalent in hyperopia of +3.0 d ( paired t - test , p  <  0.05 ) .
in addition , in patients of cycloplegic and noncycloplegic refraction of spherical power +2.0 d , there was a statistical difference between the plusoptix s09 and cycloplegic autorefractometer for the spherical equivalent ( paired t - test , p  =  0.015 ) ( table 4 ) .
there was significant difference between the plusoptix s09 and cycloplegic autorefractometer according to the scatter plot for spherical power and equivalent in hyperopia of +3.0 d ( fig .
cpr  =  cycloplegic refraction , se  =  spherical equivalent , sp  =  spherical power .
amblyopia is the leading cause of decreased vision among children and affects 2% to 5% of the population .
early diagnosis and treatment may lead to better visual outcomes and decrease the severity and prevalence of amblyopia . because of the importance of early diagnosis , several screening methods for amblyopia are used .
however , this method is limited because it requires an experienced examiner , is time consuming , and in general needs sedation of children <3 years old with limited co - operation . in contrast
, the photo refractor is easy to use in examining younger children without the need for cycloplegic drops or sedation .
although an ideal screening test would have 100% specificity , 100% sensitivity , and 100% positive predictive value , there is no screening method with this level of accuracy .
many studies have shown the plusoptix to be a rapid , accurate , and noninvasive refractometer in preschool children and in individuals with intellectual or physical disabilities , and it has excellent specificity and sensitivity .
the mean spherical power and spherical equivalent recorded using the plusoptix s09 were 1.53    2.01 d and 1.33    1.97 d , respectively , whereas using the cycloplegic autorefractometer they were 0.61    2.02 d and 0.73    2.05 d , respectively , in all the children , which were not significantly different between the 2 devices ( paired t - test , p  >  0.05 ) .
we observed significant pearson 's correlation coefficients of 0.748 , 0.893 , and 0.782 between the plusoptix s09 and cycloplegic autorefractometer for spherical , cylindrical , and spherical equivalent refractive errors , respectively .
these values are similar to those of 0.76 , 0.86 , and 0.76 , respectively , reported by rajavi et al .
in contrast , the mean spherical power and spherical equivalent were significantly different using the plusoptix s09 ( 2.91    0.90 d and 2.22    0.93 d , respectively ) and the cycloplegic autorefractometer ( 4.66    0.93 d and 4.25    0.80 d , respectively ) in hyperopia of +3.0 d , ( paired t - test , p  <  0.05 ) . because accommodative capacity leads to a myopic shift in over - moderate hyperopia , a statistical difference between the plusoptix s09 and cycloplegic autorefractometer for the spherical power and equivalent was expected .
this shift was reported to be 3.0 d and 1.9 d in some children by erdurmus et al and dahlmann - noor et al , respectively .
schaeffel et al demonstrated a myopic shift of 2.4 d in children wearing + 3.0 d glasses with noncycloplegic photorefraction . in conclusion
, the plusoptix s09 can provide a rapid and easy method of refraction for amblyopia screening in young children and detecting risk factors for refractive amblyopia .
however , when it is used to estimate the refractive error in a child with hyperopia of +3.0 d , the refractive error should be corrected after a comparison of the refractive errors of the plusoptix s09 with those of a cycloplegic autorefractometer .

Answer:
abstractthe aim of the study is to compare outcome measures of refractive error obtained using the plusoptix s09 photorefractor and an autorefractometer of noncycloplegics and cycloplegics in children.we reviewed the medical records of 40 patients ( 77 eyes ) who were classified using 2 methods .
 the patients were first assigned to 2 groups consisting of 11 eyes with +3.0 d and 66 eyes with < + 3.0 d , and then to 2 groups of 12 and 65 eyes with cycloplegic and noncycloplegic refraction of spherical powers +2.0 d and < + 2.0 d , respectively .
 we compared the outcome measures of refractive error using the plusoptix s09 photorefractor and an autorefractometer of noncycloplegics and cycloplegics.there was no statistically significant difference between the plusoptix s09 photorefractor and cycloplegic autorefractometer in the spherical power and spherical equivalent .
 in contrast , there was a statistically significant difference between the plusoptix s09 photorefractor and noncycloplegic autorefractometer ( p  <  0.001 ) .
 there was a statistically significant difference between the spherical equivalent of the plusoptix s09 photorefractor and cycloplegic autorefractometer in children with hyperopia +3.0d and with cycloplegic and noncycloplegic refraction of spherical power +2.0 d. we also found a significant difference between the outcomes of the plusoptix s09 photorefractor and cycloplegic autorefractometer in the spherical power and spherical equivalent for children with hyperopia +3.0 d.the refractive error of the plusoptix s09 photorefractor was similar to that of the cycloplegic autorefractometer , in contrast to the noncycloplegic autorefractometer .
 however , the plusoptix s09 photorefractor is an inaccurate tool to estimate the refractive errors of children with moderate hyperopia .


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 52-year - old woman with granulocytic sarcoma affecting the anterior cranial fossa and frontal sinus was commenced on ade ( cytarabine , daunorubicin and etoposide ) and mylotarg ( gemtuzumab ) through a peripherally inserted central catheter ( picc ) line as part of the aml 17 trial ( http://aml17.cardiff.ac.uk/aml17/default.aspx ) .
she was known to have a beta - lactam allergy manifest as an erythematous rash . on day 9 of chemotherapy ,
her fever resolved after 48 hours and meropenem was stopped after 7 days . on day 18 of chemotherapy
she remained febrile over the next three days and caspofungin was started in view of high - resolution computed topography ( hrct ) chest findings compatible with possible fungal infection and a positive initial serum galactomannan assay ( although the repeat specimen was negative ) .
meropenem was therefore replaced with ciprofloxacin as it was thought to be responsible for the rash .
all cultures including multiple blood cultures and picc line site swabs were culture negative . on day 31 of chemotherapy she was still febrile and blood cultures from peripheral veins and the picc line taken on day 30 yielded gram - positive cocci in pairs and chains after 24 and 11 hours ' culture respectively .
the isolate was identified as leuconostoc lactis using the bd phoenix identification ( becton , dickinson and company , usa ) and api rapid i d 32 strep systems ( biomrieux , france ) .
mean inhibitory concentrations ( mics ) determined by e - test ( ab biodisk , sweden ) were : penicillin 0.5 mg / l , vancomycin > 256 mg / l , teicoplanin 256 mg / l , ciprofloxacin 1.0 mg / l , tigecycline 0.064 mg / l , linezolid 1.5 mg / l and daptomycin 0.064 mg / l . on day 32 of chemotherapy , ciprofloxacin and teicoplanin
the next day therapy was changed to tigecycline ( 50 mg iv q12h ) because of concerns over myelotoxicity ( anaemia and thrombocytopenia ) associated with linezolid .
daptomycin was unavailable in the hospital formulary and ampicillin was not used due to concerns over beta - lactam allergy and a borderline penicillin e - test mic .
the patient continued to have low - grade fevers over the next four days , despite a negative transthoracic echocardiogram . on the fourth day of treatment , however , her fever resolved and she was discharged from hospital after completing 8 days of tigecycline , to which she had no adverse effects .
leuconostoc spp . are catalase - negative , gram - positive , facultatively anaerobic coccobacilli .
they are environmental organisms often found on plants , dairy products , vegetables , wine and occasionally in human vaginal and stool samples . although an uncommon human pathogen , cases of bacteremia , endocarditis , pneumonia , meningitis , osteomyelitis , peritonitis , brain and liver abscesses have been described .
and other gram - positive antimicrobial - resistant organisms are increasingly recognised as important pathogens in neutropenic patients probably due , in addition to immunosuppression , to the use of indwelling intravascular devices , antibiotic prophylaxis and evolution of chemotherapeutic agents .
infection with leuconostoc may cause fever , intravenous catheter - related sepsis , bacteremia , abdominal pain , gastroenteritis , colitis or meningitis in this group of patients . other reported risk factors for infection
removal of intravenous catheters alone has been shown to be curative in some patients without the need for antimicrobial therapy .
are intrinsically resistant to glycopeptides , owing to the production of peptidoglycan precursors ending in d - ala - d - lac , but are usually susceptible to penicillin , ampicillin , aminoglycosides , clindamycin , minocycline and macrolides .
in addition , linezolid and daptomycin have been used successfully to treat leuconostoc bacteremia , although linezolid mics of leuconostoc spp .
although the organism has been shown to be resistant to cefoxitin , it is susceptible to cefotaxime in vitro .
tigecycline , a glycylcycline , is a broad spectrum synthetic derivative of minocycline which has a broad spectrum of activity against various gram - positive and gram - negative bacteria including multidrug - resistant strains , anaerobic bacteria and atypical organisms .
it has proven to be useful in the treatment of hospital - acquired infections caused by vancomycin - intermediate and vancomycin - resistant enterococci ( vre ) , meticillin - resistant staphylococcus aureus ( mrsa ) , extended - spectrum -lactamase ( esbl)-producing enterobacteriaceae , multidrug - resistant acinetobacter baumanii and penicillin - resistant streptococcus pneumoniae . in the uk ,
its licensed indications are complicated intra - abdominal and complicated skin and soft tissue infection .
it is also licensed for the treatment of community - acquired pneumonia in the us .
although tigecycline has been demonstrated to be a safe and effective second - line option in microbiologically documented infections in neutropenic patients , there have been no trials to determine whether tigecycline is effective in neutropenic bacteremia and there are also theoretical concerns surrounding low serum concentrations ( due to a large volume of distribution ) and its mostly bacteriostatic activity .
it is for this reason that tigecycline is not generally recommended for primary bacteremia but it is used for secondary bacteremia associated with complicated skin and soft tissue infections , intra - abdominal infections and community - acquired pneumonia . despite these concerns , here
we report the first successful use of tigecycline in the treatment of leuconostoc bacteremia in a neutropenic patient .

Answer:
leuconostoc lactis is a recognised cause of infection in immunocompromised hosts .
 it is intrinsically resistant to multiple antibiotics and treatment options may be limited .
 we report a case of safe and effective use of tigecycline in the treatment of leuconostoc catheter - related line sepsis in a neutropenic patient . to our knowledge
 , this is the first reported case of successful use of tigecycline for leuconostoc bacteremia .


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:
patients with diabetes are at increased risk of morbidity and mortality from cardiovascular disease ( cvd ) compared to normoglycemic controls.1 several additional factors may be associated with this increased risk , including persistent hyperglycemia , untreated hypertension , and dyslipidemia characterized by raised serum triglycerides ( tg ) and low concentrations of high - density lipoprotein cholesterol ( hdl - c).2 the reduction in cardiovascular events produced by statins in patients with diabetes is broadly consistent with that in normoglycemic , dyslipidemic controls . in the collaborative
atorvastatin diabetes study ( cards ) , a primary prevention study in type 2 diabetes mellitus ( t2 dm ) , atorvastatin reduced coronary heart disease events by 36% , stroke by 48% , and mortality by 27%.3 in a meta - analysis of secondary prevention studies in t2 dm , statins reduced cardiovascular events by 28% and strokes by 32%.4 despite this efficacy , a considerable residual cardiovascular risk remains among patients receiving statin therapy.2,5 hypertriglyceridemia ( > 1.7 mmol / l ) alters the composition of atherogenic particles and may make an important pathophysiological contribution to the residual cardiovascular risk.6 indeed , the current european atherosclerosis society consensus statement recommends treating hypertriglyceridemia of 1.7 mmol / l.6 statins , as well as lowering ldl - c , reduce blood triglyceride concentrations by up to 40%.7,8 only a few previous studies have evaluated hypertriglyceridemia in statin - treated patients with t2dm.9,10 however , there is little data evaluating these patients in primary care in the uk .
therefore , this audit assessed the prevalence of residual hyperlipidemia and the potential need for additional lipid - lowering therapy in individuals with t2 dm treated with statins in primary care in the uk .
this cross - sectional , observational study audited all patients with diabetes from the first 40 primary care practices that agreed to participate from an existing panel established by an independent clinical research organization ( quintiles commercial uk limited , bracknell , uk ) .
prescriptions issued were assessed during the preceding 4 months and repeat prescriptions were included . after excluding patients with forms of diabetes other than t2 dm , the patients were stratified according to the european society of cardiology ( esc )
feasible  treatment targets in patients with diabetes : total cholesterol ( tc ) of < 4 mmol / l , ldl - c of < 2.0
mmol / l , hdl - c of > 1.0 mmol / l ( male ) or hdl - c > 1.2 mmol / l ( female ) , and fasting tg of < 1.7 mmol / l.11 due to the relatively small numbers of patients receiving combination therapy or monotherapy with lipid - lowering drugs other than statins , this analysis focused on target attainment among patients taking statin monotherapy .
descriptive statistics were performed using microsoft excel 2010 ( microsoft , redmond , wa ) .
due to limitations in the demographic data ( see  discussion  ) , inferential and comparative statistical analyses were not performed .
the audit captured data on 14,652 patients with diagnosed diabetes from 40 practices . on average ,
89.5% ( n = 13,108 ) had t2 dm ( median age : 66 years old , range : 17106 ; 44.7% female ) .
approximately one - fifth ( 22.2% ; 2916 ) of the total t2 dm cohort had not received a prescription for lipid - lowering therapy during the 4 months before the audit .
for example , only around one - fifth were within the target values for total cholesterol and ldl - c . of patients with t2 dm who received lipid - lowering therapy , 94.7% ( 9647 )
approximately half of the patients who received statin monotherapy attained the esc treatment targets for total cholesterol , ldl - c , hdl - c , or tg ( table 3 ) .
indeed , irrespective of the individual statin used , around half of patients receiving statin monotherapy attained the esc treatment targets ( table 2 ) .
table 4 summarizes the dose distribution of each statin in t2 dm patients taking monotherapy .
the audit captured data on 14,652 patients with diagnosed diabetes from 40 practices . on average ,
89.5% ( n = 13,108 ) had t2 dm ( median age : 66 years old , range : 17106 ; 44.7% female ) .
approximately one - fifth ( 22.2% ; 2916 ) of the total t2 dm cohort had not received a prescription for lipid - lowering therapy during the 4 months before the audit .
for example , only around one - fifth were within the target values for total cholesterol and ldl - c .
of patients with t2 dm who received lipid - lowering therapy , 94.7% ( 9647 ) received statin monotherapy , which was usually simvastatin or atorvastatin ( table 2 ) .
approximately half of the patients who received statin monotherapy attained the esc treatment targets for total cholesterol , ldl - c , hdl - c , or tg ( table 3 ) .
indeed , irrespective of the individual statin used , around half of patients receiving statin monotherapy attained the esc treatment targets ( table 2 ) .
table 4 summarizes the dose distribution of each statin in t2 dm patients taking monotherapy .
this large , cross - sectional , observational , systematic audit showed that , first , dyslipidemia is common among people with t2 dm in the uk and , secondly , that lipid concentrations generally and tg in particular remain elevated despite statin monotherapy .
indeed , just over a fifth of t2 dm patients were not receiving lipid - lowering therapy , despite up to approximately 80% of these subjects showing evidence of dyslipidemia ( table 1 ) .
persistent hypertriglyceridemia was common , occurring in half of those on statin monotherapy ( table 2 ) .
this audit is , as far as the authors are aware , the first large study performed solely from the perspective of primary care in the uk that assesses triglyceride concentrations in patients with t2 dm receiving statin monotherapy .
the results confirm the findings of the dyslipidemia international study ( dysis ) , which stratified patients according to the presence or absence of cvd . in patients with diagnosed cvd
, 37.5% did not reach the ldl - c target , 38.3% were not at the hdl - c target , and 49.1% did not achieve the triglyceride target . among patients without cvd ,
the proportions were 45.0% , 30.4% , and 44.8% respectively . only around a quarter ( 25.2% and 25.8% with and without cvd , respectively ) achieved all three targets.9 in another study , 20.9% of 182 patients with t2 dm taking statins showed hypertriglyceridemia ( 2.3
< 2.5 mmol / l ( 13.7% ) , ldl - c < 2.0 mmol / l ( 8.8% ) , and hdl - c  0.9 mmol / l ( 6.0%).10 in the present study , simvastatin 40 mg was the most frequently prescribed statin dose .
however , 35.2% of simvastatin users took 20 mg or less , 24.7% of atorvastatin users took 10 mg , 28.2% of pravastatin users took 20 mg , and 72.2% of rosuvastatin users took 10 mg or less ( table 4 ) .
for example , simvastatin was the most widely prescribed statin in the dysis , in which the most common regimen was 2040 mg / day simvastatin equivalent.9 in a swedish study , 76% of simvastatin users took 20 mg or less , 48% of atorvastatin users took 10 mg , 55% of pravastatin users took 20 mg , and 76% of rosuvastatin users took 10 mg or less.12 the cross - sectional nature of the present audit and lack of clinical detail about each patient precluded an examination of any dose  response relationship with statins or ascertaining of whether the low dose was clinically justified ( eg , due to concurrent conditions or adverse events ) .
nevertheless , the data and previous studies suggest that a considerable proportion of patients receives low doses of statin and , as a result , may be undertreated .
as such , there may be scope to intensify statin regimens in many t2 dm patients with dyslipidemia who are managed in primary care .
the major limitation of this study is the absence of any information regarding the possible contribution made by potential confounders ( such as coexisting obesity , dietary issues , secondary hypertriglyceridemia , impaired renal and hepatic function , and suboptimal glycemic control ) to the suboptimal management of triglyceride levels .
for example , more potent statins ( atorvastatin , rosuvastatin , and pitavastatin ) produce a  robust lowering  of tg , especially at high doses and in patients with hypertriglyceridemia.13 however , in this audit , a numerically smaller proportion of patients receiving more potent statins ( atorvastatin and rosuvastatin ) attained the treatment targets than those taking simvastatin .
similarly , the nature of the audit meant that we could not ascertain whether the subjects had relatively treatment - resistant dyslipidemia or were in the titration phase , or whether there were any differences between patients receiving statins and the group that did not receive any lipid - lowering medication .
moreover , we could not correlate hba1c levels or compliance with hypoglycemic medication with use of statins or triglyceride levels .
however , the present study is based on data from a large number of patients and , therefore , probably accurately represents the proportions of people with t2 dm who attain lipid targets currently in uk primary care . as such , the audit underscores the need to ascertain the reasons why patients failed to attain the treatment targets and to consider intensified intervention .
the esc guidelines specify treatment targets based on fasting triglyceride levels . however , the audit was unable to ascertain whether triglyceride levels were measured in the fed or fasting state .
however , postprandial lipids , partially hydrolyzed chylomicron , and very - ldl remnants apparently accelerate atherogenesis by exacerbating endothelial dysfunction , augmenting numbers of atherogenic small ldl particles , and promoting thrombosis and inflammation .
arguably , therefore , postprandial tg more accurately predict vascular risk than fasting levels.14 as a result , both fed and fasting hypertriglyceridemia are associated with increased cvd risk .
the high prevalence of hypertriglyceridemia identified in this audit suggests that tg are often undertreated .
numerous secondary causes  including hypothyroidism , renal impairment , hepatic inflammation , and poor glycemic control  may increase tg and should be diagnosed and managed.15 however , in this study , the number of patients who had secondary hypertriglyceridemia and the extent to which concurrent conditions influenced the likelihood of attaining the treatment targets could not be assessed . despite these caveats , the results of the present study have implications for management .
for example , clinicians should continue to emphasize that all patients should follow dietary advice and exercise regularly to improve glycemic control and lipid profiles , as well as implementing interventions to optimize compliance with lifestyle changes , and lipid - lowering and other medications .
the audit showed that relatively few patients with t2 dm received statins in combination with ezetimibe , fibrate , omega 3 polyunsaturated fatty acids , or nicotinic acid .
as many patients show dyslipidemic profiles that are associated with an increased risk of cvd despite statin treatment , clinicians need to consider intensifying statin regimens , offering additional lipid - modifying therapies generally , or regimens specifically aimed at lowering tg levels ( such as pharmaceutical grade , highly purified omega 3-acid ethyl esters ) , particularly to improve the management of diabetic dyslipidemia .
t2 dm patients managed in uk primary care commonly show persistent lipid abnormalities . in this study , over a fifth of t2 dm patients were found to be not receiving lipid - lowering therapy .
clinicians need to implement interventions to optimize compliance with lipid - lowering and other medications .
clinicians also need to consider intensifying statin regimens , prescribing additional lipid - modifying therapies , and specific treatments aimed at triglyceride lowering to improve dyslipidemia control in statin - treated patients with t2 dm .

Answer:
purposethis paper reports the results of an audit that assessed the prevalence of residual hypertriglyceridemia and the potential need for intensified management among patients with statin - treated type 2 diabetes mellitus ( t2 dm ) in primary care in the uk.patients and methodsa cross - sectional , observational , systematic audit of patients with diagnosed diabetes from 40 primary care practices was undertaken .
 the audit collected basic demographic information and data on prescriptions issued during the preceding 4 months .
 t2 dm patients were stratified according to the proportion that attained european society of cardiology treatment targets.resultsthe audit collected data from 14,652 patients with diagnosed diabetes : 89.5% ( n = 13,108 ) of the total cohort had t2 dm .
 of the people with t2 dm , 22.2% ( 2916 ) were not currently receiving lipid - lowering therapy .
 up to approximately 80% of these people showed evidence of dyslipidemia . among the group that received lipid - lowering therapy , 94.7% ( 9647 ) were on statin monotherapy , which was usually simvastatin ( 69.5% of patients receiving statin monotherapy ; 6707 ) .
 the currently available statins were prescribed , with the most common dose being 40 mg simvastatin ( 44.2% ; 4267 ) .
 irrespective of the statin used , around half of the patients receiving statin monotherapy did not attain the european society of cardiology treatment targets for triglycerides , low - density lipoprotein , high - density lipoprotein , and total cholesterol.conclusiont2dm patients managed in uk primary care commonly show persistent lipid abnormalities .
 clinicians need to optimize compliance with lipid - lowering and other medications .
 clinicians also need to consider intensifying statin regimens , prescribing additional lipid- modifying therapies , and specific treatments aimed at triglyceride lowering to improve dyslipidemia control in statin - treated patients with t2 dm .


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

Paper text:
a 36 year old , para 2 female with a history of chronic right adnexal pain was admitted for a laparoscopic right salpingo - oophorectomy .
the patient experienced worsening right ovarian pain which did not improve despite nonsteroidal anti - inflammatory medications .
an ultrasound revealed a 4 cm complex ovarian mass which did not change in size with serial ultrasounds .
previous surgeries included an abdominal hysterectomy for a fibroid uterus , laparoscopic left salpingooophorectomy and lysis of adhesions for pelvic pain , an appendectomy , two previous cesarean sections , a bilateral tubal ligation and an inguinal herniorrhapy as a teenager .
the patient underwent general endotracheal anesthesia and was prepped and draped in the usual manner after being placed in the dorsolithotomy position . after making a small incision in the umbilicus
, a veress needle with its 2 mm trocar was carefully inserted into the abdomen with the panniculus elevated .
the saline drop test revealed patency , and the veress needle was attached to the co2 for the pneumoperitoneum .
the co2 was immediately stopped , the veress needle removed and a 2 mm microlaparoscope ( minisite gold ; u.s .
surgical corp . , norwalk , ct ) inserted into the trocar , which revealed bowel lumen with stool .
a second 2 mm trocar was placed in the right lower quadrant , and the microlaparoscope revealed a perforation into the anti - mesenteric border of the ileum .
was inserted under direct visualization lateral to the right rectus muscle at the level of the umbilicus .
the 2 mm umbilical trocar was replaced with a new one of the same diameter . at the site of the small bowel entry ,
after irrigating the pelvic and abdominal cavities with 3 liters of normal saline with no further fecal spillage or bleeding , the decision was made to not suture the site of entry into the small bowel .
postoperatively , the patient had a nasogastric tube inserted , was placed on famotidine ( pepcid ) 20 mg every 12 hours and was given antibiotics consisting of ampicillin , gentamicin and clindamycin intravenously .
on the evening of surgery , the patient developed a fever of 101.2 degrees fahrenheit .
on postoperative day one , she had a single temperature spike of 100.9 after being afebrile .
on postoperative day three , she had a small bowel movement , was advanced to a regular diet and discharged home in the afternoon on oral cephalexin . at her
one week postoperative visit she remained afebrile , tolerating her diet and with no complaints .
one month after surgery she was symptom free and her chronic right adnexal pain was gone .
most of the current data on laparoscopic complications is based on case reports and small series .
open laparoscopy was developed to reduce the risk of blind entry into the peritoneal cavity .
however , injury to the bowel has been reported to occur at the same rate with this technique .
recent advances in microlaparoscopy have allowed us to perform both diagnostic and operative procedures through 2 mm trocars . in our patient ,
a microlaparoscope inserted through the entry site confirmed the complication . had we performed traditional laparoscopy using a 10 mm trocar , the site of bowel injury would have required suturing , possibly a laparotomy . in cases where the site of perforation is free of adhesions and in need of repair
, the bowel can be sutured externally by withdrawing the bowel through a 12 mm trocar .
our minimally invasive , conservative approach to this complication was possible because no further fecal material leaked through the site of perforation and the diameter of the injury was small .
we felt that suturing in this case was unnecessary because the margins were regular , hemostatic and self - sealing .
the stool that was forced through this site probably was a result of the increased intraluminal pressure in the bowel from the co2 insufflation .
after copious irrigation with normal saline and no further spillage , we felt that the patient 's morbidity would be greater with suturing of the bowel if it produced bleeding or further spillage .
except for an initial fever , the patient responded well to conservative management with bowel decompression , antibiotic therapy and close observation .
conditions requiring a laparotomy following a bowel perforation include any sign of peritonitis , persistent fever , ileus or prolonged vomiting .
we believe that some small bowel perforations from 2 mm instrumentation can be managed conservatively without suturing provided that the site of injury is not actively leaking stool nor bleeding .

Answer:
although laparoscopy is one of the most common surgical procedures done today , bowel perforations can and do occur during the initial insertion of the veress needle and/or trocar .
 recent advances in microlaparoscopy have reduced the morbidity of this complication when encountered .
 we report a case of small bowel perforation following insertion of a veress needle with its 2 mm trocar and our minimally invasive intra - operative and postoperative management of the patient .


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:
acute coronary syndrome ( acs ) is characterized by acute , regional reductions in coronary blood flow and myocardial ischemia .
acs describes a spectrum of clinical manifestations , including unstable angina ( ua ) , non - st - segment elevation myocardial infarction ( nstemi ) , and st - segment elevation myocardial infarction ( stemi ) [ 13 ] .
atherosclerosis is a chronic inflammatory disease of the arterial wall , characterized by endothelial dysfunction , intimal hyperplasia , and smooth muscle proliferation , as well as deposition of lipids and formation of microvessels within the vascular wall [ 1 , 46 ] .
endothelial dysfunction is accompanied by the expression of adhesion molecules ( such as the vascular cell adhesion molecule- ( vcam- ) 1 ) [ 7 , 8 ] and chemokines [ 4 , 9 ] .
the recruitment of inflammatory cells is triggered by the production of cytokines ( such as il-1 , il-6 , il-8 , tnf- , and ccl2 )   within the plaque microenvironment .
chemokines are released from endothelial cells , mast cells , platelets , macrophages , and lymphocytes .
the macrophage migration inhibitory factor ( mif ) is a molecule that consists of 115 amino acids ; it was described as the main cytokine involved in attracting immune cells such as macrophages and t and b cells [ 12 , 13 ] .
the secretion of mif by inflammatory cells can be induced by exposure to oxidized low - density lipoprotein or other cytokines , such as tnf- and interleukin - c [ 13 , 14 ] .
mif activates the expression of various proinflammatory cytokines and chemokines and recruits macrophages to the site of atherosclerosis .
mif participates in the pathogenesis of inflammatory and atherosclerosis processes [ 12 , 13 , 1517 ] .
the mif gene is located at 22q11.2   and contains several polymorphisms , including the rs5844572 .
this genetic marker is a catt short tandem repeat ( str ) at position 794 , with five to eight length variants ( alleles 5 to 8) .
there is an association between the length of the repeats and the expression of the genetic marker ; the higher alleles ( catt6 , catt7 , and catt8 ) show higher expression of the gene . since mif is an inflammatory mediator and
given the role of genetic factors that modify its expression , mif could contribute to atherosclerosis and susceptibility to acs .
the aim of this study was to investigate the association between the 794 ( catt)58 mif gene polymorphism and susceptibility to acs in a western mexican population .
the study group included 200 acs unrelated patients recruited from hospital de especialidades del centro mdico nacional de occidente del instituto mexicano del seguro social ( cmno - imss ) and classified according to the criteria of the american college of cardiology ( acc ) .
as a control group , 200 unrelated healthy subjects ( hs ) were recruited from the general population of western mexico .
we applied a standardized questionnaire to the hs group and applied routine laboratorial clinical assessments to detect any potential alterations , and those subjects with any clinical alterations were excluded of the study .
we considered mexican mestizo subjects , only those individuals who for three generations , including their own , had been born in western mexico .
the study conforms to the ethical principles contained in the declaration of helsinki , and ethical approval was obtained from centro universitario de ciencias de la salud , cucs , udeg ( c.i .
genotyping of the str 794 ( catt)58 polymorphism was achieved by conventional pcr and polyacrylamide gel electrophoresis using the primers reported by radskate et al . .
cycling conditions were as follows : an initial denaturation at 95c for 4  min followed by 30 cycles of 30s at 95c , 30s at 60c , and 30s at 72c and then a final extension of 2  min at 72c .
allele identification was done by using a 10-bp ( invitrogen ) and homemade allelic ladders containing pooled samples .
in addition , as genotyping control , automatized sequencing of one random sample of each homozygote genotype allowed confirmation of results ( abi prism 377 genetic analyzer , applied biosystems , foster city , ca , usa ) .
the hardy - weinberg equilibrium test and genotype and allele frequencies were calculated by the chi - square test or fisher 's exact test , when applicable .
odds ratios ( or ) and 95% confidence intervals ( 95% ci ) were calculated to test the probability that the genotype and allele frequencies were associated with acs . a p value < 0.05 was considered to be statistically significant .
study the sample size was calculated according to the minor allele frequency of the 794 ( catt)58   mif gene polymorphism reported in mexican mestizo population by llamas - covarrubias et al .
it means that in order to detect differences , we needed at least 82 individuals each group with 95% confidence interval and statistical power of 80% . in this respect 200 individuals were included exceeding by far the required sample size .
the median age of hs and acs groups was 61 and 63 years , respectively .
the most prevalent clinical diagnosis in the acs group was stemi ( 76% ) , while obesity was the most common risk factor ( 61% ) , followed by high blood pressure ( hbp : 60% ) .
also , in the acs group other clinical parameters such as troponin i ( tni ) , troponin t ( tnt ) , creatine phosphokinase ( cpk ) , and creatine kinase ( ck ) were evaluated in order to find a possible genetic association .
however , we did not find any statistical association with 794 ( catt)58   mif gene polymorphism .
no deviation from the hardy - weinberg equilibrium was detected in the 794 ( catt)58 mif polymorphism ( p = 0.16 ) .
the allele and genotype frequencies in both the acs and hs groups are shown in table 2 .
allele 6 was the most frequent in both groups ( acs : 54% and hs : 57% ) .
the most common genotypes in acs and hs subjects were 6/7 and 6/6 , respectively .
a significant association was found between the 6/7 genotype and susceptibility to acs ( 68% versus 47% in acs and hs , resp . ,
we also stratified the main risk factors for development of acs by genotype ( table 3 ) . despite no significant differences
, we observed that the 6/7 genotype was the most frequent in each subgroup and that the 5/5 genotype was the less common .
acute coronary syndrome is a multifactorial disease arising through a combination of both environmental and genetic risk factors .
several studies have reported a relationship between atherosclerosis and acs [ 8 , 22 ] .
activated endothelial cells express adhesion molecules and favor the recruitment of monocytes to the endothelium .
these in turn release proinflammatory cytokines including il-1 , il-6 , tnf- , and mif .
reported a correlation between the expression of mif and an increased intima - media thickness and also with lipid deposition in carotid artery plaques ; white et al . reported a proinflammatory role for mif in acute myocardial infarction ; mller et al .
this genetic marker has five to eight variants ( catt)58 . a higher repeat number is associated with an increase in the gene expression . in the present research , we reviewed the association of the 794 ( catt)58   mif polymorphism with acs in mexican mestizo individuals .
the genotype and allele frequencies were distributed in a similar way to a previous study with a mexican mestizo population by llamas - covarrubias et al . .
we also compared the frequencies with those of caucasian american and african american populations   and observed that the genotype frequencies in our population differed from them ; they found that the genotype 6/6 was the most frequent , while the 5/8 and 6/8 genotypes were less frequent in caucasian americans and african americans , respectively .
in addition , a statistical difference was found in genotypic and allelic distributions when compared with an african ethnic group where the 5/6 genotype and the 5 allele showed the highest frequency ; these differences could be attributed to the ancestry of the population .
the mexican mestizo population is a crossbreed of amerindian , european , and african populations , with an estimated contribution of 2125% , 6064% , and 15% , respectively ( rubi - castellanos , 2009 ) . in this study
, we found an association between the 6/7 genotype of the mif 794 ( catt)58 polymorphism and susceptibility to acs in a western mexican population .
there is also another single nucleotide polymorphism in the promoter of the mif gene at the position 173 that has been previously analyzed and related to the inflammatory response in coronary bypass surgery   and coronary alterations in children with kawasaki disease .
recent studies support the fact that mif is a pleiotropic cytokine mainly released from macrophages that has been shown to be increasingly expressed during atherogenesis , oxldl being a major inducer [ 14 , 23 , 24 ] .
acs is a pathology where inflammation favors the recruitment of monocytes to the atherosclerotic plaque ; otherwise , new studies have described the functional effect of mif 794 ( catt)58 , showing that the catt5 allele has the lowest transcriptional activity and the catt68 alleles increase the expression rate .
this evidence validates the association found between the 6/7 genotype of the mif 794 ( catt)58 polymorphism and susceptibility to acs .
recently , chen et al . showed that the transcriptional repressor hbp1 ( hmg box - containing protein 1 ) negatively regulates mif expression , but this is still under investigation .
we also stratified the risk factors in the acs group regarding the genotypes of the 794 ( catt)58   mif polymorphism .
as we mentioned , mif has an important function in inflammatory processes ( kleemann et al . ) , suggesting that mif controls the development of metabolic pathologies associated with acs risk factors such as obesity and type 2 diabetes mellitus .
nevertheless , we did not find any association between the genotypes of the 794 ( catt)58   mif polymorphism and the risk factors in the acs group .
however a trend is shown between the 6/7 genotype and obesity , type 2 diabetes mellitus , dyslipidemia , and high blood pressure .
we want to highlight that , as a limitation of the study , the sample size in each subgroup is not enough to find an association , but there is a marked tendency with the higher alleles , which are responsible for a higher expression .
it is worth noting that the 794 ( catt)58 promoter polymorphism of mif has not been studied in relation to susceptibility to acs .
the 6/7 genotype of the mif 794 ( catt)58 polymorphism is related with susceptibility to acs in a western mexican population .

Answer:
the macrophage migration inhibitory factor ( mif ) is related to the progression of atherosclerosis , which , in turn , is a key factor in the development of acute coronary syndrome ( acs ) .
 mif has a catt short tandem repeat ( str ) at position 794 that might be involved in its expression rate .
 the aim of this study was to investigate the association between the 794 ( catt)58  mif gene polymorphism and susceptibility to acs in a western mexican population .
 this research included 200 acs patients classified according to the criteria of the american college of cardiology ( acc ) and 200 healthy subjects ( hs ) .
 the 794 ( catt)58  mif gene polymorphism was analyzed using a conventional polymerase chain reaction ( pcr ) technique .
 the 6 allele was the most frequent in both groups ( acs : 54% and hs : 57% ) .
 the most common genotypes in acs patients and hs were 6/7 and 6/6 , respectively , and a significant association was found between the 6/7 genotype and susceptibility to acs ( 68% versus 47% in acs and hs , resp . ,
 p = 0.03 ) .
 we conclude that the 6/7 genotype of the mif 794 ( catt)58 polymorphism is associated with susceptibility to acs in a western mexican population .