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:
inflammatory bowel disease ( ibd ) is a common diagnostic and therapeutic problem , affecting patients at increasingly young ages .
a standard diagnostic method includes macroscopic assessment of the intestinal mucosa during colonoscopy and histopathological evaluation of the obtained biopsies . according to porto criteria ,
the diagnosis of ibd is based on the clinical presentation , intestinal endoscopic and histological features , laboratory tests , and radiological examination .
recently , reports on the usefulness of a noninvasive examination , that is , faecal calprotectin measurement in ibd diagnosis , have been published .
evaluation of faecal calprotectin ( fc ) seems to be a screening test selecting patients requiring further invasive diagnostics .
furthermore , there have been reports on using calprotectin assays in monitoring the treatment of crohn 's disease and ulcerative colitis in adults and children [ 14 ] . to our knowledge ,
there are no published data on the usefulness of faecal calprotectin assays in the diagnosis of other atypical forms of bowel inflammation , such as eosinophilic , lymphocytic , or nonspecific colitis .
the aim of the study is to assess the usefulness of faecal calprotectin measurement in children with various types of ibd and to evaluate fc concentration in children with crohn 's disease and ulcerative colitis in relation to disease activity .
91 patients were included in the analysis , including 49 boys ( 53.85% ) and 42 girls ( 46.15% ) , ranging from 6 to 18 years of age ( the mean age was 13.38 years ) .
the study group comprised 71 children with various types of ibd , who were subsequently divided into six subgroups : b124 ( 33.8% ) children with crohn 's disease ( cd ) , b216 ( 22.5% ) with ulcerative colitis ( uc ) , b37 ( 9.8% ) with eosinophilic colitis ( ec ) , b48 ( 11.26% ) with lymphocytic colitis ( lc ) , and b516 ( 22.5% ) with nonspecific colitis ( nc , colitis indeterminata
the control group ( k ) comprised 20 healthy , age- and sex - matched subjects .
patients with ibd underwent following procedures : anamnesis , physical examination , laboratory tests ( inflammatory state markers , biochemical parameters of liver , pancreas , and kidney function , sweat test , coprological tests , and immunoassays ) , diagnostic imaging ( abdominal ultrasound ) , and endoscopy with histopathological evaluation . in all patients ,
faecal calprotectin was measured by means of elisa method , using phical test ( calpro ) .
calprotectin concentrations ranging from 0 to 50  mg / kg were considered to be normal reference values .
the results were evaluated by using the following tests : komogorow - smirnow , t - student , u mann - whitney , fisher , and yates ; the analysis of correlation was based on the spearman 's rank correlation coefficient . a p value of < 0.05 was considered statistically significant .
all patients and their caregivers gave informed consent to participate in the study , which was approved by the bioethics committee of the medical university of silesia in katowice ( consent no .
a statistically significant increase in the mean concentrations of faecal calprotectin was observed in the group of children with cd and uc , as compared to the control group .
concentrations of fc were also higher in children with uc than in patients with cd .
faecal calprotectin concentrations were within the normal limits in patients with eosinophilic , lymphocytic , and nonspecific colitis , similarly to the healthy subjects ( table 1 , figure 1 ) in children with cd , faecal calprotectin concentrations positively correlated with the disease severity assessed according to the pcdai scale . in patients suffering from uc , faecal calprotectin
also positively correlated with the truelove - witts scale and the rachmilewitz endoscopic index ( figures 2 , 3 , and 4 ) . a significant increase in faecal calprotectin concentrations
was observed in children suffering from cd , with lesions located in both small and large intestine , and in patients presenting with inflammatory changes in 5 or more sections of the intestine ( figure 5 ) .
faecal calprotectin is a promising , noninvasive screening method for diagnosing patients suffering from gastrointestinal disorders , such as abdominal pain or diarrhea , which are also typical for ibd [ 57 ] .
so far , many authors have considered calprotectin as a useful marker in differential diagnosis of ibd and functional gastrointestinal disorders ( e.g. , irritable bowel syndrome ) [ 8 , 9 ] .
many authors evaluated faecal calprotectin concentrations in patients with suspected inflammatory process of the large intestine .
demonstrated in the group of paediatric patients that this assay is characterised by 95% sensitivity and 93% specificity , and high calprotectin concentrations show strong positive correlation with the presence of inflammatory lesions in the large intestine . according to these authors
so far , only limited studies , based on very small groups of patients , evaluated faecal calprotectin concentrations in patients with other types of bowel inflammations less common than cd and uc , such as lymphocytic , eosinophilic , and nonspecific colitis , which seem to be a considerable clinical problem in everyday pediatric practice . in studies conducted by bunn et al . , two children with nonspecific colitis and 3 children with allergic colitis were included in the analysis . in both cases ,
calprotectin concentrations were found to be within the normal ranges . in our study involving 31 children : 7 with eosinophilic colitis , 8 with lymphocytic colitis , and 16 with nonspecific colitis , respectively ,
these results support the hypothesis that in the aforementioned types of bowel inflammation , histopathological examination does not reveal infiltrations of neutrophil cells , whose cytosols contain calprotectin . therefore , its concentration in faeces is directly related to the number of neutrophils in the large intestine lumen [ 11 , 12 ] . in paediatric patients , the diagnosis of nonspecific colitis ( indeterminata colitis ) remains unchanged in approximately 36% . over time in some patients , the diagnosis may be changed into ulcerative colitis ( in approximately 3372.5% ) or crohn 's disease ( in approximately 1727.5% ) . in our group of 6 cd patients , previously diagnosed conditions included single cases of ulcerative colitis , lymphocytic colitis , and nonspecific colitis , whereas eosinophilic colitis was found in 3 subjects .
increased calprotectin concentrations may be useful when making a decision on extending diagnostic procedures in patients with less frequent types of bowel inflammation . in our study ,
the mean calprotectin concentration in the examined patients with ibd was higher than it was observed by bremner et al . ; however , patients in remission were also enrolled in the latter research . in the presented material , a significant correlation was demonstrated between calprotectin activity and the disease severity assessed by the modified pcdai scale for cd and the modified truelove - witts scale and the rachmilewitz endoscopic index for uc .
, demonstrating a strong positive correlation between calprotectin concentrations and the disease severity according to the modified truelove - witts scale only in uc . analyses performed in children assessed a correlation between fc concentrations and intensity of macroscopic and microscopic inflammatory lesions in the large intestine , observed in the course of ibd .
studies carried out by fagerberg et al . included 39 children with ibd , in whom calprotectin concentrations strongly correlated with intensity and extent of micro- and macroscopic abnormalities .
norwegian researchers also confirmed such a correlation and , moreover , suggested that intensity of inflammatory lesions rather than their extent influences faecal calprotectin concentration .
this suggestion can be supported by data obtained from our study , indicating that in patients with uc calprotectin concentration depends on disease activity and not on the extent of lesions , in contrast to patients suffering from cd . in the latter group , calprotectin concentrations correlated with the disease activity and
were significantly higher in children with inflammatory lesions present in both small and large intestine and located in 5 or more sections of the large intestine .
these results support conclusions from the studies on clinical expression of the disease , which demonstrated that in children and adolescents the disease is more severe and cd lesions are located in the small intestine [ 17 , 18 ] . so far
faecal calprotectin measurement seems a promising test to evaluate disease activity and a tool for monitoring ibd treatment . in everyday practice ,
a disadvantage of this method is its low specificity , which is connected with the fact that in patients with increased calprotectin concentration many organic diseases should be excluded .
it seems that measurement of faecal calprotectin concentration can be a useful , safe , and noninvasive test in children suspected for ibd , since it is found to be increased in children with cd and uc as compared to patients with other inflammatory diseases ( eosinophilic , lymphocytic , and nonspecific colitis ) and also in the reference to healthy subjects . when the faecal calprotectin concentration is increased in children with less common types of bowel inflammation , a further follow - up of such patients
faecal calprotectin concentration correlates positively with the disease severity in cd and uc patients ; thus , it may be useful when choosing or modifying the appropriate treatment regimen .

Answer:
introduction .
 the aim of the study was to assess the usefulness of the fc measurement in children with various types of ibd and relation to the disease activity .
 patients and methods .
 91 patients ( 49 boys : 53.85% and 42 girls : 46.15% , mean age : 13.38 years , range 618 years ) were included in the analysis .
 patients were divided into the groups : b124 children with cd , b216 patients with uc , and a group comprising 31 children with other types of colitis ; the control group ( k ) comprised 20 healthy children .
 fc was assayed by elisa method , using phical test ( calpro ) .
 results .
 the mean faecal calprotectin concentrations were higher in children with cd and uc as compared to healthy controls , patients with eosinophilic , lymphocytic , and nonspecific colitis .
 a positive correlation was observed between fc concentrations and the disease activity ( the pcdai scale , the truelove - witts scale , and the endoscopic rachmilewitz index ) .
 conclusion .
 it seems that the fc concentrations can be a useful , safe , and noninvasive test in children suspected for ibd , since fc concentration is higher in children with cd and uc than in patients with other inflammatory diseases .


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

Paper text:
the two main and comprehensive goals of health provision are promotion of quality of a healthy life and prolonging it , and deletion of health disturbing factors .
, it was believed that neonates and infants either could not feel pain or felt it less than adults due to incomplete development of their nervous system
. meanwhile , it has been found that the pain - conducting fibers are formed in the fetal period , and term neonates are sensitive to pain and experience it like infants and children . on an average
, the neonates admitted in the neonatal intensive care unit ( nicu ) experience 115 painful procedures during their 16-day stay in this ward , of which 79.2% are administered no dedicational and non - dedicational sedative methods . in about 2.1% of these procedures , the neonates receive sedative medications , in 18.2% of the procedures , they receive non - dedicational sedation , and in 20.8% of the cases , they receive both dedicational and non - dedicational interventions .
the procedure conducted most frequently among neonates in the nicu is heel stick ( 56% ) .
pain in neonates , if not treated , leads to immediate and long - term complications .
the immediate complications include intraventricular hemorrhages and high mortality in the nicu , long - term response to pain , and poor responses to stimulants .
long - term complications include learning problems , reduction of concentration , lack of adaption with new situations , and mood changes in neonates and children .
if not managed , pain and tension in neonates can disturb their sleep condition , growth and development , nutrition tolerance , and even vital signs such as respiration , heart rate ( hr ) , bp , and o2 saturation .
further education and better detection of pain signs are essential for the health care personnel due to the short- and long - term complications of the uncontrolled pain among neonates .
prevention of these destructive effects may also help in reduction of hospitalization period and costs .
neonates can be relieved of pain through non - dedicational methods such as intake of oral sucrose , non - nutritive sucking , breast feeding , mother  infant skin touch , and music during the procedures . among the effective methods of pain relief in neonates is playing a melody which can act as a tool for distracting the neonates and enhancing the secretion of endorphins . playing a melody on a piano and recorded lullaby voice results in rapid return of the hr and behavioral and facial reactions due to pain to the baseline values .
studies on the effect of music on neonatal physiological responses concluded that music is effective on hr increase and changes of respiratory rate .
reported a significant difference in neonates hr during removal of a needle as well as in the first 5 min after heel stick .
a study in the nicu showed no notable changes in neonates hr after playing music compared to before it .
taking into consideration the destructive and numerous effects of pain on neonates various physiological systems , as well as the existence of controversial results regarding the sedative effects of music therapy , and the importance of pain management and prevention of numerous and irreversible complications in neonates , the researcher investigated the effect of melody on the physiological responses of heel stick pain in neonates which is among the most frequent painful procedures done on them .
this is a quasi - experimental study conducted for 5 months in the nicu of alzahra hospital in isfahan , iran .
sampling was by consecutive convenient sampling , and the subjects comprised 50 neonates meeting the inclusion criteria , who were assigned to study and control groups through random allocation .
the neonates in the group of melody ( study ) and the neonates in the control group were selected on the first and second days of the study , respectively .
inclusion criteria were gestational age of  34 weeks , being hospitalized in the ward ( inpatient hospitalization ) , not receiving o2 before and during the study , intact hearing ability ( through startle test ) , proper neonatal consciousness , and administration of no other painful procedures before conducting the intervention .
exclusion criteria were parents not willing to continue participating in the study or a need for oxygen therapy in the neonates due to any reason during the intervention and no success in the first heel stick trial .
researcher conducted the intervention after obtaining consent form the neonates parents and explaining the study goals and method .
the tool adopted in this study was a questionnaire to record the personal characteristics and a form of physiological signs record including hr , respiratory rate / min , and atrial o2 saturation percentage in the neonates .
neonates hr and atrial o2 saturation were monitored by a saadat monitoring device connected to the neonates , which was calibrated monthly by medical equipments engineers of the hospital .
the melody adopted was the piece  golden dreams  played on piano with no lyrics . in the intervention group ,
the melody was played on an mp3 player laid at a distance of 1 m from neonates cot with a sound intensity of 65 db .
it was played 3 min before the heel stick was administered until 3 min after the end of the procedure by an experienced nurse ( voice intensity was measured by a db meter device ) .
then , the neonates heels were disinfected by alcohol disinfection cotton and the lancet was inserted from the lateral side of the heel , and the researcher measured and recorded the neonatal physiological responses ( pulse , atrial o2 saturation , and respiratory rate ) by saadat monitoring device 3 min before , during , and after the heel stick , respectively . in the control group ,
all variables ( physiological responses ) were evaluated and recorded in time points similar to the study group .
the obtained data from both groups were entered into a computer and analyzed by chi - square , repeated measure analysis of variance ( anova ) , and independent t - test using spss 15 .
informed consent was obtained from participants and the study has confirmation of ethics committee of isfahan university of medical sciences ( no 391316 ) .
informed consent was obtained from participants and the study has confirmation of ethics committee of isfahan university of medical sciences ( no 391316 ) .
results showed that most of the subjects were males ( 58% ) , and the chi - square test showed no significant difference between the two groups ( p > 0.05 ) .
independent t - test showed no significant difference in some demographic characteristics ( gestational age , birth weight , current weight , and neonates age ) of the subjects in the two groups ( p > 0.05 ) .
repeated measure anova showed a significant difference in hr in the melody and control groups at different time points ( p < 0.05 ) [ table 1 ] .
least significant difference ( lsd ) post hoc showed a significant difference in the means of hr during and before intervention , and during and after intervention in the melody group ( p < 0.05 ) .
it also showed a significant difference in the means of hr during intervention and before intervention ( p < 0.05 ) , but not at other time points ( p > 0.05 ) .
independent t - test showed no significant difference in the means of hr in the melody and control groups before intervention ( p = 0.69 ) , during intervention ( p = 0.87 ) , and after intervention ( p = 0.42 ) .
repeated measure anova also showed no significant difference in atrial o2 saturation at various time points in the melody group ( p > 0.05 ) , but the difference was significant in the control group ( p < 0.05 ) [ table 2 ] .
lsd post - hoc test showed that the difference before and after intervention had a significance level of 0.05 .
independent t - test showed no significant difference in the means of atrial o2 saturation between the melody and control groups before intervention ( p = 0.12 ) , during intervention ( p = 0.37 ) , and after intervention ( p = 0.63 ) .
repeated measure anova showed a significant difference in respiratory rate at various time points in the melody and control groups ( p < 0.05 ) [ table 3 ] .
lsd post - hoc test showed a significant difference in the means of respiratory rate before and during intervention , and during and after intervention in the melody group ( p < 0.05 ) .
it also showed a significant difference in the means of respiratory rate before and during intervention , and before and after intervention in the control group ( p < 0.05 ) .
independent t - test showed no significant difference in the means of respiratory rate in the melody and control groups before ( p = 0.96 ) , during ( p = 0.69 ) , and after ( p = 0.87 ) intervention ( p > 0.05 ) .
comparison of means of neonates heart rate in the two groups at various time points comparison of means of neonates o2 saturation in the two groups at various time points comparison of means of neonates respiration rate in the two groups at various time points
results showed that the means of hr and respiratory rate were higher during intervention compared to before and after intervention in the melody group . the increase in mean
pulse during administration of the procedure was higher in the control group compared to the melody group .
means of respiratory rate showed an increase both in the study and control groups , although the increase remained longer after ending the procedure in the control group compared to the study group .
keith et al . also reported that music positively affected hr and respiratory rate and could balances these values , which is in line with the findings of the present study .
our obtained results showed no significant difference in the means of atrial o2 saturation at various time points in the melody group , possibly due to the type of selected melody , music , or length of the played music .
for instance , standly applied a piece of music containing lullaby sang by a woman , and in the study of karimi et al .
several other studies , like the study of collabra on the effect of music on premature neonatal physiological responses , showed that music had no effect on the neonates atrial o2 saturation , respiratory rate , and hr .
karimi et al . also showed no effect of music on hr and atrial o2 saturation , which is consistent with the findings of the present study .
in addition , obtaining no significant difference in neonatal physiological responses before , during , and after intervention in the study and control groups ( p > 0.05 ) may be due to the type of selected melody or the low number of the subjects , as the difference may become significant with a higher sample size .
in general , the findings of the present study showed that playing a melody causes a balance in the neonatal physiological responses including respiratory rate and hr during heel stick .
therefore , a melody is recommended to be played for neonates during administration of painful procedures , to prevent the destructive effects of pain .
our obtained results showed that playing music is an efficient intervention to maintain balance in neonates respiratory rate and hr during administration of painful procedures .
these findings reveal the importance of the application of music in the caring of neonates .
music therapy decreases the negative effects of treatment procedures and playing musical melodies is a cost - effective and convenient independent nursing intervention which does not need a physician 's visit and extra staff , and is not so time consuming .

Answer:
background : during health care in the neonatal intensive care unit ( nicu ) , infants undergo extremely painful procedures , which may cause problems , if not controlled , such as changes in the pattern of respiratory rate , heart rate , and blood oxygen saturation .
 the present study aimed to find the effect of melody on the physiological responses of neonates heel stick pain.materials and methods : this quasi - experimental study was conducted in alzahra hospital ( isfahan , iran ) for 5 months .
 fifty infants were selected through convenient sampling method and were randomly assigned in equal numbers to two groups ( n = 25 ) . in the melody group ( intervention ) , a selected melody was played for the infants at a distance of 1 m from them , with a sound intensity of 65 db , from 3 minutes before , during , and after the heel stick procedure , respectively , and their physiological responses were observed with a monitoring system and recorded at the afore - mentioned time periods .
 physiological responses were also recorded in the control group ( no intervention ) 3 min before , during , and after the heel stick procedure , respectively.results:means of respiratory and pulse rates in the melody and control groups showed a significant difference at different time points .
 but the mean blood oxygen saturation in the melody group showed no significant difference at different time points , although the difference was significant in the control group.conclusions:the results showed that melody could maintain more balance in some physiological responses of infants , such as the respiratory rate and pulse rate during the guthrie test . therefore
 , melody is recommended to be used to prevent the destructive effects of pain in infants during painful procedures .


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

Paper text:
subcellular localization is a key feature for characterizing physiological functions of proteins : in eukaryotes compartmentalization finalizes the sets of possible interacting molecules and therefore the biological process(es ) in which a protein is involved .
to date it has been carried out only for a narrow subset of known proteins . presently only unicellular species have been extensively analyzed by means of high - throughput experiments , such as s.cerevisiae ( 1,2 ) .
different approaches , such as green fluorescent protein ( gfp)-tagging ( 2 ) and immunoluminescence ( 1 ) , agree only on 75% of the annotations and this is mainly due to experimental limitations and possible interference of the tagging procedures on the normal protein trafficking ( 3,4 ) .
although it is difficult to scale these techniques to more complex organisms , a partial map for mouse liver cells was recently produced ( 5 ) .
curated annotations of the subcellular localization , although probably not covering all the available experimental knowledge , are contained in the swissprot database .
the amount of proteins with an experimental annotation listed in swissprot is different for different species and reaches at the most half of the total amount of proteins in a genome ( see below ) .
the question remains , however , as to how one can obtain a reliable annotation of subcellular localization for the rest of the proteins .
although in principle a change in few residues could result in a change of the localization of a protein , in practice with very few exceptions natural proteins with a sequence identity > 30% share the same localization ( 68 ) . in the most successful cases ,
about two - thirds of a genome can be annotated both by experimental results and similarity search .
many predictors have been developed recently [ ( 4,711 ) , a list is available at ] .
a prerequisite for a predictive method is its capability of well performing when the query sequence shares very low sequence similarity to known proteins .
it is therefore important to implement and adopt predictors tested with a rigorous cross - validation procedure on sets of proteins < 30% identical with respect to the sequences used for the training .
another important feature to be considered in adopting a predictor is how the relative abundance of localization among different sub - compartments was treated during the training phase . indeed , with the available data it is difficult to estimate the real proportions between the proteins targeted into the different subcellular localizations ; most of the predictive methods tend in fact to overestimate localization types for which more examples are known ( 8) .
it is therefore necessary to adopt predictive methods that attempt to correct bias towards one or more localization classes .
they include ( i ) the results of large - scale experiments for the determination of subcellular localization in specific organisms [ ygfp ( 1 ) , for yeast ; and ormdb ( 5 ) , for mouse ] ; ( ii ) the annotations of proteins to be found in organelles [ plprot ( 12 ) , for proteins from plastids ; organelledb ( 13 ) , for proteins in different organelles ; and mitop2 ( 14 ) , for mitochondrial proteins ] .
a database collecting all the annotations listed in swissprot is also available [ dbsubloc ( 15 ) ] .
finally databases that implement predictors of subcellular localization based on different methods have been reported [ loctarget ( 16 ) and pa - gosub ( 17 ) ] .
loctarget ( 16 ) is specific for structural genomics targets and lists some 50  000 proteins from different organisms .
pa - gosub ( 17 ) contains the annotations of eukaryotic subcellular localization and protein function of different genomes and is based on homology search and bayesian artificial networks for prediction .
we recently developed bacello , a well - performing balanced method for the prediction of subcellular localization , outperforming previously existing methods for the same task ( 8) .
we adopt bacello to annotate whole genomes in association with methods specifically implemented for the prediction of the topology of integral membrane proteins . in this paper
we present eukaryotic subcellular localization database ( esldb ) , a database of protein subcellular localization which provides an annotation for the entire proteomes of eukaryotic organisms . for each sequence
our database contains the experimental localization , when available , the homology - based annotation , when feasible , and the predicted localization computed with the in - house developed machine learning based methods . by this the new database provides more features than other existing databases . to date , five proteomes were fully processed : homo sapiens , mus musculus , caenorhabditis elegans , saccharomyces cerevisiae and arabidopsis thaliana . in summary , esldb is , to our knowledge , the first database containing the available experimental and similarity - based annotations for eukaryotic proteomes listing for each protein sequence also the predicted subcellular localization .
five different genomes were downloaded as specified : h.sapiens ( ensembl ncbi36 ) , m.musculus ( ensembl ncbim36 ) , s.cerevisiae ( ensembl sgd1 ) , c.elegans ( ensembl cel150 ) and a.thaliana ( tair6 ) . for each protein
the corresponding swissprot entry in release 50 was found , when existing , searching for exactly matching sequences .
the amount of genomic sequences that is deposited in the swissprot database ranges from 13% for both a.thaliana and c.elegans to 79% for s.cerevisiae ( table 1 ) .
number of proteins with an experimental or a similarity - based annotation of the subcellular localization the sequences experimentally annotated are included among those annotated by similarity . for these proteins the experimental annotation was extracted by parsing the
the annotations directly or implicitly referring to one of the following 17 classes were taken into account : nucleus , cytoplasm , mitochondrion , plastid , golgi , endoplasmic reticulum , lysosome , endosome , vesicles , peroxisome , vacuole , cell wall , secretory pathway , extracellular , cytoskeleton , membrane and transmembrane ( table 1 in supplementary data lists the keywords that have been considered for assigning the localization ) .
only 22% of all the swissprot entries for the five considered species record the experimental subcellular localization .
the rate of experimental annotation ranges from 46% of the s.cerevisiae proteome to < 10% for a.thaliana and c.elegans ( table 1 ) .
the  experimental annotation column in table 2 lists the amount of proteins experimentally annotated in each one of the 17 types of considered localization .
it is worth mentioning that the same sequence can be annotated in swissprot with two ( or rarely more ) different localizations .
for example , this happens for proteins that shuttle between the nucleus and the cytoplasm . in these cases
it is evident that the amount of proteins in the different localizations spans two orders of magnitude .
number of sequences in the 17 different subcellular localizations as derived with experimental and similarity - based annotations the sequences experimentally annotated are included among those annotated by similarity .
the best way to annotate the remaining proteins is to search for experimentally annotated sequences sharing high identity ( 68 ) .
since the three eukaryotic kingdoms ( metazoa , viridiplantae and fungi ) differ in number and types of possible localizations , three kingdom - specific datasets of annotated proteins were extracted from swissprot .
these dataset contains 26  192 sequences for metazoa , 6370 sequences for viridiplantae and 4023 sequences for fungi .
all the sequences of the five considered genomes were searched for similar sequences in the appropriate dataset using blast ( 18 ) . when matches were found with an e - value < 10 ( roughly corresponding to an identity level > 30% ) the annotation of the best - scoring match was transferred to the query sequence . when multiple matches are found with the same best scoring e - value ,
similarity - based annotation column in table 2 contains the number of proteins annotated with the above described procedure in each localization ( including the sequences experimentally annotated ) .
also in this case , sequences that end up with a multiple annotation are counted several times .
it appears that a large portion of the sequences , ranging from 32% in h.sapiens up to 67% in a.thaliana , is not endowed with similar counterparts with an annotated localization . in this case
subcellular localization can be predicted with specifically suited methods . for generating our annotation system we developed a pipeline that comprises previously described methods ,
all based on machine learning tools and that are proved to outperform most of the available predictors for the same task when rigorous cross - validation procedures are adopted ( 8) . the pipeline is shown in figure 1 .
first of all , membrane proteins are discriminated with spep ( 19 ) and ensemble ( 20 ) : the former is a neural network based method for predicting the presence of signal peptide while the latter is a method based on neural networks and hidden markov models for the prediction of the topology of all - alpha transmembrane proteins .
when a signal peptide is predicted , it is cleaved from the sequence before predicting the presence and the location of the transmembrane helices .
if no transmembrane helix is found , the uncleaved sequence is analyzed using bacello ( 8) , a recently developed tool for predicting the subcellular location of eukaryotic proteins .
this is based on a decision tree of support vector machines and it discriminates four localizations in metazoa and fungi ( cytoplasm , nucleus , extracellular and mitochondrion ) and five localizations in viridiplantae ( the same as before plus chloroplast ) .
bacello , spep and ensemble are predictive methods described previously ( 8,17,18 ) . at the end of the pipeline up
to five localizations can be discriminated in metazoa and fungi and up to six in viridiplantae . although the possible types of localization are 17 ( see above ) , the actual reduction in the number of discriminated localization is due to the lack of an adequate number of non - redundant examples for training .
a novelty of bacello is that first takes into consideration that the actual proportion of proteins targeted towards each compartment remains unknown by adopting an equiprobability hypothesis and a balancing procedure ( 8) . the structure of the predictive system allows annotating the subcellular localization in a hierarchical way .
first , all membrane proteins are separated from soluble ones ; the latter are then divided into intracellular and secreted .
intracellular proteins are separated in nucleocytoplasmic and organellar ; the former are then separated in cytoplasmic and nuclear while the latter , in the case of viridiplantae , are further divided into mitochondrial and chloroplastic .
the topology of the decision tree and the balancing procedure were adopted for maximizing the prediction performances as evaluated on testing sets independent of the training sets .
the best scoring binary decisions are at the top of the tree , the worst - scoring at the bottom .
the predictions are stored in the database along with the hierarchy of the decisions in the pipeline .
all the proteins of a genome , also when experimental and/or homology - based annotation are possible , are annotated by means of the predictive method . in table 3
number of sequences in the six predicted subcellular localizations table 4 contains the evaluation of the coverage and the accuracy of the prediction for the proteins of h.sapiens , as compared with both the experimental and the similarity derived annotations .
we considered 6444 unique proteins experimentally annotated and 25 134 unique sequences for which a similarity - based annotation is available .
the coverage is computed as the fraction of correctly predicted sequences in each class over the number of proteins belonging to the class .
the accuracy is the fraction of correctly predicted proteins over the total number of proteins predicted in the class .
the agreement between the annotations and the prediction is good , especially when predictions are compared with the experimental annotations and the higher levels of the hierarchical prediction are considered .
performance of the prediction pipeline as compared with the experimental and the similarity - based annotations the indentation of the subcellular localization names reflects the hierarchy of the prediction ( see figure 1 ) .
coverage = ( no . of proteins of class i predicted as class i)/(total no .
all the data are available at the website ( ) and can be accessed by protein code , as derived from the original and above - mentioned versions of the genomic databases , or by protein description , as derived from the swissprot entries . alternatively the sequence of interest can be submitted and , by means of the md5 encoding , the match engine searches for identical sequences deposited in the database .
moreover , complex searches can be performed combining the different annotation methods and the different localizations .
the entries matching the query keys can either be displayed or downloaded in a tabular format that contains the experimental and the similarity - derived annotation and the localization prediction for each match .
pages containing more details about each one of the proteins ( figure 2 ) are linked to the protein codes and contain the sequence , the description and the link to the swissprot file when an experimental annotation exists .
when the sequence can be annotated by similarity , the swissprot entry corresponding to the most similar sequence is reported together with the e - value as computed by blast ( 18 ) . in both the tabular and the detailed pages
, the results of the prediction are given together with the complete path through the decision tree .
this information can be useful since , as we commented in the previous section , the accuracy of the prediction lowers as the number of discriminated classes increases .
this means that annotations in the macro - classes are endowed with a higher reliability .
all the data contained in the database can be freely downloaded in flat file format .
the database resides in a postgresql server and the web interface has been implemented using python , html 4.0 and css 2.0 languages .
more available eukaryotic proteomes are currently under process and will be added to the database .
moreover we plan to regularly update the database as new versions of swissprot or new releases of the considered proteomes will be available .

Answer:
eukaryotic subcellular localization database collects the annotations of subcellular localization of eukaryotic proteomes . so far
 five proteomes have been processed and stored : homo sapiens , mus musculus , caenorhabditis elegans , saccharomyces cerevisiae and arabidopsis thaliana . for each sequence ,
 the database lists localization obtained adopting three different approaches : ( i ) experimentally determined ( when available ) ; ( ii ) homology - based ( when possible ) ; and ( iii ) predicted .
 the latter is computed with a suite of machine learning based methods , developed in house .
 all the data are available at our website and can be searched by sequence , by protein code and/or by protein description .
 furthermore , a more complex search can be performed combining different search fields and keys .
 all the data contained in the database can be freely downloaded in flat file format .
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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:

 aloe vera gel is a colorless substance obtained from the parenchymatous cells in fresh leaves of aloe vera ( l ) burm .
native to north africa , aloe has been introduced and is being cultivated in the warmer areas of the world . aloe vera gel , rich in polysaccharides ( pectins , hemicelluloses , glucomannan , acemannan , and other mannose derivatives ) should not be confused with the drug  aloe   dried juice of aloe vera leaves , bitter yellow exudate containing anthracene glycosides , mainly of the aloe - emodin anthrone 10-c - glucoside type [ 1 , 2 ] .

consumed as a beverage it was not toxic in vivo for mice . on the contrary , aloe latex and its hydroxyanthrone derivatives ( aloin , aloe - emodin etc . )
have strong laxative properties and their longer use requires medical supervision . traditionally , aloe gel was widely used for the treatment of minor wounds , inflammatory skin disorders , and thermal and radiation burns . in vitro ,
aloe gel suppressed bacteria - induced pro - inflammatory [ tumor necrosis factor  ( tnf- ) and interleukin 1 ( il-1 ) ] cytokines and matrix metalloproteinase 9 ( mmp-9 ) production in human mononuclear leukocytes [ 4 , 5 ] .
 in vivo , polysaccharides derived from aloe vera gel , injected into mice , potently stimulated migration of macrophages to the peritoneal cavity . in human , oral aloe vera gel was used by patients with inflammatory bowel disease , osteoarthritis , and other inflammatory conditions .
oral and topical administration of aloe vera gel diminished inflammation and eased joint immobility and pain [ 811 ] . in ophthalmology
, aloe vera extracts may be used in eye drops to treat inflammations and other cornea ailments . besides its anti - inflammatory activity
, aloe vera gel has antimicrobial properties and in vivo exerts a protective effect on polymicrobial sepsis in mice [ 1317 ] .
anthraquinones , compounds present in the outer part of aloe leaves and in their succus or extract , have been shown to have direct anti - cancer activity in different kinds of human cancer cell lines . moreover , aloe - emodin , a hydroxyanthraquinone from aloe vera , can act as an anti - angiogenic agent .
some data suggest that the inner part of aloe vera leaves , aloe vera gel and their polysaccharide components also have tumor growth modulatory properties , probably connected with their immunomodulatory activity [ 20 , 21 ] . in our previous paper
we reported the inhibitory effect of aloe barbadensis fresh leaves aqueous extract ( herbal drug biostymina ) on tumor - induced cutaneous angiogenesis in mice .
the aim of the present study was to evaluate in balb / c mice the in vivo influence of commercial aloe vera gel product ( aloe vera drinking gel ) on the syngeneic l-1 sarcoma tumor growth and its vascularization : a ) early cutaneous neovascular response , tumor - induced angiogenesis ( tia test ) , and b ) tumor hemoglobin content measured 14 days after l-1 sarcoma cell grafting .

 drug . tru - alo 99% aloe vera drinking gel ( aloe barbadensis miller folium succus ) , aloin content < 40 ppm ; produced by hi tech aloe vera pty ltd , bundaberg , australia
the study was performed on 59 female inbred balb / c mice 6 - 8 weeks old , weighing about 20 g , delivered from the polish academy of sciences breeding colony .
for all performed experiments animals were handled according to the polish law on the protection of animals and nih ( national institutes of health ) standards .
mice were housed 4 - 5 per cage and maintained under conventional conditions ( room temperature 22.5 - 23.0c , relative humidity 50 - 70% , 12 h day / night cycle ) with free access to standard rodent diet and water .
ketamina 10% , biowet , pulawy , poland ) ; xylazine 10 mg / kg ( prep .
sedazin , biowet , pulawy , poland ) ; 3.6% chloral hydrate 0.1 ml per 10 g of body mass ( sigma aldrich , usa ) ; morbital ( biowet pulawy , poland ) .

evaluation of sarcoma l-1 growth and angiogenic activity was performed as previously described [ 23 , 24 ] .
l-1 sarcoma cells were delivered from warsaw oncology center collection , passaged twice in vivo and grafted subcutaneously ( for evaluation of tumor growth and its hemoglobin ( hb ) content ) or intradermally ( for evaluation of their angiogenic activity ) to syngeneic balb / c mice .

briefly , sarcoma l-1 cells from in vitro stock were grafted ( 106/0.1 ml ) subcutaneously into the subscapular region of balb / c mice .
after 14 days the tumors were excised , cut to smaller pieces , rubbed through the sieve and suspended in 5 ml of phosphate buffered saline ( pbs ) .
after sedimentation , the supernatant was collected and centrifuged for 10 min at 1500 rpm . obtained sarcoma cells were washed once with pbs for 10 min , then centrifuged at 1500 rpm , and resuspended in parker medium in concentration of 4  10/ml or 10/ml .
multiple 0.05 ml samples of 200 thousand sarcoma cells were injected intradermally into partly shaved , narcotized balb / c mice ( at least 2 - 4 mice per group ) . in order to facilitate the localization of cell injection sites , the suspension
mice obtained aloe vera gel ( 150 l for one mouse daily ) in drinking water for 3 days . after 72 hours mice were sacrificed with a lethal dose of morbital .
all newly formed blood vessels were identified and counted in the dissection microscope , on the inner skin surface , at magnification of 6 , in 1/3 of the central area of the microscopic field .
identification was based on the fact that new blood vessels are thin , directed to the point of cell injection , with ramifications , and some of them are tortuous ( fig .
neovascular reaction 3 days after the intradermal injection of tumor cells 0.1 ml samples of 1 million sarcoma cells were grafted subcutaneously into the sub - scapular region of balb / c mice . on the day of cell grafting and on the following 13 days mice obtained 150 l of aloe vera gel in drinking water , or water as a control .
tumors were removed , weighed and measured with an electronic caliper ( the fowler ultra - cal mark iii caliper ) .

briefly , tumors were homogenized in pbs using an ultrasonic sonificator ( virsonic , usa ) , then centrifuged for 20 min at 4000  g. 20 l of the supernatant was added to 5 ml of drabkin reagent .
the absorbance was read in a spectrophotometric reader elx800 ( biotek instruments , usa ) at 570 nm .
the reader for the hb measurement was calibrated with hemoglobin standard solutions ( sigma ) .
multiple 0.05 ml samples of 200 thousand sarcoma cells were injected intradermally into partly shaved , narcotized balb / c mice ( at least 2 - 4 mice per group ) . in order to facilitate the localization of cell injection sites , the suspension
mice obtained aloe vera gel ( 150 l for one mouse daily ) in drinking water for 3 days . after 72 hours mice were sacrificed with a lethal dose of morbital .
all newly formed blood vessels were identified and counted in the dissection microscope , on the inner skin surface , at magnification of 6 , in 1/3 of the central area of the microscopic field .
identification was based on the fact that new blood vessels are thin , directed to the point of cell injection , with ramifications , and some of them are tortuous ( fig .
0.1 ml samples of 1 million sarcoma cells were grafted subcutaneously into the sub - scapular region of balb / c mice . on the day of cell grafting and on the following 13 days mice obtained 150 l of aloe vera gel in drinking water , or water as a control .
tumors were removed , weighed and measured with an electronic caliper ( the fowler ultra - cal mark iii caliper ) .

briefly , tumors were homogenized in pbs using an ultrasonic sonificator ( virsonic , usa ) , then centrifuged for 20 min at 4000  g. 20 l of the supernatant was added to 5 ml of drabkin reagent .
the absorbance was read in a spectrophotometric reader elx800 ( biotek instruments , usa ) at 570 nm .
the reader for the hb measurement was calibrated with hemoglobin standard solutions ( sigma ) .
two - tailed p value was lower than 0.0001 ( t = = 4.467 ; df = 70 ) .
hence , the mean number of newly formed blood vessels in the experimental , aloe - fed group of mice was highly significantly lower than in the corresponding controls ( fig .
2 ) mean number of newly - formed blood vessels counted 3 days after the intradermal injection of sarcoma l-1 cells the difference between the groups of control and aloefed mice ( 150 l daily dose for 14 days ) with respect to the 14 days tumor volume was on the border of statistical significance ( fig .
no difference was observed in hemoglobin content between control and experimental tumors ( 21.3 3.1 vs. 24.1 3.6 g / mg , respectively ) . the effect of feeding mice with aloe vera drinking gel for 14 days after l-1 sarcoma subcutaneous grafting on the tumor volume ( difference on the border of statistical significance )
it was shown by other authors that some aloe vera active components slow down the experimental tumor growth . three anthraquinones ( aloesin
, aloe - emodin and barbaloin ) extracted from aloe vera leaves may exert their chemo - preventive effect through modulating antioxidant and detoxification enzyme activity levels .
aloe - emodin induces cell death through s - phase arrest and apoptosis in the dose- and time - dependent manner .
other researchers describe the anti - tumour effect of specific derivatives of the aloe vera plant .
di(2-ethylhexyl)phthalate isolated from aloe vera linne may have anti - leukemic and anti - mutagenic properties .
the anti - tumor effect was also documented for the aloe vera leaf pulp extract and the main lectin ( aloctin i ) present in it , in the ehrlich ascites tumor model .
acemannan , the compound of the extract from the parenchyma of aloe vera / aloe barbadensis , stimulates the synthesis of monokines and recruitment of immune cells and , by this mechanism , necrosis and regression of murine sarcoma .
the results of these studies suggest that this effect could be due to its immunomodulatory activity .
acemannan has been approved by the fda - us as a potent immunomodulating and anti - viral agent .
it was approved as an aid in the treatment of canine and feline fibrosarcoma . however , the critical condition for the tumor to effectively metastasize is formation of the new vessels prompted by a group of cancer cells derived from the primary , transported by the blood circulation and grafted in  permissible  tissue environment .
this  permissiveness  is conditioned by the agents released by the tumor cells that drive recipient tissue to facilitate new vessel growth in it .
we have been able to show that aloe vera drinking gel slows down an early phase of new vessel formation and their in - growth in hosting tissue .
however , aloe vera drinking gel has not caused the necrotical effect on the tumor volume and it has not influenced the vascularity of the mature tumor ( as indicated by the lack of differences in hemoglobin content of tumors between groups ) .
it may suggest that its effect is exerted only on the newly forming vessels during micrometastasis implantation .
few cytotoxic and targeted drugs have been proven effective in adjuvant systemic therapies after most of the tumor was removed by surgery or radiotherapy .
the presence of micrometastases at the time of primary therapy is emphasized as the cause of failure of loco regional therapies .
the effective chemoprevention should be directed at the micrometastasis priming mechanism , that is among most important angiogenesis .
aloe vera drinking gel , having a low profile of side effects , may be a good candidate for supplemental therapy . however , aloe vera is also known for its beneficial wound healing impact that might be partly attributed to its compound , -sitosterol , pro - angiogenic properties .
it was shown that in the presence of heparin , beta - sitosterol stimulated neovascularization in the mouse matrigen plug assay , and the motility of human umbilical vein endothelial cells in an in vitro wound migration assay .
therefore , further detailed studies on the specific compounds contribution of the antiangiogenic effect and its mechanism are warranted .
performed a randomized study of chemotherapy versus chemotherapy plus aloe arborescens , in 240 patients with lung , colorectal , gastric and pancreatic metastatic cancers .
aloe arborescens was given orally at a dose of 10 ml thrice daily of a mixture consisting of 300 g of aloe fresh leaves in 500 g of honey plus 40 ml of 40% alcohol , every day without interruption , either during or after chemotherapy , until the progression of disease , starting 6 days prior to the onset of chemotherapy .
the results of this study suggest that aloe may be successfully associated with chemotherapy to increase the tumor regression rate and survival time .

Answer:
aloe vera ( aloe arborescens , aloe barbadensis ) is a medicinal plant belonging to the liliaceae family .
 aloe vera gel prepared from the inner part of aloe leaves is increasingly consumed as a beverage dietary supplement .
 some data suggest its tumor growth modulatory properties .
 the aim of the present study was to evaluate in balb / c mice the in vivo influence of orally administered aloe vera drinking gel on the syngeneic l-1 sarcoma tumor growth and its vascularization : early cutaneous neovascular response , tumor - induced angiogenesis ( tia test read after 3 days ) , and tumor hemoglobin content measured 14 days after l-1 sarcoma cell grafting.feeding mice for 3 days after tumor cell grafting with 150 l daily dose of aloe vera gel significantly diminished the number of newly - formed blood vessels in comparison to the controls . the difference between the groups of control and aloe - fed mice ( 150 l daily dose for 14 days ) with respect to the 14 days tumor volume was on the border of statistical significance .
 no difference was observed in tumor hemoglobin content .


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 this issue of critical care , protti and colleagues   report the effects of metformin on human platelets both in vitro and ex vivo . in vitro experiments
were performed on healthy platelets incubated with increasing doses of metformin , whereas ex vivo experiments were done on platelets from patients presenting accidental metformin - induced lactic acidosis . in both situations ,
platelets ' lactate production and mitochondrial functions were measured . in vitro , a dose - dependent relationship between metformin con centration and lactate production was found . in both conditions ,
high levels of metformin decreased mitochondrial respiratory chain complex i activity , mitochondria polarization , and oxygen consumption .
metformin is a biguanide that has been used as a first - line drug for type 2 diabetes treatment since 1957 in europe and 1995 in the us .
metformin was reputed to induce lactic acidosis , partly because phenformin , another biguanide , was withdrawn from the market because of an unacceptable rate of this complication .
however , numerous clinical studies reported a similar incidence of lactic acidosis in diabetic patients with or without metformin , leading some authors to deny the existence of metformin - associated lactic acidosis . however , in usual clinical practice , metformin contraindications are not often respected .
moreover , physicians do not really monitor adequately their prescription . as a result , numerous publications reported the association between metformin and lactic acidosis . when a cause of lactic acidosis such as shock state or acute renal failure is present , the responsibility of metformin could be questioned .
but when healthy patients without risk factors develop metformin poisoning leading to lactic acidosis , there is no doubt about this link .
however , metformin inhibits hepatic gluconeogenesis in different animal species and decreases mitochondrial respiratory chain complex i activity in different organs .
the clinical research on metformin - associated lactic acidosis was limited to retrospective studies describing incidence , risk factors , and supportive treatments .
a big step forward was made when the gattinoni group   reported a decrease in oxygen consumption after metformin poisoning in humans , strongly suggesting that metformin was able to induce mitochondrial dysfunction in humans .
the study by protti and colleagues elegantly confirms the implication of mitochondria in the pathophysiology of this disease .
of course , the importance of platelet mitochondrial dysfunction per se has to be put in perspective .
however , as demonstrated previously in the pig , platelet mitochondrial dysfunction mirrors the mitochondrial dysfunction in other vital organs .
platelets are more easily accessible than vital organs like the liver or kidney . for research purposes in humans
now that serious research on this rare disease has started , we can also imagine improving its care .
currently , the treatment is only supportive : increasing blood pressure with fluid infusion and catecholamines and promoting metformin elimination by renal replacement therapy . restoring atp production during energy failure due to mitochondria dysfunction is still challenging .
another condition associated with mitochondrial dysfunction , succinate can bypass respiratory chain complex i inhibition and restore oxygen consumption . in isolated cells
, succinate is reputed not to cross the plasma membrane , but methyl succinate ( a cellpermeant succinate ) has been used to bypass metformin blockade of respiratory chain complex i .

Answer:
does metformin - associated lactic acidosis really exist ? despite an old controversy , there is no doubt about it . but
 do we understand what is going on ?
 laboratory findings raised several hypotheses explaining the pathophysiology of this disease .
 the main cause could be an inhibition of either gluconeogenesis or mitochondrial respiratory chain complex i. from bench to bedside , one hypothesis is now confirmed in humans .
 metformin poisoning involves , at least partially , a mitochondrial dysfunction .


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:
it negatively influences the child 's quality of life and is an important cause of absence from school and also a significant factor in health - related costs among children and adolescents .
its prevalence varies greatly from 5.9 to 82% , depending on the definition criteria and the age of the patients .
the international headache society classifies headaches into primary and secondary type in classification of headache disorders 2 edition ( ichd - ii ) .
primary headache is not attributed to any other disorder . in the majority of patients with primary headache , general and neurological examinations are normal and
primary headaches include migraine , tension - type headache , cluster headache , autonomic cephalalgias and other primary headache disorders .
frequency of headache increases with age in this population . in the present study we aimed to determine epidemiologic characteristics and compare socioeconomic and some clinical factors related to primary headaches in children / adolescents ( 4 - 15 year olds ) presented to neurology clinics of tabriz university of medical sciences .
the institutional review board at tabriz university of medical sciences approved the study protocol . after obtaining a written informed consent from parents , children with 4 - 15 years of age and with the diagnosis of primary headache ( migraine or tension - type headaches ) who presented to the neurology clinics affiliated to tabriz university of medical sciences , tabriz , iran from march 2009 to october 2011 were included in this cross - sectional study .
a total of 190 patients fulfilled the criteria for enrollment in the study and their demographics were collected .
we noted the type of headache , history of atopy , asphyxia during labor ( according to the history of admission in the neonatal intensive care unit after birth due to respiratory problems based on the parents report and review of the previous medical records ) and breast feeding , family history of headache , presence of headache triggers and the socioeconomic status of the family .
diagnosis of migraine and tension - type headache was based on the international headache society diagnostic criteria for the primary headache disorders .
socioeconomic status was determined according to the total monthly family income ( < 7,000,000 rl vs = 7,000,000 rl ) based on the index of statistical center of iran for grand cities in the years of study in addition to the highest level of education of the father ( < or = high school vs. > or = college ) .
statistical analysis was conducted with spss , version 16.0 for window ( spss , chicago , il ) .
data were expressed as meansd for quantitative variables and as numbers and percentages for categorical variables .
statistical analysis was performed using the chi - square test for categorical variables and the student 's t test for numerical variables .
eighty eight patients ( 46.3% ) had migraine and 102 patients ( 53.7% ) had tension - type headache .
the distributions of gender and age groups in patients with migraine or tension - type headache are shown in table 1 .

the distributions of gender and age groups in patients with migraine or tension - type headache data are presented as numbers no significant differences were seen in the distribution of gender between the patients with migraine and tension - type headache .
migraine and tension - type headache had comparable frequency in different age groups of male patients ( p=0.1 and 0.07 , respectively ) .
in female patients the frequencies of both migraine and tension - type headache were significantly higher in the age group of 10 - 15 years as compared to the age group of 4 - 9 years ( p=0.03 and 0.04 , respectively ) .
there was no significant differences regarding the prevalence of migraine or tension type headache between different genders in the same age group .
the most common clinical presentations of aura in patients with migraine are demonstrated in table 2 .
the comprehensive data regarding the epidemiologic characteristics of patients with migraine or tension - type headache in our study group are shown in table 3 .

the clinical presentations of aura in patients with migraine the characteristics compared between patients with migraine and tension - type headache as triggering factors for headache ; or : odds ratio ; ci : confidence interval history of asphyxia during labor was more prevalent among patients with migraine as compared to the tension - type headache ( p=0.007 , or = 3.24 ) . history of headache in parents was also significantly higher in patients with migraine as compared to tension - type headache ( p=0.001 , or = 3.19 ) .
moreover , the prevalence of atopy was significantly higher in patients with migraine ( p=0.01 , or = 5.70 ) .
prevalence of feeding with formula during infancy did not differ between the patients with either migraine or tension - type headache ( p=0.9 ) .
the low socioeconomic status was more prevalent in patients with migraine headache ( p=0.003 , or = 2.38 ) .
in our study primary headache was more common in older age group which is consistent with danold 's findings which showed that frequency of headache increases with age .
tension type headache in patients was more frequent than migraine which is comparable with findings of kroner - herwig et al .
the main finding in the present study was that gender can not predict the type of primary headache in younger children , as no gender differences were seen between the patients with migraine or tension - type headache in the age group 4 - 9 years .
this finding is in contrast to previous report by krner - herwig et al which showed that being female was a significant predictor for three main subtypes of primary headaches
a few other studies showed that the prevalence of migraine was higher in the males .
our results also demonstrated that the frequencies of migraine and tension - type headache were comparable in different age groups of male patients , whereas female patients in the age group 10 - 15 years had higher frequency of both types of headache especially migraine as compared to the age group 4 - 9 years .
this finding reveals that female adolescents had higher risk for developing primary headache specially migraine as compared to female children .
these results agree with those reported by krner - herwig et al who showed that children with migraine were significantly older than children in the other groups .
it could be due to hormonal effect as the trigger of migraine headache in the female adolescents .
it was previously shown that primary headache in children is closely related to history of headache in their parents .
our results demonstrated that when a parent showed combined headache , the risk of developing migraine in his or her child is more conspicuous as compared to the tension - type headache .
this finding is consistent with previous reports by fallahzadeh et al and krner - herwig et al which showed a stronger association between family history of headache and being afflicted by migraine as compared to tension - type headache in children .
our study also demonstrated that if the patients with history of peripartum asphyxia would develop primary headache it would more probably be of migraine type .
these results partly agree with those reported by maneyapanda et al who found an association between chronic migraine headache and significant perinatal insult due to neuroplasticity and its induced hyperexcitability .
however , it is recommended to design prospective studies to compare the frequency of primary headache ( either migraine or tension - type headache ) in patients with or without perinatal insults to elucidate the role of peripartum asphyxia as a risk factor for developing primary headaches .
we also showed that atopy is more prevalent in patients with migraine as compared to tension - type headache .
also ozge et al found an association between atopy and both migraine and episodic tension - type headaches .
it has been shown that alteration in several interleukins occurs in migraine which supports an association between migraine and atopic disorders .
although it was shown by pogliani et al that breast feeding has a protective role against primary headache disorders , our results showed that children and adolescents with history of formula feeding during infancy have comparable prevalence of developing either migraine or tension - type headache .
our results showed that socioeconomic status of the patients could significantly influence the frequency of migraine in comparison to tension - type headache .
ayzenberg et al in a study on 2725 adults in russia , showed that low socioeconomic status is associated with higher frequency of primary headache disorders .
moreover , katsarava et al in another study on 1145 adult patients in the republic of georgia showed that low socioeconomic status and female gender are risk factors for development of migraine , not tension - type headache .
moreover , the possible role of psychological factors and behavioral characteristics influencing primary headaches could have been considered .
while some variables have been checked by the present report , further prospective studies with larger sample sizes are needed to provide more comprehensive data regarding associated factors in childhood primary headache .

Answer:
objectiveheadache is one of the most common neurologic problems in children and adolescents .
 primary headache including migraine and tension - type headache comprises the vast majority of headaches and are associated with marked incidence , prevalence , and individual and social cost .
 we aimed to assess demographic characteristics and to compare some factors related to primary headaches in children/ adolescents presented to neurology clinics of tabriz university of medical sciences.methodschildren from 4 to 15 years of age with the diagnosis of primary headache ( migraine or tension - type headaches ) who presented to the neurology clinics affiliated to tabriz university of medical sciences , tabriz , iran from march 2009 to october 2011 are included in this cross - sectional study .
 data regarding the type of headache , history of atopy , peripartum asphyxia , and breast feeding , family history of headache and the socioeconomic status of the family were collected .
 the diagnosis was based on the international headache society diagnostic criteria for the primary headache disorders.findingsone hundred ninety children ( 107 females ) with primary headache ( 88 patients with migraine and 102 patients with tension type headache ) enrolled in the study .
 peripartum asphyxia , history of atopy , family history of headache and low socioeconomic status ( ses ) were more common in patients with migraine ( p - values : 0.007 , 0.01 , 0.001 , 0.003 ; respectively).conclusionphysicians need to extent their knowledge regarding the primary headaches .
 peripartum asphyxia , history of atopy , headache in parents and low ses have been shown in the present study to be more prevalent in patients with migraine as compared to tension - type headache .


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:
plica neuropathica is an acquired , rare condition characterized by sudden and irreversible matting of scalp hair in otherwise healthy individuals .
it was formerly supposed to be a disease peculiar to poles ( hence named as plica polonica ) and was usually the result of neglect or parasitic infestations .
subsequently , other factors such as shampoos , conditioners , herbal soaps , and psychiatric morbidity were also reported to result in matting of scalp hair .
a dermatology consult was sought for a 65-year - old female who developed severe matting of scalp hair for 1 week .
she was admitted under medical services for the management of azathioprine ( 50 mg once daily for a month ) induced pancytopenia , which was prescribed for pulmonary sarcoidosis .
she gave a history of loss of hair from frontal area of scalp , that came out in bunches , followed by spontaneous tangling of hair over the top of her head to form a stiff protuberant mass [ figure 1 ] .
she had no features of scabies or lice and shampooed her hair once a week with a non medicated shampoo .
there was no history of use of any chemical treatment for her hair such as streaking or straightening of hair .
examination of scalp revealed diffuse non scarring loss of hair over the frontal area and a mass of solid irregular matted hair located over the vertex , approximately 10 cm in height [ figure 1 ] .
investigations revealed total leucocyte count of 0.9  10/l ( reference range 4.011.0  10/l ) , hemoglobin of 7.4 g% ( reference range 1215.5 g% ) , and platelet count of 0.49  10/l ( reference range 1.54.5  10/l ) .
examination revealed noncicatricial hair loss over the frontal region and elongated stiff protuberant mass of matted hair on the vertex which could not be detangled .
the matting of hair in case 1 . also diffuse hair loss form the scalp can be appreciated a 30-year - old female was referred for the sudden loss of hair and severe tangling of hair that could not be combed for 3 days .
her medical history was significant for the development of hydatidiform mole followed by methotrexate induced pancytopenia , severe stomatitis , and erythema multiforme over hands , feet , and upper trunk [ figure 2a ] .
she was on methotrexate 25 mg once a day for 5 days , two cycles given over a period of 1 month . during her hospital stay , she found difficulty in combing her hair that became extensively tangled . over next few days , she tried to comb her hair without success and found that her hair had been irreversibly matted and also the loss of hair over frontal area of scalp [ figure 2b ] .
there was no history of skin or hair disease in past , and she regularly shampooed her hair once or twice a week .
pertinent investigations revealed total leucocyte count of 1  10/l ( reference range 4.011.0  10/l ) , hemoglobin of 8 g% ( reference range 1215.5 g% ) , platelet count of 0.55  10/l ( reference range 1.54.5  10/l ) and peripheral blood film predominantly normocytic normochromic . on examination
, she had extensive noncicatricial alopecia involving the middle two - third of the scalp .
she was managed conservatively for pancytopenia and scalp hair were shaved off as a part of treatment for plica .
a dermatology consult was sought for a 65-year - old female who developed severe matting of scalp hair for 1 week .
she was admitted under medical services for the management of azathioprine ( 50 mg once daily for a month ) induced pancytopenia , which was prescribed for pulmonary sarcoidosis .
she gave a history of loss of hair from frontal area of scalp , that came out in bunches , followed by spontaneous tangling of hair over the top of her head to form a stiff protuberant mass [ figure 1 ] .
she had no features of scabies or lice and shampooed her hair once a week with a non medicated shampoo .
there was no history of use of any chemical treatment for her hair such as streaking or straightening of hair .
examination of scalp revealed diffuse non scarring loss of hair over the frontal area and a mass of solid irregular matted hair located over the vertex , approximately 10 cm in height [ figure 1 ] .
investigations revealed total leucocyte count of 0.9  10/l ( reference range 4.011.0  10/l ) , hemoglobin of 7.4 g% ( reference range 1215.5 g% ) , and platelet count of 0.49  10/l ( reference range 1.54.5  10/l ) .
examination revealed noncicatricial hair loss over the frontal region and elongated stiff protuberant mass of matted hair on the vertex which could not be detangled .
the matting of hair in case 1 . also diffuse hair loss form the scalp can be appreciated
a 30-year - old female was referred for the sudden loss of hair and severe tangling of hair that could not be combed for 3 days .
her medical history was significant for the development of hydatidiform mole followed by methotrexate induced pancytopenia , severe stomatitis , and erythema multiforme over hands , feet , and upper trunk [ figure 2a ] .
she was on methotrexate 25 mg once a day for 5 days , two cycles given over a period of 1 month . during her hospital stay , she found difficulty in combing her hair that became extensively tangled .
over next few days , she tried to comb her hair without success and found that her hair had been irreversibly matted and also the loss of hair over frontal area of scalp [ figure 2b ] .
there was no history of skin or hair disease in past , and she regularly shampooed her hair once or twice a week .
pertinent investigations revealed total leucocyte count of 1  10/l ( reference range 4.011.0  10/l ) , hemoglobin of 8 g% ( reference range 1215.5 g% ) , platelet count of 0.55  10/l ( reference range 1.54.5  10/l ) and peripheral blood film predominantly normocytic normochromic . on examination
, she had extensive noncicatricial alopecia involving the middle two - third of the scalp .
she was managed conservatively for pancytopenia and scalp hair were shaved off as a part of treatment for plica .
in 1884 , when le page first described a case of acute matting of scalp hair , he referred to it as plica neuropathica as he believed it stemmed from hysterical tendencies .
it was prevalent in poland in the 19 century , hence was named plica polonica or polish plait .
it presents as a compact mass of scalp hair with irregular twists and irreversibly entangled plaits which are firm to hard impenetrable mass of keratin cemented together with dirt and exudates .
the process of matting is essentially similar to the phenomenon of  felting  which occurs in wool and textile industries in which there is compacting of contiguous fibers exposed to surface damage and friction .
it occurs when fibers are stirred together in a liquid medium and are subsequently exposed to increased functional forces .
if the hair is rubbed along its shaft , it gets electrically charged with positive polarity if the friction is toward the root and negative if friction is toward the free end .
probably matting of hair does not occur either from electrostatic attractions or from liquid crystal formation but from the combination of the two .
the exact mechanism for matting is not well - understood but both physical and chemical factors that damage hair shafts may play a role [ figure 3 ] .
plausible mechanisms of pathogenesis of plica neuropathica various etiologies have been propounded from time to time .
a thorough review of the available literature has led to a plethora of causes [ table 1 ] .
the various etiological factors of plica neuropathica temporary hair loss ( alopecia ) is a common side effect of chemotherapy .
hair follicles ( hf ) are  hair shaft - producing miniorgans  showing during postnatal life a unique pattern of cyclic activity with periods of active growth ( anagen ) , relative resting ( telogen ) , and apoptosis driven involution ( catagen ) .
hf 's are strongly affected by many chemotherapeutic agents because of the rapid proliferative rate of hair matrix keratinocytes during anagen .
immunosuppressive drugs commonly lead to anagen effluvium due to abrupt cessation of mitotic activity in the rapidly dividing hair matrix cells so that either no hair is produced , or a narrowed and defective hair shaft is produced and the hair loss is evident within days to weeks of drug administration .
however , azathioprine is not normally known to be a cause of anagen effluvium and it is possible that the sudden pancytopenia results in hair shaft damage leading to hair loss and hair shaft cuticular damage resulting in matting of hair .
plica neuropathica generally affects healthy persons but has been described in a 54 years and a 14-year - old chronically ill female with azathioprine - induced pancytopenia , without any history of neglect , parasitic infestation , and shampooing . on the other hand , methotrexate has not been reported to cause matting of hair though it can lead to hair fall .
antimitotic chemotherapeutic agents such as methotrexate induce arrest of the anagen phase and present a toxic insult to the rapidly dividing hair matrix .
hair loss usually begins 12 weeks after chemotherapy is started and is most noticeable by 12 months .
these antimetabolite drugs induce dystrophic changes in the new follicles as well as in the already growing hf .
they also lead to premature regression as a result of massive apoptosis in the entire proximal hair bulb leading to subsequent hair shedding .
when functional forces are applied to the already damage cuticle of the long and old hair , proximity of shafts increases , and tangling occurs leading to plica .
furthermore the unfruitful efforts by the patient to comb the unruly hair lead to electrostatic attraction and increase the chances of matting of the long and old hair .
the chemotherapy - induced hair loss and the effects on the growing hf , and the resultant cuticular damage is much more complex than previously appreciated and may require distinct molecular studies to further collaborate these theories .
both of our patients agreed to the manual removal of hair as a part of treatment .
however , it can still be prevented from developing by adequate hair care and washing habits .
prevention measures that can be adopted are :
 regular cleaning of hair with mild cleansers or shampoosgentle oiling and combing to avoid entanglingregular hair trimmingavoid hair piling over vertex while washing and backcombingavoid rotatory rubbing of hairlong hair should be given a backwash or be washed in the sink .

regular cleaning of hair with mild cleansers or shampoos gentle oiling and combing to avoid entangling regular hair trimming avoid hair piling over vertex while washing and backcombing avoid rotatory rubbing of hair long hair should be given a backwash or be washed in the sink .
matting of hair in two patients on azathioprine and in a patient on chemotherapy ( doxorubicin , cyclophosphamide and cisplatin after surgery for papillary cystadenoma ovary ) following washing of hair with a soap containing acacia concinna , have been reported previously .
the current report is probably only the third case of plica neuropathica associated with azathioprine - induced pancytopenia and first with methotrexate in literature and unusual in that it occurred not because of neglect and poor hair care or overzealous shampooing of hair but due to cuticular damage of hair shaft secondary to the immunosuppressive drug induced pancytopenia .
we consider that matting of hair is not truly a hair disorder , rather a reaction resulting from the interplay of great motley of factors . moreover , the role of myriad factors such as chronic illness , hospital stay , pancytopenia , and drug induced cuticular damage is still debatable .

Answer:
plica neuropathica also known as  birds nest  is irreversible matting of hair seen in otherwise healthy individuals and is usually associated with use of ionic / herbal soaps , shampoos , parasitic infestations , psychiatric alterations , or neglect .
 anagen effluvium is a known side effect of many immunosuppressive drugs .
 rarely matting of hair has been reported following azathioprine .
 we report plica neuropathica in two chronically ill patients on immunosuppressive drugs , that is , azathioprine and methotrexate along with a review of literature of its etiological factors and pathogenesis .


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

Paper text:
the ministry of health , labour and welfare
 of japan has recommended shortening of the length of hospital stays1 . in general , shortening the length of stay contributes to a
 reduction in the physical and mental stress of patients and rapidly returns them to their
 jobs and communities .
actually , in a previous study , it was shown that a shorter length of
 stay resulted in not only a financial benefit but also a patient benefit2 .
the patient s benefit is spending less time
 out of their home and reduction of the possibility of contracting nosocomial infections
 during a stay in the hospital2 . in stroke
 patients , stroke - related impairment , medical complications , family support , and
discharge
 destination predict the length of stay3 .
 in another previous study , impairment , activities of daily living ( adl ) , unplanned
 discharges , and discharge to facilities affected the length of stay4 . on the other hand ,
similarly , patient - related factors were found to affect rehabilitation outcome , whereas
 illness- and intervention - related factors did not6 .
this behavior pattern
 includes impatience , urgency , aggressiveness , and particularity about details .
the type a
 behavior pattern is regarded as an independent risk factor of cardiovascular diseases7 .
however , patients with type a behavior
 pattern characteristics may have better compliance with rehabilitation and other forms of
 medical and social support than those with non - type a behavior .
if patients with the type a
 behavior pattern have better compliance , they would have a shorter length of hospital stay
 than those with non - type a behavior . to examine this hypothesis , in this study , we compared
 the length of stay of patients with the type a behavior pattern with that of patients with a
 non - type a behavior pattern .
we hypothesized that length of stay of patients with the type a
 behavior pattern would be shorter than that of patients with a non - type a behavior
 pattern .
fifty - seven patients participated in this study . all patients had stayed in the
 comprehensive rehabilitation unit of omaezaki municipal hospital between april and december
 2013 .
the exclusion criteria were as follows : transfer to another hospital , medical
 facility , or welfare facility during the research term and refusal to provide informed
 consent .
type a behavior pattern was assessed by an abbreviated set of 12 questions developed by
 maeda8 .
hardly  were scored as 2 , 1 , and 0 points , respectively , for nine
 questions , and the points were doubled for three questions .
a total score of 17 or greater
 was defined as type a , and the other subjects were defined as non - type a. after the subjects
 were discharged , we counted the number of days between admission and discharge to evaluate
 the length of stay . to evaluate the ability to perform adl at discharge , we measured barthel
 index for all patients .
we used the student s t - test to examine statistical differences in
 length of stay and barthel index at discharge between subjects with type a behavior and
 those without type a behavior .
we analyzed these measurements by statistical package for social sciences ( spss )
 version 19 .
ultimately , 55 subjects ( 75.311.7  years old , 18 males and 37 females ) were classified into
 either the type a group ( n = 26 ) or the non - type a group ( n = 29 ) , as shown in table 1table 1.characteristics of the type a and non - type a behavior patternscharacteristicstype a groupnon - type a grouppatients ( n)2629male ( n)108female ( n)1621cause of admissionstroke ( n)810fractures ( n)1310disuse syndrome ( n)23others ( n)36values represent number of subjects . others
causes of admission include spinal code
 injury , spinal canal stenosis , and total knee arthroplasty .. the characteristics of subjects ( sex and cause of admission ) were similar in
 the two groups .
age was not significantly different between the two groups . also , the
 barthel index at discharge was not significantly different between the two groups .
however ,
 length of stay was significantly higher in the non - type a group compared with the type a
 group ( p < 0.05 ) ( table 2table 2.difference in length of stay between the type a group and non - type a
 groupscharacteristicstype a groupnon - type a groupage ( years)77.271.4discharge bi97.5897.08length of stay ( days)66.287.4 * * p < 0.05 vs. type a group , values represent averages .
others causes of admission include spinal code
 injury , spinal canal stenosis , and total knee arthroplasty .
our results support the hypothesis that patients with the type a behavior pattern have
 better compliance with forms of medical support than patients with a non - type a behavior
 pattern .
patients with the type a behavior pattern had a shorter length of hospital stay
 than patients with a non - type a behavior pattern . length of hospital stay can be affected by multiple factors , including medical
 complication , family support , discharge destination3 , impairment , adl4 ,
 and rehabilitation9 .
patient - related
 factors5 , especially psychological
 factors6 , affect rehabilitation
 outcomes .
the subjects in this study were patients who stayed in a comprehensive
 rehabilitation unit .
patients who stay in a comprehensive rehabilitation unit do not require
 much medical care and are able to focus on rehabilitation .
hence , our data suggest that
 psychological factors of the patients , such as type a behavior , affect rehabilitation
 compliance .
length of stay , ability to perform adl at discharge , and patient age influence
 rehabilitation outcome and whether patients can return home or not10 , 11 .
there was no significant difference in
 barthel index or patient age between patients with the type a behavior pattern and those
 with a non - type a behavior pattern .
thus , it appears likely that ability to perform adl at
 discharge , patient age , and destination at discharge do not influence length of stay .
the type a behavior pattern includes impatience , urgency , aggressiveness , and particularity
 about details .
patients who have higher levels of physical activity during rehabilitation
 were associated with a shorter length of stay12 . because patients with the type a behavior pattern might have good
 compliance with rehabilitation and increase their physical activity
the type a behavior pattern is well known to be an independent
 risk factor of cardiovascular diseases7 .
 also in the japanese , the type a behavior pattern is associated with an increased risk of
 acute myocardial infarction , especially in women13 .
so , the type a behavior pattern may be considered not a good
 characteristics in general .
in contrast , another article reported that the type a behavior
 pattern reduced the risk of coronary heart diseases in japanese men14 .
japanese men who do not express their anger may have an
 increased risk of high blood pressure15 .

this previous article indicates that non - type a japanese men may have a higher hypertension
 risk than type a japanese men . in the japanese , the type
our results also show that patients with the type a
 behavior pattern may be able to return home early .
finally , the cause of a short length of stay may not
 be rehabilitation compliance .
in conclusion , our results suggest that the type a behavior pattern shortens the length of
 hospital stay .
the data show that we should consider the patient s characteristics in
 rehabilitation to protect the patient and for financial benefit .

Answer:
[ purpose ] the aim of this study was to describe the importance of patient - related factors
 in rehabilitation .
 we focused on the type a behavior pattern .
 if individuals with the type
 a behavior pattern have better compliance , they would have a shorter length of hospital
 stay than those with non - type a behavior .
 we compared the length of stay of patients with
 the type a behavior pattern with that of patients with a non - type a behavior pattern .

 [ subjects and methods ] fifty - seven patients staying in a comprehensive rehabilitation unit
 participated in this study .
 type a behavior pattern , length of stay , and barthel index
 were assessed .
 we use the student s t - test to examine the statistical differences in
 length of stay and barthel index at discharge between subjects with type a behavior and
 those without type a behavior .
 [ results ] age and barthel index at discharge were not
 significantly different between the two groups . however , length of stay was significantly
 higher in the non - type a group compared with the type a group .
 [ conclusion ] patients with
 the type a behavior pattern had a shorter length of hospital stay than patients with a
 non - type a behavior pattern . in conclusion
 , our results suggest that the type a behavior
 pattern shortens the length of hospital stay .
 those data show that we should consider the
 patient s characteristics in rehabilitation to protect the patient and for financial
 benefit .


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:
sodium valproate is a frequently used drug for the treatment of seizure disorders , bipolar disease and chronic pain .
it is known to cause a serious complication , hyperammonemic encephalopathy which is characterized by acute onset of impaired consciousness , headache , vomiting , seizures , ataxia , generalized slowing on electroencephalography and rapid recovery after discontinuation . in this submission , we present a case of valproate - induced hyperammonemic encephalopathy where the major manifestation was restricted to bilateral cerebellar clinical features .
a 19-year - old male presented with acute onset tremulousness , staggering gait and difficulty in walking and speech .
he was a known case of idiopathic generalized epilepsy treated initially with carbamazepine ( 800 mg / day ) and recently switched over to sodium valproate ( 1000 mg / day ) before the onset of this acute complication .
the patient showed bilateral cerebellar signs in the form of defective coordination in both upper and lower limbs with severe degree of gait ataxia and scanning speech .
investigations including hemogram , liver function tests , renal function parameters , serum electrolytes and blood sugar showed normal results .
thyroid function tests ( t3 , t4 , thyroid stimulating hormone ) and nutritional parameters including vitamin b12 levels were also found in normal range . however , serum ammonia level was raised to 106 mol / l ( normal range 12 - 47 mol / l ) .
the levels of serum valproate and carbamazepine were found to be in the normal range ( serum valproate : 52 ug / ml [ range : 50 to 100 gm / ml ] and serum carbamazepine < 1.25 gm / ml [ range : 4 to 12 gm / ml ] ) .
patient underwent magnetic resonance imaging of cranium , which turned out to be normal . with this background of clinical observations and laboratory assessment , a diagnosis of valproate - induced hyperammonemic encephalopathy
the valproate was replaced by levetiracetam ( 500 mg ) two times a day along with carnitine supplementation .
the patient showed rapid recovery and was able to walk without support after a week .
his serum ammonia level normalized on repeat serum ammonia estimation ( 20 mol / l ) .
valproic acid by virtue of its broad spectrum of action has application in various disorders like epilepsy , bipolar disorders , prophylaxis and treatment of migraine and neuropathic pain .
although valproate - induced hepatic dysfunction leading to encephalopathy is a well - recognized entity , less commonly the drug can also produce an encephalopathy of non - hepatic origin by producing hyperammonemia , and is called as valproate - induced non - hepatic hyperammonemic encephalopathy ( vnhe ) .
other causes of non - hepatic hyperammonemia include inborn errors of metabolism ( urea cycle enzyme defects , fatty acid oxidation defects ) , drugs like 5-fu , asparaginase , salicylate , halothane and enflurane , hematologic diseases like multiple myeloma and acute myeloblastic leukemia , hyperinsulinemia , hyperglycemia , distal renal tubular acidosis , parenteral nutrition and reye 's syndrome .
the clinical presentation of hyperammonemic encephalopathy constitutes irritability , drowsiness , coma and occasionally these patients have paradoxical seizures .
the presence of significant hyperammonemia with cerebellar signs and reversal of hyperammonemia , encephalopathy and disappearance of cerebellar signs and symptoms after discontinuation of sodium valproate confirmed the diagnosis of valproate - induced hyperammonemic cerebellar ataxia with metabolic encephalopathy .
this view is also supported by generalized slowing in eeg suggestive of metabolic encephalopathy which also normalized after discontinuation of valproate .
we estimated serum valproate and carbamazepine levels which were within normal limits although there is little correlation between valproate level and clinical effects because of the variable absorption rate and short half - life of the drug .
in our study , there was decline in ammonia levels after withdrawal of valproate and subsequent disappearance of cerebellar symptoms and features of encephalopathy .
there is scarcity of literature on unusual symptoms of valproate - induced hyperammonemic encephalopathy presenting as mainly cerebellar ataxia .
cases have been reported where patients presented with acute onset of confusion , decline in cognitive abilities , and ataxia .
we gave carnitine supplementation to our patient as valproate is known to enhance urinary excretion of l - carnitine , leading to depletion of its blood stores .
thus we conclude that valproate - induced hyperammonemic encephalopathy can present mainly with cerebellar ataxia and a high index of suspicion is required for an early recognition , investigation , and treatment of this potentially life - threatening condition .

Answer:
valproate - induced hyperammonemic encephalopathy is a rare event clinically characterized by impaired sensorium , vomiting , headache , seizures and focal neurological deficits .
 the pathogenesis of this dreadful complication is not well understood , although hyperammonemia has been implicated in causation of encephalopathy . in this submission , we have highlighted a case of valproate - induced encephalopathy who presented mainly with bilateral cerebellar features and generalized slowing on electroencephalogram .
 high index of suspicion of valproate - induced hyperammonemic encephalopathy is required if diffuse ataxia is present as it is a potentially reversible clinical disorder .