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 syndrome with ectrodactyly , ectodermal dysplasia , cleft lip and cleft palate ( eec ) is a complex disease with a variety of abnormalities of the ectodermal and mesodermal germinal layer . the first author who described this disease was eckoldt   in 1804 .
split hands or feet are characterized by agenesis of the third ray and possible fusion of the remaining fingers or toes .
the ectodermal component of this syndrome includes hair with hypotrichosis , hypopigmentation , the teeth with hypodontia , enamel hypoplasia and microdontia and ultimately the nails , which present themselves dystrophic in most cases .
a number of associated anomalies are also frequently found . in the 230 published cases , 84% of patients presented with split hands or feet .
dysplasia of the ectoderm arises in 77% of patients and clefts appear in 68% of cases .
important hints may indicate an eec syndrome already in the clinical examination of the patient and in the investigation of family history .
two case reports of our department shall demonstrate the management of eec syndrome affected patients with  all - in - one  closure of the lip cleft and palate cleft and the treatment regimen in manifest ectodermal dysplasia .
a newborn baby with a unilateral complete cleft lip and palate ( left side- cleft palate width 23 mm )  first child of non - consanguineous marriage  was referred to our department . additionally , the child presented a deletion of the central finger on the right hand and fusion of the second and third finger on the left hand as well as fusion of the second and third toe on both feet . paper - thin , dry and reddened skin and sparse scalp hair were also visible ( figure 1 ) .
the father suffered from the eec syndrome , too- , showing similar hand malformation and a bilateral cleft lip and palate , which was treated in multiple surgeries . in our patient ,
feeding of the child was possible with a palate obturator . for ( naso)alveolar molding lip taping with an elastic plaster ( dynacleft , barrie on , canada )
the cleft lip width was still 12 mm . for improved soft - tissue conditioning , lip adhesion
two months later , the one - step procedure of the cleft lip and palate closure was performed .
the operative procedure involves firstly in intravelar veloplasty with microscopic view , secondly in restore the nasal floor with two choanes and pedicled flaps without push back and at the end doing only a gingivoperiosteoplasty but without touching the germ area . at the end , a palatal plate was fitted for 7 days . in our protocol , we do a secondary osteoplasty with 9/10 years of age .
the operation time was 60 min for the palate . during the closure of the palate to prevent pressure damage on the tongue the mouth gag was often released .
nevertheless , after surgery , the child had to be re - intubated at the intensive care unit due to an exfoliative stomatitis and dramatic swelling of the back of the tongue with impairment of the upper respiratory tract ( figure 3 ) .
supportive treatment with an anti - edematous and anti - inflammatory medication ( cortisone intravenously ) was initiated
the further post - operative course of treatment was without complications ( figure 4 ) .
we suppose that there is a connection with the eec which makes the tissue more sensitive  but this is a hypothesis that is not proven .
the clinical examinations showed a complete cleft lip and palate ( left side ) and deletion of the central finger on the right hand , fusion of second and third finger of the left hand and fusion of the second and third toe on both feet .
swelling of the back of the tongue and exfoliation after the  all in one  closure and before re - intubation .
follow - up 6 months after surgery with harmonious upper lip and no abnormalities in the epidermis . until now , no treatment concerning hands and feet was performed .
this case presents the sister of the above described boy , born 3 years and eight months later : born at 38 week of gestation with a birth weight of 2985 g she showed a bilateral cleft lip , syndactyly on all extremities and a conspicuous dryness of the skin ( figure 5 ) .
clinical findings and the family history lead again to the eec syndrome . similar to the brother an obturator plate with nasoalveolar molding was adapted . at the age of 8 weeks a lip adhesion was performed . with 4.5 months
the clinical examination of the patient 3 h after birth shows the typical characteristics for the eec - syndrome .
no complications have occurred in wound healing due to the eec - syndrome until now , no treatment concerning hands and feet was performed .
.   characterized by ectrodactyly , ectodermal dysplasia , cleft lip and/or cleft palate . since then , numerous reports in the literature have expanded the clinical appearance .
the transmission is usually autosomal - dominant trait with variable expressivity and reduced penetrance [ 4 - 6 ] .
some authors believe that the classic case of the eec syndrome is caused by mutation of the p63 gene .
the variability in the phenotypic expression is explained by the interaction of ectodermal with the mesodermal germ layer .
the eec syndrome must be differentiated from other syndromes , which also show an ectodermal dysplasia and orofacial clefts as the rapp - hodgkin syndrome , the aec syndrome ( syndrome with ankyloblepharon filiform adnatum , ectodermal dysplasia and cheilognathopalatoschisis , [ 10 - 12 ] ) .
others have their own characteristics , for example the rapp - hodgkin syndrome presenting a short stature and special lineaments .
the eec syndrome has to be distinguished from other diseases with acral anomalies and oral cleft , including the acrorenal  syndrome   and from the fetal alcohol syndrome .
minor anomalies of the eec syndrome are renal malformations , deafness , mental retardation   and choanal atresia .
other recently reported associated anomalies are the insufficiency of the pituitary gland , anorectale malformations   and hypoplasia of the thymus .
until now , three types of eec syndrome and their respective gene loci were molecularly identified .
balanced chromosome changes or interstitials deletions were found : type 1 is linked to gene locus 7q11.21q21.3 , type 2 and type 3 with chromosome 19 locus with 3q21 ( p63 ) [ 21 - 23 ] .
recently , heterozygous mutations in the p63 gene have been shown to 3q27 by amino acid substitutions in the dna - binding domain , which are considered as the main cause for the formation of the gap in hands and feet [ 25 - 27 ] .
the ultrasound in prenatal diagnosis plays an important role in the early detection of ectrodactyly and cleft lip and palate [ 28 - 30 ] . for a more accurate prenatal diagnosis of this syndrome ,
a molecular study was introduced . with the use of a dna extraction from fetal chorionic villi
, a prenatal dna analysis can be carried out in a pregnancy at risk for the eec syndrome .
, eec children will be treated like other non - syndromic cleft patients . in the first 24 h after birth , an obturator plate and
if necessary and due to dry skin possible , upper lip taping is adapted for alveolar molding .
the gastric tube see in figure 4 was removed after the obturator plate was inserted . if the cleft lip remains more than 15 mm a lip adhesion is an option .
normally , this will be performed at the age of 8 weeks , in the first case it was delayed due to surrounding circumstances . approximately 8 weeks later , a closure of all layers in a single operational step will be performed .
one - stage procedures with 34 months can lead to disturbance in growth of the maxilla , but the extend was similar to the mean values of multistage procedures assessed in the eurocleft study .
children and their parents have no further psycho - social stress due to multiple surgical interventions at an early age .
the main therapeutic approach depends on the expression of the ectodermal dysplasia and should be evaluated individually for each patient .
it is mandatory that the patient has a close follow - up with , if necessary , functional physiotherapy , speech therapy and early functional orthodontic care .
whenever cases of eec syndrome occur , it is important , according to their phenotypic characteristics , to follow an interdisciplinary approach to reduce complications , to minimize undesirable sequelae and provide the best possible medical care .
ethics and consent : a written consent from the parents for the publication of photos is available .

Answer:
we report on siblings who suffer from eec syndrome and show our experiences of the " basel concept " of cleft lip / palate repair based on the early , one - stage closure of all components .
 it is performed in the age of 34 months to provide early normal conditions for anatomy and muscle function .


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:
hypophosphatemic rickets ( hr ) is a metabolic bone disorders manifested by musculoskeletal disorders specially in the lower extremities , growth retardation and dental problems[1 , 2 ] .
this disorder affects all ages and both sexes and is characterized by a low concentration of serum phosphate , elevated alkaline phosphatase , normal or decreased serum calcium and inappropriate levels of 1,25-dihydroxy - vitamin d [ 1,25 ( oh)2 vit d][1 , 3 ] .
musculoskeletal disorders are due to mineralization impairment of the bone matrix and teeth with different etiologies .
x - linked hypophosphatemic rickets ( xlhr ) is the most common form of the genetic disorders causing rickets due to hypophosphatemia .
this disorder results from mutation in the phex gene and the product of this gene has a role in phosphatonin inactivation .
hr is more common in females with positive family history observed in 35.3% patients , nevertheless , it seems this disorder is more frequently and more severe among males in xlh form .
common features are a short stature , backache , body deformities , joint pain , and fractures .
dental abnormalities include dental taurodontism with increasing mean crown - body to root ratio , ectopic permanent canines , dental abcesses[2 , 5 ] and enamel hypoplasia .
treatment of rickets with vitamin d ( vit d ) and phosphate supplements has been shown to prevent and cure the dental anomalies in some but not all patients . from 1970 ,
dental problems were reported in 23 - 67% xlhr patients[3 , 6 , 7 ] , but these problems have not been described well in previous studies .
this study was a cross sectional investigation that was conducted in a referral pediatrics endocrinology clinic in iran during 3 years ( 2008 - 2010 ) .
the diagnosis of hypophosphatemic rickets was made on the basis of clinical and radiological findings of rickets in a patient with low level of serum phosphate , normal or low level of serum calcium ( < 8.2 mg / dl ) and normal levels of 25(oh)2-vit d ( < 15 pg / ml ) , and normal or mildly elevated pth with high level of serum alkaline phosphatase ( > 55 pg / ml ) .
patients who did not have a clear diagnosis or refused to participate in the study were excluded . after taking a dental history , all subjects had a dental examination ( including dental caries , enamel hypoplasia , taurodontism , dental abscesses and gingivitis ) ; opg was performed if necessary .
clinical examination was performed to look for dental deformities by a trained dentist for all patients .
information about dental problem including : dental abscess , enamel hypoplasia , dental caries , gingivitis , taurodontism , and delay in the primary or permanent dentition was obtained . for permanent teeth , decay , missing , or filled teeth ( dmft ) index and for primary teeth , decay or filled teeth ( dft )
delay in eruption of teeth was based on times of eruption of the primary and permanent teeth from logan and kronfeld .
taurodontism was suggested if there was any change in tooth shape and was confirmed by orthopantomography ( opg ) .
in this study we enrolled 19 patients with hypophosphatemic rickets . mean age of these patients was 104.23 years ( range 3 - 17 ) .
eleven ( 57.9% ) patients were female and 8 patients ( 42.1% ) male ( female to male ratio : 2/1.3 ) . fifteen ( 79% ) patients had regular follow - up after diagnosis of background disease and 17 ( 89.5% ) patients had at least one dental problem .
the most common dental problems were dental caries and delay in eruption of the dentition in 9 ( 47.7% ) patients .
enamel hypoplasia was found in 8 ( 42.1% ) patients and 3 ( 15.8% ) patients had taurodontism and all last group were male . both dental abscesses and gingivitis were found in 2 ( 10.5% ) patients .
six ( 54.5% ) female and 3 ( 37.5% ) male patients had dental caries .
the prevalence of dental caries was significantly more frequent in case group ( p=0.04 ) that was 10.5% in healthy control matched group .
this study showed that hr has a variable age of presentation and it was more common in females[2 , 3 ] .
dental caries was the most common finding in this study ( 47.7% ) that was similar to chaussain - miller 's study .
dental caries is one of the most common factors for pulp infection , so oral hygiene has an important role for caries prevention .
dental abscesses were found in 10.5% of the patients compared to 25 - 65% in other studies[4 , 6 , 12 ] . in patients with hr
the dentition is highly susceptible to dental caries and bacteria can invade easily from the oral cavity to the dental pulp by means of structural defects in the enamel .
difference of prevalence of dental abscess may be due to early diagnostic and treatment of these patients , although shroff et al believe that prophylactic pulpotomy therapy may have been no benefit in preserving the primary dentition in xlhr patients . in our study ,
enamel hyperplasia has been reported in 16.6% patients with permanent teeth by bender and naidorf , however they said the incidence of this disorder is 36.8% ( 14/38 ) in cases reported in the literature , this is similar to our study .
although this phenomena is expectable in hr patients , no significant differences was reported in dental age compared with the respective chronological age in a study .
genetic mechanisms have a main role causing defective dentition and dentine mineralization . in this study taurodontism had a significantly increased tendency in male xlhr subjects .
similar findings were reported by seow et al . in a controlled , longitudinal study , they showed taurodontism had a significantly higher tendency in male xlhr patients . patients respond well to a combination of oral phosphate and 1,25(oh)2-vitd ( calcitriol)[4 , 6 ] .
the beneficial dental effect of phosphate supplements after birth and the possible influence of maternal phosphate homeostasis suggest that most abnormal dental features are linked to hypophosphatemia and deficient renal production of 1,25(oh)2-d .
some effects of 1,25(oh)2-d on dentin may be indirect , through an increased intestinal absorption of calcium and phosphorus .
1,25(oh)2-d may also exert some direct effect on dental cells , as odontoblasts and ameloblasts express the vitamin d receptor and respond in vitro to this vitamin .
it seems , the best results were achieved when medication started during early childhood[4 , 18 ] .
dental care of these patients should consist of periodic examination , topical fluoride application , pit and fissure sealants and maintenance of good oral hygiene .
dental caries as common as delay in dentition were the most prevalent problems in xlhr patients that could be reduced by proper dental care and good oral hygiene .
so the dentist as well as pediatrician should be made aware of the features of disorder and early intervention .

Answer:
objectivehypophosphatemic rickets is an uncommon metabolic bone disorder which affects all ages and both sexes .
 it is characterized by low concentration of serum phosphate levels , impairment of mineralization of bone matrix and teeth with variable etiology .
 dental problems in this disorder have not been described well in previous studies.methodsall hypophosphatemic rickets patients who came to a referral clinic during 2008 - 2010 enrolled in this study .
 all patients had low phosphorous and high alp , normal pth and 25-hydroxy - vitamin d and normal or low level of serum calcium .
 after diagnosis all patients were examined by a dentist for enamel hypoplasia , taurodontism , dental abscess , gingivitis , dental caries , and dentition delay.findingsnineteen patients were enrolled in this study .
 the average age of the patients was 10 ( 4.23 ) years ( range 3 - 17 ) .
 seventy - nine percent of patients had regular follow - up after diagnosis of background disease .
 dental caries and delay in the dentition were most prevalent ( each one 47.7% ) followed by enamel hypoplasia in 42.1% of the patients .
 other problems were taurodontism in 15.8% patients , dental abscess and gingivitis in 10.9%.conclusionhypophosphatemic rickets is a disease with different clinical features ; one of them is dental problem , dental caries is the most common problem .


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:
recent studies revealed that plants contain populations of small rnas ( 2025 nt ) that belong to two major classes  micrornas ( mirnas ) and endogenous short - interfering rnas ( sirnas ) .
mirna gene transcripts adopt imperfect foldback structures and are processed by dicer - like 1 ( dcl1 ) , resulting in 2022 nt mirnas .
mature mirnas function as post - transcriptional regulators that guide either site - specific cleavage or non - degradative repression of target mrnas ( 1 ) . in many cases ,
sirnas arise from endogenous transcripts that form dsrna structures , or that are substrates for rnai pathways .
processing of sirnas often requires other dcl proteins , such as dcl3 ( 11 ) .
in addition , biogenesis of several classes of endogenous sirnas requires rna - dependent rna polymerases , such as rdr2 ( 11 ) .
sirna - generating loci often yield multiple , overlapping clusters of small rnas , in contrast to mirna loci that generally yield a single mirna .
endogenous sirnas arise from repetitive sequences , transposons and retroelements , genomic regions containing inverted duplications , as well as other genic and intergenic regions .
a subset of sirnas also act to guide or assist formation of heterochromatin ( 1214 ) .
a subclass of sirnas has been shown to guide cleavage of specific target mrnas in trans , similar to mirnas .
biogenesis of trans - acting sirnas ( ta - sirnas ) requires dcl1 and rdr6 ( 15,16 ) .
in contrast to mirna genes , ta - sirna precursor transcripts do not form a foldback structure , but rather both sense and antisense small rnas are processed from perfectly complementary rna duplexes .
several small rna libraries have been constructed from arabidopsis thaliana plants with the primary goal to identify mirnas and endogenous sirnas ( 1722 ) .
the aim of the arabidopsis small rna project ( asrp ) is to analyze small rnas from different tissues and genotypes of arabidopsis , provide a public database of cloned small rna sequences and develop web - based tools to assist in analysis of small rna populations .
these resources are intended to aid the identification of mirnas and mirna genes , and to enable functional analysis of sirna - producing regions of the genome .
the collection represents small rna sequences from both in - house cloning projects and sequences deposited in the mirna registry ( 23 ) . for sequences derived in - house ,
multiple small rna libraries were constructed from arabidopsis ( columbia-0 ecotype ) at various developmental stages , including embryos , 3-day post germination seedlings , aerial tissues ( including rosette leaves and apical meristems ) and inflorescences ( stages 112 ) . to genetically enrich for mirna populations ,
libraries were constructed from rdr2 - 1 and dcl3 - 1 mutants that have defects in the chromatin sirna pathway .
. the asrp graphical user interface ( gui ) is composed of web pages delivered by an apache http server ( http://httpd.apache.org ) . in addition , the server incorporates mod_perl ( http://perl.apache.org ) and mason ( http://www.masonhq.org ) to dynamically produce web pages based upon user input .
the vast majority of the gui is generated by custom perl code that increasingly incorporates object - oriented coding practices to improve extensibility and re - usability of the individual software components .
bioperl ( 24 ) is used for specific tasks , such as parsing the genbank files containing the arabidopsis chromosomes .
the gui interacts with a custom database backend utilizing structured query language ( sql ) and the open source mysql ( http://www.mysql.com ) database engine .
table structures and specific query statements conform to standard sql language syntax and are portable to other sql database engines .
currently , the asrp database resides on a custom - configured server managed by the redhat linux as operating system .
the asrp database web interface enables users to view and analyze the small rnas in text and graphical formats .
data for each small rna is stored in mysql database tables that are easily sorted and searched . through the web interface
, users may sort and view the small rna data in the following ways :
 all small rnas .
this page displays basic information about all unique small rnas in the database , including , if applicable , the mirna or ta - sirna name , number of loci in the arabidopsis genome , number of near predicted loci in the rice genome , number of potential mrna targets and number of times isolated .
more information about a specific small rna is available by following the database number ( dbe # ) link.small rna clusters .
this page displays clusters containing a minimum of four small rna loci , with each within 500 nt of the next small rna loci . from this page
, the user can view the sequences and positions of the small rnas in each cluster in text format or the cluster can be viewed graphically in relation to the arabidopsis genome using an open access genome viewer ( 25).mirnas . all small rnas characterized as mirnas are displayed in a similar format as section ( i ) ( figure 1a ) .
the display page for each individual mirna is split into four sections ; general information , arabidopsis mirna genes , predicted and validated target genes , and oryza sativa mirna genes ( figure 1b ) .
the predicted foldback structure for the pre - mirna , the flanking sequence around the mirna gene and the graphical genome view are available through links on the arabidopsis mirna genes section ( figure 1c ) .
information about the predicted target genes , the target - mirna binding site , and the computational or experimental validity of the target - mirna binding site is displayed in the third section ( figure 1b ) .
the fourth section displays information about the small rna in o.sativa , including the predicted secondary structure of validated precursor mirnas.ta-sirnas .
general information , ta - sirna - generating locus information , and predicted target genes are displayed .
the user can view the information about the ta - sirnas in a manner similar to the mirna section of the database.annotated small rnas .
automated annotation programs such as repeatmasker ( http://ftp.genome.washington.edu/rm/repeatmasker.html ) are used to identify small rnas that originate from genomic regions of highly repetitive sequences , as well as transposons and retroelements .
the user can display and sort small rnas by the specific class of annotated repeat element such as mudr or sine .
this page displays basic information about all unique small rnas in the database , including , if applicable , the mirna or ta - sirna name , number of loci in the arabidopsis genome , number of near predicted loci in the rice genome , number of potential mrna targets and number of times isolated .
more information about a specific small rna is available by following the database number ( dbe # ) link
this page displays clusters containing a minimum of four small rna loci , with each within 500 nt of the next small rna loci . from this page
, the user can view the sequences and positions of the small rnas in each cluster in text format or the cluster can be viewed graphically in relation to the arabidopsis genome using an open access genome viewer ( 25 ) .
all small rnas characterized as mirnas are displayed in a similar format as section ( i ) ( figure 1a ) .
the display page for each individual mirna is split into four sections ; general information , arabidopsis mirna genes , predicted and validated target genes , and oryza sativa mirna genes ( figure 1b ) .
the predicted foldback structure for the pre - mirna , the flanking sequence around the mirna gene and the graphical genome view are available through links on the arabidopsis mirna genes section ( figure 1c ) .
information about the predicted target genes , the target - mirna binding site , and the computational or experimental validity of the target - mirna binding site is displayed in the third section ( figure 1b ) .
the fourth section displays information about the small rna in o.sativa , including the predicted secondary structure of validated precursor mirnas .
general information , ta - sirna - generating locus information , and predicted target genes are displayed .
the user can view the information about the ta - sirnas in a manner similar to the mirna section of the database . annotated small rnas .
automated annotation programs such as repeatmasker ( http://ftp.genome.washington.edu/rm/repeatmasker.html ) are used to identify small rnas that originate from genomic regions of highly repetitive sequences , as well as transposons and retroelements .
the user can display and sort small rnas by the specific class of annotated repeat element such as mudr or sine .
in addition to the sorting features , the web interface provides users with a variety of searching capabilities .
quick searches enable users to locate specific mirnas based on either the mirna names or the asrp database identifiers ( dbe # ) .
to search for small rnas predicted to target specific arabidopsis genes , or that originate from generic sequences , the locus identifiers ( e.g. at3g60630 ) or user - defined fasta formatted sequences are used , respectively .
finally , users can determine if a small rna sequence is represented in the asrp database by searching the sequence against the entire population of small rnas .
all small rnas in the asrp database are available through the publicly available website ( http://asrp.cgrb.oregonstate.edu ) or can be downloaded in fasta format from the website download page ( http://asrp.cgrb.oregonstate.edu/downloads/ ) .
the asrp database was created to serve as a repository and tool to facilitate the analysis of mirnas and endogenous sirnas and their targets . to increase accessibility of the database , we are working to more completely integrate the asrp database with existing arabidopsis resources , such as tair .
in addition , integration of mirnas , ta - sirnas and endogenous sirnas from the database with other research projects , such as genomic tilling microarrays and chromatin immunoprecipitation arrays ( 14,26 ) , will enhance the information acquired from these experiments and further expand our understanding of small rna function .
there are still many unanswered questions concerning mirnas , ta - sirnas and endogenous sirnas .
the regulatory roles of mirna - target gene interaction , the regulation of mirna gene expression , and the function of sirnas in the regulation of chromatin structure and gene silencing are just a few questions currently being studied .
future plans include the integration of data from genome - scale microarray projects into the asrp database ( 27 ) .
the scope of the database may widen with the addition of other plant genomes , libraries or computational analysis .
the inclusion of additional plant genomes will enable a more in - depth study of mirna evolution and conservation and activities of endogenous sirnas .
we thank christopher m. sullivan for developing the infrastructure for the computing cluster and compiling the software technologies used for the database and heather fitzgerald for critical reading of the manuscript .
the arabidopsis small rna project database is supported by a 2010 project grant from the national science foundation ( mcb-0209836 ) .

Answer:
eukaryotes produce functionally diverse classes of small rnas ( 2025 nt ) .
 these include micrornas ( mirnas ) , which act as regulatory factors during growth and development , and short - interfering rnas ( sirnas ) , which function in several epigenetic and post - transcriptional silencing systems . the arabidopsis small rna project ( asrp ) seeks to characterize and functionally analyze the major classes of endogenous small rnas in plants .
 the asrp database provides a repository for sequences of small rnas cloned from various arabidopsis genotypes and tissues .
 version 3.0 of the database contains 1920 unique sequences , with tools to assist in mirna and sirna identification and analysis .
 the comprehensive database is publicly available through a web interface at http://asrp.cgrb.oregonstate.edu .


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 prevalence of child obesity is increasing rapidly worldwide . based on the data of the world health organization ( who ) , over 30% of the people in the middle east are overweight .
a review of some studies from iran reveals that the prevalence of obesity among iranian children has been doubled between 1993 and 1999 , which could be attributed to the changes in lifestyle.1
 ,
 3
 ,
 4 obesity in adults is not easy to treat and is often correlated with obesity during childhood .

 in the last decade ,
consumption of soft drinks and fast foods together with less activity and exercise contributed to the increasing number of overweight people worldwide . along with increasing caries risk ,
increased consumption of sugar - sweetened beverages and snack foods also has been linked to obesity .
health risks associated with childhood overweight and obesity are strong indicators for predisposition to adult morbidity and mortality and include type 2 diabetes , cardiovascular disease , fatty liver disease , early maturation , endometrial , colon , breast and other cancers , psychological stress , as well as orthopedic problems , general poor health , and hepatic problems.7
 -
 10 an iranian study detected a high prevalence of cardiovascular risk factors in overweight and obese children aged 7 - 12 years .

obesity is also related to several aspects of oral health , such as caries , periodontitis and xerostomia .
fruit drinks and other sweetened beverages represent high sugar sources , which may contribute to cariogenic potential .
oral health is strongly influenced by the daily intake of food and can also play a significant role in nutritional intake and general status of health , particularly in the elderly . who recommends limiting added sugars to 10% of total calories on the grounds that added sugars contributed to overall caloric density of the diet .
a study in scotland showed that among 165 children aged 3 - 11 years , whom with the worst decay were significantly thinner also severe dental decay was associated with underweight .
one brazilian study concluded that there was no statistically significant association between dental caries and obesity in adolescents aged 12 to 15 years .

 among children and teenagers aged 2 - 20 years , body fat amount changes as the body grows and is different for boys and girls .
unlike body mass index ( bmi ) assessments for adults , assessments for children and teenagers take these growth and gender specific differences into account .
these child - specific bmi values are referred to as  bmi - for - age .
categories describing amount of body fat for children and teenagers is also different from the categories describing amount of body fat in adults . among adults ,
bmi categories include  underweight ,   normal ,   overweight ,  and  obese .
 among children and teenagers , bmi - for - age categories include  underweight ,
since the frequent consumption of high caloric and cariogenic substances are two of the many factors associated with caries and obesity , and to the best of our knowledge there are no studies that have investigated the association between bmi - for - age and dental caries in iran to date , the purpose of this study was to determine whether bmi - for - age , might be associated with dental caries in children in isfahan , iran .

 this cross - sectional study was conducted from june to august 2007 in isfahan , iran . using a random cluster sampling , a total of 1003 pupils aged 6 - 11 years from six private and state elementary schools with different social backgrounds
the children thoroughly chewed one disclosing tablet ( svenska dentorama ab , stockholm , sweden ) and rinsed their mouth with water , according to the manufacturer s instructions .
the children who had 70% or fewer teeth surfaces with plaque were invited for further evaluations .
the sample size was estimated allowing for caries prevalence of 60% , and significance level of 0.05 .
all of the children participated in the clinical examination were iranians and permanent residents of the city .
body weight was recorded to the nearest 100-gram using a standard beam balance scale with the subject barefoot and wearing light dresses .
the balance was calibrated at the beginning of each working day and at frequent intervals throughout the day .
body height was recorded to the nearest 0.5 cm according to the following protocol : no shoes , heels together and head touching the ruler with line of sight aligned horizontally . to avoid subjective errors ,
bmi - for - age percentiles , representing eating habits in children and teenagers , were used .
bmi - for - age [ ( weight in kilograms ) / ( height in meters) ] percentiles are dependent on gender and age - specific weight for height curves for those aged 2 - 20 years . according to these curves ,
 underweight  is defined as bmi - for - age < 5th percentile ,
normal  is defined as 5th percentile < bmi - for age < 85th percentile ,  at risk of overweight  is defined as 85th percentile < bmi - for - age < 95th percentile , and
overweight  is defined as bmi - for - age > 95th percentile . since the number of samples in underweight group was insufficient ( three samples ) , this group was excluded from the study .
the remaining 633 children ( 317 boys and 316 girls ) enrolled in the study .

all selected children were clinically examined for dental caries by a specialist utilizing the who criteria for diagnosis of dental caries .
the examination was carried out using a cycle and cow horn two - headed dental explorer ( aesculap ag , tuttlingen , germany ) , a plane mouth mirror ( aesculap ag ) and cotton rolls to remove any plaque or debris where necessary , and recorded on special charts .
teeth were considered as decayed when in addition to showing clinical signs such as a color change , wedging and catching of an explorer tip during the examination of occlusal surface encountered some degree of resistance .
, a surface is diagnosed as decayed if the explorer is retained . dressed and restored teeth that had recurrent caries
teeth filled with temporary materials were considered as filled , and not as decayed ; no radiographs were taken .
missing teeth were not marked correspondingly , since no definite statement could be made without a proper anamnesis whether the tooth really existed , or if an early extraction had taken place . to assess the caries frequency
the dft index for the permanent dentition and the dft index for primary dentition were used , since it gives a good insight into the state of decay in the patient .
if both the deciduous and permanent teeth were present , only the permanent teeth were evaluated .

t - test was used to analyze the mean decayed and filled permanent / primary teeth ( dft / dft ) and the difference between groups , chi square test for evaluation of association between bmi - for - age and gender , and multiple linear regression for evaluation of association between bmi - for - age and dft / dft indices .
the authors certify that all applicable institutional and governmental regulations concerning the ethical use of human volunteers were followed during this research .

 the findings showed that 16% of the children were within normal weight range , 16.9% at risk of overweight , and 67.1% overweight .
there was no statistically significant association between bmi - for - age and gender ( p = 0.2 ) ( table 1 ) .
the mean  se of dft in the normal weight , at risk of overweight and overweight groups were 0.34  0.08 , 1.23  0.13 and 0.73  0.05 , respectively ; and mean  se of dft were 2.01  0.19 , 2.76  0.18 and 2.59  0.13 , respectively .
multiple linear regression showed that there was no statistically significant association between bmi - for - age and dft ( r = 0.06 ; ci : 0.01 to 0.09 ) , and bmi - for - age and dft ( r=0.07 ; ci : 0.003 to 0.046 ) .

 by taking the bmi - for - age into account , 27.7% of the children with normal weight were caries free , whereas only 14% of children at risk of overweight and 37.2% of the overweight children were caries free .
there was statistically significant association between bmi - for - age and being caries free ( p = 0.0001 ) .

 given the causative relation between refined carbohydrates and dental caries , it is appropriate to hypothesize that overweight might also be a marker for dental caries in children and teenagers .
although bmi is widely used to screen adults for obesity , its use in adolescents is controversial .
bmi is a commonly used measure of adiposity , because it is easy to calculate , quick to measure , and noninvasive .
unfortunately , it is a fairly poor index in children unless age and gender are taken into consideration .
therefore , bmi - for - age categories were used in this study which might produce controversial results compared to the other studies .
results of the present study showed the high prevalence of overweight and at risk of overweight in the 6 - 11-year - old children in isfahan .
a study showed that prevalence of overweight was 20.8% in 3 - 9 year - old children according to bmi .

palmer implicated that the relationship between obesity and caries in children needs further exploration ; it is clear that there are common denominators that both diseases share .
negative changes in eating and activity patterns , increased frequency of snacking and increased consumption of fermentable carbohydrates are common in both obesity and caries in children .

the mean dft / dft indices in the normal weight children were less than children at risk of overweight and the overweight .
although it was hypothesized that bmi - for - age would be associated with increased dental caries prevalence , there was no association between bmi - for - age and dft / dft indices ( r  0.07 ) .
the relationship between nutrition and dental caries is complex because it is a multifactorial disease ; oral hygiene , available nutrients , saliva , and oral flora influence dental caries .
chen et al investigated bmi index and dft score in three - year - old children .
they concluded that there were no significant differences in the dft score of carious children among different bmi groups and there is no relationship between carious deciduous teeth and weight status .
kantovitz et al in a systematic review on the relationship between obesity in childhood found that only one study with high level of evidence showed direct association between obesity and dental caries .
macek & mitola concluded that there is no statistically significant association between bmi - for - age and dental caries prevalence for children in either dentition and overweight children with a positive history of dental caries in the permanent dentition exhibit fewer dmft than do their normal weight peers .
the authors found that overweight children aged 6 - 17 years had a significantly lower dental caries severity than did children of normal bmi - for - age .

hilgers et al found that the mean caries average for permanent molars significantly increased with increased bmi , even after adjusting for age and gender .
they concluded that elevated bmi is associated with an increased incidence of permanent molar interproximal caries .
burt & pai reported that children of low birth weight subsequently developed more caries in the primary dentition than did children with normal to high birth weight .
they concluded that this may be related to social deprivation factors during the development of the primary dentition .
willerhausen et al indicated a strong association of obesity and caries in 1290 children of elementary schools in a city in germany .
another study found that there was a significant correlation between the bmi and caries frequency even after adjustment for the age of the children .
one finnish study followed 516 children from birth to age 12 and used weight to predict caries experience ( dmft / dmft ) .
the investigators reported that obesity alone was not a very good predictor of dental decay .

the present study demonstrated a significant association between bmi - for - age and being caries free ( p = 0.0001 ) .
this is in line with the results of the study of willerhausen et al that showed number of healthy teeth decreased with age and bmi.a swedish study examined the relationship between dental caries and risk factors for atherosclerosis and reported that children with a dmft score greater than 9 had significantly higher bmi - for - age values than caries - free children .

glick noted that , while the consequences of obesity will have an indirect effect on oral conditions , this alone is not justification to get involved .
rather , there needs to be a stronger desire to have an impact on the patients general health .
these findings might also show that further investigation should be conducted to determine if an association exists between dental caries and bmi - for - age and to address what factors specific to overweight in children might be protective against dental caries especially in permanent dentition .
the future preventive programs must include strategies for nutrition control to avoid obesity as well as dental caries .

 there is a high prevalence of at risk of overweight and overweight in 6 - 11-year - old children in isfahan . at risk of overweight and overweight children
had higher dft / dft score than did normal children , but there was no association between bmi - for - age and dft / dft indices .

Answer:
background and aims
 childhood obesity has been associated with high refined sugar intake .
 the relationship between sucrose intake and development of dental caries has been established .
 the aim of this study was to determine the association between age - specific body mass index ( bmi - for - age ) and dental caries in children .

 materials and methods
 in this cross - sectional study a total of 1003 children were screened .
 weight , height , bmi - for - age and dental caries of 633 ( 317 boys , 316 girls ) 6 - 11-year - old children were clinically examined for dental caries using the world health organization criteria by a dentist on a dental chair .
 decayed and filled teeth ( dft / dft ) indices were used .
 bmi - for - age and dental caries were analyzed with multiple linear regression , chi - square , and t - tests using spss computer software .

 results
 the findings showed that 16% of the children had a normal weight , 16.9% were at risk of overweight , and 67.1% were overweight . in the normal weight , at risk of overweight , and overweight groups , the mean  se for dft were 0.34  0.08 , 1.23  0.13 and 0.73  0.05 , respectively ; and 2.01  0.19 , 2.76  0.18 and 2.59  0.13 respectively , for dft .
 multiple linear regression showed that there was no statistically significant association between bmi - for - age and dft ( r = 0.06 ) and dft ( r = 0.07 ) indices .
 27.7% , 14% and 37.2% of children with normal weight , at risk of overweight and with overweight were caries free , respectively .
 there was statistically significant association between bmi - for - age and being caries free ( p = 0.0001 ) .

 conclusion there was no association between bmi - for - age and dft / dft indices .
 in addition , a high prevalence of at risk of overweight and overweight was seen among 6 - 11-year - old children in isafahan , iran .


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:
culicoides spp . latreille ( diptera : ceratopogonidae ) or biting midges are small ( 0.5 - 2.0 mm in length ) bloodsucking insects that have a broad distribution and impact on human and veterinary health as vectors of viruses ( bluetongue , african horse sickness , epizootic hemorrhagic disease of deer , akabane , aino , chuzan , and bovine ephemeral fever viruses ) , protozoan parasites ( haemoproteus and leucocytozoon spp . ) , and filarial worms ( onchocerca and dipetalonema spp . ) throughout their range [ 1 - 15 ] .
the first nationwide biting midge surveys in the republic of korea ( rok ) were reported in 1974 , with seasonal abundance and host blood meal analysis of culicoides spp . collected from cattle and poultry farms in gyeonggi - do ( province )
more recently , a brief summary of the history of research into the culicoides fauna and seasonal prevalence of culicoides spp . collected at 9 cowsheds in the southern part of the rok were reported by kim et al .   along with new records of 3 culicoides spp .
( c. nasuensis kitaoka , c. pallidulus yu , and c. jacobsoni macfie ) , bringing the total number of culicoides spp .
vector - borne disease surveillance is conducted by the 65th medical brigade in collaboration with the public health command region - pacific ( phcr - pac ) to determine the species composition and seasonal and geographical distributions for mosquitoes and other biting flies , e.g. , culicoides spp . , and pathogens they harbor using mosquito magnet traps in / near the demilitarized zone ( dmz ) that separates north and south korea in northern gyeonggi - do , rok .
, lititz , pennsylvania , usa ) use counter - flow technology and propane gas to produce heat and co2 as attractants to capture mosquitoes and other biting flies , such as culicoides .
collections were made at 4 sites , including the neutral nations supervisory commission ( nnsc ) camp ( 37 57 ' 16.39 " n , 26 40 ' 50.03 " e ) , daeseongdong village ( 37 56 ' 26.92 " n , 126 40 ' 37.42 " e ) inside the 2-km wide demilitarized zone ( dmz ) and adjacent to the military demarcation line ( mdl ) that separates north and south korea and at warrior base , a us army training site ( 37 55 ' 17.01 " n , 126 44 ' 30.22 " e ) , and a beef farm at tongilchon ( 37 54 ' 32.18 " n , 126 44 ' 01.88 " e ) located north of the imjin river and approximately 3 km from the dmz , gyeonggi - do , rok , from may - october 2010 - 2012 ( fig .
daeseongdong is a village of approximately 200 residents that is under the protection of south korea and is approximately 100 - 200 m from the mdl .
rice farming is the principal activity , with an enclosed ( not pastured ) beef farm of < 50 cattle .
the mosquito magnet was placed at the northern most edge of daeseongdong and approximately 100 m north of the beef farm .
warrior base is a us military training site approximately 3 km south of the dmz .
tongilchon is a small village of approximately 200 residents with 2 enclosed ( not pastured ) beef farms of approximately 50 cattle each .
it is located approximately 2 km west of warrior base and 3 km from the dmz .
the mosquito magnet was placed outside one of the beef farms adjacent to a rice paddy and dry land vegetable farming .
mosquito magnet traps were operated continuously , with specimens collected twice weekly from may - october in 2010 - 2012 .
specimens were transported to the 5th medical detachment , us army garrison , yongsan , seoul , rok , where mosquitoes and other biting flies were separated .
specimens of culicoides were transferred into 70% ethanol and identified using the keys of arnaud   and the checklist of bellis et al . .
voucher specimens were submitted to the northern territory quarantine insect collection ( ntqic ) in darwin , northern territory , australia , for future reference and genetic studies .
a total of 18,677 culicoides females ( 18,399 ; 98.7% ) and males ( 248 ; 1.3% ) comprising 16 species were collected from may - october over a 3-year period from 2010 - 2012 .
culicoides nipponensis tokunaga was the most commonly collected species ( 42.9% ) , followed by culicoides erairai kono and takahasi ( 29.2% ) , culicoides punctatus ( meigen ) ( 20.3% ) , culicoides arakawae ( arakawa ) ( 3.3% ) , c. pallidulus ( 1.8% ) , and culicoides circumscriptus kieffer ( 1.4% ) , while the remaining 10 species accounted for only 1.1% of all culicoides spp .
collected ( table 1 ) . c. nipponensis was the most frequently collected species ( females and males ) at daeseongdong village ( 67.1% ) , and was commonly collected from the nnsc camp ( 35.6% ) , tongilchon ( 33.9% ) , and warrior base ( 19.5% ) . c. erairai was the
most frequently collected species at nnsc camp ( 53.6% ) and accounted for 85.1% of c. erairai collected at all 4 sites ( table 1 ) , while c. punctatus was the most frequently collected species at both tongilchon ( 54.4% ) and warrior base ( 28.7% ) . c. nipponensis females demonstrated bimodal capture rates , with large numbers collected during may ( 1,754 , 82.4% ) , june ( 1,479 , 29.5% ) , and then again during september ( 3,332 , 81.7% ) ( table 2 ) .
c. erairai was more frequently collected during june ( 2,962 , 59.2% ) and july ( 2,154 , 76.0% ) followed by a sharp decline in numbers collected from august - october . c. punctatus was collected infrequently from may - september ( range , 84 - 372 ) with large numbers only collected during october ( 2,756 , 88.0% ) .
overall , low numbers of c. nipponensis were collected during 2011 , while higher numbers were observed during may - june and again during september 2012 at the nnsc camp and daeseongdong ( fig .
2 ) . c. erairai was collected more frequently at the nnsc camp during the months of june - july 2011 and 2012 , with few collected from august - october for either year .
low numbers of c. punctatus were collected from may - september , with a sharp increases in numbers observed primarily at the beef farm at tongilchon during october for both 2011 and 2012 .
this is the first report for collections of culicoides using mosquito magnet traps that use only heat and co2 as attractants .
the addition of other chemical attractants , e.g. , octenol , has been shown to repel some species of culicine mosquitoes , while enhancing the collection of others , but the relative attractiveness of this attractant has not been investigated for most species of culicoides .
a major difference between mosquito magnet and light traps is that mosquito magnet traps operate continuously without bias toward nocturnal and diurnal active species .
this difference , however , indicates that comparative analysis between data obtained from mosquito magnet and light traps should be viewed with caution .
biting midges are both nuisance biters and vectors of medical and veterinary important pathogens that impact the economy of the animal industry in the rok . c. nipponensis , and c. punctatus were the most commonly collected species by mosquito magnets during this study and
have been associated with the transmission of important livestock pathogens , e. g. , fukuoka , aino , and ibaraki viruses , or as biting pests of humans ( c. erairai ) .
consequently , surveillance of these and other species of culicoides and associated pathogens are an important part of the veterinary health service to identify relative vector populations , their distributions throughout the rok , and the presence and prevalence of pathogens affecting livestock and poultry .
the dominance of c. nipponensis and c. punctatus in the mosquito magnet collections is similar to findings by cho and chong   and kang and yu   using new jersey light traps . similarly , lee   found that c. punctatus , c. arakawae , and c. tainanus kieffer were the most commonly collected species at inland sites , whereas c. nipponensis and c. sinanoensis tokunaga were the predominant species collected from the south and eastern coastal areas in the rok .
recently kim et al .   found that c. punctatus and c. arakawae were the dominant species collected from light traps set in 9 cowsheds in the southern part of the rok .
the unprecedented predominance of c. erairai and relatively low numbers of c. arakawae in the mosquito magnet traps compared to these and other previous reports   may reflect the relative attraction of these species to light and the attractants associated with the mosquito magnet traps .
the dominance of c. nipponensis and c. punctatus at a cowshed at tongilchon agrees with the host preference of these species for cattle .
although c. arakawae appears to have a preference for feeding on birds , it also readily feeds on cattle , which would explain its abundance around cowsheds in other reports but not the low numbers collected at the cowshed at tongilchon in this survey .
the variable distribution of culicoides spp . over a limited area ( 2 km radius ) demonstrates the focal species abundance due to little understood environmental and host attraction factors .
for example , high numbers of c. erairai were observed at the nnsc camp where humans are believed to be the primary host , while c. nipponensis was the primary species collected at daeseongdong and tongilchon where a variety of hosts ( e.g. , cattle , dogs , large water birds , and humans ) serve as potential hosts .
thus , further studies comparing light and mosquito magnet traps and range of available hosts may reveal differential attraction for different species and assist in surveys targeting particular species .
additionally , studies on the geographical and seasonal distributions , host attraction ( e.g. , placement of traps near human habitation and poultry , cattle , and swine farms ) , temporal biting activity , pathogen infection rates , and their role as potential vectors of zoonotic pathogens that impact on human and animal health are warranted .
although limited , the data presented herein provide a better understanding of the biology , ecology , and environmental parameters that affect relative population abundance of culicoides spp .
that can be used to predict potential human and animal health risks and develop and implement mitigation strategies .

Answer:
biting midges ( culicoides : ceratopogonidae ) were collected by mosquito magnet traps at the neutral nations supervisory commission ( nnsc ) camp and daeseongdong village inside the demilitarized zone ( dmz ) and near the military demarcation line ( mdl ) separating north and south korea and at warrior base ( us army training site ) and tongilchon 3 km south of the dmz in northern gyeonggi province , republic of korea ( rok ) , from may - october 2010 - 2012 , to determine their seasonal distributions .
 a total of 18,647 culicoides females ( 18,399 ; 98.7% ) and males ( 248 ; 1.3% ) comprising 16 species were collected .
 overall , the most commonly collected species was culicoides nipponensis ( 42.9% ) , followed by c. erairai ( 29.2% ) , c. punctatus ( 20.3% ) , c. arakawae ( 3.3% ) , c. pallidulus ( 1.8% ) , and c. circumscriptus ( 1.4% ) , while the remaining 10 species accounted for only 1.1% of all culicoides spp .
 collected .
 the seasonal distribution of c. nipponensis was bimodal , with high numbers collected during may - june and again during september .
 c. erairai was more frequently collected during june - july , followed by sharply decreased populations from august - october . c. punctatus was collected in low numbers from may - september with high numbers collected during october . c. erairai was predominantly collected from the nnsc camp ( 85.1% of all c. erairai collected ) located adjacent to the mdl at panmunjeom in the northernmost part of gyeonggi - do ( province ) , while other sites yielded low numbers of specimens .


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 - glucose cotransporter 2 ( sglt2 ) inhibitors are oral hypoglycemic agents that augment the urinary excretion of glucose , thereby regulating glycemic control and promoting weight loss ( 1 ) .
sglt2 inhibitors have an insulin - independent mechanism of action , which is being explored in patients with type 1 diabetes ( 2 ) .
the incidence of diabetic ketoacidosis in patients treated with sglt2 inhibitors is rare ( 4,5 ) .
recently , the us food and drug administration issued a drug safety communication that sglt2 inhibitors may lead to ketoacidosis with mild to moderate glucose elevation ( euglycemic diabetic ketoacidosis ) ( 6 ) .
however , only a few cases of euglycemic diabetic ketoacidosis with persistent diuresis after the discontinuation of sglt2 inhibitors have been reported .
we herein report a case of euglycemic diabetic ketoacidosis with persistent diuresis in a diabetic patient undergoing treatment with an sglt2 inhibitor , canagliflozin .
a 27-year - old woman of asian descent from north america was admitted to our hospital for the treatment of euglycemic diabetic ketoacidosis .
she had been taking oral antidiabetic drugs ( gliclazide 300 mg , metformin 3,000 mg , and sitagliptin 150 mg per day ) , but her glycemic control was poor .
three months prior to admission , she started taking canagliflozin ( 300 mg / day ) . during that time , she lost 3 kg and her urinary frequency increased .
two days before admission , she experienced dizziness , and the following day , she developed upper abdominal pain .
on the day of admission , she visited the emergency department with complaints of thirst and malaise .
she did not smoke or drink alcohol , and she followed carbohydrate restriction for weight loss . on examination ,
the patient 's blood pressure was 145/103 mmhg , her heart rate was 123 beats / min , and her temperature was 36.2. her weight , height , and body mass index were 63 kg , 150 cm , and 28 kg / m , respectively .
the other neurological and general examination results were normal . a urinalysis detected ketone bodies , while an arterial blood gas analysis showed high anion gap metabolic acidosis and a normal lactate level .
her biochemistry results revealed electrolyte disturbance and mild hyperglycemia ( 240 mg / dl ) .
in addition , her hba1c level was 9.9% , and her fasting serum c - peptide level was < 0.1 ng / ml ( reference range , 0.61 - 2.09 ng / ml ) ; this finding indicated the severe impairment of insulin secretion .
taken together , these findings were compatible with a diagnosis of type 1 diabetes mellitus and diabetic ketoacidosis without hyperglycemia .
cpr : c - peptide immunoreactivity , gad : glutamic acid decarboxylase , hba1c : glycated hemoglobin , pco2 : partial pressure of carbon dioxide , po2 : partial pressure of oxygen
  the patient was initially administered isotonic saline and a continuous insulin infusion with the discontinuation of all oral antidiabetic agents .
an hour after the administration of saline and the insulin infusion , her glucose level decreased to < 200 mg / dl ; thus , an infusion 5% dextrose was initiated . on the following day ,
her venous blood ph level still showed acidemia , despite a normal glucose level , and her urine output was > 5,000 ml / day .
, oral food intake was initiated and the continuous insulin infusion was switched to multiple daily injections of insulin . at this point ,
however , we prohibited ad libitum water intake . on day 4 of treatment , her venous blood ph level recovered , and her urinary output peaked ( figure ) . we could not measure the urinary output after the fifth day of treatment due to the discontinuation of urinary catheterization and the patient 's menstruation . on the eighth day of treatment , she was discharged but the nocturnal urination had not resolved .
the course of osmotic diuresis in a patient with euglycemic diabetic ketoacidosis who was treated with canagliflozin . on the second day of treatment
, the patient s urine output increased to over 5,000 ml in the absence of hyperglycemia . on the third day of treatment , oral food intake
was initiated , and the patient s urine output increased to over 9,000 ml . at this point ,
cvii : continuous intravenous insulin infusion , egfr : estimated glomerular filtration rate , fpg : fasting plasma glucose , mdi : multiple daily injections of insulin , na : not available , u - glucose : urinary glucose , u - osm : urine osmolality , serum na : serum sodium , u - na : urinary sodium
second , euglycemic diabetic ketoacidosis can accompany persistent diuresis after the administration of sglt2 inhibitors is discontinued . to our knowledge , this is the first report of euglycemic diabetic ketoacidosis with persistent diuresis during treatment with an sglt2 inhibitor .
euglycemic diabetic ketoacidosis is defined as a blood glucose level of < 300 mg / dl , and a plasma bicarbonate level 10 meq / l ( 7 ) . in a previous study of patients with type 2 diabetes ,
the incidence of diabetic ketoacidosis in patients treated with canagliflozin was more than twice as high as that in patients treated with antidiabetic drugs without canagliflozin ( 8) .
only a few case reports have described the characteristics of euglycemic diabetic ketoacidosis due to the administration of sglt2 inhibitors .
the possible causative factors for euglycemic diabetic ketoacidosis due to the administration of sglt2 inhibitors include an insulin dose reduction , alcohol intake , and a low insulin secretion capability .
gastroparesis and a low - carbohydrate diet also can trigger euglycemic diabetic ketoacidosis , especially among diabetic patients who do not use insulin ( 9 - 12 ) .
the time from the first dose of an sglt2 inhibitor to the onset of euglycemic diabetic ketoacidosis has been reported to range from 2 to 13 days in diabetic patients who do not use insulin ( 9,11,12 ) . in the present case ,
there are several possible reasons for the patient 's development of euglycemic diabetic ketoacidosis , including her low adherence to treatment , the relatively acute autoimmune destruction of  cells , and her extreme carbohydrate restriction .
this patient experienced euglycemic diabetic ketoacidosis with persistent diuresis via glycosuria , even after the discontinuation of the sglt2 inhibitor .
the possible mechanisms of this pathology are as follows : ( 1 ) her estimated glomerular filtration rate might have been increasing in association with early type 1 diabetes , thereby promoting glycosuria ; ( 2 ) exogenous insulin may have augmented the effect of sglt2 inhibition on glycosuria ( 13 ) ; and ( 3 ) canagliflozin delays the reversibility of sglt2 inhibition in comparison to its short half - life ( 10 - 13 hours ) . in a previous case ,
burr et al . reported that their patient had persistent glycosuria in the absence of hyperglycemia for 11 days after the discontinuation of an sglt2 inhibitor ( 11 ) .
the correction of hypovolemia is important for the treatment of diabetic ketoacidosis ( 3 ) . in the present case ,
the patient received 3,650 ml of fluid in 12 hours of fluid therapy , which was reasonable from the point of view of treating diabetic ketoacidosis .
after the second day of admission , fluid therapy was administered according to her urine volume .
thus , the volume of fluid that the patient received was appropriate for her clinical course . however , we did not rule out central diabetes insipidus .
previous studies have reported cases of central diabetes insipidus during diabetic ketoacidosis ( 14,15 ) . in our case ,
thus , it remains unclear whether canagliflozin induced the patient 's osmotic diuresis or masked central diabetes insipidus .
the insulin - independent actions of sglt2 inhibitors are associated with short - term tolerability and the enhancement of urinary glucose excretion in patients with type 1 diabetes ( 2 ) . on the other hand
, off - label use of sglt2 inhibitors in patients with type 1 diabetes sometimes leads to euglycemic diabetic ketoacidosis ( 6,9 ) .
in addition , sglt2 inhibitor - treated type 2 diabetes patients who develop euglycemic diabetic ketoacidosis are often misdiagnosed as having autoimmune diabetes ( 8) . the possible pathophysiologic characteristics of euglycemic diabetic ketoacidosis due to sglt2 inhibitors are as follows : ( 1 ) the urinary glucose excretion of patients with euglycemic diabetic ketoacidosis due to the administration of sglt2 inhibitors is more prominent than that in patients with diabetic ketoacidosis ( 13 ) ; ( 2 ) sglt2 inhibitors inhibit the transportation of glucose into  cells , thereby enhancing the release of glucagon , resulting in ketogenesis ; and ( 3 ) sglt2 inhibitors may augment the renal tubular reabsorption of ketone bodies ( 1 ) . in the present case ,
the patient 's intake of canagliflozin , the restriction of carbohydrates , and low insulin secretion capability led to euglycemic diabetic ketoacidosis .
clinicians should therefore be cautious when prescribing sglt2 inhibitors to diabetic patients who restrict their intake of carbohydrates or who display insufficient insulin secretion . in conclusion , the diuresis of the present patient with euglycemic diabetic ketoacidosis persisted , even after the administration of the sglt2 inhibitor was discontinued .
the findings of this case emphasize that euglycemic diabetic ketoacidosis should be considered in sglt2 inhibitor - treated patients who develop nausea or fatigue .
furthermore , adequate hydration may enhance persistent diuresis via glycosuria in patients with euglycemic diabetic ketoacidosis who are treated with sglt2 inhibitors .

Answer:
diabetic ketoacidosis is characterized by hyperglycemia , anion - gap acidosis , and increased plasma ketones . after the resolution of hyperglycemia ,
 persistent diuresis is rare .
 we herein report the case of a 27-year - old asian woman with type 2 diabetes who was treated with a sodium - glucose cotransporter 2 ( sglt2 ) inhibitor ( canagliflozin ) who developed euglycemic diabetic ketoacidosis and persistent diuresis in the absence of hyperglycemia .
 physicians should consider euglycemic diabetic ketoacidosis in the differential diagnosis of patients treated with sglt2 inhibitors .


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:
on february 13 , 1996 , a 7-year - old boy from doihue in administrative region vi was admitted to the hospital clnico fusat of rancagua in the region ( figure 1 ) with a 2-day history of adynamia and dizziness . on admission ,
, progressive paralysis developed that evolved to respiratory failure ; the boy was connected to a mechanical ventilator .
cat scan showed diffuse cerebral edema , and the electroencephalogram indicated no electric activity . intracranial hypertension developed , and the patient
map of south america showing the geographic position of chile and map of chile presenting the geographic distribution of the administrative regions of the country .
a virus was considered the most probable cause , laboratory tests were conducted to determine the presence of the following viruses : herpes , measles , coxsackie , echo , and polio .
interviews with relatives and the boy s nanny revealed that bats had been observed in the family s house .
the nanny also reported that she had seen a bat flying away from the child s toy box . even though these interviews failed to reveal any direct contact with bats or any history of an animal bite , this epidemiologic information prompted the physicians to suspect rabies . on february 26 , 1996
, a serum sample and corneal smear were obtained from the patient and sent to the rabies laboratory of the instituto de salud pblica de santiago ( isp ) .
a rabies antibody titer of 1:625 was found in the serum specimen by using the indirect fluorescent - antibody ( ifa ) technique ( 14 ) .
the patient had no history of rabies vaccination to account for the presence of antibodies .
the corneal smear was negative for rabies antigen by the direct fluorescent - antibody ( dfa ) assay ( 15 ) . on march 4 , a second serum sample ,
the second serum sample was tested simultaneously with the first one by ifa assay , and a titer of 1:15,625 was detected .
the saliva sample was negative by dfa assay and suckling mouse inoculation ( 15,16 ) .
the patient died on march 5 , 1996 , when artificial respiratory support was disconnected .
postmortem tissue samples of cerebral cortex , hippocampus , cerebellum , and nuchal skin biopsy were sent to the isp rabies laboratory for diagnosis .
rabies postexposure prophylaxis with the suckling mouse brain fuenzalida - palacios vaccine was administered to the victim s mother and to 10 health - care providers who had possible contact with the patient s saliva .
the rabies postexposure prophylaxis schedule used was 2 ml of vaccine , subcutaneously , on each of days 1 , 2 , 3 , 4 , 5 , 6 , 21 , and 90 .
blood samples were taken from vaccinees on day 14 after the initial dose of vaccine ; ifa assay showed that adequate immune responses had developed .
the virus was isolated from the patient s brain tissue by intracerebral inoculation of suckling mice ( 16 ) . to help identify the possible source of infection , the virus was antigenically and genetically characterized .
antigenic characterization of the virus was carried out by using a panel of eight monoclonal antibodies directed against the viral nucleoprotein , provided by the centers for disease control and prevention .
these analyses identified a rabies antigenic variant associated with tadarida brasiliensis ( free - tailed bat ) in chile , which had been designated as antigenic variant 4 ( agv4 ) ( 9,17 ) .
genetic characterization was done by sequencing a 320-bp portion of the rabies virus nucleoprotein gene from nucleotide position 1,157 to 1,476 , as compared with the sadb 19 strain ( 18,19 ) .
briefly , genomic viral rna was extracted from infected tissue by using trizol ( invitrogen , san diego , ca , formerly gibco - brl inc . ) according to the manufacturer s instructions .
complementary dna was produced by a reverse transcription polymerase chain reaction with primers 10 g and 304 ( 19 ) and was sequenced by using the taq big dye termination cycle sequencing ready reaction kit ( applied biosystems , foster city , ca ) , according to the manufacturer s protocol , on an applied biosystems 377 dna automated sequencer ( applied biosystems ) .
this human rabies virus isolate was compared with viruses obtained from domestic animals and insectivorous bats in urban centers in chile from 1977 to 1998 ( 18 ) .
pileup and pretty programs of the wisconsin package , version 10 ( genetic computer group , 2000 , madison , wi ) , were used to produce sequence alignments and comparative nucleotide analyses .
the programs dnadist ( kimura - two parameter ) , neighbor ( neighbor - joining method ) , and dnapars ( parsimony method ) from the phylip package , version 3.5 ( 20 ) , were used in the phylogenetic studies .
the bootstrap method , as implemented by the seqboot program from phylip , was followed by the use of dnadist and neighbor for the distance matrix analyses .
although five genetic variants of rabies virus are found in chile ( 18 ) ( figure 2 , groups a to e ) , a reservoir has been identified for only two : t. brasiliensis ( figure 2 , group d ) and lasiurus sp .
phylogenetic analyses of the chilean human isolate demonstrated that it segregated in group d. this group represents the genetic variant of rabies virus most frequently isolated throughout the country , formed by viruses from the metropolitan region and regions iv , v , vi , vii , viii , ix , and x ( figure 1 ) .
the high bootstrap value that supports the inclusion of this virus in group d and the very close genetic relationship it has with the other members of this group ( average genetic distance 0.5% ) clearly show that t. brasiliensis is the likely reservoir of the rabies virus isolated in this case .
neighbor - joining tree comparing the human rabies isolate with representatives of the rabies genetic variants obtained from insectivorous bats and domestic animals in chile ( 18 ) .
bootstrap values obtained from 100 resamplings of the data by using distance matrix ( top ) and parsimony methods ( bottom ) are shown at nodes corresponding to the lineages representing the rabies virus variants ( a , b , c , d , and e ) currently circulating in chile . only bootstrap values
duvenhage virus , genbank accession number , european bat lyssavirus , myotis chiloensis , roman numerals indicate the administrative region where the sample was obtained , tadarida brasiliensis , metropolitan region , lasiurus borealis .
the absence of a history of an animal bite , the clinical presentation of the disease without the classic signs of hydrophobia or aerophobia , and the absence of any human rabies cases for a period of 24 years in chile were the primary reasons that rabies was not first suspected and a definitive diagnosis was delayed in this case .
retrospective studies of human rabies epidemiology have demonstrated that it is not uncommon to observe rabies cases in which there is no history of a bite , mainly in situations involving insectivorous bat rabies variants .
for example , of the 17 human rabies cases associated with insectivorous bats reported in the united states from 1980 to 1996 , only one had clear documentation of a bite ( 22 ) . without proper education , patients may not be aware of the risks from a bat bite .
moreover , the wound may not be appreciated as a concern because of the limited injury inflicted by the bat 's small teeth ( 23 ) .
finally , there may not be an opportunity to obtain a history from a pediatric patient or to discern an exposure that occurs during sleep or other circumstances ( 24 ) . in cases in which a patient shows clinical signs of central nervous system involvement of unknown or suspected viral origin
, health - care providers should be aware of the importance of conducting a thorough medical history to appropriately assess the possibility of rabies . with the important changes in the epidemiologic patterns of rabies in latin america , this disease
should be included in the differential diagnosis of neurologic diseases characterized by acute encephalitis and progressive paralysis , even when no previous history of an animal bite exists and even in regions where canine rabies has been eradicated .

Answer:
the first human rabies case in chile since 1972 occurred in march 1996 in a patient without history of known exposure .
 antigenic and genetic characterization of the rabies isolate indicated that its reservoir was the insectivorous bat tadarida brasiliensis .
 this is the first human rabies case caused by an insectivorous bat rabies virus variant reported in latin america .


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:
elastosonography is an ultrasound based diagnosis which measures the elasticity or stiffness of the tissue .
compressibility of the tissue is a parameter evaluated by an elastogram and it is expressed as the change in tissue displacement as a function of its distance from the probe which is recognised as strain . among the 400450 lymph nodes ( lns ) of the human body , 6070 are located in the head and neck area .
lns display reactive enlargement in infection and also when they are primarily or secondarily involved in malignancies of head and neck .
an important criterion is the hardness of the ln , because lns might demonstrate increased stiffness on the elastogram if affected by a malignant process [ 24 ] .
the purpose of this study is to determine the reference sonoelastography values of cervical lns .
after obtaining the approval of the ethical committee , patients referred to the radiology department for cervical vascular doppler ultrasonography examination from january to march 2013 were enrolled in this prospective study .
97 cervical lns of 89 consecutive patients ( 70 lns in 64 females , 27 lns in 25 males ; mean age 54 years old ; age range , 2184 years ) who were referred to our clinic for the examination of cervical vasculature were analysed by elastosonography .
one radiologist with 20 years of conventional sonography and 5 years of elastosonography experience performed the examination .
the scanner used was esaote gold platform mylab 60 ( italy ) equipped with elasto software ( elaxto ) .
b - mode images were first obtained for each ln . afterwards elastosonography was performed by applying light vertical pressure followed by decompression until a good quality image was obtained .
elaxto software also made the sonographer aware of the compression degree by the help of its unique optimal compression scale for measurement .
real time b - mode and elastosonographic images were demonstrated next to each other on the screen .
a region of interest ( roi ) box was placed in the ln taking the adjacent subcutaneous fat tissue as the reference .
depth , length , width , length to width ratio , hilar thickness , and cortical thickness of the lns were measured .
lns with cortical thickness less than half of its hilar thickness were categorised as group a , and lns with cortical thickness equal to or more than half of the hilar thickness were categorised as group b. first strain ratio ( sr ) of the lns was measured .
afterwards , elastographic images were given 1 of 4 elasticity scores ( ess ) based on the percentage of stiff areas modified from choi et al . which was introduced for the differential diagnosis of axillary lns in breast cancer .
es 1 ( figure 1 ) , an absent or a very small red area ( i.e. , stiff ) ; es 2 ( figure 2 ) , small , scattered red areas , total red area < 45% ; and es 3 ( figure 3 ) , large red area , total red area  45% ; and es 4 ( figure 4 ) , red area occupying the entire ln , were the classifications used in the study .
64 ( 66% ) of the lns were found on the right side and 33 ( 34% ) were found on the left side of the neck .
the mean size of the lns was 17  mm with a range of 628  mm .
the mean depth of the lns was 11  mm , with a range of 519  mm .
18 lns ( 18.6% ) were categorised as group a. 79 lymph nodes ( 81.4% ) were categorised as group b. 67 lns ( 69.1% ) had sr less than 3 and were categorised as group 1 .
30 lns ( 30.9% ) with sr equal to or more than 3 were categorised as group 2 .
32 lns ( 33% ) displayed es 1 ; 30 lns ( 30.9% ) demonstrated es 2 ; 22 lns ( 22.7% ) showed es 3 ; 13 lns ( 13.4% ) had es 4 .
62 lns ( 63.9% ) with scores 1 and 2 were assigned as es grade 1 ; 35 lns ( 36.1% ) having scores 3 and 4 were assigned as es grade 2 .
there was a statistically significant correlation between thickness ratio groups and elasticity score grades ( p : 0.011 ) .
a statistically significant correlation was also demonstrated between sr groups and elasticity score grades ( p : 0.000 ) .
elastosonography , a noninvasive imaging modality , can potentially help the differentiation of benign and malignant lns by reducing the number of unnecessary biopsies . in the literature ,
several studies have been published for the sonographic diagnosis of metastatic cervical lns by b - mode [ 610 ] .
b - mode criteria for evaluating superficial lns are size , shape , the presence or the absence of the hilum , ratio of the cortex to hilum , borders , echogenicity , and homogeneity of internal structures . however
no single ultrasonography criterion for malignant lns had high sensitivity and specificity [ 11 , 12 ] .
specific criteria to differentiate reactive and metastatic cervical lns are still not well established . a simple , reproducible , noninvasive imaging technique for diagnosis of malignant lns is necessary .
sohn et al . investigated the b - mode criteria to differentiate metastatic lns from benign lns taking fine needle aspiration biopsy as the gold standard .
they evaluated the diagnostic performance of each ultrasound feature ( loss of fatty hilum , presence of cystic change or calcification , hyperechogenicity , and round shape ) .
they concluded that the most accurate ultrasound criterion to differentiate metastatic from benign lymph nodes was the presence of one of these malignant ultrasound findings , excluding the loss of fatty hilum .
the 5-point elasticity scoring system was introduced by itoh et al . for breast lesions .
published their results in the diagnosis of cervical ln metastasis using gray - scale sonographic elastography .
they utilized a 4-point scale including visibility , relative brightness , margin regularity , and margin definition of the ln .
they measured strain index of the lns by comparing the absolute strain values of the lymph nodes with the absolute strain values values of the nearby muscles .
strain index greater than 1.5 was the most useful criteria in metastatic ln classification , having 98% specificity , 85% sensitivity , and 92% accuracy .
alam et al . used a 5-pattern color scoring system based on distribution and percentage of area with high elasticity in the cervical lns .
the cut - off line for reactive versus metastatic lns was set between patterns 2 and 3 ; patterns 35 were considered metastatic .
they evaluated the sum of scores of five criteria , that is , short - axis diameter , shape , border ( regular or irregular ) , echogenicity ( homogeneous or inhomogeneous ) , and presence or absence of hilum for b - mode diagnosis .
the cut - off line for reactive versus metastatic was set between scores 6 and 7 .
sensitivity , specificity , and accuracy of b - mode sonography were 98% , 59% , and 84% , respectively ; 83% , 100% , and 89% for elastography ; and 92% , 94% , and 93% for the combined evaluation .
they concluded that the combination of elastography and b - mode sonography has the potential to improve the diagnosis of metastatic enlarged cervical lns .
concluded that elastosonography had 93.8% sensitivity and 89.5% specificity in the differentiation of benign and malignant cervical lymph nodes . in a meta - analysis of the real - time elastography for the differentiation of benign and malignant superficial lns ying et al . concluded that even though es measurement had a good diagnostic accuracy , it had significant interobserver variability
thus , a quantitative method such as strain ratio measurement was needed for analysis of elasticity of the ln .
although the accuracy of strain ratio measurement was similar to es measurement , it improved the diagnostic sensitivity value .
their meta - analysis suggested that real - time elastography could be used as a good identification tool for malignant lns .
nevertheless only a limited number of studies have been carried out to determine the elasticity of various tissues .
levinson et al . evaluated the elasticity of skeletal muscles   and arda et al .
conducted a study to determine the elasticity values of normal soft tissue including thyroid , parotid , and submandibular glands , gastrocnemius and masseter muscles , supraspinatus and achilles tendons , renal cortex , and pelvis , spleen , and pancreas of healthy volunteers .
estimation of tissue elasticity is useful for characterization of normal tissue . to our knowledge , the normal elasticity values of cervical lymph nodes have not been studied so far .   in our study 36.1% of the evaluated cervical lns
the aim of elastography is not necessarily to diagnose malignancies but to help reduce the number of unnecessary biopsies for benign processes by determining soft versus hard tissues due to its high specificity [ 2 , 3 , 19 ] .
elastosonography is a user dependent technique closely related to experience . due to the shape of the neck ,
the pulsations from the neighboring great vessels may also make it difficult to obtain good quality elastograms .
the primary aim of this research was to determine the reference values of cervical lns to guide elastographic studies not to establish the benign versus malignant nature of the lymph nodes .

Answer:
background . it is crucial to differentiate between reactive and malignant lymphadenopathies .
 elastosonography measures the elasticity of the tissue .
 having a reference value for benign lymph nodes ( lns ) is important in interpretation .
 the purpose of this study is to determine the reference elastosonography values of cervical lns
 . methods .
 97 lns were evaluated by b - mode and elastosonography .
 depth , length , width , length to width ratio , hilar - cortical thickness , strain ratio , and elasticity scores were measured .
 results . in 18.6% of the cervical lns cortical thickness was less than the hilar thickness ( group a ) and in 81.4% it was equal or more ( group b ) .
 69.1% of lns showed strain ratio ( sr ) less than 3 ( group 1 ) and 30.9% equal to or more than 3 ( group 2 ) .
 33% of lns displayed elasticity score ( es ) 1 ; 30.9% es 2 ; 22.7% es 3 , and 13.4% es 4 .
 there was a significant correlation between thickness ratios and elasticity scores ( p : 0.011 ) .
 a significant correlation was also demonstrated between sr groups and elasticity scores .
 conclusion . a simple , reproducible , noninvasive imaging technique for diagnosis of malignant
 lns is necessary .
 elastosonography can aid in the differentiation of benign versus malignant cervical lns , thus help reduce the number of unnecessary biopsies for benign processes .