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

Paper text:
in the 19th century , robert koch postulated a causal relationship between a pathogenic microbe and a disease .
this was later extended to the role of autoantibodies in the pathogenesis of human disease by witebsky et al . .
in 1957 , they proposed the fulfillment of several criteria to proof the pathogenic effects of autoantibodies , namely , the direct demonstration of free , circulating , or cell - bound antibodies by indirect means , the recognition of specific antigen against which the antibody is directed , the production of antibodies against the same antigen in experimental animals and finally the appearance of pathological changes in the corresponding tissues of an actively sensitized experimental model that is similar to that in the human disease .
molecular mimicry  was proposed as a mechanism by which infectious agents trigger an immune response against autoantigens , resulting in the development of autoimmune diseases .
similar criteria must be satisfied to conclude that a disease is triggered by molecular mimicry     .
they are as follows : ( i ) the establishment of an epidemiological association between the infectious agent and the immune - mediated disease ; ( ii ) the identification of t cells or antibodies directed against the patient 's target antigens ; ( iii ) the identification of microbial mimics of the target antigen ; ( iv ) reproduction of the disease in an animal model .
although there have been a number of diseases proposed to exhibit the mechanism of molecular mimicry , none has been proven in examples of human diseases based on fulfilment of all four criteria .
guillain - barr syndrome ( gbs ) , characterized by limb weakness and areflexia , has become the most frequent cause of acute flaccid paralysis since the near elimination of poliomyelitis in the world .
most gbs patients have had either gastrointestinal or upper respiratory symptoms one to three weeks prior to the onset of their neurological symptoms , making gbs the prototype of postinfectious autoimmune diseases .
gbs can be classified into two major subtypes , acute inflammatory demyelinating polyneuropathy ( aidp ) and acute motor axonal neuropathy ( aman ) depending on whether the myelin or the axonal components of the peripheral nerves are affected .
ean can be transferred to animals by t cells sensitized to peripheral nerve proteins such as p2 protein .
however , no investigators have shown conclusive evidence that such autoreactive t - cell response is seen in patients with gbs , indicating that ean is not a true model of aidp . in this paper
, we describe the development of a true model of aman , which fulfills all the four criteria of molecular mimicry as well as witebsky 's postulate as stated above .
this verifies gbs as the first paradigm of an autoimmune disease triggered by molecular mimicry .
we also discuss how this disease model has helped uncover the precise mechanism of muscle weakness in gbs , which will potentially lead to the development of better treatments .
gram - negative bacterium campylobacter jejuni , a leading cause of acute gastroenteritis , is the most common antecedent microorganism in gbs .
a prospective case - control study detected evidence of recent c. jejuni infection in 26% of patients with gbs in comparison to only 2% of the household controls ( a member of the patient 's household ) and 1% of the age - matched hospital controls     .
a study showed that c. jejuni infection was associated with aman , but not aidp     , although this finding has yet to be verified by other investigators .
autoantibodies are considered to be the pathogenic components which trigger gbs because plasma exchange is proven to be an effective treatment in gbs .
gangliosides constitute a large family of predominantly cell - surface glycosphingolipids bearing a ceramide moiety anchored in the external leaflet of the lipid bilayer and a sialylated oligosaccharide core exposed in the extracellular space .
autopsy studies show that , in aman , igg is deposited on the axolemma of the spinal anterior root     , indicating that igg , which binds effectively with complement , is an important factor in the development of aman .
patients who develop aman subsequent to c. jejuni enteritis have igg antibodies against gm1     .
in contrast , patients who have c. jejuni enteritis with no neurological sequelae did not have similar autoantibodies .
these findings suggest that gm1 is an autoantigen for igg antibodies in patients with aman subsequent to c. jejuni enteritis .
igg anti - gd1a antibodies are also associated with aman subsequent to c. jejuni infection     .
lipo - oligosaccharides ( loss ) are a family of phosphorylated glycolipids anchored on the outer surface membrane of c. jejuni .
a c. jejuni strain isolated from an aman patient carrying igg anti - gm1 antibody expressed an oligosaccharide structure [ gal 13 galnac 14 ( neuac 2 - 3 ) gal ] which protruded from the los core ( figure 1 )     .
this terminal structure was identical to that of the terminal tetrasaccharide of the gm1 ganglioside .
this was the first definitive evidence of molecular mimicry between human peripheral nerves and antecedent agents in gbs .
further evidence regarding the role of antiganglioside antibodies in gbs came in the form of adverse reactions to therapeutic gangliosides extracted from bovine brain tissue .
these were previously used in the treatment of various neurological disorders . in a study investigating seven patients who developed aman following intravenous bovine brain ganglioside administration
, anti - gm1 antibodies were discovered in six patients and anti - gd1a and -gt1b antibodies in one patient     .
these findings set the scene for the work done in the development of a suitable experimental animal model for gbs .
an aman model was established by the sensitization of rabbits with a bovine brain ganglioside mixture that included gm1 or with an isolated gm1     .
the rabbits developed high titres of igg anti - gm1 antibodies , followed by an acute onset of flaccid limb weakness with a monophasic course .
pathological findings in their peripheral nerves showed predominant wallerian - like degeneration with neither lymphocytic infiltration nor demyelination features .
igg was deposited on the axons of the anterior roots , internodal axolemmas , and nodes of ranvier .
cauda equina and spinal nerve root specimens from the paralyzed rabbits showed macrophage infiltration in the periaxonal space .
these findings correspond well with pathological findings for human aman     [ 10 , 18 ] .
the most straightforward way of verifying that molecular mimicry between microbes and autoantigens cause gbs is to establish a gbs model by the immunization of animals with components of antecedent infectious agents .
an aman model was established by the immunization of rabbits with c. jejuni los bearing a gm1-like structure     .
on sensitization with this gm1-like los , rabbits developed igg anti - gm1 antibodies and subsequent flaccid limb weakness ( figure 2 ) .
their nerve roots had occasional macrophages in the periaxonal spaces surrounded by an almost intact myelin sheath .
these findings , which are compatible with the features of human aman , provided the evidence that rabbits inoculated with c. jejuni los constitute a valid aman model .
this represents the first replica of human autoimmune disease in an animal model immunized by a microbial mimic of a self - antigen .
in contrast to the active immunization models above , a passive transfer model was developed to further proof the molecular mimicry theory .
ex vivo nerve - muscle preparations from gd1a - overexpressing mice were exposed to mouse igg anti - gd1a monoclonal antibodies in the presence of a complement source     .
this allowed the morphological and neurophysiological features of such an exposure to be investigated further .
dense antibody and complement deposits were shown to only be present on the presynaptic motor axons .
this was accompanied by severe ultrastructural damage and electrophysiological blockade of motor nerve terminal function .
a similar paralyzing effect was found when human sera with igg anti - gd1a reactivity were used instead .
these findings indicate that anti - gd1a antibodies arise from molecular mimicry and are the likely trigger of peripheral nerve injury . in summary
, gbs is the first true model of molecular mimicry having fulfilled all four criteria as follows : ( i ) establishment of an epidemiological association between gbs and c. jejuni infection by a prospective case - control study     , ( ii ) identification of autoantibodies against gm1 and gd1a gangliosides in patients with aman subsequent to c. jejuni enteritis     [ 11 , 12 ] , ( iii ) identification of molecular mimicry between gm1 or gd1a and los of   c. jejuni isolated from aman     [ 13 , 14 ] , and ( iv ) reproduction of the aman models by active immunization of rabbits with gm1 or the c. jejuni los     [ 16 , 19 ] as well as by passive transfer of anti - gd1a antibodies in mice .
this makes gbs the first disease in humans to verify that an autoimmune disease is triggered by molecular mimicry .
in both human and rabbit aman , the earliest pathological changes consist of lengthening of the node of ranvier with distortion of the paranodal myelin     [ 17 , 21 ] .
voltage - gated sodium channel dysfunction is postulated to occur at the nodes of ranvier     .
there has been some controversy as to whether anti - gm1 antibodies truly affect sodium channels at the nodes of ranvier     [ 23 , 24 ] . in the spinal anterior roots of aman rabbits ,
this binding of autoantibodies triggers complement activation with deposition of c3 components followed by membrane attack complex formation at the nodal axolemma .
the sodium channel clusters are then altered by the destruction of their stabilizing components which include the axonal cytoskeleton at nodes , schwann cell microvilli , and paranodal axo - glial junctions .
this apparent  disappearance  of sodium channel clusters significantly lowers the safety factor for impulse transmission , thus causing muscle weakness in aman .
this is a novel mechanism by which autoantibodies can modulate sodium channel properties to cause the development of certain neurological disorders .
plasma exchange and intravenous immunoglobulins are equally effective treatments in gbs . despite the administration of either immunotherapeutic agent , there are still mortality and significant morbidity in patients with gbs ; 310% death and 20% immobile after 6 months .
research into new treatment options to improve the final outcome of gbs is urgently required .
as previously described , complement activation products are deposited on the outer membrane of schwann cells in aidp patients     , and on the axolemma of motor fibres in aman     .
these postmortem studies show that complement activation followed by membrane attack complex formation is an important mechanism for the glial and neuronal injury seen in gbs .
this suggests that complement inhibitors have the potential of being a new , more rational treatment for gbs .
nafamostat mesilate is a synthetic serine protease inhibitor that has been used clinically in japan for over 20 years with no serious adverse effects to patients .
as the complement system contains several serine proteases such as c1r , c1s , and c3/c5 convertases , nafamostat mesilate can efficiently inhibit these serine proteases , thus blocking the formation of the membrane attack complex .
this inhibition of complement deposition and sodium channel cluster disappearance has been demonstrated in aman rabbits .
these experimental findings along with the autopsy findings would justify establishing clinical trials to investigate the use of complement inhibitors as a potential treatment for gbs .
in this paper , we have demonstrated how the animal model of aman has contributed to the proof of the molecular mimicry theory .
only the first criterion has been achieved with the association of aidp with cytomegalovirus infection . until the target antigen in aidp
is ascertained , identification of its microbial mimics and reproduction of the disease in an animal model remain unresolved .

Answer:
molecular mimicry between self and microbial components has been proposed as the pathogenic mechanism of autoimmune diseases , and this hypothesis is proven in guillain - barr syndrome .
 guillain - barr syndrome , the most frequent cause of acute neuromuscular paralysis , sometimes occurs after campylobacter jejuni enteritis .
 gangliosides are predominantly cell - surface glycolipids highly expressed in nervous tissue , whilst lipo - oligosaccharides are major components of the gram - negative bacterium c. jejuni outer membrane .
 igg autoantibodies to gm1 ganglioside were found in the sera from patients with guillain - barr syndrome .
 molecular mimicry was demonstrated between gm1 and lipo - oligosaccharide of c. jejuni isolated from the patients .
 disease models by sensitization of rabbits with gm1 and c. jejuni lipo - oligosaccharide were established .
 guillain - barr syndrome provided the first verification that an autoimmune disease is triggered by molecular mimicry .
 its disease models are helpful to further understand the molecular pathogenesis as well as to develop new treatments in guillain - barr syndrome .


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:
an initial search using three different search engines : google ( www.google.com ) , yahoo ( www.yahoo.com ) , and ask jeeves ( www.ask.com ) for the term  thumb sucking habit  was performed on 20 march 2014 .
it was found that google ( www.google.com , mountain view , ca ) incorporated the vast majority of the links to websites which the other two search engines produced and , therefore , the search for this investigation was conducted using google .
as it is unlikely that patients will investigate beyond the first few pages of a search , the initial 100 links generated by google were considered .
images of all websites in the study were stored for any necessary future analysis . the discern instrument
discern is a validated rating tool that can be used by health professionals and the general public to assess the quality of health information contained on the internet .
the discern instrument asks 16 questions related to the quality of a medical information website table 1 .
each question is given a score from 1 to 5 , with 1 being  no ,  2 to 4 being  partially ,  and 5 being  yes
.  the last question pertains to the overall quality of the website and is rated 1 ( poor ) to 5 ( good quality ) .
this requires compliance with these eight criteria : authority ( give qualifications of authors ) , complementarity ( information to support , not replace ) , confidentiality ( respect the privacy of site users ) , attribution ( cite the sources and dates of medical information ) , justifiability ( ability to back claims ) , transparency ( accessibility , provide valid contact details ) , financial disclosure ( provide details of funding ) , and advertising ( clearly distinguish advertising from editorial content ) .
the hon website was used to confirm the validity of each site presenting an hon seal .
websites were included in the investigation if they provided information pertaining to the thumb sucking habit .
websites that were unrelated to search term or only provided a list of website links were removed . sponsored links and banner advertisements
were excluded as they are normally ignored .  for profit  websites were excluded : if their only intention was to sell a product , if the site promised quick and unrealistic dramatic results , made claims that one remedy will cure a variety of illnesses through some miraculous breakthrough , or used excessive sensational writing .
journal articles , news , video feeds , academic press , abstracts listings , discussion group , and duplicate sites were also eliminated .
websites were included in the investigation if they provided information pertaining to the thumb sucking habit .
websites that were unrelated to search term or only provided a list of website links were removed . sponsored links and banner advertisements
were excluded as they are normally ignored .  for profit  websites were excluded : if their only intention was to sell a product , if the site promised quick and unrealistic dramatic results , made claims that one remedy will cure a variety of illnesses through some miraculous breakthrough , or used excessive sensational writing .
journal articles , news , video feeds , academic press , abstracts listings , discussion group , and duplicate sites were also eliminated .
sixty - four of the 100 websites were excluded from the analysis as they did not meet inclusion criteria . of the remaining 36 websites that were scored ,
discern indicated the majority of websites fell well below the maximum score . the maximum score achieved by one of the websites according to the discern tool was 55 of 80 , and the lowest score achieved was 16 of 80 .
the five websites with the highest quality information in relation to thumb sucking was :
 children.webmd.com : 55healthmantra.com : 54medicinenet.com : 44users.forthnet.gr : 41ivillage.com : 37 .

children.webmd.com : 55 users.forthnet.gr : 41 discern scores for the 36 websites in relation to the hon seal , out of 36 websites only three had hon seal .
as of today , there are no standards required for medical information on the internet , taking advantage of this ; some websites that appear to be educational are actually promotional in nature while others may be inefficient , incomplete , out of date , difficult to understand , or contain conflicting information .
this is the first study investigating the quality of information available on the internet relating to thumb sucking habit , at a single moment in time .
we used google as the internet search engine for this investigation after an initial search using yahoo and ask jeeves as well found that there was considerable overlap among the websites that google would find .
the other search engines such as bing ( www.bing.com ) and aol ( www.search.aol.com ) are also available .
google was selected because is the most popular search engine , examines all aspects of a pages content and the content of the pages linking to it .
no one can buy a higher ranking with their software , which makes it an easy way to find high - quality sites .
in addition , it may find many pages that are off - line for many other search engines , it updates their index very often by recalculating the page rankings of each of the websites and the fluctuations usually occur toward the end of the month .
the results of our study indicated that very few sites achieve high standards according to the discern tool .
in fact , none of the websites scored five points in all the 16 questionnaires .
the discern project is based at the division of public health and primary care of the institute of health sciences of the university of oxford ( united kingdom ) , and is financed by the british national health service executive research and development program .
it has been designed to help users to evaluate the quality of written information on treatment options , and to facilitate the generation of evidence - based data .
the discern is a validated and reliable instrument . in our study , the item  does it describes how treatment choices can affect quality of life ?
 yielded a very low score in all the websites , which were assessed , which is in line with lopez - jornet and camacho - alonso . although discern has been criticized for not analyzing the quality of the information on websites in significant detail . when compared to other tools such as the jama benchmarks , the discern tool has been shown to have good internal consistency and is user - friendly . in this
respect , clinical teams can use the discern tool to evaluate websites that patients may suggest to determine if the information they are likely to find is of use for other patients .
the discern questionnaire is a valid and reliable instrument for analyzing written consumer health information .
it is the first standardized quality index of consumer health information that can be used as a critical appraisal tool to evaluate health information by not only health professionals , but also by patients and the general population .
this questionnaire was derived systematically with the input of an expert panel , health information providers and patients from a self - help group .
this study found that discern score was highly rated among the initial search results displayed and was same with the hon seal .
the health on the net foundation criteria were developed by a swiss - based nonprofit , nongovernmental organization that provides certification of websites based on an  ethical standard aimed at offering quality health information .
health on the net is established in 1995 and is one of the first uniform resource locator to guide both lay people and those in the medical profession to reliable sources of healthcare information on the internet .
sites may display the hon code seal if they agree to comply with the standards listed , and they are subjected to random audits for compliance .
the external accreditation of quality of health - related websites is not an easy task as it would be an enormous and costly task requiring a large staff with expertise in varying fields to monitor thousands of medical sites .
hon 's mission is to guide internet users to reliable , understandable , accessible , and trustworthy sources of medical and health information .
therefore , the internet users do not have a way to identify the quality sites unless ; they have a medical background or perform a scientific immersion in the topic . in light of the results of the present study ,
the internet is a potentially powerful tool for patients to search for health - related information , there are many sources that when encountered , may mislead them about their diagnosis , treatment , and potential outcomes . in the extreme , patients may feel a false empowerment to self - diagnose and treat , leading to disastrous results . despite these concerns ,
it is likely that the use of the internet by patients will continue to increase in the future .
it is , therefore , important for the patients to exercise caution when relying on the internet for health - related information .
patients should be counseled to avoid commercial websites , except for the most reputable sites and look for the hon code seal of compliance for transparency and accountability .
it appears that the principles of clarity and full disclosure of sources are still only practiced by a minority of the websites at this point .
it is our hope that by raising awareness of the poor overall quality and content of the internet information , better accountability may be active or , at least , that patients may become best informed that information on the internet is not accurate or up to date .
apart from the quality of health information on the web , patients also find many websites , presenting health information using highly technical language .
scientific presentations may be advantageous for researchers and clinicians ; however , this specialized language can be overwhelming and confusing , especially if it is not properly explained .
therefore , it is also imperative to systematically assess the presentation of online health information using readability algorithms to ensure that such information is easily assessable to lay audiences in their native language .
patients seeking thumb sucking habit information on the internet should be encouraged to exercise caution and to utilize only well - known sited and those that display the hon code seal of compliance with transparency and accountability practices . by directing patients to validated websites on the thumb sucking habit

Answer:
aims : the aim of this study was to evaluate the reliability of websites on the thumb sucking habit using discern instrument and health on the net ( hon ) seal code at a single moment in time.subjects and methods : an internet search engine ( www.google.com ) was used to identify websites comprising information on  thumb sucking habit .  of over 204,000 links for thumb sucking habit , the first 100 were analyzed in detail . after excluding discussion groups , news and video feeds , and removing carbon copy sites , only 36 relevant websites remained , which were then assessed using the discern instrument and hon seal code . using the 16 questions of discern for assessing the reliability and quality of the consumer information which were scored from 1 to 5 , an appropriate index of the quality of the information
 was generated .
 all the assessed websites were also checked for presence or absence of hon seal code.results:the maximum score attainable for an outstanding website is 80 . of the 36 websites that were scored the highest score obtained by one of the websites according to the discern tool was 55 of 80 , and the lowest score achieved was 16 of 80 .
 the websites achieving the maximum and minimum score were children.webmd.com and thebehaviorsolution.com , respectively .
 the hon seal was displayed only in three websites , which were medicinenet.com , righthealth.com , and children.webmd.com.conclusions:by directing patients to validated websites on the thumb sucking habit , clinicians can ensure patients find appropriate information .


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:
ghent university multidisciplinary research partnership  bioinformatics : from nucleotides to networks ; fund for scientific research ( fwo)flanders ( belgium ) ( postdoctoral research fellowship to f.i .
) ; institute for the promotion of innovation through science and technology in flanders ( iwt - vlaanderen ) ( phd to k.p . )
; proteomexchange project , funded by the european union 7th framework program under grant agreement number [ 260558 to n.h . ] ; prime - xs project , funded by the european union 7th framework program under grant agreement number [ 262067 to k.g . and l.m . ] .

Answer:
we here present the online protein processing resource ( toppr ; http://iomics.ugent.be/toppr/ ) , an online database that contains thousands of published proteolytically processed sites in human and mouse proteins .
 these cleavage events were identified with combinded fractional diagonal chromatography proteomics technologies , and the resulting database is provided with full data provenance .
 indeed , toppr provides an interactive visual display of the actual fragmentation mass spectrum that led to each identification of a reported processed site , complete with fragment ion annotations and search engine scores .
 apart from warehousing and disseminating these data in an intuitive manner , toppr also provides an online analysis platform , including methods to analyze protease specificity and substrate - centric analyses .
 concretely , toppr supports three ways to retrieve data : ( i ) the retrieval of all substrates for one or more cellular stimuli or assays ; ( ii ) a substrate search by uniprotkb / swiss - prot accession number , entry name or description ; and ( iii ) a motif search that retrieves substrates matching a user - defined protease specificity profile .
 the analysis of the substrates is supported through the presence of a variety of annotations , including predicted secondary structure , known domains and experimentally obtained 3d structure where available . across substrates , substrate orthologs and conserved sequence stretches can also be shown , with icelogo visualization provided for the latter .


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 bacterial isolates were collected throughout finland during 19982007 as described ( 10 ) . of
bionumerics version 5.1 software ( applied maths , kortrijk , belgium ) was used for sequence assembly .
allele numbers , sequence types ( sts ) , and clonal complexes ( ccs ) were assigned by using the pubmlst database ( 5 ) .
a serum sensitivity assay was conducted with 73 c. jejuni isolates according to a described protocol ( 8) . the same pool of serum samples from 10 healthy blood donors was used in all experiments . c. jejuni
all statistical analyses were performed by using graphpad prism version 4.03 ( graphpad software , san diego , ca , usa ) and pasw statistics version 18 ( spss inc . , chicago , il , usa ) .
a total of 72 c. jejuni isolates from blood were successfully typed by mlst ; 1 isolate had a mixed mlst pattern .
five isolates were in unassigned sts , and the rest were distributed among 11 ccs ( table ) .
genetic relatedness of these isolates was further confirmed by using pulsed - field gel electrophoresis .
* mlst , multilocus sequence typing ; st , sequence type ; nd , none detected .
however , bacteremia episodes caused by st-677 cc isolates were exclusively diagnosed during the seasonal peak during may  august ( figure 1 ) . of c. jejuni blood culture isolates detected during may  august , most ( 64% ) were st-677 cc .
furthermore , st-677 cc was the most prevalent complex in 4 geographic regions of finland . annual and seasonal distribution of 72 camplyobacter jejuni blood culture isolates belonging either to the st-677 clonal complex ( cc ) or to the other multilocus sequence typing ( mlst ) ccs .
one isolate with a mixed multilocus sequence type was not included . c. jejuni bacteremia was diagnosed during may  august ( m  a ) or during any other month of the year ( o ) .
susceptibility to human serum varied between c. jejuni isolates from different ccs ( figure 2 ) .
st-677 cc isolates were significantly less susceptible to human serum than all other isolates ( p<0.0001 ) .
st-45 cc isolates were significantly more susceptible to human serum than all other isolates ( p<0.0001 ) .
percentage of surviving bacteria in human serum for 73 blood culture isolates of campylobacter jejuni ( cj ) , grouped according to major multilocus sequence typing clonal complexes ( ccs ) , and for controls c. jejuni cj11168 and c. fetus .
we characterized a unique collection of 73 c. jejuni isolates from blood obtained during a nationwide study in finland over a 10-year period . despite the high population diversity of c. jejuni , nearly half of the isolates from blood showed clustering within the st-677 cc , a rare cc in other countries ( 12,13 ) .
thus , invasiveness of blood culture isolates could not be solely explained by their serum resistance , although the predominant isolates of st-677 cc were more serum resistant than other isolates . c. jejuni has high st diversity . as of may 2 , 2013 , a total of 6,564 sts were registered ( 5 ) . in this study , we detected clustering of c. jejuni isolates from blood in an uncommon st-677 cc .
further studies are needed to clarify whether bacterial characteristics might explain this finding . in our previous study , which included human fecal c. jejuni isolates obtained in finland from the mid-1990s through 2007 ,
which is nearly the same period as in the current nationwide study , 11.7% of the isolates belonged to st-677 cc ( 11 ) .
the 2 most prevalent ccs in that study , st-45 cc ( 43.6% of fecal isolates ) and st-21 cc ( 19.4% of fecal isolates ) , were detected only among 12 ( 16% ) and 10 ( 14% ) of blood culture isolates , respectively , in the present study .
st-45 cc and st-21 cc have been shown to be prevalent in several countries ( 4,13 ) . however , our results suggest that these 2 ccs are not common among c. jejuni isolates from blood in finland , which cluster more in the st-677 cc . on the basis of the present results , we speculate that st-677 cc might have a special invasive capability or has adapted to the environment in finland .
in general , complement - mediated killing of serum - susceptible isolates plays a major role in restricting access of pathogens to the bloodstream . however , available information about possible serum sensitivity of c. jejuni isolates from blood is scarce ( 8,9 ) . in our study of nonselected c. jejuni isolates from blood , susceptibility to human serum varied according to mlst cc . in conclusion , in this nationwide study during a 10-year period in finland , we found by mlst analysis that half of the bacteremia isolates of c. jejuni clustered within an otherwise uncommon st-677 cc . whether this finding indicates special adaptation of st-677 cc to finland or to the human bloodstream
our findings emphasize the role of using well - defined clinical materials in studies on bacterial pathogenicity and severity of human disease .

Answer:
campylobacter jejuni bacteria are highly diverse enteropathogens .
 seventy - three c. jejuni isolates from blood collected in finland were analyzed by multilocus sequence typing and serum resistance .
 approximately half of the isolates belonged to the otherwise uncommon sequence type 677 clonal complex .
 isolates of this clonal complex were more resistant than other isolates to human serum .


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:
abdominal wall pain is a common complaint , and patients can present with it in the acute perioperative period as well as in a chronic pain state.1 pain - relieving therapies are varied , and range from oral medication to interventional procedures .
recently , the ultrasound - guided transversus abdominis plane ( tap ) block has become more widely used as an alternative technique for perioperative analgesia for abdominal procedures.24 the abdominal wall is innervated by the anterior division of the lower thoracic and upper lumbar nerves .
the nerves course within the fascial plane between the internal oblique and transverse abdominis muscle  the tap.5 with this anatomy and its innervation ,
the tap block has been shown to provide effective postoperative analgesia , reducing opioid requirements and improving patient satisfaction in the early postoperative period.5 the tap block had been used previously with a nonguided or  blind double - pop  technique that relies on tactile sensation to determine the appropriate level of local anesthetic infiltration.6 cadaver studies have established the petit triangle , defined medially by the latissimus dorsi muscle , laterally by the external oblique muscle , and inferiorly by the iliac crest .
these superficial landmarks , when combined with knowledge of the path of the thoracolumbar nerves , have allowed clinicians to perform blind tap blocks with varying degrees of success.7,8 there are 2 potential pitfalls with a blind tap block .
first , the final needle tip position may be superficial to the transversus abdominis fascial plane , resulting in intramuscular or subcutaneous deposition of the injectate .
second , the final needle tip position may be deep to the intended target , resulting in an intraperitoneal injection .
both of these aberrant injections would produce a failed block that results in pain , requiring rescue pain management because of liver laceration or bowel injury , to name just a few complications.9 with the advent of ultrasound guidance , the transversus abdominis fascial plane in which the thoracolumbar nerves reside can be identified and accurately injected with the intended medication.10,11 the ideal volume for a tap block is unknown .
different techniques ( ie , subcostal versus midaxillary ) have been described , and one study suggests that the more subcostal tap compartment does not communicate with the more lateral triangle of petit.12 volumes of injectate have varied among studies , with some using weight - based volumes versus standard volumes , without any conclusions regarding optimal volume .
a recent retrospective review by abdallah et al13 suggested that 15 ml may be an optimal volume , although findings were inconclusive .
we therefore sought to further investigate the spread of various volumes of contrast injected under ultrasound guidance into the tap layer as identified by computed tomography ( ct ) imaging .
after receiving approval from the mayo clinic institutional review board , we obtained two unembalmed adult cadaveric torso specimens .
no specimens exhibited signs of prior surgery , trauma , or major deformity around the abdomen , specifically at the injection sites .
each cadaver was imaged with a 64-slice ( 2  32 detectors ) siemens somatom definition ct scanner ( siemens healthcare , erlangen , germany ) using a scan protocol consisting of 2-mm axial sections obtained in a soft - tissue kernel .
all images were interpreted by an experienced musculoskeletal radiologist using a ge advantage workstation ( ge healthcare institute , waukesha , wi , usa ) .
all ultrasound procedures were performed with a philips cx50 ultrasound machine ( philips healthcare , andover , ma , usa ) , using a 12-mhz linear array transducer with a 35-mm footprint , standard ultrasound gel , a 22-gauge , 89-mm diamond point stainless steel spinal needle ( covidien , mansfield , ma , usa ) , and iodinated contrast agent ( omnipaque 300 , ge healthcare as , oslo , norway ) diluted with 0.9% saline to a concentration of 36 mg / ml ( 10% ) .
the tap layer was identified along the midaxillary line by an ultrasound of each cadaver by an experienced sonographer . from superficial to deep
, the external oblique muscle , internal oblique muscle , and transversus abdominis muscle , including the tap fascial plane between the internal oblique and transversus abdominis muscles , were identified along the midaxillary line between the iliac crest and the subcostal margin , as previously described in the medical literature.4 a 22-gauge , 89-mm spinal needle was advanced under direct ultrasound visualization in a slightly oblique anterior to posterior direction toward the tap . once the needle tip was observed to enter this fascial plane , hydrolocation with 0.9% normal saline was performed to confirm the fascial plane and facilitate better sonographic visualization14 ( figure 1 ) .
each cadaver was then placed in the ct scanner to verify the anatomical placement of the needle and to obtain baseline imaging of the relevant anatomy prior to contrast administration . following the initial ct scan ,
the needle was left in place and extension tubing with a syringe containing the dilute iodinated contrast agent was connected to the needle .
a predetermined amount of contrast was then injected under direct ultrasound visualization into the tap layer , and the cadaveric torso was rescanned using the same ct scan parameters .
this procedure was repeated on both sides of each cadaver with different volumes of contrast : cadaver a ( left , 5 ml ; right , 10 ml ) ; cadaver b ( left , 15 ml ; right , 20 ml ) .
all needle entry points were between the level of the lumbar ( l)3 disk space and the middle of the l4 vertebral body .
contrast injected under ultrasound guidance was identified in the tap in both cadavers on ct imaging ( figure 2 and 3 ) .
intraperitoneal contrast spread was also noted with the 15 ml injection ( figure 3 ) .
caudal spread of injected contrast correlated with increasing volumes of injectate ( table 1 ) .
caudal distribution was roughly 1 vertebral level ( end plate to end plate ) for the 5 ml injection and 2 vertebral levels for the 10 , 15 , and 20 ml injections .
anterior - posterior and transverse spread of injected contrast did not correlate with increasing volumes of contrast ( table 1 ) .
as described in prior studies , there exists a difference in spread when a tap block is performed under ultrasound guidance , versus a nonguided approach to the triangle of petit.13 we chose to perform the injection using ultrasound guidance , with the goal of accurately measuring injectate spread delivered reliably into the transversus abdominis fascial plane .
it is not uncommon to see a small amount of intramuscular spread of contrast within the tap layer that is likely related to incomplete separation of the fascial planes under pressurization .
however , we were surprised to discover contrast in the peritoneal space despite direct visualization of the needle placement with ultrasound . logically , the ability to see the injection under live imaging guidance should be safer and more successful ; however , the possibility of accessing an unintended target exists , regardless of experience or technique.15,16 the entrance of the needle and thus injectate could pose risk to patients including bowel penetration , injury , or infection . furthermore , when performing injections on cadavers there is no movement such as breathing or bowel peristalsis which may make injections easier but can also make identifying structures more difficult .
this is true for the tap block , where the peritoneum can be identified by movement and the muscle layer superficial to it can be identified as the transversus abdominis muscle followed by the internal and external oblique muscles .
importantly , in this study , increased volumes of injectate correlated with increased cranial  caudal spread , and demonstrated good spread around the midaxillary line where the iliohypogastric , subcostal , and intercostal nerves have been shown to course in the tap.1
this study helps further the understanding of injectate spread following ultrasound - guided tap injections .
specifically , it suggests that 15 ml provides additional cranial  caudal spread and may be an optimal volume of anesthesia .
the optimal volume required to achieve an adequate sensory block will vary , depending on the site of planned incision or the severity of abdominal pain .
furthermore , the degree of injectate spread may be different for live patients compared with that in fresh cadavers , and in addition , may also vary according to variability of patient height , weight , and previous abdominal surgeries .
therefore , further in vivo studies are warranted to investigate the minimum volume of ultrasound - guided injectate required to cause a sensory blockade of the anterior abdominal wall .

Answer:
backgroundultrasound - guided transversus abdominis plane ( tap ) injections are increasingly being used as an alternative to traditional perioperative analgesia in the abdominal region . with the use of a
  blind
 tap block technique , these procedures have had variable success in cadaver and in vivo studies . for more accurate injection with the intended medication ,
 ultrasound guidance allows visualization of the correct layer of the abdominal wall planes in which the thoracolumbar nerves reside.objectiveto assess the spread of various volumes of contrast placed under live ultrasound guidance into the tap using computed tomography ( ct).methodsfour tap blocks were performed on 2 fresh frozen cadaver torsos with predetermined contrast volumes of 5 , 10 , 15 , or 20 ml .
 a ct scan of the cadaver was then performed and interpreted by a musculoskeletal radiologist .
 this cadaver study was carried out at a tertiary care academic medical center.resultscranialcaudal spread of injected contrast correlated with increasing injectate volume and was roughly 1 vertebral level ( end plate to end plate ) for the 5 ml injection and 2 vertebral levels for the 10 , 15 , and 20 ml injections .
 however , the degree of injectate spread may be different for live patients than for cadavers.conclusionthis study helps further the understanding of injectate spread following ultrasound - guided tap injections .
 specifically , it suggests that 15 ml provides additional cranial  caudal spread and may be an optimal volume of anesthesia .


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:
spastic torticollis , also known as stiff neck or wryneck , is a condition in which the head is laterally flexed and rotated on the neck , secondary to painful spasm of the neck muscles .
there may be a report of the patient having slept in a draft from a fan , open window , or air conditioner .
the patient is generally afebrile , and if there is any history of trauma , it is of the mildest variety .
chloroethane ( ethyl chloride ) spray is a vapocoolant applied topically in the treatment of athletic injuries .
the manufacturer indicates that it may be used as a counterirritant in the management of myofascial pain and muscle spasm .
we reviewed the literature and could find no large study on pediatric patients regarding this usage .
we report our experience with the use of chloroethane spray treating torticollis in 66 patients ranging in age from 1 to 16 years .
patients presenting to the pediatric emergency service of a 600-bed inner - city hospital with the compliant of  stiff neck  were selected for treatment .
an initial evaluation was performed , which included a medical and family history , a physical examination , and x - ray study of the cervical spine ( a - p , lateral , and open mouth views ) .
the patients were enrolled into either group 1 , usage of ethyl chloride spray , or group 2 , usage of normal spray . in the patients enrolled in group 1 ( after explaining the procedure to the parent and child and obtaining informed consent ) , the chloroethane spray bottle was held inverted 12 inches directly over the point of maximal neck tenderness .
the valve of the bottle was opened , allowing the liquid to leave as a fine jet stream .
the stream was left in contact with the skin for 4 to 5 seconds or until frosting of the skin occurred .
the procedure was considered successful if , after a 5-minute waiting period , the patient was able to freely and painlessly move his or her head and neck in the opposite side . for the control group , normal
saline is applied as a spray using a syringe with plastic catheter over the point of maximum tenderness and asked to move the neck after 5 minutes and note if patient can move the head and neck freely in the opposite side .
a total of 132 children with a mean age of 8.97 years ( range = 1 - 16 years ) presented to the emergency room with torticollis over a period of 3 years and were enrolled in the study .
of the 132 , patients in group 1 were treated with chloroethane spray and those in group 2 were treated with normal saline spray .
of the 66 patients treated with chloromethane spray , 63 ( 95% ) responded to the treatment as evidenced by their subsequent ability to move the head and neck freely ( see table 1 ) .
no patients returned for additional treatment . of the patients in group 2 , who treated with normal saline spray
, no patient responded to saline spray with ability to move the head freely in the opposite side ( see figure 1 ) .
series 1 : patients rxed with chloroethane spray ( 63/66 positive response and 3/66 negative response ) .
the torticollis was in several cases associated with a local head or neck condition , but 46.97% of the cases involved no underlying pathology ( table 2 ) .
of the 3 treatment failures , 2 occurred in patients with neck trauma and 1 failure occurred in a patient with cystic hygroma .
conditions associated with spastic torticollis . abbreviation : uri , upper respiratory infection . to test the null hypothesis that the percentages improved in the 2 groups equally , we calculated the z statistic .
the z statistic of 24 corresponded to a p value < .0001 , whether the test is 1-sided or 2-sided .
to test the null hypothesis that the percentages improved in the 2 groups equally , we calculated the z statistic .
the z statistic of 24 corresponded to a p value < .0001 , whether the test is 1-sided or 2-sided .
torticollis is a condition in which the head is laterally flexed and rotated on the neck due to shortening or spasm of the sternocleidomastoid muscle .
acquired torticollis can be caused by a variety of problems including cold exposure , minor neck muscle trauma , and any inflammatory condition of the neck such as cervical lymphadenitis , or retropharyngeal abscess .
less common causes include drug ingestion ( eg , phenothiazines ) and a variety of neurological conditions such as dystonia musculorum deformans , brain stem , or posterior fossa tumor or cyst .
we focus on describing chloroethane treatment for spastic torticollis caused by sternomastiod spasm that may be primary or secondary to a local inflammatory condition .
this form of torticollis is most often treated with warm compresses , analgesics , and muscle relaxants .
it is thought that the relief is the result of the wrong acting as a counterirritant or a local anesthetic or by a placebo effect .
similarly , a vapocoolant therapy has been described to successfully relieve acute myofascial trigger with point pain in children .
in conclusion , from our study , for children and adolescents with spastic torticollis , chloroethane spray was more superior to normal saline in the pediatric emergency room .

Answer:
objective . a study to determine the efficacy of chloroethane spray compared to normal saline in the treatment of spastic torticollis in children and adolescents . hypothesis .
 chloroethane spray is more superior to normal saline for the treatment of spastic torticollis in children and adolescents in the pediatric emergency room .
 design .
 prospective randomized study . setting .
 urban inner - city hospital pediatric emergency department .
 methods and results . all children and adolescents ( between the ages of 1 and 16 years ) presenting to the author with the complaint of stiff neck were enrolled in the study .
 a total of 132 patients were enrolled .
 after complete evaluation to rule out cervical spine injury , a central neurological cause , patients were enrolled in the study .
 sixty - six patients were treated with chloroethane spray to the neck and the other 66 were given normal saline as placebo .
 sixty - three out of 66 patients treated with chloroethane spray achieved relief in 5 minutes as demonstrated by painless and free movement of the head and neck .
 no adverse effects were observed .
 the patients treated with placebo have no relief in 5 minutes . to test the null hypothesis that the percentages improved in the 2 groups equally , we calculated the z statistic .
 the z statistic of 24 corresponded to a p value of < .0001 , whether the test is 1-sided or 2-sided .
 chloroethane spray treatment was superior to placebo with a high statistical significance . conclusion .
 for children and adolescents with spastic torticollis chloroethane spray was more superior to normal saline in the pediatric emergency room .


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:
combinations of dental and skeletal factors ranging from mild to severe are multiple characters of this discrepancy . the treatment protocols for class ii can vary widely according to professional ability , time of treatment , severity of malocclusion and patient compliance .
one of the recommended therapeutic approaches to class ii malocclusion in growing patients is functional jaw orthopedics for mandibular advancement .
fixed devices for sagittal advancement of the mandible can be used in association with fixed mechanotherapy and is a recent advancement .
the effects of several compliance - free appliances for mandibular anterior repositioning in association with fixed appliances have been investigated .
the forsus ( forsus fatigue resistant device [ ffrd ] ) is a semirigid telescoping system incorporating a superelastic nickel - titanium coil spring that can be assembled chair - side .
it is compatible with complete fixed orthodontic appliances and can be incorporated into pre - existing appliances .
forsus ffrd attaches at the maxillary first molar and onto the mandibular archwire , distal to either the canine or first premolar bracket , creating a mesial force on the mandibular arch and a distal force on the maxillary arch . as the coil is compressed , opposing forces
thus , the spring exerts equal and opposite forces onto the maxillary molars as well as the mandibular incisors .
the intrusive force on maxillary molars can decrease posterior vertical dimension , and the intrusive force on mandibular incisors will bring about their intrusion .
this appliance shows a greater range in activation and a less likelihood of breakage when compared to other inter arch compression springs .
teuscher suggested that forward and downward growth of the maxilla could be altered using headgear , and the mandible could also change its growth direction to a forward and upward position with condylar adaptation .
a combination of forsus ffrd and headgear can bring about dramatic changes in the management of space deficiency and correction of class ii malocclusions .
a 13-year - old male patient reported to the author 's private clinic with a chief complaint of unerupted teeth in the upper front region and sought treatment for the same .
extra orally patient presented with a symmetrical face , convex profile and competent lips [ figure 1 ] .
intraoral examination revealed class ii molar relation on both sides , deep bite , ectopically erupting and blocked out maxillary canines , upper left lateral incisor was in cross bite and crowding in the mandibular anterior teeth and insufficient space for 33 . on radiographic examination , it was observed that the patient also has a deficient and backwardly placed mandible [ figure 2 ] .
pretreatment extraoral and intraoral photographs pretreatment lateral cephalogram and opg the following treatment objectives were established :
 to correct the skeletal and dental class ii malocclusion , which would include restriction of maxilla and advancement of mandibleto correct crowding in both the arches and space management for ectopically erupting canineto achieve ideal overjet and overbiteto improve his facial appearance .
  to correct the skeletal and dental class ii malocclusion , which would include restriction of maxilla and advancement of mandible to correct crowding in both the arches and space management for ectopically erupting canine to achieve ideal overjet and overbite to improve his facial appearance .
this would help to manage space for ectopically erupting canines along with open coil spring .
a fixed orthodontic appliance ( mbt 0.022 3 m unitek ) was initially bonded to the maxillary arch and 0.016  niti round arch wire was placed in the maxillary arch for the initial leveling and aligning phase [ figure 4 ] .
headgear therapy was started along with orthodontic strap up to distalize molars and to restrict downward and forward growth of the maxilla [ figure 3 ] .
( a - c ) leveling and aligning with 0.016 ss and creating space for ectopic canines .
( g - i ) finishing and detailing after sagittal correction space was created for the ectopically erupting maxillary canines using open coil niti springs , which were placed between the maxillary lateral incisors and first premolars [ figure 4 ] .
once sufficient space was created by headgear and open coil spring , the maxillary canines were bonded and ligated to the arch wire .
the ligature was activated periodically till the canines were brought into the maxillary arch . after the canines had been brought into their respective places , the maxillary arch wire was engaged into the canine brackets .
the lower arch was bonded 1-month after commencement of treatment and 0.016  round niti wire was placed in the mandibular arch .
the 016  round niti wires were then followed by the 019   025  rectangular niti wires . then
0.019   0.025  rectangular stainless steel wires were placed in the upper and the lower arch .
after 9 months of commencement of treatment , forsus ffrd was placed [ figure 4 ] .
the total treatment time was about 18 months with satisfactory results [ figure 5 ] .
the molar relationship was corrected from a class ii to a class i. ideal overjet , and overbite were established [ figure 5 ] .
the deep bite and cross bite were corrected along with the correction of the ectopically erupted maxillary canines .
periodontal evaluation showed acceptable gingival contour and adequate width of keratinized attached gingival tissue around the maxillary canines .
a fixed retainer was bonded in the lower arch and a removable retainer with anterior bite plane was placed in the upper arch .
occlusion remained stable 2 and 3 years after the orthodontic treatment [ figures 7 and 8 ] .
post treatment photographs post treatment lateral cephalogram and opg post retention photographs after 2 years post retention photographs after 3 years
the following treatment objectives were established :
 to correct the skeletal and dental class ii malocclusion , which would include restriction of maxilla and advancement of mandibleto correct crowding in both the arches and space management for ectopically erupting canineto achieve ideal overjet and overbiteto improve his facial appearance .
  to correct the skeletal and dental class ii malocclusion , which would include restriction of maxilla and advancement of mandible to correct crowding in both the arches and space management for ectopically erupting canine to achieve ideal overjet and overbite to improve his facial appearance .
this would help to manage space for ectopically erupting canines along with open coil spring .
a fixed orthodontic appliance ( mbt 0.022 3 m unitek ) was initially bonded to the maxillary arch and 0.016  niti round arch wire was placed in the maxillary arch for the initial leveling and aligning phase [ figure 4 ] .
headgear therapy was started along with orthodontic strap up to distalize molars and to restrict downward and forward growth of the maxilla [ figure 3 ] .
( a - c ) leveling and aligning with 0.016 ss and creating space for ectopic canines .
( g - i ) finishing and detailing after sagittal correction space was created for the ectopically erupting maxillary canines using open coil niti springs , which were placed between the maxillary lateral incisors and first premolars [ figure 4 ] .
once sufficient space was created by headgear and open coil spring , the maxillary canines were bonded and ligated to the arch wire . the ligature was activated periodically till the canines were brought into the maxillary arch .
after the canines had been brought into their respective places , the maxillary arch wire was engaged into the canine brackets .
the lower arch was bonded 1-month after commencement of treatment and 0.016  round niti wire was placed in the mandibular arch .
the 016  round niti wires were then followed by the 019   025  rectangular niti wires .
then 0.019   0.025  rectangular stainless steel wires were placed in the upper and the lower arch .
after 9 months of commencement of treatment , forsus ffrd was placed [ figure 4 ] .
the total treatment time was about 18 months with satisfactory results [ figure 5 ] .
the molar relationship was corrected from a class ii to a class i. ideal overjet , and overbite were established [ figure 5 ] .
the deep bite and cross bite were corrected along with the correction of the ectopically erupted maxillary canines .
periodontal evaluation showed acceptable gingival contour and adequate width of keratinized attached gingival tissue around the maxillary canines .
a fixed retainer was bonded in the lower arch and a removable retainer with anterior bite plane was placed in the upper arch .
occlusion remained stable 2 and 3 years after the orthodontic treatment [ figures 7 and 8 ] .
post treatment photographs post treatment lateral cephalogram and opg post retention photographs after 2 years post retention photographs after 3 years
optimal timing for class ii treatment with fixed functional appliance is at the pubertal growth spurt with enhanced mandibular skeletal changes and minimal dentoalveolar compensation .
studies have shown that functional appliances improve the sagittal effect on the mandible by a significant overjet reduction .
skeletal changes in functional appliances are brought about by stimulation of condylar growth as well as remodeling of fossa . besides the sagittal skeletal base improvement influencing overjet , the dentoalveolar effect on overjet is brought about by retroclination of maxillary and proclination of mandibular incisors .
the use of headgear not only restricts the sagittal growth of the maxilla but also moves posterior teeth backward .
however , combination of extra oral and functional appliances seem to affect the sagittal intermaxillary relationship by acting mainly on the mandibular skeletal base and also having effect on dentitions .
ruf and pancherz reported that herbst and multibracket appliance combination was found to be a powerful tool for nonsurgical nonextraction treatment of class ii div 1 subjects in early and late adulthood .
as opposed to rigid fixed functional devices , the spring of the ffrd allows flexibility in the position of the mandible .
since it is fixed in the patient 's mouth , the clinicians do not have to rely on a patient 's cooperation . in this case ,
space for the alignment of ectopically erupting canines was created partly by open coil spring and partly by molar distalization .
( 2 ) distalization of maxillary molars . ( 3 ) correction of ectopically erupting canine ( 4 ) retrusion of maxillary incisors . ( 5 ) extrusion of posteriors . ( 6 ) intrusion of lower anteriors , ( 7 ) correction of overjet and overbite .
the treatment results showed a balanced facial profile , good interdigitations , improvement in maxillomandibular relationship .
this case report demonstrates the efficiency of the combined clinical use of headgear and forsus with fixed appliance to distalize the maxillary molar and also to advance the mandible .

Answer:
correction of class ii relationship , deep bite and ectopically erupting canines is an orthodontic challenge for the clinician .
 a 13-year - old male patient presented with class ii malocclusion , ectopically erupting canines , and cross bite with maxillary left lateral incisor .
 he was treated with a combination of headgear , forsus fatigue resistant device [ ffrd ] with fixed mechanotherapy for the management of space deficiency and correction of class ii malocclusions .
 headgear was used to distalize upper first molars and also to prevent further downward and forward growth of the maxilla .
 then forsus ffrd was used for the advancement of the mandible .
 the molar and canine relationship were corrected from a class ii to a class i. the objectives were to establish good occlusion and enable eruption of unerupted canines .
 all these objectives were achieved and remained stable .


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

Title:
Bifunctional Catalyst Promotes Highly Enantioselective Bromolactonizations to Generate Stereogenic C\xe2\x80\x93Br Bonds

Paper sections:

Halolactonization of unsaturated carboxylic acids is an important reaction that has been widely used in organic synthesis, especially for the preparation of molecules of biological relevance.1,2 Accordingly, the development of methods for inducing catalytic, enantioselective halolactonizations in general has become of great interest, and some notable successes have been recorded.3,4 Despite considerable effort, there remain some significant gaps in the area that arise, in part, from the propensity of iodonium and bromonium ions to undergo facile racemization via exchange with olefins prior to cyclization with an internal nucleophile.5 In particular, we are aware of no examples of catalytic, halolactonizations of unsaturated, alkyl-substituted carboxylic acids 1 (n = 1, 2; R1–R3 = H, alkyl) that proceed via 5- or 6-exo modes of ring closure to give lactones 2 in which new carbon-halogen bonds are created at stereogenic centers with high enantioselectivity (eq 1);3h however, enantioselective bromolactonizations of 1 (n = 2, R1 = aryl, and R2 or R3 = alkyl) via 6-exo closures have been recently disclosed.3k The 5-exo cyclizations of unsaturated alcohols to generate stereogenic carbon-halogen bonds by haloetherification are known,6 but the products, which are cyclic ethers, are arguably less versatile as synthetic intermediates than the corresponding lactones. For example, halolactones may be readily converted into halohydrins and epoxides. Finally, we are aware of no examples of catalytic, enantioselective halolactonizations involving prochiral dienes.

In the context of several ongoing projects in natural product synthesis, we encountered a requirement to induce the enantioselective bromolactonizations of a number of structurally different alkenes. We thus sought to address the existing problems in the field with a novel approach to bifunctional catalyst design.7 Mechanistic considerations suggest that a Lewis base can mediate proton transfer and/or stabilize the intermediate bromonium ion,5c and a Lewis or Brønsted acid can activate the brominating agent.4b These catalytic elements must then be incorporated on a suitable chiral scaffold. There are a number of possibilities, but we decided to use the binaphthyl backbone, which has been widely used as a chiral template for catalyst design.8 Although BINOL-derived catalysts have been used to promote enantioselective iodo–diene cyclizations 9 and haloetherifications,6 binaphthyl-derived ligands do not appear to have been used in halolactonizations. Accordingly, we envisioned that 5, employing a bifunctional partnership of an amidine moiety3e,k and a phenolic –OH group,10 might be an effective catalyst. Bulky groups at the 3- and/or 3′-position of binaphthyl ligands can enhance stereoselectivity, so a 3-phenyl group was incorporated in the first generation catalyst. Catalyst 5 can be readily made on multigram scale in seven steps and 41% overall yield from commercially available material. Monotriflation of 3-phenyl-BINOL (3), which was prepared by the protocol of Shi,11 followed by nickel(0)-catalyzed cyanation provided 4 in 78% yield (2-steps). Reduction of nitrile 4 to the amine and subsequent amidine formation delivered the catalyst 5 in 71% yield (2-steps) (Scheme 1).

The validity of this new catalyst design was quickly confirmed in preliminary experiments. At the low temperatures required to minimize the background reaction, the commonly used "Br+" sources N-bromosuccinimide (NBS) and N,N′-dibromodimethyl hydantoin (DBDMH) gave only trace amounts of product. However, we found that bromolactonizations of a series of 5-alkyl-4(Z)-pentenoic acids 6a–e using 2,4,4,6-tetrabromocyclohexadienone (TBCO) (1.2 equiv) as the brominating agent and 10 mol % of the catalyst 5 proceeded with high regioselectivity to deliver the corresponding γ-lactones 7a–e in excellent yields (eq 2), with enantiomeric ratios (er) between 95:5 – 98:2 for branched alkyl substrates 6b–e and 85:15 for the n-alkyl substrate 6a (Table 1, entries a–e).12 The observation that TBCO is superior to NBS and DBDMH is surprising as in other reports TBCO has been shown to be less efficacious than NBS and DBDMH as a source of electrophilic bromine. 3h,j

These reactions represent the first examples of catalytic bromolactonizations of alkyl-substituted olefinic acids that proceed via a 5-exo mode of ring closure to give products in which stereogenic carbon–bromine bonds have been formed with high enantioselectivity. The enantioselectivity for the bromolactonizations of Z-olefins was significantly higher than those for the corresponding E-olefins. For example, E-6c (R1 = i-Pr, R2 = H) underwent cyclization to give the diastereomer of 7c in 98% yield but in 71:29 er. Similar to the findings of Yeung,3g 5-aryl-4(E)-pentenoic acids 6f–h underwent bromolactonization via a 6-endo cyclization mode to give the corresponding δ-lactones 8f–h in uniformly high yield and enantioselectivity (Table 1, entries f–h).

Enantioselective halolactonizations of 4-aryl-4-enoic acid substrates via a 5-exo cyclization mode are well precedented (eq 3), 3b,d–f and we found that 5 also catalyzes the cyclizations of 9a–c in the presence of TBCO to furnish the γ-lactones 10a–c in high yield and er (Table 2, entries a–c). The electronic nature of aryl substituents plays an important role in these reactions; greater electron withdrawing power enhances the enantioselectivity.13 When the 5-substituted-5-eneoic acids 9e,f are used as substrates, the bromolactonization proceeds via a 6-exo mode to give δ-lactones 11e,f (Table 2, entries e,f).3d,e To our knowledge the exo cyclizations of 9d,f are the first examples of a catalytic, enantioselective halolactonization of a trialkyl-substituted olefinic acids to give lactones in which a stereogenic carbon- bromine bond is formed (Table 2, entries d,f), although a related bromolactonization of an aryl-substituted unsaturated acid was recently reported.3k It is noteworthy that the enantioselectivity for the 6-exo cyclization of 9f is somewhat higher than that for the 5-exo cyclization of 9d.

A major challenge to any catalytic, enantioselective transformation is its application to the desymmetrization of prochiral substrates. It is thus significant that 5 catalyzes the bromolactonization of prochiral dienoic acids as exemplified by the conversion of 12 into 13, the absolute stereochemistry of which was established by x-ray analysis, with high regioselectivity and 73:27 er (eq 4). It is noteworthy that similar bromolactonizations to give racemic products have been used as key steps in the syntheses of several naturally occurring compounds.14

The basic mechanistic features of bromonium ion-initiated cyclizations are reasonably well established.4b,5c Catalyst 5 is unusual in that it contains relatively acidic phenolic- and highly basic amidine-functions, so determining the identities of the Brønsted acid and the Lewis base is somewhat problematic. With this caveat in mind, one tentative working model that is consistent with the stereochemical outcome of bromolactonizations catalyzed by 5 is shown in Figure 1. We assume that hydrogen bonding between the phenolic –OH and the carboxyl group orients the substrate relative to the catalyst and that the substituent on the olefin is directed away from the face of the binaphthyl scaffold in a way that minimizes torsional strain within the substrate and steric interactions with the catalyst. The bromonium ion is presumably then stabilized by interaction with the amidine moiety. Our preliminary analysis suggests that the amidine may be an important stereochemical control element in these reactions, although the 3-phenyl group does appear to help by compressing the substrate toward the amidine moiety. In support of this hypothesis, we performed a test experiment and found that the norphenyl analog of 5 catalyzed the bromolactonization of 9a to give 10a with somewhat lower (81:19 er) enantioselectivity than 5 (Table 2, entry a).

In summary, we have developed 5 as a novel bifunctional catalyst to promote highly efficient and enantioselective bromolactonizations of an unusually broad array of structurally distinct, unsaturated acids. Like other known catalysts, 5 promotes highly enantioselective bromolactonizations of 4- and 5-aryl-4-pentenoic acids, but unlike those catalysts, it induces the bromolactonizations of alkyl-4(Z)-pentenoic acids via 5-exo cyclizations to give lactones in which new carbon–bromine bonds have been formed at stereogenic centers with high enantiomeric ratios. Bromolactonizations of trisubstituted olefinic acids that proceed via 5- and 6-exo cyclizations occur with good enantioselectivity. We also disclose the first example of the desymmetrization of a prochiral dienoic acid by a catalytic, enantioselective bromolactonization. Although the enantiomeric ratios observed for the bromolactonizations of more demanding substrates is modest, the chiral framework of 5 offers numerous opportunities for structural modification to improve enantioselectivities and to extend the utility of this class of catalysts to other electrophile-initiated cyclizations, including iodo- and chloro-lactonizations. These developments as well as the use of catalysts related to 5 in key steps in complex molecule synthesis will be reported in due course.

Answer: A novel bifunctional catalyst derived from BINOL has been developed that promotes the highly enantioselective bromolactonizations of a number of structurally distinct unsaturated acids. Like some known catalysts, this catalyst promotes highly enantioselective bromolactonizations of 4- and 5-aryl-4-pentenoic acids, but it also catalyzes the highly enantioselective bromolactonizations of 5-alkyl-4(Z)-pentenoic acids. These reactions represent the first catalytic bromolactonizations of alkyl-substituted olefinic acids that proceed via 5-exo mode cyclizations to give lactones in which new carbon\xe2\x80\x93bromine bonds are formed at a stereogenic center with high enantioselectivity. We also disclose the first catalytic desymmetrization of a prochiral dienoic acid by enantioselective bromolactonization.


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 may 2001 , 24 cases of s. typhimurium dt160 salmonellosis were reported in the auckland region compared with an average of four sporadic cases each month with this serotype in the previous 7 months .
raw and undercooked egg consumption was commonly reported by the first 10 case - patients interviewed .
a case - control study and environmental investigation were undertaken to identify the vehicle of infection and source of the outbreak .
recognizing the potential for a widely dispersed foodborne outbreak , we expanded the investigation throughout new zealand .
we defined a case as diarrhea ( 3 loose stools in a 24-hour period ) or vomiting after april 28 , 2001 , with a stool specimen positive for s. typhimurium dt160 .
patients were excluded if they had a history of contact with another person with culture - confirmed s. typhimurium dt160 infection , or if they had a history of recent overseas travel . each case
was matched with two controls found from randomly drawn telephone numbers , matching for neighborhood and age ( < 1 , 14 , 514 , > 14 years ) .
the questionnaire covered symptoms ( patients only ) and contact with other symptomatic persons , bird or animal contact , and food consumption in the 3-day period before onset of illness ( cases and controls ) . parents or guardians were interviewed on behalf of children ages < 12 years .
stepwise conditional logistic regression analyses were performed , also using sas , to identify the combination of variables that best explained the differences between case - participants and controls .
samples from the drinking water supply of case - patients with a history of recent consumption of nonreticulated water were collected and tested for coliforms and s. enterica by using standard methods ( 6 ) .
brands of eggs eaten raw within the incubation period were sampled at random from retail displays at the case - patients purchase site .
eggshell surfaces and contents were tested with standard methods ( 7 ) . broken or cracked eggs were excluded from analysis .
salmonella isolates were serotyped by using the kauffman - white scheme ( 8) and s. typhimurium isolates were phage typed by using the laboratory of enteric pathogens method ( 9 ) . from may
to august 2001 , a total of 170 case - patients meeting the case definition were identified . of these , 119 ( 70% )
agreed to participate and were enrolled in the study , along with 235 matched controls .
the median age of case - patients was 8 years ( range 4 months to 90 years ) , and 57% were female .
the most frequently reported symptoms were diarrhea ( 97% ) , abdominal pain ( 77% ) , excessive tiredness ( 67% ) , and fever ( 66% ) .
the median duration of illness was 7 days ( range 144 days ) ; 17 ( 15% ) patients were hospitalized , and none died .
case - patients and controls did not differ significantly according to age , sex , immunosuppressive therapy , treatment to reduce gastric acidity , or use of antibiotics .
all s. typhimurium dt160 isolates were sensitive to ampicillin , cephalothin , chloramphenicol , ciprofloxacin , co - trimoxazole , gentamicin , streptomycin , sulfonamides , tetracycline , and trimethoprim .
four represented different levels of contact with other persons with gastrointestinal illness ( i.e. , within 28 days of illness onset ; within 3 days of onset ; within the household ; or outside the household ) . direct handling of dead wild birds , consumption of fast food , and consumption of food at a large gathering , such as at a party or large barbecue , were also significantly associated with illness .
after stepwise regression , contact with a person with gastrointestinal illness in the 28 days before onset of illness in the case - patient ( adjusted odds ratio [ or ] 2.8 ; 95% confidence interval [ ci ] 1.4 to 5.4 ) , exposure to dead wild birds ( adjusted or 10.5 ; 95% ci 2.3 to 47.5 ) , and consumption of fast food ( adjusted or 1.7 ; 95% ci 1.0 to 2.9 ) had independent significant associations with illness .
dt , definitive type ; d&v , diarrhea and vomiting ; or , odds ratio ; ci , confidence interval .
twelve case - patients throughout new zealand indicated that they had drunk water from nonreticulated and untreated water sources .
seven patients used roof - collected rainwater , and one used rainwater plus water from a dam .
four of the five patients who had eaten raw eggs could identify the retail brand and outlet of purchase .
these four patients had purchased six different brands of eggs from seven different retail outlets .
samples for two brands were positive for s. thompson , both from shell surface washings .
epidemiologic investigation of an outbreak of s. typhimurium dt160 infection in new from may to august 2001 found that contact with dead wild birds , contact with other persons with gastrointestinal illness , and consumption of fast food were all significantly associated with illness .
in addition , s. typhimurium dt160 was found in roof - collected rainwater drunk by five patients .
s. typhimurium dt160 had been previously identified as the cause of large numbers of sparrow deaths in new zealand in 2000 , and analysis by pulsed - field gel electrophoresis ( using the method described by barrett et al
.   and restriction enzyme xbai ) demonstrated that bird and human isolates in 2000 were indistinguishable ( 4 ) . in our study , information was not collected on exposure to environments contaminated by wild bird feces , such as parks and play areas , a fact that may have underestimated the avian contribution to human illness .
s. typhimurium dt160 has previously been recognized as a bird pathogen in canada ( 11 ) and in england ( 12 ) . before its emergence in new zealand , the human s. typhimurium
dt160 infection had only been reported in the context of a 1979 institutional outbreak in the united kingdom , linked to food contamination by sparrow droppings ( 13 ) .
consumption of undisinfected water has previously been identified as a risk factor for salmonellosis linked to bird transmission ( 14 ) .
this risk factor was not confirmed by our case - control study , despite the finding of s. typhimurium dt160 in roof - collected rainwater .
this discrepancy is probably because case - patients and controls were matched by neighborhood , and types of water sources are usually consistent within neighborhoods .
the association of illness with contact with another person with gastrointestinal illness is likely underestimated because secondary salmonellosis cases were excluded .
consumption of fast food was associated with illness ; however , no single type of food outlet or food was identified .
case - patients were equally likely to have eaten food from chain fast - food restaurants as from family - owned fast - food outlets .
consumption of fast food may have occurred in environments contaminated by bird feces , or the foods themselves may have been contaminated , either during production or by infected foodhandlers ( 15 ) .
asymptomatic salmonella carriers would not have been excluded from selection as controls , potentially reducing the magnitude of observed associations .
recall may have been influenced by delays between exposure and interview , although participants were asked to refer to a memory aid ( personal diary or calendar ) .
the investigation successfully excluded a single common source exposure for this outbreak and instead suggested that multiple exposures contribute to s. typhimurium dt160 infections in new zealand .
strategies for addressing these exposures include routine treatment of roof - collected rainwater , hygienic disposal of dead birds , and promotion of hand - hygiene protocols and sick foodhandler policies in fast - food outlets .
the source of this incursion of s. typhimurium dt160 into new zealand remains unknown : bird isolates have been exclusively from nonmigratory birds , s. typhimurium dt160 has not been identified in neighboring countries in the pacific basin , and early case - patients did not have a history of overseas travel .

Answer:
an outbreak of human salmonella enterica serotype typhimurium dt160 infection in new zealand was investigated from may to august 2001 .
 handling of dead wild birds , contact with persons with diarrheal illness , and consumption of fast food were associated with infection .
 contaminated roof - collected rainwater was also detected .


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

Paper text:
a 20-year - old refugee from liberia was referred to our hospital because of a loud murmur .
, he had been admitted to a hospital in his home country several times because of respiratory tract infections and  heart
problems. he had a low body weight of 45  kg at a height of 1.63  m. he was hypertensive with a 50  mmhg difference in systolic blood pressure between his upper and lower extremities : 170 vs. 120  mmhg .
the electrocardiogram showed sinus rhythm 84 beats / min with signs of left ventricular hypertrophy .
1 ) revealed a dilated , hypertrophied and hyperdynamic left ventricle due to a large pda with a continuous left - to - right shunt .
just distal to the pda , narrowing of the aorta was visible , with an increased systolic flow velocity .
the absence of a classic  sawtooth pattern in the continuous wave signal from the descending aorta as well as the presence of holodiastolic flow reversal in the abdominal aorta suggested non - severe coarctation .
the cardiac valves showed no abnormalities except for a mild pulmonary regurgitation with an early - diastolic flow velocity of around 3  m per second , suggestive of elevated pulmonary artery pressure .
the descending thoracic aortic wall had an irregular aspect and its narrowing was most severe just distal to the pda .
right ventricular and main pulmonary artery pressures were elevated ( systolic right ventricular pressure 55  mmhg , main pulmonary artery pressure 48/31  mmhg at a systemic blood pressure of 167/84  mmhg ) , but peripheral pulmonary artery pressures were normal .
a peak - to - peak gradient of 50  mmhg was measured in the descending aorta .

1transthoracic echocardiography in patient a. a apical four - chamber view showing dilated and hypertrophied left ventricle .
b parasternal view of the pulmonary trunk and arteries showing turbulent flow due to a pda with left - to - right shunting ; a stenosis of the proximal right pulmonary artery is also visible ( asterisk ) . c suprasternal view showing pda ( asterisk ) as well as coarctation of the aorta .
d continuous wave doppler signal from the descending aorta , showing elevated systolic flow velocity of about 4  m per second .
2preoperative and postoperative magnetic resonance angiography . a preoperative magnetic resonance angiography ( mra ) of the aorta ( sagittal plane ) , showing large pda ( black arrow ) and irregular aspect of the descending aorta with coarctation distal to the pda ( white arrow ) .
b repeat mra of the aorta after surgical correction of the pda , showing irregular aspect and ( mild ) residual stenosis / coarctation of the descending aorta transthoracic echocardiography in patient a. a apical four - chamber view showing dilated and hypertrophied left ventricle .
b parasternal view of the pulmonary trunk and arteries showing turbulent flow due to a pda with left - to - right shunting ; a stenosis of the proximal right pulmonary artery is also visible ( asterisk ) . c suprasternal view showing pda ( asterisk ) as well as coarctation of the aorta .
d continuous wave doppler signal from the descending aorta , showing elevated systolic flow velocity of about 4  m per second .
a typical  sawtooth pattern is lacking preoperative and postoperative magnetic resonance angiography . a preoperative magnetic resonance angiography ( mra ) of the aorta ( sagittal plane ) , showing large pda ( black arrow ) and irregular aspect of the descending aorta with coarctation distal to the pda ( white arrow ) .
b repeat mra of the aorta after surgical correction of the pda , showing irregular aspect and ( mild ) residual stenosis / coarctation of the descending aorta the patient was referred for surgery .
closure of the ductus arteriosus was performed and the pulmonary artery was reconstructed ( fig .
after ligation of the pda , the pressure gradient in the descending aorta had decreased from 50 to 20  mmhg and this ( mild ) residual coarctation was left untreated . whether it will need ( percutaneous ) treatment in the future remains to be seen .
he had previously been diagnosed with severe hypertension with a poor response to medical therapy .
approximately eight years prior to referral to our hospital , echocardiography had already revealed left ventricular hypertrophy .
moreover , it showed a pda with a continuous left - to - right shunt . a murmur had never been heard . at that time
when he was referred to our outpatient clinic he did not have any cardiac complaints , although his exercise capacity had gradually deteriorated over the past year .
in addition to the pda , echocardiography now showed not only left , but also right ventricular hypertrophy and an estimated right ventricular systolic pressure of 57  mmhg .
he was referred for treatment of his pda on the assumption that it had contributed to the development of pulmonary hypertension .
it must be noted that the pda was silent and did not appear very large on echocardiographic and mri .
moreover , diastolic dysfunction due to left ventricular hypertrophy may have played an important role in the development of pulmonary hypertension as well .
however , a contribution of the pda to the development of pulmonary hypertension could not be excluded and the patient was therefore accepted for percutaneous closure of the pda .
angiography of the aortic arch and the occluded pda with coil in situ can be seen in fig .
in due time , echocardiography will be repeated to document whether his pulmonary artery pressure will decrease .

mri visualised the jet of the pda flow entering the pulmonary bifurcation ( black arrow)fig .
mri visualised the jet of the pda flow entering the pulmonary bifurcation ( black arrow ) angiography of the aortic arch .
pda is usually diagnosed shortly after birth , and treated surgically or percutaneously to prevent the development of pulmonary hypertension and heart failure .
the first case represents a more complex form of pda , associated with additional congenital cardiovascular anomalies and with left ventricular volume overload as one of its main characteristics . in the second patient ,
pulmonary hypertension was the sole reason for closure of the pda , and left ventricular dilation had not developed .
a difference in shunt size is probably the main reason for this difference . in addition
, it may be possible that patient b s severe left ventricular hypertrophy due to hypertension prevented left ventricular dilatation .
closure of a pda is only feasible when irreversible pulmonary hypertension has not yet developed . in adults ,
a , surgical correction of the pda was performed because of its large size and concomitant anomalous aortic anatomy .
pda patients who are beyond surgical or percutaneous closure should be treated according to the guidelines for eisenmenger syndrome .

Answer:
patent ductus arteriosus ( pda ) is a rare diagnosis in adults , since symptoms and signs usually occur in infancy and most cases are treated shortly after diagnosis .
 we present two patients who were first diagnosed with pda during adulthood .
 the first case represents a more severe form of pda , where the need for closure of the pda is obvious . in the second case
 the sequelae of the pda are less clear . in both
 patients , closure of the pda ( surgically in one case , percutaneously in the other ) was successful .