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:
carcinomas producing granulocyte colony - stimulating factor ( g - csf ) are extremely malignant and have a poor prognosis [ 1 , 2 ] .
thus , a liposarcoma producing g - csf is particularly rare and has only been described in a few case reports [ 1 , 3 ] . here ,
the tumor also showed spontaneous rupture , which has not been previously reported for retroperitoneal liposarcoma .
positron emission tomography using f - fluorodeoxyglucose ( f - fdg - pet ) is used to detect tumors based on elevated glucose metabolism in carcinoma cells .
it has also been shown that f - fdg uptake by bone marrow is correlated with the peripheral blood neutrophil count , since uptake reflects increased marrow metabolism .
we performed f - fdg - pet with computed tomography ( pet / ct ) for imaging of the g - csf - producing tumor and found high f - fdg uptake by the tumor itself and diffuse uptake throughout the bone marrow .
these are the first pet / ct images of a g - csf - producing tumor in a urological disease .
the patient was a 63-year - old man with a history of hypertension and no specific family history .
he was taken to the emergency department of our hospital due to significant aggravation of the pain in late july 2008 . an abdominal ct imaging ( fig .
1 ) revealed a non - fatty , non - fibrotic , and non - calcified right retroperitoneal tumor of 15 cm in size and retroperitoneal hemorrhage .
hemorrhagic shock occurred due to spontaneous rupture of the retroperitoneal tumor during the examination , and an emergency transcatheter arterial embolization was conducted .
the nutrient vessels were the superior and inferior suprarenal arteries , inferior phrenic artery , renal capsular artery , and the first lumbar artery .
three days after admission , the patient was transferred to our department for a more detailed examination of the retroperitoneal tumor .
a routine peripheral hematological examination indicated a high white blood cell ( wbc ) count of 37,820/l and a strong left - shift of the differential leukocyte count , with a neutrophil count of 34,794/l .
however , no infection appeared to be present based on physiological and biochemical findings , and endocrinological tests showed no abnormal findings .
since the wbc count remained high after the transfer to our department , further tests were carried out at the department of hematological internal medicine , based on the suspicion of a g - csf - producing tumor or a comorbid hematological disease . in parallel ,
elevated uptake of < f - fdg correlated with the tumor site ( maximum standardized uptake value , suvmax , was 18.5 ) and the case was diagnosed as malignant .
pet / ct imaging also indicated diffuse uptake throughout the bone marrow , and particularly elevated uptake in the vertebral bone ( suvmax : 10.5 ) ( fig .
2 ) . however , bone scintigraphy showed no bone metastasis , and bone marrow biopsy revealed little fat , significant hyperplasia , and increased neutrophils , but no findings of metastasis or bone marrow involvement .
based on all the above findings and the high serum g - csf level of 2,670 pg / ml ( normal < 8 pg / ml ) , the cause of the increased wbc count was determined to be a g - csf - producing tumor .
a malignant tumor was suspected and right nephrectomy and retroperitoneal tumorectomy were conducted in mid - september .
however , since the tumor had infiltrated into the inferior vena cava , diaphragm and abdominal wall already , only partial resection of the tumor was performed .
histopathological tests using hematoxylin - eosin staining showed findings for malignant fibrous histiocytoma mixed with those for well - differentiated liposarcoma ( fig .
the tumor was diagnosed as dedifferentiated liposarcoma based on the diagnostic criteria of the world health classification ( who ) [ 5 , 6 ] .
the postoperative peripheral wbc count was 21,000/l and the serum g - csf level was 1,170 pg / ml , both of which showed a transient decrease . with informed consent from the patient , only symptomatic therapy , but no chemotherapy or radiotherapy , was carried out while observing the prognosis .
liposarcomas are morphologically subdivided into five main subgroups : well - differentiated , myxoid , round cell , pleomorphic , and dedifferentiated .
dedifferentiated liposarcoma was first recognized by evans in 1979   and was defined in 2002 as a tumor with a clear - cut and well - differentiated component clearly separated from or occupying a large area beside a poorly differentiated component [ 5 , 6 ] . among 78 cases of retroperitoneal liposarcoma ,
fabre - guillevin et al .   described 52 cases of dedifferentiated liposarcoma with a differentiated component with features of malignant fibrous histiocytoma ( 36 undifferentiated pleomorphic sarcoma ; 14 fibrosarcoma ; 1 myxofibrosarcoma ; 1 osteosarcoma ; and/or 4 leiomyosarcoma ) , 21 of well - differentiated liposarcoma , 2 of myxoid liposarcoma , 2 of round cell liposarcoma , and 1 of pleomorphic liposarcoma .
the cases of dedifferentiated liposarcoma had local recurrence and metastasis at rates of about 40 and 20% , respectively , and a poorer clinical outcome compared to well - differentiated liposarcoma [ 6 , 7 ] .
the production of g - csf has been reported in cases of hepatocellular carcinoma , pancreatic cancer , and gastric cancer [ 8 , 9 , 10 ] .
g - csf - producing carcinomas show aggressive growth and a very poor prognosis [ 8 , 9 , 10 ] .
there have only been a few previous case reports of a g - csf - producing liposarcoma [ 1 , 3 ] .
six cases of liposarcoma accompanied by leukocytosis have been described in the english literature . however
, the g - csf level has only been evaluated in 3 cases : in an upper arm dedifferentiated liposarcoma described by sakamoto et al .
, in a mesenteric pleomorphic liposarcoma reported by nakamura et al . , and in the current case .
in all 3 cases , the g - csf level and peripheral wbc counts were correlated with the clinical course .
the g - csf level and wbc count showed a transient postoperative decrease in our patient , but this was followed by an aggressive clinical course and the wbc count was 145,800/l at the time the patient died .
no hematological diseases such as leukemia or a leukemoid reaction were observed and bone marrow biopsy only showed hyperplasia .
these findings led to the diagnosis of a g - csf - producing retroperitoneal dedifferentiated liposarcoma .
this is an extremely rare clinical presentation , with the description of spontaneous rupture of a renal liposarcoma by mazuch et al .
the rapid aggressive growth of the g - csf - producing tumor may have caused the rupture , and palliative surgery was performed because of the rupture .
pet / ct is useful for the evaluation of malignant lesions . in cases of carcinoma , diffuse f - fdg uptake in bone marrow is often indicative of bone metastasis or bone marrow involvement . in our case ,
pet / ct showed diffuse f - fdg uptake throughout the bone marrow , which indicated multiple bone metastases .
described 2 cases of g - csf - producing lung cancer that showed diffuse f - fdg uptake throughout the bone marrow .
commented that diffuse elevated f - fdg uptake in bone marrow may be helpful in the diagnosis of a g - csf - producing tumor .
bone metastasis is a differential diagnosis , and in our case bone scintigraphy and bone marrow biopsy were useful for ruling out bone metastasis .
murata et al .   showed that f - fdg uptake by bone marrow is strongly correlated with the wbc count ( especially neutrophil count ) and suggested that f - fdg uptake by bone marrow reflects marrow metabolism , which is mainly regulated by granulocyte progenitors and stimulated by endogenous hematopoietic growth factors .
found increased f - fdg uptake in patients treated with g - csf and showed that the increased uptake returned to the pretreatment value approximately 1 month after discontinuation of g - csf . the serum g - csf level is likely to be higher in patients with a g - csf - producing tumor than in those treated with g - csf
thus , for a g - csf - producing tumor , at least 1 month is needed before a pet / ct evaluation after removal of the primary lesion .
other conditions associated with diffuse f - fdg uptake in the bone marrow include marrow hyperplasia resulting from hemolytic / iron - deficiency / blood - loss anemia .
in addition , van de weile et al .   examined the relationship between bone marrow f - fdg uptake and levels of serum cytokines . in patients with non - small cell lung carcinomas , which are known to produce cytokines , f - fdg uptake by bone marrow
thus , bone marrow f - fdg uptake in patients with a g - csf - producing tumor may also be related to cytokines such as tgf-. in conclusion , we encountered a rare case of a g - csf - producing retroperitoneal dedifferentiated liposarcoma that underwent spontaneous rupture due to rapid aggressive growth .
this case is also the first report of pet / ct imaging of a g - csf - producing tumor in a urological disease .
in such cases , one needs to be careful to avoid a misdiagnosis of bone metastasis , but imaging may be useful for differential diagnosis of a g - csf - producing tumor in patients with abnormally high wbc counts in the absence of infection .

Answer:
the patient was a 63-year - old man who was referred to our hospital as an emergency case with the chief complaint of abdominal pain .
 an abdominal ct revealed a right retroperitoneal tumor of 15 cm and retroperitoneal bleeding .
 after a transcatheter arterial embolization was performed , the patient was transferred to our department .
 there was no infective focus .
 the white blood cell ( wbc ) count ( 37,820/l , normal range < 8 pg / ml ) and the serum granulocyte colony - stimulating factor ( g - csf ) level ( 2,670 pg / ml , normal range < 8 pg / ml ) were high .
 bone marrow biopsy revealed little fat , significant hyperplasia , and predominantly increased neutrophils , but no findings of bone metastasis or bone marrow involvement .
 a g - csf - producing tumor was diagnosed and right nephrectomy and retroperitoneal tumorectomy were performed .
 however , the tumor had infiltrated into the inferior vena cava , diaphragm and abdominal wall , and only part of the tumor could be removed . in histopathological tests ,
 hematoxylin - eosin staining showed malignant fibrous histiocytoma - like findings mixed with those for well - differentiated liposarcoma , and the case was diagnosed as dedifferentiated liposarcoma .
 preoperative 18f - fdg - pet computed tomography showed diffuse 18f - fdg uptake throughout the bone marrow and elevated uptake at the tumor site .
 however , since bone biopsy and bone scintigraphy indicated no bone metastasis or bone marrow involvement , we concluded that pet / ct imaging gave false - positive results in the bone marrow .
 this is the first report of pet / ct imaging of a g - csf - producing tumor in a urological disease .
 the imaging results may be useful for differential diagnosis for this tumor in patients with high wbc counts without infection .


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:
achaete - scute homolog 1 basic helix - loop - helix chromodomain helicase dna binding protein 7 central nervous system gamma - aminobutyric acid histone acetyl transferase long interspersed nuclear element 1 neuroepithelial precursor nucleosome remodelling and deacetylase oligodendrocyte precursor cell silencing mediator for retinoid and thyroid receptors nuclear receptor corepressors
a look into the pubmed database reveals that sox2 is one of the most studied transcription factors of recent years . in 2013 alone , there are about 750 publications mentioning sox2 in title or abstract .
after all , sox2 is intimately linked in the scientific consciousness to stem cells , both embryonic and neural , where it is key to induction and maintenance of pluripotency .
it is also one of the 4 classical reprogramming factors that are necessary for the generation of induced pluripotent stem cells .
sox2 is originally expressed in all blastomeres , and later in all cells of the inner cell mass and the epiblast .
high sox2 expression results both in the suppression of mesendodermal differentiation , and the induction of a neuroectodermal fate . in the early neuroectoderm
, sox2 is expressed in all nep ( neuroepithelial precursor ) cells often together with its close relatives sox1 and sox3 .
these 3 related proteins constitute the soxb1 group , and jointly ensure expansion and maintenance of nep cells .
expression of sox2 remains associated with nep cells throughout development of the early neuroectoderm into the cns ( central nervous system ) , and is even maintained in the adult where sox2 is found in adult neural stem cells in the subventricular zone of the lateral ventricle walls and in the subgranular zone of the dentate gyrus .
. one of the mechanisms by which this is achieved , is suppression of premature neurogenesis . in accord ,
soxb1 proteins have been shown to counteract the activity of proneural bhlh ( basic helix - loop - helix ) proteins such as ascl1 and ngn1 in the early neural tube , and to repress neuronal gene expression . at first glance soxb1 proteins therefore appear to function prominently as repressors .
indeed , such functions have been described for sox2 in studies on the transcriptional regulation of the neurod1 transcription factor and line-1 retrotransposons which both exert neurogenic activity .
it has been postulated that sox2 represses neurod1 and line-1 expression by direct binding to the corresponding regulatory regions and recruitment of transcriptional co - repressors such as hdac1 ( histone deacetylase1 ) so that wnt/-catenin - dependent activation of transcription can not take place . while such function as a classical transcriptional repressor exists for a subset of its target genes and is thus biologically relevant , there is ample evidence that soxb1 proteins  when acting as transcription factors
this is already suggested by standard in vitro tests for transcriptional activity , which readily identify a transactivation domain in the proteins carboxyterminal half , but fail to detect repressor functions .
results from in ovo electroporation experiments in the early chicken neural tube also point to a predominantly transactivating function . in this type of experiment ,
sox2 function is mimicked by a chimeric protein in which the aminoterminal half of sox2 ( which includes its dna - binding hmg - domain ) is combined with a constitutively active heterologous transactivation domain from the herpesviral vp16 protein .
analogous combination of the aminoterminal half of sox2 with the strong repressor domain of the drosophila engrailed protein in contrast changed properties completely and reversed sox2 from an anti - neurogenic into a neurogenic factor as the resulting chimeric protein forced nep cell cycle exit and induced premature expression of neuronal markers .
this argues that suppression of neurogenesis is mostly indirect and involves the induction of factors , that then act as inhibitors of neurogenic proteins . what these factors are has not yet been analyzed in detail .

sox2 exerts its diverse effects on gene expression during cns development by influencing epigenetics , transcription and micrornas .
it regulates histone modifying enzymes and chromatin remodellers as a pre - patterning factor , and at the same time acts as an activating ( or repressing ) transcription factor to influence transcription of pluripotency and differentiation genes .
additionally , it impacts on neural and glial gene expression through modulation of micrornas .

sox2 exerts its diverse effects on gene expression during cns development by influencing epigenetics , transcription and micrornas .
it regulates histone modifying enzymes and chromatin remodellers as a pre - patterning factor , and at the same time acts as an activating ( or repressing ) transcription factor to influence transcription of pluripotency and differentiation genes .
in addition to its role as transcription factor , sox2 has epigenetic , chromatin - associated functions ( fig .
genome - wide chromatin immunoprecipitation studies suggest that sox2 functions as a pre - patterning or pioneer factor ( for review see ref .
such factors have the capacity to preselect and bind regulatory regions and thereby configure the local chromatin in a way that the corresponding genes are kept in a poised state . as such
they are not yet actively transcribed , but have the potential to be easily activated in ensuing developmental stages , provided certain preconditions are met . in the context of neurogenesis , this means that sox2 not only binds to regulatory regions of genes whose products are required for realization and maintenance of nep cell properties .
it is also bound to regulatory regions of many neuronal differentiation genes , and thereby ensures that these genes can later be activated . for this to happen
, sox2 is down - regulated and replaced on these regulatory regions by other factors , in particular the soxc proteins sox4 and sox11 , which then cooperate with proneural and other neurogenic factors to drive neurogenesis .
this role as pioneer factor is supported by results from recent proteomic analyses , that find sox2 associated with many different histone modifying and chromatin remodelling complexes and proteins including nurd , smrt / ncor , swi / snf , chd7 , hats and hdacs .
this aspect of the overall function of sox2 is equally important as its classical transcription factor function .
although impossible to separate , one might argue in a somewhat simplistic manner that the role as transcription factor is most obvious for maintenance of nep cells and suppression of premature neuronal differentiation , whereas its role as pre - patterning / pioneer factor defines developmental potential and thus guarantees pluripotency . during development ,
oligodendroglia develop through the opc ( oligodendrocyte precursor cell ) stage into mature oligodendrocytes , the myelinating glia of the cns .
we noted that expression of sox2 and sox3 is maintained after nep cell specification into opc , and is downregulated in the oligodendroglial lineage not earlier than during terminal differentiation to mature myelinating oligodendrocytes .
by analogy to neuronal development we initially assumed that soxb1 proteins would ensure opc maintenance and suppress differentiation into oligodendrocytes .
neither deletion of sox2 alone nor in combination with sox3 interfered with proper proliferation or generation of opc in normal numbers .
thus , the role of sox2 and the related sox3 during oligodendrogenesis differs dramatically from the one during neurogenesis with soxb1 proteins being involved in oligodendroglial differentiation events rather than the maintenance of progenitor characteristics . despite this clear - cut overall difference
, it should be noted that differentiation functions have also been detected or proposed in late developmental phases of certain subtypes of retinal or gabaergic telencephalic neurons .
this argues that it is not a complete black - and - white between neurons and glia .
our mechanistic studies indicated that sox2 is bound to regulatory elements of myelin genes and that soxb1 proteins can act as moderate transactivators of glial differentiation genes ( fig .
however , activation potential appears much less than that of other activators of myelin gene expression such as sox10 and olig2 .
considering that expression of the latter is essentially unaltered in the combined absence of sox2 and sox3 , it appears unlikely that the differentiation defect observed in soxb1-deficient oligodendroglia is attributable to the lack of direct activation of differentiation genes by sox2 and sox3 .
rather we found evidence for an alternative mode of action that involved a microrna ( fig .
, sox2 counteracts expression of mir145 , which targets pro - differentiation factors such as the transcription factor myrf ( myelin gene regulatory factor ) or the mediator subunit med-12 that is equally required for terminal differentiation of oligodendrocytes . in the absence of sox2 , terminal differentiation of oligodendrocytes and hence myelination
are reduced at least in part because mir145 is de - repressed and inhibits expression of myrf and other factors that favor myelination .
our studies thus identify sox2-dependent modulation of microrna expression as another important facet of its action .
intriguingly , we also found evidence for a repressive influence of mir145 on sox2 expression , similar to what has been described in glioblastoma cells .
these findings argue that a reciprocal negative feedback - loop may exist in developing oligodendroglia between the 2 regulators .
the overall impression from current studies therefore is that  in addition to its role as a transcriptional activator
sox2 primarily functions as a pre - patterning / pioneer factor during neurogenesis and as a microrna regulator during oligodendrogenesis ( fig .
thus , it is legitimate to ask whether sox2 function during the 2 processes is indeed mechanistically as different as the evoked effect .
although there is no definite answer to this question , we like to suggest that this is not the case .
we rather assume that sox2 relies on all its different modes of action in both processes .
as already mentioned , we have found sox2 on regulatory regions of myelin genes in our study .
while this is compatible with a role of sox2 as a weak activator of myelin gene expression , it could equally be interpreted as the result of a pre - patterning function in which sox2 preselects those regulatory regions in opc that have to be activated later on in differentiating oligodendrocytes following the exchange of sox2 on these regions by sox10 .
thus , it seems perfectly plausible that sox2 also functions as a pre - patterning / pioneer factor in oligodendroglial differentiation . on the other side , a first functional link between sox2 and a microrna was recently detected during in vitro neurogenesis .
sox2 was found to activate expression of lin28 , which is a potent inhibitor of expression of the let-7 microrna family . let-7i in turn inhibits neuronal differentiation , by targeting among others the 2 proneural genes ascl1 and ngn1 .
these findings provide support for the assumption that at least some of the long known repressive effects of sox2 in nep cells on neurogenesis may be mediated by micrornas that are under direct or indirect control of sox2 . in our opinion , sox2 is a true central regulator of gene expression because it acts not only at the transcriptional level , but also pretranscriptionally as a chromatin - associated pioneer factor and posttranscriptionally as a microrna modulator .
its mechanistic versatility is not only basis for its central role in many regulatory networks , but also endows it with a tremendous flexibility that allows it to acquire different tasks in diverse developmental setups including maintenance of the precursor state , suppression of neurogenesis and promotion of glial differentiation .

Answer:
the transcription factor sox2 is best known as a pluripotency factor in stem and precursor cells and its expression generally correlates with an undifferentiated state .
 proposed modes of action include those as classical transcription factor and pre - patterning factor with influence on histone modifications and chromatin structure .
 recently , we provided the first detailed analysis of sox2 expression and function during development of oligodendrocytes , the myelin - forming cells of the cns .
 surprisingly , we found evidence for a role of sox2 as differentiation factor and found it to act through modulation of microrna levels .
 thus , we add new facets to the functional repertoire of sox2 and throw light on the networking activity of this multitasking developmental regulator .


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 gene expression pathway initiates at nuclear transcription generating a pre - mrna , which very often undergoes splicing , post - transcriptional regulation , and then translation into a protein . during the pre - mrna splicing process
, introns are removed and exons are joined in order to generate the mature mrna [ 13 ] .
the formation of this functional megacomplex is an orchestrated assembly of proteins and rna that requires identification of exon - intron boundaries .
exons are regularly alternatively spliced , meaning that they are either included or excluded from the final mature mrna transcript .
a recent comprehensive sequencing study observed that more than 90% of the genes undergo alternative splicing .
this vastly increases the transcriptome repertoire , and emphasizes both the significance of splicing and the requirement for its accurate execution .
in addition to protein coding genes , noncoding genes are transcribed . micrornas ( mirna ) , the most comprehensive noncoding group , are a class of   ~22 nt noncoding rnas that inhibit gene expression through binding to the 3 untranslated region ( utr ) of target mrna transcripts [ 6 , 7 ] .
there are hundreds of unique mirnas in a given species , each predicted to regulate a plethora of target genes [ 913 ] .
in fact , computational predictions indicate that mirnas may regulate 60% of all human protein coding genes .
therefore , it came as no surprise that mirnas were linked to many cellular processes such as differentiation , growth , and apoptosis , while mirna perturbations were associated with numerous diseases , including cancer [ 16 , 17 ] . in the past few years
, the pivotal role played by mirnas in gene regulation has been recognized [ 1820 ] .
mirnas are processed through a series of post - transcriptional biogenesis steps . the canonical maturation pathway , similar to protein - coding genes , initiates at transcription ( mostly by rna polymerase ii ) generating a primary ( pri- ) mirna .
the pri - mirna is characterized by a hairpin rna structure recognized by the nuclear rnase - iii enzyme drosha , and its cofactor dgcr8 .
the microprocessor cleaves the pri - mirna to generate a shorter hairpin of about 70 nt length  the pre - mirna .
this intermediate mirna is exported from the nucleus to the cytoplasm via   exportin-5 where the rnase iii endonuclease dicer generates the final mature mirna .
this short rna loses one of its strands ( the complementary mirna * strand ) while the other is loaded onto an argonaute - containing rna - induced silencing complex ( risc ) which mediates gene silencing .
once the mirna binds to its target gene , regulation takes place mainly through mrna degradation or translation inhibition [ 22 , 23 ] ( see figure 1 ) . for simplicity , the widely used term
mirnas can be located inter- or intragenically . when intergenic , their expression is coordinated with other mirnas as a cluster [ 25 , 26 ] .
when intragenic , namely , positioned within a protein - coding gene ( almost exclusively in introns ) , they are often expressed from the same strand as their host - gene [ 2730 ] and at correlated levels . given that both coding mrnas and mirnas are generated from the same transcriptional unit , and that they cooccur in close cellular proximity , it would be puzzling if these events exhibited total independence .
recent studies , from transcription , mirna - processing , and splicing oriented perspectives , have investigated these fascinating interactions and yielded interesting , yet somewhat controversial findings .
relationships between intronic mirnas and the processing events of their host mrna , namely , transcription and splicing have been addressed . here
we outline the major studies in the field .   expressed sequence tag ( est ) libraries of expressed mrnas
the ests represent a snapshot of cellular transcripts at a particular time point and thus display the given mrna plethora and its variety at a particular cellular state .
analysis of this data revealed several chimeric transcripts containing mirna and part of the adjacent mrna sequences . at an early stage of mirna research
notably , at a later stage , some of these est fragments were shown to be partially spliced , with either 5 or 3 ends matching putative drosha cleavage sites .
these results strengthened the possibility that mirnas and mrnas are processed from the same rna substrate .
in addition , the correlated expression pattern of host - gene transcripts and their mirnas   suggested that mirnas have coevolved to use the same promoter for transcription .
along with this work , by comparing mirna processing in a construct containing only the intronic sequence versus one that also includes the flanking exons , pawlicki and steitz   found that the levels of pri - mirna transcribed from introns are increased in the presence of flanking exons , due to prolonged retention at the site of transcription .
this supported the notion that flanking exons may facilitate mirna processing by increasing the time pri - mirnas spend tethered to the dna template [ 33 , 34 ] .
altogether , the data indicates that intronic mirna processing is enhanced by physical proximity to the site of transcription , and possibly also by splicing of the host gene .
several groups have isolated and identified various proteins associated with the human microprocessor complex [ 3537 ] . in these studies ,
numerous microprocessor - associated proteins were identified as splicing factors ( e.g. , hnrnph1 ; ) or involved in pre - mrna processing ( e.g. , dhx15 ; ) . taken together , based on mirna - mrna transcriptional ( est ) evidence ; shared promoters ; facilitated biogenesis when flanked by exons ; and overlapping proteins between the functional complexes , the data suggests that the microprocessor is potentially enhanced and present during transcription and most likely also during splicing .
if the same rna substrate is subjected to both host - gene and intronic mirna maturation , the intriguing question raised is how do all these processes  transcription , pre - mrna splicing , and mirna processing
the complexity of the mirna - host - gene interaction model has increased recently when studies from the proudfoot laboratory demonstrated that pre - mirnas are generated through cotranscriptional cleavage by drosha .
suggested that efficient clearance of intronic sequences following microprocessor ( drosha ) cleavage may act to enhance the splicing efficiency .
these researchers showed that the microprocessor complex , as well as 5-3 and 3-5 rna exonucleases , are recruited to chromatin associated with intronic mirnas during transcription of the host primary transcript , and that drosha cleavage occurs before host intron splicing .
they found that mirna - harboring transcripts preferentially associated with chromatin fractions , from which they concluded that both pre - mirna cleavage and intronic splicing must occur on the same nascent transcripts .
the rapid exonucleolytic removal of intronic sequences may clear the proximal vicinity of rna processing for the purpose of efficiently completing the pre - mrna splicing task .
the enhancement of splicing by the microprocessor does not agree with other studies [ 30 , 40 ] ( discussed below ) and does not concur with experiments in yeast that showed enhanced processing for sirna flanked exons in splicing mutants .
dependencies are seen , for example , during the biogenesis process of small nucleolar rna ( snorna ) [ 4244 ] . in the process of snorna maturation , functional links between intronic snornp assembly ,
an antithesis to this dependency is the alternative mirna biogenesis pathway that bypasses the microprocessor via   generation of  mirtrons  [ 48 , 49 ] .
this mechanistically distinct class of intronic mirnas stem from very short introns where splicing substitutes the first step of mirna biogenesis . in this case , splicing activities replace the requirements for a microprocessor . however , not all roads lead to the observed dependency between microprocessing and splicing .
ying and lin   have designed an artificial intron containing a pre - mirna secondary structure .
they used this construct to show that the mature mirna was released only from the spliced intron .
this suggested that spliced introns are subsequently used by drosha and argued against any physical link between the microprocessor and the transcriptional unit or between the microprocessor and the spliceosome .
.   showed that exons of pre - mrna are tethered to the elongating rna polymerase ii either directly or indirectly without affecting processing , indicating that cotranscriptional cleavage of nascent intronic mirna transcripts does not affect splicing efficiency [ 40 , 51 ] . supporting the same view , kim and kim   addressed mirna biogenesis in light of the splicing mechanism .
they demonstrated that cleavage of an intronic mirna did not significantly affect the production of mature mrna and , conversely , the production of mature mirna was not significantly affected by splicing . in their experiments ,
knockdown of drosha , or mutations in the mirna hairpin , eliminated mirna generation without dramatically affecting mrna splicing .
this suggested that mirna biogenesis and splicing are coordinated but not functionally linked or interdependent . taking a closer look
, however , they also mention that drosha knockdown led to a modest increase in spliced mrna production and so did mutations in the mirna hairpin .
their work showed that the adjacent introns were spliced more rapidly than mirna - encoding introns , suggesting that binding of the microprocessor may eventually interfere with the splicing to some extent .
taken together , kim and kim 's data   imply mostly independent activities but can not exclude the possibility that the microprocessor interferes , to some level , with splicing . attempting to explain how both mirna and mrna are generated from the same dna locus , reconciling with the studies described here , we come up with two distinct models .
the second predicts generation of an mirna and mrna products arising from two independent rna transcripts ( see figure 2 ) . if the latter scenario was true , microprocessing and splicing would be independent of each other
. the outcome would be either no functional hindrance between the microprocessor and spliceosome activities or a competition for available pre - mrna substrates .
in the event that both rna products originate from the same precursor , it is conceivable that the two processes happen consecutively .
this would imply that execution of one process would be a prerequisite for the other to occur .
alternatively , mirna processing and mrna splicing may be coordinated so that the microprocessor and spliceosome interact with each other .
this interaction may be minimal , without affecting the amounts of mirna and mrna produced  as was suggested recently , or it may constitute a level of regulation .
we note that these events should always be looked at in the spatial - temporal context meaning that the microprocessor might act at an independent rate prior to the spliceosome assembly , and thus their direct interaction would be prevented . due to accumulating evidence , both in favor and against dependencies between splicing and microprocessing ,
the potential coordinated activity between the microprocessor and the spliceosome can be stratified into four possible relationships .
the microprocessor can inhibit or activate the spliceosome , and the spliceosome can inhibit or activate the microprocessor ( figure 3 ) .
, the microprocessor could activate the spliceosome by recruiting splicing factors to intronic mirnas , while at the same time the spliceosome could inhibit microprocessing .
we can not rule out , however , that these relationships occur in one large complex depending on the presence of particular rna processing proteins within the microprocessor .
many complex regulatory loops , both positive and negative , were seen in other cellular systems ( e.g. ,   see [ 52 , 53 ] ) .
the microprocessor , on the other hand , is composed of a handful of proteins [ 21 , 36 ] , minimally described as a two - protein complex [ 24 , 35 ] ( alternatively , see ) .
it is hard to visualize these two very differently - sized complexes aligned at the same position , competing for the same substrate .
thus , a coordinated processing and crosstalk seems necessary for these complexes  the microprocessor and the spliceosome  to be able to process the same transcript with intricate accuracy . during the mrna splicing process
, the rate at which transcription takes place may affect the transcripts ' pattern of splicing .
thus , kinetics of intron removal and exon ligation may play a role in selecting particular spliced isoforms .
given that some introns undergo mirna excision , unless the removal is extremely rapid , one can imagine a possible effect on splicing outcome .
thus , from an evolutionary perspective , an intronic mirna might evolve to participate in determining splicing kinetics .
consequently , an evolutionary driving force may direct mirna positioning within the intron to prevent disruption of relevant splice signals ( also see ) . in summary
how widespread is the mechanism and does it govern all intronic mirnas ? to date , not all microprocessor and spliceosome crosstalk scenarios ( as described in figure 3 ) have been identified . yet , given the complexity of cellular pathways , it is probably only a matter of time before their elucidation .

Answer:
micrornas ( mirnas ) are often hosted in introns of protein - coding genes . given that the same transcriptional unit can potentially give rise to both mirna and mrna transcripts
 raises the intriguing question of the level of interaction between these processes .
 recent studies from transcription , pre - mrna splicing , and mirna - processing perspectives have investigated these relationships and yielded interesting , yet somewhat controversial findings . here
 we discuss major studies in the field .


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:
MOLECULAR DOCKING STUDY TO IDENTIFY POTENTIAL INHIBITOR OF COVID-19 MAIN PROTEASE ENZYME: AN IN-SILICO APPROACH

Paper sections:

However, information about intermediary reservoir is still unknown [1]. Coronaviruses (CoVs) are the enveloped positive stranded RNA viruses, supposed to be possessing largest viral RNA genome known till date [2,3]. As per the recent situational report released by World Health Organization (WHO) on March 28, 2020, 571678 COVID-19 cases have been confirmed globally, including 62514 new cases and total 26494 deaths [4]. SARS-CoV-2 a highly infectious and pathogenic coronavirus has become global concern [5].

Recently sequence analysis confirmed that the SARS-CoV-2 belongs to the class of β-coronaviruses including SARS-CoV and MERS-CoV. [6)]. Since, SARS-CoV-2 is novel pathogenic coronavirus, till date no effective antiviral therapy is available. Preventive and supportive therapies are main approach for management of COVID-19. Around the globe researchers are endeavoring for the development of effective prevention and treatment strategies for COVID-19. Preliminary studies have suggested potential repurposing of available anti-viral drugs like protease inhibitors lopinavir/ritonavir, nucleoside analogues, neuraminidase inhibitors, remdesivir, umifenovir (arbidol), tenofovir disoproxil (TDF), and lamivudine (3TC), etc. for the treatment of COVID-19 infected patients [7]. In another study Camostat mesylate, a clinically approved TMPRSS2 inhibitor was found to block SARS-CoV-2 entry to human cells, indicating its therapeutic potential as a drug against COVID-19 [8]. Xu et al. (2020) in another investigation screened 1903 approved drugs by homology modeling, molecular docking and binding free energy calculation and suggested nelfinavir as potential inhibitor against SARS CoV-2 [9].

A sizeable body of data demonstrates anti-coronaviral effect from several natural products and herbal medicines. In separate investigations Phenolic compounds of Isatisindigotica, Amentoflavone isolated from Torreya nucifera and Houttuyniacordata water extract have shown SARS-CoV 3CL protease enzyme inhibitory potential against SARS-CoV. (10)(11)(12) Since the Main Protease M pro or Chemotrypsin-like-protease (3CL) which is highly conservable among SARS CoV and SARS-CoV-2 proved by sequential analysis; is suggested to be potential target to fight SARS-CoV-2 [6]. Recently, Khaerunnisa et al, reported M pro Inhibitory potential of kaempferol, quercetin, luteolin-7-glucoside, demethoxycurcumin, naringenin, apigenin-7-glucoside, oleuropein, curcumin, catechin, and epicatechin-gallate against COVID-19 [13]. Prompted by this, in present study we investigated Caffeine, Capsaicin, Hypericin, Gossypol, Luteolin, Berberine, Embelin,Oxyacanthine, Sanguinarine and Emodin as potential inhibitor candidates for SARS-CoV-2 M pro with the help of molecular docking study.

Material and Methods

The crystal structure of the molecular target, protease enzyme (COVID-19 3cl pro /M pro (PDB ID: 6LU7), was retrieved from RCSB protein data bank (https://www.rcsb.org/) [14]. Target needs to be prepared before starting the molecular docking process, which involves removal of the water molecules and native ligand attached with target and other heteroatoms which may provide hindrance in the simulation. Besides, hydrogen atoms were added into target. These all processes were carried out in the Auto Dock window execution file. Investigational ligands were designed using ChemSketch (ACD 2012) and optimized for energy minimization using MM2 force field and saved in.mol format subsequently converted into .pdb format by Open Bable -2.3.2 software. The investigation ligand was loaded and their torsion salong with rotatable bonds are assigned and the files are saved as ligand. PDBQT. In the current study, identification of binding modes of the herbal molecules with targetwas identified using Auto Dock 4.2 software program. Moreover, to confirm actual binding interaction with targets blind docking was performed and the best conformers were represented with lowest binding energy (-kcal/mol) which might pave the way to disclose the mode of actions of these ligands. The docking parameters were defined as coordinates of the center of binding site with x = 126, y = 126, z = 126 and binding radius = 0.375 Å. All AutoDock output file (.dlg) were then analyzed through Analysis option provided in MGLTools-1.5.6 rc3. Top-scoring molecules in the largest cluster were analyzed.

Conformers of the ligand were automatically docked to the enzymes and most stable conformer in terms of binding affinity (most negative) was used for post-docking analysis.

Results and Discussion

Table1 shows the ligands structures and necessary hydrogen bond formation by ligands with targets required for inhibition of target enzyme of covid-19. The rationale of choosing these ligands is only that they have shown efficacy in preclinical experimental models in different diseases. The SARS coronavirus main peptidase (SARS-CoVMpro) plays an essential role in the life cycle of the virus and is a primary target for the development of effective antiviral agents in case of COVID-19 infection. Figure 1 indicates the active site of target to confirm the binding site of investigational ligands if they were interacted with the amino acids in the active site of target or found to be attached any other site inside the target. The active site of this target enzyme comprises The active site of this target enzyme is composed of HIS41, MET 49, PHE140, LUE141, ASN142, GLY143, HIS163, HIS164, MET165, GLU166, LEU167, PRO168, HIS172, GLN189, THR190, ALA191 (Figure 1).

The best poses of natural ligands and enzyme complexes are described, and the number of hydrogen bonds formed by both proteins with the drug are displayed in figure 2(a-j) as well as in the table1.

Figure1: Active site of target enzyme.  GLY143, HIS163, HIS164, GLU166, GLU189 and THR190. In the current study, molecular docking analysis reveals that although all-natural ligands interacted in the active site of target enzyme but some of them could not interact through hydrogen bonds with target which are required for enzyme inhibition.Caffeine is a CNS stimulant, exhibited least binding affinity (-4.520 kcal/mol) towards enzyme but could afford to form required some hydrogen bonds with GLY143 and HIS163 amino acids residues of enzyme. Berberine is an alkaloid, showed slightly good binding energy (-7.910 kcal/mol) than that of Caffeine but could interact with enzyme through different amino acid viz. ASP187 and produced different conformational changes in the target enzyme after binding than that of caffeine (see figure2 b and 3b).

Although Luteolin exhibited moderate binding affinity (-6.890 kcal/mol) to target but could not make mandatory hydrogen bonds with enzyme for demonstrating inhibitory activity and made hydrogen bonds with ASP187 and GLU192 amino acids residues of enzyme and revealed quite similar conformational changes in the target enzyme (see figure 4b).

Therefore, Berberine and Luteolin could not be used as inhibitors of main protease enzyme.

Sanguinarine also demonstrated a good binding energy but could not afford any hydrogen bond with virus enzyme. Embelin, Capsaicin, Emodin and Gossypol were found to be in the active site and interacted with enzyme through requisite hydrogen bonds but could not exhibit good binding affinity toward target enzyme (-4.940 kcal/mol, -5.510 kcal/mol, -6.490 kcal/mol and -6.290 kcal/mol respectively). Hypericin is a naphthodianthrone, an anthraquinone derivative expressed better binding affinity i.e. -9.050 kcal/mol but made unsuitable hydrogen bond with ASN142 residue in the active site of target enzyme also made a necessary hydrogen bond with HIS 164 residue required for enzyme inhibition.Oxyacanthine displayed the highest binding affinity those of among other ligands involved in the study i.e. -10.990 kcal/mol and produced in the significant changes in the conformations of main protease enzyme (see figure.11b).

CONCLUSION

A new strain of coronavirus has now been extended from Wuhan city of China to the other parts of world for which not any approved medications are existed. Therefore, from the current molecular docking study it has been concluded that Oxyacanthine can act as Mpro inhibitor but need to be explored for more experimental work regarding development of anti SARS-Mpro inhibitor.

Answer: Coronavirus became pandemic very soon and is a potential threat to human lives across the globe. No approved drug is currently available therefore an urgent need has been developed for any antiviral therapy for COVID-19. For the molecular docking study, ten herbal molecules have been included in the current study. The three-dimensional chemical structures of molecules were prepared through ChemSketch 2015 freeware. Molecular docking study was performed using AutoDock 4.2 simulator and Discovery studio 4.5 was employed to predict the active site of target enzyme. Result indicated that all-natural molecules found in the active site of enzyme after molecular docking. Oxyacanthine and Hypericin (-10.990 and -9.05 and kcal/mol respectively) have shown good binding efficacy among others but Oxyacanthine was the only natural product which made some of necessary interactions with residues in the enzyme require for target inhibition. Therefore Oxyacanthine may be considered to be potential inhibitor of main protease enzyme of virus but need to be explored for further drug development process.


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 35-year - old male farm - worker presented to the emergency room with alleged history of horse bite to the right forearm about 2 hours prior to presentation while feeding the horse .
there was deformity of the forearm with multiple puncture wounds , deep abrasions and small lacerations on the distal - third of the forearm .
copious irrigation with normal saline was done and he was administered anti - tetanus and postexposure rabies prophylaxis .
he underwent emergency wound debridement , and the ulna was stabilised with an intra - medullary square nail .
he had an uneventful recovery and at three - month follow - up , the fractures had healed radiographically in anatomic alignment . at two - year follow - up , he is doing well , is pain free and has a normal range of motion compared to the contralateral side .
horse bites behave as compound fractures however rabies prophylaxis will be needed and careful observation is needed .
early radical debridement , preliminary skeletal stabilisation , re - debridement and conversion osteosynthesis to plate , and antibiotic prophylaxis were the key to the successful management of our patient .
falls and kicks are common mechanism of injuries in people handling horses [ 1 - 3 ] .
we present a case of forearm open fracture due to horse bite and its management .
a 35-year - old male farm - worker presented to the emergency room with alleged history of horse bite to the right forearm about 2 hours prior to presenting to us .
he had recently bought the horse for renting it for marriages and other social and religious functions . on examination , there was deformity of the forearm with multiple puncture wounds , deep abrasions and small lacerations on the distal - third of the forearm .
1(a ) and ( b ) ) front and dorsal view of the forearm on presentation showing the bite wounds .
he was given 0.5 ml tetanus toxoid and 500 iu tetglob ( human tetanus immunoglobulin bp ) , and received post - exposure rabies prophylaxis with vaxirab ( purified duck embryo vaccine for rabies ip ) .
radiographs revealed fracture of radius and ulna in the mid - shaft region ( fig .
he was taken to the operating room ( or ) where careful debridement of the wounds was done under loupe - magnification .
the ulna was stabilised with an intra - medullary talwalkar square nail ( inor , mumbai , india ) .
seventy - two hours later , he was taken to the or for re - debridement .
the nail in ulna was removed and conversion osteosynthesis using dynamic compression plate and screws for radius and ulna was done ( fig .
he was changed to oral cephalexin and ciprofloxacin on day 6 which were given till suture removal .
he had an uneventful recovery and was discharged from the hospital on the 10th day from injury .
the patient , however , sold the horse as he was too scared to keep it . at three - months
three - month follow - up radiographs showing fracture healing in anatomic alignment . at two - year follow - up
, he is doing well , is pain free and has a normal range of motion compared to the contralateral side .
he is able to use his hand for all routine work and has returned to his work in the farm .
in horse - related accidents , the majority of injuries occur when the person falls from a horse [ 1 - 3 ] .
blow by a horse , getting struck by an object while riding a horse , being kicked by a horse , the horse falling on the patient , being entangled by reins , and being bitten by a horse are other less common horse - related accidents .
most people bitten by horses do not seek medical advice as most bite injuries are minor and self - treated or do not require admission to hospital .
thomas et al   in their study estimated that 102,900 people are treated yearly in emergency rooms in the us due to nonfatal horse related injuries , and about 1800 patients are treated each year after horse bites .
our patient was too frightened to keep the horse and risk another bite , and hence , sold it not caring for the implications of financial loss .
domestic animals at home differ between societies , and therefore , local traditions affect the epidemiology of animal - related injuries . comparing animal bite wounds , cat bites result in punctured deep wounds , dog bites cause rather superficial abrasion and laceration type wounds ; because of the great deal of force exerted by an equine in closing its jaws , in horse and donkey bites , the severity of injuries may range from mild superficial pressure trauma , cutaneous breaks of the skin , deep lacerations with loss of tissue , to amputations of digits and even the nose .
peel et al   reported a case of fracture of the forearm bones following horse bite that was treated with open reduction and internal fixation primarily .
he sustained repeated infections with purulent wound discharge from which mixed cultures of bacteria , including staphylococcus aureus , prevotella melaninogenica , escherichia coli , and pasteurella multocida were isolated .
more than 3 months after the initial attack by the horse actinobacillus suis was isolated by bone biopsy specimen . though the acute trauma is readily apparent from a biting event ,
there is also the risk of exposure to various microbes in the oral secretions of equines .
transmission of such agents with zoonotic potential can also occur from the non - bite exposures to the oral and respiratory secretions .
because of the large number of bacteria in the mouth , animal bite wounds are generally contaminated and their treatment is difficult , particularly in extensive lesions .
the occurrence of bacterial infection after animal bites depends on several factors , such as species of animal aggressors ( humans would be associated with a higher infection risk ) , type and site of the injuries ( wounds located in hands have a higher infection risk ) , care given to the wound , inherent factors in the individual ( greater risk in elderly , those with diabetes mellitus , vascular disease , etc ) . in relation to wound type , puncture wounds
have been reported to have a higher infection rate after animal bites , possibly due to the deposition of bacteria deep in the skin .
there is evidence that the use of antibiotic prophylactic after bites of the hand reduces infection .
horse bites most commonly lead to infections with burkholderia , streptococcus , staphylococcus , rhodococcus , actinobacillus , yersinia , and pasteurella , escherichia , neisseria , prevotella , pseudomonas , listeria , hendra virus , vesicular stomatitis virus species .
bites , kicks or strikes , animal contact and cutting or scratching were the most frequent mechanisms of injury reported .
nearly 20% of reported horse - related injuries , 14% of cattle and cats and 11% of dog - related injuries resulted in admission .
brouwer et al   reported a case of streptococcus equi meningitis complicated by brain abscesses , as a result of a horse bite .
kse et al   performed a retrospective evaluation of 24 patients presenting with animal bites ( 19 horse and 5 donkey bites ) .
the head and neck were the most frequent bite sites ( 14 cases ) , followed by the extremities ( eight cases ) and the trunk ( two cases ) .
our primary aim was damage - control  to aggressively debride and at the same time give stability to the limb for wound dressings .
preliminary stabilisation of the forearm by an intramedullary talwalkar square nail ( inor , mumbai , india ) in the ulna was done following debridement of the wounds and excision of devitalised tissues . fixing the ulna with a nail also helped in maintaining forearm length .
re - debridement at 72 hours , showed no features of infection and decision of internal fixation with plate and screws was taken .
we also wish to highlight to the journal reader community that putting in implants when there is any doubt of contamination is risking long term bone infection and other associated complications of delay - in - union and non - union with compromised hand function .
intra - medullary nail was preferred over external fixator in this case , though in fractures with severe soft tissue damage the use of external fixator is indicated .
the problems of using external fixation in the forearm include : pin - track - infection , nerve damage due to insufficient anatomical exposure and a relatively high rate of non - union .
conversion osteosynthesis to internal fixation after primary external fixation is associated with high rates of osteomyelitis .
plating is established as the standard method in the operative treatment of forearm fractures in adults .
we successfully converted the fixation from intra - medullary nail to plating with no incidence of infection or delay - in - union .
therefore , it makes sense to debride wounds which have necrotic tissue early rather than later .
considering the most common complication of zoonotic infection related to animal bite injuries , our successful surgical treatment without complication appears to have definite clinical relevance .
the systematic treatment protocol of early radical debridement , preliminary skeletal stabilisation , re - debridement and conversion osteosynthesis to plate , and antibiotic prophylaxis were the key to the successful management of our patient .
horse or other animal bites are uncommon injuries . the management of these cases should be staged with the principles of damage control and infection control taking precedence . through this publication
we wish to highlight these rare injuries in the orthopaedic community and the journal readers .

Answer:
introduction : fractures have been described mainly following falling accidents in horse - related injuries .
 horse bites are uncommon accidents .
 we present a case of open fracture of the forearm due to horse bite.case report : a 35-year - old male farm - worker presented to the emergency room with alleged history of horse bite to the right forearm about 2 hours prior to presentation while feeding the horse .
 there was deformity of the forearm with multiple puncture wounds , deep abrasions and small lacerations on the distal - third of the forearm . copious irrigation with normal saline was done and he was administered anti - tetanus and postexposure rabies prophylaxis .
 prophylactic antibiotic therapy was commenced .
 radiographs revealed fracture of radius and ulna in the mid - shaft region .
 he underwent emergency wound debridement , and the ulna was stabilised with an intra - medullary square nail .
 seventy - two hours later , he underwent re - debridement and conversion osteosynthesis .
 he had an uneventful recovery and at three - month follow - up , the fractures had healed radiographically in anatomic alignment . at two - year follow - up , he is doing well , is pain free and has a normal range of motion compared to the contralateral side.conclusion:horse bites behave as compound fractures however rabies prophylaxis will be needed and careful observation is needed .
 early radical debridement , preliminary skeletal stabilisation , re - debridement and conversion osteosynthesis to plate , and antibiotic prophylaxis were the key to the successful management of our patient .


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

Paper text:
gastric volvulus is characterized by a rotation of the stomach along its axis in variable degrees and may present either acutely or chronically .
it may cause a complete gastric outlet obstruction and strangulation , leading to ischemic necrosis and perforation with a mortality rate of 3050% .
primary gastric volvulus results from abnormalities of the four gastric ligaments that restrict rotation : gastrocolic , gastrophrenic , gastrosplenic and hepatogastric .
we report a case of a gastric volvulus in a patient with a history of a diaphragmatic hernia .
an emergent laparoscopic diaphragmatic hernia mesh repair and gastropexy was performed , resulting in a complete recovery .
a 49-year - old woman presented to our emergency department with a 2-week history of epigastric pain and vomiting with no prior trauma . her past medical history included hypertension , iron deficiency anemia , laparoscopic cholecystectomy and an open uterine myomectomy .
upon arrival to the emergency department , she had a pulse of 135 beats per minute , a blood pressure of 110/90 mmhg , a respiratory rate of 20/min , a body temperature of 37.6c and an oxygen saturation of 98% on room air .
her clinical examination revealed tenderness over the epigastric region , and her bowel sounds were hyperactive . she had decreased air entry at the left basal region of the chest .
the initial laboratory results were white blood cell count 22.1  10/l ( neutrophilic ) , blood urea nitrogen 7.8 mmol / l , creatinine 121 umol / l and normal liver function tests , amylase and lipase .
a chest radiograph demonstrated a significant air - fluid level near the left lung base ( fig .  1 ) .

figure  1:chest x - ray showing an elevated air - fluid left in the left basal lung region .
chest x - ray showing an elevated air - fluid left in the left basal lung region .
two days prior to her admission , she had undergone upper gastrointestinal endoscopy for the same complaint in another center that revealed a dilated gastric lumen with herniation of the distal stomach , pylorus and first part of the duodenum into the left hemi - thorax ( fig .  2 ) .
resuscitation was commenced with immediate nasogastric decompression , intravenous hydration and analgesia , proton - pump inhibitors and electrolyte replacement .
a double contrast - enhanced computed tomography ( ct ) scan of the chest and the abdomen demonstrated a large diaphragmatic defect ( 7  7 cm ) and a left diaphragmatic hernia containing a dilated stomach , suggestive of a gastric outlet obstruction ( fig .
3 ) . a water - soluble gastrografin meal was performed , showing an intra - thoracic , mesentero - axial gastric volvulus ( fig .
figure  2:flexible upper endoscopy showing herniation of the distal stomach , the pylorus and the first part of the duodenum into the left hemi - thorax .

figure  3:different views of a double contrast - enhanced ct scan showing a left diaphragmatic hernia with an acute dilated stomach .

figure  4:water - soluble gastrografin meal showing an intra - thoracic mesentero - axial volvulus .
flexible upper endoscopy showing herniation of the distal stomach , the pylorus and the first part of the duodenum into the left hemi - thorax .
different views of a double contrast - enhanced ct scan showing a left diaphragmatic hernia with an acute dilated stomach . water - soluble gastrografin meal showing an intra - thoracic mesentero - axial volvulus .
the patient was listed emergently , underwent general anesthesia and was placed in a 30-degree split - leg reverse trendelenburg position .
a four - port approach was used after verres pneumoperitoneum was achieved . on inspection of the peritoneal cavity ,
the stomach and the first part of the duodenum were incarcerated in the peritoneal sac in the left hemi - diaphragm ( fig .
the rotated stomach and the first part of the duodenum were completely reduced from the thoracic cavity into the abdomen .
once the dissection of the sac was complete , we confirmed that there was no visceral injury and proceeded to repair of the 7  7 cm diaphragmatic hernia ( fig .
a gore bio - a tissue reinforcement absorbable mesh ( 15  12 cm ) was selected to encourage the formation of vascularized neotissue .
it was fixed in place using ethicon securestrap absorbable strap fixation device ( fig .
a gastropexy was then performed to the anterior abdominal wall using a 2 - 0 polypropylene suture .

figure  5:laparoscopic view showing the incarcerated content in the peritoneal sac with a twisted stomach .
 figure  6:laparoscopic view showing a large ( size 7  7 cm ) diaphragmatic defect .

figure  7:laparoscopic view showing the primary closure of the diaphragmatic defect using an interrupted pds ii suture .

figure  8:laparoscopic view showing bio - a tissue reinforcement absorbable mesh ( size 15  12 cm ) fixed intraperitoneally below the defect .
laparoscopic view showing the primary closure of the diaphragmatic defect using an interrupted pds ii suture .
laparoscopic view showing bio - a tissue reinforcement absorbable mesh ( size 15  12 cm ) fixed intraperitoneally below the defect . on the first post - operative day
, a water - soluble meal study was repeated and revealed a marked regression of the stomach size and a normal intra - abdominal position of the stomach and the first part of the duodenum with no evidence of obstruction ( fig .
the patient had an unremarkable recovery and was discharged on post - operative day 3 .
she was followed up in clinic 2 weeks post - operatively , and a follow - up upper gastrointestinal endoscopy was performed , which showed normal anatomy to the second part of the duodenum ( fig .
figure  9:water - soluble gastrografin meal showing normal intra - abdominal position of the stomach .

a detailed history of the risk factors associated with gastric volvulus including previous surgical procedures , gastro - oesophageal reflux disease or history of trauma should be obtained .
the initial management includes nasogastric decompression ( endoscopically if necessary ) , fluid resuscitation and correction of electrolyte imbalances [ 1 , 6 ] .
endoscopic decompression , de - rotation and percutaneous endoscopic gastrostomy ( peg ) fixation of the stomach to the posterior abdominal wall are the first - line management for cases of primary gastric volvulus .
it is also employed in cases of secondary gastric volvulus who are unfit for surgical repair under anesthesia .
the use of two peg tubes is optimal as the stomach may still rotate over a single peg .
surgical intervention is the treatment of secondary gastric volvulus and cases of volvulus in which an endoscopic or nasogastric decompression and de - rotation have failed .
there are no randomized control trials available ; however , observational studies support laparoscopy for its benefits of reduced inpatient stays and improved post - operative morbidity
. a recurrence rate of 42 vs. 15% post laparoscopic and open gastropexy , respectively , has been described in one study .
however , it is important to stress that this is for gastric fixation alone and does not compare recurrence rates after hernia repair .
the laparoscopic approach is defined by the need to de - rotate and reduce the gastric contents into the abdominal cavity .

Answer:
gastric volvulus is an uncommon but serious surgical condition mandating an early diagnosis and surgical intervention .
 it may present either acutely or chronically with epigastric pain , retching and vomiting .
 there are two types of gastric volvulus : organo - axial and mesentero - axial .
 we report a case of a mesentero - axial gastric volvulus in a 49-year - old woman with a left - sided diaphragmatic hernia .
 she presented with a significant epigastric pain and vomiting .
 a flexible upper endoscopy , a barium meal and a contrast - enhanced computed tomography imaging had confirmed the diagnosis .
 she was treated with a laparoscopic mesh repair of the diaphragmatic defect followed by a gastropexy .
 she had an uneventful postoperative course and was asymptomatic thereafter .


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 assessment of intravascular volume and the adequacy of volume resuscitation are among the most difficult clinical challenges .
systolic blood pressure , heart rate and urine output change minimally in early hemorrhagic shock .
hypotension , tachycardia , cold extremities , decreased urine output and poor capillary refill are only present in patients who have lost in excess of 30% of their blood volume ( classiii hemorrhage ) .
furthermore , both the central venous pressure and the changes in the central venous pressure in response to volume loading are poor indicators of intravascular volume and recruitable cardiac index .
while flow to the brain and the myocardium is preserved in patients with ' compensated shock ' , splanchnic and renal perfusion may be seriously compromised .
splanchnic hypoperfusion leads to both functional and structural changes in the gut mucosa , with increased permeability and translocation of bacteria and bacterial products .
increased mucosal permeability has been strongly associated with the development of the multiorgan dysfunction syndrome .
the expedient detection and correction of tissue hypoperfusion associated with ' compensated shock ' may limit organ dysfunction , may reduce complications and may improve patient outcome .
it is probable that the earlier tissue hypoperfusion is detected and corrected , the greater the likelihood that outcome will be improved .
indeed , rivers and colleagues reported a 32% relative reduction in the 28 day , all cause mortality of patients with severe sepsis who received early aggressive volume resuscitation in the emergency department .
used the central venous oxygen saturation as the endpoint of resuscitation in the intervention group , while treatment in the control group was guided by standard clinical endpoints including the central venous pressure .
while their study clearly demonstrates the value of early aggressive volume resuscitation , the use of central venous oxygen saturation to guide early resuscitation is not practical and has important limitations .
the base excess ( be ) has become the standard endpoint of resuscitation in trauma patients .
remarkably , while the be has been demonstrated to be of prognostic value , it has never been assessed prospectively in trauma patients .
the use of the be is based on the principle that tissue hypoxia associated with poor perfusion will result in the generation of hydrogen ions and a metabolic acidosis .
however , it is probable that tissue hypoperfusion may occur in the absence of a significant change in the be .
furthermore , as significant time is required for the liver and kidney to regenerate bicarbonate , it can be expected that there will be a long lag phase between the correction of intravascular volume and normalization of the be .
both of these assumptions are elegantly demonstrated in the study by totapally and colleagues reported in the present issue of critical care . in a rat hemorrhage model these authors demonstrated that the be responded slowly to changes in intravascular volume and that there was a significant increase in the be only when the mean arterial blood pressure fell by greater than 50% .
however , totapally etal . demonstrated that changes in the esophageal carbon dioxide gap closely mirrored changes in the intravascular volume .
similar findings have been reported by other investigators . in patients with penetrating trauma , baron and
colleagues demonstrated that sublingual carbon dioxide measurements correlated well with the degree of blood loss .
both ivatury and colleagues and kirton and coworkers have demonstrated that gastric intramucosal ph correlates well with the degree of injury and that optimizing the gastric intramucosal ph in the first 24 hours following trauma is associated with a reduction in the incidence of organ failure and death .
the study by totapally and colleagues suggests that the be is an insensitive indicator of the degree of the intravascular volume deficit following hemorrhage and that it responds slowly to volume resuscitation .
esophageal and sublingual capnometry , however , appear to provide near instantaneous information regarding the degree of the volume deficit and the adequacy of volume resuscitation .
this technology is simple and noninvasive , and is ideally suited for use in the emergency room and the trauma bay .
the esophageal or sublingual pco2 gap may prove to be a useful endpoint for the resuscitation of trauma victims .
the author has received a research grant from optical sensors inc , minneapolis , mn , usa , the manufacturer of the nellcor n-80 capnoprobe sl device .

Answer:
although it has never been prospectively validated , the base excess ( be ) is regarded as the standard end - point of resuscitation in trauma patients . in a rat hemorrhage model , in this edition of critical care , totapally and colleagues demonstrate that the be is an insensitive and slowly responsive indicator of changes in intravascular volume .
 this contrasts with changes in the esophageal - arterial carbon dioxide gap which more closely followed changes in blood volume .
 esophageal or sublingual capnometry may prove to be a useful tool for monitoring the adequacy of resuscitation in trauma victims .


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:
Solid-Phase Synthesis of 2-Aminobenzothiazoles

Paper sections:

Libraries of compounds based on diverse heterocyclic scaffolds comprise a key aspect of modern drug discovery. In this context, solid supported synthesis has proved to be a powerful tool leading to a wide-range of heterocyclic compounds.1 However, to the best of our knowledge, a procedure for the solid phase synthesis of 2-aminobenzothiazoles has not been reported. The 2-aminobenzothiazole scaffold is one of the "privileged" structures in medicinal chemistry.2 Indeed, various examples featuring this particular scaffold have been prepared, many exhibiting remarkable biological activities.3,4 Given the importance of this particular chemical entity to the field of medicinal chemistry, the development of improved and/or alternative methods for the rapid construction of libraries of derivatives is desirable. Although examples of solid supported synthesis of benzothiazoles have been reported,5,6 these methods are not applicable to 2-aminobenzothiazoles. We thus undertook a focused study to adapt previously disclosed methods for solution phase synthesis to the solid phase for this particular class of heterocycles.

The now classical synthesis of 6-substituted 2-aminobenzothiazoles entails treatment of 4-substituted anilines with potassium thiocyanate in the presence of bromine in acetic acid (Scheme 1 A).7 This method, however, is not generally applicable as thiocyanation in the para position of anilines is often the predominant reaction when 4-unsubstituted anilines are employed under these or similar oxidation conditions (Scheme 1 B).8,9 Alternative methods for the syntheses of 4, 5, 6, and 7 substituted 2-aminobenzothiazoles employ phenylthioureas as the synthetic precursors (Scheme 1 C). In these cases, heterocycle ring formation can be carried out, albeit non regioselectively, by treating the phenylthioureas with bromine in chloroform10 or acetic acid.11 Alternatively, regiospecific cyclizations can be performed via SNAri reactions, employing phenylthioureas obtained from the appropriate ortho-fluoroanilines in the presence of sodium methoxide.12 We report here adaptation of these reaction conditions onto solid support beginning with resin-bound isothiocyanate.

The resin-bound isothiocyanate 3 was prepared as previously described in two steps from carboxy-polystyrene (Scheme 2).13 Conversion of 3 to the N-acyl, N′-phenylthioureas of general structure 4 was then readily achieved upon treatment of 3 with the appropriate aniline at room temperature in N,N-dimethylformamide.14 This reaction can be conveniently monitored by infrared spectroscopy following the disappearance of the characteristic isothiocyanate band at ∼1910 cm-1 (Figure 1). When X = H cyclization of 4 to 2-acylaminobenzothiazole 5 was then performed by treatment with six equivalents of bromine in acetic acid (Scheme 2, Method A14). Alternatively, when X = F or Br, benzothiazoles obtained (e.g., entries e, and h Table 1), were formed by treatment of the corresponding N-acyl, N′-phenylthioureas with sodium hydride (Method B & C14) via an SNAri mechanism.

Finally, the desired 2-aminobenzothiazoles of general structure 6 were obtained in good overall yield and >85% purity upon treatment of 5 with 4% hydrazine monohydrate in ethanol (Table 1).14 Alternative TFA-mediated cleavage conditions were also investigated, however, the optimized hydrazine cleavage conditions proved more reliable, and generally proceeded with little or no trace of contaminants or by-products (cf., Figure 2).

As anticipated, when 3-subtituted anilines (e.g., entries c and f, Table 1) were employed, oxidative cyclization conditions (Method A) led to mixtures of two regioisomers (i.e., 5- and 7-substituted 2-aminobenzothiazoles); the relative ratio apparently determined by the steric encumbrance of the substituent in the meta position of the starting aniline. Thus, while 3-bromoaniline furnished a separable 1:1 mixture of 5- and 7-bromo-2-aminobenzothiazoles, under the above reaction conditions, the 3-phenylaniline generated a mixture (95:5) in favor of the 5-substituted-2-amino-benzothiazole (cf., entries c and f, Table 1), which could be readily separated and purified by column chromatography or crystallization. Single crystal X-ray analysis confirmed the structure of 6f (Figure 3).

Although mixtures of regioisomers are often acceptable in the generation of libraries for HTS, single isomers could be obtained when ring formation was performed via SNAri, as exemplified by entries e (Method B) and h (Method C); each proceeded regiospecifically to furnish the 7-chloro- and the 5-bromo-2-aminobenzothiazole 6e and 6h (Table 1), respectively.

Finally, in order to exemplify the utility of this synthetic protocol for the construction of libraries of 2-aminobenzothiazole derivatives, we evaluated representative resin-bound bromobenzothiazoles 5c and 5h as possible starting points for further structural elaboration. Thus, 5c and 5h were treated under either Suzuki15 or Buchwald-Hartwig16 conditions to yield products of cross-coupling. Representative examples of C–C, and C–N bond forming reactions are summarized in Table 2.

Both cross-coupling reactions were carried out under microwave promoted conditions. For these reactions, 0.05-0.1 mol% of Pd(PPh3)4 was found to be the preferred catalyst (cf., Table 3).

In summary, we have developed an effective method for the solid supported synthesis of 2-aminobenzothiazoles, with an application to the preparation of a focused library of 2-aminobenzothiazole derivatives.

IR spectra.

LC/MS Analysis of the crude reaction obtained after hydrazine-mediated cleavage (entry f, Table 1); A: photodiode array detector; B: total ion current; C: mass spectrum.

X-ray crystal structure of compound 6f (CCDC 753930).

Commonly employed methods for the solution phase synthesis of 2-aminobenzothiazoles (A and C); thiocyanation of 4-unsubstituted anilines upon treatment with potassium thiocyanate in the presence of bromine in acetic acid (B).

Reagents and Conditions: (a) oxalyl chloride, DCE, rt, 16 h; (b) Bu4NNCS, DCE/THF, rt, 16 h; (c) aniline, DMF, rt, 16 h; (d) For X = H, Method A: Br2 (6 eq.), acetic acid, rt, 16 h; for X = F, Method B: NaH (6 eq.), DMF, rt, 16 h; for X = Br, Method C: NaH (10 eq.), DMF, 100 °C, 16 h (e) hydrazine monohydrate, EtOH, 150 °C, MW, 30 min.

Representative examples of 2-aminobenzothiazoles prepared.

Overall yield after purification.

Approximately a 50:50 mixture of 5- and 7-bromo-2-aminobenzothiazoles;

Approximately a 95:5 mixture of 5- and 7-phenyl-2-aminobenzothiazole.

Representative examples of cross-coupling reactions.

Approximately a 50:50 mixture of 5- and 7-phenyl-2-aminobenzothiazoles (separable).

Cross-coupling reaction investigation.

Conversion of the starting material by LC-MS analysis after cleavage of the product.

Answer: A traceless solid supported protocol for the synthesis of 2-aminobenzothiazoles is described, employing resin-bound acyl-isothiocyanate and a series of anilines. Cyclization of the resulting N-acyl, N\xe2\x80\xb2-phenyl-thioureas generates the 2-aminobenzothiazole scaffold, which can be further elaborated prior to hydrazine-mediated cleavage of the final products from the carboxy-polystyrene resin. A small, focused library of 2-aminobenzothiazoles was prepared.


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:
spasticity is a frequent consequence of stroke1 ,
 2 . in the lower leg ,
this malposition or
 malalignment causes mechanical stress to foot joints in the lateral forefoot area , and
 joints under this stress are likely to be inflamed and painful4 .
foot pain causes difficulty in standing and walking , and thus
 limits daily living activities .
the malposition or malalignment of the foot can be managed by the
 control of spasticity .
it was proposed that correcting the malposition or malalignment can
 reduce abnormal mechanical pressure in specific areas of the foot , which leads to a
 reduction in foot pain . of the several options available for the management of spasticity
,
 the clinical usefulness of nerve and motor point blocks with alcohol has been well
 demonstrated5,6,7 . in the current study , whether a reduction of ankle spasticity using nerve and motor point
 blocks with 20% ethyl alcohol can manage foot pain was examined .
a 58-year - old woman visited the rehabilitation department of a university hospital due to
 piercing pain ( numeric rating scale [ nrs ] : 8) in the left fifth metatarsal head for two
 years .
erythema and edema were present on the lateral aspect of the head of the fifth
 metatarsal bone ( fig .
1.(a ) an image of the patient s left foot shows erythema and edema
 in the fifth metatarsal head area .
( b ) the left foot x - ray showed that the fourth and
 fifth intermetatarsal angle was 7.7 ) . the patient provided informed signed consent
 for participation in the study .
the study was approved by the research ethics committee of
 yeungnam university hospital ( yuh-16 - 0425-d7 ) . on the foot x - ray ,
the fourth and fifth
 intermetatarsal angle of the left foot was 7.7 ( fig .

she had a history of intracerebral
 hemorrhage on the right basal ganglia about five years previously .
the degree of her spasticity was a modified
 ashworth scale ( mas)8 of 1 + .
additionally , slight motor weakness ( medical
 research council9 : 4 + ) in the left upper
 and lower extremities was shown .
other neurological symptoms , including sensory and
 cognitive deficits , were not present . at first , 0.5  ml of 2% lidocaine with 10  mg
 triamcinolone acetonide was injected into the tender point of the left fifth metatarsal head
 area .
( a ) an image of the patient s left foot shows erythema and edema
 in the fifth metatarsal head area .
( b ) the left foot x - ray showed that the fourth and
 fifth intermetatarsal angle was 7.7 it was proposed that the ankle spasticity in the patient caused repetitive pressure and
 shearing between the soft tissue and head of the fifth metatarsal bone .
thus , we considered
 the possibility that controlling spasticity might be helpful in the management of pain from
 the tailor s bunion , and decided to control spasticity in this patient using a nerve or
 motor point block with 20% ethyl alcohol . to reduce the spasticity of the left ankle plantar
 flexor , the medial and lateral motor branches to the gastrocnemius muscle of the left tibial
 nerve
the block of nerve branches
 was performed based on the method described by jang et al5 . to manage spasticity in the left ankle supinator
a motor point
 block was performed in the left tibialis posterior muscle with 5  ml of 20% ethyl alcohol .

both nerve and motor points were
 located using the nerve stimulator at the popliteal area and at the mid - calf level ,
 respectively .
the cathode stimulating needle ( teflon - coated , 23-gauge needle ) was slowly
 advanced in the direction of the nerve and posterior tibialis muscle .
the needle hub was
 connected to injection tubing that bore the syringe containing the 20% ethyl alcohol .

contractions were seen and palpated as the tip came close to the nerve or motor point of the
 tibialis posterior . at this stage ,
the intensity of the current was between 3 ma and 5 ma .
 after the needle was placed close to the targeted nerve or motor point ,
the tip is assumed to be in contact with the nerve or motor
 point when maximum contraction is obtained with minimum current .
the needle was finally
 positioned at a current of 1 ma with nerve block and 3.5 ma with motor point block .

additionally , the patient underwent the stretching exercises for the left ankle plantar
 flexors and ankle supinators for 2 weeks after the alcohol block ( monday through friday : 15
 mins  1 time / day ) . to evaluate dynamic foot pressure , the foot pressure measurement system ( fpms ) ( tpscan ;
 biomechanics , goyang , korea ) was used10 .

dynamic foot contact pressure data during gait were recorded on the fpms floor mat ( 40.5
 40.5  cm ) at the middle of the gait test .
the foot pressure was presented as a
 color : red is the highest pressure followed by orange , yellow , green , and blue .
foot contact
 pressure was evaluated twice before and one- month after the nerve and motor point block
 procedure . before the procedure
, contact pressure was highly distributed to the lateral
 forefoot , however , reduced distribution was observed in the medial forefoot and hindfoot
 ( fig .
2.foot
 pressure measurement imagethe foot pressure image of a normal foot and the
 images of the patient s foot pressure showing alterations pre - alcohol block and
 post - alcohol block . ) .

after the procedure , the distribution of foot contract pressure was found to be similar to
 that of a normal control ( 56-year - old female individual ) .
foot
 pressure measurement image the foot pressure image of a normal foot and the
 images of the patient s foot pressure showing alterations pre - alcohol block and
 post - alcohol block .
at the follow - up evaluation , two weeks after the alcohol block , the spasticity in the left
 ankle plantar flexor and supinator had disappeared ( mas : 0 ) .
in addition , ankle clonus was
 not present . moreover , the pain in the left fifth metatarsal head was significantly reduced
 from nrs 8 to nrs 1 . at one , two , and three
months after the alcohol block the effects on
 ankle spasticity and foot pain were sustained .
in the present study , foot pain related to tailor s bunion was reduced after spasticity
 treatment using nerve and motor point block with 20% ethyl alcohol .
although the incidence of foot pain in patients with stroke has not been investigated ,
 patients with stroke are prone to have foot pain due to deteriorated musculoskeletal
 position or alignment induced by spasticity or motor weakness .
the tailor s bunion or
 bunionette , which was first described by davies in 194911 , is a painful bony prominence on the lateral , dorsolateral , or
 plantar aspect of the head of the fifth metatarsal bone12 .
the conflict between the fifth metatarsal head and footwear has
 been reported to be the cause of tailor s bunions12 . in the patient ,
the spasticity in the ankle plantar flexor and
 supinator appeared to cause repeated mechanical stress and chronic irritation in the fifth
 metatarsal head area , which is thought to induce a tailor s bunion . for the management of foot pain due to tailor s bunion , corticosteroids were injected into
 the tender point of the fifth metatarsal head area ; however , the patient s pain was
 unresponsive to this injection .
it was considered that non - controlled spasticity can lead to
 continuous mechanical stress or irritation and repeated occurrence of inflammation in the
 fifth metatarsal head area .
therefore , the spasticity was controlled using a block with 20%
 ethyl alcohol on the motor branches to the gastrocnemius muscle of the tibial nerve and the
 motor points of the posterior tibialis muscle .
after the block with ethyl alcohol , spasticity in this
 patient had almost disappeared ( from mas 1 + to mas 0 ) .
also , the patient received the
 stretching exercises for the ankle plantar flexors and the ankle supinators .
the stretching
 exercise is known to effectively reduce spasticity13 ,
 14 by increasing tissue
 extensibility15 .
it was thought that
 the reduced spasticity in the patient was attributed , at least in part , to the stretching
 exercises .
it is thought that the mechanical stress and irritation in the fifth metatarsal
 head area during walking were significantly reduced with the disappearance of spasticity in
 this patient .
when the stress and irritation were reduced after the management of
 spasticity , the pain due to tailor s bunion appeared to be significantly reduced .
in addition , the fpms was used for detailed evaluation of the effect of the 20% ethyl
 alcohol block . before the alcohol block ,
after the control of spasticity with the alcohol
 block , increased contract foot pressure in the hindfoot and medial forefoot were observed .

this change in pressure distribution is concurrent with the results of several previous
 studies10 , 16 , 17 . using fpms ,
it was
 confirmed that mechanical stress abnormally concentrated on the fifth metatarsal head area
 was corrected to near normal following the alcohol blocks on the tibial nerve branches and
 the motor point of the tibialis posterior muscle .
the correction of foot contact pressure
 distribution appears to have contributed to the pain reduction in the fifth metatarsal head
 area . in conclusion ,
the case of a patient with chronic hemiparetic stroke whose pain due to
 tailor s bunion showed relief following the control of spasticity using nerve and motor
 point blocks with 20% ethyl alcohol was reported .
this study showed that deteriorated foot
 position or alignment induced by spasticity and malposition / malalignment - related foot pain
 can be successfully managed by nerve and motor point blocks with 20% ethyl alcohol . on the
 basis of the clinical experience in this study ,
when clinicians treat foot pain in patients
 with stroke , they should consider the possibility that spasticity can contribute to the
 development of foot pain .
this is first study to show that management of spasticity can
 reduce foot pain in a patient with hemiparetic stroke . however , since this study reports a
 single case , further studies involving a larger number of patients are necessary .

Answer:
[ purpose ] this study report a case of a patient with hemiparetic stroke who showed
 significantly reduced foot pain when ankle spasticity was reduced using nerve and motor
 point blocks with 20% ethyl alcohol .
 [ subject and methods ] a 58-year - old woman with left
 hemiparesis following intracranial hemorrhage five years previously presented with pain in
 the left fifth metatarsal head for two years ( numeric rating scale[nrs ] : 8) .
 erythema and
 edema were observed on the lateral aspect of the head of the fifth metatarsal bone .
 she
 was diagnosed with a tailor s bunion .
 spasticity was observed in the left ankle plantar
 flexor and ankle supinator ( modified ashworth scale : 1 + ) . using 20% ethyl alcohol , a block
 in the medial and lateral motor branches to the gastrocnemius muscle of the left tibial
 nerve and the motor point of the left posterior tibialis muscle was performed .
 [ results ]
 after the alcohol block , spasticity had almost disappeared and foot pain was significantly
 reduced ( nrs : 1 ) .
 results from the foot pressure measurement system test showed foot
 contact pressure was highly distributed to the lateral forefoot pre - block .
 after the
 block , the distribution of foot contract pressure was similar to normal distribution .

 [ conclusion ] clinicians should consider the possibility that spasticity can contribute to
 foot pain .