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

Paper text:
in 1912 , crouzon described a syndrome that consisted of brachycephaly , shallow orbits , and maxillary hypoplasia .
since then , craniofacial syndromes have been subcategorized into over a hundred syndromes based on the severity of the craniofacial and associated congenital malformations .
crouzon syndrome , along with apert , carpenter , chotzen , and pfeiffer syndromes , is one of the most common genetic disorders associated with a craniofacial syndrome .
other facial deformities in crouzon syndrome may include prominent nose , frontal bossing , and ocular proptosis due to shallow orbits with or without hypertelorism , although age - related phenotype modifications have been reported .
patients of crouzon syndrome may occasionally present with hydrocephalus , seizures , and mental retardation .
the incidence of hydrocephalus in craniosynostosis ranges from 4% to 26% [ 4 , 5 ] .
nonetheless , short stature with growth hormone deficiency ( ghd ) and/or iron deficiency anemia ( ida ) have rarely been reported in the literature . here
we report a case of crouzon syndrome with hydrocephalus , also presenting with severe short stature due to ghd and ida .
an 11 and a half - year - old boy visited our out - patient clinic for frequent dizziness and marked growth retardation .
the positive facial features were brachycephaly , hypoplasia maxilla , severe ocular proptosis ( hertel 's exophthalmometry measuring 22 - 23  mm on both eyes ) with hypertelorism , and low - set ears .
he had a 3200  gm birth weight and was born to a generally healthy mother via nsd at 40  wks ' gestational age . owing to severe hydrocephalus and cerebellar tonsil herniation ( chiari i malformation ) revealed by magnetic resonance imaging ( mri ) , he had endoscopic third ventriculostomy and
six months later , he received frontal advancement and ventricular shunting because of a progressive increase in ventricular size and rising intracranial pressure ( icp ) .
his head circumference remained at around the 50th percentile , but he had frequent respiratory tract infections during early childhood .
the patient had not been followed up regularly after the age of 6  years until recently .
he was 18.5  kg and 111.2  cm , which represented 3 standard deviation ( sd ) in body weight and 5 sd in height of his age .
his brother , who is 4 and a half years older , was 182  cm .
his parents are grossly normal and the mid - parent height is 168  cm . on admission , his general condition was stable and intelligence quotient ( iq ) around 90 .
chromosome analysis was normal in g - banding karyotype ; however , molecular analysis identified a common mutation point of cys278phe in exon iiia of the fibroblast growth factor receptor 2 ( fgfr2 ) gene ( figure 1 ) .
his bone age was only 4.55  years according to the greulich and pyle atlas ( figure 2 ) , which was a 6.5 - 7-  year delay .
mri revealed obstructive hydrocephalus of both lateral ventricles with an interruption of pituitary stalk , shallow orbits , and chiari i malformation .
pituitary height was 5.6  mm in midsagittal t1-weighted spin - echo mri ( figure 3 ) , which was around mean according to tsunoda 's study .
a biochemistry profile revealed thyroid hormones and cortisol within normal limits , but blood routine showed microcytic anemia .
a growth hormone provocative test revealed a reduced peak growth hormone response of 4.57  uiu / ml in the insulin test and 2.63  uiu / ml in the clonidine test .
the concentrations of insulin - like growth factor 1 ( igf - i ) and insulin - like growth factor binding protein 3 ( igf - bp3 ) were also very low ( igf - i < 10.0  ng / ml , igfbp-3 : 1.5  g / ml ) .
severe iron deficiency anemia without thalassemia was noted ( hemoglobin : 8.8  g / dl , rbc : 4.18  million / ul , mcv : 68.2  fl ; serum iron : 7  mg / dl , ferritin : 4  ng / ml , uibc : 525  mg / dl ) with regards to the microcytic anemia . iron supplements at a dose of 100  mg / day were subscribed immediately .
human growth hormone ( hgh ) subcutaneous replacement at a dose of 0.3  mg / kg / week in seven divided doses was also subscribed , and the growth velocity was 3  cm per year during the first half year .
after his hemoglobin and serum iron levels gradually returned to normal , his dizziness disappeared and his growth velocity increased to 5  cm per year under hgh therapy .
we reviewed the literature for the incidence of hydrocephalus in crouzon syndrome and the association with ghd , only one case report :  crouzon syndrome with short stature due to partial ghd    was found .
however , with the progressive improvement and higher usage of imaging studies , cases of the incidence of hydrocephalus in crouzon syndrome are not uncommon . from proudman 's large study of central nervous system imaging in crouzon syndrome performed in south australia ,
most of those taken with follow - up computed tomographic scans were nonprogressive , even in cases of severe ventriculomegaly ( hydrocephalus ) .
, he suggests that hydrocephalus occurs secondary to the defective formation of the cranium , so it is reasonable that in many cases the hydrocephalus is nonprogressive .
most ventriculomegaly in crouzon syndrome is asymptomatic and does not necessitate any treatment , unless there is a clear evidence of significantly raised intracranial pressure .
fronto - orbital advancement and shunt system are treatments of choice . in our report case , ghd may have resulted in this patient 's growth retardation , which is not a common finding in crouzon syndrome .
there have been a few reports of endocrine disorders in children with shunted hydrocephalus , such as sexual precocity [ 10 , 11 ] or decreased basal levels of gh and igf-1 .
increased intracranial pressure has been perceived as a possible cause of pituitary dysfunction . in a series of papers by lppnen et al .
[ 1316 ] , the growth pattern of 114 children with shunted hydrocephalus was analyzed .
it was characterized by slow linear growth in prepuberty , accelerated physical maturation during puberty , and reduced final height .
this has also been shown to be associated with accelerated pubertal development in both boys and girls .
furthermore , they studied these patients ' serum growth hormone , plasma igf-1 , and   igfbp-3 concentrations .
they concluded that reduced growth hormone secretion may contribute to the pattern of slow linear growth and reduced final height observed in these patients . since there was an association with growth hormone , lppnen et al . designed a study performing radiography of the sella turcica , mri of the pituitary gland , and pituitary hormone stimulation tests in a subgroup of this large series ( 54 out of 114 ) to assess pituitary size and functional capacity .
the results indicated that children with shunted hydrocephalus had an increased pituitary size on average .
about one - third of these patients had signs of reduced gh secretion and a significantly lower pituitary height , which probably contributed to their poor linear growth .
increased pituitary size was associated with enhanced gonadotrophin secretion , which may result in early puberty in children with shunted hydrocephalus .
another review article about disorders of growth and puberty in children with nontumoral hydrocephalus had similar results .
they concluded that central early puberty was the most frequent endocrine disorder in 21 out of 31 patients . in their cases , short stature was frequently due to meningomyelocele and rarely to gh deficiency .
in our case , the pituitary height in mri was not smaller than normal for his age , but an interruption of the pituitary stalk was found .
his hydrocephalus and chiari i malformation were stationary except for the shallow orbits becoming more prominent .
he had severe proptosis but his visual acuity was normal . although chiari i malformation could also cause headache or dizziness , his dizziness might have been caused by severe ida , since the symptoms disappeared after anemia correction .
the results of hgh treatment were not satisfactory during the first half year , but became better after ida had been corrected . therefore , besides the compliance and method of hgh injection , other underlying diseases should be considered and treated if the therapeutic effect is not as expected .
tubbs et al . reported a study which showed that a small group of children with ghd had small posterior fossa , which was similar to the features of chiari patients .
they hypothesized that ghd might lead to chiari i malformation through the underdevelopment of the posterior fossa . in one of their following case studies , by presenting the case of 3 brothers , 2 with ghd and chiari , and one with neither , they provided evidence of this
. therefore , it would be interesting to see if hgh therapy leads to the improvement of chiari malformation .
although surgery is not necessary in our case so far , we hope to see hgh therapy contributes to improvement of chiari malformation by the annual mri survey .
the diagnosis of crouzon syndrome is usually made by the patients ' clinical signs , including acrocephaly , orbital proptosis , midfacial hypoplasia with
nose , short upper lip , high narrow palate , narrowly spaced teeth , and prognathism . to date , most patients have been shown to carry mutations of the fgfr2 gene . in   chiang 's mutation analysis of crouzon syndrome in taiwanese patients ,
three of the 12 patients carried the cys342arg mutation , which is the most frequent mutation found in taiwanese patients .
molecular analysis of the fgfr2 gene can help to confirm and classify the diagnosis of craniosynostosis syndrome .

Answer:
crouzon syndrome is one of the most common craniofacial syndromes and is inherited as autosomal dominant with variable expression .
 we report an 11 and a half - year - old boy with crouzon syndrome with severe growth retardation .
 he had hydrocephalus since infancy and recently suffered from frequent dizziness .
 his bone age was only 5 years according to the greulich and pyle atlas .
 magnetic resonance imaging showed shallow orbits , obstructive hydrocephalus , and cerebellar tonsil herniation .
 growth hormone provocative tests revealed a reduced peak growth hormone response in both insulin and clonidine tests .
 severe iron deficiency anemia was noted at the same time .
 molecular analysis identified a common mutation point of cys278phe for crouzon syndrome in exon iiia of the fibroblast growth factor receptor 2 ( fgfr2 ) gene .
 since growth retardation is not a common feature of crouzon syndrome , we reviewed the literature for the incidence of hydrocephalus in crouzon syndrome and the association with growth hormone deficiency .


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:
sinonasal teratocarcinosarcoma ( sntcs ) is a very unusual and aggressive neoplasm first characterized as a separate entity by heffner and hyams in 1984.1 it is currently defined by the world health organization as  a complex malignant sinonasal neoplasm combining features of teratoma and carcinosarcoma  that typically includes benign and malignant epithelial , mesenchymal , and neuroepithelial elements including immature tissue with blastomatous features.2 unlike other malignant mixed germ cell tumors ( gcts ) , sntcs lacks embryonal carcinoma , yolk sac tumor , choriocarcinoma , and seminoma components .
based on an inadequate sample , this heterogenous tumor can be misdiagnosed as olfactory neuroblastoma , squamous cell carcinoma , undifferentiated carcinoma , adenocarcinoma , malignant salivary gland - type tumors , or adenosquamous carcinoma.2 a recent comprehensive review of the literature by wei et al revealed  <  60 cases reported in the english literature.3 the primary treatment in 82% of the cases reviewed was surgery , with or without adjuvant radiation therapy ( rt ) .
there were high rates of recurrence and metastasis overall , although no clear prognostic factors were identified .
overall , 1-year and 3-year survival rates were 36% and 25% , respectively , for those patients with reported outcomes.3 of all the reported cases of sntcs , only one has shown any hormone secretion : antidiuretic hormone , causing hyponatremia.4 in that case , sodium levels were a reliable marker of tumor control and were an early postoperative indicator of tumor recurrence . to date , no sntcs with elevated gct markers has been reported .
we present a case in which a highly radiosensitive sntcs was associated with elevated -hcg .
a 22-year - old african american woman presented to the emergency department at  16 weeks of gestation with a 2- to 3-month history of worsening headaches and a 3-week history of increasing somnolence , nausea , vomiting , weight loss , and personality changes .
a magnetic resonance imaging ( mri ) of her head revealed an 11-cm right frontal mass with a 7-cm cystic component causing significant compression of the right frontal and temporal lobes , mild herniation of the right uncus , and mild hydrocephalus .
the tumor extended through the anterior cranial base to the nasal cavity and paranasal sinuses ( fig .
noncontrast magnetic resonance imaging of the head showing a large cystic mass in the paranasal sinuses and frontal lobe . on day 2 of admission , she had rapid mental status decline and underwent an emergent decompressive craniotomy .
the tumor was extra - axial , and the cyst expressed a dark fluid  similar to crankcase oil .  the small biopsy specimen taken during this procedure revealed neoplastic cells with squamous and basaloid differentiation and necrosis , leading to the impression of basaloid squamous cell carcinoma .
she subsequently underwent a combined endoscopic transnasal and cranial resection of the entire anterior cranial fossa and nasal cavity mass on day 28 of admission . the surgical specimen consisted of a 9.0    8.5    3.5-cm aggregate of tan - brown soft tissue and bony fragments .
histologically , the tumor consisted of a heterogeneous mixture of malignant epithelial , mesenchymal , and primitive neuroepithelial elements .
tumor infiltration of brain tissue was observed . the epithelial component included squamous and basaloid carcinoma features ( fig .
the mesenchymal component included areas of hypercellular smooth muscle , ranging from mildly anaplastic to overtly malignant , with focal areas of osteoid deposition ( fig .
3 ) . the neuroepithelial component included neuroblastoma - like and primitive neuroectodermal tumor - like areas ( fig .
immunohistochemical staining revealed expression of vimentin , pancytokeratin , and 34e12 , with focal positivity for cd99 and synaptophysin among the heterogeneous tumor components .
( a ) stromal smooth muscle with mitoses ( hematoxylin and eosin [ h&e ] ) . ( b ) osteoid
( lower right ) admixed with epithelial component ( upper left ) ( h&e ) .

( b ) primitive neuroectodermal tumor  like area ; hematoxylin and eosin ; synaptophysin ( inset ) .
postoperative rt was recommended after surgery but was delayed for 5 months due to a complicated hospital course and family concerns about her pregnancy .
the radiation planning mri showed some residual soft tissue thickening and gyral enhancement in the floor of the craniotomy site but no gross tumor .
after delivery of a healthy infant , she underwent a 2-month course of rt to the surgical bed to a total dose of 60 gy .
the follow - up mris showed no evidence of recurrent disease for 18 months post - rt .
two years ( 27 months ) after finishing her postoperative rt , she was admitted for evaluation through the emergency department following an alleged sexual assault by a family member .
her quantitative serum -human chorionic gonadotropin ( hcg ) was elevated ( 60 u / l ; normal nonpregnant range : 03 ) but did not rise as would be expected for pregnancy .
mri of the head showed a recurrent intracranial mass in the right frontal lobe ( fig .
she was deemed a high surgical risk , so reirradiation of the tumor was recommended .
radiation was delayed by 45 days , and the planning mri showed significant interval growth of the tumor with further elevation of -hcg to 130 u / l ( fig .
( a ) magnetic resonance imaging ( mri ) showing frontal lobe recurrence 27 months after radiation therapy .
( b ) mri showing tumor growth 45 days later , before reirradiation . ( c )
mri showing complete response of frontal lobe mass ( and new posterior fossa disease ) 1  month after reirradiation .
because of clinical concern over the origin of the serum -hcg elevation , the previous tumor tissue was examined with additional immunohistochemical staining for smooth muscle actin and -hcg expression .
the patient received 48  gy ( of a planned 50 gy ) of rt to the recurrent mass in 24 fractions .
she missed many appointments but finished most of her prescribed course in a 6-week period with no acute morbidity . computed tomography scan after the 10th fraction showed significant tumor response , and the treatment was replanned to account for the smaller tumor volume .
her serum -hcg level dropped from a peak of 130 u / l , measured at the start of rt , to 6 u / l ( almost within normal limits ) at the end of treatment ( fig .
7 ) ,
 serum -human chorionic gonadotropin levels before and after radiation therapy ( rt ) for recurrence in frontal lobe .
one month later she was admitted to the hospital again for increasing ataxia and falls .
5c ) but revealed at least five intracranial masses in the posterior fossa , outside of the prior rt fields . serum -hcg level was in the normal range .
the decision was made to palliate with 30  gy of rt to the posterior fossa in 10 fractions .
by definition , sntcs do not contain areas of embryonal carcinoma , choriocarcinoma , yolk -sac tumor , or seminoma .
they are hypothesized to arise from primitive pluripotent olfactory epithelial cells rather than germ cells .
thus they are traditionally believed to be incapable of producing gct markers including -hcg or -fetoprotein , although they have rarely been noted to produce pituitary hormones.4 these tumors comprise varying combinations of epithelial , mesenchymal , and neuroectodermal components exhibiting varying maturation
. the mesenchymal component may appear along a continuum from benign to malignant and can include mature components such as cartilage , bone , and striated or smooth muscle .
malignant sarcomatous transformation is also documented.1
 5
 6
 7
  in this case , smooth muscle actin highlighted an anaplastic smooth muscle component in this heterogeneous tumor .
there are rare reports of pure leiomyosarcomas secreting -hcg in the literature.8
 9
 10 in the absence of the gct components just mentioned , the neoplastic smooth muscle component of the tumor with expression of -hcg was the likely source for the elevated serum -hcg levels . because this patient was pregnant on initial presentation , any tumor - related -hcg production at that time
however , on recurrence , tumor production of -hcg was confirmed with elevation of serum -hcg , expression of -hcg on the smooth muscle component of the tumor tissue , and correlation of serum -hcg levels with changes in tumor size seen on imaging .
this patient 's recurrent tumor initially showed a complete response to rt by both serum marker and imaging criteria .
subsequent tumor growth outside of the rt field was not associated with elevation of serum -hcg .
sntcs is a rare and unusual neoplasm that lacks embryonal carcinoma , yolk sac tumor , choriocarcinoma , and seminoma components .
the source of -hcg production was traced to a neoplastic smooth muscle component of the tumor .
serum levels of this hormone were a reliable tumor marker during the patient 's first recurrence and subsequent rt .

Answer:
background and importance  sinonasal teratocarcinosarcoma ( sntcs ) is an unusual and aggressive neoplasm characterized by the combination of teratoma and carcinosarcoma features that is often misdiagnosed based on a biopsy sample .
 approximately 60 cases have been reported in the english literature , but none have been associated with serum tumor markers .
 we report a case of sntcs with elevation of serum -human chorionic gonadotropin ( hcg ) level .

 clinical presentation  the patient was a 22-year - old pregnant woman at diagnosis , and her -hcg level was appropriately elevated .
 her initial treatment was a surgical resection followed by radiation therapy ( rt ) .
 two years later , the patient had a pregnancy work - up after a sexual assault . her serum -hcg was elevated , but a nongravid uterus was seen on ultrasound . magnetic resonance imaging ( mri ) of the head revealed an intracranial tumor recurrence in the right frontal lobe . during salvage rt , -hcg decreased rapidly to normal levels , with a complete tumor response on mri .
 retrospective examination of the initial surgical specimen showed expression of -hcg associated with the anaplastic mesenchymal component .

 conclusion  this is the first reported case of a -hcg secreting sntcs . the source of -hcg production was traced to a neoplastic smooth muscle component of the tumor .


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 treatment options for graves ' disease consist of antithyroid drugs , radioactive iodine ( rai ) therapy , and surgery .
rai therapy has been used for the treatment of graves ' disease for more than seven decades , and in most studies , it has not been associated with an increased risk of cancer . on the other hand ,
several studies have proposed the potential increase in thyroid malignancies with rai treatment [ 2 - 4 ] . here , we describe a very rare case of anaplastic thyroid carcinoma ( atc ) associated with graves ' disease , following rai treatment .
a 42-year - old woman was referred to our clinic in 1998 , because of palpitations , hand tremor , and laboratory findings of hyperthyroidism ( serum thyrotropin [ thyroid - stimulating hormone , tsh ] 0.05 iu / ml [ reference range , 0.17 to 4.05 ] , free thyroxine 4.01 ng / dl [ reference range , 0.79 to 1.86 ] , and positive tsh receptor antibody at 201.7% [ percent binding inhibition index , radioreceptor assay , reference range ; 15.0% ] ) , and had been diagnosed as graves ' disease .
a technetium-99 m thyroid scan showed enlarged and homogeneously increased uptake , and ultrasonography revealed a diffuse goiter without nodules .
the patient received 200 mg / day of propylthiouracil and -adrenergic blocking agents for 1 year .
however , due to recurrent hyperthyroidism , she received rai therapy twice with an administered dose 370 mbq ( 10 mci ) , 296 mbq ( 8 mci ) , each .
two years later , she received thyroid hormone replacement due to subsequent hypothyroidism at a local clinic . in september 2010 , over 10 years later , she revisited us with complaints of hoarseness , dysphagia , and dyspnea , which had been presented for 2 months .
an anterior neck mass , which was hard and fixed , and some lymph nodes ( lns ) around the mass were palpable .
her chest radiography showed a tracheal narrowing and deviation to the right without active lung lesion . on computed tomography ( ct ) of the neck ,
positron emission tomography - ct , an intense hypermetabolic lesion was noted in the thyroid gland and lns on her left neck without distant metastasis .
a total thyroidectomy with selective neck dissection , tracheal sleeve resection , and end - to - end anastomosis were performed .
subsequently , she had concurrent cisplatin - based chemoradiotherapy for her neck and superior mediastinum ( total 6,600 cgy/33 fractions ) .
after 4 months of follow - up , despite the aggressive treatment , the disease progressed .
on neck ct , a new focal necrotic mass on the left side of her neck was noted , suggesting local recurrence .
the mass extended up to the tracheal lumen and the patient died of sudden uncontrolled bleeding in the airway .
the patient in this case received rai therapy twice for recurrent hyperthyroidism . after more than 10 years , she developed respiratory symptoms and was finally diagnosed with atc .
this case raises questions about the causal relationship between rai therapy for graves ' disease and the subsequent occurrence of thyroid cancer .
although it has been widely accepted that rai is safe , some studies have suggested that rai therapy is possibly associated with a small increased risk of thyroid cancer [ 2 - 4 ] .
degroot   reported that the rai treatment can induce an increase of thyroid antibodies , such as tsh receptor antibody , and it was suggested that thyroid stimulating antibodies play an important role in thyroid carcinogenesis .
these antibodies also can stimulate angiogenesis , which contributes to thyroid tumor cell growth , by activating vascular endothelial growth factor .
sturgis   reported cytomorphologic alterations in thyroid follicular epithelium , which is associated with rai therapy . before treatment , graves ' disease typically lack significant atypia , while after rai therapy , nuclear atypia , and progressive cellular metaplasia could be seen microscopically .
furthermore , it was prominent in those who remain in a hyperthyroid state despite rai treatment .
in addition to our case , two previously reported cases of atc after rai therapy for documented graves ' disease are summarized in table 1 .
baker   reported a 64-year - old woman with atc 12 years after rai therapy . because thyroid toxicity persisted after one course of rai therapy , the patient received a second therapy in 4 months .
gossage et al .   reported a 46-year - old woman who had her first rai therapy , when aged only 23 years .
although she underwent partial thyroidectomy prior to the rai therapy , hyperthyroidism recurred and she received several subsequent doses of radioiodine .
an analysis of these cases is noteworthy , because since the interval to cancer diagnosis was over 10 years in all cases , it supports the importance of long - term vigilance in patients receiving rai therapy .
in addition , these cases had something in common in terms of the occurrence of atc after repetitive , small doses of rai therapy .
the cooperative thyrotoxicosis therapy follow - up study showed that thyroid neoplasms developed in children treated with lower , rather than higher , doses of rai therapy , which is compatible with our finding .
therefore , it can be hypothesized that multiple courses of rai therapy , with small doses , may play a role in carcinogenesis , especially in the poorly differentiated type .
.   demonstrated that i treatment inactivates the tumor suppressor gene that is frequently found in atc rather than in the differentiated type .
however , to discuss the causal relationship between rai therapy and the occurrence of cancer , the number of reports is too small , therefore a population - based study is required and this is a limitation of our report .
in addition to the rai therapy , we can not exclude that graves ' disease itself might also increase the risk of cancer . although our patient had no thyroid nodule by ultrasonography ,
the palpable thyroid nodules found in graves ' patients have a 16.9% malignancy rate , which is higher than that of the general population .
moreover , the finding that thyroid autoantibody stimulates the malignant transformation of the thyroid gland supports this suggestion .
it is not clear that the occurrence of atc reported here was influenced by rai therapy or , alternatively , it may only represent the delayed recognition of a rare change in the natural history of graves ' disease .
nevertheless , this report is worthwhile since it presents a very rare case of atc that occurred 11 years after rai therapy for graves ' disease .

Answer:
radioactive iodine ( rai ) therapy has been used as a treatment option for graves ' disease , and it has been widely accepted to be safe . on the other hand , some evidence suggests that rai therapy is possibly associated with a small increased risk of thyroid cancer .
 herein , we report a rare case of anaplastic thyroid carcinoma ( atc ) associated with graves ' disease , following rai treatment . a 42-year - old woman had been diagnosed with graves ' disease and although she was treated with an antithyroid drug , she remained in a hyperthyroid state , which led to two rai treatments .
 more than 10 years later , the patient revisited our clinic due to hoarseness , dysphagia , and dyspnea , which had lasted for 2 months .
 neck computed tomography suggested thyroid carcinoma and a lymph node biopsy showed metastatic papillary carcinoma .
 the patient underwent total thyroidectomy and was finally diagnosed as having an atc .
 it is not clear if the occurrence of atc reported here was influenced by the rai therapy or alternatively , it may only represent the delayed recognition of a rare change in the natural history of graves ' disease .
 nevertheless , this report is worthwhile since it presents a very rare case of atc that occurred eleven years after the rai therapy for graves ' disease .


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:
lemierre 's syndrome is a septic thrombophlebitis of the internal jugular vein ( ijv ) commonly caused by anaerobic oropharyngeal flora that is usually followed by fulminant sepsis and rapid death in the pre - antibiotic era . since the introduction of antibiotics , the morbidity and mortality associated with this syndrome have been dramatically decreased .
however , delay in diagnosis and antibiotic treatment resulting in poor clinical outcome is not uncommon as physicians are less familiar with this infection and initial manifestations are often non - specific .
we describe a case of a patient with lemierre 's syndrome whose the diagnosis was not suspected until blood culture grew fusobacteirum necrophorum .
an otherwise healthy 36-year - old male presented to our institute with a 4-day history of low - grade fever accompanied by sore throat , myalgia and nausea .
physical examination was remarkable for a temperature of 38.1c and an injected pharynx without any neck tenderness or swelling .
complete blood cell count showed thrombocytopenia with platelet of 45,000/ul , hemoglobin of 14.8 g / dl and cell count of 8700 cells / ul ( neutrophil of 85% and band form of 6% ) .
he was diagnosed with viral upper respiratory tract infection and was admitted to general medicine service for rehydration .
he received 2 l of intravenous normal saline over night ; however , on the 2 day of hospitalization , he developed high fever of 39.2c along with pleuritic chest pain and low blood pressure of 80/50 mmhg .
blood cultures were obtained and empirical antibiotics ( vancomycin and piperacillin / tazobactam ) were initiated .
chest x - ray revealed bilateral patchy and irregular parenchymal opacities and subsequent chest computed tomography demonstrated right - sided pleural effusion and multiple thick - walled cavitary and nodular opacities consistent with septic emboli [ figure 1 ] .
his blood cultures grew f. necrophorum on the following day and his antibiotic therapy was narrowed down to piperacillin / tazobactam .
his blood pressure was normalized without using any vasopressor or mechanical ventilation ( he received 5 l of intravenous normal saline in total ) .
venous duplex ultrasonography was immediately obtained after the blood culture and demonstrated thrombus in the left ijv .
patient was finally diagnosed with lemierre 's syndrome and remained stable through rest of the hospital course .
piperacillin / tazobactam was continued for 7 days and he was discharged home with a 4-week course of intravenous ertapenem and recovered well from the infection .
( b - d ) chest computed tomography showed multiple thick - walled cavitary and solid nodules ( arrows ) and right - sided pleural effusion ( arrow heads )
lemierre 's syndrome or postanginal sepsis is a rare , but potentially fatal infection of the ijv .
it is usually caused by f. necrophorum although a wide variety of bacteria , including bacteroides , eikenella , porphyromonas , prevotella , proteus , streptococcus , peptostreptococcus and staphylococcus aureus has been reported as causative organisms .
the infection typically starts in the palatine tonsils or peritonsillar tissue and spread into the ijv - containing lateral pharyngeal space though causing septic thrombophlebitis though infection originated from pharynx , middle ear , sinus and parotid gland has also been described .
this septic thrombophlebitis is usually followed by distal septic embolization , resulting in multi - organ involvement with lung being the most commonly affected site with reported incidence of 97% .
other commonly involved sites are joints , muscle , soft - tissue , meninges , spleen and liver .
why f. necrophorum , a normal inhabitant of human oropharynx , becomes invasive is unclear .
loss of pharyngeal mucosal integrity caused by bacterial or viral infection might play a major role as several cases of lemierre 's syndrome proceeded by acute mononucleosis have been reported .
the increased production of leucotoxin is also pivotal for the pathogenesis as it can avidly activate platelet resulting thrombus formation in the ijv .
lemierre 's syndrome is classically described as a constellation of symptoms of fever , sore throat , neck swelling , pulmonary involvement and arthralgia that frequently affects young healthy adults .
nevertheless , initial clinical presentation can be subtle and sometimes persistent fever is the only prominent symptom and the syndrome is frequently not suspected until the microbiologic data is available hence high - level of clinical suspicion is needed for the timely diagnosis .
physical examination might reveal an exudative tonsillitis or milder form of pharyngitis ; however , these oropharyngeal signs might not be evident as the septic thrombophlebitis or metastatic complication usually occurs 1 - 3 weeks after the primary infection .
typical signs of ijv thrombophlebitis are pain and swelling along the sternocleidomastoid muscle , but they are found in only approximately a half of patients .
diagnosis of lemierre 's syndrome is established on the presence of thrombus in ijv and positive blood culture .
computed tomography of neck with contrast is the diagnostic modality of choice to demonstrate the thrombus .
doppler ultrasonography is an alternative since it is less invasive and can be done at bedside though it is less sensitive particularly in the area deep to clavicle and mandible and can miss newly formed thrombus with low echogenicity .
prolonged course of intravenous antibiotic ( 3 - 6 weeks ) covering f. necrophorum and oral streptococci is the cornerstone of treatment . as beta - lactamase producing strain of f. necrophorum
appropriate first - line antibiotics should be one of the following : beta - lactam / beta - lactamase inhibitor , carbapenem , ceftriaxone + metronidazole and clindamycin .
the role of anticoagulation is unclear , but is generally not indicated unless there is evidence of expansion of the thrombus .
surgical ligation or excision of the ijv might be necessary in the case of uncontrolled sepsis or septic emboli despite adequate antibiotic .
we report a case of healthy young male who presented with flu - like symptoms and was initially mistaken for viral upper respiratory tract infection .
intensivists should have a high index of suspicion for this diagnosis in otherwise healthy young adult .
history of preceding pharyngitis or evidence of septic emboli , especially to the lung may provide an additional clue to the diagnosis .

Answer:
lemierre 's syndrome is an uncommon , but fatal infection of the internal jugular vein ( ijv ) that is usually caused by fusobacteirum necrophorum although a wide range of bacteria has been reported as causative agents .
 typical symptoms include fever , sore throat , neck swelling , pulmonary symptoms and arthralgia ; however , the diagnosis of this infection is frequently overlooked as initial manifestation might be subtle and non - specific .
 definite diagnosis requires positive blood culture and radiological evidence of thrombus in the ijv .
 we describe a case of a patient with lemierre 's syndrome who was initially misdiagnosed with viral upper respiratory tract infection .
 high index of suspicion is pivotal to the diagnosis of this infection and lemierre 's syndrome should always be considered as a potential cause of sepsis in an otherwise healthy 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:
a 68-year - old male presented complaining of sudden and profound loss of central vision in his left eye following blunt eye trauma .
he reported seeing a large , dense , central scotoma that began fading 1 h after the injury .
he was emmetropic , phakic , and had no significant ophthalmic history . on examination , 24-h postinjury , best - corrected visual acuity ( bcva ) in the left eye
oct of the left macula ( spectralis , heidelberg engineering , 5-line raster acquisition protocol ) revealed abnormal hyper - reflectivity and nodularity of the photoreceptor os layer .
interestingly , the patient was found to have prominent abnormalities on infrared imaging using the infrared reflectance protocol of the spectralis oct [ fig . 1 ] .
infrared imaging of the left fundus revealed diffuse infrared hypo - reflectance dotted with spots of very low pixel value ( dark ) , creating a stippled appearance .
point - to - point correlation between the infrared and oct images using the spectralis software ( heidelberg engineering , germany ) demonstrated that the infrared dark spots correlated with foci of thickened os seen on 5-line raster oct .
no pathology of the superficial retina , retinal pigment epithelium or choroid was detected using red - free reflectance , fundus auto - fluorescence , and enhanced - depth imaging ( edi ) , respectively .
30 posttrauma , and at 8 months posttrauma , bcva in the left eye was 20/25 and the retina appeared normal on examination and when imaged with infrared reflectance , 5-line raster oct , fundus auto - fluorescence , and edi [ fig .
2 ] . left fundus images at day 1 postblunt trauma to the left eye .
( b ) infrared confocal scanning laser ophthalmoscope fundus image demonstrating stippled hypo - reflectance at the macula . ( c )
optical coherence tomography of the macula demonstrating abnormal hyper - reflectivity of the outer segments ( between arrowheads ) .
( b ) infrared confocal scanning laser ophthalmoscope fundus image reveals resolution of the infrared hypo - reflectance
in this case , there is a clear temporal relationship between eye trauma , transient vision loss , transient oct changes consistent with cr , and transient infrared hypo - reflectance .
cases of cr detectable on oct , but not fundus examination have been described , confirming that some cases of cr are subclinical . to the best of the authors knowledge
the pathology of cr has been studied histologically and on oct , and comprises fragmentation of the photoreceptor os without injury to the inner retina .
as demonstrated by our case , this manifests on 5-line raster oct as abnormal hyper - reflectivity of the os layer .
this oct feature is subtle and is easily overlooked if the study is not carefully scrutinized .
our case implicates infrared imaging as a diagnostic adjunct for detecting subclinical cr . since focal dark spots on infrared imaging correlated with points of nodular os thickening in our case
, we infer that the infrared hypo - reflectance in cr is caused by increased absorption of infrared light by an abnormal os layer . with a wavelength of 820 nm ,
the infrared mode of the spectralis oct penetrates deeper into the retina than modalities using visible wavelengths of light .
it is , therefore , useful for detecting outer retinal pathology , such as that of cr .
the spectralis uses a confocal scanning laser ophthalmoscope ( cslo ) and records infrared reflectance without barrier filters . compared with conventional recording techniques
, cslo improves image resolution by using a higher emission of light energy and by reducing the capture of scattered light .
further studies are required to determine whether infrared hypo - reflectance is a consistent feature in all cases of cr , and whether this imaging modality has greater sensitivity for detecting subclinical cr than 5-line raster oct .
nevertheless , this case suggests that infrared imaging may have a role as a diagnostic adjunct for detecting subclinical cr .
we recommend that clinicians consider performing infrared imaging of the retina when managing a patient who presents with unexplained vision loss after blunt trauma and a normal - appearing fundus .

Answer:
commotio retinae ( cr ) is an outer retinal disorder following blunt trauma to the eye .
 histologically it is characterized by disruption of the photoreceptor outer segments ( os ) , typically without injury to other retinal layers .
 using spectral - domain optical coherence tomography ( oct ) the condition is visible as hyper - reflectivity of the os .
 most cases of cr are associated with transient grey - white discoloration of the retina and are easily diagnosed clinically , but there have been reports of oct - confirmed cr without retinal discoloration .
 it is likely that this subclinical variant of cr is under - recognized as the oct features of cr are subtle .
 here , we report a case of oct - confirmed subclinical cr that demonstrated prominent infrared hypo - reflectance , using the infrared protocol of the spectralis oct , heidelberg engineering .
 this case suggests that infrared reflectance may have a role in diagnosing cases of subclinical cr .


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 calcifying odontogenic cyst ( coc ) was first described by gorlin and his colleagues ( 1962 ) , as a separate entity of odontogenic origin .
as all lesions are not cystic and the biological behavior is often not compatible with a cyst , there is a controversy as to whether coc is a cyst or a tumor .
based on the dualistic concept , some authors consider that coc contains two entities : a cyst and a neoplasm .
however , others regard coc as a tumor with a tendency for cyst formation . based on this monistic concept the world health organization ( who ) has classified all cocs as neoplasms .
the cystic lesions are termed as  calcifying cystic odontogenic tumors  ( ccot ) and the neoplastic entity as a  dentinogenic ghost cell tumor(dgct ) .
microscopically , it consists of ameloblastomatous epithelial islands , with areas of ghost cell formation and varying amount of dentinoid material . the purpose of this article is to report a case of dentinogenic ghost cell tumor in a 21-year - male , in the posterior region of the mandible , which is at a comparatively younger age and at an infrequent site .
a 21-year - old male patient reported to the department of oral pathology and microbiology , government dental college and hospital , aurangabad , with the complaint of swelling in the left posterior region of the lower jaw , of one - month duration .
extraorally a diffuse swelling was seen over the left mandibular angle region [ figure 1 ] .
diffuse swelling over mandibular angle region on left side intraoral examination revealed the presence of a bony hard swelling , extending from 37 to the retromolar region [ figure 2 ] .
the color of the lesional area was the same as that of the adjacent mucosa .
it showed a smooth surface all over , except a small growth distal to 37 , which subsided after antibiotic treatment .
bony hard swelling extending from 37 to retro - molar region with a small 1  1 cm reddish growth , distal to 37 radiographs revealed a well - defined lesion extending from 34 to the ramus of the mandible with scalloped borders .
an occlusal radiograph showed buccal cortical expansion in the retromolar region on the left side [ figure 4 ] .
root resorption of 36 and 37 buccal cortical expansion in the left retro - molar region histopathological examination revealed a tumor mass composed of islands of odontogenic epithelial cells with hyperchromatic nuclei in a mature connective tissue stroma .
ameloblastoma - like islands with peripheral columnar , polarized basal cells , and central stellate reticulum - like cells were also noted .
numerous ghost cells with faint eosinophillic cytoplasm and a shadow of nuclear outlines were noted within the epithelial islands as well as in the connective tissue [ figure 5 ] .
many foreign body - type multinucleated giant cells were observed surrounding the ghost cells in the connective tissue stroma [ figure 6 ] . some ghost cells exhibited calcification .
masses of dentinoid - like material were present in close proximity to the epithelial islands ; in which some showed calcification [ figure 7 ] .
ameloblastomatous epithelial island with ghost cells and dentinoid material ( h and e ,  40 ) giant cells surrounding ghost cells in the connective tissue stroma ( h and e ,  100 ) calcifying ghost cells and dysplastic dentin ( h and e ,  100 ) tumor cells infiltrating adjacent bone ( h and e ,  400 )
calcifying odontogenic cyst constitutes 1 to 2% of all odontogenic tumors in which 88.5% are cystic and the remaining 11.5% are solid tumors .
( 1981 ) , termed these solid tumors as  dentinogenic ghost cell tumors  as they are made up of an ameloblastomatous epithelium with areas of ghost cell formation and varying amounts of dentinoid .
fejerskov and krogh ( 1972 ) , interpreted it as a tumor or hamartoma with a marked tendency for cystic degeneration .
they stated that there is no reason to assume that epithelial change can develop only in the pre - existing cyst wall , but rather cystic degeneration can take place in the of the proliferating epithelial island .
these authors also noted that the lesion is not invariably cystic and suggested the term  calcifying ghost cell odontogenic tumor  .
as it appeared to be one variety of ameloblastoma and could recur after conservative surgical treatment , shear ( 1983 ) , preferred the term  dentinoameloblastoma  .
ellis and shmookler ( 1986 ) , preferred the term  epithelial odontogenic ghost cell tumor  as epithelial cells appearing like ghost cells were the most distinctive feature of this neoplasm .
( 1990 ) , suggested the term  odontogenic ghost cell tumor  for the same neoplastic form of coc .
the average age for the presentation of this lesion is 50 years , ( range 17  72 years ) with slight male predilection .
tumor occurs in the maxilla and the mandible with equal frequency , with canine to first molar region the most often the affected site .
patients are usually without symptoms , although with a few complain of pain or discomfort .
the present lesion was seen in a 21-year - old male , in the posterior region of the mandible on the left side , at a comparatively younger age , and contrary to the common anterior region of the jaw .
root resorption or an impacted tooth in relation to the tumor mass is also noted in some cases .
microscopic features show islands of odontogenic epithelial cells with hyperchromatic nuclei in a mature connective tissue .
loosely arranged stellate reticulum - like cells may be seen enclosed by the odontogenic epithelium .
the epithelium may show ameloblastomatous proliferation with a well - defined basal layer of columnar or cuboidal cells and hyperchromatic nuclei , which are polarized away from the basement membrane . on account of the multipotentiality of odontogenic epithelium , the histological presence of areas similar to different odontogenic tumors , such as , ameloblastoma
, odonto - ameloblastoma , ameloblastic fibro - odontoma , odontoma , adenomatoid odontogenic tumor , and cementoma may be seen .
two characteristic features of dgct distinguish it from ameloblastoma and other odontogenic tumors , numerous ghost cells , and masses of dentinoid material .
ghost cells are characterized by the loss of nuclei , preservation of basic cellular outlines , and resistance to degradation .
although cellular outlines are usually well defined , they may be blurred , and as a result the groups of ghost cells appear fused .
dystrophic calcification may occur in some of the ghost cells , initially seen as fine basophilic granules and later as small spherical bodies .
sometimes ghost cells break through the basement membrane and come in contact with the connective tissue , where they evoke a foreign body reaction with the formation of multinucleated giant cells .
most authors interpreted the changes in the ghost cells as aberrant or incomplete keratinizations or even as true keratinizations .
abram and howell ( 1968 ) , presented the concept that the keratin appeared to originate from the degeneration of squamous cells .
levy ( 1973 ) , investigated the ghost cells in odontomas and suggested that they represented squamous metaplasia with subsequent calcification caused by ischemia .
sedano and pindborg ( 1975 ) , thought that ghost cells represented different stages of normal and aberrant keratin formation and that they were derived from the metaplastic transformation of odontogenic epithelium .
other investigators were of the opinion that ghost cells might be the product of abortive enamel matrix in the odontogenic epithelium , however , the morphology of ghost cells seems to be different from that of the enamel matrix .
another characteristic feature is the formation of dentinoid or osteoid material , which represents an inflammatory response of the body to the presence of ghost cells .
abrams and howell ( 1968 ) , stated that masses of ghost cells induce granulation tissue to lay down the juxtaepithelial osteoid , which may calcify .
sauk ( 1972 ) , sapp and gardner ( 1977 ) , and nagao et al .
( 1982 ) , stated that the juxtaepithelial osteoid or dentinoid are frequently found in areas free of either granulation tissue or ghost cells and postulated that it might be an inductive phenomenon rather than an inflammatory response .
to date , it is not clear whether this material represents a true inductive effect or merely a metaplastic change in the connective tissue .
similar histopathological features are seen in the present case , and hence it has been diagnosed as
dentinogenic ghost cell tumor  . in the immunohistochemical evaluation of a case of dgct, by piatelli a et al .
the epithelial cells were positive for cytokeratins , characterizing the presence of an odontogenic epithelium , while the calcified bodies and ghost cells were devoid of any immunoreactivity , representing that they were derived from the metaplastic transformation of the odontogenic epithelium or were a product of the coagulative necrosis of the odontogenic epithelium .
there was also a strong positivity of the odontogenic epithelium for bcl-2 and mib-1 , whereas , only a rare positivity for p-53 .
the ghost cells , giant cells , and dentinoid material were completely negative . it was concluded that the cells that expressed bcl-2 and mib-1 probably represented the portion of the tumor that proliferated and that could undergo malignant transformation . initially enucleation was the primary treatment for central dgct , but local recurrence was noted .
the patient has been under observation since nine months and no recurrence has been noted till now .
coc has been seen to be of extensive diversity in its clinical and histopathological features as well as in its biological behavior .
the present case of 21-year - old male was diagnosed as dgct , a tumorous form of coc , due to its characteristic histological features ; numerous ghost cells and dentinoid material .

Answer:
dentinogenic ghost cell tumor ( dgct ) is a rare tumorous form of calcifying odontogenic cyst and only a small number of cases have been described .
 it is a locally invasive neoplasm that is characterized by ameloblastoma - like epithelial islands , ghost cells and dentinoid .
 the present report describes a case of a 21-year - old male with a tumor in the posterior region of the mandible , showing features of dgct .


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:
to foster greater coordination on surveillance , research , education , and prevention of tickborne diseases , cdc established ticknet during 2007 .
ticknet is a public health network that includes partners from state health departments and academic institutions collaborating through the emerging infections program ( eip ) , staff of state and local health departments collaborating through the epidemiology and laboratory capacity ( elc ) cooperative agreement , and cdc staff in the division of vector - borne diseases and the division of parasitic diseases and malaria .
ticknet provides funding to state and local health departments through the elc cooperative agreement to help sustain and enhance routine surveillance for tickborne diseases .
approximately 18 state and local health departments are funded annually for lyme disease surveillance , with priority given to states with a reported incidence of lyme disease greater than the national average and to bordering states where the disease may be spreading . during 2014 , an additional 7 state and local health departments received elc funding to support surveillance for other tickborne diseases . together with elc funding for program support , funding through eip has allowed ticknet partners in maryland , minnesota , and new york to undertake special studies to quantify underreported tickborne diseases .
these studies include a review of patient charts and codes from the international classification of diseases , ninth edition , and provide insights into the use of electronic medical records for public health surveillance .
other studies in massachusetts , minnesota , and new york are examining ways to streamline the evaluation of positive laboratory reports by using random sampling methods .
, ticknet partners at eip sites in connecticut , maryland , minnesota , and new york conducted a survey of commercial , clinical , and state laboratories to evaluate practices and volume of testing for 5 leading tickborne diseases . collectively , 7 large commercial laboratories reported testing 2.4 million patient specimens for evidence of b. burgdorferi infection during 2008 , at an estimated cost of $ 492 million . after correcting for test sensitivity , specificity , and stage of illness ,
the overall frequency of infection among patients for whom samples were tested was estimated at 12% .
applied to the total number of specimens , this percentage yielded an estimated 288,000 true b. burgdorferi infections ( range 240,000444,000 ) among source patients during 2008 ( 18 ) .
results of this study will be compared with results of other ongoing cdc studies to estimate the overall frequency of lyme disease and other tickborne infections in the united states .
to better quantify the public health burden of tickborne diseases , ticknet eip partners in connecticut , maryland , minnesota , and new york have undertaken a study to quantify current costs associated with individual cases of lyme disease . begun during 2014 ,
the cost of lyme disease study uses a prospective survey design to capture individual and societal costs of lyme disease , including out - of - pocket medical costs , nonmedical costs , and productivity losses , as well as total direct medical costs to society by using billing codes from enrolled patients providers .
this estimate will be used to guide impact assessments of current and future prevention methods . as an adjunct to personal protective measures such as use of insect repellents ,
several yard - based interventions have been proposed to reduce tick abundance in the home environment . to assess the efficacy of such interventions in preventing human illness , ticknet sites have instituted a series of studies to evaluate the efficacy of novel and commercially available prevention strategies .
one study , a randomized , blinded , placebo - controlled , multistate trial assessing the effectiveness of acaricide barrier sprays , will cover 2,700 households in 3 states , with outcomes measures including tick density on acaricide - treated properties , the number of tick  human encounters , and the number of tickborne diseases in humans .
a second study , begun in connecticut during 2012 , uses a similar design to evaluate the effectiveness of bait boxes that apply fipronil to rodents that are the reservoirs of b. burgdorferi
. used by veterinarians to prevent flea and tick infestations on dogs , fipronil kills ticks on the rodents for several weeks and may potentially interrupt the local transmission cycle of b. burgdorferi .
recent experience indicates that additional tickborne pathogens are waiting to be discovered . in collaboration with the tennessee and minnesota health departments , the mayo clinic , and vanderbilt university ,
ticknet has recently initiated a study to identify novel agents of tickborne disease . over the next 3 years ,
> 30,000 clinical specimens from us patients with suspected tickborne diseases will be screened by using high - throughput molecular methods designed to detect bacteria , followed by use of genomic sequencing to characterize detected pathogens .
the ultimate goal is to better describe the epidemiologic and laboratory features associated with recognized and novel tickborne pathogens and to guide the development of new diagnostic methods .
although sometimes overlooked , tickborne diseases pose an increasing threat to public health . factors driving the emergence of tickborne diseases are poorly defined , but current prevention methods are clearly inadequate . addressing this problem
requires a multidisciplinary approach with input of entomologists , epidemiologists , educators , and infectious disease and communications specialists .
built on the pillars of the eip and the elc cooperative agreements , ticknet provides a collaborative network that brings together these resources at the federal and state levels to enhance surveillance , improve prevention , and identify new tickborne diseases .

Answer:
ticknet , a public health network , was created in 2007 to foster greater collaboration between state health departments , academic centers , and the centers for disease control and prevention on surveillance and prevention of tickborne diseases .
 research activities are conducted through the emerging infections program and include laboratory surveys , high - quality prevention trials , and pathogen discovery .


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:
infections are common in patients with cirrhosis and have been found in up to 66% of patients with variceal hemorrhage .
prophylactic treatment with third generation cephalosporins is recommended in patients with advanced cirrhosis and gastrointestinal bleeding to cover for the predominant causative gut flora organisms , .
treatment is recommended even if no causative organism is identified as up to 50% of patients with cirrhosis and clinical sepsis have negative cultures . identifying appropriate antimicrobials
can be challenging without a causative organism , and the empiric use of broad spectrum antimicrobials contributes to multidrug resistant organisms .
we report the first known case of paracoccus yeeii bacteremia in a patient with decompensated cirrhosis who presented with variceal hemorrhage . this rare gram negative organism may not be susceptible to third generation cephalosporins .
this finding may have implications for the management of infected but culture negative patients with cirrhosis .
a 42  year old gentleman with decompensated cirrhosis from genotype 1a ( g1a ) hepatitis c ( hcv ) had been treated with 24 weeks of ledipasvir and sofosbuvir which ended 4.5 months earlier .
the patient presented with new onset jaundice ( total bilirubin 23  mg / dl , direct bilirubin 18  mg / dl , alkaline phosphatase 99  u / l , alanine aminotransferase 31  u / l , aspartate aminotransferase 86  u / l ) that peaked to total bilirubin 44  mg / dl and direct bilirubin 31  mg / dl . model for end - stage liver disease ( meld )
score on admission was 27 . given the report of subjective fevers in the setting of recently treated k. pneumoniae bacteremia of unknown source , admission blood and urine cultures were obtained but were without growth .
molecular studies revealed hcv relapse ( hcv viral load  =  4.44 log iu / ml ) without ns5b resistance ( insufficient sample for ns5a ) and undetectable hepatitis b ( hbv ) and adenovirus .
there was no serologic evidence of acute infection with hepatitis e , cytomegalovirus ( cmv ) , or epstein barr virus ( ebv ) .
liver biopsy demonstrated cirrhosis with moderate chronic inflammation , focal severe neutrophilic infiltrates with cholestasis , and ductular proliferation .
magnetic resonance imaging ( mri ) and magnetic resonance cholangiopancreatography ( mrcp ) showed no cholangitis or abscess . although drug induced liver injury from ciprofloxacin was clinically suspected , two sets of blood cultures were obtained daily due to concern for infection and lack of clinical improvement . the patient elected discharge but was readmitted within 24  hours with hematemesis from variceal hemorrhage and portal hypertensive gastropathy .
empiric treatment for undifferentiated septic shock including spontaneous bacterial peritonitis prophylaxis were ceftriaxone 2  g iv every 24  hours , metronidazole 500  mg iv every 8  hours , and vancomycin 2  g iv every 12  hours .
diagnostic paracentesis was again attempted but the patient had minimal ascites . given the lack of clinical improvement and the finding of bowel edema and severe colitis on computer tomography , infectious disease was consulted .
it was recommended to adjust antimicrobials to piperacillin - tazobactam 3.375  mg every 6  hours , metronidazole 500  mg iv every 8  hours , and vancomycin 125  mg po every 6  hours to cover for gut flora including clostridium difficile until it could be ruled out .
blood cultures collected the day before discharge of the previous admission flagged as  positive  after 5  days of incubation in the aerobic bottle ( bactec plus aerobic / f ) , but no organisms were seen upon gram stain . however , after two days of incubation , small mucoid colonies of oxidase positive gram negative coccobacilli were seen growing on chocolate agar only . the team was notified and antimicrobials were adjusted to only piperacillin - tazobactam 4.5  g every 6  hours .
after an additional two days of incubation , an identification of paracoccus yeeii was made by matrix assisted laser desorption ionization time of flight mass spectrometry ( maldi - tof ms ; vitek ms ) with a match of 99.9% to the vitek ms ivd unclaimed database .
identification was confirmed by sequencing of the first 500  bp of the 16s gene . upon speciation ,
the patient was switched to ceftazidime 1  g every 12  hours to cover for p. yeeii as well as concern for a hospital acquired pneumonia .
the patient completed a 2 week treatment course of gram negative antimicrobial coverage with two beta lactam agents and had clinical improvement with no other culture growth of p. yeeii .
unfortunately , the patient developed end - stage liver disease and eventually succumbed to death due to septic shock from citrobacter freundii pneumonia .
to our knowledge , this is the first reported case of p. yeeii in a patient with cirrhosis .
patients with decompensated cirrhosis are at high risk of infection from immune dysregulation , a heightened inflammatory response , altered gut flora , and bowel translocation .
however , no causative organism is found in up to 50% of patients with decompensated cirrhosis presenting with clinical sepsis .
this case of bacteremia with a rare gram negative organism is instructive regarding optimal diagnosis and treatment of infection in patients with decompensated cirrhosis who have an unclear source of infection as they have an extremely high risk of morbidity and mortality .
p. yeeii is an aerobic gram negative coccobacillus that has been isolated in soil and marine sediment , and has been rarely reported as infections in humans .
p. yeeii has been identified in the past through commonly available biochemical tests , and this case demonstrates the utility of maldi - tof ms for the identification of this infrequently encountered organism , .
the few reported cases of p. yeeii to date have entailed peritonitis among peritoneal dialysis patients , , myocarditis in a heart transplant patient , corneal graft infection , and heart failure with bullous skin lesions .
all cases identified p. yeeii through culture of affected tissues . only 2 cases , including ours , have been associated with bacteremia and ours is the first case of a patient with cirrhosis . the source of bacteremia in our case remains unclear , but it is plausible that the patient s lymphedema and bowel edema could be sources for this environmentally found organism . over the previous year , the patient had several episodes of bacteremia thought to be from bowel translocation including group g -hemolytic streptococci , streptococcus mitis / oralis , citrobacter braakii , and enterococcus faecium ( the patient was not on chronic antimicrobials ) .
maldi - tof may help with rapid diagnosis and guide appropriate treatment when initial cultures in patients with decompensated cirrhosis and clinical sepsis are negative .
it is recommended that patients with advanced cirrhosis who develop gastrointestinal bleeding be treated empirically with third generation cephalosporins , .
however , this case illustrates that uncommon gram negative organisms may not necessarily be covered with third generation cephalosporins .
although we did not have antimicrobial susceptibilities performed in our case , the existing literature on p. yeeii suggests that the organism is susceptible to fluoroquinolones and beta - lactams though higher minimum inhibitory concentrations ( mics ) were reported with third generation cephalosporins .
this case reinforces the challenges in isolating rare infections in patients with cirrhosis . in the absence of obvious infectious sources in a patient with decompensated cirrhosis
collaboration with infectious disease specialists and microbiologists is warranted in these cases to isolate infectious organisms and to identify appropriate antimicrobials promptly .
this research did not receive any specific grant from funding agencies in the public , commercial , or not - for - profit sectors .

Answer: highlightsno organism is found in up to 50% of infected patients with decompensated cirrhosis.in the absence of obvious infectious sources , consider rare gram negative organisms.uncommon gram negative organisms may not be covered by empiric antibiotics.maldi-tof may help with diagnosis when cultures are negative in these patients.human infections with paracoccus yeeii , a gram negative coccobacillus , is rare .


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:
vascular malformation is known as one of the major therapeutic problem even to the most experienced clinicians .
these malformations grow proportionately with age , and may involve multiple anatomical spaces and encase critical neuromuscular structures , associated with nerve damage , massive bleeding , and deformity .
management of arteriovenous malformations ( avms ) remains challenging because of their unpredictable behavior and high recurrence rate if treated by curettage alone without inadequate ligation of the feeder vessels .
these lesions are treated by variety of techniques over the years , including surgical excision , irradiation , electrocoagulation , cryotherapy , intravascular magnesium or copper needles , systemic corticosteroids , interferon- , embolization , cryotherapy , lasers and sclerotherapy .
sclerotherapy is an effective , conservative and low cost technique for the treatment of benign vascular lesions , included vascular malformation .
the sclerosant agents used are 5% sodium morrhuate , sodium psylliate , quinine urethrone , 5% ethanolamine oleate , 1% polidocanol , sodium tetradecil sulfate , and hypertonic saline .
we present our experience in treating palatal vascular malformation using direct ethanol sclerotherapy as a cheep therapeutic modality for treatment of deeply seated vascular lesion .
twenty one - year old saudi male patient presented to the department of oral and maxillofacial surgery clinic at king abulaziz university complaining of swelling on the right side of the face ( figure 1a ) .
extra - oral clinical examination revealed swelling on the right side of the face , which is soft and compressible .
intraoral examination showed a bluish swelling at the junction of soft and hard palate that bleed easily on touch .
computerized tomography ( ct ) and magnetic resonance image ( mri ) studies revealed that it is a vascular malformation that extends to the infratemporal area ( figure 2 ) .
the patient was advised to have ethanol directly injected into the lesion as surgical excision was hazardous and difficult to achieve .
patient disagree with that option and disappear for 18 months and returned back with severe gingival inflammation around the whole right maxillary quadrant which appeared covered by heavy calculus as he could not brush his teeth because of bleeding that he described as extensive ( figure 1c ) .
advised was given to the patient that the only treatment option we can offer him is the ethanol injection .
the procedure and possible complications were explained to the patient and family and they agreed to that option . under general anesthesia using fibro optic intubations , as the lesion was approaching the soft palate and there was a fear that routine nasal intubations could be hazardous to the airway , contrast medium was injected toward the engorged vascular lesion using a no .
18 venipuncture catheter ( to determine the volume of the growths before treatment ) , followed by injection of one - third to one - quarter cavity volume of 95% ethyl alcohol into the tumor cavity according to lee and chen ( figure 3 ) .
the patient was kept intubated for 48 h to guard his airway , as there was edema .
intravenous dexamethasone ( 0.1 mg / kg ) was given for 3 days postoperatively to control inflammation .
patient was discharged from the hospital on the fifth post injection day and kept follow up every week for the first three months , then every 2 weeks for another 3 months .
the lesion remarkably shrinks and the hygienist was able to thoroughly scale his teeth without any bleeding ( figure 4 ) .

figure 1a ) clinical picture of the patient showing facial asymmetry as result of right zygomatic swelling ; b ) intraoral view shows bluish mass extending to the soft palate when the patient presented to the clinic for the first time ; c ) intraoral photograph of the same patient 18 months after first presentation .
the lesion increased in size , bled easily and appeared darkens with bad oral hygiene and heavy calculus at the right side of the jaw .

a ) clinical picture of the patient showing facial asymmetry as result of right zygomatic swelling ; b ) intraoral view shows bluish mass extending to the soft palate when the patient presented to the clinic for the first time ; c ) intraoral photograph of the same patient 18 months after first presentation .
the lesion increased in size , bled easily and appeared darkens with bad oral hygiene and heavy calculus at the right side of the jaw .

figure 2a ) axial and b ) coronal computed tomography scan obtained with contrast material shows dilated vessels that extend into the infratemporal area and multiple phleboliths can be seen .
c ) and d ) axial t2 weighted magnetic resonance image shows high intensity lesion with flow representing vessels of different sizes .

a ) axial and b ) coronal computed tomography scan obtained with contrast material shows dilated vessels that extend into the infratemporal area and multiple phleboliths can be seen .
c ) and d ) axial t2 weighted magnetic resonance image shows high intensity lesion with flow representing vessels of different sizes .

figure 3a ) the catheter loaded with ethanol in place during injection ; b ) contrast medium is injected into the lesion and an x - ray is taken to make sure that the catheter is within the lesion itself ; c ) an angiogram shows ethanol injection within the lesion .

a ) the catheter loaded with ethanol in place during injection ; b ) contrast medium is injected into the lesion and an x - ray is taken to make sure that the catheter is within the lesion itself ; c ) an angiogram shows ethanol injection within the lesion .

figure 4a ) postoperative picture of the lesion one and b ) three months following injection .

a ) postoperative picture of the lesion one and b ) three months following injection .
there were no complications reported in this case except some palatal ulceration which is improving with every visit .
treatment success was determined clinically by reduction in lesion size , ability of the patient to chew and to clean his teeth without bleeding , patient experience to pain and by patient satisfaction .
for example : surgical excision can lead to significant loss of motor function , cosmetic problems , nerve damage , or massive bleeding and the complicated anatomy of the face and neck , may result in significant loss of motor function , cosmetic problems , nerve damage , or massive bleeding if surgery is adopted .
laser therapy presents higher costs to the patient and may result in skin atrophy , transient or permanent hyperpigmentation , slight depression of the skin and scarring .
intralesional injection of corticosteroids may cause adrenal suppression , slowed weight gain , atrophy , and necrosis .
the use of sclerotherapy in the management of vascular anomalies has increased and replaced the traditional role of surgical therapy , especially for the venous lesions that are surgically difficult or at inaccessible areas .
it has the advantage of low cost , no external scaring , and few complications compared to surgical treatment .
varieties of sclerosing agents have been used for the management of various vascular malformations such as 5% sodium morrhuate , sodium tetradecyl sulphate , ethanolamine oleate , ok432 , bleomycin , ethanol , and hypertonic saline , alone or in various combinations .
absolute ethanol was adopted as a new scleroagent for this complex form of venous defects to improve overall treatment results with acceptable morbidity and recurrence rates .
ethanol is used most of often due to its low cost , antiseptic quality , wide availability and easy of use ; however , it requires general anesthesia because the procedure is very painful .
the aim of treatment is to eradicate the lesion nidus completely , which is the fundamental abnormality as even the smallest residual nidus may expand to form a recurrence . in the presented case it was difficult to achieve complete eradication of the lesion by surgical approach because of the possible hazards that are associated with the affected site .
it has been suggested that ethanol cause protoplasm precipitation which subsequently causes permanent obliteration of the vessel lumen . also do et al .
reported that ethanol has shown the ability to induce protein denaturation of the endothelial cells with subsequent vessel wall denudation and interruption , which results in the complete obliteration of the vessel lumen rather than just simple obstruction .
although various complications were reported to develop during the procedure such as local skin necrosis and fibrosis , haemoglobinuria , anaphylaxis , and some major complications were rarely reported including blood loss , acute pulmonary hypertension with cardio - pulmonary collapse , therefore , lee and chin used rubber bands to compress the patient 's forehead and chin to occlude facial venous return and minimize complications , also hammer et al . recommended to inject the ethanol slowly , over a period of several minutes and not exceeding 1 cc / kg of body weight while monitoring the pulmonary artery pressure to avoid such a catastrophic situation
also , ethanol should only be used in the head and neck region by individuals and centers with professional expertise and experiences including maxillofacial surgeon , general radiology , general medicine , cardiovascular medicine , physical medicine and rehabilitation , dermatology , psychiatry , nuclear medicine , and social services with maximum efficiency to handle or at least minimize various anticipated complications .
also , careful and routine monitoring of pulmonary arterial pressure are required by the interventional radiologist , and anesthesiologist .
vascular malformations were treated with direct percutaneous injection of absolute ethanol , which resulted in remission , and alleviation of their symptoms , with no major complications .
this technique provides a simple , low cost and reliable alternative treatment for venous malformation in the face and neck .
absolute ethanol sclerotherapy can deliver excellent results as an independent therapy to the infiltrating type of extra - truncular form of vm .
complications can occur but are rare . the morbidity involved should be clearly understood and accepted by the patient and family , and the risk of acute and chronic complications , either major or minor ,

Answer:
arteriovenous malformation is treated by variety of techniques over the years .
 sclerotherapy is considered an effective and conservative technique for the treatment of benign vascular lesions and replaced the traditional role of surgical therapy , especially for the venous lesions that are surgically difficult or at inaccessible areas .
 absolute ethanol was adopted as a new sclerosant agent for this complex form of venous defects to improve overall treatment results with acceptable morbidity and recurrence rates .
 sclerotherapy has the advantage of no external scaring , low cost , and few complications in comparison to the surgical treatment .


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:
antiphospholipid syndrome ( aps ) is an autoimmune disease characterized by the presence of antiphospholipid antibodies , venous and/or arterial thrombosis , and repetitive fetal loss [ 1 , 2 ] .
the laboratory criteria to diagnose aps are high serum levels of lupus anticoagulant as well as anticardiolipin and -2 glycoprotein - i antibodies .
aps can occur with other systemic diseases such as systemic lupus erythematosus or as a single entity .
deep vein thrombosis represents the most frequent aps complication , as it occurs in 2955% of patients ; however , acute or indolent chronic ischemic presentations can involve any organ including the lung , skin , brain , liver , kidneys , adrenal glands , heart , and eyes .
ocular involvement can occur in 888% of patients [ 5 , 6 , 7 ] and it can be the first sign at presentation .
it is therefore important to make a quick diagnosis in order to consider anticoagulant treatment to prevent further thrombosis , as the risk of this complication is up to 29% in untreated aps patients .
visual symptoms at presentation vary from a reduction of visual acuity and amaurosis fugax to transient scotoma and visual field defect , all of which can be unilateral or bilateral .
it is important to underline that , when amaurosis fugax involves both eyes simultaneously , it is often a manifestation of central nervous system ischemia .
ocular discomfort , conjunctival hyperemia , and pain have often been reported in the literature as common symptoms of aps patients .
a 38-year - old female patient presented with reduced vision in the right eye , which had occurred the same day .
the patient had a negative ocular and medical history and no previous miscarriage as well as no relevant family history for ophthalmic pathologies .
visual acuity was finger count in the right eye ( 1-meter distance ) and 20/20 in the left eye .
fundoscopic examination revealed a subhyaloid hemorrhage , engorged and tortuous retinal veins , intraretinal hemorrhages , and cotton wool spots ( fig .
1 ) . fundus fluorescein angiography demonstrated a delayed inferior hemiretinal venous filling ( fig .
3 ) . as choroidal ischemia has been previously reported with aps , indocyanine green angiography was performed , which did not show any significant modification of choroidal perfusion .
prothrombotic conditions secondary to other factors such as sepsis , homocystinemia , and genetic defects of coagulation factors ( thrombin mutations , factor v leiden , antithrombin deficiency , etc . ) were ruled out .
laboratory investigations showed that the erythrocyte sedimentation rate , igg anticardiolipin , and -2 glycoprotein - i antibody were above normal limits .
thromboplastin inhibition test was strongly positive for lupus anticoagulant , while antinuclear antibody and antinative dna antibodies were negative .
serum total complement ( c3 , c4 ) , proteins s and c , and antithrombin iii were within normal limits .
other studies were normal or negative , including complete blood count , platelet count , renal , liver , and thyroid functions , hemoglobin a1c , ferritin , transferrin , and ldl cholesterol .
the patient met the criteria for aps ; however , according to the american college of rheumatology classification criteria , a concomitant diagnosis of systemic lupus erythematosus could not be established .
she started treatment with hydroxychloroquine 200 mg / daily and ticlopidine 250 mg / daily . considering the central location of the hemorrhage , we deferred any invasive treatment and opted for watchful waiting .
the subhyaloid hemorrhage resolved spontaneously and the patient recovered a visual acuity of 20/20 in her right eye 3 months after the initial episode ( fig .
this is the first reported case of simultaneous subhyaloid hemorrhage and branch retinal vein subocclusion as presentations of aps .
a prompt diagnosis of this condition is fundamental to consider a systemic treatment to avoid any further thrombosis .
this is often difficult , as ocular manifestations of aps can be variable . assessing the patient 's thrombotic risk by investigating the presence of high blood pressure and hypercholesterolemia ,
the use of tobacco and oral anticontraceptive agents as well as the history of previous of thrombosis , fetal loss , and acute ischemic events is mandatory in the process of deciding whether to start systemic treatment .

Answer:
we report an atypical presentation of antiphospholipid syndrome ( aps ) with concomitant subhyaloid hemorrhage , engorged and tortuous retinal veins , intraretinal hemorrhages , and cotton wool spots in a 38-year - old female .
 medical treatment was preferred to any invasive treatment .
 the subhyaloid hemorrhage resolved spontaneously and the patient recovered a visual acuity of 20/20 in her right eye 3 months after the initial episode .
 a prompt diagnosis of this condition is fundamental to consider a systemic treatment to avoid any further thrombosis .


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:
cancer is one of the leading causes of death worldwide and accounted for 7.6 million cases ( 13% of all deaths ) in 2008 ; in 2013 in the united states there are 12,340 estimated new cases and 4,030 deaths by cervical cancer [ american cancer society : cancer facts and figures 2013 ] .
meanwhile in romania , based on statistical data from 2012 , cervical cancer is ranked third place taking in account the women cancer incidence , after the breast and colorectal cancer .
cervical cancer develops in a multi - stage process , successively passing from a cervix with a normal epithelium to cervical intraepithelial neoplasia and finally leading to invasive cervical cancer . a relevant epidemiologic risk circumstance for the progress of the cervical cancer is represented by the presence of high risk human papillomavirus infections .
consequently , considerable importance has been given to the molecular premise which leads to the progression of cervical cancer .
rnai ( rna interference ) is a natural mechanism able to specific inhibit a target gene .
the prospective exploitation as a therapeutic has lately been strengthened by the small interfering rna ( sirna ) delivery to human tumours .
rnai has been demonstrated as a relevant investigation device for particular target genes by using exogenous sirnas .
sirnas are single - stranded non - coding rnas with 2023 nucleotides length , being able to negatively modulate gene expression profile at post - transcriptional level .
sirnas represent an encouraging novel type of medicaments for cancer therapy , as a result of targeting the mutated tumour suppressor genes or activated oncogenes .
many recent investigations have shown that sirna can efficiently inhibit oncogene expression in cancer cells .
various investigations demonstrated clearly that the deactivation of p53 constitutes a crucial step in carcinogenesis .
the present study was designed to investigate the potential use of p53 rnai to block p53 expression , as well as the subsequent effect on cell invasion and gene expression on the human cervical cancer cell .
hela is a human cervical carcinoma cell line ; this was incubated in a 5% co2 incubator at 37c . for maintenance
, cells were cultured in dmem medium , 10% fcs ( foetal bovine serum ) , 100 u / ml penicillin and 100 mg / ml streptomycin , 2 mm l - glutamine , 1% nonessential amino acids , all purchased from sigma - aldrich , bucharest , romania . for this investigations 510 hela cells
/ well were used for reverse - transfection , based on a preliminary optimised protocol for p53sirna , using siport neofx as transfection agent ( ambion , usa ) .
a validated p53sirna pool ( sc-29435 , santa cruz ) was used at a concentration of 50 nm in serum starvation condition using optimem medium ( gibco , invitrogen , romania ) , in accordance with the producer recommendations .
siport neofx 0.25% concentration was able to achieve the maximum inhibition of target gene with no effects on cell viability .
we performed the invasion assays on hela cells to evaluate the impact of p53sirna treatment using the cim - plate 16 with the xcelligence rtca dp instrument ( roche applied science ) according to the described protocol by .
the total rna for the cells treated with 50 nm p53sirna andthe control group respectively at 24 hours post treatment was extracted using trireagent ( sigma - aldrich , bucharest romania ) based on the producer recommended protocol for each triplicate specimen .
all of the samples had a rin ( rna integrity number ) higher than 7.5 .
the 8 genes selected were assessed using specific primer and upl based on in silico design . the total rna ( 500 ng ) from all the samples was reverse transcribed using the first strand cdna synthesis kit for rt - pcr ( roche , bucharest romania ) . for the gene amplification we used taqman universal pcr master mix , in a 20 l volume in a 96-well plate using the roche lightcycler 480 system .
the qrt - pcr reaction amplification program was as follows : 10 minutes at 95c for enzyme activation followed by 45 cycles of 15 seconds at 95c and 1 minute at 60c for the amplification step .
the data analysis was carried out to compare the gene expression values for the treated and untreated groups using ct method . as housekeeping gene
the evaluation of the vegf protein expression at 48 hours post treatment was done using human vegf quantikine elisa kit ( r&d , catalog no .
hela is a human cervical carcinoma cell line ; this was incubated in a 5% co2 incubator at 37c . for maintenance
, cells were cultured in dmem medium , 10% fcs ( foetal bovine serum ) , 100 u / ml penicillin and 100 mg / ml streptomycin , 2 mm l - glutamine , 1% nonessential amino acids , all purchased from sigma - aldrich , bucharest , romania . for this investigations 510 hela cells
/ well were used for reverse - transfection , based on a preliminary optimised protocol for p53sirna , using siport neofx as transfection agent ( ambion , usa ) .
a validated p53sirna pool ( sc-29435 , santa cruz ) was used at a concentration of 50 nm in serum starvation condition using optimem medium ( gibco , invitrogen , romania ) , in accordance with the producer recommendations .
siport neofx 0.25% concentration was able to achieve the maximum inhibition of target gene with no effects on cell viability .
we performed the invasion assays on hela cells to evaluate the impact of p53sirna treatment using the cim - plate 16 with the xcelligence rtca dp instrument ( roche applied science ) according to the described protocol by .
the total rna for the cells treated with 50 nm p53sirna andthe control group respectively at 24 hours post treatment was extracted using trireagent ( sigma - aldrich , bucharest romania ) based on the producer recommended protocol for each triplicate specimen . the rna concentrations and quality were assessed by the nanodrop-1100 agilent 2100 bioanalyzer spectrophotometer .
all of the samples had a rin ( rna integrity number ) higher than 7.5 .
the 8 genes selected were assessed using specific primer and upl based on in silico design .
the total rna ( 500 ng ) from all the samples was reverse transcribed using the first strand cdna synthesis kit for rt - pcr ( roche , bucharest romania ) .
for the gene amplification we used taqman universal pcr master mix , in a 20 l volume in a 96-well plate using the roche lightcycler 480 system .
the qrt - pcr reaction amplification program was as follows : 10 minutes at 95c for enzyme activation followed by 45 cycles of 15 seconds at 95c and 1 minute at 60c for the amplification step .
the data analysis was carried out to compare the gene expression values for the treated and untreated groups using ct method . as housekeeping gene
the evaluation of the vegf protein expression at 48 hours post treatment was done using human vegf quantikine elisa kit ( r&d , catalog no .
xcelligence system is an innovative device that allows the scanning of cellular response via an impedance - based technology in real time , lacking any exogenous labels .
the cim - plate 16 furnishes a kinetic cell - response profile to p53sirna throughout an investigation , specifying the commencement and ratio of invasion and migration of hela cells .
this data can facilitate to comprehend the response to treatment in dynamic . in figure 1
we can observe a delay and a reduction of the cell migration after the p53sirna treatment .
taqman qrt - pcr assay was used to examine the effect of p53sirna on a panel of 8 genes related to apoptosis and angiogenesis .
relative gene expression quantification using ct method leads to the downregulation of the selected gene , presented in the figure 2 .
after 48h post transfection with p53 sirna inhibition in hela cell line , vegf protein was found dowregulated in the culture medium than in the control group ( figure 3 ) .
xcelligence system is an innovative device that allows the scanning of cellular response via an impedance - based technology in real time , lacking any exogenous labels .
the cim - plate 16 furnishes a kinetic cell - response profile to p53sirna throughout an investigation , specifying the commencement and ratio of invasion and migration of hela cells .
this data can facilitate to comprehend the response to treatment in dynamic . in figure 1
we can observe a delay and a reduction of the cell migration after the p53sirna treatment .
taqman qrt - pcr assay was used to examine the effect of p53sirna on a panel of 8 genes related to apoptosis and angiogenesis . relative gene expression quantification using ct method leads to the downregulation of the selected gene , presented in the figure 2 .
after 48h post transfection with p53 sirna inhibition in hela cell line , vegf protein was found dowregulated in the culture medium than in the control group ( figure 3 ) .
although at this moment cervical cancer is considered as a preventable disorder there is a significant risk of disease recurrence causing a persuasive necessity to research new therapeutic targets for this disease management .
it is now well recognized that the tumour progression of all cancers is characterized by intensified proliferation and invasion rate and diminished in apoptosis . at the same time
the apoptosis and angiogenesis are interconnected as can be observed from figure 4 , using string.9 database .
the idea of this study is in agreement with the previous studies which are based on the hypothesis that once mutated , p53 exercised oncogenic role . by using sirna
the role of the present study is to emphasize the cooperation between oncogenic mechanisms , confirming the crosstalk between apoptotic and angiogenic mechanisms .
this has a significant therapeutic relevance based on the fact that mutated p53 is related to cancer aggressiveness   or to promoting metastasis . in a similar study
was observed that , by using sirna targeting p53/p73 , tumoral cells were sensitized to chemotherapy . in a recent study , pinx1 was displayed as a novel target gene of p53 , proposing the suppression of p53/pinx1 pathway as a novel mechanism to enhance the telomerase activity in cervical cancer cells , and leading to reduction of cell proliferation .
targeting oncogenic signals such as the mutated p53 gene that gains oncogenic role , we observed a downregulation of specific genes involved in apoptosis but also in angiogenesis , connected with a reduction of the invasion rate in the case of p53sirna therapy .
after 24 hours of treatment with p53sirna we can observe downregulations of important genes involved in apoptosis and angiogenesis , as displayed in figure 2 .
this study confirmed our hypothesis that p53 plays a central role in carcinogenesis as displayed in figure 3 , as important therapeutic target .
p53 could promote the convergence of the apoptotic and angiogenic pathways in cervical cancer cells .
it has been proved that p53 is able to indirectly downregulate vegf gene expression , via the retinoblastoma ( rb ) , in a p21-dependent mode , confirming its function in cell - cycle regulation as displayed by recent studies .
the complete comprehension of the cross - talk between p53 and angiogenic pathways represents a challenge in cancer therapy [ 2426 ] .
another study reveals that mutant p53 correlates with overexpression of vegf . in a similar study
the inhibition of mutant p53 represents a significant therapeutic target , a fact emphasized by walerych as  rebel angel .
p53 gene knockdown in hela cells plays an important role not only in apoptosis but also in angiogenesis through various mechanisms that regulate tumour cell development and migration .
the angiogenic phenotype related to p53 targeted by sirna in human cancers is frequently associated with resistance to conventional genotoxic anticancer agents .
therefore , p53 inhibitions become dependent and rely on angiogenesis for growth and metastasis . the results in the current research
may also have an important significance outside the context of cervical cancer , by using specific inhibitors for p53 for increasing therapeutic response in a wide range of tumoral pathology .

Answer:
background and aimssirnas represent an encouraging novel alternative in cancer therapy as a result of targeting the mutated tumour suppressor genes or activated oncogenes .
 targeting oncogenic signals , as the mutated p53 gene that gains oncogenic role , we observed inhibition of migration , a downregulation of specific genes involved in apoptosis but also in angiogenesis , connected with a reduction in invasion rate in the case of p53sirna therapy.methodsthe study was designed to assess the role of p53 by using rnai ( rna interference ) in hela in vitro cell culture model . therefore cell migration rate was assessed by using xcelligence systems , gene expression for a panel of genes involved in apoptosis and angiogenesis , and validation of gene expression data at protein level.resultson the selected in vitro model p53 sirna therapy was correlated with the reduction of cell migration .
 the downregulation of p53 , pten , tnf , nfkb , bcl-2 , icam-2 , vegf , and fgfb was evidenced as response to p53 inhibition.conclusionrnai may be a valuable technology in order to restore the normal cellular phenotype .
 the results in the current research may also have an important significance outside the context of cervical cancer , by using specific inhibitors for p53 for increasing the therapeutic response in a wide range of tumoral pathology .