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 family is the cornerstone of human social support network and its presence is essential in everyone s life . changes inevitably occur in families with illness and hospitalization of a family member . in other words , among the sources of stress for families are accidents leading to hospitalization particularly intensive care unit ( icu ) .
statistics show that 8% of hospital beds in the united states are occupied by the intensive care units .
stress in the family while the patient is in the icu can disrupt the harmony power of the family members and finally , it may causes disturbances in the support of the patient .
in addition to the various sources of stress in intensive care units such as the patient s fear of death , financial problems , lack of awareness about the environment and etc . , their satisfaction level is another important source of stress for the patient s family .
today , the family needs of hospitalized patients in the icu are summarized in five sections .
these factors may include receiving assurance , staying close to the patient , receiving information , feeling comfortable and receiving support .
however , in many cases , the patient s family needs and their expectations in the icu will not be fulfilled which will cause dissatisfaction . since , how families deal with mental stress is the most important components of comprehensive care , it should be known that attention to the family needs of the patients hospitalized in intensive care units could increase their satisfaction and thus a reduction in stress disorders .
studies showed that the nurses in particular sections focus primarily on the patient and the disease .
therefore , attention to the families should be considered as an important part in patient management .
effective interventions targeted at the needs and expectations of family members should help to reduce the stress and improve their satisfaction .
fox et al . stated that the needs of the family members were not often overlooked by the nurses .
however , the nurses spend a lot of time with the patients and their families and are in a good position to assess their needs and plan for meeting these needs with appropriate interventions .
the reason of investigating the satisfaction of the families of the patients in the icu is that the patients are facing life - threatening illness experiences and complex treatments , different technologies and different equipment are used for them .
these cases could potentially lead to the dissatisfaction of their families . in the meantime ,
the families of trauma and neurosurgical patients are more vulnerable than the other groups of patients .
they need supports that are more emotional and should be accepted by the icu staff . today , there are many theories expressed that in intensive care units , the patient and his family should be considered as a single unit . by providing care to this unit ,
the aim of this study was to analyze the satisfaction of the families of icu patients .
the tool of society of critical care medicine s family needs assessment ( sccmfna ) ( which has been validated in 1998 by johnson ) was used in that study .
the results showed that most of the family satisfaction was related to the communication and patient care and the lowest level of satisfaction was about the ability of staff to patients family comfort .
bailey et al . have conducted a study in 2009 with the purpose of investigating the relationship between informational support to families of special care patients and their anxiety and satisfaction .
they showed that there is a direct link between the informational support and their satisfaction .
the study of fumis et al . in 2008 also showed that the increase in the availability of physicians for giving the information to the patient s family and as well as nurses efforts to provide understandable explanations about the patient s condition to them will increase the patient s family satisfaction .
this clinical trial was performed with respect to the existing gap for a study carried out for investigating the interventions for the satisfaction of the patients in the special care units and their families in iran .
the purpose of the study was to determine the effectiveness of nursing interventions based on family needs on family satisfaction level of hospitalized patients in the neurosurgery intensive care unit of al - zahra hospital in 2010 .
the statistical research community was the families of hospitalized patients in neurosurgery intensive care unit of al - zahra ( sa ) hospital , isfahan , iran from may to september 2010 .
with respect to inclusion criteria , the families of 64 patients were selected with simple sampling . after obtaining the informed consents from the hospitalized patients , by using the envelopes , which were prepaid by using a table of random numbers , they were divided into two groups ( intervention and control ) .
the inclusion criteria was included as the following cases : to be a first - degree member of the family , to be older than 18 years , willing to participate in the study , having the power to speak and write in farsi , to be hospitalized one day before the study , lack of physical or mental problem in the family member , no responsibility for the care of another patient , introduced as the first person responsible for the patient care .
obtaining the written informed consent , completion of the questionnaires about demographic information and the families satisfaction were performed in the second day of hospitalization of the patients in icu in both groups .
johnson questionnaire for the satisfaction of the family of icu patients was used to measure the family satisfaction .
the rating of the questionnaire was performed by using the likert scale with four options of 0 to 4 as follows : almost all the time ( 3 scores ) , often ( 2 scores ) , only occasionally ( 1 score ) and never ( zero score ) .
johnson s questionnaire was the modified type of multer patient s family needs , which was evaluated in various scientific researches and there are extensive evidences for its validity .
the interventions were performed in the second and the third day of hospitalization of the patient in the neurosurgery icu by the researcher in the morning shift for the intervention group .
thus , the researcher provided understandable explanations about the disease to the patient s family and answered honestly to the questions about the patient and the disease .
the researcher ensured them for providing the best care in the section and spoke about the prognosis of the disease .
the researcher took the family member to the patient s room and gave the necessary information about the room space , equipment , personnel departments and the actions that were done for the patient .
the patient family member was contacted if there was a change in the patient condition .
they let the family help the patient in some cases of the public health ( such as hand and foot massage and giving food ) .
locations of rest , nutrition , prayer room , bathroom and buffet of the hospital were introduced to them .
the telephone numbers of hospitals and wards ( and if necessary , the social worker and supervisor ) were given .
various departments and personnel of the hospital were taught to accept the families and communicate with them . the hospital social worker was introduced and if necessary , the patient s family was allowed to express their feelings .
these interventions were performed in the evening shift of the second and the third day of the patient reception .
the actions were carried out by the fellow researcher . while , for the control group , only the routine work was done . on the fourth day , the satisfaction survey was completed by the selected family member in both of the intervention and control groups .
statistical methods used in this study were 2 test , man - whitney , independent student s t - test and paired t - tests .
the findings did not show statistically significant difference in the demographic characteristics of the intervention and control groups , such as : age ( p < 0.99 ) , gender ( p < 0.79 ) , marital status ( p < 0.41 ) , educational level ( p < 0.12 ) and relation with patient ( p < 0.54 ) . as shown in table 1
, there was no significant difference in the mean satisfaction score before the intervention in the intervention and control groups ( p > 0.05 ) .
the mean satisfaction score after the intervention in the intervention group was significantly more than the control group ( p < 0.001 ) .
the mean satisfaction score in the intervention group after the intervention was significantly higher than before the intervention ( p < 0.001 ) .
there was no significant difference in the mean satisfaction score in the control group before and after the intervention ( p > 0.05 ) ( table 2 ) .
comparison of mean satisfaction score ( 100 * ) of participants in the intervention and control groups the mean of satisfaction score changes of the studied subjects in the intervention and control groups after intervention
the results of the present study showed that the nursing interventions based on the family needs increased the patient s family satisfaction in the neurosurgery intensive care unit of al - zahra hospital .
due to the differences in the study design , study population , the number of samples and methods of intervention , it would be difficult to compare the results . in chien et al .
study , the results showed that performing the training based on the patients family needs in the icu , decreased the anxiety and increased their satisfaction . in the study of myhren et al . indicated that effective communication of the staff with the families of icu patients would increase their satisfaction .
in the study by rosher and robinson , it showed that involving the families in patient care led to increase their satisfaction than before the intervention .
the mentioned results were consistent with the results of this study , because all of these interventions were some parts of the interventions performed in this study .
however , the study of steele et al . indicated that clinical training had no impact on the family satisfaction of the patient hospitalized in the icu
. therefore , there was no statistically significant difference in the satisfaction level in the control and intervention group .
in this study , it was shown that the use of nursing interventions based on family needs ( confidence , support , information , proximity and convenience ) had significant impact on the family satisfaction of the patient hospitalized in intensive care unit .
they should be based on the family investigation and recognition and their priority needs should be determined in order to cause the greatest satisfaction .
the icu nurses must also accept their role in the care of patient s family members .
the findings of this study could be a basis for performing further studies about family needs of the patients in the icu especially with the different forms of culture and economy .
consequently , the increase in family satisfaction of patients can reduce the stress disorders and improve their mental state and ultimately better support of the patient by the family .
this study only examined the effect of nursing interventions in the first days of hospitalization on the satisfaction of the families but the effects on the patient s entire hospitalization period has not been assessed . by performing other researches in this field
, it would be possible to compare the differences in the effects of nursing interventions based on the needs of families in the early days and the whole period of the patient s hospitalization .

Answer:
background : since the family is a social system , the impairment in each of its component members may disrupt the entire family system .
 one of the stress sources for families is accidents leading to hospitalization particularly in the intensive care unit ( icu ) . in many cases ,
 the families needs in patient care are not met that cause dissatisfaction . since the nurses spend a lot of time with patients and their families , they are in a good position to assess their needs and perform appropriate interventions .
 therefore , this study was conducted to determine the effectiveness of nursing interventions based on family needs on family satisfaction level of hospitalized patients in the neurosurgery icu.materials and methods : this clinical trial was conducted in the neurosurgery icu of al - zahra hospital , isfahan , iran in 2010 .
 sixty four families were selected by simple sampling method and were randomly placed in two groups ( test and control ) using envelopes . in the test group ,
 some interventions were performed to meet their needs . in the control group ,
 the routine actions were only carried out .
 the satisfaction questionnaire was completed by both groups two days after admission and again on the fourth day.findings:both of the intervention and control groups were compared in terms of the mean satisfaction scores before and after intervention .
 there was no significant difference in mean satisfaction scores between test and control groups before the intervention .
 the mean satisfaction score significantly increased after the intervention compared to the control group.conclusions:nursing interventions based on family needs of hospitalized patients in the icu increase their satisfaction .
 attention to family nursing should be planned especially in the icus .


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 12-year - old female patient visited the department of oral medicine and radiology , yenepoya dental college , with a complaint of missing anterior teeth since three years ago .
she had a history of exfoliation of decidious teeth due to mobility three years ago and there was no eruption of the permanent teeth .
there was a history of presence of two mandibular natal teeth which were exfoliated two weeks after birth .
her parents had no consanguineous marriage , however her elder sibling died of similar medical problem .
her medical history revealed that she had visited genetic clinic and they have diagnosed her with ellis - van creveld syndrome .
she also had dyspnoea because of congenital lobar emphysema for which she had undergone left upper lobectomy when she was one and half year old .
intraoral examination showed v - shaped notching of the upper lip at the mid line ( fig .
2a ) , absence of mucobuccal fold in maxillary and mandibular anterior region ( figs .
2b and c ) , conical shaped teeth , missing mandibular permanent anterior and retained deciduous mandibular canines , and right lateral incisor teeth ( fig . 2c ) .
chest radiograph showed homogenous opacity in the left upper zone associated with elevation of hilum and left dome of diaphragm suggestive of left upper lobectomy ( fig .
antero - posterior view of the legs showed genu valgum , hypoplasia of lateral end of tibia associated with medial tibial diaphysial outgrowth called exostosis , and mild shortening of fibula ( fig .
hand - wrist radiograph showed carpal fusion , postaxial polydactyly , and shortening of metacarpal and phalangeal bone with cone shaped epiphysis .
there was fusion of capitate and hamate on the right hand and hamate and triquadral on the left hand ( fig .
a team work of pedodontist , oral and maxillofacial surgeon , and prosthodontist was required to correct the craniofacial and dental defects in this patient .
since the patient was in growing phase , the prosthodontist decided to give acrylic partial dentures for the missing teeth .
oral and maxillofacial surgeon performed frenectomy for the high labial frenum as it was hindering the placement of the partial denture .
ellis - van creveld syndrome ( evc ) otherwise known as chondroectodermal dysplasia has autosomal recessive inheritance .
it is a syndrome found in amish population of pennsylvania in usa , affecting male and female equally.2 familial history may include parental consanguinity or affected siblings or family members .
our patient was the second child of non - consanguineous and normally developed parents , however her elder sibling had died of similar medical problem .
these patients die due to either cardiac problem or respiratory distress.2 our case did not have any cardiac problem , however there was congenital lobar emphysema because of her dyspnoea .
she had undergone left upper lobectomy for the same reason when she was one and half year old child .
the syndrome affects mainly the bones such as the lower limb with genu valgum , which requires surgical correction .
the upper limbs show the characteristic bilateral postaxial polydactyly.3,4 our case had all these limb anomalies .
other ectodermal features in this syndrome are the absence or hypoplastic features of finger and toe nails , natal teeth , conical shaped or missing teeth , and absence of labial vestibule because of fusion of upper lip to the gingival margin , leading to the notching of upper lip
. this could be due to the continuation of the normal serrated condition of the gingiva from the third to seventh month in the uterine life of the fetus .
it is considered as the characteristic and diagnostic feature of this syndrome.5 - 7 all of these features were also present in this case .
there are about 40 independent evc / evc2 mutations.8 ruiz - perez and goodship mentioned that the abnormalities in evc syndrome resulted from the tissue specific disruption of the response to hh ligands.9 weyer 's syndrome , asphyxiating thoracic dystrophy , and orofacial digital syndrome should be considered in the differential diagnosis of this syndrome .
evc syndrome and weyer 's acrodental dysastosis are allelic conditions caused by loss of function mutation in evc and evc2 .
these are separated by 2 - 6 kb of genomeric sequence on chromosome 4p16.10 all the features are similar in both conditions except for the fact that there is delay in fusion of mandibular symphysis in acrodental dysastosis.6 patients with evc syndrome and asphyxiating thoracic dystrophy will have identical features in hand , pelvis , and long bones .
presence of cardiac anomalies , nail hypoplasia , fusion of upper lip to gingiva and neonatal teeth in evc syndrome , and renal failure with hypertension in asphyxiating thoracic dystrophy will help in distinguishing these two disorders from each other.6,11 presence of multiple gingivolabial frenula is similar to evc in orofacial digital syndrome .
hypoplastic nasal cartilage , moderate mental retardation , fissured tongue , and ankyloglossia helps to differentiate this from evc syndrome.11 in conclusion , the effective management of this syndrome will require a team which includes pedodontist , oral and maxillofacial surgeon , prosthodontist , clinical geneticist , cardiologist , pulmonologist , orthopaedician , urologist , psychologist , pediatrician , and pediatric neurologist . since the oral manifestation is one of the characteristic diagnostic features , and it affects the esthetic problem , speech , jaw growth of the child , the dentists have an important role to play in proper management of such cases .

Answer:
ellis - van creveld syndrome is a rare congenital genetic disorder having autosomal recessive inheritance .
 it is a syndrome affecting the amish population of pennsylvania in usa with prevalence rate of 1/5,000 live at birth . in non - amish population ,
 the birth prevalence is 7/1,000,000 .
 the syndrome is characterized by bilateral postaxial polydactyly of the hands , chondrodysplasia of long bones resulting in acromesomelic dwarfism , ectodermal dysplasia affecting nails as well as teeth and congenital heart malformation .
 there were very rare reports of this syndrome in dentistry .
 the present case focuses on the striking and constant oral findings of these patients , which are the main diagnostic features of this syndrome .
 since the oral manifestations affect the esthetic , speech , and jaw growth of the child , the dentists have an important role to play in proper management of such case .


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:
after initial establishment and derivation of human embryonic stem cells ( hesc ; thomson et al . , 1998 ; reubinoff et al . , 2000 )
first the infection free status of the donors has to be addressed , in europe couples are tested before any fertility treatment is offered , but the cells themselves have to be tested , too ( hovatta , 2011 ) .
second , optimized good manufacturing practice ( gmp ) compliant systems must be implemented for derivation , scaling - up , banking of cells , and their corresponding quality assurance controls ( unger et al . , 2008 ; ausubel et al . , 2011 ) .
the culture systems currently encounter the problem of suboptimal quality of xeno - free culture constituents . thus strategies are needed to overcome this difficulty ( sidhu et al . , 2008 ) .
steps have been taken ; initially , hesc were grown on irradiated mouse feeders , later human fore - skin fibroblast were used ( hovatta et al . , 2003 ) , now we can use gmp compliant coating substrates specially designed for hesc growth ( rodin et al . ,
steps were also taken for the generation defined xeno - free gmp compliant medium for derivation and for expansion ( ludwig et al . , 2006 ;
the potential of somatic cell reprogramming via expression of specific transcription factors and thus the generation of hesc induced pluripotent stem cells ( hipsc ; takahashi and yamanaka , 2006 ; takahashi et al . , 2007 ) has the advantage that they could be generated from the recipient patients own cells .
there is no deep understanding of the effects that the reprogramming events have ; for instance on extracellular signaling ( okita et al . , 2011 ) , and the way that this could lead to immune reaction .
hence fast reactivity is already present in healthy individuals for controlling any rapidly amplifying cells ( dhodapkar et al . , 2010 ) .
un - silenced expression of the reprogramming factor oct-4 might then cause undesired immunoreactivity on the transplanted cells .
immunoreactivity toward graft - derived hipsc of the same genetic background was also shown in animal models ( zhao et al . , 2011 ) .
for successful reprogramming of somatic cells , many epigenetic changes must occur in an adequate manner .
dna methylation changes during reprogramming must occur in important developmental and oncogenic regions , which increases the oncogenic risk of the reprogrammed cells ( doi et al .
there is an additional risk for abnormalities and high tumorigenic potential , especially if c - myc is used as one of the transcription factors ( okita et al . , 2007 ) .
also , genetic and epigenetic stability and large - scale genomic rearrangements after reprogramming and subsequent culture ( kim et al .
, 2010 ; gore et al . , 2011 ; hussein et al . , 2011 ; lister et al . , 2011 )
it is also important to address the safety of long - term culture , as shown recently ; the occurrence of chromosomal rearrangements in long - term culture of 125 hesc and 11 hipsc ( amps et al . , 2011 ) .
there is a consensus that undifferentiated pluripotent stem cells ( psc ) will not be used directly in any clinical transplantations procedure , but instead their psc derived differentiated cells recently , results using hesc derived dopaminergic neurons have shown correct phenotype differentiation and grafting potential given by no tumor formation , maintenance of the grafted cells , and functional recovery in parkinsonian animal models in mice , rats , and monkeys ( kriks et al . , 2011 ) .
the protocols designed for this cell replacement assay were optimal regarding the phenotype , quantity of the cells , functionality , and immunological properties .
integration of transplanted cells was achieved when single cells were transplanted , the use of proper biodegradable scaffolds must also be considered .
in addition to this initial report regarding the neural lineage , differentiation protocols for other cell types are needed . even if transplantation in animal models is successful , it is important to generate safety strategies before clinical trials to appropriately remove undifferentiated psc from their psc derived therapeutic cells .
strategies such as inserting suicide gene ( drobyski et al . , 2003 ; uchibori et al . , 2009
) might have controversial outcomes under clinical trials given their safety ( yi et al .
alternatively , strategies such as removal of undifferentiated cells using antibodies might be safer ( tang et al . , 2011 ) .
as discussed earlier , an optimal engraftment and cell replacement strategy should account for a minimal immune reaction in the recipient .
this immune reaction occurs because the immune system of the recipient recognizes the grafted cells as foreign material or mismatched cellular components and thus generates a cascade of events that ultimately results in destruction and rejection of the grafted cells .
this destruction can also compromise the recipient s immune status ( petersen et al . , 1975 ) .
immunoreactivity toward the graft is mainly caused by t cell response toward unmatched major histocompatibility complex ( mhc ) ; in humans called human leukocyte antigen ( hla ) .
if the profile is unmatched , it will result in rejection ( lechler et al . , 2005 ) .
this rejection can occur via direct allorecognition of the donor antigen presenting cells ( apc ) or via indirect recognition of apoptotic cells ingested by the recipients apc , in both cases apcs presenting unmatched mhcs ( walsh et al . , 2004 ) .
several groups have studied mhc profiles of hesc and their differentiated cells ( swijnenburg et al . , 2008 ; pearl et al . , 2011 ) .
findings are that undifferentiated cells express mhc i antigens , though at low levels compared with somatic cells ; but they do not express mhc ii molecules ( drukker et al . , 2002 , 2006 ; li et al . , 2004 ) .
during in vitro differentiation toward germ lineages , embryoid body ( eb ) formation , or teratoma formation mhc i expression increases dramatically ( drukker and benvenisty , 2004 )
. also culture methods of hesc can change antigen expression levels ( rajala et al . , 2010 ) .
careful selection of culture conditions , both for the undifferentiated hesc and for their differentiated derivatives is needed .
human embryonic stem cells adopts the expression of non - human cell surface markers if exposed to such substances during culture ( martin et al . , 2005 ; hisamatsu - sakamoto et al . , 2008 )
hence , optimal culture conditions must be xeno - free from the initial derivation and onward .
these culture conditions must be carefully analyzed and scientific consensus must be achieved in order to raise current methodologies .
challenges with the immunoreactivity of the transplantable cells could be addressed by rigorous immunosuppressive treatments . unfortunately , this is not desired , since there is a clear correlation between the length and intensity of exposure to immunosuppressive therapy and post - transplant risk of malignancy and tumor aggressiveness ( gutierrez - dalmau and campistol , 2007 ) .
an interesting solution is costimulatory blockage of t cell response ( grinnemo et al . , 2006 , 2008 ; swijnenburg et al . , 2008 ; pearl et al . , 2011
. this immunosuppression strategy will generate tolerance to the grafted cells and thus increase graft survival ; initial pharmaceutical agents have been developed and pending clinical applications to the fda are to give in the near future more information .
in this mini - review we highlighted the most important areas to be considered under a cell replacement therapy .
the possibility of using hipsc derived therapeutic cells in cell replacement therapies requires still long - term studies in non - human animal models addressing the questions of immunogenicity , epigenetic and genetic stability of these cells , and the optimized differentiation of the cells .
the importance of profiling immunogenic markers as part of the stem - ness characterization and profiling of cells allocated in stem cell banks must be consider .
such information has to be well protected so that it will not be lost in any given situation .
adequate culture conditions , supporting correct immunogenicity of the cells under a transplantation assay is also required .
next , the management of immunosuppression schemes must aim to a minimal time influencing the immunological status of the recipient . from all the information obtained ,
these profiles can then be used in combination with methodologies focused at monitoring the status of the transplanted cells . in a given scenario that undesired cells persist in the transplant , adequate counteracting actions have immediately to be taken .
such possibilities have to be tested and the removal of undesired effects confirmed before starting cell transplantations .
the authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest .

Answer:
human embryonic stem cells ( hesc ) and induced pluripotent stem cells ( hipsc ) are an attractive cell source for regenerative medicine .
 these cells can be expanded to vast numbers and can be differentiated to many desired pluripotent stem cells ( psc ) derived therapeutic cells .
 cell replacement bears promises , but also challenges
 . the introduction of exogenous cells in a recipient must address several different topics ; its safety , the exclusion of tumor formation , the immunological response and possible rejection , the cells cleanliness and their biological quality , and quantity representing the functionality of the psc derived therapeutic cells .
 tumor formation requires the removal of any psc remaining after differentiation .
 immunological rejection can be addressed with immunomodulation of the cells and the recipient .
 cleanliness can be optimized using good manufacturing practice quality systems . at last
 , the functionality of the cells must be tested in in vitro and in animal models . after addressing these challenges ,
 precise strategies are developed to monitor the status of the cells at different times and in case of undesired results , corresponding counteracting strategies must exist before any clinical attempt .


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:
thirty patients with zygomatic complex fractures were treated with one point fixation [ figures 13 ] .
preoperative peripheral nerve stimulation x - ray preoperative computed tomography scan under general anesthesia , nasoendotracheal intubation was done .
the incision can be made from anterior to posterior or from medial to lateral and should extend through mucosa , submucosa , and any buccinators muscle fibers [ figure 4 ] .
rowe 's zygomatic elevator was then inserted behind the infra temporal surface of the zygoma , and bone was reduced into its correct anatomical position using superior , lateral and anterior force . an audible click and fullness of the cheek together with palpation for normal contour of the zygomatic bone and orbital rim gave an idea about the adequacy of the reduction .
one hand over the side of the face was used to assist in the reduction .
a four hole plate with a gap was fixed with 4 mm  2.5 mm screws on the zygomatic buttress [ figure 5 ] .
immediate post operative immediate peripheral nerve stimulation x - ray six months postoperative and peripheral nerve stimulation x - ray
for all the patients , immediate postoperative and 6 months postoperative peripheral nerve stimulation x - rays were taken , and the x - rays review successful reduction .
none of the patients complained of any paresthesia , bony movements or pain in the frontozygomatic or zygomatic buttress region .
since intraoral approach was used , all the patients had an aesthetic facial profile without any unsightly scars .
the integrity of the zygoma bone is critical in maintaining normal facial width and prominence of the cheek .
the zygomatic bone is a major contributor to the orbit and plays an important role in protecting the eyes .
zygomatic bone alone is rarely involved in fractures ; usually its articulating surfaces which are maxilla , temporal , frontal and sphenoid bones are also involved .
the fractured fragments of a tripod or tetrapod zygomatic complex fracture near these suture lines needs to be restabilized by open reduction followed by fixation .
studies suggest that two point gives a considerable stabilization , and three point fixation gives the maximum stabilization .
however other studies suggest that one point fixation for zymatic complex fractures gives an excellent results considering the esthetics and stabilization for simple tripod fractures without any comminution of the zygomatic bone or the lateral orbital wall one point fixation with a single mini plate in the frontozygomatic area through the lateral eyebrow incision have been suggested by many authors .
i n these cases it was found that when a tripod fracture without any comminution or mild or no displacement can be stabilized very well with a single point fixation in the frontozygomatic area without any complications of diplopia or enopthalmos .
however , zygoma provides the attachment point for muscles of mastication and facial animation , but amongst these , it is the masseter that provides the most significant intrinsic deforming force on the zygomatic body and arch .
the integrity of zygomatic buttress is necessary for withstanding the contraction force of the masseter muscle . in 2002
fujioka et al .
 in vivo studies successfully proved that one point fixation at the zygomaticomaxillary complex gives three point alignment and sufficient rigidity when the fractures are not comminuted . in 2011
kim et al . found out that lateral eyebrow incision for mini plate fixation at the frontozygomatic area led to unaesthetic scar and few patients underwent plate removal through a second surgical re - entry through the existing scar of the lateral eyebrow incision which further enhanced the unsightly scars and compromised facial esthetics . since the skin over the lateral eyebrow region is thin there are more chances of palapation of the mini plates after fixation , and it may lead to pain . as early as in 1994 tarabichi et al .
proved that in vitro studies are misleading regarding the mini plate fixation along the orbital margins and successfully applied transsinus reduction through anterior comminuted sinus wall . in 2012 kim et al .
successfully reduced the zygomatic complex fractured fragments through intraoral approach and gained sufficient rigidity and excellent esthetics with one point fixation at the zygomatic buttress region .
we also found that one point fixation with a single mini plate at the zygomatic buttress through intraoral incision provided excellent stability and esthetics in the selected cases of simple zygomatic complex fractures without any comminution of the zygoma or the lateral orbital rim without or with minimal displacement and none of our patient complained of pain or palpation or bony movements in the postoperative study period of 6 months rather they were happy to get operated without any unaesthetic facial scars .

Answer:
for decades , facial beauty and esthetics have been one of the most important quests of the human race . the lateral prominence and convexity of the zygomatic bone
 makes it the most important bone for providing the aesthetic facial look and sets up the facial width but at the same time this prominence and convexity makes this bone more vulnerable to injury .
 zygomatic complex fractures or tripod fractures are the second most common fractures after nasal fractures among facial injuries .
 several studies have been undertaken regarding the reduction and fixation of zygomatic fractures with mini plates and screws . in 2002
 fujioka et al
 in vivo studies successfully proved that one point fixation at the zygomaticomaxillary complex gives three point alignment and sufficient rigidity when the fractures are not comminuted . in this article ,
 30 cases have been reviewed with one point fixation of zygomatic complex tripod fractures at the zygomatic buttress through keen 's intraoral approach along with advantages and disadvantages .


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:
 parent - of - origin effects is a broad term that encompasses two distinct phenomena
parent - of - origin effects on transcription , and parent - of - origin effects on mutation rates .
a parent - of - origin effect on transcription , or genomic imprinting , results from epigenetic modification of the genome which , in turn , results in unequal transcription of parental alleles . for these imprinted genes , expression of the alleles is dependent upon the sex of the parent from which they were inherited ( 1 ) . a parent - of - origin effect on mutation rate
, however , refers to the preferential occurrence of some spontaneous mutations in either the father 's or the mother 's germ line .
the mechanisms by which these spontaneous mutations arise depend upon the parental germ line in which the mutation occurred .
for example , base substitutions , arising from errors during replication , tend to be paternal in origin , owing to the greater number of cell divisions in spermatogenesis as compared with oogenesis ( 2 ) .
oocytes are arrested in prophase of meiosis i until sexual maturity , when one oocyte per month is selected to resume the cell cycle .
it is thought that the longer the oocytes are arrested in meiosis , the greater the chance for a nondisjunction event to occur ( 3 ) .
advanced parental age seems to influence the development of some , but not all , of these mutations ( also referred to as the paternal or maternal age effect ) ( 2 ) .
in 1998 , the catalogue of imprinted genes and parent - of - origin effects was first published ( 4 ) .
this catalogue served as the basis for the development of a more comprehensive , searchable , online database , made publicly available in 1999 .
the original database included 41 imprinted genes , and other parent - of - origin effects , including some records on the parental origin of spontaneous mutations ( 5 ) .
we have added recently a comprehensive section on spontaneous mutations that show a bias with respect to their parental origin .
this new part of the database can be searched according to mutation type , disorder , chromosomal location , gene name and inheritance pattern .
outcomes of the search are presented in a tabular format with the following information : disorder , inheritance pattern , incidence of disorder , gene name , chromosomal location , evidence of a paternal or maternal age effect , mutation type and any recurrent mutations associated with a parent - of - origin effect , number of paternal mutations , number of maternal mutations and pubmed reference ( e.g. table 1 ) . in the case of base substitutions , data are separated according to the type of base substitution ( missense mutation , nonsense mutation or splice site mutation ) , whether the mutation is a transition or transversion mutation , and whether the base substitution falls within a cpg dinucleotide . for deletions and insertions , the distinction is made between large deletions and insertions ( > 20 bp ) and small deletions and insertions ( < 20 bp ) .
this size distinction is made based upon the possibility of different mechanisms contributing to these different types of mutations , and therefore potentially different parental origins ( 2 ) . in general , large deletions do not appear to have a parent - of - origin effect , whereas small deletions tend to be more paternal in origin .
currently , > 1700 mutations with a parent - of - origin effect are catalogued in this database .
the other major section of the database includes known imprinted genes and observations of other putatively imprinted genes .
of the 464 database entries , 152 entries describe 85 unique imprinted genes in humans , mice , cattle , sheep , pigs , rats and marsupials , as well as 14 genes for which the evidence of imprinting is conflicting or provisional .
an additional 186 entries report parent - of - origin effects in the transmission or linkage of simple and complex genetic conditions including human diseases and animal quantitative traits .
the imprinted gene and parent - of - origin effect database is housed at the university of otago in dunedin , new zealand and can be accessed at .
the database is maintained by the corresponding authors who welcome submissions and comments and is updated as new literature is published .
submissions to the imprinted gene database should be directed to i.m.m . and submissions to the parental origin of de novo mutations database
example of report for parental origin of de novo mutations showing base substitutions within a cpg dinucleotide ad , autosomal dominant ; xd , x - linked dominant ; xr , x - linked recessive ; p , point mutation ; ms , missense mutation ; ns , nonsense mutation ; cpg , mutation in a cpg dinucleotide ; ts , transition mutation ; tv , transversion mutation .

Answer:
the imprinted gene and parent - of - origin effect database ( ) consists of two sections .
 one section catalogues the current literature on imprinted genes in humans and animals .
 the second , and new , section catalogues current reports of parental origin of de novo mutations in humans alone .
 the addition of a catalogue of de novo mutations that show a parent - of - origin effect expands the scope of the database and provides a useful tool for examining parental origin trends for different types of spontaneous mutations .
 this new section includes > 1700 mutations , found in 59 different disorders .
 the 85 imprinted genes are described in 152 entries from several mammalian species .
 in addition , > 300 other entries describe a range of reported parent - of - origin effects in animals .


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:
viruses are divided into two similar - sized groups depending on whether the virus particle contains dna or rna , and , as causes of human fatality , rna viruses are by far the more important ( 1 ) . new viral diseases continue to appear as a result of several changes in human activity : travel , population growth , interaction with wild habitats etc .
well - known novel , or emergent , rna diseases include severe acute respiratory syndrome ( sars ) ( 2 ) , human immunodeficiency virus 1 ( hiv-1 ) ( 3 ) , and may come to include avian influenza h5n1 virus ( 4 ) .
these emergent diseases are an important factor behind the increase in the number of genome sequences that ncbi treats as representing new species ( figure 1 ) . in 2005
, more than 200 new virus species were submitted to genbank ( more recent dates are less reliable because there is typically a delay between submission and public availability ) . as more emergent viruses appear , it is important to have a site that allows their genomes to be compared to those of known viruses . the origin of most major infectious diseases is unknown because of our ignorance of the diversity of pathogens in wild animals .
this restricts our ability to both predict risks and develop treatments ( 5 ) .

dates are the earliest given in the accession ( either of submission or publication ) .
submissions after 2006 are excluded because accessions are made public typically only following publication and thus the frequency of submissions is more recent time periods is underestimated .
dates are the earliest given in the accession ( either of submission or publication ) .
submissions after 2006 are excluded because accessions are made public typically only following publication and thus the frequency of submissions is more recent time periods is underestimated . despite some advances ( 6,7 ) ,
the evolutionary history of rna viruses is in general poorly known , especially the deep phylogenetic relationships between virus families ( 8,9 ) .
we believe that one of the reasons for this is a lack of easily available translated genes and genomes for all species , and the lack of aligned genome sequences representing different isolates of the same species .
in addition to the need to facilitate greater comparative analysis of rna viruses is the need to link together the existing virus web sites and their underlying databases .
there are many web sites that provide genomic data , tools for genetic analysis and/or biological information for some viruses ( see  links on our site home page ) .
the rna virus database is intended to complement these other sites by providing basic genomic information and tools for all rna viruses and linking the user to more specialist sites , where they exist , e.g. for hiv-1 and hepatitis c virus ( hcv ) , we provide links to sites such as the los alamos laboratory on the main page for each of these viruses ( find by typing hiv-1 or hcv into the search window in the top toolbar ) . for such viruses ,
we do not duplicate the work of other groups by attempting to display the available diversity of genomes .
we intend that the rna virus database should develop further as a hub for other sites and we therefore encourage other workers to contact us with details of their sites that they wish linked to ours . also , we encourage workers to  adopt a virus and improve and/or expand the information that we provide for individual species . this can be done by emailing us or getting involved directly in developing the database , which is an open source project available at our googlecode site ( http://code.google.com/p/rnavirusdb ) . some of the data and tools on the rna virus database can be found elsewhere , but not all of them can
, e.g. ncbi 's genome site provides genomic overviews of virus species and pairwise alignments of other isolates to the reference sequence , but it does not provide multiple alignments or complete translated genomes as we do .
similarly , its general entrez site provides pair - wise alignments of the query sequence and similar sequences in the database , plus a phylogenetic tree calculated from those distances ; however , no multiple alignment is built .
we also corrected the ( few ) errors in the genbank entries , and our database records features such as rna editing ( 10 ) that make genome translation problematic .
we have , therefore , created the rna virus database as a user - friendly site devoted to rna viruses , providing essential genomic data and tools ( discussed in more detail below ) and links to the other virus web sites .
provide multiple whole - genome alignments , gene and whole - genome translations for all rna virus speciesidentification and taxonomic searching facilityguidance to other web resources .
provide multiple whole - genome alignments , gene and whole - genome translations for all rna virus species identification and taxonomic searching facility guidance to other web resources .
we provide multiple alignments of whole genomes ( as nucleotides ) for all species where genbank contains multiple representatives .
our database , thus , currently has multiple alignments for approximately half the species ( available from the main page of any virus species under
these alignments were made by downloading from genbank all complete ( or near - complete ) genomes using the bioperl genbank modules ( 11 ) .
accidental mismatches were excluded by performing a preliminary alignment using blastalign ( 12 ) , which is designed to cope with non- or poorly homologous sequences and reports such matches .
the sequences that showed clear homology to the ncbi reference sequences ( we used a cutoff of a maximum of 40% of positions being represented by gaps in the blastalign alignment ) , up to a maximum of 50 , were then aligned using clustalw ( default parameter values ) ( 13 ) . for species for which we have at least three sequences ,
a neighbor - joining tree was then constructed using paup ( with hky - adjusted genetic distances ) ( 14 ) , and this tree is displayed both as a pdf [ via the treegraph program ( 15 ) ] and using figtree , which is a new java - based tree - drawing application created by one of us ( rambaut , a . , unpublished data ) .
our site allows virus nucleotide or amino acid sequences submitted by the user to be identified or , if the query is a new species , its closest relative to be found .
in addition , the genomic location of any matched region of the library sequences is shown .
for this we use ncbi 's suite of blast programs ( 16 ) ( go to the  blast link on the toolbar of the home page ) . once the most closely related reference species has been located , the query sequence can then be placed into a whole - genome multiple alignment for that species ( where such an alignment is present ) in order to show the query 's phylogenetic relationships to the genomes in our database ( go to
( i ) a blast of the query to the reference species sequence provides coordinates from the resulting pair - wise alignment .
these coordinates are then used to select homologous regions from the reference multiple alignment , and a new multiple alignment is then built using clustalw along with a phylogenetic tree using paup as described above .
( ii ) blastalign ( described above ) is used to generate a new multiple alignment using the query sequence plus the sequences from the reference multiple alignment .

figure 2.screenshots illustrating use of the rna virus database to investigate a submitted virus nucleotide sequence .
screenshots illustrating use of the rna virus database to investigate a submitted virus nucleotide sequence .
isolates , includes the biological data of the isolates used in the whole - genome multiple alignments [ except for hiv-1 , hcv and hepatitis b virus ( hbv ) , where we used manually built multiple alignments ; for these three species , accession numbers for the isolates are given in the supplementary data as accessionhivhcvhbv.xls ] .
we provide amino acid sequences for all virus genes ( or , more strictly , for all open reading frames ) plus complete translated genomes for each virus species ( go to
the translated genomes are intended to facilitate phylogenetic analysis of more distantly related viruses ( 9 ) .
one feature that makes annotation of rna viruses difficult is that most species have some gene overlap ( 17 ) , i.e. where the same nucleotides code for two different genes by being read in two different frames .
we , therefore , allow the user to select from three possible options for dealing with this feature : ( i ) have overlapped regions excised from the translated genome , ( ii ) have one only of any overlapped amino acid sequences represented or ( iii ) have all the amino acids sequences present , with overlapped sequences placed sequentially ( and thus the nucleotides represented twice ) . using a key word search of the genbank entries , and a standard reference work ( 18 ) where this did not reveal a match ,
the rna virus database is a php web application on top of a mysql database .
php is available at http://www.php.net , but should come pre - installed on unix machines .
all data have been taken from the ncbi 's genome and nucleotide sites at the following two urls .

table names are in large bold font and interlinking column names are in small regular font . relationships of tables in the underlying mysql database .
table names are in large bold font and interlinking column names are in small regular font .
species names , nucleotide sequences and accession numbers were downloaded directly from genbank using bioperl modules , while further details of the virus  gene coordinates , taxonomic affinities etc.were subsequently extracted from the flatfile of all genbank entries that can be downloaded from the ncbi genome site ( 19 ) .
our approach was to treat all entries in the ncbi virus genome sites as species and to follow their taxonomic classification , although we only give virus type ( e.g. single - stranded positive - sense , retrotranscribing ) , family and genus at our site .
we , therefore , follow ncbi 's inclusion of hepadnaviruses , which include hbv , and caulimoviruses among the rna viruses despite their mature virion containing dna rather than rna ( their possession of reverse transcriptase clearly places them biologically and evolutionarily among the reverse - transcribing group of rna viruses ) .
the php scripts can be accessed using subversion ( http://subversion.tigris.org/ ) from our googlecode site at http://code.google.com/p/rnavirusdb .
the mysql database ( a gzipped 16 mb dump ) may also be downloaded from the same site for installation on the user 's computer if required .
if required , the database can subsequently be updated by other users following instructions and perl scripts given in the supplementary material ( perl_scripts.tar ) .
this updating involves a series of short intervening manual steps ( we find that complete automation of such processes is inefficient ) .
we intend to update the database on at least a 6-monthly basis in order to include newly discovered viruses , and are currently working to incorporate biological and epidemiological data .
as discussed in introduction , we are keen to collaborate with other groups over further developments of our database .
wellcome trust ( to r.b . ) ; eu marie curie fellowship scheme ( to t.d.o . ) ; the royal society ( to a.r . )

Answer:
the rna virus database is a database and web application describing the genome organization and providing analytical tools for the 938 known species of rna virus .
 it can identify submitted nucleotide sequences , can place them into multiple whole - genome alignments ( in species where more than one isolate has been fully sequenced ) and contains translated genome sequences for all species .
 it has been created for two main purposes : to facilitate the comparative analysis of rna viruses and to become a hub for other , more specialised virus web sites .
 it is available at the following four mirrored sites .

 http://virus.zoo.ox.ac.uk/rnavirusdbhttp://hivweb.sanbi.ac.za/rnavirusdbhttp://bioinf.cs.auckland.ac.nz/rnavirusdbhttp://tree.bio.ed.ac.uk/rnavirusdb


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 online version of this article ( doi:10.1007/s13555 - 015 - 0084 - 3 ) contains supplementary material , which is available to authorized users .
finasteride 1  mg is used successfully all over the world for the treatment of androgenetic alopecia in male pattern baldness .
various clinical trials have established finasteride s efficacy in adult men with predominant vertex , anterior and midscalp region [ 2 , 3 ] . on average ,
common side effects are loss of libido , erectile dysfunction and decreased ejaculate volume . these side effects were found in less than 0.5% of patients . to assess the huge difference [ 2 , 11 ] in reporting the side effects
, we conducted a 2-year randomized , questionnaire - based research study on patients receiving finasteride 1  mg tablets for androgenetic alopecia .
for this , we used a questionnaire based on the international index of erectile function ( iief ) ( supplementary table  1 ) .
this checks five domains : erectile function , orgasmic function , sexual desire , intercourse satisfaction and overall sexual satisfaction .
a higher iief score indicates better sexual function and low score ( below 25 ) indicates erectile dysfunction .
the aim of the present study was to evaluate an age - matched comparison and evaluation of sexual function in patients treated by finasteride 1  mg for early androgenetic alopecia by using iief .
inclusion criteria were age 1840  years , who came for an outpatient consultation for male pattern androgenetic alopecia , which was diagnosed using the norwood
 hamilton s grading of male pattern alopecia with grade 3 to 5 on treatment with finasteride 1  mg , with good physical health .
exclusion criteria were patients being treated for various other causes of hair loss other than androgenetic alopecia .
those selected patients were briefed about the iief questionnaire and , with their consent , the questionnaire was provided for completion .
a mean duration of approximately 16  weeks of medication was consumed by the patients at the time of answering the questionnaire .
our controls were 586 patients who attended outpatient consultation for various other non - hair related diseases such as psoriasis vulgaris , lichen planus , allergic contact dermatitis , irritant contact dermatitis , nail disorders , etc .
the resultant scores of erectile function domain and iief domain of both the study group taking finasteride 1  mg and their age - wise control group were analyzed with the ibm software package ( spss statistics , ny , usa ) . all procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation ( institutional and national ) and with the helsinki declaration of 1964 , as revised in 2013 .
both the study group and controls were asked to answer the iief questionnaire anonymously to avoid any identity on sexual weakness .
the results were compared in an age - wise manner . comparing the age - wise finasteride - consuming patients and the control group ,
there was no statistical difference between the groups regarding their sexual function in total iief score or in any of the five domains mentioned .
1 ) show the scores in the erectile function domain ( a ) and international index of erectile function domain ( b ) in patients on finasteride and their controls.fig .
1age controlled 3d graphs showing the scores of domain in erectile function ( a ) and international index of erectile function domain ( b ) in patients on finasteride and their controls with age and scores both depicted in y axis age controlled 3d graphs showing the scores of domain in erectile function ( a ) and international index of erectile function domain ( b ) in patients on finasteride and their controls with age and scores both depicted in y axis
the main mechanism in androgenetic alopecia is miniaturization of hair follicles from terminal to vellus hair   due to the effect of androgen , especially dihydrotestosterone .
testosterone is converted by 5 alpha reductase to 5 alpha dihydrotestosterone , which is five times more potent than testosterone .
this dihydrotestosterone binds to the androgen receptors of the genetically marked hair follicle and leads to miniaturization of that hair follicle .
finasteride is an azasteroid type 2 isoenzyme , 5 alpha reductase inhibitor , which inhibits dihydrotestosterone conversion from testosterone .
this type 2 isoenzyme is present in the hair follicles and its activity is important in controlling the end organ hyper - reactivity causing androgenetic alopecia .
observation of eunuchs and prepubertal boys highlighted the role of testosterone in the induction of androgenetic alopecia .
therefore , it is evident that finasteride should not cause any side effects , relating to sexual health , as there will be no decrease in the quantity or quality of the testosterone level .
however , clinical trials conducted by leyden et al .   and kaufman et al .
resulted in 2% of patients experiencing sexual side effects such as the loss of libido , erectile dysfunction and decreased ejaculate volume . in this study
, patients taking finasteride 1  mg for androgenetic alopecia and the control group were provided with the iief questionnaire and their responses analyzed .
the results indicated that erectile and sexual function was not reduced compared to the controls .
so , not only theoretically , finasteride was found to be a comparatively safe drug in this indian male population .
this study was conducted in the indian context on the basis of the iief   and the european study by tosti et al . .
further studies should be conducted in a multi - center , double - blind manner .
in both our study and the study conducted by tosti et al . , sexual and erectile function of those subjects who were orally treated with finasteride was not reduced compared with their age - related controls .
supplementary material 1 ( pdf 301  kb ) supplementary material 2 ( docx 19  kb )
all procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation ( institutional and national ) and with the helsinki declaration of 1964 , as revised in 2013 .
this article is distributed under the terms of the creative commons attribution - noncommercial 4.0 international license ( http://creativecommons.org/licenses/by-nc/4.0/ ) , which permits any noncommercial use , distribution , and reproduction in any medium , provided you give appropriate credit to the original author(s ) and the source , provide a link to the creative commons license , and indicate if changes were made .

Answer:
introductionfinasteride is one of the most common drugs used in androgenetic alopecia .
 the literature discusses the sexual side effects of the drug ; however , in practice there is little evidence to support this .
 the aim of the present study was to investigate the sexual dysfunction in patients taking finasteride 1  mg for androgenetic alopecia.methodsa questionnaire , based on the international index of erectile function , was given to approximately 586 patients with androgenetic alopecia who were being treated with finasteride 1  mg for an average of 16  weeks .
 these patients were compared to an age - related control group who were attending the dermatology out patients department for various other skin ailments not related to hair disorders.resultsstatistical analysis of the results showed no significant difference in the scores between patients taking finasteride and the control group.conclusionanalysis showed no significant difference in sex - related problems with that of patients taking finasteride and age matched controls , suggesting that sex - related issues are not a side effect of finasteride.electronic supplementary materialthe online version of this article ( doi:10.1007/s13555 - 015 - 0084 - 3 ) contains supplementary material , which is available to authorized users .


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:
systemic chemotherapy is the main treatment modality in the management of patients with metastatic disease . after chemotherapy ,
oncologists evaluate tumor response by observing tumor behavior , i.e. growth , reduction or stability in its dimensions [ 2 , 3 ] . nowadays
, tumor response to therapy as determined by imaging methods is generally used to inform decisions regarding either maintenance or interruption of treatment . in the late 1970s the world health organization ( who ) introduced a standard assessment of tumor response , proposed by miller et al .   and adopted internationally , defining objective responses of lesions measurable in two dimensions , such as pulmonary metastasis assessed by x - rays .
this evaluation is performed by comparison of tumor area , the sum of all lesions greater perpendicular diameter products , measured in a planar image .
more recently a new set of guidelines has been introduced by the response evaluation criteria in solid tumors ( recist ) group with the purpose of reviewing the former criteria and better standardizing response evaluation .
this model uses a unidimensional approach taking the sum of the longest diameters instead of the sum of the areas . with the introduction of cross - sectional imaging methods ,
the number of measurable metastatic lesions detected in a single patient has increased dramatically , and most oncologists ( as well as study protocols ) recommend the use of one lesion or a few  representative lesions to evaluate response in individual patients with multiple lesions .
metastatic nodules are not uniform and consist of a heterogeneous cell population with diverse biological behavior that could account for differences in chemotherapy response . a wide range of growth patterns in pulmonary metastases of patients not previously submitted to treatment has been observed .
this variation in behavior , if observed in patients being evaluated for chemotherapy response , could influence the response perception .
the selection of one or a few nodules , instead of including all identifiable nodules in the response evaluation , could lead to misevaluation and consequently to the continuity of ineffective treatment or the interruption of potentially effective therapy . the present study used ct to quantify the variation in tumor response of pulmonary metastases of solid tumors of varied histology in individual consecutive patients that were submitted to ct studies in order to evaluate response to chemotherapy .
we submitted each pulmonary nodule individually , as if it were a solitary metastasis , as well as all the nodules of the same patient combined , to both the who and the recist criteria and compared the response evaluations in each setting .
we prospectively evaluated two consecutive chest ct scans of patients with the diagnosis of solid tumor and pulmonary metastases receiving systemic chemotherapy and being routinely evaluated for tumor response .
we included in this study 41 chemotherapy response evaluations in 33 patients ( 20 women and 13 men ) , with ages ranging from 14 to 81 years ( median 46 years ) . in eight patients
the attending physician ( department of clinical oncology ) established the diagnosis of pulmonary metastases usually by the presence of new pulmonary nodules and progression of metastatic disease and the type of chemotherapy used .
the interval between the ct evaluations varied from 1.25 to 8.8 months ( median : 3.9 ; mean ( sd ) 3.8 ( 1.6 ) months ) and the number of cycles varied from 2.0 to 6.0 cycles ( median : 4 ; mean  sd : 3.7  1.2 cycles ) .
helical scan techniques were performed on ct prospeed and ct hispeed scanners ( general electric ) .
the slices obtained were contiguous with 7 mm thickness and a pitch of 1.5 or less .
the two larger perpendicular diameters on the axial plane were measured in images printed in lung windows .
the number of nodules in an individual patient varied from 2 to 69 ( median : 7 ; mean  sd : 13.8  15.0 nodules ) .
the nodules initial larger diameter ranged from 2 to 82 mm ( median : 10 ; mean  sd : 11.6  8.5 mm ) . in each set of ct scan examinations performed to assess tumor response to chemotherapy , who and recist criteria classified each nodule individually . for the patient s response evaluation a modified version of the who and recist criteria was used by considering the sum of measurements of all pulmonary nodules in each patient to better represent the total tumor volume change for each patient .
the bidimensional who criteria of tumor response categories are : ( a ) partial response when area reduction is 50% or more ; ( b ) stable disease for a reduction of less than 50% or an increase less than 25% ; and ( c ) disease progression for an increase of 25% or more .
the unidimensional recist criteria of tumor response categories are : ( a ) partial response if linear larger dimension reduction is 30% or more ; ( b ) stable disease for a reduction less than 30% or an increase less than 20% ; and ( c ) disease progression for an increase of 20% or more .
the disappearance of the lesion(s ) is considered a complete response by both assessment criteria and both consider the presence of any new nodule as progression of disease , independent of the behavior of any other nodule .
the following parameters were determined : ( a ) individual nodule response rate evaluation ; ( b ) response evaluation for each patient , as a whole , according to the who and the recist criteria ; ( c ) intra - individual distribution of response for every patient s nodule ; and ( d ) the proportion of nodules evaluated differently from the patient s response , taking the sum of all nodules into consideration .
the nodules response category distributions for different types of cancer , chemotherapy , and initial number of nodules were compared by chi - square test .
the agreement between both response evaluation criteria was calculated by the kappa - interrater agreement index .
half ( n=283 ) of the nodules showed a reduction in size considering only the larger measured diameter , while 126 ( 22% ) remained unaltered comparing both ct scan studies and 157 ( 28% ) increased in size . according to the who criteria , 113 ( 20% ) had a complete response , 66 ( 12% ) had a partial response , 258 ( 46% ) were stable and 129 ( 23% ) progressed . using the recist criteria , 134 nodules were considered measurable as having a diameter twice the size of the slice thickness utilized ( > 14 mm ) .
of these , 22 ( 16% ) nodules had a complete response , 17 ( 13% ) a partial response , 67 ( 50% ) were stable and 28 ( 21% ) progressed .
classification was different by the two criteria in 13 ( 10% ) of the 134 measurable nodules .
the kappa interrater agreement for both criteria evaluations was 0.85 ( table 2 ) .   evaluating the patients response , taking into account the sum of all nodules , by the who criteria
, one patient was classified as having complete response , five partial response , 15 stable disease and 20 progressive disease ; and by the recist criteria one patient was classified as having complete response , five partial response , 16 stable disease and 19 progressive disease .
the kappa interrater agreement for both criteria evaluations was 0.90 ( table 3 ) .
the intra - individual variation for metastases response evaluation was quite diverse by both criteria , with no relation to type of cancer , chemotherapy or number of nodules . by the who criteria : from the total of 41 response evaluations ,
all the patients nodules had the same response classification in four ; in 16 evaluations there were nodules in two distinct classifications ; in 12 three different classifications ; and in seven , nodules in the four possible categories ( fig .
1 ) .   by the recist criteria : measurable nodules were present in 33 of the 41 response evaluations ; in seven there was only one nodule ; in 11 all the patients nodules had the same response classification ; in 12 evaluations there were nodules in two distinct classifications ; and in three evaluations there were nodules in three different classifications ( fig .
eighteen patients presented 82 new nodules observed at the second ct scan , varying from 1 to 21 per patient ( median 2 , mean 4.8 ) , in a proportion of the initial total number of nodules ranging from 5% to 525% ( median 25% , mean 75% ) . by the recist criteria , in one of the 19 patient evaluations resulting in disease progression no new nodule was present and in 14 a new nodule was the sole criterion for disease progression classification ( table 4 ) .   by the recist criteria , the proportion of measurable nodules classified differently from the patient evaluation , taking the sum of all measurable nodules into consideration , varied from 0% to 100% ( median : 25% ; mean  sd : 30%  33% ) . in a patient with three lung metastases ,
the patient evaluation by comparison of the sum of diameters of the three nodules resulted in partial response . in 15 evaluations
there were measurable lesions and there were no new nodules ; when the measurable response was the only considered factor , the proportion of measurable nodules classified differently from the patient evaluation , taking the sum of all measurable nodules into consideration , varied from 0% to 100% ( median : 33% ; mean  sd : 35%  35% ) .
after chemotherapy , evaluation of tumor response is obtained by observing the progress of lesion size .
difficulties arose when the number of lesions per patient that could be evaluated increased , mainly after the introduction of cross - sectional imaging methods .
nowadays most radiologists and oncologists use only one lesion or a few  representative lesions to evaluate tumor response in patients presenting with multiple nodules .
thus , it is important to know the intra - individual variability of response rate evaluation for different tumors in the same patient . clinically , the response rate of solid tumors has been calculated by taking the tumor diameters in observations separated by the treatment , and by determining tumor shrinkage , stability or growth . for many years
the world health organization criteria for treatment response evaluation have been the criteria used by most oncologists and in most clinical trials .
more recently , several organizations involved in clinical research have reviewed these criteria on the basis of experience acquired since they were introduced and a new set of guidelines has been developed with a model by which response rates could be derived from unidimensional measurement lesions instead of the former bidimensional approach . according to this model , the use of only one lesion dimension simplifies the task of evaluating tumor response and correlates well with the lesion s area , previously used .
the recist group tested their criteria in several historical study protocols and obtained good correlation with the who criteria .
more recently , studies have shown both good and poor correlation between the unidimensional and bidimensional response evaluations [ 8 , 9 ] . in this present study a high correlation between the who and the recist criteria in the evaluation of individual nodules and patients was achieved .
the advantage of using the recist criteria is the simplicity of taking only one measurement per lesion .
nowadays , the best method of assessing tumor response in most clinical situations is ct scan , leading to detection of a larger number of lesions , with smaller diameters , and more precision on measuring when compared to other methods [ 10 , 11 ] .
even though pulmonary metastases evaluated by ct scan should be one of the best scenarios in terms of measurement of lesions , since the low - density lung provides natural contrast for the dense pulmonary nodule , variability in the application of response criteria could compromise the reproducibility of results .
major potential sources of response evaluation variation are imaging techniques , inter - observer variability , and the selection of target lesions [ 12 , 13 ] . in order to minimize observer variation ,
this study applied helical ct scanning and had the lesions measured by the same radiologist to evaluate response of the multiple metastases in the same patient , as routinely done in the clinical setting and in study protocols .
the presence of a new nodule was the main factor for determining disease progression , and the proportion of these new nodules in some cases was as low as 5% .
the systematic evaluation of all the patients nodules is then necessary to guarantee the identification of a new nodule .
the individual nodules in the same patient have individual and unpredictable behavior and can be evaluated as independent lesions . by using the who and the recist criteria of tumor response to therapy we verified that there were nodules labeled as disease progression in patients classified as stable , and unaltered nodules in patients evaluated as having progressive disease . in our patient population the proportion of nodules in a patient with response evaluation different from that obtained taking the sum of all nodules together amounted to 35% .
the results confirmed our previous impression that the application of the who or the recist method to one or some nodules in a patient , as frequently utilized by protocols , could also be misleading . in the same patient , one could select a stable nodule , a nodule with growth or a nodule in regression , and this could result in a decision error regarding the treatment regimen .
the use of the sum of the evaluation of all nodules together maximizes the reproducibility of response evaluations . in this study
we tried to reproduce what seem to be the usual conditions for tumor response evaluation in most protocols and institutions ; some of these conditions are limitations for the best possible response evaluation accuracy , but are close to clinical practice standard conditions .
there was no histological proof of the metastatic nature of the lung nodules , and some could have been infectious or inflammatory ; in clinical practice , however , histological proof is rarely required and the presence of new pulmonary nodules and overall oncologic disease progression are the criteria adopted by the oncologist for a diagnosis of lung metastases . when this study was conducted
nowadays many institutions with faster and multiple detector cts adopt 5 mm or less in the evaluation of lung metastases .
however , the recommendation of the authors of the recist group criteria was followed in measuring lesions no smaller than twice the size of the slice thickness .
hard copy measurements were taken , despite having been shown to be less reproducible than computer display methods , as computer measurement is not always available , especially to the oncologist . in conclusion , there is a high correlation between the world health organization criteria and the recist group criteria .
intra - individual variation in tumor response of pulmonary metastases is elevated in some patients , and chemotherapy response evaluation utilizing only one or some of the patient s nodules could lead to inappropriate reproducibility in therapeutic response perception .
intra - individual distribution of response evaluation of pulmonary metastases by world health organization criteria .
intra - individual distribution of response evaluation of pulmonary metastases by the response evaluation criteria in solid tumors ( recist ) group criteria .
distribution of primary types of metastatic solid tumor   response evaluation of measurable nodules ( > 14 mm ) assessed by the who and the recist criteria   response evaluation of patients assessed by the who and the recist criteria   impact of the presence of new nodules in the patient s global response evaluation assessed by the recist criteria   bold type indicates evaluations in which a new nodule was the sole criterion for disease progression .

Answer:
objective : with the introduction of cross - sectional imaging methods the number of lesions per patient that can be evaluated is frequently large and most oncologists and study protocols use only one lesion or a few  representative lesions to evaluate chemotherapy response
 . intra - patient response variability can therefore affect evaluation reproducibility .
 this study evaluates intra - individual variation in response to chemotherapy in patients with multiple lung metastases .
 methods : we prospectively studied chest ct images of patients with solid tumors and pulmonary metastases under systemic chemotherapy being evaluated for tumor response .
 the response of 566 pulmonary nodules in 41 evaluations was determined by both who and recist criteria in order to determine intra - individual tumor response variation .
 results : there was almost perfect agreement between the who and the recist criteria for the evaluation of tumor response .
 high intra - individual variability of tumor response was observed in a significant proportion of the evaluations .
 a new nodule was the main criterion for determination of disease progression .
 a mean of 35% of the total number of nodules of a patient have a response evaluation different from that calculated with all the nodules together .
 conclusions : intra - individual variation in tumor response of pulmonary metastases is elevated in some patients . selecting any or some nodules for response evaluation could significantly influence therapeutic response perception .


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

Title:
A straightforward approach towards combined α-amino and α-hydroxy acids based on Passerini reactions

Paper sections:
Introduction

Multicomponent reactions (MCR) are a very popular and powerful tool in modern organic synthesis [1][2][3][4]. Besides a wide range of heterocycle syntheses [5] and catalytic cross coupling reactions [6], the isonitrile-based MCRs (IMCR) especially have developed exceptionally well during the last few decades [7,8]. Based on the pioneering work of Passerini, who observed the first three-component coupling of carbonyls with carboxylic acids and isonitriles in 1921 [9], the so-called Passerini reaction became a powerful tool for the synthesis of acylated α-hydroxyacid amides [10]. Later on, in 1961, Ugi and Steinbrückner reported the extension of this protocol by incorporating also a primary amine as a fourth component [11].

Therefore, the Ugi reaction is even more flexible than the Passerini approach, but both reactions together have made the IMCR highly popular in combinatorial chemistry [7,8].

Our group has been involved in amino acid and peptide synthesis for nearly two decades [12,13], and multicomponent reactions are known to play a dominant role [14,15]. In particular, the Ugi reaction has so far been used for the construction of exotic peptides [16][17][18][19] and cyclopeptides [20,21]. Herein we describe a straightforward protocol towards combined α-amino and α-hydroxy acids through Passerini reactions. Suitable amino acid precursors with an oxygen functionality in the side  chain can be obtained by chelated enolate Claisen rearrangement [22,23] or transition metal-catalyzed allylic alkylation of chelated enolates [24] and subsequent oxidative cleavage of the γ-δ-unsaturated amino acids obtained.

Results and Discussion

An alternative approach is based on regioselective ring opening of epoxides, followed by oxidation of the hydroxy amino acid formed. While aryl-substituted epoxides react preferentially at the benzylic position giving rise to the terminal primary alcohols [25], the corresponding alkyl-substituted epoxides provide secondary alcohols 1 by nucleophilic attack of the enolate at the sterically least-hindered position [26]. These alcohols can easily be oxidized by Swern-oxidation [27] or with Dess-Martinperiodinane (DMP) [28], giving rise to the required γ-oxoamino acids 2 (Table 1). In principle both protocols are suitable for oxidation, but in general the yields obtained were better with DMP (82-93%), while under Swern conditions the yields were in the range of 75 ± 3%.

With these γ-oxo-α-amino acids 2 in hand, we investigated the Passerini reactions under neat conditions with acetic acid as the (liquid) acidic component and isocyano acetates as the reactive component (Table 2). Interestingly, no reaction was observed Scheme 1: Passerini reactions of α,β-unsaturated aldehyde 5.

with the methyl-substituted oxo acid 2a (entry 1); only the starting material was recovered. For this reason, we switched to activated ketones bearing an electron-withdrawing group at the α-position. With the chlorinated ketone 2b the yield was 65% (entry 2), and similar results were obtained with a range of aryloxy-substituted derivatives 2c-2f (entries 3-7). The new stereogenic center was formed without significant selectivity.

To increase the synthetic potential of this protocol we also applied the Pd-catalyzed opening of a vinyl epoxide with our chelated enolate (Scheme 1) [29]. In this case an amino acid 4 with an allyl alcohol side chain was formed which could be oxidized to the α,β-unsaturated aldehyde 5. Although these types of aldehydes are critical candidates in Passerini and Ugi reactions [30], we were interested to see if we could also obtain unsaturated Passerini adducts by this procedure. Our first attempts in CH 3 OH and CH 2 Cl 2 were unsuccessful. While no reaction was observed in CH 2 Cl 2 , in CH 3 OH the only product (besides starting material) was the unsaturated acetal resulting from a nucleophilic attack of the solvent on the aldehyde group. Therefore, we decided to run the reaction also under neat conditions as reported for the γ-oxo-amino acids. With acetic acid as the acidic component the yield of 6a was comparable to the previous examples. In principle, other acids such as benzoic acid or Cbz-protected glycine can be used as well. The lower yield obtained in these cases probably results from stirring problems under these solvent-free conditions.

To circumvent the problems caused by the α,β-unsaturated aldehyde, we hydrogenated 4 before oxidation to obtain the saturated aldehyde 7. And indeed, under our optimized reaction conditions the addition product 8 could be obtained in 80% yield (Scheme 2). In principle, Ugi reactions are also possible, as illustrated with the formation of 9, although the yield was significantly lower in this case and the products are formed as a 1:1 diastereomeric mixture.

Conclusion

In conclusion, we showed that the ring opening of epoxides, either directly or Pd-catalyzed, with chelated enolates combined with Passerini reactions is a suitable tool for the synthesis of highly functionalized α-hydroxy and α-amino acid derivatives. These new compounds are interesting building blocks for peptide-derived drugs. Attempts to improve the yields and to evaluate the scope and limitations are currently underway.

Supporting Information

Supporting Information features detailed experimental procedures, NMR as well as analytical data of all compounds.

Supporting Information File 1

Experimental section.

[http://www.beilstein-journals.org/bjoc/content/ supplementary/1860-5397-7-151-S1.pdf]

Answer: Complex amino acids with an α-acyloxycarbonyl functionality in the side chain are easily available through epoxide opening by chelated enolates and subsequent oxidation/Passerini reaction. This protocol works with both, aldehyde and ketone intermediates, as long as the ketones are activated by electron-withdrawing groups. In principle Ugi reactions are also possible, allowing the generation of diamino acid derivatives.


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:
ectopic thyroid tissue is a common abnormality and results from abnormal embryologic development and migration of the thyroid gland .
such tissue is usually found along the path of descent of the thyroid gland in the anterior midline of the neck .
a lingual thyroid is the most common presentation of thyroid ectopy   along with thyroglossal duct remnants .
ectopic thyroid tissue has been described in other parts of the head and neck such as the submandibular [ 3 , 4 ] and parotid salivary glands .
there are case descriptions of thyroid tissue identified in diverse locations such as the axilla , trachea [ 710 ] , adrenal , small intestine , and porta hepatis .
the most frequent noncervical location for ectopic thyroid tissue is the thoracic cavity [ 1418 ] .
, the authors describe a case of ectopic anterosuperior mediastinal thyroid mass excised through a cervical incision and the subsequent investigation to exclude malignancy .
an 80-year - old nonsmoker female patient presented with an incidental finding of a mediastinal mass on mri scan for investigation of vertigo ( figures 1 and 2 ) .
thyroid stimulating hormone ( tsh ) and free thyroxine ( ft4 ) were within the normal range , and routine preoperative blood tests were normal .
an anteroposterior chest radiograph demonstrated deviation of the intrathoracic trachea around the mass ( figure 3 ) . a subsequent ultrasound scan demonstrated a superior mediastinal mass separate from the inferior pole of the right thyroid lobe measuring 4.8  cm in maximal diameter ( figure 4 ) .
the first sample was inadequate ( thy1 ) , the second sample demonstrated only colloid and a few follicular cells .
since malignancy could not be definitively ruled out , the mass was excised through a cervical incision .   under general anesthesia , the patient was placed in the supine position with the neck extended , prepared , and draped .
endotracheal laryngeal nerve monitoring was used with nim contact emg endotracheal tube and nim - response 2.0 monitor ( medtronic usa , inc.6743 southpoint drive north , jacksonville , florida , usa , 32216 - 0980 ) . through a standard 5  cm midline cervical incision
, the right thyroid lobe was dissected , found to be grossly normal , and excised .
the right recurrent laryngeal nerve was identified in the normal position , confirmed functioning with nerve stimulation at 2  ma , and preserved .
separate and inferior to the right thyroid lobe a discrete encapsulated mass was identified in the superior , mediastinum .
this extended across the anterior surface of the trachea to the left side , adjacent to the thymus .
the mass was separated from the thyroid gland by fat , in the same tissue plane but with no identifiable connection to the cervical region .
the mass was excised through the cervical incision . during excision of the mass , a double vascular pedicle , arising from inferiorly in the mediastinum ,
histopathologic evaluation of the excised mediastinal specimen demonstrated a 5.3  cm by 2  cm thyroid tissue mass with large oedematous loose areas and foci of calcification and fibrosis ( figure 5 ) .
the excised right thyroid lobe had a nodular architecture composed of follicles of varying sizes with focal lymphoid aggregates.thyroid function tests at 3 months were normal .
further investigation with whole body radioiodine i123 scintigraphy demonstrated expected residual uptake in the remaining left thyroid lobe and surgical bed but no uptake suggestive of other ectopic thyroid tissue or metastatic disease .
ultrasound surveillance of a 9  mm nodule in the remaining left lobe demonstrated no change in size over 6 months .
in humans , the thyroid gland begins to develop at the 24th day of gestation .
the thyroid is the first endocrine gland to develop and originates from between the first and second branchial arches .
an invagination of endodermal epithelial cells begins at the midline of the developing pharyngeal floor forming a diverticulum .
this site , known as the foramen caecum , lies between the tuberculum impar ( median tongue bud ) and the hypobranchial eminence ( copula ) .
the foramen caecum can be observed in adults as a small pit at the base of the tongue where the tongue is divided into an oral anterior two - thirds and pharyngeal posterior third by the sulcus terminalis .
the initial path of descent of the bilobed thyroid diverticulum is anterior to the pharyngeal gut , the hyoid bone , and the laryngeal cartilages . at the same time
embryological studies have shown that the strap muscles pull downward on the hyoid bone during development causing a forward tilt .
this tilt pulls the tract posteriorly and causes it to be hooked up behind the hyoid bone .
this explains the importance of excision of the median portion of the hyoid bone in the sistrunk procedure to excise a thyroglossal duct cyst .
the gland reaches its final location anterior to the trachea by the 7th week gestation . by this stage , it has acquired a median isthmus and two lateral lobes .
as it descends , it is joined by the ultimobranchial bodies which form the parafollicular c cells .
thyroid function begins at around the end of the 3rd month when the follicular cells commence production of colloid and follicles appear .   during migration , from the 5th week gestation
, the thyroid is still connected to the tongue by the thyroglossal duct . in normal development , this tubular structure subsequently obliterates entirely at approximately the 8 to 10th week . in some individuals , however , abnormalities in the embryologic development and migration of the thyroid gland can result in ectopic thyroid tissue .
these remnants can appear at any point along the migratory path and are always located at or near the midline .
the majority of remnants are found at , or just inferior to , the body of the hyoid bone as a thyroglossal cyst .
remnants can also be found in the tongue base as a lingual thyroid or close to the thyroid cartilage .
the inferior end of the thyroglossal duct may fail to obliterate , and in at least half of individuals , a pyramidal lobe of the thyroid can be seen to persist .
this pyramidal lobe itself may be attached to the hyoid bone or may be incorporated into a thyroglossal duct cyst .
ectopic thyroid tissue in other locations is rare and generally the subject of single case reports .
the most important diagnosis to exclude is metastatic lymph node deposits of well - differentiated thyroid carcinoma .
indeed , it is generally accepted that early reports of  lateral aberrant  thyroid tissue may represent papillary thyroid carcinoma metastases .
another hypothesis is that a thyroid nodule may become detached from the gland . in this case
, the vascular supply should come from branches of the superior or inferior thyroid artery .
there are reports of thyroid deposits in the soft tissues of the neck representing surgical implantation of thyroid neoplasms . in one case ,
infiltrating thyroid tissue in muscle and fibrous tissue presented 3 years after major blunt trauma to the neck .
the tissue resembled that in a disrupted thyroid nodule present in the gland itself and was regarded as traumatically implanted .
there are , however , a number of ectopic thyroid masses reported which do not have features consistent with these theories and are considered truly developmental .
animal studies suggest that ectopic location of thyroid tissue may be related to vascular development .
the normal arterial supply of the thyroid gland consists of paired superior and inferior thyroid arteries . the superior thyroid artery is generally considered to be present in 100% of cases , and its absence has only been reported once . an unusually large superior thyroid artery may replace the contralateral vessels or the inferior thyroid artery .
the inferior thyroid artery when unusually small or absent may be replaced or supplemented by a thyroidea i m a artery .
published reports place the incidence of a thyroidea i m a artery   between 2% and 12% .   in the case
the ectopic mass was separate from the thyroid gland but in the same anatomical plane .
careful histological examination of the mass and the excised ipsilateral thyroid lobe demonstrated no evidence of neoplasia , and exhaustive investigations showed no evidence of thyroid malignancy elsewhere .
the authors therefore conclude that this represents developmentally ectopic sequestered thyroid tissue in the anterior mediastinum . despite this
, the authors suggest that abnormally situated thyroid tissue , other than that in the central neck along the path of embryological descent of the thyroid gland , should be excised for careful histological analysis in order to exclude metastatic disease .

Answer:
an 80-year - old female presented with an incidental finding of a retrosternal mass on magnetic resonance imaging .
 ultrasound demonstrated a mediastinal lesion adjacent to but separate from the inferior pole of the right thyroid lobe .
 fine needle aspiration cytology demonstrated colloid and follicular cells . at surgery
 , the right thyroid lobe was found to be normal .
 a discrete 5 cm nodule was found in the anterior mediastinum separate from the thyroid and just anterior and to the right of the trachea and thymus .
 the nodule had a vascular pedicle arising from the mediastinum .
 the differential diagnosis included metastatic thyroid carcinoma .
 histology was consistent with a benign ectopic sequestered thyroid nodule .
 extensive investigations demonstrated no sign of a thyroid malignancy .