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 use of medical devices for temporary use or implantation in the blood circulation has resulted in an increased demand for evaluation of complications brought about by these devices .
this resulted also in - better defined iso requirements for testing   one important and relevant aspect of testing of medical devices is the condition of blood exposed to the device .
anticoagulation and flow conditions must be as similar as possible as in the clinical setting in order to achieve relevant test results .
for some devices , including grafts , stents , and catheters , this implies similar anticoagulation treatment as used in clinical situations , but also high flow through or around the device to obtain relevant shear stress conditions [ 2 , 3 ] .
however , in some reports , blood was treated with other anticoagulants than in clinical situations .
animal models should be avoided if equally quality results may be obtained in other ways . in addition
, animal blood has essential differences compared with human blood , particularly with regard to clotting and platelet function .
two types of in vitro flow models ( often with human blood ) have been used extensively : the modified chandler loop and the roller pump closed - loop system .
the modified chandler loop   consists of closed tubing partly filled with air . on rotation , devices in the tubing
use of this system may induce artefacts due to major forces applied to blood elements and protein denaturation at the air - liquid interface [ 911 ] .
this model appeared effective for short circulation times [ 1214 ] , but intrinsic blood damage reduces sensitivity and does not allow prolonged exposure to blood . to overcome the disadvantages of these models , the hemobile was constructed .
in addition , the tubing contains no air , and there is no mechanical device compressing the tubing . in this way it was attempted to reduce damage and activation and to simulate pulsatile flow in a frequency similar to the arterial circulation .
the hemobile model was compared with the chandler loop and roller pump model for intrinsic damage to blood components and activation of platelets .
the hemobile was further used in testing tubular structures made of various polymers to show its effectiveness in determination of hemocompatibility by means of in vitro circulation of human blood .
fresh human blood was obtained by vena puncture with a 19 gauge needle under low pressure from five healthy adult volunteers and anticoagulated with a clinical dose of heparin ( 1.5  iu / ml ) ( leo pharmaceutical products bv , weesp , the netherlands ) . before starting the experiment , cell count ( cell counter medonic ca 530 , medonic , sweden ) and platelet function analysis ( platelet function analyzer-100 )
were performed and platelet aggregation was determined by adding 50  mmol adp to a mixture of 500  l of blood and 500  l of saline and with the use of a whole blood aggregometer ( chrono log corp .
aggregometer , kordia life sciences , leiden , the netherlands ) to confirm proper blood quality relevant for this study and to provide baseline characteristics .
three circulation models were compared ; the modified chandler loop , roller pump , and hemobile model ( figure 1 ) .
the principle of the modified chandler model is based on a chamber of air that remains on top of a vertical rotating circular loop ( de spatel bv , roden , the netherlands ) .
the roller pump is a nonocclusive pump for clinical use in extracorporeal circuits ( stckert , munich , germany ) .
the hemobile ( haemoscan bv , groningen , the netherlands ) consists of a cylinder , which is forced in a semirotating movement . on this cylinder the circular loop circuits can be positioned .
due to the semirotating movement and the slowness of blood , a pulsating movement of blood through the circuits is generated which mimics pulsatile flow .
a ball valve ensures a directed flow of up to 40  ml / min through 3  mm tubing at 60  beats / min , thus creating shear stresses of 12  dynes / cm .
also , the flow wave form generated by the model is more physiological compared to the roller pump and chandler model .
a comparative study was performed to assess intrinsic blood damage for three different closed - loop circulation models , without any test device in the circuit .
each set of experiments ( three different circuits in triplicate ) was performed five times with fresh venous blood from a different donor for each set . due to restrictions of the chandler loop model , the flow through 3  mm tubing
was limited to 25  ml / min ( 6  dynes / cm ) in all experiments .
the first set of experiments was performed under circumstances of similar flow ( 25  ml / min ) in all three test systems .
the following sets of experiments ( n = 4 ) were performed with the roller pump and hemobile at an exceeded blood flow of 40  ml / min ( 12  dynes / cm ) , which resembles shear stresses in the coronary blood circulation .
after these validation experiments , the hemobile was used to test the hemocompatibility of woven tubular structures from polyester ( pet ) fiber and dyneema purity uhmwpe fiber , in comparison with expanded polytetrafluoroethylene ( eptfe ) tubes .
all experiments were performed with closed pvc tubing circuits ( raumedic ) with a length of 45  cm and an internal diameter of 3  mm .
the hemobile circuits were fitted with a ball valve connector ( halkey - roberts , street petersburg , fl , usa ) .
the roller pump circuit was partially immersed in water , whereas the chandler loop and hemobile were completely placed in an oven ( figure 1 ) .
the circuits of the roller pump and hemobile were filled with 4.5  ml of blood and the circuits rotating on the chandler loop system with 4.0  ml of blood and 0.5  ml of air .
cell count , platelet function analysis , and platelet aggregation measurements were performed on the circulated blood , as described above .
the rest of the blood was mixed with 0.2  m edta and centrifuged at 11,000  g for one minute .
plasma was used for analysis of thromboxane b2 ( txb2 ) , thrombin - antithrombin iii ( tat ) complexes , elastase , and hemoglobin concentrations .
activation of the arachidonic acid pathway in platelets results in the release of the potent platelet aggregating agent thromboxane a2 , which is rapidly converted to the inactive product txb2 .
txb2 was measured by means of an enzyme immunoassay ( biotrak , amersham , uk ) , based on competition of labelled txb2 with sample txb2 . in this test
the label is a peroxidase , which converts the substrate tetramethylbenzidine , yielding a yellow colour which is measured at 450  nm by a spectrophotometer ( powerwave 200 , biotek instruments , winooski , vt , usa ) .
thrombin formation during the in vitro experiments was determined by means of tat complexes in edta plasma .
a tat elisa was performed with capture and detection of antibodies from cederlane laboratories ( hornby , canada ) .
release of polymorphonuclear ( pmn ) elastase in vivo is a specific marker for inflammation reactions .
free in plasma , elastase is rapidly neutralised by 1-antitrypsin inhibitor to form a stable complex .
elastase was determined by elisa by means of capture antibody against human elastase and labelled detection antibody against alpha1 antitrypsin ( affinity biologicals , ontario , canada ) .
complement activation was determined by elisa based on a mouse anti human c5 - 9 antibody ( dako , glostrup , denmark ) and goat anti - c5 detection antibody ( quidel , san diego , ca , usa ) .
free hemoglobin as an index for erythrocyte damage was measured as described by harboe   and using a spectrophotometer ( power wave 200 ) .
the emptied pvc circuits and the incubated graft material were washed with tris - buffered saline ( ph 7.4 ) .
platelet adhesion onto the surface of the circuits was measured by means of a colorimetric assay , based on the presence of acid phosphatase in platelets .
platelet binding was measured based on the release of platelet acid phosphatase in citrate buffer ( ph 5.4 ) , containing p - nitrophenyl phosphatase and triton x100 .
substrate conversion is proportional to the amount of platelets , which was determined by a standard curve and platelet counting .
scanning electron microscopy ( sem ) was achieved on material fixated in 2% glutaraldehyde in cacodylate buffer , treated with osmium tetraoxide in cacodylate buffer and gold sputtered critical point dried samples .
these were visualized at 2  kv ( jeol 6301 f , jeol ltd . ,
anova was performed for all blood parameters to assess any difference in blood cell damage or activation between the circuits .
platelet - count was significantly reduced by the roller pump and by the modified chandler loop , but not by the hemobile ( figure 2 ) .
platelet function was partially decreased in all systems , in particular in the roller pump system .
platelet adhesion to the pvc tubing was lowest in the chandler loop ( table 1 ) .
txb2 and free hemoglobin were significantly higher after roller pump circulation than after chandler loop and hemobile circulation ( table 1 ) .
pump and hemobile could be applied at a flow of 40 ml / min , which was not possible with the chandler model .
platelet number remained higher , and hemolysis was lower in the hemobile circuits ( table 2 ) .
platelet count was reduced in the circuits containing a test chamber with eptfe , pet , or dyneema purity uhmwpe fiber by approximately 30% following circulation compared to baseline .
platelet function was reduced in all circuits to a similar extent ( figure 3 ) .
platelet binding based on the adhesion of antibody against the platelet gpiib receptor showed increased values on pet , whereas dyneema purity uhmwpe fiber had lowest gpiib receptors ( figure 4 ) . in the eptfe circuits ,
release of txb2 and tat was lowest , whereas elastase , complement activation , and hemolysis were lowest in dyneema purity uhmwpe fiber circuits ( table 3 ) .
more detailed pictures showed platelets and fibrin usually separate and not as a dense thrombus on the surface .
differences between the 3 types of graft materials were not clear from these pictures , although eptfe seemed to remain more devoid of deposition than pet and dyneema purity uhmwpe fiber ( figure 5 ) .
initial experimental blood circulation models with a roller pump , already refined in previous studies [ 13 , 14 , 18 ] , appeared efficient , reliable , and cost - effective to assess the haemocompatibility of grafts before their clinical use .
however , blood damage induced by the pump caused a limitation of the exposure of the test object to circulating blood .
the modified chandler loop model is currently most frequently used for these purposes [ 19 , 20 ] .
first , the continuous blood - air contact induces leukocyte and platelet aggregation , protein denaturation [ 911 ] , and shear forces on particulate material , which can result in detachment [ 21 , 22 ] . in our experiments , indeed less platelets were observed on tubing exposed to blood - air contact in the chandler loop than in the roller pump or hemobile circuit .
the second disadvantage of the chandler loop is the limitation of blood circulation due to the requirement to keep the air on top of the circuit .
thus , our 3  mm tubing did not allow a blood flow over 25  ml / min , which is half of the arterial flow in the coronary system . at a flow of 25  and 40  ml / min ,
the hemobile could be used and was less traumatic for blood than the roller pump model .
it is well known that any type of foreign body material can be thrombogenic by promoting the formation of thrombin and platelet activation , which facilitates platelets to adhere and to express surface receptors ( gp iibiiia ) of activated phase .
platelet binding becomes then irreversible and can promote more thrombus formation . therefore , proper testing of the characteristics of graft material is an important issue in modulating blood interaction .
the small tubular system used in the present models allows multiple tests with fresh human blood .
the modified chandler loop and hemobile can be easily loaded with a number of circuits at a time . fast screening of thrombogenicity of vascular grafts and other small medical devices is possible .
the adjustable flow and shear and the pulsatility in the hemobile renders it in a model that allows standardised testing of these devices at the cost of low intrinsic blood damage , while closely mimicking the in vivo conditions .
our results indicated that the changes in circulating blood are most of all dependent on the material used in the test loop . moreover
a direct comparison of material surfaces was possible by using blood of the same donor for different circuits .
the feasibility of the hemobile has been demonstrated by applying the model in hemocompatibility studies of different vascular graft materials .
woven tubes made of pet fiber and dyneema purity uhmwpe fiber have been compared to commercially available eptfe vascular graft .
our results showed that dyneema purity uhmwpe fiber has in many ways better properties than eptfe by lower activation of the inflammatory response and lower hemolysis .
a limitation of in vitro models is mainly represented by the absence of an endothelial layer in the circulating system . throughout the release of cytokines , the endothelium has a major role in mediating the interplay between the injured vessel wall and circulating blood cells [ 2426 ] .
this is effectuated by the release of cytokines and ( anti)thrombotic components as well as the expression of adhesion molecules .
prior to use in patients an animal model should prove the validity of the in vitro data .
nevertheless , all the other elements depicting the blood - graft phase boundary scene are present , while the use of human blood from one donor in test and control circuits is a major advantage for comparison of the materials .

Answer:
three different models , a modified chandler loop , roller pump , and a new ball valve model ( hemobile ) , were compared with regard to intrinsic damage of blood components and activation of platelets .
 the hemobile was used for testing of polymer tubes .

 high flow was not possible with the chandler loop .
 the roller pump and the hemobile could be adjusted to high flow , but he pump induced hemolysis .
 platelet numbers were reduced in the roller pump and chandler loop ( p < 0.05 ) , but remained high in the hemobile .
 platelet aggregation was reduced in all models .

 the hemobile was applied for testing vascular graft materials , and allowed different circuits circulated simultaneously at 37c .
 eptfe , dyneema purity uhmwpe fiber and pet fiber based tubes , all showed hemolysis below 0.2% and reduced platelet count and function .
 binding of fibrin and platelets was higer on pet , inflammatory markers were lowest on dyneema purity uhmwpe .

 we concluded that the hemobile minimally affects blood and could be adjusted to high blood flows , simulating arterial shear stress .
 the hemobile was used to measure hemocompatibility of graft material and showed dyneema purity uhmwpe fiber in many ways more hemocompatible than eptfe and pet .


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:
both tues and rcn - ube support the community to catalyze change within undergraduate biology education and , in effect , act synergistically .
tues supports change in the way courses are taught , development of new materials ( including new assessment materials to support these approaches ) , and research into undergraduate education in general .
tues funds can be used to support course development by funding faculty time and other resources , including some funds for initial purchase of instrumentation essential to the development and implementation of transformative changes in student laboratories and/or lecture classes .
tues funds also may be used for faculty development activities that prepare other faculty to incorporate these new ideas into their own teaching ( nsf , 2006 ) .
tues also supports evaluation , webinars , conferences , and a project information portal ( american association for the advancement of science [ aaas ] , 2011 ) .
the current ( fy2013 ) program has tracks ranging from small pilot projects with funding caps of $ 200,000 to large national projects with funding caps of $ 6 million .
the rcn - ube program focuses on forming alliances of faculty , professional societies , and institutions active in developing , among other things , learning in emerging technologies in the biology curriculum , strategies and approaches for engaging biology faculty in professional development , incorporating emerging subdisciplines into the biology curriculum , improving assessment of student learning , improving the transition of students from 2-yr to 4-yr institutions , and incorporating authentic research experience into undergraduate laboratory courses ( nsf , 2012b ) .
the coordination efforts may include holding workshops , generating websites , or other appropriate means of developing a community of practice .
the rcn - ube program has two tracks , a full proposal track that funds projects up to $ 500,000 and an incubator track that funds projects up to $ 50,000 .
the incubator track accepts proposals that request support for the initial development of networks that will catalyze positive changes in biology undergraduate education . about a half - dozen incubator awards
while the number of proposals submitted to the program has declined , the funding rates have remained high ( table 1 ) .
( the average funding rate across the 5 yr of the program is 41.8% ; this is nearly double the average nsf funding rate [ nsf , 2012a ] . )
yearly distribution of proposals and awards within the rcn - ube program data from nsf report server .
www.nsf.gov / awardsearch/. a glance at the recently funded projects within these programs ( see the supplemental material ) should help the reader understand the scope of these two programs and how they relate to one another .
principal investigators do not need to have an ongoing project in one program in order to apply to the other , but may apply to both programs , as appropriate .
tues serves all science , technology , engineering , and mathematics ( stem ) disciplines , as well as projects that involve interdisciplinary approaches , research on undergraduate stem education , assessment of student learning , and evaluation of teaching approaches .
biology proposals are handled by one of the nine teams ( biology , chemistry , computer science , engineering , geology , mathematics , physics , interdisciplinary , and research and assessment ) within the program . in 2012 ,
1007 proposals were submitted to the program . of these , only 97 ( 10% ) focused on biology education ( table 2 ) .
table 2 also shows that 41% of all stem graduates in the united states are biology majors , and 22% of all u.s .
if we compare these data with the results for engineering , which has 24% of all stem graduates each year and 14% of the stem faculty , we see a great disparity in the degree to which faculty in these two disciplines seek funding for instructional changes in their classrooms .
fully 28% of the tues proposals submitted in 2012 were submitted by engineering faculty , while only 10% were submitted by biology faculty .
distribution of tues type 1 proposals submitted during fy 2012 and the number of majors and faculty members in the united states in the stem disciplines data from nsf report server .
we chose to compare engineering and biology undergraduate education because both are undergoing major reorganization ; engineering due to the pressures from the accreditation board for engineering and technology , and biology due to the pressures of the association of american medical colleges / howard hughes medical institute report scientific foundations for future physicians ( aamc / hhmi , 2009 ) , as well as the vision and change initiative ( aaas , 2011 ) .
the reasons for these strikingly disproportionate proposal submissions , despite similar demands for change in engineering and biology , are not apparent .
it is our hope that articles such as this , along with frequent presentations by nsf staff at professional societies annual and regional meetings , will encourage the community of life sciences faculty to seek funding from this versatile program , which encourages a range of projects from small pilots to test new ideas through large multi - institutional collaborations designed to disseminate effective practices more broadly ( singer et al . , 2012 ) .
because rcn - ube is a relatively new program , its impact on undergraduate biology education is only beginning to emerge . designed specifically to develop communities of people who are working on similar projects , but who otherwise may be unaware of others with similar interests , it generated a flurry of proposals in the first 3 yr , but this was followed by a dramatic decrease in the number of submissions .
we are hopeful that the increase in the number of proposals between 2011 and 2012 represents an appreciation of the value of this program to build and strengthen current or future collaborative efforts , as well as an awareness of the program within the community .
it is certainly a program that can serve a crucial role in the development and dissemination of ideas generated to support the vision and change initiative call for action .
the number of proposals funded within any program depends not only on the number of proposals submitted but also on the quality of the proposals received .
writing a proposal for an educational initiative is essentially the same as writing a research proposal .
it is important to :
 be sure the proposal is being submitted to the appropriate program;clarify the subject matter to be addressed in the instructional materials or practices;establish the evidence for the effectiveness of the instructional practices that the project builds on and intends to adds to;describe outcomes from any preliminary work you have done to test the potential of the approach;present implementation plans succinctly , so panelists can easily understand them and judge their potential for success;state the outcomes expected and how they will be determined and documented ; andindicate the level of support and/or interest either by colleagues within the department or elsewhere .
be sure the proposal is being submitted to the appropriate program ; clarify the subject matter to be addressed in the instructional materials or practices ; establish the evidence for the effectiveness of the instructional practices that the project builds on and intends to adds to ; describe outcomes from any preliminary work you have done to test the potential of the approach ; present implementation plans succinctly , so panelists can easily understand them and judge their potential for success ; state the outcomes expected and how they will be determined and documented ; and indicate the level of support and/or interest either by colleagues within the department or elsewhere .
for example , to determine whether the project is appropriate for a particular program , read the program solicitation carefully ; program officers are always available via email or telephone to answer specific questions .
the program solicitation provides the names of program officers associated with the program , as well as links to recent awards .
the evidence base for instructional best practices can be found in journals such as this one , as well as in publications such as vision and change in undergraduate biology education : a call to action ( aaas , 2011 ) and discipline - based education research : understanding and improving learning in undergraduate science and engineering ( singer et al . , 2012 ) .
this literature provides information on instructional best practices that inform the project being proposed and ground it in that research base .
in addition to the tues and rcn - ube programs within nsf , there are a variety of other funding opportunities for faculty and students in the life sciences , including the following :
 the hhmi science education alliance helps
bring good ideas in science education to a broader audience by offering educators models of research - based curricula developed to engage college students in true scientific discovery as early as possible in their academic careers
( www.hhmi.org/grants/sea/index.html).the nih has internship , scholarship , and fellowship programs for undergraduates ( www.training.nih.gov/programs).the nih institutional research and academic career development awards help postdoctoral students develop teaching skills and pedagogical knowledge as they work with established faculty in minority - serving institutions , with the aim of facilitating the progress of postdoctoral candidates toward research and teaching careers in academia ( http://grants.nih.gov/grants/guide/pa-files/par-12-245.html).the u.s .
department of agriculture ( usda ) offers different pathway opportunities for students and recent graduates to work in agriculture , science , technology , math , environmental , management , business , and many other fields .
the usda offers internships to students and recent graduates to help them to excel in their chosen fields ( www.dm.usda.gov/employ/student/index.htm ) .
bring good ideas in science education to a broader audience by offering educators models of research - based curricula developed to engage college students in true scientific discovery as early as possible in their academic careers
the nih has internship , scholarship , and fellowship programs for undergraduates ( www.training.nih.gov/programs ) .
the nih institutional research and academic career development awards help postdoctoral students develop teaching skills and pedagogical knowledge as they work with established faculty in minority - serving institutions , with the aim of facilitating the progress of postdoctoral candidates toward research and teaching careers in academia ( http://grants.nih.gov/grants/guide/pa-files/par-12-245.html ) . the u.s .
department of agriculture ( usda ) offers different pathway opportunities for students and recent graduates to work in agriculture , science , technology , math , environmental , management , business , and many other fields .
the usda offers internships to students and recent graduates to help them to excel in their chosen fields ( www.dm.usda.gov/employ/student/index.htm ) .
the biology staff of the division of undergraduate education has compiled a resource for those seeking information on the nsf programs that support improvement of undergraduate education in biology .
this document includes helpful information on proposal preparation , insights into the review process , and post - award management .
while the information is useful for faculty in any discipline , the examples and advice given are oriented to the needs of biologists .
the document is updated in august of each year and can be obtained electronically by contacting helen vasaly ( hvasaly@nsf.gov ) .
the program officers and staff members at the nsf are looking forward to receiving your tues and rcn - ube proposals .

Answer:
many life sciences faculty and administrators are unaware of existing funding programs and of the strategies needed for writing an educationally related proposal .
 we hope to remedy this problem by making the life sciences audience aware of two national science foundation programs underutilized by the biology community .


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:
hailey - hailey disease ( hhd ) or familial benign chronic pemphigus first described in 1939 , is a rare autosomal dominant genodermatosis , which presents with recurrent vesicles , erythematous crusts and erosions in the areas subjected to friction , including , the neck and intertriginous areas .
abnormalities in the tonofilament  desmosome  keratin complex results in marked acantholysis , giving the histological appearance of a dilapidated brick wall , which is pathognomonic of the disease . ultra violet b rays
the treatment is often not satisfactory and hence , various modalities of treatment have been tried .
we describe a case of hhd with a positive family history , in which various treatment modalities were tried without any benefit but responded well to thalidomide .
a 30-year - old unmarried male presented with a history of recurrent painful fluid and pus filled lesions followed by painful erosions over the neck , axillae , trunk and groins of 15 years duration exacerbated over the past 10 - 15 days .
he gave family history of similar disease in his father , paternal grandmother and paternal uncles . before coming to us ,
he had been treated with dapsone following which he developed agranulocytosis and dapsone was discontinued .
several other treatment modalities including oral and topical antibiotics , corticosteroids were tried but resulted in only partial or temporary improvement .
large macerated plaques studded with foul - smelling pus along with erosions , fissures , and crusts were present on the anterior and the lateral aspect of the neck , axillae , back , lower abdomen , pubic area , gluteal cleft , groins , upper medial thighs and scrotum [ figure 1 ] .
erosions and crusts were seen on the glans with purulent foul smelling discharge in the prepucial sac , sparing rest of the penis .
the skin biopsy specimen for histopathological reconfirmation of the diagnosis revealed focal suprabasilar clefting , few acantholytic cells , intercellular edema with dilapidated brick wall appearance which confirmed our diagnosis [ figures 2 and 3 ] . macerated plaques with erosions and crusts over the scrotum , glans penis and upper medial thighs focal suprabasal clefting and lacunae ( h and e , 10 ) suprabasalar clefting with few acantholytic cells , intercellular edema and dilapidated brick wall appearance ( h and e , 40 ) patient was started on intravenous ( iv ) betamethasone 4 mg , 8 h which was tapered off with the introduction of 40 mg of oral prednisolone , iv ceftriaxone 1 mg twice daily and later iv piperacillin - tazobactam based on pus culture and sensitivity reports along with a combination of fusidic acid and betamethasone for topical application .
he continued to develop new lesions with the deterioration of his general condition and was febrile throughout . in spite of controlling the secondary infection , the vesicular eruptions persisted .
therefore , he was started on oral thalidomide 100 mg three times a day and a combination of betamethasone and gentamycin for topical application .
marked improvement was seen within a week of starting thalidomide [ figure 4 ] and hence we discontinued corticosteroid after rapid tapering of its dose and continued treating him with oral thalidomide 100 mg three times a day for one more week , which was then tapered off in 3 - 4 weeks and maintained on 50 mg daily .
after 6 months of receiving 50 mg thalidomide , the drug was stopped in view of no recurrence of the lesions . he has improved well and comes to us for regular follow - up .
mucosal involvement is unusual in hhd and has been very rarely reported and can involve oral , conjunctival , vaginal , or in very rare instances esophageal mucosa .
our patient had oral , pharyngeal , and genital mucosal involvement , which were resistant to the symptomatic treatment .
apart from the symptomatic therapy , drugs such as corticosteroids , dapsone , etretinate , methotrexate , cyclosporine , topical 5-fluorouracil , topical vitamin d analogs , topical zinc oxide , alefacept , psoralen plus ultraviolet a therapy and photodynamic therapy have been tried with varying results .
as hhd is often recalcitrant to treatment , further options including invasive methods such as grenz ray therapy , carbon dioxide laser abrasion , erbium : yag laser ablation , dermabrasion , electron beam therapy , botulinum toxin and full - thickness excision of affected skin with repair by split - thickness grafting have been reported as useful in treatment of hhd . in the study conducted by galimberti et al .
hhd is linked to mutations in the calcium - transporting atpase type 2c member 1 gene encoding the human secretory pathway ca / mn atpase .
topical gentamicin was found to be very effective in inducing remission in a hhd patient carrying a premature stop mutation .
it may be an important alternative in the treatment of hhd in patients not responding to the other modalities of treatment or when the conventional drugs are contraindicated .
mucosal involvement is unusual in hailey - hailey disease ( hhd ) and has been very rarely reported .
our patient had oral , pharyngeal , and genital mucosal involvement.thalidomide may be an important alternative in the treatment of hhd in patients not responding to the other modalities of treatment or when the conventional drugs are contraindicated .

mucosal involvement is unusual in hailey - hailey disease ( hhd ) and has been very rarely reported .
thalidomide may be an important alternative in the treatment of hhd in patients not responding to the other modalities of treatment or when the conventional drugs are contraindicated .

Answer:
familial benign chronic pemphigus or hailey - hailey disease ( hhd ) is a rare autosomal dominant disorder characterized by the development of recurrent blisters and erosions in the intertriginous areas .
 various topical and systemic treatment options include corticosteroids , topical 5-fluorouracil , topical vitamin d analogs , topical zinc oxide , dapsone , psoralen plus ultraviolet a , systemic retinoids , cyclosporine , methotrexate , and photodynamic therapy . in recalcitrant cases , further options including , invasive methods such as grenz ray therapy , carbon dioxide laser abrasion , and erbium : yag laser ablation , dermabrasion , electron beam therapy , botulinum toxin , and full - thickness excision of affected skin with repair by split - thickness grafting have been reported as useful in treatment of hhd .
 we describe a case of hhd who was treated with several treatment modalities including antibiotics , corticosteroids , and dapsone earlier and when presented to us had a severe recalcitrant disease .
 thalidomide , as a modality of treatment has been successfully used in few cases earlier .
 our patient responded well to thalidomide .


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:
as is the most common cause of left ventricular outflow obstruction in children and adults . it is most common type of valvular heart disease in europe and north america , occurring in 27% of the population over 65 years of age .
medical therapy alone is not effective for the long - term management of aortic valve disease , thus valve replacement remains the standard of care in patients with an acceptable risk profile .
we present a case of critical as with significant symptom manifested as chest pain that was managed successfully without surgical avr or tavr .
we will also briefly review incidence , etiology , grading of as and current guidelines for avr .
a 91-year - old gentleman with history of hypertension , dyslipidemia and as presented to our office on 7/2015 with complaints of new onset sub sternal burning pain of 6 weeks duration .
prior to 6 weeks patient could walk 2 blocks on level ground without shortness of breath or chest pain .
blood pressure was 140/90 mm hg and pulse was regular at 60 beats per minute .
cardiovascular exam revealed a grade 4/6 ejection systolic murmur best heard in the right second intercostal region radiating bilaterally to the neck .
ecg revealed left ventricular hypertrophy ( lvh ) with non specific st - t wave changes in inferior leads ( figure 1 ) .
echocardiography ( echo ) done in may of 2014 had revealed critical as with aortic valve area of 0.6 - 0.7 centimeter square and ejection fraction of 65 percent . the aortic valve ( av ) was heavily calcified .
aortic valve peak velocity ( av vmax ) 4.66 m / s ( figure 2 ) .
the patient was directly referred for a cardiac catheterization to evaluate his coronary anatomy prior to avr .
hemodynamic measurement revealed left ventricle ( lv ) pressure 240/0 with left ventricular end diastolic pressure ( lvedp ) of 10 .
pulmonary artery wedge pressure ( pawp ) , mean of 24 , right atrium ( ra ) mean of 8 , right ventricle ( rv ) 60/10 with an right ventricular end diastolic pressure ( rvedp ) of 14 , pulmonary artery ( pa ) 60/17 .
the aortic valve area was calculated at 0.6 centimeter square , which was unchanged from echo done may 1 , 2014 .
the left ventriculogram in the right anterior oblique ( rao ) view revealed normal lv systolic motion and ejection fraction of 55 - 60 percent . left main coronary artery revealed a common ostium - giving rise to the left anterior descending ( lad ) and the circumflex .
right coronary artery ( rca ) revealed a 99 % ostial narrowing ( figure 3 ) .
lad revealed a 60 % narrowing in its proximal segment and a 90% ostial diagonal narrowing ( figure 4 ) .
after a detailed discussion involving the patient , his son , interventional cardiologist and the cardio thoracic surgeon , patient requested that only pci of the rca be considered , as the chest pain was of recent duration with no change in aortic valve finding .
thus , a successful pci was done in the proximal rca with a bare metal stent ( figure 6 ) .
patient did extremely well after pci of the rca and the patient has remained asymptomatic to date .
thus , this new onset chest pain in patient with critical as was due to concomitant coronary artery lesion and was amenable to stenting and thus spared this elderly patient from the aortic valve replacement which would have been a high risk surgery for him .
as is the most common valvular heart condition in the developed world , affecting 3% of people between ages 75 and 85 and 4% of people over age 85 .
congenitally unicuspid , bicuspid , tricuspid , or even quadricuspid valves may be the cause of as . in adults who develop symptoms from congenital as
the main causes of acquired as include degenerative calcification and , less commonly , rheumatic heart disease .
other , infrequent causes of as include obstructive vegetations , homozygous type ii hypercholesterolemia , paget disease , fabry disease , ochronosis , and irradiation . based upon a variety of hemodynamic and natural history data
, clinicians generally grade the severity of stenosis as mild , moderate , severe , or critical .
grading of as are as follows : i ) mild : valve area exceeds 1.5 cm ; transvalvular velocity 2.0 to 2.9 m / s ; mean gradient < 20 mmhg ; ii ) moderate : valve area of 1.0 to 1.5 cm ; transvalvular velocity 3.0 to 3.9 m / s ; mean gradient 20 to 39 mmhg ; iii ) severe : valve area is less than 1.0 cm ; transvalvular velocity 4 m / s ; mean gradient 40 mmhg .
the term critical stenosis was defined based upon theoretical considerations showing that the aortic valve area must be reduced to one - fourth of its natural size before significant changes in circulation occur . as a result , since the triangular orifice area of the normal ( adult ) aortic valve is approximately 3.0 cm , an area exceeding 0.75 cm would not be defined as critical .
avr and tavr remain the only treatment proven to reduce the rates of mortality and morbidity in this condition . under current guidelines , the onset of symptoms of exertional angina , syncope and dyspnea in a patient who has severe as is a class i indication for surgery .
the annual rate of sudden death in patients with this condition is estimated at 1% to 3% but the surgical mortality rate in avr has been as high as 6% . with improvements in surgical techniques and prostheses , mortality rates have been reduced to 2.42% making a case for earlier intervention .
tavr has become widely available , but further investigation into its use in this patient cohort is warranted . while assessing the cases of asymptomatic as we have both traditional as well as novel markers at our disposal now . left ventricular ejection fraction ( lvef ) < 50 percent , peak aortic jet velocity > 4.0 m / s , valve area < 1 cm and mean pressure gradient > 40 mm hg are the traditional markers to denote severe as in asymptomatic patients . while , indexed left atrial size > 12.2 cm / m , lvh with wall thickness > 15 mm , global left ventricular longitudinal strain < 15.9 , bnp ( b - natriuretic peptide ) level > 130 pg / ml and increase in mean pressure gradient of > 20 mm hg during exercise testing are the novel markers of asymptomatic severe as .
bnp level does not appear to be significantly associated with the degree of as severity but does reflect heart failure status .
the american college of cardiology and american heart association ( acc / aha ) have issued the following recommendations for avr , based on the severity of stenosis and on whether the patient has symptoms : i ) severe stenosis , with symptoms : class i recommendation ( surgery should be done ) . without surgery ,
these patients have a very poor prognosis , with an overall mortality rate of 75% at 3 years ; ii ) severe stenosis , no symptoms , in patients undergoing cardiac surgery for another indication ( example coronary artery bypass grafting , ascending aortic surgery , or surgery on other valves ) : class i recommendation for concomitant aortic valve replacement ; iii ) moderate stenosis , no symptoms , in patients undergoing cardiac surgery for another indication : class iia recommendation ( i.e. , aortic valve replacement is reasonable ) ; iv ) very severe stenosis ( aortic peak velocity > 5.0 m / s or mean pressure gradient 60 mm hg ) , no symptoms , and low risk of death during surgery : class iia recommendation ; v ) severe stenosis , no symptoms , and an increase in transaortic velocity of 0.3 m / s or more per year on serial testing or in patients considered to be at high risk for rapid disease progression , such as elderly patients with severe calcification : class iib recommendation ( surgery can be considered ) .
on revisiting the above case description we realize that the patient did have critical as but was asymptomatic .
his chest pain was only due to concomitant coronary artery disease but was not due to as per se .
age and comorbidity of the patient posed a high risk for coronary artery bypass graft ( cabg ) with avr .
besides , the patient s symptoms were of new onset and subsequent cardiac catheterization revealing critical rca stenosis and the patient s preference for treating the cause of his recent symptoms , encouraged us to think otherwise . the decision to perform pci alone with the belief that this chest pain and cad would be amenable to the minimal risk procedure paid dividends .
in addition , patient received a bare metal stent with the option of undergoing surgical avr if symptoms were not relieved .
awareness amongst physicians about the fact that all critical aortic stenosis with chest pain may not require aortic valve replacement is important .
this can lead to less invasive treatment tailored to the need of the patient especially in those with advanced age , significant comorbidities and an extremely high risk for cabg with avr and can also result in decreased cost of care .
pharmacological nuclear stress testing may be another modality that can be used to differentiate etiology of the symptoms .

Answer:
aortic valve replacement ( avr ) remains the cornerstone of treatment for symptomatic critical aortic stenosis ( as ) .
 it is a class i indication that symptomatic patients with critical as undergo either surgical or transcatheter aortic valve replacement ( tavr ) .
 we present a patient with critical as and new angina that was managed successfully with percutaneous coronary intervention ( pci ) of the right coronary artery .
 physicians should consider that not all patients with critical as and angina necessarily require avr .
 concomitant pathology leading to the symptoms should be carefully ruled out .
 this leads to a less invasive , cost effective care plan especially in patients with advanced age and comorbidities for which any type of surgical valvular intervention may pose high risk .


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:
bullous systemic lupus erythematosus ( bsle ) is a subepidermal blistering disease that occurs in a subset of patients with systemic lupus erythematosus ( sle ) [ 1 , 2 ] .
cutaneous lesions are reported during the course of sle in 76% of patients ; however , it has been reported that bsle is very rare and occurs in less than 1% of patients with sle [ 35 ] .
clinically , in addition to the features of sle , the bsle patients especially present with a rapid , widespread development of tense fluid - filled vesicles and bullae .
moreover , this blistering disease may vary from a small group of vesicles to large tense blisters with urticarial eruptions , erosions , itching , and crustations .
histologically , bsle is characterized by a subepidermal blister , with a predominantly neutrophilic dermal infiltrate and only occasional eosinophils .
furthermore , immunofluorescence examination showed linear deposition of lgg , lga , c3 , and c1q along the basement membrane zone [ 5 , 6 ] .
because of the particularly clinical and histological presentation of bsle , camisa and sharma proposed diagnostic criteria for bsle ; these include a diagnosis of sle based on the following criteria of the acr ; vesicles and bullae mainly located on sun - exposed areas ; the histopathology is characterised by subepidermal bullae with microabscesses of neutrophils in the dermal papillae , similar to those found in dermatitis herpetiformis and deposition of igg , igm , or both and often iga in the basement membrane zone .
although blse may exhibit any of the symptoms associated with sle , the onset and course of blistering eruption do not necessarily parallel the activity of the systemic involvement .
furthermore , the therapeutic options for sle are not usually fit for bsle [ 9 , 10 ] . in some cases
, the eruption flared after systemic corticosteroid administration for sle [ 11 , 12 ] .
however , most of the patients have a striking therapeutic response to dapsone [ 1316 ] . a response may be seen with very small doses of dapsone . in the case of the present paper ,
other drugs such as cyclophosphamide , azathioprine , and mycophenolate mofetil and biologic drugs may also be effective for bsle treatment . in the part of literature review , we provide a review of all the available treatment options for bsle .
steroids and antimalarials are the standard treatments for the cutaneous manifestations of sle . in unresponsive patients , azathioprine and high dose or pulse steroids , cyclosporin , and pulse cyclophosphamide are the most commonly used alternative therapies [ 1820 ] .
dapsone is less used in the control of the sle rash but has a dramatic improvement in the eruption of bsle patients [ 15 , 16 ] .
we also found that a 22-year - old woman with bsle had multiple tense vesiculobullous lesions on the face , trunk , and limb ( figure 1 ) .
a biopsy from the upper limb showed a subepidermal blister with a predominantly neutrophilic dermal infiltrate and only occasional eosinophils ( figure 2(a ) ) .
immunofluorescence showed a granular band of c1q , c3 , and igg at the basement membrane ; less iga and igm were observed ( figures 2(b)2(f ) ) .
the skin condition showed no response in the methylprednisolone , while a considerable improvement after dapsone administration was observed .
regarding the special clinical feature and the discriminative therapies from the sle treatments , we review all the available treatment for bsle .
dapsone is a sulfone that has played a critical role in the eradication of leprosy . besides , a number of cutaneous eruptions are effectively controlled by dapsone . due to these eruptions that are largely characterized by the presence of cutaneous neutrophilic dermal infiltrate , such as dermatitis herpetiformis and the inflammatory variant of epidermolysis bullosa acquisita
, the mechanism of its anti - inflammatory action mainly relies upon its inhibition of the functions of polymorphonuclearleukocytes and of complement activation via the alternative pathway that has been postulated [ 15 , 23 ] .
although a new or recurrent rash was considered a factor of sle disease activity index , the eruption of bsle was not constantly associated with a flare of sle .
consequently , because of being unparallel with the disease activity , the eruption of bsle patients is often unresponsive to corticosteroid therapy . due to the striking histologic resemblance to dermatitis herpetiformis
, the patients who were treated with dapsone ( 2  mg / kg / day ) usually obtained a dramatic improvement in the eruption .
patients tend to have an efficacious response with cessation of new blister formation in 1 - 2 days and healing of existing lesions within several days . a relatively low dose ( 2550  mg ) has also been shown to have a response [ 1 , 15 , 24 ] .
interestingly , improvement of the eruption did not correlate with amelioration of the systemic manifestations .
the dramatic response to dapsone therapy demonstrated that dapsone is useful in treating bullous lesions of sle [ 5 , 15 , 16 , 26 ] .
notably , the blistering eruption was not improved by dapsone in some cases , and even worsening has been noted after its administration . it has been reported that patients with bsle , who initially presented with lesions clinically resembling erythema multiform , experienced exacerbation of their disease with dapsone [ 2729 ] .
furthermore , dapsone has been assigned to pregnancy category c ; bsle patients with pregnancy might not be fit for administration of this drug .
hemolysis and hepatic and renal toxicity usually accompany administration of the drug in a dose related fashion [ 3134 ] ; therefore its clinic use was confined and a careful monitoring of its toxicity is required .
corticosteroids are usually required to improve clinical symptoms and laboratory abnormalities and are still a mainstay for inducing remission in sle patients [ 18 , 20 , 35 ] .
unexpectedly , many bullous sle patients tend to be unresponsive to systemic corticosteroid therapy that has been described .
furthermore , in some cases of sle patients , the eruption flared a few days after systemic corticosteroid administration [ 11 , 12 ] .
interestingly , some patients responded effectively to corticosteroids , although they required relatively high doses .
a patient with sle who presented with vesiculobullous lesions during the third trimester of pregnancy has been presented .
a skin biopsy of this patient was performed , and it showed significant necrosis of keratinocytes in the epidermis and granular , dense , and continuous deposits of moderate igg positivity in the basement membrane zone .
dapsone has been assigned to pregnancy category c. the pregnant woman treated with high - dose corticosteroids obtained a satisfactory response .
as the dapsone administration often causes hepatic and renal toxicity [ 32 , 33 , 3840 ] , prednisone alone or in combination with low doses dapsone might be the treatment of choice for these bsle patients .
these observations demonstrated that corticosteroids may act as an alternative treatment for bsle when patients are unresponsive or unfit for other drugs .
biologic agents , such as infliximab , rituximab , and anakinra , have emerged as effective therapies for treating a wide spectrum of diseases which includes various rheumatic , gastrointestinal , and cutaneous diseases [ 4144 ] .
the involvement of all of the key components ( especially cytokines and immune cells ) of the immune system in the pathogenesis of sle offers many potential targets for therapeutic management of this disease .
b cells , a critical immune cell , which can act as antigen - presenting cells , differentiate into plasma cell to produce pathogenic autoantibodies and secrete various cytokines and chemokines in the immune response [ 45 , 46 ] .
these functions of the b cell support the fact that it plays an important role in the development of pathogenesis of sle . therefore , use of b cell depletion therapy in sle has emerged as a novel and promising therapeutic alternative for sle patients [ 4749 ] .
rituximab which is a chimeric monoclonal antibody that reacts with cd20 , an antigen that is present on immature , naive , and memory b cells but not on mature plasma cells , has been approved in the treatment of sle . up to now
the patient was treated with hydroxychloroquine ( hcq ) twice daily , mycophenolate mofetil 1000  mg / d , and varying doses of corticosteroids , while the eruption was not improved .
dapsone and azathioprine were added but had to be stopped because of elevated liver enzymes and leukopenia .
mycophenolate mofetil was increased to 2000  mg / d , but her skin disease remained active .
the skin lesions improved within 10 days after the first dose and cleared by day 15 after the second dose . furthermore , prednisone was successfully tapered , and the patient has remained free of recurrence of cutaneous and oral blistering lesions .
the results of this case suggest a potential role for treatment of refractory bsle with rituximab .
methotrexate ( mtx ) has been widely proved to be an effective agent in control of the rheumatoid arthritis .
it has proved that mtx was beneficial in sporadic cases of scle refractory to therapy with conventional therapy [ 5254 ] , such as antimalarials and corticosteroids .
furthermore , in a randomized and double - blind trial in 41 patients with sle , mtx reveals a role for controlling the skin lesions in 75% of cases , with a mean reduction of prednisone dose of 44% .
these reports demonstrated that mtx could represent a valid therapeutic option in controlling the cutaneous sle and in sparing the steroid dose .
however , bsle is a subepidermal blistering disease that occurs in a subset of patients with systemic lupus erythematosus ( sle ) .
cutaneous lesions of bsle are reported during the course of sle in less than 1% of patients , while lesions are not in line with the disease activity .
, a rapid and full resolution of cutaneous lesions was obtained with methotrexate alone . a case of 40-year - old female with systemic lupus erythematosus ( sle ) developed a severe bullous eruption on sun - exposed areas , while the previous manifestations of the disease were quiescent . in consideration of prior intolerance to many drugs ,
hcq is a commonly used drug for controlling the cutaneous lesions and the disease activity of the sle [ 58 , 59 ] , while it does not act effectively in the eruption of bsle .
the conventional treatment for sle only revealed modest improvement in steroids and antimalarials . although cyclophosphamide has been shown to produce moderate improvement of skin lesions of sle , the beneficial role in bsle has not been demonstrated .
mycophenolate mofetil ( mmf ) has been widely used for suppressing the lupus activity , while it also was not valid for bsle , even at a high dose [ 10 , 37 ] . in cases nonresponsive to dapsone
, the eruption has been controlled by prednisone or with combination therapy of prednisone and azathioprine .
in the treatment of bullous sle , dapsone is the effective basic therapy , and it often induces a dramatic response . in some cases , where an adequate response is not achieved with dapsone or the sle disease activity index is high , other immunosuppressants , such as prednisolone , methotrexate , and azathioprine , can be used for controlling the eruption and suppressing the systemic symptoms . moreover , in some special case , where dapsone administration or other chemical drugs ( mtx , azathioprine , etc . )

Answer:
bullous systemic lupus erythematosus ( bsle ) is an autoantibody - mediated vesiculobullous disease in patients with sle .
 autoimmunity in bsle is characterized by the presence of circulating anti - type vii collagen antibodies .
 bsle patients often present with multiple , tense , clear fluid - filled vesicles and bullae overlying erythematous edematous plaques .
 skin biopsy from bsle patients shows subepidermal bullae with numerous neutrophils and only occasional eosinophils .
 furthermore , immunofluorescence examination showed linear deposition of lgg , lga , c3 , and c1q along the basement membrane zone .
 bsle patients with corticosteroids treatment constantly do not receive a marked improvement , while dapsone generally dramatically improved the skin condition .
 recently , it has been reported that quite a few cases of bsle were successfully treated with other immune suppressive drugs .
 therefore , a comprehensive review of the treatment of bsle would be beneficial to cure the disease .


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

Paper text:
the facial nerve trunk exits through the stylomastoid foramen , and enters the parotid gland where it divides into the cervicofacial and temporofacial divisions . then divides into five peripheral branches to supply the muscles of facial expression ( 1 ) .
the branches arising from the rami form to parotid plexus in parotid gland . the superior buccal nerve arising from temporofacial ramus and the inferior buccal nerve arising from the cervicofacial ramus form to the buccal plexus without parotid gland ( 1 ) . the zygomatic ( 2 ) , the marginal mandibular ( 3 - 5 ) , the buccal ( 6 ) , and the temporal branches ( 7 ) of the facial nerve were investigated by many researchers . different surgical approaches and landmarks to the trunk of the facial nerve have been reported ( 8 - 12 ) .
many landmarks such as the mastoid process ( 8 - 10 ) , the transverse process of the atlas ( 8) and axis ( 11 ) , the temporomandibular joint , the angle of the mandible ( 9 , 11 ) , insertion of the sternocleidomastoid muscle , pointer cartilage of the ear ( 10 ) , tragal pointer ( 11 ) and the marginal mandibular branch of the facial nerve ( 12 ) can be used to identify the trunk of the facial nerve . but
identification of this trunk may be difficult because it is encompassed by dense connective tissue ( 13 ) . in this paper
the double facial nerve trunk emerged from the stylomastoid foramen and petrotympanic fissure was found in a 65-yr - old caucasian male cadaver during a routine dissection course .
firstly , the skin and superficial fascia between the mastoid process and ramus of the mandible were reflected in all subjects .
the anterior border of the parotid gland was carefully elevated and the rami of the nerves followed proximally up to the stylomastoid foramen under a stereomicroscope ( stemi 2000 ; carl zeiss , jena , germany ) .
finally , magnetic resonance ( mr ) imaging was performed by using 1.5 t scanner to this cadaver . to be able to demonstrate the stylomastoid foramen and the petrotympanic fissure in same section
, we obtained t1 and t2 weighted oblique sagittal scans . in the present cadaver , difference with the exit point of the facial nerve was observed . in this specimen ,
in this side , although cervicofacial ramus of the facial nerve exited from the stylomastoid foramen , temporofacial ramus of the facial nerve exited from petrotympanic fissure ( fig .
the buccal branch dividing from temporal branch of temporofacial ramus and first buccal branch dividing from cervicofacial ramus formed to first buccal plexus .
the buccal branch dividing from zygomatic branch of temporofacial ramus and second buccal branch dividing from cervicofacial ramus formed to second buccal plexus ( fig .
2 ) . these two buccal plexuses and other branches formed to structures like to polygon ( fig .
the temporofacial ramus exiting from petrotympanic fissure was seen on magnetic resonance image ( fig .
several studies relating to the trunk of the facial nerve have been reported in the literature ( 14 - 19 ) .
katz and catalano ( 14 ) reported three cases ( 3% ) presenting two main trunks , known as the major and minor trunks , with the latter joining the larger temporofacial division , the origin of the main buccal branch .
the minor trunk of the facial nerve was noted in eight of 30 cases ( 26.7% ) and , in all of them , the minor trunk entered the lower division of the facial nerve ( 15 ) .
botman and jongkees ( 16 ) reported that the facial nerve within the mastoid segment of the temporal bone can split into two or three branches , and each branch exits through a separate osseous foramen . in this study ,
a trunk of the facial nerve exiting from the petrotympanic fissure is present one case .
in addition , baker and conley ( 17 ) reported the possibilities of trifurcation , quadrifurcation , or even a plexiform branching pattern of the trunk of the facial nerve .
salame et al . ( 18 ) identified one case of trifurcation out of 46 cases .
but we did not identify any case of trifurcation , quadrifurcation or a plexiform branching pattern of the trunk .
the facial nerve can easily be injured by sharp or penetrating trauma to the cheek .
there are number of studies concerning protection extracranial branches of the facial nerve during plastic surgery procedures and operations intended for the parotid gland , but relatively little care has been given exit point of the facial nerve .
knowledge of the trunk of the facial nerve is essential for preserving the nerve during surgical procedures of the mastoid process , parotid gland , the cranial base and the facial nerve ( 13 , 17 ) . in this study , we exposed exit point of the trunk of the facial nerve through the cranium .
surgeons should be aware of the possible anatomical variations of the trunk of the facial nerve , because a trunk of the facial nerve exiting from the petrotympanic fissure may also be present .

Answer:
there are several studies concerning branches of the facial nerve , but we encountered less information about the trunk of the facial nerve in the literature . during the routine dissection of a 65-yr - old caucasian male cadaver , double facial nerve trunk emerged from the stylomastoid foramen and petrotympanic fissure were encountered .
 because of an extremely rare variation , we presented this case report .
 in addition this cadaver had two buccal plexuses .
 these plexuses and other branches were formed to structures like to polygon .
 these anatomic peculiarities were described , photographed and illustrated .
 finally , magnetic resonance imaging was performed by using 1.5 t scanner to this cadaver .
 the facial nerve trunk can be damaged during surgical procedures of the parotid gland tumours and submandibular region .
 surgeons who are willing to operate on this area should be aware of the possible anatomical variations of the facial nerve trunk .


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:
strains carrying proa - tev - rpt1 were grown in 6 l of sd medium to od600 0.8 to 1.2 .
cells were harvested , washed once with ice - cold water and drop - frozen in liquid nitrogen .
frozen yeast samples were then ground using an mm301 grinding mill ( restch ) under liquid nitrogen following manufacturer s instructions , or using a mortar and a pestle as previously described24 .
ground powder was hydrated in proteasome buffer ( 50 mm tris - hcl [ ph7.5 ] , 5 mm mgcl2 , 1 mm edta , and 10% glycerol ) supplemented with 2 mm atp , protease inhibitor tablets ( complete , roche ) , 2 mm pmsf , 1 mm benzamidine , 10 g / ml pepstatin a , and 1 g / ml antipain .
cell extracts were cleared at 30,000  g for 30 min at 4c , and the supernatants were mixed with rabbit igg resin ( cappel , mp biomedicals ) for 90 min at 4c .
resins were collected at 900  g for 2 min at 4c and washed with proteasome buffer containing 50 mm nacl three times , followed by a final wash with proteasome buffer alone .
bp1 was then released from the resin by incubating with actev protease ( invitrogen ) at 2.5 unit / l culture in proteasome buffer containing 2 mm atp and protease inhibitors for 1 hr at 30c .
eluates were concentrated using ultrafree-0.5 centrifugal filter device with 30 kda nmwl ( millipore ) .
strains carrying proa - tev - rpt1 were grown in 6 l of sd medium to od600 0.8 to 1.2 .
cells were harvested , washed once with ice - cold water and drop - frozen in liquid nitrogen .
frozen yeast samples were then ground using an mm301 grinding mill ( restch ) under liquid nitrogen following manufacturer s instructions , or using a mortar and a pestle as previously described24 .
ground powder was hydrated in proteasome buffer ( 50 mm tris - hcl [ ph7.5 ] , 5 mm mgcl2 , 1 mm edta , and 10% glycerol ) supplemented with 2 mm atp , protease inhibitor tablets ( complete , roche ) , 2 mm pmsf , 1 mm benzamidine , 10 g / ml pepstatin a , and 1 g / ml antipain .
cell extracts were cleared at 30,000  g for 30 min at 4c , and the supernatants were mixed with rabbit igg resin ( cappel , mp biomedicals ) for 90 min at 4c .
resins were collected at 900  g for 2 min at 4c and washed with proteasome buffer containing 50 mm nacl three times , followed by a final wash with proteasome buffer alone .
bp1 was then released from the resin by incubating with actev protease ( invitrogen ) at 2.5 unit / l culture in proteasome buffer containing 2 mm atp and protease inhibitors for 1 hr at 30c .
eluates were concentrated using ultrafree-0.5 centrifugal filter device with 30 kda nmwl ( millipore ) .

Answer:
substrates of the proteasome are recognized and unfolded by the regulatory particle ( rp ) , then translocated into the core particle ( cp ) to be degraded1 .
 a hetero - hexameric atpase ring , containing subunits rpt1-rpt6 , is situated within the base subassembly of the rp1 .
 the atpase ring sits atop the cp , with the rpt c - termini inserted into pockets in the cp26 .
 we have identified a novel function of the rpt proteins in proteasome biogenesis through deleting the c - terminal residue from each rpt .
 our results indicate that assembly of the hexameric atpase ring is templated on the cp .
 we have also identified an apparent intermediate in base assembly , bp1 , which contains rpn1 , three rpts , and hsm3 , a chaperone for base assembly .
 the rpt proteins with the strongest assembly phenotypes , rpt4 and rpt6 , were absent from bp1 .
 we propose that rpt4 and rpt6 form a nucleating complex to initiate base assembly , and that this complex is subsequently joined by bp1 to complete the rpt ring .
 our studies show that assembly of the proteasome base is a rapid yet highly orchestrated process .


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

Paper text:
baseline flt imaging in this patient with metastatic malignant melanoma demonstrated splenic ( s ) , peritoneal ( p ) and bm metastases .
after 14 days of treatment with a novel antiangiogenesis agent the upper abdominal peritoneal deposit ( vertical arrow ) had substantially decreased activity while the lower abdominal focus could no longer be visualised . uptake at sites of baseline abnormality in the spleen ( horizontal arrow ) and right femoral bm ( oblique arrow ) were relatively photopaenic compared to adjacent normal tissues . fdg  pet scanning ( not shown ) demonstrated no change over the same period .
most clinical studies of hypoxia imaging have utilized the nitroimadozole , [ f]fluoromisonidazole ( fmiso ) .
slow blood pool clearance and high lipophilicity contribute to significant background activity and relatively low contrast between hypoxic and normal tissues . a new agent
[ f]fluoro - azomyacinarabinofuranoside ( faza ) has lower lipophilicity as demonstrated by low brain uptake in the left panel .
more rapid blood clearance with similar absolute uptake in hypoxic tissue leads to higher contrast as demonstrated in this comparative study of faza ( left ) and fmiso ( right ) scans in a patient with locally advanced retropharyngeal cancer .

Answer:
despite the excellent clinical performance of fluorodeoxyglucose ( fdg ) as a cancer - imaging agent for positron emission tomography ( pet ) , false positive and false negative results can be problematic in some clinical settings .
 radiopharmaceutical development has recently focussed on the search for new pet tracers that could complement or replace fdg in such settings . due to the general availability and favourable physical properties of fluorine-18
 , much effort has been directed to fluorinated compounds .
 the most promising of these are discussed .


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:
primary plasma cell leukemia ( ppcl ) is a very aggressive form of plasma cell disorder .
ppcl is very rare , reported in only 4 - 6% of patients with multiple myeloma ( mm ) .
ppcl is defined as the presence of more than 20% plasma cells in the peripheral blood and an absolute plasma cell count greater than 2  10/l , without previous evidence of mm .
consistent with the high tumor burden , extramedullary involvement , such as hepatosplenomegaly , lymphadenopathy , soft - tissue plasmacytomas , or leptomeningeal infiltration , is more frequent in ppcl than in mm .   despite the development of new agents , such as proteasome inhibitors or immunomodulatory drugs ( imids ) , for plasma cell disorders , the median overall survival of ppcl
although ppcl is difficult to treat , high - dose melphalan followed by autologous stem cell transplantation ( auto - sct ) and/or allogeneic stem cell transplantation ( allo - sct ) seems to improve outcomes in younger selected patients .
however , patients with ppcl who had central nervous system ( cns ) relapse after auto- and/or allo - sct were refractory to various treatments , and had an extremely poor prognosis .
we herein present a ppcl patient with cns relapse after allo - sct who underwent concurrent intrathecal therapy ( it ) and radiotherapy ( rt ) followed by maintenance therapy with pomalidomide and low - dose dexamethasone ( pd ) .
a 46-year - old man without a previous significant medical history was referred to our hospital with complaints of anorexia and generalized fatigue .
laboratory findings revealed significant abnormalities , including a white blood cell ( wbc ) count of 19.710/l with 45% plasma cells , a hemoglobin level of 11.6 g / dl , a platelet count of 7.010/l , a creatinine level of 7.63 mg / dl , and a ldh level of 301 iu / l ( table 1 ) . on a peripheral blood smear ,
the plasma cells were medium - sized , with round nuclei , basophilic cytoplasm , and occasional cytoplasmic vacuoles ( figure 1a ) .
g / l , and the serum free light chain ( flc ) k/ ratio was 161.11 ( table 1 ) . in this case , a m - component of the igg - k type was identified by serum protein electrophoresis .
moreover , flow cytometry on the peripheral blood showed that these plasma cells were positive for cd38 , cd49e , cd54 , cd138 and cytoplasmic kappa light chain .
t(11;14)(q13;q32 ) in 9 metaphase cells ( figure 1b ) and 46,xy in 11 metaphase cells , and a fluorescent in situ hybridization analysis revealed ccnd1/igh gene fusion rearrangement .
the patient was admitted to an intensive care unit ( icu ) for continuous hemodiafiltration ( chdf ) . on the same day
, we started induction therapy with lenalidomide ( 15 mg / day orally on days 1 - 14 ) , bortezomib ( 1.3 mg / m subcutaneously on days 1 , 4 , 8 , and 11 ) , and low - dose dexamethasone ( 20 mg / day orally on days 1 , 2 , 4 , 5 , 8 , 9 , 11 , and 12 ) , also known as rvd induction therapy , each for a 21-day cycle .
eight days after starting the induction therapy , the circulating plasma cells in the peripheral blood disappeared , and he was transferred from the icu after withdrawal of chdf . after a total of 3 cycles of chemotherapy , the laboratory abnormalities markedly subsided , consistent with a very good partial response ( vgpr ) , because serum immunofixation was positive .
he and his family consented to undergo allo - sct . at our outpatient department , because of grade 2 peripheral neuropathy , he continued induction therapy with lenalidomide ( 25 mg / day orally on days 1 - 14 ) , bortezomib ( 1.3 mg / m subcutaneously on days 1 and 8) , and dexamethasone ( 20 mg / day orally on days 1 and 8) in each 21-day cycle . after a total of 6 courses ,
allo - sct was performed with the bone marrow from an unrelated donor ( hla - a one allele mismatch ) .
the conditioning regimen consisted of fludarabine 120 mg / m ( 30mg / m on day -5 , -4 , -3 , and -2 ) , melphalan 180 mg / m ( 90mg / m on day-4 and -3 ) , and rabbit anti - thymocyte globulin 2.5 mg / m ( 1.25mg / m on day -2 and -1 ) .
for the prevention of graft - versus - host - disease ( gvhd ) , tacrolimus was started from day -1 , and methotrexate was given on days 1 , 3 , and 6 .
complete donor chimerism was detected in the bone marrow on day 29 . during this admission ,
however , serum immunofixation was positive despite normal igg and flc levels ; therefore , he was still considered to have a vgpr .
two months after discharge , the patient developed cervical , mediastinal , and axillary lymphadenopathy .
he was therefore diagnosed with ebv - associated lymphoproliferative disease and was immediately treated with 2 cycles of rituximab monotherapy , resulting in a complete response .
tacrolimus was discontinued on day 180 , and there was no evidence of chronic gvhd .
however , 6 months after allo - sct , he had marked cytomegalovirus ( cmv ) antigenemia .
the protein level in the cerebrospinal fluid was 53 mg / dl , and the glucose level was 55 mg / dl ; 17 monocytes per microliter were detected .
cytological examination revealed that some of these cells resembled plasma cells ( figure 2a ) .
magnetic resonance imaging ( mri ) with gadolinium ( gd ) enhancement revealed a small , enhanced nodule in the lateral medulla oblongata ( figure 2b , arrowhead ) . enhanced computed tomography ( ct ) showed no extramedullary tumors .
moreover , we still observed complete donor chimerism , without leukemic plasma cells , in his bone marrow .
the patient underwent 4 courses of weekly it , consisting of methotrexate 15 mg , cytarabine 20 mg , and prednisolone 40 mg in combination with local cranial rt ( 5 fractions of 2 gy for a total dose of 10 gy ) . after this combined treatment , his neurological symptoms resolved and the plasma cells in the cerebrospinal fluid disappeared . to prevent cns recurrence , we administered pomalidomide 4 mg / day on days 121 , with 20 mg of dexamethasone weekly for each 28-day cycle .
subsequently , a reduced dose of 2 mg was administered for 2 cycles , but grade 4 neutropenia occurred again .
he resumed pomalidomide at 1 mg and continued the low dose without severe hematological abnormalities .
twelve months after the cns relapse , both enhanced ct and brain mri with gd enhancement revealed no extramedullary tumors . in our outpatient follow - up , he maintained vgpr without major complications for more than 18 months after the diagnosis of cns relapse .
the prognosis of plasma cell disorder has improved following the introduction of new agents and the development of sct , but a cure remains elusive .
the long - term survival rate of ppcl is low due to the aggressive nature of the disease that comprises high tumor burden and extramedullary involvement . in the us ,
upfront allo - sct is still one of the treatment options for young ppcl patients without major complications . in our study , we performed upfront allo - sct with a myeloablative - conditioning regimen for our young patients without major complications .
the center for international blood and marrow transplant research ( cibmtr ) conducted a retrospective sct study in ppcl , and demonstrated high survival rates in an autologous group compared with those in an allogeneic group . in the cibmtr study ,
non - relapse mortality in the allogeneic group was much higher at 3 years ( 42% vs. 5% ) , despite this group possessing a lower relapse rate ( 39% vs. 61% ) .
our patient survived for more than 2 years after allo - sct , although he unfortunately suffered from cns relapse on day 350 .
consolidation and maintenance therapy after auto- and/or allo - sct in plasma cell disorder is still controversial .
however , some clinical trials have recently shown that lenalidomide maintenance after auto - sct for mm significantly prolonged progression - free survival ( pfs ) and overall survival . moreover
, a prospective clinical trial by the intergroupe francophone du mylome group showed that a bortezomibbased regimen followed by auto - sct and subsequent maintenance therapy with lenalidomide , bortezomib , and dexamethasone for ppcl significantly improved pfs compared with those who received a reduced intensity conditioning allograft . in the future
, auto - sct and maintenance therapy combined with novel agents may be a treatment option for young ppcl patients .
the prognosis of plasma cell disorders with cns involvement is extremely poor . in a retrospective study on cns
myeloma conducted in 12 greek institutions , there was no significant difference in median survival of cns myeloma ( called post cns - mm ) between novel drug - treated patients and those given other treatments ( 4 months vs. 2 months ) . by multivariable analysis ,
extramedullary lesions , prior to treatment with novel drugs , and high ldh levels at myeloma diagnosis were statistically independent predictors of post cns - mm survival .
these findings corroborate our observations that our patient with cns relapse of ppcl had an extremely short - term outcome .
it has been reported that 19% of post cns - mm patients met the criteria for ppcl .
furthermore , some of these ppcl patients developed isolated cns relapse during systemic remission after auto - sct . in a prospective study by royer et al .
, 2 ppcl patients experienced neuromeningeal relapse after autologous- and allo - sct , respectively , and both patients soon died despite intrathecal chemotherapy . in the present case , although vgpr was maintained by rvd induction therapy followed by allo - sct , isolated cns relapse occurred within 1 year .
several drugs used in multiple myeloma , including bortezomib and lenalidomide , do not efficiently cross the blood
of note , bbb penetration of lenalidomide was 11% in a rhesus monkey model , whereas that of thalidomide was 42% . in a murine model , pomalidomide displayed 39% bbb penetration and high anti - tumor activity in the cns . to the best of our knowledge ,
the anti - tumor effect of thalidomide is inferior to that of pomalidomide . additionally , pomalidomide is more effective in ameliorating extramedullary involvement . in our case ,
concurrent it and rt followed by pd was initiated after the diagnosis of isolated cns involvement after allo - sct .
in addition , maintenance therapy by pd might prolong survival to prevent systemic recurrence , including cns involvement , for more than 18 months .
the role of pomalidomide for ppcl patients with cns involvement should be further explored in clinical trials .
our ppcl patient received rvd induction therapy followed by up - front allo - sct .
however , concurrent it and rt followed by pomalidomide - based maintenance therapy well controlled his cns recurrence and prolonged his survival . to find an optimal treatment for this rare but aggressive ppcl , prospective clinical trials for this disorder should take into account the importance of myeloma drug penetration across the bbb in order to enhance the treatment of cns recurrence

Answer:
primary plasma cell leukemia ( ppcl ) is a rare aggressive variant of plasma cell disorder and frequently presents with extramedullary disease .
 central nervous system ( cns ) involvement with ppcl has an extremely poor prognosis .
 we describe a 46-year - old man with ppcl treated with a combination of lenalidomide , bortezomib , and dexamethasone as induction therapy following upfront allogeneic stem cell transplantation ( allo - sct ) . despite achieving a very good partial response
 , the patient suffered from an isolated cns relapse 12 months after allo - sct .
 he was immediately started on concurrent intrathecal chemotherapy ( it ) and cranial irradiation ( rt ) .
 subsequently , pomalidomide and low - dose dexamethasone ( pd ) were given as maintenance therapy .
 he has been without cns recurrence for more than 18 months .
 our case suggests that concurrent it and rt followed by pd maintenance therapy may be an effective option to control cns relapse of ppcl after allo - sct .


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:
all chemicals and reagents were of high performance liquid chromatography ( hplc ) or analytical grade .
pyrrole ( 99  % ) , thiophene ( 99  % ) , and tetrabutylammonium perchlorate ( 98  % ) were purchased from sigma - aldrich ( schnelldorf , germany ) .
medical steel wires ( ni  cr ,   =  750  m ) were purchased from b. braun surgical s.a .
polypyrrole ( ppy ) and polythiophene ( pth ) coatings were synthesized by electropolymerization with a linear sweep voltammetry technique .
the three - electrode cell was filled with electrolyte solution consisting of 100  mm pyrrole / thiophene ( fig .  4 ) and 250  mm tetrabutylammonium perchlorate in acetonitrile.fig .
4chemical structures of ppy ( a ) and pth ( b ) spme fiber coatings chemical structures of ppy ( a ) and pth ( b ) spme fiber coatings polymerization was performed using medical steel wires as working electrodes . an ag / ag electrode was applied as a reference electrode , with platinum net bent into a cylinder as a counterelectrode . for ppy , a potential range from 0.2 to + 2.5  v and seven scans
second , an additional 14 scans in the higher potential range from 0.2 to 2.7  v were used ( fig .
5electropolymerization of pyrrole ( a ) and thiophene ( b ) electropolymerization of pyrrole ( a ) and thiophene ( b ) the morphologies of the polypyrrole and polythiophene fibers were investigated using a scanning electron microscope ( leo 1430vp ; carl zeiss smt , oberkochen , germany ) coupled with a backscattered electron ( bse ) detector .
small angle x - ray scattering ( saxs ) data were collected using a nanostar system ( bruker axs gmbh , karlsruhe , germany ) with pinhole collimation and a two - dimensional hi  star detector with resolution of 1,024    1,024 pixels , mounted on an x - ray tube with a copper anode and equipped with crossed gbel focusing mirrors .
samples were mounted between two mica windows in sample holders with thickness of 1 or 2  mm .
the sample - to - detector distance was 650  mm , and the exposure time for a single frame was 10,000  s. each sample was measured three times , and the obtained data were averaged .
the saxs data were recorded within the scattering vector range of 0.15  nm  <  s  <  3.5  nm ( where s  =  4sin/ , 2 is the scattering angle , and  is the x - ray wavelength ) .
the saxs data were corrected for the detector response and normalized to the intensity of the incident beam , and the background scattering ( empty holder ) was subtracted using the saxs_nt  v4.1 program package ( bruker axs gmbh , karlsruhe , germany ) .
electropolymerization was performed using a homemade electrochemical cell coupled with a high performance potentiostat  galvanostat ( pgstat128n series ; metrohm - autolab b.v . ,
all chemicals and reagents were of high performance liquid chromatography ( hplc ) or analytical grade .
pyrrole ( 99  % ) , thiophene ( 99  % ) , and tetrabutylammonium perchlorate ( 98  % ) were purchased from sigma - aldrich ( schnelldorf , germany ) .
medical steel wires ( ni  cr ,   =  750  m ) were purchased from b. braun surgical s.a .
polypyrrole ( ppy ) and polythiophene ( pth ) coatings were synthesized by electropolymerization with a linear sweep voltammetry technique .
the three - electrode cell was filled with electrolyte solution consisting of 100  mm pyrrole / thiophene ( fig .  4 ) and 250  mm tetrabutylammonium perchlorate in acetonitrile.fig .
4chemical structures of ppy ( a ) and pth ( b ) spme fiber coatings chemical structures of ppy ( a ) and pth ( b ) spme fiber coatings polymerization was performed using medical steel wires as working electrodes . an ag / ag electrode was applied as a reference electrode , with platinum net bent into a cylinder as a counterelectrode . for ppy , a potential range from 0.2 to + 2.5  v and seven scans
second , an additional 14 scans in the higher potential range from 0.2 to 2.7  v were used ( fig .
5electropolymerization of pyrrole ( a ) and thiophene ( b ) electropolymerization of pyrrole ( a ) and thiophene ( b )
the morphologies of the polypyrrole and polythiophene fibers were investigated using a scanning electron microscope ( leo 1430vp ; carl zeiss smt , oberkochen , germany ) coupled with a backscattered electron ( bse ) detector .
small angle x - ray scattering ( saxs ) data were collected using a nanostar system ( bruker axs gmbh , karlsruhe , germany ) with pinhole collimation and a two - dimensional hi  star detector with resolution of 1,024    1,024 pixels , mounted on an x - ray tube with a copper anode and equipped with crossed gbel focusing mirrors .
samples were mounted between two mica windows in sample holders with thickness of 1 or 2  mm .
the sample - to - detector distance was 650  mm , and the exposure time for a single frame was 10,000  s. each sample was measured three times , and the obtained data were averaged .
the saxs data were recorded within the scattering vector range of 0.15  nm  <  s  <  3.5  nm ( where s  =  4sin/ , 2 is the scattering angle , and  is the x - ray wavelength ) .
the saxs data were corrected for the detector response and normalized to the intensity of the incident beam , and the background scattering ( empty holder ) was subtracted using the saxs_nt  v4.1 program package ( bruker axs gmbh , karlsruhe , germany ) .

Answer:
abstractpolymeric polypyrrole and polythiophene solid phase microextraction ( spme ) coatings were prepared using electropolymerization with a linear sweep voltammetry technique .
 physicochemical properties were measured using different methods , in particular small angle x - ray scattering and scanning electron microscopy . by using innovative approaches for pore size measurement , we were able to calculate a maximum of the pore size range from 80 to 90  nm . additionally , film thicknesses measured from 90 to 150  m . using scanning electron microscopy
 , we describe the characteristics of polymer growth on the support surface.graphical abstract