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 relationship between the clotting cascade and the promotion or inhibition of the anti - inflammatory response continues to be defined through basic research .
the potential key role of proteins that were originally believed to be exclusively involved in coagulation in the inflammatory response provides an exciting potential mechanism(s ) for modification through the application of new therapies .
the accompanying review by riewald and ruf   outlines the available information on the possible steps involving some of the various proteins that are common to both coagulation and inflammation .
the complexity of the multiple actions of the proteins in both inflammation and coagulation should excite the clinician with regard to potential new therapies that may be beneficial via activation of one or both of the concurrent pathways .
however , before clinicians can administer new therapies that utilize new knowledge on the actions of coagulation cascade components , and hence improve the outcomes of their patients , several gaps in our current understanding must be addressed .
this information is imperative if the clinician is to take basic knowledge ' to the bedside ' , where individual patients can benefit .
administration of intrinsic or synthetic analogues of coagulation cascade components ( e.g. protein c , thrombin , and factor viia or xa ) , coagulation inhibitors ( e.g. heparin or analogues ) , or agonists or antagonists of the protease - activated receptors , in an attempt to alter the individual patient 's coagulation / inflammation balance , could theoretically produce responses ranging from beneficial to detrimental .
knowledge of the ' most beneficial ' balance between augmenting or inhibiting the contribution of the clotting cascade components to inflammation would be required for determining the selection and dosing of potential new therapies .
a safe assumption is that any new therapies that alter the intrinsic response to coagulation and inflammatory stimulants would also potentially produce detrimental effects on these , and potentially other , physiological responses .
a simple example of such a potential for detrimental effects is the administration of protein c resulting in undesirable haemorrhage .
this example illustrates that a broader knowledge of the impact of altering the coagulation/ inflammatory response will be required before clinicians can comfortably utilize new therapies in patient care .
it is unlikely that any new therapies resulting from the new knowledge of the contribution of the clotting cascade to inflammation can be applied to all patients .
it can be anticipated that certain patients would have contraindications to the new therapies or that dosages would need to be adjusted on the basis of pharmacokinetic or pharmacodynamic variables .
the clinician will need to know what these contraindications and variables are before the new therapies can be used confidently .
some , such as coagulation disorders , may be known and obvious , but any new strategies that could potentially alter the balance of a complex physiological response may be anticipated to be influenced by many , as yet unknown , factors in the individual patient .
an example is the concurrent administration of heparin , which appears to antagonize the anti - inflammatory effect of antithrombin iii in septic patients .
a more complete understanding of the impact of concurrent conditions , therapies and the patient 's genetic make - up on outcome will be required if we are to obtain the maximum benefit from new therapies .
for any new therapy resulting from our expanded knowledge of the clotting cascade in the inflammatory response to be tailored to the needs of the individual patient , a method(s ) for rapidly and easily assessing the patient 's dynamic inflammatory response will be required .
unless any new therapies have very benign toxicities , the need to assess the need , dosage and response to treatment will mandate sensitive and specific monitoring techniques .
bedside or clinical laboratory techniques that could be applicable to most clinical environments would allow the benefit of any new therapies to be applied to the greatest number of patients .
conversely , any new treatments that require complex , laborious monitoring techniques will have limited applicability .
as our knowledge of the contribution of the intrinsic coagulation components increases , the development of many potential new therapies will hopefully emerge for clinical use
. these may be totally new therapeutic entities or new strategies for using existing drugs or clotting factors .
such developments will create the new dilemma for the clinician , namely that of trying to select between different treatment options for the individual patient .
clinical trials outlining the potential anticipated benefit(s ) and the appropriate target patient population for each new therapeutic strategy will need to be completed
. this will allow the clinician to ensure that the most appropriate strategy can be selected for the individual patient .
the above - mentioned concerns aside , the clinician should be excited about the expanding knowledge of the role of coagulation cascade components in modifying the inflammatory response
. such knowledge will hopefully result in new strategies and therapies to manage the septic patient .

Answer:
the relationship between blood coagulation factors and the promotion or inhibition of the anti - inflammatory response continues to be defined through basic research .
 the potential key role of blood coagulation factors in the response during sepsis provides an exciting potential mechanism(s ) for modification through the application of new therapies .
 the complexity of the potential multiple actions of the proteins , such as protein c , should allow for development of new therapies to minimize the detrimental inflammatory response .
 however , several gaps in our current understanding must be bridged before the clinician can take the basic knowledge ' to the bedside ' , where individual patients will benefit .


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:
for the invasive treatment of symptomatic aortic stenosis several attractive options became available beyond conventional cardiosurgical implantation of stented bioprostheses or mechanical valves . besides stentless prostheses , in particular transcatheter procedures are of growing importance .
nevertheless the number of implanted stented bioprostheses in germany expanded or at least remained stable over the last years .
thus , 9.704 bioprostheses were implanted in germany in 2010 , according to 84% of all implanted prostheses in aortic position .
implantation of bioprostheses was associated with a 30-day - mortality of 3,3 % , which is higher than for mechanical valves ( 1,5% ) due to the fact that patients for bioprostheses are significantly older or suffer from more complex co - morbidities .
the purpose of this review is to summarize the features of the currently available bioprostheses in the light of competing procedures .
there has been a continuous development to improve the design of stented bioprostheses with respect to hemodynamic profile , biological durability and ease of implantation .
various designs are available , allowing a valve selection according to individual patient factors or anatomical criteria including techniques for intra - annular and supra - annular positioning [ 3 , 4 ] .
it would have the same biological and hemodynamic properties as a normal valve and would not undergo degeneration .
stented bioprostheses have proven to be effective even in small aortic roots regarding hemodynamic improvement , left ventricular mass reduction and improvement of the patient s quality of life . in vitro examinations showed pericardial valves to be slightly superior to porcine valves with regard to gradient and orifice area .
associated with the scalloped designs of stented bioprostheses a tension - free implantation with avoidance of paravalvular leaks can be expected .
implantation techniques evolved over the last decades which resulted in short cross - clamp times in normal findings .
surgeons learned that meticulous care in decalcifying the aortic annulus and sizing helps to prevent paravalvular leaks .
additionally , accurate sizing prevents a patients - prosthesis - mismatch which could result in poor postoperative clinical performance . avoiding the use of running suture for stented valve implantation
the evolvement of low profile valves reduces the risk of coronary occlusion in patients with a small distance between annulus and coronary ostia .
the currently available and established bioprostheses show rates of degeneration at 20 years around 15% in patients aged 65 or higher . the freedom from repeat aortic valve replacement reaches over 85% after 20 years in patients older than 60 years and 65% in all age groups . along with these convincing results of durability and freedom of re - implantation stented bioprostheses became also attractive for younger patients .
if a repeated valve replacement is necessary due to functional deterioration the operative mortality is acceptable with 4 to 6% and is mainly due to active endocarditis and comorbidities .
lately transcatheter aortic valve implantation ( tavi ) with valve - in - valve implantation into the degenerated xenograft showed to be an additional option in high risk patients with the need for redo valve replacement .
stentless porcine valves were initially believed to have superior hemodynamic properties resulting in more effective reduction of left ventricular mass and better clinical performance according to nyha class .
these findings could nt be yet approved by long - term follow up investigations [ 15 , 16 ] .
bearing this in mind calls the more demanding implantation technique of stentless prostheses in question .
stented bioprostheses are still used more commonly than stentless ones because of their relative ease of implantation , their extensively documented long - term results , and the low risk associated with reoperation .
another  biological  approach is the use of an autograft like the ross procedure , where the patient s pulmonic valve is transferred to the aortic position .
these pulmonic autografts have excellent hemodynamic properties as well as low rates of thrombosis , degeneration , and endocarditis .
the ross procedure is suitable for children and young adults because it is compatible with further growth of the aortic root .
nevertheless since the pulmonary valve has to been replaced by a bioprosthesis it is a demanding two valve procedure with prolonged cross clamping times .   aside from this , special means are necessary for pulmonary autograft stabilization to prevent its degeneration .
there are only a few current randomized trials comparing the long - term results of biological and mechanical valves .
a large - scale review revealed no difference in survival rates at 10 years and a slightly higher survival rate at 15 years for patients with mechanical prostheses .
the reoperation rate for mechanical valves in the aortic position is less than 5% at 10 years and less than 10% at 15 years , while the corresponding figures for bioprostheses are 10% and 30% , respectively .
hemorrhagic complications are significantly more common in patients with mechanical valves because of anticoagulation .
chronic atrial fibrillation is no longer a contraindication to bioprostheses since permanent oral anticoagulation can be avoided if concomitant ablative surgery results in permanent conversion to sinus rhythm .
end stage renal failure was also defined a contraindication to bioprostheses since a rapid degeneration was feared due to altered metabolism in these patients .
it has been found that life expectancy is already curtailed to such an extent that bioprosthesis degeneration often does not occur in the remaining lifetime .
the supposed advantage of the longer durability of a mechanical valve is also offset by the potential complications of oral anticoagulation , especially because anticoagulation is more difficult to manage in dialysis patients than in others .
nevertheless aortic valve replacement using a tissue valve remains controversial for patients younger than 60 years since there are studies reporting reduced mid - term results .
some younger patients are averse to oral anticoagulation and therefore prefer a biological valvular prosthesis .
thus , younger patients opting for a bioprosthesis can enjoy a normal quality of life without anticoagulation for many years but may need to undergo a second valve replacement procedure with an acceptable degree of risk .
implantation of conventional prostheses can be performed through a limited direct access like a hemi - sternotomy or a lateral access . reported large series show that aortic valve operations can be safely performed in experienced centers .
substantial progress in valve technology led to the development of self - expanding valves . since a few years a number of bioprostheses are available for suture - less implantation which is usually combined with a limited surgical access .
.   future will show the benefits of this procedure characterized by short cross clamping times and whether it can coexist with tavi procedures .
after its clinical inauguration by cribier in 2002 the transcatheter aortic valve implantation gained widespread use in high risk patients with aortic stenosis .
in germany a massive increase of its application can be observed ; in 2010 nearly every fourth aortic valve replacement was performed as a tavi procedure .
the partner trial was a randomized trial comparing tavi with standard - of - care therapies in high risk patients .
a 2-year follow - up of patients in the partner trial supports lately tavi as an alternative to surgery in high - risk patients .
the two treatments were similar with respect to mortality , reduction in symptoms , and improved valve hemodynamics , but paravalvular regurgitation was more frequent after tavi and was associated with increased late mortality .
there are a growing number of publications reporting promising short term results in high risk patients .
nevertheless there is still a lack of evidence that tavi is superior to open valvular replacement as the gold standard regarding long - term results .
current guidelines recommend the use of tavi restricted to patients with contraindications for open surgery or inacceptable perioperative risks .
current studies reveal that bioprostheses of the most recent generation last longer than earlier types .
because life expectancies in general have risen , more and more elderly patients are presenting for valve replacement and for these patients a bioprosthesis is usually chosen .
in addition the cost effectiveness of stented bioprostheses appears unbeatable and the surgical ease of implantation allows for cross - clamp times between 30 and 60 minutes .
overall , even in face of more innovative biological alternatives the implantation of stented bioprostheses is still a very interesting option and represents actually the most frequent valve implantation technique for aortic stenosis . especially in the light of growing use of interventional valve replacement
there is the urgent need for complete nationwide registry with adequate long term follow up , quality of life information and relevant subgroup analysis to define new standards in the treatment of patients with aortic stenosis .

Answer:
introductionbiological stented prostheses are currently the main type of prosthetic valve used for aortic valve replacement .
 the ratio of bioprotheses to mechanical prostheses has switched in the last 15 years ; the percentage of biological   prostheses implanted has risen from 30 % to 85 % .
 moreover the total number of implanted stented bioprostheses remained stable over the last years despite competing procedures like stentless prostheses or transcatheter aortic valve implantation.methodsa literature search of all published aortic valve replacement studies was performed from january 2000 through may 2012.resultsthe recommendations guiding the type of heart valve replacement have been revised in recent years .
 of particular interest are the new generation of biological prostheses with extended durability , a decrease in mortality of reoperation and an increase in life expectancy .
 comorbidities such as chronic renal insufficiency or chronic atrial fibrillation are no longer contraindications to bioprostheses.conclusionoverall , even in face of more innovative biological alternatives the implantation of stented bioprostheses is still a very interesting option and represents actually the most frequent valve implantation technique for aortic stenosis .


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:
pseudohypoparathyroidism ( php ) is a disorder of end - organ resistance primarily affecting the actions of parathyroid hormone ( pth)1 ) .
it is characterized by hypocalcemia and hyperphosphatemia in association with increased secretion of pth due to decreased target tissue responsiveness to pth .
patients with php ia are not only resistant to pth , but also to other hormones that bind to receptors coupled to stimulatory g protein ( gs alpha)2 ) .
the gnas gene is located on chromosome 20q13.11 and consists of 13 exons and 12 introns3 ) .
php - ia is caused by heterozygous mutations affecting one of the 13 gnas exons encoding gs alpha4 ) .
we report here a 9-yr - old boy with php ia with a nonsense mutation of c.637 c > t in the gnas gene , which is novel .
9-year - old boy was admitted to hallym university medical center with painful subcutaneous soft tissue masses with calcifications on the right toes and posterior chest wall . he had a history of repeated convulsive episodes from the age of 2 months .
physical examination showed short stature ( 120 cm , 3rd percentile ) , round face ( fig .
2 ) and subcutaneous ossifications on the 2nd toe tip and 1st web space of the right foot and the left lower posterior chest wall ( fig .
3 ) . his weight was 30 kg ( 50th percentile ) , thus having a normal body mass index ( 20.83 kg / m , 85th-90th percentile ) .
he was born at full term by cesarean section with a birth weight of 3.3 kg .
family history revealed that his maternal grandmother had features suggestive of aho , such as short stature , round face , obesity and brachydactyly .
his mother had normal appearance apart from short stature , but two of her siblings had short stature , round face and obesity .
we could not make further investigation because the patient lost contact with his mother and maternal family after his parents got divorced .
laboratory tests revealed hypocalcemia ( 4.2 mg / dl ; normal range , 8.8 - 10.8 mg / dl ) , hyperphosphatemia ( 8.9 mg / dl ; normal range , 3.7 - 5.6 mg / dl ) and elevated serum pth ( 146.5 pg / ml ; normal range , 9 - 65 pg / ml ) .
he also showed elevated plasma thyroid - stimulating hormone ( 6.978 iu / ml ; normal range , 0.5 - 4.8 iu / ml ) , follicle stimulating hormone ( 5.6 iu / ml ; normal range , 0.26 - 3.0 iu / ml ) , and luteinizing hormone ( 1.2 iu / ml ; normal range , 0.02 - 0.3 iu / ml ) , which suggest multiple hormone resistance .
urinary phosphorous and cyclic adenosine monophosphate response after infusion of synthetic human pth ( teriparatide acetate ) was attenuated ( ellsworth - howard test ) ( table 1 ) .
his intellegence scale ( korean educational development institute - wechsler intelligence scale for children ) indicated mild mental retardation ( intelligence quotient , 67 ) .
he was diagnosed as having php ia based on physical and laboratory findings ; hypocalcemia , hyperphosphatemia , pth resistance , presence of aho , multiple hormone resistance and mental retardation .
he was started on phosphate - binding substance ( aluminum hydroxide , 80 mg / kg / day ) , vitamin d ( alfacalcidol , 1 mcg / day ) and calcium carbonate ( 50 mg / kg / day ) .
three months later , his serum calcium was elevated from 4.2 to 6.0 mg / dl , and phosphorus was decreased from 8.9 to 8.6 mg / dl .
the patient 's clinical symptoms of pain , seizure and hyperactivity were reduced . to support the diagnosis of php ia , we performed dna analysis of the gnas gene .
genomic dna was extracted from peripheral blood leukocytes using the wizard genomic dna purification kit following the manufacturer 's instructions ( promega , madison , wi , usa ) .
all coding exons and their flanking introns of the gnas gene were amplified using primer sets designed by the authors .
polymerase chain reaction was performed with a thermal cycler ( model 9700 , applied biosystems , foster city , ca , usa ) as follows : 32 cycles of denaturation at 94 for 30 seconds , annealing at 60 for 30 seconds , and extension at 72 of 30 seconds .
after treatment of amplicon ( 5 ul ) with 10 u shrimp alkaline phosphatase and 2 u exonuclease i ( usb co. , cleveland , oh , usa ) , direct sequencing was performed with the bigdye terminator cycle sequencing ready reaction kit ( applied biosystems ) on the abi prism 31001 genetic analyzer ( applied biosystems ) .
sequencing of the amplified gnas genomic dna fragments revealed a heterozygous nonsense mutation within exon 11 ( c.637 c > t ) ( fig . 5 ) .
the c > t transversion results in an amino acid substitution from gln to stop codon at codon 213 ( p.gln213 ) . to our knowledge , this is a novel mutation in gnas .
we also performed dna sequencing of the gnas gene of his father , but no mutation was detected .
php is a heterogeneous disease characterized by pth resistance and classified as types ia , ib , ic , and ii , according to its different pathogenesis and phenotype5 ) .
in contrast to the situation in hypoparathyroidism , in php the parathyroid glands are normal or hyperplastic and they can synthesize and secrete pth6 ) .
heterozygous inactivating mutations within gs alpha - encoding gnas exons are found in patients with php - ia , who also show resistance to other hormones and a constellation of physical features called aho .
patients who exhibit aho features without evidence for hormone resistance , who are said to have pseudopseudohypoparathyroidism ( pphp ) , also carry heterozygous inactivating gs alpha mutations1,7 ) .
there is some evidence to suggest that the gs alpha mutation is paternally transmitted in patients with pphp and maternally transmitted in patients with php - ia .
the gene may be imprinted in a tissue - specific manner6,8,9 ) . in our case ,
dna sequencing of the patient and his father revealed that only the patient had mutations .
the presence of slight aho in the mother 's side of the patient may suggest that the mutation came from his mother , but we were unable to confirm this because the dna of the patient 's mother or maternal family was not available at the time of the study .
although we could not obtain molecular data from the maternal family of the patient , considering variation of phenotypes due to genomic imprinting , we were able to explain that the patient had the genotype and phenotype of php ia . in the maternal family of the patient ,
his mother had milder features suggestive of aho , whereas her mother and two siblings had characteristics that were more strongly suggestive of aho .
we can suspect the possibility of a hypofunctioning gnas mutation like mosaicism , but it was impossible to validate .
mutational analysis of gnas gene is a useful method for identifying genetic abnormalities as well as making diagnosis and differentiation of various subtypes of php10 ) .
there are previous reports of korean patients with php ia and pphp who were confirmed by genetic analysis .
park et al.11 ) reported a nonsense mutation of c.94a > t ( p.k32x ) and a frame shift mutation of c.344_345inst ( p.v117rfsx23 ) in patients with php ia , of which the former was novel . in a study of patients with php ia and pphp , jin et al.10 ) identified two novel mutations ; c.569_570del mutation ( p.tyr190cysfsx19 ) and a splicing mutation ( c.659 + 1g > a ) .
gnas has been termed one of the most complex gene loci in the human genome3 ) .
although many mutations have been identified in gnas , c.637 c > t nonsense mutation is deemed novel .

Answer:
pseudohypoparathyroidism type ia ( php ia ) is a disorder characterized by multiform hormonal resistance including parathyroid hormone ( pth ) resistance and albright hereditary osteodystrophy ( aho ) .
 it is caused by heterozygous inactivating mutations within the gs alpha - encoding gnas exons .
 a 9-year - old boy presented with clinical and laboratory abnormalities including hypocalcemia , hyperphosphatemia , pth resistance , multihormone resistance and aho ( round face , short stature , obesity , brachydactyly and osteoma cutis ) which were typical of php ia .
 he had a history of repeated convulsive episodes that started from the age of 2 months .
 a cranial computed tomography scan showed bilateral calcifications in the basal ganglia and his intelligence quotient testing indicated mild mental retardation .
 family history revealed that the patient 's maternal relatives , including his grandmother and 2 of his mother 's siblings , had features suggestive of aho .
 sequencing of the gnas gene of the patient identified a heterozygous nonsense mutation within exon 11 ( c.637 c > t ) .
 the c > t transversion results in an amino acid substitution from gln to stop codon at codon 213 ( p.gln213 * ) .
 to our knowledge , this is a novel mutation in gnas .


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:
emphysematous cystitis is a distinct complicated lower urinary tract infection ( uti ) characterized by air within the bladder wall and lumen .
patients with chronic utis , indwelling urethral catheters , urinary tract outlet obstruction , or neurogenic bladders are predisposed to complicated utis such as emphysematous cystitis .
air within the urinary tract can also occur due to instrumentation , fistula to a hollow viscus , tissue infarction with necrosis .
patients might have varied presentations , ranging from incidental diagnosis on abdominal imaging to severe sepsis .
gas - forming infections or emphysematous conditions of the urinary tract are potentially life - threatening , and require prompt evaluation and management .
we describe a case of emphysematous cystitis that was managed successfully with bladder drainage , intravenous antibiotics , and strict glycemic control .
a 45-year - old male who was a known case of type-2 diabetes mellitus for last 16 years , complained of on and off fever , dysuria and turbid colored urine for last 3 months .
he had past history of suprapubic catheterization for obstructive uropathy due to meatal stenosis 15 years back . clinical examination revealed pallor , penile hypospadias , meatal stenosis , bilateral nonproliferative diabetic retinopathy and evidence of sensory neuropathy .
investigations showed anemia ( hb7.7 gm / dl ) , neutrophilic leukocytosis ( total leukocyte count 19800 cells / cmm ( n , 400011000 cells / cmm ) with 90% neutrophils .
serum creatinine was 3.5 mg / dl ( n , 0.6 - 1.2 mg / dl ) and hba1c was 8.5%
ct abdomen revealed intraluminal and intramural gas in the bladder with thickening of bladder wall [ figure 1a  c ] .
kidneys were normal in size and shape and there was no perinephric stranding or gas in renal parenchyma or renal pelvis .
figure 1d shows disappearance of intramural and intraluminal gas on follow up ct imaging after 8 weeks .
serum creatinine was decreased to 2 mg / dl , but not normalized probably because of underlying diabetic nephropathy .
( c ) axial ct image through lower pelvis showing pneumobladder , intramural air and circumferential mural thickening .
( d ) axial ct image through lower pelvis after treatment showing disappearance of air ; however , mural thickening is persisting
other organisms reported include klebsiella pneumoniae , pseudomonas aeruginosa , proteus mirabilis , candida albicans , and candida tropicalis , aspergillus fumigatus , staphylococcus aureus , group d streptococcus , enterococcus faecalis , enterobacter aerogenes , and clostridium perfringens and cl .
the clinical presentation of emphysematous cystitis is varied ; patients can be asymptomatic , describe pnematuria , or irritative voiding symptoms , or present with an acute abdomen with severe sepsis . of reported patients with emphysematous cystitis ,
predisposing factors for emphysematous cystitis include diabetes mellitus , neurogenic bladder , lower urinary tract obstruction , urethral catheter placement , vesicourethral reflex , and end stage renal disease .
the effects of diabetes mellitus on the urinary tract include diabetic nephropathy , renal papillary necrosis , renal artery stenosis , and bladder dysfunction secondary to neuropathy .
these factors combined with glycosuria and impaired leukocyte function place diabetic patients at greater risk of complicated utis such as emphysematous cystitis .
overall , two - thirds of reported cases of emphysematous cystitis were diabetic and 64% were women
. the symptoms of emphysematous cystitis are similar to those of uncomplicated cystitis , consisting of frequency , urgency , and dysuria .
therefore , a high index of suspicion is required for diagnosis especially in patients with risk factors .
plain radiographs of the abdomen reveal radiolucency within the lumen of the bladder as a ring of radiolucency outlining the bladder wall .
computed tomography of the abdomen is superior to plain radiographs as a diagnostic tool because it clarifies the extent and location of the gas collection as observed in our case .
a pathological assessment of involved bladder tissue might show bladder wall thickening with vesicles of varying size , and microscopically there are multiple gas filled vesicles predominantly within the bladder mucosa , lined by flattened fibrocytes and multinucleated giant cells .
it is thought that the high glucose concentration within the tissues acts as a favourable substrate for organisms to produce carbon dioxide through facultative anaerobic glycolysis .
however , this does not account for the significant number of non - diabetic patients with emphysematous infections . in such patients , urinary albumin might act as the substrate for gas production by urinary pathogens .
another theory suggests that an impaired host response , involving vascular compromise and impaired catabolism within the tissues , predisposes patients to gas production within these tissues . the pathogenesis is not yet fully understood , but a multifactorial aetiology of impaired host responses with sugar or protein fermentation seems to be a plausible explanation for the production of gas within the affected tissues .
management consists of adequate urinary drainage , appropriate antibiotic treatment , and good blood glucose control .
however , delayed diagnosis may lead to extension to the ureters and renal parenchyma , bladder rupture , and death .
the gas is reabsorbed once the infection is eliminated as was seen in our patient [ figure 1d ] .
history of pneumaturia and evidence of intraluminal and intramural gas along with bladder thickening on imaging clinches the diagnosis of emphysematous cystitis .

Answer:
emphysematous cystitis is a relatively rare clinical entity caused by gas - fermenting bacteria or fungus .
 presentation is often nonspecific and imaging is the best diagnostic modality .
 we report a case of a 45-year - old male who presented with fever , dysuria , and pneumaturia , and was found to have emphysematous cystitis .


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:
soft tissue coverage for wounds remains a difficult management problem for patients sustaining traumatic injury and burns .
there are several methods to achieve wound coverage  secondary healing , primary suturing , skin grafting , and flap surgeries as described in reconstruction ladder .
a skin graft is the most commonly used modality for coverage of wounds in reconstructive plastic surgery . the skin graft needs to undergo various stages of healing for a good take on the recipient bed .
there are different methods employed to secure the graft to recipient bed for a few days with a basic idea to ensure that the graft is not elevated off the bed by formation of haematoma / seroma under it .
repeated tie over dressings are required in situations where the dressing needs to be changed more frequently as in cases of infected raw area , bleeding tendency , patients on anticoagulant drugs , and in convex areas of body such as buttocks , breast , and the scalp , where the dressing is difficult to secure .
in this novel method , a sterile sample container was cut at its upper part [ figures 1 and 2 ] .
the skin graft was applied on the raw area and fixed with skin staplers and tie over sutures . once paraffin gauze and adequate padding is applied on the raw area , the tie over threads were passed from inside out of the container [ figures 3 and 4 ] and pulled at the appropriate tension to keep the dressing in place .
the lid of the container was tightened to complete the dressing ensuring that the graft was maintained in close approximation with the wound surface .
sterile plastic container upper part of the sterile container is cut tie over threads being passed from inside out the lid is tightened over the dressing the dressing can be changed repeatedly with sterile precautions depending on the requirement , as an outpatient procedure by unscrewing the lid [ figures 5 - 8 ] which can then be easily reapplied .
the procedure can be used on wounds of any size by changing the size of the sterile container chosen .
post - toilet mastectomy raw area covered with the skin graft the tie over dressing applied in ot tie over dressing repeated in an outpatient department we have used this method in eight cases of the post toilet mastectomy raw areas with very good results [ figures 9 and 10 ] . post - toilet mastectomy raw area
skin graft once applied has to be covered with petrolatum gauze to avoid its separation from the wound bed at the time of change of dressing .
an ideal method of graft fixation should be simple , rapid , repeatable , able to be performed in the outpatient department , prevent hematoma or seroma formation , soak the exudates well , and allow the graft bed to be inspected easily .
there are multiple methods of securing dressings over the skin graft , some of them can be applied only once and some can be repeated .
the dressings that can be applied only once are like foam , hydro cellular dressing ( highly absorbent and can be easily changed ) , negative pressure therapy dressing ( stabilises the graft , increases the vascularity of bed , takes away toxic chemicals ) , and gas bag ( transparent , can see graft and monitor any haematoma ) .
these traditional methods can stabilize the graft till the first dressing post operatively . in some contaminated wounds ,
the dressing needs to be removed earlier , especially if there is drainage or foul smell .
this approach may also be proper for graft , used to cover defects of some anatomical regions with increases risk of contamination , such as perineal , axillary , and genital or it can be used in areas where base of wound is difficult to immobilize like breast / pectoral region .
repeated tie over dressings can be done by keeping interrupted sutures long to be used as tie over dressings .
these ties over dressing can be made of sutures or rubber bands . when taking a tie over stitch , both
the threads can be left long and only one thread is tied at a time , the other thread is left long for next time .
these techniques are difficult for small dressings especially the bra hooks ; the silk loops method is very cumbersome and takes long time to do .
the novel method being discussed has a very small learning curve and is very fast .
it hardly takes 5 min in the hands of a plastic surgeon to complete the dressing .
this dressing technique maintains the advantage of conventional tie over dressing with rapidity and repeativity .
good graft take can be expected whether split - thickness or full - thickness with appropriate methods of stabilisation .
we recommend a novel , low cost , simple , rapid method of graft fixation that can be used repeatedly and can be applied to a wound of any size .

Answer:
tie overdressing is commonly used to secure the graft against the raw surface and prevent loss due to of hematoma or seroma . a conventional tie over dressing with silk sutures ,
 is a useful method of securing the graft to raw area .
 refixation is difficult when repeated tie over dressings are needed .
 we assessed a low cost repeated tie over dressing method using sterile sample collection containers and silk suture threads in eight patients .
 after the graft is applied on the bed , tie - over stitches are taken , and paraffin gauze is applied over with adequate padding ; the tie over sutures are passed through the container and the lid is tightened over it to complete the dressing .
 the lid can be unscrewed easily at any time to inspect the graft and can be easily reapplied in the outpatient department .
 the skin graft take in all the patients was complete without any seroma or hematoma .
 a novel and low - cost tie over dressing that enables simple fixation of the dressing , to maintain proper position of grafts that require repeated fixation is reported here .


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:
Substituent Control of s-interference Effects in the Transmission of Saturated Molecules

Paper sections:
MANUSCRIPT

Saturated organic molecules are considered to be good molecular insulators and find widespread use in studies of electronic and magnetic communication between functional molecular units. [1][2] Destructive quantum interference in the s-system can further enable the design of saturated molecules where the electronic transmission is almost completely suppressed. [3][4][5] Destructive sinterference may appear in saturated molecules when all through-bond paths in the molecular backbone have at least one gauche defect, i.e., a dihedral angle approaching 0°. [3][4][5][6][7][8] However, full suppression of the single-molecule conductance is not often achieved and it is not always clear if the partial suppression is due to an interference effect. 5 For example, the gauche conformations of simple linear alkanes have lower conductance than the trans conformations; however, clear signatures of destructive quantum interference are missing, such as sharp antiresonance dips in the electronic transmission. [8][9][10][11][12][13][14][15][16] When s-interference effects manifest, the conductance is highly sensitive to details in the molecular geometry. Based on the extensive topological understanding of interference effects in p-systems, we expect a similar intuition should be found for s-systems. [17][18][19][20][21] However, it is an ongoing challenge to understand the structure-property relationships for the single-molecule conductance of saturated group 14 systems. 9,[22][23][24][25][26][27] We reported a surprising chemical sensitivity of the s-interference effect. 5 Despite the benign nature of the substituents, the electronic transmission of functionalized cyclohexane, cyclohexasilane, bicyclo[2.2.2]octane, and bicyclo[2.2.2]octasilane is systematically lower when the molecules are permethylated. This is exemplified in Figure 1  Substituent effects are well-established for destructive quantum interference effects in conjugated molecules. [28][29][30][31] The destructive p-interference effect can be systematically manipulated depending on the electron donating or withdrawing character of the substituent. [32][33][34][35][36][37][38][39][40] Here, we examine the substituent effect on the electronic transmission of methylthiomethyl-functionalized bicyclo[2.2.2]octane (C222), bicyclo[2.2.2]octasilane, and bicyclo[2.2.2]octagermane (Ge222).

Fully X-substituted C222-X, Si222-X, and Ge222-X structures are sampled using RDKit as described in Supporting Information part A. 41 Common to all the methylthiomethyl-functionalized bicyclo[2.2.2]-systems, the molecular core is chiral but has no conformational freedom. Therefore, the orientations of the two linkers relative to each other provide three conformations. These are shown in Figure 2 as a Newman projection along the bridgehead axis of the molecule, and as the optimized conformations of Si222-H. It is the Si-Si-CH 2 -S dihedral angles of the linkers that must be rotated to sample the three conformations. In accordance with previous work, we refer them as the anti, ortho, and cis conformers. We sample these three in all studied molecules. For a control system, we examine the equivalent linear molecule in its all-trans conformation as shown in bottom panel of Figure 2. All structures are optimized using density functional theory as implemented in Gaussian09 using the PBE exchange-correlation (XC) functional with 6-311G(d,p) basis set. [42][43] Single-molecule junctions were made by placing the optimized molecules between two four-atom Au pyramids on 5x5 Au fcc(111) surfaces. The initial junction structure is built using Au-S bond length of 2.5 Å and Au-S-C bond angle of 110°. The terminal methyl groups are rotated to a dihedral angle of ±90° in order to make space for the Au atoms in the transoid position (±170°). 44 Junctions are relaxed to a force threshold of 0.06 eV/Å using DFT with the PBE XC functional and double-z plus polarization basis set as implemented in ASE and GPAW. 43,[45][46][47] Finally, the Landauer transmission is calculated using the NEGF approach as implemented in ASE. 45 We devise an extensive list of substituents based on the criterion of some extent of chemical realism, though in some cases also on chemical curiosity. The different substituents on C222-X, Si222-X, and Ge222-X are to some extent limited by the size of the molecular frame, and therefore not all substituents can be used. Scheme 1 provides an overview of all 34 molecules studied.

Optimizations of cyano-substituted Ge222-CN did not converge. It is a molecule we do not expect to be experimentally realistic, but it would have been of interest because CN is a very strong electron acceptor. Scheme 1: Overview of substituents in C222-X, Si222-X, and Ge222-X.

In the low-bias regime we study here, an insulating molecule must have strong suppression of the transmission near the Fermi energy in all its conformers. The constrained structure of the bicyclo[2.2.2]octane frame makes them shorter than the equivalent butane-motif molecules (methylthiomethyl-functionalized C4-X, Si4-X, and Ge4-X). Despite being shorter molecules (shorter tunneling barriers), previously studied the bicyclo[2.2.2]octane systems have similar or lower transmission than their linear counterparts as testament to their superior insulating properties. 3-5, 25, 48  The transmission is plotted against energy for select Si222, Ge222, and C222 molecules in  3b), however, there is some variation of the transmission depending on the conformation. The transmission of Ge222-Me is a bit higher than in the equivalent Si222-Me, and phenyl substituents may offer slightly lower conductance for germanium than methyl.

Similar suppression and variation are seen in the ethyl, vinyl, and ethynyl substituted cases of Si222 and Ge222 (Figure S3 and S4). Carbon-based substituents thus seem particularly promising for fine-tuning the insulating properties of Si222 and Ge222 systems. Although alkyl and phenyl substituents are quite benign from a chemical point of view, they are particularly promising because they are realistic synthetical targets for silicon and germanium based molecular cores. [49][50][51][52][53][54][55][56][57] We hope these results will motivate studies of the properties of substituted cyclic and bicyclic silanes and germanes. The transmission suppression is less clear in the C222 systems than for the silanes and germanes. Shown in Figure 3c, the transmission of C222-Me and C222-F does have antiresonances for some conformers. However, looking broadly at the C222 systems in Figure S2, it appears there are few cases with s-interference. We note the transmission of linear alkanes is much lower than that of linear silanes and germanes in general, 58 and the suppression effect is thus quite small in C222. For example, the suppression of the transmission in C222-H is below an order of magnitude compared to C4-H, in good agreement with experimental results. 5,48 Peralkylated bicyclo[2.2.2]octanes are not the most realistic synthetic targets, while fluorinated alkanes make for more realistic targets for single-molecule junction studies. [59][60][61] The transmissions of all C222-F conformers are suppressed over a broad energy-range compared with C4-F. Of the substituents studied for C222, fluorinated bicyclo[2.2.2]octanes are thus an interesting prospect for organic interference-based singlemolecule insulators. Generally, however, they are still not as promising as the Si and Ge based systems as only the anti-conformer has a deep antiresonance near the Fermi energy.

Certain substituents seem to promote the insulating properties of the three molecular cores. We further assess substituents based on their electron withdrawing and donating properties. Such effects have been classified in the extensive physical organic chemistry literature. 62 In Figure 4a, the transmission at the Fermi energy is plotted for all substituted molecules sorted by their oftused Hammett constants s p , which are based on the substituent effect in para-substituted benzenes. 62 Except for F and Cl, the substituent effect is fairly similar across the C222, Si222, and Ge222 series. However, there is no clear correlation across the full transmission data set when plotted against s p . Motivated by the strong transmission suppression seen for many of the carbon-based substituents, we separate the data set into two types of substituents: those based on carbon (blue in Figure 4a) and the remaining that are not carbon based (red in Figure 4a). We search further for quantitative correlations in substituent parameters that are determined in systems with suppressed or separated p-conjugation. 62 In addition to s p , we plot the transmission values against the Hammett constant, s m , which are determined on meta-substituted benzenes and the inductive parameter F.

While all these parameters are determined empirically, F may provide a better measure of the substituent effect on the s-system as it uses a bicyclo[2.2.2]octane compound for reference. 62 Shown in Figure 4b, the transmission of the three cores with carbon-based substituents is plotted against the three different Hammett constants. While there is a weak correlation for C222, both Si222 and Ge222 transmission show strong correlation with all three empirical parameters. These correlations are consistently weaker for the non-carbon substituents as plotted in Figure 4c. There is some correlation for these substituents in the Ge222 with s m and F, but in the remaining systems there is no correlation between the transmission and the Hammett constants.

The carbon-based substituents (listed in blue in Figure 4a) stand out from their non-carbon counterparts. They enable the lowest transmission for the Si222 and Ge222 systems, and their transmission correlates with the electron withdrawing properties of the substituents as given by the empirical Hammett constants. These correlations are quite strong compared to the correlations reported in other single-molecule conductance studies. [63][64][65] Carbon-based substituents thus provide an opportunity for fine-tuning s-interference effects in silicon and germaniumbased compounds.

The carbon-based substituents we find here appear to be special for the silicon-and germaniumbased cores, but do not systematically promote interference effects in the carbon-based core. As previous studies have suggested, the s-interference effect is highly sensitive to several structural and electronic parameters. [3][4][5][6][7]24 We have tested for correlations with structural parameters in our dataset but have not found any clear correlation, see Supporting Information part B for details. This indicates the effect of substituents is electronic (donor/acceptor effect) rather than from the distortion of the structure in molecular core. While these two effects (electronic and structural) are not independent of each other, the clear correlation we see for the carbon-based substituents with the Hammett constants suggests the effect is primarily electronic. Most likely, carbon-based substituents are special because they tune the electronic structure within an ideal range where there is s-interference in the transmission. This balance of parameters that enables interference effects in saturated molecules is still not well-described, but clearly the s-interference effect is very sensitive to both chemical and structural changes.

To summarize, a wide range of substituents can result in significant destructive interference effects in the transmission of Si and Ge cores. These are substituents based on carbon, such as alkyl and phenyl substituents, and we show that this substituent effect is systematic by correlating the transmission with different Hammett constants. However, we find that fluorination appears to be the only substituent that is likely to result in significant conductance-suppression in the carbonbased bicyclo[2.2.2]octane we have studied here. s-interference thus appears to be much more sensitive to chemical changes than the more well-established p-interference effect. Until recently, we may have thought that saturated molecules are some of the simplest and best understood systems in molecular electronics. Recent results by us and other groups suggest there is much more potential, 5, 66 which may be applied for novel chemical designs. This letter is a step in this direction, and future work must continue to build on the electron transport structure-property relationship of saturated carbon molecules and their heavier group 14 analogues.

Answer: The single-molecule conductance of saturated molecules can potentially be fully suppressed by destructive quantum interference in their s-system. However, only few molecules with s-interference have been identified and the structure-property relationship remains to be elucidated. Here, we explore the role of substituents in modulating the electronic transmission of saturated molecules. In functionalized bicyclo[2.2.2]octanes, the transmission is suppressed by sinterference when fluorine substituents are applied. For bicyclo[2.2.2]octasilane andoctagermanes the transmission is suppressed when carbon-based substituents are used, and such molecules are likely to be highly insulating. For the carbon-based substituents we find a strong correlation between the appropriate Hammett constants and the transmission. The substituent effect enables systematic optimization of the insulating properties of saturated molecular cores.


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:
Facile synthesis of functionalized spiro[indoline-3,2'-oxiran]-2-ones by Darzens reaction

Paper sections:
Introduction

The spirooxindole unit is a privileged heterocyclic motif that forms the core structure of a large family of natural alkaloids and many pharmacological agents with important bioactivity and interesting structural properties [1][2][3][4][5]. The unique structures and the highly pronounced pharmacological activity displayed by the spirooxindoles have made them attractive synthetic targets [6][7][8][9]. In various heterocyclic and carbocyclic spirooxindoles, the spiro-oxirane-oxindoles are a particular class of compounds with both spiro-carbon and unstable oxirane features in the molecule. These fascinating spiranic frameworks can serve as important building blocks in organic synthesis for the synthesis of large-ring heterocycles [10][11][12][13]. As a consequence, in recent years much attention has been paid to the diastereoselective and enantioselective synthesis of versatile spiro-oxirane-oxindoles [14][15][16][17][18][19]. With the aim of expanding our previous studies on the synthesis of various spirooxindoles [20][21][22][23][24][25], we decided to systematically investigate the Darzens reactions of a series of isatins with phenacyl bromides and report the facile synthesis of versatile spiro[indoline-3,2'oxiran]-2-ones.

Results and Discussion

In recent years we have found that pyridinium salts react with versatile reactive methylene compounds to give different kinds of products, including functionalized cyclopropanes, 2,3-dihydrofurans, polysubstituted pyridines, pyrido[1,2-a]benzimida-Scheme 1: Synthesis of spiro-epoxyoxindole with pyridinium ylide. zoles and charge-separated zwitterionic salts [26][27][28][29][30][31]. We envisaged that in situ generated pyridinium ylide might react with the reactive carbonyl group of isatins to afford spiro epoxyoxindoles (Scheme 1). To test this feasibility, the reactions of various substituted isatins with pyridinium salt in the presence of base were examined under different conditions. We were disappointed that the reactions produced much complicated mixtures and no acceptable results were obtained. Thus, our attention was turned toward the development of straightforward reactions of phenacyl bromides with isatins.

In a preliminary experiment, a model between 5-methylisatin (1) and phenacyl bromide (2) was examined under a broad set of conditions (Table 1). A careful screening of bases revealed that potassium afforded the product in better yields. The main problem is that the N-alkylated spiro epoxyoxindole 4 is accompanied by the formation of spiro epoxyoxindole 3 even if equivalent reactants are used, which is consistent with the recently reported reactions of isatins with alkylating agents having an acidic methylene group by Blanco et al. [19]. To our delight, the spiro epoxyoxindole 3 could be selectively obtained in 85% yield when the reaction was carried out in the system of K 2 CO 3 /CHCl 3 at about 50 °C for 10 h. On the other hand the N-alkylated spiro epoxyoxindole 4 was also successfully prepared in 90% yield in this system when more than two equivalents of phenacyl bromide were utilized. After obtaining the optimized reaction conditions, various substituted isatins and phenacyl bromides were employed in the reaction. The results are summarized in Table 2. All reactions proceeded very smoothly and eight spiro epoxyoxindoles 3a-h were obtained in satisfactory yields. Similarly the N-substituted spiro epoxyoxindoles 4a-e were synthesized in high yields by using an excess of phenacyl bromide. The results are summarized in Table 3. The structures of compounds 3a-h and 4a-e were characterized by IR, 1 H, 13 C NMR, and HRMS spectra and were further confirmed by single-crystal X-ray diffraction determination of the compound 3c (Figure 1) and 4a (Figure 2).

It should be pointed out that some of the spiro epoxyoxindoles 3a-h have been previously prepared by other methods and the related references are also listed in Table 2. The 1 H NMR spectra of compounds 3a-h and 4a-e usually show one set of characteristic peaks for each group, especially one singlet at about 5.10 ppm for one proton of the epoxy unit, which clearly indicates that only one isomer exists in each sample. However, 1 H NMR spectra of compounds 3a and 3f clearly displayed that the trans-isomer existed mainly with ratios of cis/trans isomers of 1:14 and 1:8, respectively. From Figure 1 and Figure 2 it is seen that the phenyl group of the oxindole unit and the benzoyl  group existed in the cis-position. This result also indicated that the thermodynamic reaction produces a more stable transisomer.

To further illustrate the power of this reaction procedure, the N-substituted isatins were also employed to react with phenacyl bromides under similar reaction conditions. A series of new spiro epoxyoxindoles 5a-p were prepared in high yields (Table 4). The structures of the spiro compounds 5a-p were also established by spectroscopic methods and were confirmed by single-crystal X-ray structure determination of compound 5o (Figure 3). 1 H NMR spectra showed that a mixture of cis/trans isomers existed in most samples with a large range of different cis/trans ratios. It is known that the closure of the epoxy ring would form cis/trans isomers in the Darzens reaction process.

Here the N-benzyl and the N-butyl group in the oxindole moiety may decrease the steric effect of formation of the epoxy ring and lead to the easier formation of the relatively unstable cisisomer.

Conclusion

In summary, we have systematically investigated the Darzens reaction of phenacyl bromides with isatins for the efficient synthesis of the functionalized spiro epoxyoxindoles. Both the nonsubstituted isatins and N-alkylated isatins were successfully used in the reactions. The scope and limitation of the reaction was established. The N-alkylation of the isatins is usually accompanied by the formation of spiro epoxyoxindoles.

Experimental

Reagents and apparatus: Melting points were taken on a hotplate microscope apparatus. IR spectra were obtained on a Bruker Tensor 27 spectrometer (KBr disc). NMR spectra were recorded with a Bruker AV-600 spectrometer with DMSO-d 6 as solvent and TMS as internal standard (600 and 150 MHz for 1 H and 13 C NMR spectra, respectively). HRMS were measured on a UHR-TOF maXis instrument. X-ray data were collected on a Bruker Smart APEX-2 diffractometer. Isatins, phenacyl bromide and other reagents are commercial reagents and were used as received. Solvents were purified by standard techniques. All reactions were monitored by TLC.

Typical procedure for the preparation of spiro[indoline-3,2'-oxiran]-2-ones 3a-h:

A mixture of isatin (1.0 mmol), phenacyl bromide (1.0 mmol) and potassium carbonate (1.2 mmol) in 20.0 mL chloroform was stirred at 50 °C for 10-24 h (TLC analysis). After cooling the reaction was quenched with water. The solvent was evaporated under reduced pressure. The residue was recrystallized from ethanol to give the pure product for analysis.

3'-benzoylspiro[indoline-3,2'

-oxiran]-2-one (3a) [32] Typical procedure for the preparation of spiro[indoline-3,2'-oxiran]-2-ones 5a-p: A mixture of isatin (1.0 mmol), phenacyl bromide (1.2 mmol) and potassium carbonate (1.5 mmol) in 20.0 mL of chloroform was stirred at 50 °C for 10-24 h (TLC analysis). After cooling, the reaction was quenched with water. The solvent was evaporated under reduced pressure. The residue was recrystallized with ethanol to give the pure product for analysis.

3'-benzoyl-1-benzylspiro[indoline-3,2'-oxiran]-2-one (5a) [35]

Answer: A series of functionalized spiro[indoline-3,2'-oxiran]-2-ones was efficiently synthesized by Darzens reaction of phenacyl bromides with isatins both with N-alkyl groups and without N-substituent in the presence of potassium carbonate as a base catalyst. When two equivalents phenacyl bromides were used in the reaction, the N-substitution reaction of isatin also finished with the formation of spiro-oxirane-oxindoles.


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

Paper text:
the treatment of chronic hepatitis c ( chc ) has evolved in the last 15 years from monotherapy with interferon alpha ( ifnalpha ) to the combination treatment with pegylated ifn ( peg - ifn ) plus ribavirin for 24 - 48 weeks . up to now , several viral , host and drug - related reactions in response to ifnalpha - based therapy have been identified .
recent studies suggest that liver inflammation in chc is controlled by several mechanisms , including host regulatory immune responses and viral polypeptides interacting with cells involved in innate and adaptive immunity .
it is well known that cutaneous side effects of treatment with ifnalpha alone or ifnalpha plus ribavirin in patients with chc have been widely reported , beyond the fact that the virus itself can cause skin lesions . however , the cutaneous side effects during therapy of chc are of inflammatory type with local erythema , edema and , much less frequently , necrosis at the injection skin sites . by contrast ,
skin side effects of such drugs have few data available in the literature , although the number of reports has been increasing in the last years , including cosmetic filler site injections .
roughly one half of these patients had cutaneous findings , either alone or with systemic involvement .
more recently there have been reported dermatological diseases in patients receiving the combination of ifn / ribavirin or ifn / ribavirin / amantadine for the treatment of chc .
a 44-year - old man with chc genotype 1a and a viral load of hcv > 800,000 iu / ml , a2-f1 on liver biopsy according to metavir criteria , was treated for the hepatic disease .
peg - ifnalpha-2b 1.5 g / kg weekly and 1,000 mg of ribavirin daily was introduced . in the 40th week
the patient reported sudden intense pain , pruritus , erythema and skin hypertrophy in the left deltoid area over the seahorse tattoo and in a scar on his face ( fig .
1 ) . a skin biopsy on the scar and tattoo showed granulomatous dermatitis ( fig .
chest x - ray was normal and the level of angiotensin enzyme converter was 50 iu / ml ( range 18 - 55 iu / ml ) .
we intend to call attention especially to dermatologists to the possibility of a granulomatous tattoo reaction as a side effect during chc treatment with peg - ifnalpha-2b plus ribavirin . until now
, eight cases of sarcoidosis as a complication of ifn therapy in chc have been reported in the english language literature .
the most relevant topic in this case is the occurrence of disease on a tattoo area .
six months later retreatment using peg - ifnalpha-2a 180 g once a week plus ribavirin 1,000 mg daily was tried . in the 6th week , cutaneous symptoms relapsed in an unbearable way .
the patient did not accept to continue therapy , since hydrocortisone cream was prescribed again but no satisfactory pruritus and pain improvement was noticed . a prompt regression of skin reaction occurred after stopping therapy .
sarcoidosis is a granulomatous disorder of unknown etiology and whose epidemiology suggest a genetic tendency face to infectious agents being supposed to result of immune system deregulation leading to non - caseating granulomas as an immune reaction to an unknown persistent antigenic stimulus .
ifn has been linked to pulmonary macrophage activation , a characteristic feature of sarcoidosis which has been assumed an exaggerated t helper 1 ( th-1 ) immune response to a variety of exogenous antigens .
it seems very likely that a potent immunoregulatory protein for th-1 response such as ifn may induce the disease . in january 2003 the eighth case of ifn - related sarcoidosis was reported with a review of the literature .
chest x - ray revealed hilar lymphadenopathy in three patients , with reticulonodular shadows in another three , while the patient with only cutaneous involvement had a normal chest x - ray .
the case we report presented with cutaneous sarcoidosis during chc therapy and spontaneous regression of the lesions was noted with treatment discontinuation .
we intend to emphasize , especially to dermatologists , the risks of a granulomatous tattoo and other cutaneous sites during chc treatment with peg - ifnalpha-2b plus ribavirin .
thalidomide has been also shown to have specific activity to the inflammatory mediators of sarcoidosis and to be an alternative beneficial therapy .

Answer:
the treatment of chronic hepatitis c ( chc ) has evolved in the past 15 years and combination of pegylated interferon plus ribavirin is its current standard therapy . however , several side effects are commonly observed and frequently lead to transient or definitive interruption of treatment .
 although sarcoidosis in its systemic or cutaneous form is a very rare side effect in such circumstances , some cases have been reported even with conventional interferon .
 this brief review of the literature and description of a case of sarcoidosis occurring in a tattoo and a scar patient 's face , during treatment with pegylated interferon alpha-2b plus ribavirin , is an educative report directed in special to dermatologists .
 the lesion improved after drug interruption and recurred after retreatment with pegylated interferon alpha-2a .
 we conclude that this side effect must call the attention of doctors to seek for the diagnosis and therapy as soon as possible in such circumstances .
 no differences were noticed neither with alpha-2a nor alpha-2b pegylated interferon employment .


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:
geriatric population is on rise globally because of increasing life span . as per the us census ,
people above 60 years constituted 6.4% of the total population in 1900 , which increased to 18.4% in 2010 and predicted to go up to 25.5% by 2050.1 spinal problems and spine surgeries in geriatric population are also showing a similar trend .
lumbar fusion surgeries in people aged 60 years and above have increased by 230% in a decade from 1991 to 2001.2 desire to lead a more active life in advanced age , improved diagnostic techniques , and better operative results are some of the reasons for increasing spine surgeries in the elderly . in general , spine surgery in the elderly in the presence of comorbidities
is feared among both patients and surgeon , as it is presumed to have higher perioperative complications and increased cost .
many articles can be found in literature supporting this.345 a study by daubs et al .
involving adult spinal deformity in people over 60 years of age has reported that age and complication rates do not affect the surgical outcome.6 similar studies have reported 91%96% good to excellent results following surgical treatment of lumbar canal stenosis ( lcs ) by decompression and decompression with fusion on people aged above 6570 years.789 this indicates that in the absence of complications , spinal decompression and fusion surgeries would result in a satisfied patient even in the elderly with comorbidities .
therefore , measures to reduced complications in such patients should be looked at rather than denying surgical management in symptomatic patients due to their old age or comorbidities .
this study evaluates the perioperative complications and the contributing factors in patients over 60 years of age undergoing lumbar fusion surgeries .
patients aged 60 years and above with one or more comorbidities undergoing lumbar decompression and instrumented fusion at our institute between january 2012 and december 2013 ( 2-year period ) were included in the study . in all these patients ,
perioperative complications ( intraoperative and complications occurring within 3 weeks postoperative period ) and their incidence were recorded .
the technique was a standard open technique of pedicle screw instrumentation and fusion , either interbody by transforaminal approach or posterolateral using morcellized bone from the posterior elements or rarely with iliac crest .
age , number of levels instrumented and fused , operative time , blood loss , comorbidities , and the duration of stay were correlated with the incidence of perioperative complications using spss software ( ibm , spss statistics v 23.0 , new york , united states ) .
factors contributing to perioperative complications were noted and measures to reduce them were suggested by these results and compared with the available literature in discussion .
analysis of our medical records revealed a total of 52 patients operated by lumbar fusions in the 2-year study period , who were aged 60 years and above and had one or more comorbidities .
most common indication for surgery was spondylolisthesis in 17 ( 32.7% ) followed by lcs in 15 ( 28.8% ) patients .
hypertension ( htn ) was the most common comorbidity found in 39 patients ( 75% ) , followed by diabetes mellitus ( type 2 ) in thirty patients ( 56.4% ) .
twenty patients had single comorbidity while 18 patients had two comorbidities and 13 patients were found to have three comorbidities [ table 1 ] .
preoperative mri t2w , midsagittal ( a ) and axial ( b ) images showing multilevel listhesis and canal stenosis .
postoperative x - ray lumbosacral spine anteroposterior ( c ) and lateral ( d ) views showing implant ( pedicle screws ) in situ following instrumented fusion diagnosis and comorbidites of patients forty six patients were operated under general anesthesia ( ga ) while the remaining six patients were operated in regional or spinal anesthesia .
3.8 levels were the average levels instrumented per patient while one patient underwent 9 levels instrumentation .
interbody fusions were performed at single level in 24 , 2 levels in 22 , and 3 levels in 6 patients .
average operative time and blood loss were 150 min ( range 60270 min ) and 369 ml ( range 901050 ml ) , respectively . both operative time and blood loss
the levels of instrumentation and fusions were decided on segmental instability observed on dynamic radiographs .
the interbody fusions were based on degree of segmental stenosis , disc degeneration , and instability .
clinical details of patients operative time and blood loss with respect to the number of interbody fusion levels a total of 11 complications were noted , 3 systemic and 8 local . among the systemic complications , 2 were hypostatic pneumonia with secondary infection and one was a psychiatric illness called ganser 's syndrome . all the three patients required transfer to icu and one patient with pneumonia expired due to septicemia and shock .
the average total duration of stay in the hospital was 6.2 days ( range 4 - 14 days ) .
on comparing the complication rates with other variables , we found that the patients with complications had higher blood loss , operative time , number of instrumented levels , and number of interbody fusion levels [ tables 4 and 5 ] .
similarly , the duration of stay was longer in these patients . on analyzing these results statistically by anova , the association of blood loss with complications was found to be statistically significant with p = 0.002 .
the duration of stay , operative time , and number of interbody fusion levels were close to significance with p = 0.63 , 0.58 , and 0.61 , respectively , while number instrumented levels and the number of associated comorbidities showed no significance [ tables 4 and 5 ] .
the complications and their incidence comparisons of different variables in patients with and without complications on analyzing the correlations between different variables , we found that there was a strong positive correlation of blood loss with operative time , number of instrumented levels , and number of interbody fusions which was statistically significant .
similarly , operative time showed a strong positive correlation with number of interbody fusions and a significant but a weaker positive correlation with number of instrumented levels [ table 6 ] .
the perioperative complication rates in the present study occurred in 11 of 52 patients with an incidence of 21% . increased blood loss strongly correlated with the incidence of complications .
age , operative time , number of levels of fusion , and the duration of stay were also more in patients with complications and were close to statistical significance while number of instrumented levels and number of associated comorbidities were unrelated to the complication rates .
perioperative complication rates in instrumented lumbar fusions in patients above 60 years of age described in literature range from 29% to 62% [ table 7 ] .
reported increased complications in patients with advanced age and surgeries with increased blood loss and number of levels of fusions.1112 carreon et al.11 found increased complication rates with increased operative time while cho et al.12 found no such association .
guigui et al.10 found comorbidities to influence the complication rates and a similar study by acosta et al.4 found ten times higher complication rates in patients with htn while others found no association between comorbidities and the perioperative complications.612 the incidence of complications and factors affecting it described in the literature considering the group of population included , the complication rate in our series was within the acceptable limits compared to literature [ table 7].4611121314 our patients were 60 years and above with the average age of 69 years , all of them had one or more comorbidities , and the average number of levels fused was 3.8 , making this group more vulnerable for complications . despite this , the complications in our series were about 21% with most of them being minor reversible complications such as dural tear , transient root deficits , and postoperative persistent radicular pain .
similarly , the operative time and blood loss , in our series , was lesser compared to that described in literature for multilevel fusions [ table 7].4611121314 the blood loss in literature ranged from 206 ml in single level to 2056 ml in 9-level fusions and the operative time ranged from 145 min in single level to 415 min in 10.5-level fusions [ table 7].4611121314 in comparison in our series with an average of 3.8 levels of fusion , the average operative time and blood loss were 150 min ( range 60270 min ) and 367.45 ml ( range 901050 ml ) , respectively .
this could possibly explain the lesser complication rates in our study as the complications were strongly related to the operative time and blood loss .
on reviewing literature and analyzing our surgical technique , we found several strategies that helped in reducing the blood loss and operative time , and hence the complications .
injection tranexamic acid 1 g intravenous was given routinely preoperatively , immediately before skin incision in all cases .
literature describes that a single dose of tranexamic acid 15 mg / kg can effectively reduce blood loss without increasing the risk of deep vein thrombosis.15 the other technique employed in our surgeries was simultaneous exposure and instrumentation on either side by two trained spine surgeons [ figure 2 ] .
this reduced the surgery time and also the blood loss as compared to a single surgeon exposing and instrumenting one side after the other .
we employed a laminectomy technique described by okuda et al.16 in which lamina was removed as a single fragment using osteotome and making cuts at pars on either side .
this further reduced the operative time as compared to the classical technique of removing the lamina piecemeal by rongeurs .
( a and b ) intraoperative images showing the technique of bilateral exposure and bilateral instrumentation operative time and blood loss were strongly related to the number of levels of vertebra instrumented and fused . even though operative time and blood loss could be reduced by reducing the number of instrumented and fused levels , not instrumenting or fusing the levels when indicated would compromise the principles of surgery and therefore affect the clinical outcome .
hence , the number of vertebrae fused or instrumented should be restricted to the minimum indicated levels , without compromising on indications .
we also found that the blood loss increased steeply with number of interbody fusion levels .
the average blood loss in single level interbody fusion was 307 ml which increased to 362 ml in 2 levels and almost doubled in 3-level interbody fusions [ table 3 ] .
the reason for this exponential increase being continued bleeding from the bed of prepared interbody levels while performing the next level .
performing interbody fusions at selected levels such as the most stenotic or unstable levels or at the bottom of the construct and posterolateral fusions at other levels also could reduce the blood loss and hence the complications [ figures 3 and 4 ] . bar diagram showing the relation between the intraoperative blood loss and number of interbody fusion levels postoperative x - rays anteroposterior and lateral views of lumbosacral spine showing interbody fusions at l2l3 , l4l5 , l5s1 with posterolateral fusion at l3l4 images apart from reduction in operative time and blood loss , a thorough preoperative workup with concerned specialist consultations such as pulmonologist , cardiologist , and optimization of the medical conditions helped in reducing the anesthetic risks during surgery .
six of our patients in the series underwent surgery under spinal or combined spinal epidural anesthesia , due to poor pulmonary or cardiac status .
studies have shown regional anesthesia ( ra ) in spine surgery to have many advantages over ga in high - risk patients , like lesser anesthetic intraoperative complications , lesser postoperative htn , respiratory and cardiovascular complications , lesser postoperative vomiting , longer postoperative analgesia , and shorter hospital stay.1718 as surgeons we found spinal anesthesia to be satisfactory with reduced blood loss due to stable blood pressure one of these patients underwent surgery in sitting position which has shown in literature to be more convenient for the patient under ra , with the blood draining by gravity , resulting in clearer operative field and also reduce anesthesia complications by creating a hemodynamic status similar to that in othostasis.19 early mobilization postoperatively with optimal control of medical comorbidities also helped in reducing the early postoperative complications .
lumbar fusion surgeries in the elderly with comorbidities have higher complications rates . increased intraoperative blood loss significantly correlated with the complication rates .
spinal decompression and fusion surgery when indicated should not be denied merely considering the age and comorbidities of the patients , fearing complications .
causes and measures to reduce complications should be considered as the outcome of surgeries in these patients in the absence of complications is good .
the authors propose some of the measures to reduce the operative time , blood loss , and hence the complication rates in these patients .

mahesh - research grant by ulrich india and consultancy from medtronic india ltd.upendra - research grant from medtronic india .

 mahesh - research grant by ulrich india and consultancy from medtronic india ltd.upendra - research grant from medtronic india .

Answer:
background : spine surgery in elderly with comorbidities is reported to have higher complication rates and increased cost . however , the surgical outcome is good irrespective of the complications .
 hence , it is essential to identify the factors affecting the complication rates in such patients and the measures to reduce them .
 this retrospective observational study determines the perioperative complications , their incidence and the measures to reduce complications in the elderly with comorbidities , operated by instrumented multilevel lumbar fusion.materials and methods : patients aged 60 years and above with one or more comorbidities operated by multilevel instrumented lumbar fusion in our center between january 2012 and december 2013 were included in the study .
 perioperative complications and their incidence were calculated .
 age , number of levels fused , operative time , blood loss , and complication rates were correlated with the duration of stay and the incidence of perioperative complications using spss software . measures to reduce complications
 are determined by these results and by review of literature.results:fifty two patients were included in the study ( 28 females and 24 males ) with an average age of 69 years ( range 60 - 84 years ) .
 hypertension was the most common comorbidity followed by diabetes .
 spondylolisthesis was the most common indication .
 eleven complications were noted with an incidence of 21% .
 three were systemic complications which required transfer to intensive care unit .
 local complications were incidental durotomy ( three ) , transient root deficits ( two ) , wound infections ( one ) , and persistent radicular pain ( two ) .
 operative time and blood loss were significantly higher in patients with complications.conclusion:complication rates strongly correlate with the blood loss and operative time . reducing the operative time and blood loss by intraoperative tranexamic acid , laminectomy using osteotome , simultaneous bilateral exposure and instrumentation and reducing the number of interbody fusions can help in reducing the complications .


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:
Reactivity of bromoselenophenes in palladium-catalyzed direct arylations

Paper sections:
Introduction

(Hetero)aryl-substituted selenophenes represent a class of molecules which exhibit useful physical properties, especially for the preparation of artificial photosynthetic systems for solar energy conversion or for thin film transistor applications [1][2][3]. In most cases, these (hetero)arylated selenophenes are currently prepared through the use of transition-metal-mediated reactions such as Stille [3][4][5][6][7][8][9], Suzuki [10][11][12][13][14][15][16][17][18][19], or Kumada [20] couplings [21] (Scheme 1a and b). However, all these procedures require the preparation of an organometallic or a boron derivative of one of the coupling partners, and provide an organometallic salt (MX) as waste. In recent years, the Pd-catalyzed arylation, via a C-H bond activation, of a broad range of heteroaromatics using aryl halides as reaction partners was demonstrated to be particularly effective for the preparation of bi(hetero)aryls [22][23][24][25][26][27][28][29][30][31]. Among the reported results, a few examples of Pd-catalyzed direct arylations via the C-H bond activation of selenophenes using aryl halides as coupling partners have been reported [32][33][34][35]. Conversely, C-H bond activation methodology was employed in only in one case for the preparation of a heteroarylated selenophene from a haloselenophene. Wipf et al. reported in 2014 that using ethyl oxazole-4-carboxylate as reaction partner, the corresponding 2,5-bis(oxazol-2-yl)selenophene derivative was formed in 45% yield (Scheme 1c) [17]. Moreover, to our knowledge the Pd-catalyzed direct heteroarylation of 2-bromoselenophene has not yet been described. Therefore, the reactivity of 2-bromo-and 2,5-dibromoselenophenes in Pd-catalyzed direct couplings with heteroarenes needed to be investigated.

Herein, we wish to report on the reactivity of 2-bromoselenophene, 2,5-dibromoselenophene and 2-aryl-5-bromoselenophenes in palladium-catalyzed direct heteroarylations with a variety of heteroarenes using a phosphine-free palladium catalyst.

Results and Discussion

First, we examined the influence of the reaction temperature, using DMA as solvent, KOAc as base and 2 mol % Pd(OAc) 2 as catalyst (Table 1). We had previously observed that these reaction conditions allowed the coupling of several heteroaro-matics such as thiazole, pyrrole, furan or imidazole derivatives with aryl bromides [36]. 2-Bromoselenophene, which was easily prepared by reaction of selenophene with N-bromosuccinimide [37], and 2-ethyl-4-methylthiazole were employed as model substrates for our study. Reactions performed at 130 °C or 110 °C gave the expected arylated selenophene 1 in 55% and 64% yields, respectively, with complete conversions of 2-bromoselenophene; whereas 1 was obtained in a higher yield of 80% when the reaction was conducted at 90 °C (Table 1, entries 1-3). At elevated temperature (110-130 °C), 2-bromoselenophene seems to afford larger amounts of selenophene oligomers as side-products. The use of PdCl 2 or PdCl(C 3 H 5 )(dppb) as catalysts instead of Pd(OAc) 2 or other bases such as K 2 CO 3 , Cs 2 CO 3 , CsOAc or NaOAc afforded 1 in lower yields (Table 1, entries 4-9). The influence of two other solvents in this cross-coupling reaction was also examined. We observed that both DMF and xylene in the presence of 2 mol % Pd(OAc) 2 catalyst with KOAc gave 1 in moderate yields (Table 1, entries 10 and 11). Then, we investigated the scope of the coupling of 2-bromoselenophene with a set of heteroarenes in the presence of 2 mol % Pd(OAc) 2 , KOAc as the base in DMA at 90 °C (Scheme 2). The reaction of 2-isopropyl-4-methylthiazole gave the desired product 2 in 82% yield. Conversely, low yields in the target products 3-5 were obtained for the reactions with thiophene-2-carbonitrile, 2-chlorothiophene and 2-pentylthiophene, although complete conversions of 2-bromoselenophene were observed. A similar result was obtained for the reaction with 1-phenylpyrrole. Reactions performed at a higher temperature with thiophene-2-carbonitrile, 2-chlorothiophene afforded 3 and 4 in slightly lower yields. Gorelsky calculated that the Gibbs free energies of activation for the cleavage of C-H bonds at C5-position of thiophene or pyrrole derivatives, for reaction which proceed via concerted metallation-deprotonation [38][39][40], are higher than that of thiazoles (see bottom of Scheme 2) [42]. We assume that, due to these higher energies of activation for reactions with thiophene or pyrrole, larger amounts of selenophene oligomers were formed in the presence of these less reactive heteroarenes. Then, the reactivity of imidazo[1,2a]pyridine, which contains a very reactive C-H bond at C3-position was examined. The expected product 7 was obtained in a high yield of 81%. Thus, for Pd-catalyzed direct heteroarylations of 2-bromoselenophene, only the heteroarenes containing C-H bonds with low Gibbs free energies of activation [41] should be employed.

By contrast, the direct arylation reactions with 2,5-dibromoselenophene were found to tolerate both thiazole and thiophene derivatives (Scheme 3). The coupling of 3 equiv of thiazole derivatives with 2,5-dibromoselenophene in the presence of 2 mol % Pd(OAc) 2 and KOAc as base gave the corresponding 2,5-diheteroarylated selenophenes 8 and 9 in 78% and 80% yields, respectively. The use of 2-pentyl-and 2-chlorothiophenes also gave the desired products 10 and 11 in high yields. In general, the Pd-catalyzed direct arylation of 3-substituted thiophenes with aryl halides afforded quite regioselectively the C2-arylated thiophenes [30]. A similar regioselectivity was oberved for the coupling of thiophene derivatives containing methyl-or chloro-substituents at the C3-position with 2,5dibromoselenophene. In both cases, regioselective arylations at the C2-positions were observed, affording the 2,5-diarylated selenophenes 12 and 13 in 69% and 72% yields, respectively. From 2,5-dibromoselenophene and an excess of 1-methylpyrrole, the expected 2,5-diarylated selenophene 14 was obtained in 81% yield. Finally, we show a sequential transformation leading to 2-aryl-5-(heteroaryl)selenophenes in three steps from commercially available compounds (Scheme 4). Bromination at the C5-position of 2-arylselenophenes containing nitrile, acetyl or chloro substituents on the aryl moiety, could be easily obtained in good yields from selenophene and aryl bromides via a Pd-catalyzed direct arylation using a reported procedure [33], afforded the 2-aryl-5-bromoselenophenes 15-17 in 84-90% yields. Then, a second Pd-catalyzed direct arylation using heteroarenes and 15-17 as reaction partners, provided the target compounds 18-26 in high yields. Both thiazole and thiophene derivatives were successfully employed in this transformation. The reaction tolerates useful functional groups on both coupling partners such as nitrile, acetyl or chloro. It should be mentioned that again a regioselective arylation at the C2-position of 3-chlorothiophene was observed affording 26 in 72% yield.

Although the mechanism of these reactions was not elucidated, the catalytic cycle shown on Scheme 5 can be proposed. The first step is probably the oxidative addition of the 2-bromoselenophene to Pd(0) to afford the Pd(II) intermediate A.

Then, after elimination of KBr with KOAc, a concerted metalation-deprotonation pathway involving an heteroarene gives B. Reductive elimination affords the 2-heteroarylated selenophene with regeneration of the Pd(0) species.

Conclusion

In summary, the reactivity of 2-bromoselenophenes was investigated and revealed that the C2-heteroarylation of 2-bromoselenophene in high yields is only possible with specific heteroarenes such as thiazoles and imidazopyridines, whereas thiophene or pyrroles gave the desired products in low yields. Conversely, 2,5-dibromoselenophene was successfully coupled with both thiazoles and thiophenes in the presence of phosphine-free Pd(OAc) 2 catalyst precursor and KOAc as inexpensive base, affording the desired 2,5-diheteroarylated selenophenes in high yields. We also described that the sequential catalytic C2-arylation, bromination, and catalytic C5-arylation of selenophene provides the controled double (hetero)arylation at the C2 and C5 positions of selenophene in good yields.

Experimental

General procedure for palladium-catalyzed direct mono-heteroarylations of 2-bromoselenophene

The reaction of the heteroarene (1.5 mmol), 2-bromoselenophene (0.210 g, 1 mmol) and KOAc (0.196 g, 2 mmol) at 90 °C during 24 h in DMA (4 mL) in the presence of Pd(OAc) 2 (4.5 mg, 0.02 mmol), under argon affords the coupling products 1-7 after evaporation of the solvent and purification on silica gel. Eluents: Pentane for compounds 3 and 4. EtOAc/pentane 2:98 for compounds 1 and 6. EtOAc/pentane 10:90 for compound 2 and 5 and EtOAc/pentane 40:60 for compound 7.

General procedure for palladium-catalyzed direct diheteroarylations

The reaction of the heteroarene (3 mmol), 2,5-dibromoselenophene (0.289 g, 1 mmol) and KOAc (0.392 g, 4 mmol) at 90 °C during 40 h in DMA (4 mL) in the presence of Pd(OAc) 2 (4.5 mg, 0.02 mmol), under argon affords the coupling products 8-14 after evaporation of the solvent and purification on silica gel. Eluents: Pentane for compounds 10-13. EtOAc/ pentane 5:95 for compounds 8, 9 and 14.

General procedure for the synthesis of 5-bromo-2-arylselenophenes 15-17

To a mixture of the 2-arylselenophene [2] (2 mmol) in DMF (5 mL) at 0 °C, N-bromosuccinimide (0.392 g, 2.2 mmol) was slowly added. Then, the mixture was allowed to increase to room temperature and stirred during 20 h. After addition of water, the extraction was carried out with diethyl ether. Then, the organic phase was dried over magnesium sulphate. Finally, evaporation of the solvent and purification on silica gel afforded the 5-bromo-2-arylselenophenes 15-17. Eluents: Pentane for compounds 15 and 16. EtOAc:pentane 5:95 for compound 17.

General procedure for palladium-catalyzed direct mono-heteroarylations of 2-bromo-5arylselenophenes

The reaction of the heteroarene (1.2 mmol), 2-bromo-5-arylselenophene 15-17 (1 mmol) and KOAc (0.392 g, 4 mmol) at 150 °C during 16 h in DMA (4 mL) in the presence of Pd(OAc) 2 (4.5 mg, 0.02 mmol), under argon affords the coupling products 18-26 after evaporation of the solvent and purification on silica gel. Eluents: Pentane for compounds 21 and 22. EtOAc/pentane 5:95 for compounds 18 and 19. EtOAc/pentane 10:90 for compounds 20, 23, 24 and 26. EtOAc/pentane 20:80 for compound 25.

ORCID ® iDs

Ridha Ben Salem -https://orcid.org/0000-0002-5179-351X Jean-François Soulé -https://orcid.org/0000-0002-6593-1995 Henri Doucet -https://orcid.org/0000-0002-1410-3663

Answer: The reactivity of 2-bromo-and 2,5-dibromoselenophenes in Pd-catalyzed direct heteroarylation was investigated. From 2-bromoselenophene, only the most reactive heteroarenes could be employed to prepare 2-heteroarylated selenophenes; whereas, 2,5dibromoselenophene generally gave 2,5-di(heteroarylated) selenophenes in high yields using both thiazole and thiophene derivatives. Moreover, sequential catalytic C2 heteroarylation, bromination, catalytic C5 arylation reactions allowed the synthesis of unsymmetrical 2,5-di(hetero)arylated selenophene derivatives in three steps from selenophene.


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:
most of the children with cerebral venous thrombosis have an underlying chronic disease and those who are previously well have an acute infectious illness .
obstructive hydrocephalus as a complication of cerebral venous thrombosis is rare and few cases are described .
a previously healthy 4-year - old boy presented with 5 days of headache and vomiting .
magnetic resonance imaging of the patient revealed obstructive hydrocephalus and magnetic resonance venography revealed thrombosis of the right transverse sinus [ figure 1 ] .
low molecular weight heparin was started at a dosage of 1 mg / kg twice a day .
control magnetic resonance imaging and magnetic resonance venography 1 month after the first event revealed partial resolution of hydrocephalus along with recanalization of the affected sinus [ figure 2 ] .
hydrocephalus and absent flow in the right transverse sinus showing acute thrombosis improvement of hydrocephalus and recanalization of the affected sinus after a month of heparin therapy with folic acid and vitamin b6 and b12 replacement , the follow - up of the patient was given up by the family and he did not receive any treatment for 5 months .
six months after the first event , the patient was again admitted to hospital with a similar clinical picture along with new thrombosis at the sagittal sinus .
the patient is still followed up with low molecular weight heparin treatment after the second thrombosis attack .
cerebral venous system thrombosis is an unusual event in childhood and clinical presentations , complications , diagnostic procedures , etiological investigations , and treatment modalities were not well established .
clinical findings of cerebral venous system thrombosis include seizures , headache , vomiting , drowsiness , lethargy , and confusion .
the patient may show acute or subacute picture related to progression of the disease . the present case presented with acute symptoms secondary to increased intracranial pressure . increased intracranial pressure
is a well - known complication of cerebral venous thrombosis , but accompanying hydrocephalus is rarely described .
the mechanism of hydrocephalus is considered to be secondary to an increase in venous pressure resulting in the blockade of cerebrospinal fluid flow into the sinuses by arachnoid villi .
most of the patients with cerebral venous thrombosis have an increased intracranial pressure without an increase in ventricular size .
why some patients develop hydrocephalus is not clearly understood and only a few adult cases were described .
the etiologies regarding cerebral venous thrombosis are diverse and include head and neck infections and chronic disorders such as collagen tissue disorders , cardiac disease , and hematological abnormalities .
half of the patients have prothrombotic states which include anticardiolipin antibodies , deficiencies of protein c and s , antithrombin iii and prothrombotic gene mutations such as prothrombin 20210 , factor v leiden , and mthfr mutations .
the most frequent two common mthfr polymorphisms are c677 t ( alanin to valin transition ) and a1298c ( glutamine to alanine transition ) .
evaluation of nine case control studies with total 382 patients having cerebral venous thrombosis revealed that carrying mthfr was not a risk factor for cerebral venous thrombosis . on the contrary
a canadian study revealed that 29% of patients with cerebral venous thrombosis had mthfr polymorphisms .
our case had a prothrombotic state with mthfr 1298 homozygous polymorphism without any risk factors .
occurrence of clinical findings after cessation of heparin treatment suggests that mthfr polymorphism may be an important risk factor for cerebral venous thrombosis .
anticoagulation is not recommended for asymptomatic and hemorrhagic cases . when used , low molecular weight heparin is the standard anticoagulant treatment in children .
treatment may last for 36 months or it may be continued until recanalization if risk factors are eliminated .
our patient responded well to low molecular weight heparin with recanalization of sinuses and recovery of hydrocephalus in both the attacks . in conclusion
mthfr 1298 polymorphism may be an important risk factor and low molecular weight heparin should be the choice of treatment in cases without hemorrhage .

Answer:
cerebral venous thrombosis is a rare form of stroke in childhood .
 increased intracranial pressure is a well - defined complication of cerebral venous thrombosis but obstructive hydrocephalus as a presentation finding of cerebral venous thrombosis is rarely described . a child case of cerebral sinus thrombosis presenting with obstructive hydrocephalus and management of clinical condition
 is presented with discussion of reported cases and treatment recommendations .