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:
Synthetic in vitro circuits

Paper sections:
Introduction

Breakthroughs in our ability to read and write DNA have enabled researchers to construct sophisticated, circuit-like behavior in living systems [1]. More than ten years ago, pioneering efforts by Elowitz and Leibler and Gardner et al. [2,3] provided a conceptual framework for viewing cells as a system of interacting circuits – structures composed of several elements that are capable of information processing by accepting an input, executing a series of logical computations, and producing an output. This framework, championed by many synthetic biologists [4], has inspired new applications and shed light on our understanding of fundamental biological phenomena. Nevertheless, in vivo circuitry is often unpredictable. Even if the functions of individual `parts' are known, they may not work as expected in different cellular contexts due to intertwined circuit dependencies and crosstalk between biomolecules. Thus, the complexity of successfully implemented in vivo circuits to date is limited in size and scope to tens of molecules [4]. This pales vastly in comparison to the simplest living organisms, which consist of several hundred to thousands of genes, non-coding RNA species, and small molecules.

As a complement to in vivo-based approaches, in vitro systems provide an unprecedented freedom to modify and control biochemical systems for technological applications and to understand the design principles of biological circuits. Removing genetic regulation, for instance, drastically reduces complexity by negating a cells' ability to adapt and evolve [5]. For decades, in vitro systems have made integral contributions to biological research in both discovery and technology - from discovery of the genetic code [6] to the development of core techniques such as the Polymerase Chain Reaction [7] as well as disruptive technologies for manufacturing-scale cell-free protein synthesis [8]. Now, the study of complex biological circuits is emerging as a novel application of in vitro systems that can complement and guide in vivo studies.

This review will focus on recent developments in the field of synthetic in vitro circuits over the last 3 years. We first examine minimal nucleic-acid based systems that offer unparalleled experimental flexibility and predictability. Next, we discuss circuits created in hybrid systems – containing purified enzymes and nucleic acids. We end our discussion of in vitro circuits on complex systems that are capable of transcription and translation.

Nucleic acid systems

While the classical sense of the word "circuit" conjures up images electricity flowing through transistors, DNA is capable of both carrying information and performing computations on that information [9,10]. Circuits constructed in this manner have relatively few possible interactions and points of control (Figure 1
(top)) making their quantitative description more manageable and comprehensive. They provide theoretical insight into the generalized function of chemical circuits based on diffusion and stochastic binding – principles that must be understood to make genetic circuit design a predictive science.

Dramatic increases in circuit complexity in DNA systems over the last three years partly stem from the development of `seesaw' gates that make use of toehold exchange reactions (Figure 2A,B) [11–13••]. In classical toehold displacement reactions, a single-stranded DNA (ssDNA) molecule displaces one strand of a double-stranded DNA (dsDNA) complex by binding to a complementary short overhang (toehold) region on the dsDNA. The ssDNA (input) displaces the previously bound strand of DNA (output), which can then serve as an incoming signal for another reaction. From this starting point, researchers have built a diversity of nano-scale devices and circuits capable of complex computation (see [14•] and [15] for more comprehensive reviews).

In the case of toehold exchange reactions, the reverse reaction is made possible by including a toehold design on both sides of the dsDNA molecule (Figure 2A). Only two cascaded seesaw gates are required to produce the OR and AND logical functions (Figure 2B) and more complex cascades can compute NOT, NAND, NOR, and XOR. To show the scalability of these gate units, Qian et al. constructed a neural network consisting of 112 DNA strands that demonstrates associative memory capable of answering 81 possible questions [16], as well as a 130-stranded DNA circuit capable of computing the square root of a 4 digit binary number [17•].

Models derived from experimental investigations [11,12] are increasingly accurate at predicting the kinetics of strand displacement reactions and have allowed construction of increasingly complex implementations. Further, experiments guided by thermodynamic models have verified designs that perform within a 20°C range of temperatures, 1–5 μM concentrations of nucleic acid, and 1–47 mM Mg2+ [18•]. This robustness illustrates that the understanding gained from these systems may be generalized to a range of conditions and not limited to particular experimental set-ups. A suite of computational tools, theoretical frameworks and even dedicated programming languages can be used to design and analyze DNA circuits [19–23]. Concurrently, novel theoretical possibilities [24] and practical implementations are continually being developed such as those utilizing hairpins [25,26], cooperative binding [27], deoxyribozymes [28,29], photochemical activation [30] and associative toehold activation [31].

Importantly, studying strand displacement circuits in vitro has led to practical uses that would have been difficult to anticipate prior to the expansion of this largely theoretically motivated work. Researchers have shown that in vitro DNA circuits can amplify signals and detect RNA and small molecule analytes using different reporting methods [32]. Further, an area of research that is likely to expand involves using DNA circuits as visualization tools for imaging DNA based reaction cascades [33], mRNA's [34] and reversibly imaging proteins [35].

Hybrid systems

Understanding and exploiting transcriptional logic is a complex problem that unites many fields of biology, but the vast number of interacting species and circuit cross talk within cells makes it difficult to characterize individual transcriptional gates. In vitro hybrid systems composed of DNA templates and purified enzymes, however, allow researchers to isolate the performance of small circuits before exploring how they interact within larger biochemical systems [36–39]. DNA still acts as the logic gate for signal integration (see Figure 3A for sample AND gate implementation), but the inputs and outputs can be DNA, RNA, or metabolites.

Hybrid systems are able to amplify signals, produce new signals, and degrade waste products – functionality that is difficult to implement in nucleic acid systems. Pioneering studies in 2011 highlight the diversity of these circuits, and the fact that similar high-level designs can be implemented in different ways. Montagne et al. created a system (the "Oligator") capable of sustained oscillations using DNA polymerase, a nicking enzyme, and an exonuclease that were responsible for amplification, propagation, and destruction of information carrying DNA oligonucleotides [40••]. This circuitry used only three template strands and three enzymes but was able to couple a positive feedback and a delayed negative feedback loop in a computationally predictable manner that used readily attainable parameters.

Using a different molecular implementation, Kim and Winfree produced a system capable of sustained oscillations by using RNA polymerase and RNaseH to produce and degrade cascading DNA/RNA signals [41••]. They showed oscillations using three distinct designs: a seven-stranded two-switch negative feedback oscillator, an amplified negative feedback oscillator which included the use of a positive feedback system, and finally a novel molecular implementation of a three-switch ring oscillator that was the focus of pioneering in vivo studies [2]. Franco et al. later expanded on this oscillating system and displayed potential applications by using the negative feedback oscillator as a timing device to separately activate DNA nanotweezers and produce an RNA aptamer [42••]. As with Montagne et al., modeling was integral to understanding system behavior and parameters – including concentrations and sequences – that would produce desired results. Merely by introducing the novel interaction that was required to time their device, the oscillations were severely restricted compared to the original system. This problem of coupling distinct systems was elegantly overcome through the use of an insulator circuit that isolated the output signal and prevented it from disrupting the timing device.

While the previous studies showed successful implementations of designs, they varied in their predictability and quantitative understanding of the systems. Deviations from kinetic models, especially with regards to the repressilator implementation, highlight the shortcoming of our knowledge and make a strong case for studying these systems before attempting to explain more complex cellular oscillators. For instance, incomplete degradation products may partially inhibit reactions in ways that are difficult to predict. In addition, small differences in transcription and degradation rates can compound over time and result in unstable oscillations with growing amplitudes or mono-stable behavior. Nevertheless, studies aimed at predicting and modeling more complex systems show a clear path forward for creating autoregulatory switches [43], neural networks [44], incoherent feed forward loops [45], pattern formation reactions [46•], as well as transcriptional rate regulation based on self-repression [47] and positive feedback [48].

As with DNA circuits, hybrid circuits have a variety of potential applications that are just beginning to emerge. In work that stems partly from initial theoretical and in vitro research[49], hybrid circuits were demonstrated inside Drosophila embryo lysates [50] providing insight on the functioning of circuits in a much more complex chemical environment. Several studies showed successful in vivo implementations of logical computing for potential applications in diagnosis and therapeutics [51,52].

Complete systems

Although previously mentioned studies may include the use of proteins, complete (either purified, or extract based) systems produce proteins in vitro and integrate them into circuits. Logical integration occurs at the DNA level but inputs and outputs may be DNA, RNA, protein, or metabolites – all of which may be produced, degraded, or modified in response to signals. Importantly, the diversity of interactions means that there are many more steps that must be understood for predictive implementation of complex circuits (Figure 1). However, these extra steps are also novel points of control that, once thoroughly characterized, may be exploited by researchers to construct highly complex logic systems.

Complete cell-free circuits began with the seminal work in 2003 of Noireaux et al. who showed that activating and inhibitory proteins could be produced in vitro and that one-, two-, and three-stage cascades could be created using these proteins as circuit elements [53]. Rather than relying on orthogonal promoters from these previous studies, Shin and Noireaux have recently recreated [54] and comprehensively characterized the endogenous sigma factor-based regulation system for use in Escherichia coli extracts [55••]. This allowed for the construction of the logical AND gate (Figure 3B), negative feedback loops, and multiple stage cascades. They also demonstrated the modularity of their toolkit for future applications of in vitro metabolic engineering and as a possible testing ground for in vivo recombinant circuit design. In complementary work, Asahara and Chong expressed promoter subunits and sigma factors in a single tube and showed promoter specific transcription initiation from solely in vitro translated and assembled products [56]. Taking an alternative route towards a similar goal, Karig et al. expanded on the original work of Noireaux et al. by showing that tool-kits based on orthogonal T7 promoters are capable of complex computations by characterizing several inducible and repressible variants and creating a negative feedback loop in vitro [57].

An overarching theme of these studies is the precise characterization of individual circuit elements, which are then implemented into complex cascades where their interactions may be controlled. While the search for biological `parts' has proven fruitful for in vivo synthetic biologists, many of these parts are still highly context dependent. In cell-free systems, these parts exist in a context outside of cellular adaptation and evolution and the results are therefore expected to be more tunable and reproducible. However, before controlling protein levels based on logic integration, we must understand the range of possible points of control and parameters that are important to steady-state protein levels. Karig et al. looked at the effects of ribosome binding sites and plasmid usage on target protein levels that were essential components of their circuit [57]. Though they did not explicitly recreate circuits, in separate studies Ahn et al. used cell-free systems to characterize the effects of 3' transcript stability, fusion partner leader sequences, and initial codons on protein production rate and steady state levels [58–60]. Many of these studies look at determinants of single protein production, but Du et al. have taken this work one step farther and studied the complications that arise when trying to express multiple proteins in vitro [61]. Karzbrun et al. took a step towards integrating the effects of these different components by creating a computational framework for predicting protein levels [62•]. With this knowledge, researchers may be able to implement logical control at specific processes to enable diverse circuit designs and some even dream of minimal cells [63].

Finally, in what we believe will be an increasing trend during the coming years, several studies have designed and analyzed circuits in vitro and successfully implemented those designs in vivo. Saito et al. developed a translational regulatory system based on L7Ae, an archael ribosomal protein, binding to mRNA molecules [64••]. They describe different mRNAs that are capable of activation and repression in response to the same protein input. This elegant study highlights the diversity of possible inputs that can be accepted by circuits composed in complete systems and exploits a unique control point that is only available in systems capable of translation. Importantly, their design was first tested in a purified cell-free translational system before being successfully implemented inside of a human cell-line. Similarly, Karig et al. tested their T7-driven negative feedback constructs in a purified cell-free translation system, cell extracts, and E. coli cells and showed the expected functionality across all systems [57]. These studies indicate that in addition to an increasing number of in vitro applications [65,66], in vitro environments can be a training ground for in vivo circuit design.

Conclusion

There has been dramatic growth in the construction, complexity, and predictability of cell-free biological circuits over the past three years. This growth underscores the importance of cell-free systems as a novel environment for engineering and analyzing complex biological circuits at the molecular level. In addition, designs that rely on DNA strand displacement reactions are yielding tremendous insight into the emergent behavior of complex chemical systems that lies at the heart of cellular life. Recent growth in this field also reflects an increasing interest in exploiting the unprecedented freedom of design afforded by cell-free biology for compelling applications [5,65–67]. The in vitro circuits described above, being structurally and functionally diverse, are poised to impact chemical, physical, biological, and computational research in diverse and unpredictable ways. This is precisely what makes their continued development necessary and exciting.

Answer: Inspired by advances in the ability to construct programmable circuits in living organisms, in vitro circuits are emerging as a viable platform for designing, understanding, and exploiting dynamic biochemical circuitry. In vitro systems allow researchers to directly access and manipulate biomolecular parts without the unwieldy complexity and intertwined dependencies that often exist in vivo. Experimental and computational foundations in DNA, DNA/RNA, and DNA/RNA/protein based circuitry have given rise to systems with more than 100 programmed molecular constituents. Functionally, they have diverse capabilities including: complex mathematical calculations, associative memory tasks, and sensing of small molecules. Progress in this field is showing that cell-free synthetic biology is a versatile training ground for understanding native biological circuits and engineering novel functionality.


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

Paper text:
primary amenorrhea is usually the result of a genetic or anatomic abnormality . in young women with primary amenorrhea ,
it is commonly caused by x - chromosome aberrations such as in turner syndrome , but individuals with a normal chromosome complement and ovarian dysgenesis also exist .
a 35-year - old female patient presented to our medical outpatient department with complaints of palpitation and chest pain of 6 months duration .
patient had paroxysmal episodes of palpitations that lasted few minutes , resolved spontaneously , and were not associated with exertion or other aggravating factors . patient had chest pain that was retro - sternal , intermittent not related to exertion and resolved spontaneously .
menstrual history revealed that she never attained menarche . on examination she had dolicocephaly , arachnodactyly , high arched palate , she was tall statured [ height 165 cm ; figure 1 ] , her arm span ( 176 cm ) was more than her height , arachnodactyly [ figure 2 ] , reduced upper to lower body segment ratio ( 0.83 ) , and she had positive wrist and thumb sign .
patient had underdeveloped rudimentary breasts ( tanner stage 2 ) , sparse pubic hair ( tanner stage 1 ) , and absent axillary hair .
cardiovascular examination revealed mid - systolic click with a late systolic murmur , other systems were essentially normal .
her blood glucose , renal function tests , liver function tests , and serum electrolytes were within normal limits .
echocardiogram echo / doppler revealed prolapse of anterior mitral leaflet , mitral regurgitation and normal left ventricular systolic function .
she had low levels of estrogen ( estradiol-10 pg / ml ; normal 15 - 200 pg / ml ) , serum testosterone ( 0.16 pg / ml , normal 0.6 - 6.8 pg / ml ) , and progesterone ( 0.56 ng / ml ) . she had elevated levels of gonodotropins , follicle - stimulating hormone ( fsh ) ( 101.3
serum prolactin ( 12 ng / ml , normal 0 - 20 ng / ml ) and thyroid function tests ( free t4 - 9.2 mcg / dl , normal 4.6 to 11.2 mcg / dl ; tsh-3.49mu / l , normal 0.4 - 5.0
marfanoid habitus : tall stature , height 165 cm ; arm span to height ratio of 1.067 ; upper segment to lower segment ratio of 0.83 arachnodactyly with high metacarpal index mci list of investigations that contributed in diagnoses of primary amenorrhea
perrault and his colleagues in 1951 published the first report on two sisters with gonadal dysgenesis and with additional sensorineural deafness .
hypothesized that there is a form of ovarian dysgenesis that is inherited as an autosomal recessive , female - limited disorder .
neurologic data are available on 14 of 21 girls ; 7 of 14 had neurologic abnormalities .
they concluded that high incidence of neurologic anomalies suggest that ataxia or mental retardation may not be just coincidental findings , but pleiotropic manifestations of perrault syndrome .
reported on two sporadic and two familial new cases with sensorineural hearing impairment and ovarian dysgenesis , which are the cardinal signs of perrault syndrome in females .
reported on two pairs of sisters with gonadal dysgenesis and deafness , cerebral , and ocular involvement who developed a progressive , severe sensory , and motor neuropathy .
based on the clinical observations of known patients ; two forms of ps may be distinguished : one apparently non - progressive form and another with apparently progressive axonal - cerebellar degeneration .
nishi et al . reviewed 21 patients from the literature , added ataxic gait , pes equinovarus , nystagmus , limited extraocular movements to the spectrum of neurologic defects in ps .
absence of deafness in a patient with xx female gonadal dysgenesis ( xx - gd ) does not rule out perrault syndrome because the patients could develop deafness much later , at an older age .
most patients had moderate to severe sensorineural deafness with mutism among patients with early onset of deafness .
the findings of abnormal body proportions noted in our patients have been previously reported by jacob et al . in their observation of two siblings with perrault syndrome with marfanoid habitus . the pathogenetic basis for the ps is still unclear .
studied a small family of mixed european ancestry includes two sisters with well - characterized perrault syndrome .
whole - exome sequencing of genomic dna from one of these sisters revealed exactly one gene with two rare functional variants : hsd17b4 .
further studies on other families are awaited to confirm the homogeneity of the genetic defect and the underlying molecular defect .
these issues were discussed with our patient . during the follow up visits , we noticed depression and suicidal tendencies .
after a comprehensive psychiatric evaluation , she was diagnosed with major depression and was put on anti - depressant medication .
we did not advice any therapy for mitral valve prolapse as the prognosis in asymptomatic patients with nonsustained arrhythmias and structurally normal hearts is quite good .
thus , the potential deleterious effects of drug therapy probably outweigh any risk from the arrhythmia in this setting .
similarly , no antibiotic prophylaxis or anti - thrombotic prophylaxis was suggested as present guidelines recommends endocarditis prophylaxis for patients only at the highest risk .
perrault syndrome is a rare cause of primary amenorrhea or ovarian dysgenesis , but should be considered in a female child with deafness / mutism .
several reported cases have some form of neurologic deficit but our patient did not have any obvious neurological signs or symptoms , but she had marfanoid habitus , an association that was described only once in the literature .
the marfanoid features could be considered as a part of extended phenotype of perrault syndrome .

Answer:
gonadal ( ovarian ) dysgenesis with normal chromosomes ( 46 , xx ) , xx female gonadal dysgenesis ( xx - gd ) is a rare genetically heterogeneous disorder . in 1951 , perrault reported the association of gonadal dysgenesis and deafness , now referred to as perrault 's syndrome .
 perrault syndrome is a rare autosomal recessive condition affecting both females and males ; only females have gonadal dysgenesis associated with sensorineural deafness , which is present in both sexes .
 we present a case of sporadic perrault syndrome in a 35-year - old female with primary amenorrhea , sensorineural deafness , marfanoid features and normal karyotype .
 there are very few case reports describing the condition , even lesser reports of association with marfanoid habitus .
 we report this case for its rarity and add to the spectrum of the disease that remains undetermined .


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:
hyperthyroidism is commonly associated with atrial fibrillation ( af ) , particularly in the elderly .
we hereby report a case of patient with primary hypothyroidism presenting with af and pericardial effusion which resolved with levothyroxine therapy .
he complained of chest pain which was substernal , nonradiating , and throbbing in nature .
he smoked 10 cigarettes per day for past 25 years , and denied use of alcohol , caffeine , or drugs .
physical examination was unremarkable except for the irregular heart rate ( approximately 130 beats per min ) and muffled heart sounds on auscultation .
electrocardiogram [ figure 1 ] confirmed af with rapid ventricular rate , which responded to initial treatment with metoprolol [ figure 2 ] .
af with rapid ventricular rate normalization of af with metoprolol thyroid function tests revealed a sensitive thyroid stimulating hormone ( tsh ) concentration of 34.70 iu / ml ( normal : 0.40 - 4.70 iu / ml ) , and thyroxine ( t4 ) of 5.57 g / dl ( normal : 8 - 12 g / dl ) confirming primary hypothyroidism .
transthoracic echocardiography showed normal left ventricular systolic function ( ejection fraction of 63% ) , decreased left ventricular diastolic compliance , and massive pericardial effusion ( posterior 17 mm , anterior 13 mm ) .
right atrial and right ventricle showed 30% collapse during diastole , mild left ventricular hypertrophy was present with no regional wall motion abnormalities .
patient was treated with levothyroxine which lead to resolution of symptoms and restoration of normal sinus rhythm .
repeat echocardiography showed no collapse of right atrium and right ventricle during diastole ) and mild pericardial effusion ( 11 mm circumferential ) .
the most common cardiovascular signs and symptoms of hypothyroidism include bradycardia , mild hypertension ( diastolic ) , narrow pulse pressure , cold intolerance , pericardial effusion , cardiomyopathy and fatigue .
hypothyroidism is often associated with electrocardiographic changes like bradycardia , right bundle branch block , flat or inverted t wave , qrs prolongation , qt prolongation , and infrequently ventricular arrhythmia , torsades de pointes .
treatment of hypothyroidism is well - documented to cause af due to inadvertent overdosing of levothyroxine .
although atrial arrhythmias are common and ventricular ectopy is rare in patients with hyperthyroidism , it is rarely associated with hypothyroidism .
af is seen in 5 - 15% patients of hyperthyroidism and may be the presenting feature . increased chronotrophic activity
due to increased thyroid hormones and increased sympathetic tone are the proposed underlying mechanisms . the physiological chronotropic response and normal tension of the heart muscle in
diastolic phase depend on the action of triiodothyronine in the heart cells and its stimulating influence on na - k atpase and ca atpase in endoplasmic reticulum .
normal contractility is also related to triiodothyronine stimulated transcription of the myosin heavy - chain alpha gene and inhibition of the heavy - chain beta gene .
moreover , triiodothyronine acts on the cardiac muscle affects the number of beta adrenergic receptors and their sensitivity to catecholamines .
few case reports have demonstrated that hypothyroidism may cause a prolongation of the qt interval which predisposes the patient to ventricular irritability .
the canadian registry of atrial fibrillation investigators reported that 1.5% of 726 patients with af had hypothyroidism over a period of 1.7 years .
studies have also reported that up to 8% of patients with atrial fibrillation were hypothyroid .
hypothyroidism is known to cause nodal defects , but the mechanism of af in hypothyroidism is not known .
it is also not clear whether its presence is causally related or is a mere manifestation of an underlying unrecognized structural heart disease .
however in our case , reversal of af with levothyroxine treatment negates underlying structural damage of the heart nans suggests causal relationship .
previous case reports have shown association of af with hypothyroidism but pericardial effusion was absent in those cases .
this is possibly the first reported case of af and pericardial effusion in a case of hypothyroidism .
young patients with no evidence of organic heart disease may be started on a full replacement dose of thyroxine .
older patients or those with known or suspected ischemic heart disease , should initially be given about 25% of the anticipated replacement dose , and the dose should be increased gradually at 6 - 8 week intervals .

Answer:
a 72-year - old man presented with palpitation , dyspnea , and chest discomfort .
 initial investigations revealed atrial fibrillation ( af ) and pericardial effusion , further investigations unraveled primary hypothyroidism ( thyroid stimulating hormone ) of 34.7 iu / ml and total thyroxine ( t4 ) of 5.57 g / dl ) .
 treatment with levothyroxine led to resolution of symptoms , af , and pericardial effusion .


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:
extraskeletal soft tissue chondroma is a very rare , slow - progressing , benign tumour .
chondromas are tumour - like masses formed by proliferation of chondrocytes in a mature hyaline matrix .
a 22-year - male came with chief complaints of asymptomatic swelling on the palate since birth .
he had symptoms of cleft palate , i.e. , nasal regurgitation and poor speech . on examination
, there was a complete cleft of secondary palate and the cleft was filled by non - tender , globular swelling of size 3 sq .
there was a linear band of soft tissue extending from the anterior part of the swelling to the upper lip mucosal surface after passing through the diastasis of the upper central incisors [ figure 1 ] .
pre - operative photograph showing palatal swelling completely obliterating the cleft with linear band extending to the lip on computed tomography scan , a 30 mm  28 mm size , well - defined , globular soft tissue mass was seen in the region of the hard palate , which showed fusion defect anteriorly .
plain computed tomography coronal section of the swelling differential diagnosis of dermoid cyst and chondroma were kept .
intraoperatively , the tumour was seen attached by a small pedicle to the nasal mucosa of the cleft margin on the right side .
the tumour was excised along with the linear band of tissue extending to the mucosal surface of the upper lip [ figure 3 ] .
histopathological examination revealed hypercellular lobules of cartilage composed of evenly spaced chondrocytes of uniform size and separated by collagen and adipose tissue .
there was no recurrence after 2 years of follow - up [ figure 5 ] .
histopathological appearance of the chondroma two - year follow - up photograph showing repaired palate having adequate length with no recurrence
soft tissue chondromas are benign cartilage - forming tumours that are usually found in close proximity to the tendon or joint capsules .
only five cases of soft tissue chondroma of palate have been reported in the literature.[36 ] it has never been reported in a patient of cleft palate .
one theory is that these lesions are from residual embryonal tissue ( embryonic remnant theory ) .
the other theory is that these lesions are from metaplasia of pluripotential mesenchymal cells ( metaplastic theory ) . in our case , because the swelling was present since birth , this goes in favour of embryonic remnant theory . even after a meticulous review of the literature , we could not establish the cause and effect relationship between chondroma and cleft palate .
in fact , we feel that the embryonic changes in the palate during the process of cleft might lead to entrapment of mesodermal tissue ( mesoderm giving rise to cartilage / bone ) .
clinically , these tumors present as slow - growing , firm masses not attached to the underlying bone and are , occasionally , painful .
radiologically , soft tissue chondroma show well - demarcated , extraskeletal , soft tissue masses .

Answer:
soft tissue chondroma of palate is very rare .
 it has never been reported in a cleft palate patient .
 we report a case of 22-year - old male who came with asymptomatic swelling on the palate since birth , along with complete cleft of secondary palate .
 he had symptoms related to cleft palate only , i.e. , nasal regurgitation and speech abnormalities .
 swelling was excised and the cleft palate was repaired .
 histopathological examination revealed chondroma of the palate .
 the patient had no recurrence after 2 years of follow - up .


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:
takotsubo   cardiomyopathy , or  transient apical ballooning syndrome  , is a non - ischemic cardiomyopathy that mimics the onset of an acute myocardial infarction .
its incidence was recently reported to be 1.72.2% among patients presenting with acute coronary syndrome .
takotsubo is also called  broken heart syndrome  because a strong emotional psychological stress may act as a potential trigger .
originally described in japan in 1990 , its eponym was coined using the two japanese terms tako ( octopus ) and tsubo ( pot ) , due to the resemblance between the cardiac apical ballooning ( hallmark of the syndrome ) and the octopus trap ( a kind of ceramic pot ) used by japanese fishermen .
the acute functional and instrumental abnormalities accompanying takotsubo cardiomyopathy occur in the absence of significant coronary alterations , and could be completely recovered within a few weeks up to two months . if promptly recognized and correctly managed , despite the severity of its onset and the potentially life - threatening characteristics ( those of a cardiogenic shock ) , this syndrome normally presents a good prognosis with low morbidity and in - hospital mortality rates , , .
this paper reports a rare case of association between takotsubo and hip fracture surgery , which has been described only by two previous studies , .
the female patient we describe , an 81-year - old caucasian woman living at home with a son , was completely independent in katz s basic activities of daily living ( adl  =  6/6 ) and lawton s instrumental activities of daily living scales ( iadl  =  8/8 ) before the hospitalization . her clinical history evidenced osteoporosis with multiple previous vertebral incomplete collapses , in treatment with oral calcium and vitamin d , hypertension controlled with ramipril , and dyslipidemia for which she took statins .
she had no cognitive decline ( normal score at iqcode questionnaire ) , allergies , or weight loss .
the woman was admitted during night time in the emergency department ( ed ) of san gerardo university hospital after an accidental fall at home , reporting trauma of the right hip .
1a ) and partial collapse of multiple vertebrae , the latter without evidence of recent fractures .
no significant abnormalities were reported at the blood examinations ( i.e. , blood count , electrolytes , liver and kidney function indexes , protein electrophoresis , coagulation parameters , blood gases ) or at the standard electrocardiogram ( ecg , fig .
the patient was firstly admitted in the orthopedic ward , and then transferred to the orthogeriatric unit ( ogu , within the geriatric ward ) the day after , once the geriatricians confirmed the eligibility criteria for admission .
the comprehensive geriatric assessment did not reveal cognitive deterioration or delirium ( 4at score  =  2/12 ) .
the pain was on average well controlled with the standard protocol of treatment ( acetaminophen 1  g three times intravenously / day ) .
score  =  2 ) , which was performed 60  h after the admission .
ten minutes after the injection of cement , when the orthopedic surgeons were performing haemostatic maneuvers and a check of joint movements , the surgical act was complicated by severe bradycardia and cardiogenic shock with consequent cardio - pulmonary arrest . without perturbing the sterility of the surgical site ,
the patient was placed supine and promptly treated with cardiopulmonary resuscitation maneuvers , oro - tracheal intubation , and intravenous administration of atropine and epinephrine , obtaining return of spontaneous circulation after 7  min .
upon restoration of spontaneous circulation , the surgical procedure was completed with saline washing , local instillation of tranexamic acid , layered suture , and plain medication with plaster . the first suspected diagnosis , considering the time relationship with cement injection , was  bone cement implantation syndrome ( bcis )  .
the patient was then transferred from the operating theater to the intensive care unit ( icu ) , where dopamine ( 5.33  mcg / kg / min , increased to 16  mcg / kg / min ) and norepinephrine ( 0.060.13  mcg / kg / min ) were administered intravenously reaching treatment maximization .
hydroelectrolytic solutions ( 3500  ml ) were infused to increase the circulating volume and furosemide 40  mg iv was administered to stimulate the diuresis . in the absence of clinical benefits , due to the persistence of hypotension ( systolic blood pressure  =  80  mmhg , mean arterial pressure  =  50  mmhg ) and the presence of sinus tachycardia , the anesthetist added bisoprolol 1.25  mg four times / day .
the echocardiography revealed akinesia of the apex and the mid segment of the septum , extending to the anterior and infero - lateral cardiac wall , accompanied by apical ballooning and significant reduction of the left ventricular ejection fraction ( lvef  =  25%30% during amine iv infusion ) .
additional examinations excluded the presence of cerebrovascular diseases , myocarditis , hypertrophic cardiomyopathy , and pheocromocytoma .
these results oriented toward a diagnosis of takotsubo syndrome , so that the cardiologist prescribed iv treatment with heparin ( 2000  ui in bolus  +  20,000  ui in 24  h ) , gradually reduced and discontinued the aminic support , and positioned an intraortic balloon pump .
the day after surgery , despite an observed initial reduction of the troponin t levels ( ctnt  =  185  ng / ml after 24  h , 154  ng / ml after 32  h ) , the echocardiography showed further reduction of the lvef ( 20% ) with apical akinesia in toto .
the finding of anemia ( hb  =  8.5  g / dl , mcv  =  78.5  fl ) was corrected with the transfusion of 2 units of concentrated red blood cells .
on the second post - operative day , considering the persistence of low cardiac output and atrial tachycardia , the patient started iv treatment with levosimendan 0.1  mcg / kg / min for 7  h , amiodarone 907  mcg / day and metoprolol 2  mg , with gradual amelioration of cardiac output and heart rate . during the third post - operative day we discontinued iv treatment with heparin
, we removed the intraortic balloon pump and the oro - tracheal device , supporting the patient with low - intensity oxygen by mask .
therapy with acetylsalicylic acid 100  mg / day and captopril 6.25  mg three times / day was initiated . on the fourth post - operative day
we report a single episode of hyperactive delirium occurred during the night , efficiently managed with the administration of haloperidol 2  mg intramuscular  +  quetiapine 50  mg per os . during the fifth post - operative day
she was transferred to the cardiology icu , where she underwent echocardiography re - evaluation that showed significant restore of the contractile function ( lvef  =  56% ) . on the seventh post - operative day
the patient was transferred back to the ogu , where she started specific physical therapy oriented towards passive and active mobilization of the right leg , achievement and maintenance of the standing position , and ambulation with the support of a walker . before discharge ,
the hemoglobin levels were stabilized ( hb  =  12.3  g / dl ) . during the hospital
she was discharged sixteen days after the operation and the takotsubo syndrome , in good physical and mental conditions ( mmse score   before discharge  =  25/30 ) , able to walk ( walker  +  supervision ) without pain in the surgical area .
the follow - up performed two months after surgery revealed absence of cardiac symptoms and good recovery of the walking ability with a walking stick .
we suggested to continue strengthening the lower limb muscles with domiciliary physiotherapy and allowed walking without any aid . at the 6-month follow - up , the woman was still asymptomatic from a cardiovascular point of view .
she reached a functional level comparable with the pre - fracture status ( katz s adl  =  6/6 , lawton s iadl  =  7/8 ) .
she was able to walk without aids at home , but she needed a walking stick when going outside because of a residual fear of falling .
finally , the echocardiogram confirmed good cardiac function ( lvef  =  55% ) in the absence of other abnormalities . her son , the caregiver living with her , confirmed an overall good functional and nutritional status and no signs of cognitive decline compared with the pre - fracture status .
the patient fulfills several criteria for a diagnosis of takotsubo syndrome : physically stressful event as a trigger , female elderly patient ( at higher risk than young subjects and males ) , apical ballooning with akinesia ( echocardiogram ) , st - segment alterations immediately after the onset ( electrocardiogram ) , lack of significant coronary artery stenosis , recovery of the left ventricular function . indeed
, approximately 90% of the cases occur in the female population , mostly between 58 and 75 years of age , though it is not uncommon among older individuals , . in this case report
, the symptomatology seemed to be triggered by the injection of pressurized cement during the hemiarthroplasty procedure , mimicking a bcis of grade 3 ( the more severe grade ) with acute myocardial infarction , accompanied by the classic instrumental cardiac findings .
bcis was previously reported to be a sporadic adverse event of bone cement injection , still incompletely understood , and was defined only recently .
it is characterized by the association of multiple signs of different severity , which contribute to a heterogeneous presentation : hypoxia , hypotension , alteration of vascular pulmonary resistance , cardiac arrhythmias , and cardiac arrest . however , in this case , the coronary angiography did not show major obstructions or arterial abnormalities , and the echocardiography did not demonstrate the presence of emboli , thus suggesting a different diagnosis and orienting the physicians toward takotsubo cardiomyopathy .
this is the second case of takotsubo we recently encountered in our medical practice , the first being described in 2012 in an 80-year - old woman with severe alzheimer s disease .
pathophysiological mechanisms underlying takotsubo are still not well understood , and the reported cases suggest a number of potential etiologies . in several cases a multifactorial mechanism might be involved , and different variants of the classic takotsubo syndrome have been progressively described , , . altogether , a single pathophysiological mechanism does not clarify the existence of several takotusbo s variants .
hip fracture and the related surgery are even more stressful experiences : healthcare professionals working in this area should be aware of the severe physical ( pain , immobility , functional disability ) and psychological / emotional ( transfers , total dependence , anxiety ) burden that affects the geriatric population .
strength of our approach was the availability and coordination of multiple specialists as consultants 24/24  h , with the geriatrician as the primary attendant according to our orthogeriatric protocol of co - management .
these allowed to set up promptly the necessary support therapies and instrumental evaluations in order to identify the potentially life - threatening diagnosis .
limitations include the initially wrong diagnostic orientation and the resources required to complete the differential diagnosis before confirming the takotsubo .
despite being a rare condition , takotsubo syndrome is a possible differential diagnosis of the bcis , which recently emerged
regardless its severity  as a frequent complication of surgical orthopedic procedures involving the pressurized injection of bone cement , with a prevalence of about 2530% , . moreover , porto et al .   recently reviewed the correlation between neurologic disorders and transient left ventricular dysfunction , called neurogenic stunned myocardium and characterized by findings which resemble the classic takotsubo cardiomyopathy .
the authors concluded that the available literature suggests treating them as different entities . to the best of our knowledge , the association of takotsubo syndrome with hip fracture in the preoperative phase   or after surgery   has been rarely reported ( two cases ) .
, the correct management of elderly subjects could potentially reduce the stress experience related with hip fracture . promoting the  gentle care
informed consent for the acquisition of data to present in this case report was obtained during the hospitalization , and signed by the patient itself .
the consent form is stored in the archive of san gerardo university hospital ( monza , italy ) .
written informed consent was obtained from the patient for publication of this case report and accompanying images .
a copy of the written consent is available for review by the editor - in - chief of this journal on request .
all demographic and patient - specific personal information have been de - identified according to the italian law for the privacy and protection of personal information (  codice in materia di protezione dei dati personali , d. lgs .
dp , mc , and gb took care of the patient during the hospitalization and obtained informed consent for this report .

Answer: highlightsdespite the good prognosis when diagnosed early , takotsubo is a life - threatening event.takotsubo must be differentiated from bone cement implantation syndrome ( grade 23).a portable ultrasound scanner allows recognizing the apical ballooning and akinesia hallmark.approaches to reduce the hospitalization - related stress must be pursued in the elderly .


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:
apart from the correlation studies mentioned above , the ability to innovate and solve novel problems flexibly , proxies for flexible cognitive capacities and potentially for domain - general intelligence , have not been investigated comparatively .
few experimental studies have specifically focused on innovativeness , and flexible problem solving per se .
the majority of experiments in animal cognition , in both the physical and social domain , present animals with specific problems and investigate how the animals solve them in order to examine specific cognitive abilities / processes .
mostly , these tasks have been tailored to be ecologically valid for one particular species , or have focused on contexts/ questions so specific that they could not be reproduced in other species easily ( e.g. , dolphins ; food - storing srub jays ) .
other problem solving tasks , particularly in physical cognition , have secondarily become comparative paradigms and have been established as so - called
benchmark tests for examining the existence of certain cognitive abilities in different species , e.g. , the  trap - tube for examining an understanding of causality in terms of surface continuity , povinelli s cane task and heinrich s  string - pulling task for testing responsiveness to connectivity etc .
most of these typically started off from a single experiment designed for testing a particular species and some subsequently applied to other species , sometimes without paying sufficient attention to species differences in morphological ( hand or beak ) , behavioral ( e.g. , object exploration , affordance learning ) and perceptual features ( e.g. , field of vision ) , in addition to psychological variables ( such as motivational , emotional or attentional states , inhibitory control or neophobia / neophilia ) . yet
all these factors can potentially have a big impact masking cognitive skills actually present in a species and producing misrepresentative results .
another methodological problem of comparative cognition is that paradigms are applied to many species , but with slightly converted methodologies ( better fitting the newly compared species demands ) , hence at a cost of comparability . if the methodology is not standardised , it is hard to interpret the findings of comparative studies , because any detected differences between species could be owing to the different procedures .
an odd handicap for comparative cognition in this context appears to be that modification or
improvement of an already used comparative paradigm , instead of merely replicating it in a new species , may increase the chances of a study to become published .
often however , a direct comparison would have been scientifically more valuable than yet another improvement to an existing experimental paradigm . recently ,
this has been acknowledged and several research groups have begun to run comparative studies with the exact same methods .
the difficulty of comparative cognition therefore is to find comparative paradigms that are compatible with many different species ( i.e. , that are ecologically valid for all the species to be compared , and not influenced by potentially confounding species - specific variables ) , and that have a standardised methodology that can be applied to different species in exactly the same way .
because of the potentially confounding impact of different methodologies , the same cognitive ability should be investigated with not just a single but several tests with slightly different angles in any given species .
recently , comparative studies carry out entire batteries in different species tests , e.g. , those comparing cognitive abilities in the social and physical domain . yet
, what is missing is to have a battery of tests establishing species differences that might affect performance in different cognitive tests , such as object exploration , motivation , attentiveness and fear / neophobia .
a new such comparative approach is the multi - access - box ( mab ) , recently published in plos one ( see fig .  1 ) .
it presents the animal with a novel problem that can be solved in four different ways , thus offering the possibility to examine species differences in how novel problems are perceived , explored and approached and in which order solution(s ) are discovered .
this provides several data that can be used for establishing a behavioral ( e.g. , object exploration , ) and psychological profile ( e.g. , motivation , flexibility , impulsivity , persistence , inhibitory control ) and hence extract behavioral and perceptual determinants of different species performance in the tasks .
simultaneously , it is a suitable paradigm to collect data about problem solving ability , innovativeness and flexibility , i.e. , theoretical covariates of  general intelligence , across species in a standardized manner .
multi access box ( mab ) ( as in plos one , copyright 2011 by the public library of science . reprinted with permission of the author ) .
a food reward presented in the center of a transparent box can be retrieved by one of four possible methods , which are built in the four walls of the mab : opening a window , pulling a string , inserting a ball or inserting as stick tool .
the mab approach comprises not just one but several solutions to an extractive foraging problem at the same time ( food out of reach in the center of a transparent box ) , i.e. it consists of a battery of alternative tasks that all lead to the same goal .
two solutions ( opening a window and pulling a string ) could be discovered by haptic exploration ( touching the box at particular sites ) , while the other two additionally required the handling of objects , either wooden sticks or marbles , as tools ( inserting a ball or a stick tool into specific openings ) .
the other important feature of the mab is that subjects were forced to continue exploring alternative solutions , once they had successfully discovered and consistently used one particular solution , by blocking the one in use .
this creates an order system which allows to detect species differences in which tasks are approached and explored first and how , how many solutions are discovered and how fast , whether and how quickly the subjects switch between options or whether they focus or settle on particular ones , as well as which tasks are problematic and why . in this manner
we can detect not only species differences in problem solving performance , but also learn about the various underlying non - cognitive factors that may affect it .
although designed for large scale comparisons of different closely- and distantly related species from different ecological backgrounds , the initial mab study compared just two avian species from different families , a corvid , the new caledonian crow ( ncc ; corvus moneduloides ) and a parrot , the kea ( nestor notabilis ) ( see fig .  2 ) .
both species are known for their large brains , their innovativeness and problem solving skills , but nccs are naturally tool - using species while kea have not been observed to use tools in the wild , but are famous for their neophilia .
subjects were exposed to the transparent mab with the food reward in the center , which could be extracted by the four different methods corresponding to the four walls of the box .
once a method was mastered , it was blocked and the bird s performance in reaching criterion in any of the others was recorded until all four methods had been discovered . figure  2 .
kea and new caledonian crow using the stick ( left ) and the ball - shaped ( right ) tool on the multi access box .
found that one kea and one ncc detected all four solutions , demonstrating that the solutions offered were within both species capacity .
the kea were much quicker in discovering multiple solutions than the habitually tool - using nccs and showed more individual variation .
the keas were also more flexible once openings were blocked , switching to other solutions much quicker than the ncc .
innovation rate as well as performance in this paradigm were strongly impacted by differences in exploration technique and neophilia rather than by cognitive discrepancies .
the highly neophilic kea explored the apparatus more in a haptic than in a visual manner .
they found its functional properties , while manipulating the affordances of the mab they perceived as most salient .
in contrast to the kea and probably due to their more visually guided exploration technique , the nc crows had problems solving the window solution .
the window mechanism could not be deduced by visual inspection alone ( without knowledge of hinge - mechanisms ) , but could be readily discovered by haptic exploration .
another difference was that the nc crows tended to persist with the first option that worked , whereas the kea , owing to their higher level of neophila , switched between solutions .
differences in beak morphology also affected the birds performance : the kea had problems maneuvering the stick tool because of their beak curvature , whereas the crows with their straight beaks had a good grip of the tools . yet
, the nc crows used their straight beak more for pecking than tearing actions , which would have been advantageous in detecting the mab apparatus s affordances in case of the window option ( grasping and pulling the window crank ) .
an important new tool that could be incorporated in the mab procedure and that could be revealing in comparisons of flexible problem solving may be
reversal learning. species with different ecological backgrounds may have been selected for different strategies in trial and error learning and problem solving . in terms of energy pay - off it may
, under certain circumstances , be advantageous to persist ( e.g. , in the case of nccs fishing for particularly nutritious wood - boring beetle larvae in rotten wood as , which can take considerable time but has a high potential return ) .
in other contexts it may save energy to give up if something does not work and try something else instead .
reversal learning tasks reflect differences in flexibility and are informative of how fast animals can adjust their behavior to new external feedback , let go of previously reinforced behavioral patterns , but at the same time they offer a measure of persistence .
to illustrate how reversal learning could be implemented , we present some data not published in the original auersperg et al .
once a subject had discovered all solutions , we incorporated a reversal learning task for the two solutions incorporating a tool ( see fig .  2 ) .
for the two successful subjects , uk , a ncc and kermit , a kea , the last used tool option was blocked and the previous tool option was reopened .
as can be seen the crow required a similar amount of trials to relearn the previous option as the kea , although of course data on more individuals would be desirable .
illustrate how even diminutive differences in non - cognitive behavioral components such as neophilia or morphology can mask and/or interfere with the respective cognition involved and impact on the species performance .
it highlights how different performance in problem solving task are not always symptomatic of species differences in cognitive ability or general intelligence .
it highlights in particular , what major impact differences in object exploration ( haptic or visual exploration mode ) and affordance learning , which have only recently become a topic in animal cognition , can have on performance in artificial experimental tasks , and hence how this affects the comparability of two species in the same task . in future comparative research , establishing behavioral and psychological profiles of the species to be compared ought to precede comparative tests of specific cognitive skills or general intelligence .
this may help to identify problem solving tasks that are equivalently applicable to the target species and hence achieve a high degree of

Answer:
comparative cognition aims at unfolding the cognitive processes underlying animal behavior and their evolution , and is concerned with testing hypotheses about the evolution of the brain and intelligence in general .
 it is a developing field still challenged by conceptual and methodological issues .
 systematic cross - species comparisons of cognitive abilities , taking both phylogeny and ecology into account are still scarce .
 one major reason for this is that it is very hard to find universally applicable paradigms that can be used to investigate the same cognitive ability or
 general intelligence in several species .
 many comparative paradigms have not paid sufficient attention to interspecific differences in anatomical , behavioral and perceptual features , besides psychological variables such as motivation , attentiveness or neophobia , thus potentially producing misrepresentative results . a new stance for future comparative research may be to establish behavioral and psychological profiles prior or alongside to comparing specific cognitive skills across species .
 potentially revealing profiles could be obtained from examining species differences in how novel experimental ( extractive foraging ) tasks are explored and approached , how solutions are discovered and which ones are preferred , how flexibly multiple solutions are used and how much individual variation occurs , before proceeding to more detailed tests .
 such new comparative approach is the multi - access - box .
 it presents the animal with a novel problem that can be solved in several ways thus offering the possibility to examine species differences in all the above , and extract behavioral and perceptual determinants of their performance .
 simultaneously , it is a suitable paradigm to collect comparative data about flexibility , innovativeness and problem solving ability , i.e. , theoretical covariates of
 general intelligence , in a standardized manner .


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:
sarcoidosis is a multisystemic , granulomatous disease of unknown etiology that may affect any organ system .
it is characterized by the accumulation of t lymphocytes and mononuclear phagocytes with the formation of noncaseating epithelioid granulomas in affected organs .
the trigger for this t cell and macrophage interaction is still uncertain , although bacterial , viral , and environmental antigens have all been studied .
recent literatures renewed the interest in mycobacteria as a causative agent in sarcoidosis tissue [ 2 , 3 ] . here
we present a case of presumed ocular sarcoidosis diagnosed by ocular manifestation and treatment course , who developed tuberculous lymphadenopathy 6  years later without recurrence of ocular inflammation .
a 35-year - old female was referred to our department with severe visual impairment for months .
she was quite healthy until 1  year ago when she began to suffer recurrent episodes of uveitis with mutton fat keratic precipitates ( kps ) in both eyes . on presentation ,
ocular examination showed mild anterior uveitis with mutton fat kps and dense vitreous hemorrhage in both eyes .
systemic workup including general physical examination , complete blood counting , differential classification , blood biochemical tests , rheumatic factor , antinuclear antibody , human immunodeficiency virus , venereal disease research laboratory test , anticardiolipin antibody , and chest radiography were within normal ranges . due to persistent vitreous hemorrhage and disabled vision ,
pars plana vitrectomy was performed in the left eye and then the right eye 2  months later .
sign of peripheral vasculitis with nodular choroid infiltration was noted during operation in both eyes .
gallium-67 scans showed panda sign of increased uptake in lacrimal glands and lambda sign of lymph nodes in the mediastinum ( fig .  1 ) .
chest computed tomography ( ct ) showed a small ground glass opacity nodule in the subpleural space of the right lower lobe , more in favor of inflammatory process .
based on these findings , ocular sarcoidosis was impressed and systemic and topical steroids administered in a tapering dose over 6  months .
unfortunately , painless enlargement of lymph node at her right neck was noted 6  years later .
lymph node biopsy showed granuloma with caseous necrosis , langhans giant cell , as well as acid - fast bacilli ( fig .  2 ) .
three combined antituberculosis medications ( rifampin , isoniazid , and pyrazinamide ) were given for 6  months .
the eyes remained silent except cataract progression and glaucoma under two medications during this period ( fig .
1gallium-67 scans showed panda sign of increased uptake in lacrimal glands and lambda sign of lymph nodes in the mediastinumfig .
2pathological finding from lymph node biopsy showed granuloma with caseous necrosis ( hematoxylin and eosin , 40 ) ( a ) , langhans giant cell ( hematoxylin and eosin , 400 ) ( b ) , as well as acid - fast bacilli ( kinyoun 's crystal fuchsin acid - fast stain , 1,000 ) ( c)fig .
3postoperative color fundus picture of both eyes showed sheathing vessels and scattered laser scars at the inferior retina . a right eye .
b left eye gallium-67 scans showed panda sign of increased uptake in lacrimal glands and lambda sign of lymph nodes in the mediastinum pathological finding from lymph node biopsy showed granuloma with caseous necrosis ( hematoxylin and eosin , 40 ) ( a ) , langhans giant cell ( hematoxylin and eosin , 400 ) ( b ) , as well as acid - fast bacilli ( kinyoun 's crystal fuchsin acid - fast stain , 1,000 ) ( c ) postoperative color fundus picture of both eyes showed sheathing vessels and scattered laser scars at the inferior retina . a right eye .
the gold standard for diagnosis of sarcoidosis is histopathologic examination . considering the fact that ocular sarcoidosis may occur in the absence of apparent systemic involvement , and the fact that biopsy is usually reluctantly accepted by uveitis patients , the international workshop on ocular sarcoidosis ( iwos ) established an international criteria for the diagnosis of ocular sarcoidosis .
although there was no pathologic proof of sarcoidosis in our case , her ocular manifestations met at least five of the iwos criteria . though the lacrimal gland uptake of gallium ( panda sign ) is not a specific sign for sarcoidosis , her simultaneous presence of lambda and panda sign on ga-67 scans gave some support to sarcoidosis .
as guided , other granulomatous diseases , including tuberculosis , foreign body reaction , bacterial and viral infections , should be excluded before the diagnosis of sarcoidosis .
other laboratory and image study ruled out the other possible etiologies . besides , the ocular inflammation subsided after pars plana vitrectomy and systemic corticosteroid .
there was no recurrence of inflammation even at the time of tuberculous lymphadenopathy . presumed ocular sarcoidosis was impressed based on the ocular manifestations and treatment course .
we could not make any conclusion whether ocular sarcoidosis and tb lymphadenopathy in this patient is just coincident or in real association with each other . despite the increasing understanding of the immune responses behind the formation and maintenance of the granulomatous process in sarcoidosis
mycobacteria have been implicated as a cause of sarcoidosis , although the demonstration of mycobacterial dna was inconsistent in different reports [ 6 , 7 ] .
recent studies by detecting mycobacterium tuberculosis catalase  peroxidase have renewed interest in mycobacteria as a causative agent in sarcoidosis [ 2 , 3 ] . in our case , tb was ruled initially due to negative results of chest x - ray , aqueous tb culture , and pcr .
tuberculin skin test was not done as our cdc did not identify the significance of ppd in adult who received routine bacille calmette  guerin vaccination .
the ocular inflammation revolved after systemic steroid , and remained silent even at the presence of tb lymphadenopathy .
our speculation is that the presumed ocular sarcoidosis might be triggered by tb antigen in extraocular infection , which reactivated and presented as tb lymphadenopathy 6  years later .
tb could occur coincidently or in association with sarcoidosis , continued follow - up is important for patients with ocular sarcoidosis , even in silent case .

Answer:
tuberculosis and sarcoidosis share similarity in histopathologic findings and clinically occur in association with each other occasionally .
 tuberculosis should always be ruled out before the diagnosis of sarcoidosis .
 but , the diagnosis is often complicated , especially in extrapulmonary cases . here
 we present a case of bilateral vitreous hemorrhage with uveitis .
 ocular sarcoidosis was initially diagnosed based on the characteristic ocular findings , negative results on chest radiography , tuberculosis culture , and polymerase chain reaction of aqueous , as well as simultaneous presence of panda and lambda sign on gallium-67 scans .
 the ocular condition improved after pars plana vitrectomy and systemic steroid therapy .
 however , tb lymphadenopathy but no recurrent ocular inflammation was found 6  years later .
 the patient received anti - tb treatment for 6  months thereafter .
 the eyes remained silent except cataract progression and glaucoma under two medications during this period . in conclusion , tb could occur coincidently or in association with sarcoidosis , continued follow - up is important for patients with ocular sarcoidosis .


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:
immunocompromised patients might bear a variety of presentations such as rhino - orbito - cerebral , pulmonary , gastrointestinal , cutaneous , central nervous system and disseminated form .
rhino - orbito - cerebral and pulmonary mucormycosis are the most common forms ; the latter progresses rapidly to devastating diseases .
presentation of pulmonary mucormycosis may be confused with several infectious and non infectious diseases ; therefore its diagnosis is difficult .
chest ct scan of a patient with pulmonary mucormycosis might demonstrate such presentations as air crescent sign , ct halo sign , solitary or multiple pulmonary nodules or masses , bronchopulmonary fistula and pulmonary artery pseudo aneurysm .
the occurrence of pneumothorax and its subsequent rhs along with sinusitis , supported by radiology and pathology in a 33 years old patient , is considered as a rare case of pulmonary mucormycosis .
following is the treatment history of a man , 33 years old in july 2014 ( day + 14 ) , when he died in our hospital as a result of multiorgan failure .
he was a farmer , married , with no history of alcohol consumption , illicit drugs use and extramarital relationships . on day 330 : because of edema he visited a medical center in another city , where he was admitted and membranous glomerulonephritis was diagnosed .
consequently the followings administered ; prednisolone and cyclosporine for 2 months , cellcept for 1 month , prednisolone and cyclophosphomide for 7 months . on day 75 : because of progressive generalized edema he was admitted again .
he was discharged under treatment with prednisolone ( 50  mg / daily ) and tacrolymus ( 1 cap / bd ) . during the next 2 months he was feeling fine . on day 28 , he travelled to village for a few days and he had close contact with sheep . on day
14 the patient reported fever , cough and dyspnea with mild erythema and pain in right eye .
anorexia , weakness , dyspnea and conjunctivitis developed and persisted despite of outpatient antibiotic treatment . in the emergency department (
day 0 ) : the patient suffered from dyspnea , weakness and right eye pain . on examination , he was agitated but completely conscious with diaphoretic skin .
the vital signs have been as follows ; temperature , 36.7  c ; blood pressure , 100/60  mmgh ; pulse rate , 99 beats per minute ; respiratory rate , 22 beats per minute and oxygen saturation in air room , 99% .
in right eye , there was moderate conjunctivitis with eyelid erythema ; its movement was normal .
the first day chest ct scan revealed large pleural effusion with pneumothorax in the left side and a shift of mediastinum to the right side .
1 ) . consequently drainage with chest tube was administered by the surgeon immediately . because of the immunocompromised state of the patient , parenteral trimethoprim- sulfamethaxazol ( 160  mg / iv / tds ) and meropenem ( 1  g / iv / bd ) were administered for pneumocystis jiroveci and multi drug resistant organisms .
we also started fluconazole for oral lesions . on day + 3 , right eye erythema was extended with small size necrosis in right nasal ala without bleeding ( fig .
with doubt of rhino - orbital mucormycosis , biopsies of tongue and nasal septa were carried out and amphotericin b deoxycholate ( 1  mg / kg / daily ) was administered . on day + 4
, paranasal sinuses ( pns ) ct scan revealed soft tissue density lesion in left ethmoid sinus and nasal passage with extension to left orbit ( fig .
, he was transferred to intensive care unit ( icu ) because of respiratory distress and was intubated after 48  h ; his conscious level was 14+t/15 .
smear of sputum for acid fast bacilli , stain and culture of sputum for pneumocystis jiroveci were negative .
hiv antibody test , d - dimer enzyme -linked immunosorbent assay ( elisa ) and collagen vascular diseases screening tests were negative ( table 1 ) .
pleural fluid cytologic examination and polymerase chain reaction ( pcr ) for fungi were negative . on day + 6 , laboratory results revealed pancytopenia ( table 1 ) , however in peripheral blood smear there was no schistocyte or immature cells .
bone marrow biopsy which could help in finding the cause of pancytopenia was nevertheless postponed due to the patient 's poor condition and low platelet count .
meanwhile his blood pressure was decreased and we started inotropic drugs.hemodynamic instability of the patient prohibited further attempts such as bronchoscopy and ct guided lung biopsy to identify the causative agent . on day + 9 ,
section of tounge biopsy showed ulcerated squamous epithelial mucosa with subepithelial fibro fatty tissue and skeletal muscle fibers of tongue that is on site of ulceration .
the inflammatory granulation tissue and inflammatory multinucleated giant cells were also seen in gimsa staining , but no cyst and trophozoite of pneumocystis jiroveci were identified .
pulmonary mucormycosis is a devastating infection when it affects immunocompromised patients such as diabetes mellitus , hematologic malignancies , chronic renal failure , post transplantaion and immunosuppressed persons . herein , we present a rhino - orbital mucormycosis with pulmonary involvement .
reticulation inside the rhs , presence of pleural effusion , multiple nodules and concomitant rhino - orbital mucormycosis as well as documented pathology , collectively were considered as indicating that pulmonary involvement has been due to mucormycosis .
the pathological finding is achieved by tongue tissue ; lung biopsy has not been possible due to poor condition of the patient .
our case was an immunocompromised patient with documented rhino - orbital mucormycosis ( figs . 3 , 5 and 6 ) .
chest ct scan showed bilateral pleural effusion , multiple nodules and rhs with thin reticulation ( figs . 1 and 4 ) .
although histopathology findings are usually needed to establish the diagnosis of pulmonary mucormycosis , using ct imaging and clinical presentation we can avoid the invasive procedures such as lung biopsy
. there are few case reports of pneumothorax in pulmonary mucormycosis , some of which are iatrogenic during mechanical ventilation and bronchoscopic procedure [ 911 ] .
combined mucormycosis and methicillin - resistant staphylococcus aureus ( mrsa ) were found to be responsible for life threatening pneumothorax in an immunocompromised patient .
mucormycosis and aspergillus have been recognized as leading to pneumonia and pneunothorax in a dialysis patient .
however , spontaneous pneumothorax in pulmonary mucormycosis that is followed by rhs seems to be a unique case . based on patient 's background and clinical signs , amphotericin b deoxycholate ( 1  mg
the lower dose of antifungal drug has been due to the patient 's renal insufficiency .
ambisome would have certainly been a better choice than amphotericin b ; however , the former has not been available in iran .
however the lack of bone erosion in sinus ct scan , delay in pathologic result and patient 's poor clinical condition , lead into the reluctance of surgeon for extensive debridement that had negative impact on patient 's prognosis .
pneumothorax which is due to mucormycosis can be fatal particularly in immunocompromised persons , so clinicians should take immediate measures ( follow up imaging and pathology ) to confirm or reject the presence of invasive fungal infection . if confirmed , antifungal therapy is necessary as soon as possible .

Answer:
mucormycosis , an invasive fungus with a variety of clinical presentation , is a devastating infection in immunocompromised host . here
 an unusual case of pulmonary mucormycosis is introduced in an immunodeficient patient in which pneumothorax was followed by reversed halo sign ( rhs ) .
 the clinicians , who visit immunocompromised persons with pneumothorax , should be considerate to take immediate imaging and pathologic measures to confirm or reject mucormycosis .


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:
first performed in 1989 , laparoscopic cholecystectomy quickly became the gold standard for surgical extirpation of the gallbladder . soon after , reports began to emerge of an increased incidence of significant bile duct injuries . reported injury rates varied from 0.1% to 2.2% compared with 0.1% for open cholecystectomy .
the increased rate of bile duct injury has been attributed to a steep learning curve for laparoscopic cholecystectomy .
subsequent referral to tertiary centers for repair of transected common bile ducts resulted in published series that outlined the mechanisms of injury .
risk factors for iatrogenic injury to the common duct appear to be the surgeon 's inexperience , patient obesity , scarring and acute inflammation .
a common factor in the reported cases of bile duct injury is the misidentification of common duct for cystic duct , resulting in resection of a portion of the common bile and hepatic ducts and a right hepatic artery injury .
precautions suggested to decrease the possibility of bile duct injury have included : routine cystic duct cholangiography , cholecystocholangiography , confirmed identification of the junction of the cystic duct with the common bile and hepatic ducts and identification of the junction of the cystic artery with the right hepatic artery .
our experience with laparoscopic cholecystectomy supports the importance of anatomic identification in the safe performance of the procedure and also suggests the presence of a useful and reproducible anatomic landmark which can help define a zone of safe dissection within the triangle of calot .
this study is derived from a single surgeon 's experience with more than 300 laparoscopic cholecystectomies performed since 1991 .
all patients with acute or chronic gallbladder disease were considered for the laparoscopic approach with the exception of those with suspected gallbladder masses or neoplasm .
the anatomy of the biliary tree was defined prior to division of the cystic duct and artery .
cholangiograms were abandoned only if the lumen of the cystic duct would not accommodate the epidural catheter used for this purpose . during 1996 ,
patients were chosen in one of three representative categories as they randomly presented in the course of our practice .
these were chronic disease , acutely inflamed gallbladder and intra - operatively identified aberrant anatomy .
i.m . , a 67 year - old - female with biliary colic systems and ultrasound proven cholecystolithiasis , underwent outpatient laparoscopic cholecystectomy .
two 1 mm veins were demonstrated within the triangle of calot between the cystic duct and cystic artery ( figure 1 ) .
case i : acute chdeaystititis and multiple cystic veins m.b . , a 56-year - old female with biliary colic symptoms and cholecystolithiasis on ultrasound , underwent outpatient laparoscopic cholecystectomy .
a small venous structure was found to be crossing it and extending to the gallbladder ( figure 2 ) .
further dissection showed the artery to be an aberrant right hepatic artery with a short cystic artery identified later .
, a 49-year - old female , was admitted with acute abdominal pain , fever , leukocytosis and thickened gallbladder containing stones on ultrasound .
dissection within the triangle of calot demonstrated venous structures between the later confirmed cystic duct and artery ( figure 3 ) .
early in our experience with laparoscopic cholecystectomy , the presence of small tubular structures within the triangle of calot became evident as being necessarily divided to proceed with the dissection . among these was a structure that presented as a bridge between the cystic artery and duct ; the division of which , unless controlled , resulted in insignificant but annoying bleeding .
it quickly became a standard part of the procedure to clip or cauterize this ves sel during the dissection .
its color and non - pulsatile bleeding when divided , indicated that this was a vein , ostensibly unnamed .
it was subsequently determined that these venous channels were named as the cystic veins and their courses documented in early textbooks of anatomy .
i.m . , a 67 year - old - female with biliary colic systems and ultrasound proven cholecystolithiasis , underwent outpatient laparoscopic cholecystectomy .
two 1 mm veins were demonstrated within the triangle of calot between the cystic duct and cystic artery ( figure 1 ) .
m.b . , a 56-year - old female with biliary colic symptoms and cholecystolithiasis on ultrasound , underwent outpatient laparoscopic cholecystectomy .
a small venous structure was found to be crossing it and extending to the gallbladder ( figure 2 ) .
further dissection showed the artery to be an aberrant right hepatic artery with a short cystic artery identified later .
n.m . , a 49-year - old female , was admitted with acute abdominal pain , fever , leukocytosis and thickened gallbladder containing stones on ultrasound .
dissection within the triangle of calot demonstrated venous structures between the later confirmed cystic duct and artery ( figure 3 ) .
early in our experience with laparoscopic cholecystectomy , the presence of small tubular structures within the triangle of calot became evident as being necessarily divided to proceed with the dissection . among these was a structure that presented as a bridge between the cystic artery and duct ; the division of which , unless controlled , resulted in insignificant but annoying bleeding .
it quickly became a standard part of the procedure to clip or cauterize this ves sel during the dissection .
its color and non - pulsatile bleeding when divided , indicated that this was a vein , ostensibly unnamed .
it was subsequently determined that these venous channels were named as the cystic veins and their courses documented in early textbooks of anatomy .
a consistent anatomic feature during laparoscopic cholecystectomy has been the presence of venous twigs that run parallel to the cystic duct and perpendicular to the common bile duct , bridging the gap between cystic artery and cystic duct . as the veins do not cross the common hepatic duct , their presence can serve as an anatomic feature of a safe dissection space between the important structures of the triangle of calot .
during surgical residency a common question intended to " trip up " junior residents during division of the cystic artery , has been to ask them to define the cystic vein .
it is usually pointed out to the less assured that there is no cystic vein per se , but that the venous drainage is through the bed of the liver . in contradistinction to this , however , grant 's anatomy , in illustrating the veins of the extrahepatic bile passages and gallbladder ( figure 4 ) , clearly demonstrates venous drainage directly into the liver , and describes venous twigs which  clinging to the passages .... join branches of the portal vein .
gray 's anatomy of the human body likewise describes cystic veins which join at the neck of the gallbladder to form either single or double cystic veins which flow along the cystic duct and upward along the hepatic ducts .
textbooks of surgery , however , do not assign much importance to the venous drainage of the gallbladder .
the textbook of surgery edited by sabiston reports only that the venous drainage of the gallbladder and extrahepatic ducts is into the portal vein .
 schwartz 's principles of surgery describes the venous drainage as  variable and generally does not run parallel with the arteries .
a prominent surgical atlas similarly omits all veins from it 's anatomic diagrams and does not describe operative management of these structures during the procedure .
one of the differences between laparoscopic and open surgery is that magnification of the anatomy gives a new perspective to the dissection process .
the magnified field of view demands meticulous attention to operative detail lest bleeding from a source not significant during open cholecystectomy , completely obscures the field during laparoscopic cholecystectomy .
this fractal * anatomic view uncovered the presence of venous structures within the triangle of calot , which , if not clipped or cauterized prior to division , would obscure the operative field . only with experience
did we find the presence of the cystic veins to be constant . during difficult cases
, the cystic veins can serve as a landmark for that space between cystic duct , cystic artery and common bile duct , that allows for safe handling and isolation of these vital structures .
a review of anatomy texts has shown that the cystic veins were known to classical anatomists .
it was only later that , without apparent clinical relevance , a description of the cystic veins was omitted from surgical textbooks and their very existence devolved into a trick question for unsuspecting house staff .
i do not doubt that experienced laparoscopic surgeons have encountered these venous structures and are dealing with them on a regular basis , but that they exist as a reliable anatomic feature of the region is not well appreciated .
its importance , however , may lie in the fact that the cystic vein can serve as a landmark during a difficult laparoscopic cholecystectomy to decrease the risk of inadvertent bile duct injury .

Answer:
the cystic vein , a portion of biliary anatomy whose insignificance in open gallbladder surgery led to its being relegated to mythology , has been rediscovered by the magnified view of laparoscopic surgery .
 its presence is an important anatomic feature that helps distinguish between cystic duct and common hepatic duct , thus diminishing the risk of inadvertent bile duct injury during laparoscopic cholecystectomy .


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:
pasteurella multocida was first described by revolee in 1877 and further characterized by pasteur in 1880 .
pasteurella species usually have low virulence in humans , but serious manifestations sometimes occur and can lead to bacteremia .
we present a patient who developed septic shock as a result of p. multocida bacteremia , presumptively from an intra - abdominal infection .
a 52-year - old african american female was brought to the emergency department for generalized abdominal discomfort , altered mental status , diarrhea , fevers and chills for 4 - 5 days .
her past medical history was significant for alcohol abuse and alcohol - related liver cirrhosis . in the emergency department , vital signs were as follows : blood pressure of 74/42 mmhg , heart rate of 112 beats / min , respiratory rate of 20 breaths / min and temperature of 98.6 f. remarkable findings on physical examination included jaundice as well as abdominal distention and tenderness to palpation , especially in the right upper quadrant .
as per family , she did not have recent travels or exposure to sick people .
they denied having domestic animals at home or any contact to the patient with pets .
admission diagnosis was systemic inflammatory response syndrome with sepsis and septic shock with multi - organic dysfunction syndrome , presumptively secondary to community - acquired pneumonia , possible biliary tract infection ( ascending cholangitis ) , probable spontaneous bacterial peritonitis ( sbp ) and alcoholic hepatitis .
empiric intravenous antimicrobial therapy , composed by piperacillin / tazobactam ( 2.25 g every 8 h ) and azithromycin ( 500 mg every 24 h ) , was initiated .
laboratory results on admission were : a complete blood cell count of 21,000/mm(90% neutrophils ) , a platelet count of 51,000/mm , a sodium level of 127 meq / l , a potassium level of 5.3 meq / l , a bicarbonate level of 15 meq / l and a creatinine level of 6.3 mg / dl .
alkaline phosphatase level was 290 iu / l , gamma - glutamyl transpeptidase level was 290 u / l and lactate dehydrogenase level was 482
total bilirubin level was 14.5 mg / dl , with a direct bilirubin level of 10.1 mg / dl .
arterial blood gases showed a ph of 7.15 , a pco2 of 23 , and a po2 of 132 while the patient was receiving mechanical ventilation with fio2 of 60% .
after 24 h of admission , patient remained in critical condition and requiring maximum doses of vasopressors , despite of what it seems to be the appropriate empiric antimicrobial therapy .
blood culture system bact - alert 3d was used for the recovery of the organism .
no minimal inhibitory concentrations for these antimicrobials were reported . in spite of all medical efforts ,
p. multocida is a small gram - negative non - spore forming facultative anaerobe organism that is a natural inhabitant of the normal gastrointestinal flora and the upper respiratory tract of wild and domestic animals , especially cats and dogs .
it is easily overgrowing by other flora in the sputum and might be regularly missed , as it resembles haemophilus influenzae , francisella tularensis and yersinia pestis .
the five species that cause the majority of pasteurellosis are : multocida , septica , canis , stomatis , and dagmatis .
human p. multocida infections have been reported to occur with and without animal exposure , the former mostly associated with the domestic cat and dog bites or scratches .
most of the infections involve the skin and soft - tissues and they can be complicated by abscess formation , osteomyelitis or septic arthritis .
the respiratory tract is the second most common site of infection with a wide spectrum of diseases that includes rhinosinusitis , tracheobronchitis , epiglottitis , pneumonia , empyema and lung abscesses .
the majority of p. multocida pneumonia cases occur in elderly patients with underlying chronic pulmonary disease .
invasive forms of p. multocida infection usually occur in immunocompromised patients , such as those with advanced age , chronic renal failure , solid tumors , hematological malignancies , diabetes mellitus or liver cirrhosis .
p. multocida causes a wide variety of disease , including abdominal and pelvic infections , endocarditis , meningitis and endophtalmitis .
von graevenitz et al . reviewed 21 proven cases of p. multocida bacteremia . a remarkable number of those cases involved patients with liver diseases , including liver cirrhosis of any etiology , hepatitis and infiltrating tumors .
impaired function of the reticuloendothelial system and the presence of portosystemic shunts in patients with liver disease seem to play a major role in the development of bacteremia .
this case seems peculiar in that no direct contact with a domestic animal could be documented .
our patient had a history of alcohol - induced liver cirrhosis , which predisposed her to the development of bacteremia . however , retrospectively , it is difficult to establish the primary source of infection in this case .
the findings of the abdominal examination may suggest that the primary source was the intra - abdominal cavity .
unfortunately , the medical team was not able to performed paracentesis to obtain ascitic fluid for cytology and cultures due to patient s medical condition .
no abdominal imaging was available . on the other hand , the chest radiography findings of infiltrate and pleural effusion may point the respiratory tract as the primary source of infection .
we believed that , given the history of symptoms on admission and the presence of underlying liver disease , the intra - abdominal cavity was the most likely primary source of infection in this patient .
nasopharyngeal colonization with p. multocida with transient bacteremia and seeding of the peritoneal cavity in immunosupressed cat owners could play an important role in the development of sbp .
ten of these patients were exposed to animals , nine had positive blood cultures and four patients died .
however , penicillin - resistant strains in human infections have been described . in these cases , 2 and 3 generation cephalosporins , macrolides , fluoroquinolones , tetracyclines , and trimethoprim - sulfamethoxazole
outcome is associated with severity of the infection , the extent of the underlying disease and the early initiation of appropriate therapy .
although cases of bacteremic p. multocida infections has been infrequently reported in the literature , clinicians should considered this organism as an important and potentially lethal pathogen in humans , where it can cause life - threatening infections .
p. multocida should be included in the microbiologic differential diagnosis in patients with underlying chronic liver diseases who presents with possible intra - abdominal infection , even without history of exposure to domestic animals .

Answer:
pasteurella multocida is a gram - negative organism characterized morphologically as coccobacillus .
 it is the commonest organism infecting pet bites .
 however , severe infections may occur in the absence of animal bites or scratches .
 pasteurella multocida serves as an opportunistic pathogen in humans , especially in patients with depressed immune system .
 few cases in the literature identify pasteurella multocida as the causative agent of septic shock , especially in cirrhotic patients .
 we report a patient who presented with septic shock as a result of pasteurella multocida bacteremia , without prior history of animal exposure .