Genetically determined heterogeneity of lung disease in a mouse model of airway mucus obstruction

Mucus clearance is an important airway innate defense mechanism. Airway-targeted overexpression of the epithelial Na(+) channel β-subunit [encoded by sodium channel nonvoltage gated 1, beta subunit (Scnn1b)] in mice [Scnn1b-transgenic (Tg) mice] increases transepithelial Na(+) absorption and dehydrates the airway surface, which produces key features of human obstructive lung diseases, including mucus obstruction, inflammation, and air-space enlargement. Because the first Scnn1b-Tg mice were generated on a mixed background, the impact of genetic background on disease phenotype in Scnn1b-Tg mice is unknown. To explore this issue, congenic Scnn1b-Tg mice strains were generated on C57BL/6N, C3H/HeN, BALB/cJ, and FVB/NJ backgrounds. All strains exhibited a two- to threefold increase in tracheal epithelial Na(+) absorption, and all developed airway mucus obstruction, inflammation, and air-space enlargement. However, there were striking differences in neonatal survival, ranging from 5 to 80% (FVB/NJhemorrhage and lung atelectasis. The spontaneous occurrence of a high surviving BALB/cJ line, which exhibited delayed onset of Na(+) hyperabsorption, provided evidence that: 1) air-space enlargement and postnatal death were only present when Na(+) hyperabsorption occurred early, and 2) inflammation and mucus obstruction developed whenever Na(+) hyperabsorption was expressed. In summary, the genetic context and timing of airway innate immune dysfunction critically determines lung disease phenotype. These mouse strains may be useful to identify key modifier genes and pathways.

Tuning curve of type-0 spontaneous parametric down-conversion

We study the tuning curve of entangled photons generated by type-0 spontaneous parametric down-conversion in a periodically poled potassium titanyl phosphate crystal. We demonstrate the X-shaped spatiotemporal structure of the spectrum by means of measurements and numerical simulations. Experiments for different pump waists, crystal temperatures, and crystal lengths are in good agreement with numerical simulations.

Spontaneous peristaltic airway contractions propel lung liquid through the bronchial tree of intact and fetal lung explants

Spontaneous contractions of the fetal airways are a well recognized but poorly characterized phenomenon. In the present study spontaneous narrowing of the airways was analyzed in freshly isolated lungs from early to late gestation in fetal pigs and rabbits and in cultured fetal mouse lungs. Propagating waves of contraction traveling proximal to distal were observed in fresh lungs throughout gestation which displaced the lung liquid along the lumen. In the pseudoglandular and canalicular stages (fetal pigs) the frequency ranged from 2.3 to 3.3 contractions/min with a 39 to 46% maximum reduction of lumen diameter. In the saccular stage (rabbit) the frequency was 10 to 12/min with a narrowing of approximately 30%. In the organ cultures the waves of narrowing started at the trachea in whole lungs, or at the main bronchus in lobes (5.2 +/- 1.5 contractions/min, 22 +/- 8% reduction of lumen diameter), and as they proceeded distally along the epithelial tubes the luminal liquid was shifted toward the terminal tubules, which expanded the endbuds. As the tubules relaxed the flow of liquid was reversed. Thus the behavior of airway smooth muscle in the fetal lung is phasic in type (like gastrointestinal muscle) in contrast to that in postnatal lung, where it is tonic. An intraluminal positive pressure of 2.33 +/- 0.77 cm H(2)O was recorded in rabbit fetal trachea. It is proposed that the active tone of the smooth muscle maintains the positive intraluminal pressure and acts as a stimulus to lung growth via the force exerted across the airway wall and adjacent parenchyma. The expansion of the compliant endbuds by the fluid shifts at the airway tip may promote their growth into the surrounding mesenchyme.

Diagnosis and therapy of acute hemorrhage in patients with pelvic fractures

Within the past 15 years, significant advances in the imaging of multiorgan and complex trauma primarily due to the improvement of cross-sectional imaging have resulted in the optimization of the expedient diagnosis and management of the polytrauma patient. At the forefront, multidetector computed tomography (MDCT) has become the cornerstone of modern emergency departments and trauma centers. In many institutions, MDCT is the de facto diagnostic tool upon trauma activation. In the setting of pelvic imaging, MDCT (with its high spatial resolution and sensitivity as well as short acquisition times) allows for rapid identification and assessment of pelvic hemorrhage leading to faster triage and definitive management. In trauma centers throughout the world, angiography and minimally invasive catheter-based embolization techniques performed by interventional radiologists have become the standard of care for patients with acute pelvic trauma and related multiorgan hemorrhage. In an interdisciplinary setting, embolization may be performed either alone or as an adjunct procedure with open or closed reduction and stabilization techniques. A team-based approach involving multiple disciplines (e.g., radiology, traumatology, orthopedic surgery, intensive care medicine) is crucial to monitor and treat the actively bleeding patient appropriately.

Still frame from the hour of death: Acute intracerebral hemorrhage on post-mortem computed tomography in a decomposed corpse

We report a case of an acute hypertensive, intracerebral hemorrhage on post-mortem computed tomography (PMCT) in a decomposed corpse. In clinical radiology, the appearance of blood on cross-sectional imaging is used to estimate the age of intracranial hemorrhage. The findings from this case indicate that characteristics of intracerebral blood on PMCT provide a still frame of the hemorrhage, as it was at the time of death. This observation suggests that the appearance of blood on PMCT may be used to estimate the age of an intracerebral hemorrhage but not to estimate the post-mortem interval.

Ultra-early intravenous stroke thrombolysis: do all patients benefit similarly?

BACKGROUND AND PURPOSE We previously reported increased benefit and reduced mortality after ultra-early stroke thrombolysis in a single center. We now explored in a large multicenter cohort whether extra benefit of treatment within 90 minutes from symptom onset is uniform across predefined stroke severity subgroups, as compared with later thrombolysis. METHODS Prospectively collected data of consecutive ischemic stroke patients who received i.v. thrombolysis in 10 European stroke centers were merged. Logistic regression tested association between treatment delays, as well as excellent 3-month outcome (modified Rankin scale, 0-1), and mortality. The association was tested separately in tertiles of baseline National Institutes of Health Stroke Scale. RESULTS In the whole cohort (n=6856), shorter onset-to-treatment time as a continuous variable was significantly associated with excellent outcome (P<0.001). Every fifth patient had onset-to-treatment time≤90 minutes, and these patients had lower frequency of intracranial hemorrhage. After adjusting for age, sex, admission glucose level, and year of treatment, onset-to-treatment time≤90 minutes was associated with excellent outcome in patients with National Institutes of Health Stroke Scale 7 to 12 (odds ratio, 1.37; 95% confidence interval, 1.11-1.70; P=0.004), but not in patients with baseline National Institutes of Health Stroke Scale>12 (odds ratio, 1.00; 95% confidence interval, 0.76-1.32; P=0.99) and baseline National Institutes of Health Stroke Scale 0 to 6 (odds ratio, 1.04; 95% confidence interval, 0.78-1.39; P=0.80). In the latter, however, an independent association (odds ratio, 1.51; 95% confidence interval, 1.14-2.01; P<0.01) was found when considering modified Rankin scale 0 as outcome (to overcome the possible ceiling effect from spontaneous better prognosis of patients with mild symptoms). Ultra-early treatment was not associated with mortality. CONCLUSIONS I.v. thrombolysis within 90 minutes is, compared with later thrombolysis, strongly and independently associated with excellent outcome in patients with moderate and mild stroke severity.

Management of postpartum hemorrhage (PPH): algorithm of the interdisciplinary D-A-CH consensus group PPH (Germany – Austria – Switzerland)

Postpartum hemorrhage (PPH) is one of the main causes of maternal deaths even in industrialized countries. It represents an emergency situation which necessitates a rapid decision and in particular an exact diagnosis and root cause analysis in order to initiate the correct therapeutic measures in an interdisciplinary cooperation. In addition to established guidelines, the benefits of standardized therapy algorithms have been demonstrated. A therapy algorithm for the obstetric emergency of postpartum hemorrhage in the German language is not yet available. The establishment of an international (Germany, Austria and Switzerland D-A-CH) "treatment algorithm for postpartum hemorrhage" was an interdisciplinary project based on the guidelines of the corresponding specialist societies (anesthesia and intensive care medicine and obstetrics) in the three countries as well as comparable international algorithms for therapy of PPH.The obstetrics and anesthesiology personnel must possess sufficient expertise for emergency situations despite lower case numbers. The rarity of occurrence for individual patients and the life-threatening situation necessitate a structured approach according to predetermined treatment algorithms. This can then be carried out according to the established algorithm. Furthermore, this algorithm presents the opportunity to train for emergency situations in an interdisciplinary team.

Pre- and postnatal imaging of Pai syndrome with spontaneous intrauterine closure of a frontal cephalocele.

Pai syndrome is a rare congenital disorder characterized by cutaneous polyps of the face, pericallosal lipoma and median cleft lip. We report on a newborn girl with a variant of Pai syndrome presenting with all typical findings except a median cleft. In addition, fetal sonography and MRI showed the unique intrauterine evolution of a cephalocele into an atretic cephalocele.

Spontaneous supersymmetry breaking in the 2D N=1 Wess-Zumino Model

We study the phase diagram of the two-dimensional N=1 Wess-Zumino model on the lattice using Wilson fermions and the fermion loop formulation. We give a complete nonperturbative determination of the ground state structure in the continuum and infinite volume limit. We also present a determination of the particle spectrum in the supersymmetric phase, in the supersymmetry broken phase and across the supersymmetry breaking phase transition. In the supersymmetry broken phase, we observe the emergence of the Goldstino particle.

The rabbit blood shunt subarachnoid haemorrhage model.

The recently introduced rabbit blood shunt subarachnoid haemorrhage model is based on the two standard procedures of subclavian artery cannulation and transcutaneous cisterna magna puncture. An extracorporeal shunt placed in between the arterial system and the subarachnoid space allows examiner-independent SAH in a closed cranium. Despite its straightforwardness, it is worth examining some specific features and characteristics of the model. We outline technical considerations to successfully perform the model with minimal mortality and morbidity. In addition, we discuss outcome measures, advantages and limitations, and the applicability of the model for the study of early brain injury and delayed cerebral vasospasm after SAH.