Transient hysteresis and inherent stochasticity in gene regulatory networks.

Cell fate determination, the process through which cells commit to differentiated states is commonly mediated by gene regulatory motifs with mutually exclusive expression states. The classical deterministic picture for cell fate determination includes bistability and hysteresis, which enables the persistence of the acquired cellular state after withdrawal of the stimulus, ensuring a robust cellular response. However, stochasticity inherent to gene expression dynamics is not compatible with hysteresis, since the stationary solution of the governing Chemical Master Equation does not depend on the initial conditions. We provide a quantitative description of a transient hysteresis phenomenon reconciling experimental evidence of hysteretic behaviour in gene regulatory networks with inherent stochasticity: under sufficiently slow dynamics hysteresis is transient. We quantify this with an estimate of the convergence rate to the equilibrium and introduce a natural landscape capturing system's evolution that, unlike traditional cell fate potential landscapes, is compatible with coexistence at the microscopic level.

Pontocerebellar hypoplasia type 2 (PCH2): report of two siblings.

We describe two sisters affected by pontocerebellar hypoplasia type 2 associated with microcephaly, hypertonia, severe choreiform movements, an almost complete lack of psychomotor development, and generalized tonic-clonic seizures. Clinical and neuroradiological findings ruled out other conditions associated with pontocerebellar hypoplasia, i.e. pontocerebellar hypoplasia type 1, carbohydrate-deficient glycoprotein syndrome, and olivopontocerebellar hypoplasia/atrophy.

Arteriovenous shunts between dural branches of the carotid artery and the cavernous sinus.

Three cases with dural arteriovenous shunts of the cavernous sinus are reported. The clinical signs usually were mild and included frontal headache, dilated conjunctival veins, exophthalmos, bruit, and oculomotor nerve palsy. Arterial contributions to the fistulae arose from meningeal branches of the internal and external carotid arteries. The precise diagnosis was made by selective angiography supplemented by subtraction and magnification techniques. The distal occlusion of the feeding arteries close to the shunt offers advantages when compared with conventional vessel ligation because of a more effective exclusion of vascular abnormalities from the circulation.

Cerebral cavernous angioma. Diagnostic considerations.

Eighteen cases of cerebral cavernous angiomas are reported, and their histopathological, clinical and radiological features are reviewed. MR complements TC in characterizing cavernomas and in distinguishing them from similar-appearing lesions. However, when such lesions are seen with atypical features, discrimination from hemorrhagic tumors remains problematic. More malignant lesions present, on MRI, a much larger area of abnormality and make themselves obvious in a shorter period. Gadolinium administration may allow a more specific interpretation of small lesions.

Post-traumatic cerebral air embolism. Case report.

A case of post-traumatic cerebral air embolism is presented. In the chest-X-radiography fractures of many ribs and hemo-pneumothorax were visible on the right side associated with intra-alveolar, interstitial hemorrhages and mediastinal emphysema. At the end of a CT scan of the head appeared features of arterial air embolism. The patient was diagnosed as brain dead and cardiac arrest occurred one hour after.

Herniated disk in adolescents.

Twenty-one patients (9 female and 12 male) aged from 13 to 22 years were observed for lumbago and lumbo-sciatica caused by a discopathy which was subsequently confirmed by radiology and surgery. None of these patients had a history of trauma. It must be underlined that the painful symptoms exhibited and the young age of the patients suggest such pathologies as infections, tumours or malformations, but the possibility of discopathy must always be considered. It is also interesting to note the differences observed in symptomatology between adults and adolescents and to consider the various pathogenetic factors which might cause discopathy in adolescents while it was until now believed to be reserved to adults.

Generic parameterization for a pharmacokinetic model to predict Cd concentrations in several tissues of different fish species.

In the present work, a set of generic parameters was proposed for a pharmacokinetic model, with the objective of predicting Cd concentration in the tissues of diverse fish species under different environmental conditions. Cd concentrations in a number of tissues of Oncorhynchus mykiss and Cyprinus carpio were estimated by a structurally identifiable multicompartmental model (unique solution). The 13 generic parameters of the model comprised exchange rates, tissue-blood partition coefficients, and weight-corrected elimination rate constants accounting for the routes of water respiration, excretion and egestion. On the other hand, absorption efficiencies from water and food were considered to be condition-specific and estimated for each experiment. These two parameters reflected the differences in fish exposure to diet (food type and metal concentration) or water (water chemistry and bioavailable metal concentration). A data set of 27 experiments of Cd bioaccumulation in fish tissues was compiled for model calibration. The selected dynamics on trout and carp were performed under very different experimental conditions, involving water and/or food exposure, different fish weights and exposure concentrations and the presence/absence of depuration periods. Model predicted, for most compartments and experiments, the tendency of Cd dynamics. However, accumulation in liver and kidney was underestimated in approximately a half of the experiments, due mainly to a rapid metallothionein (MT) sequestration phenomena and subsequent saturation on liver and kidney produced under high exposure concentrations. On the other hand, both generic and condition-specific parameter values were in accordance with the values reported in literature when available. Therefore, the results obtained in this work are an initial step indicating that a generic global input parameter set could be applied to physiology-based pharmacokinetic (PBPK) models for estimating Cd accumulation in fish in different types of scenarios.

Computed tomography for diagnosis of empty sella associated with enhancing pituitary microadenoma.

Ten cases of primary empty sella with clinical findings of a secreting pituitary adenoma were studied using computed tomography (CT). Scans performed before contrast medium infusion confirmed the diagnosis of empty sella. After infusion, eight cases were found to have a nodular area of increased density within the sella turcica. In two patients, the enhancement probably corresponded to the pituitary stalk; the other six patients demonstrated CT evidence of pituitary microadenoma. These six patients had surgical confirmation of the existence of neoplasm. Tomodensitometric diagnosis of empty sella combined with microadenoma allows transsphenoidal microsurgery for complete tumor removal with preservation of the residual pituitary gland. For comparison, in a series of 21 patients suspected of having microadenomas, but without evidence of empty or enlarged sella, enhancing microadenomas were shown in 13 (62%).

Cavernous angioma does not exist?

12 cases of cerebral "venous angioma" are reported; pathological, clinical and radiological features of the lesion are reviewed. "Venous angioma" should be regarded as a developmental anatomic variation of the venous drainage system of the white matter. Its clinical significance is controversial, although it has been reported to cause hemorrhage, seizures, progressive neurological deficits, headaches. The clinical presentation of our patients was variable and, in some of them, dependent also on associated lesions. An hematoma was found in three patients, infarction in one and tumor in one. Angiography, CT and MRI demonstrated the typical appearance of the anomaly. Surgery was performed in one patient harboring a significant cerebellar hematoma and the coexistence of a cavernoma was pathologically confirmed. Venous developmental anomalies are often identified as the source of symptoms due to other conditions, that should be treated independently sparing the anomaly.

Cavernous sinus meningiomas.

Analysing 12 cases of cavernous sinus meningiomas the authors conclude that: the clinical history is characteristic; CT scan has proved to be more sensitive than carotid angiography in detecting small lesions. However in large lesions the vascular supply pattern is the only feature that exactly identifies the site of the lesion. Both angiography and CT scan allow a near definitive diagnosis of meningioma; because of their location it is almost always impossible to remove these tumours completely. Actually the best treatment is a piecemeal subtotal microsurgical removal via a subtemporal approach. Radiotherapy is indicated for partially resected lesions. On the basis of the revision of the anatomy of this region and looking forward to a widespread use of the Cavitron in neurosurgery, a more radical approach to this lesion is foreseen.