Computational modelling of cerebral oedema and osmotherapy following ischaemic stroke.

In ischaemic stroke, a large reduction in blood supply can lead to the breakdown of the blood brain barrier and to cerebral oedema after reperfusion therapy. Cerebral oedema is marked by elevated intracranial pressure (ICP), tissue herniation and reduced cerebral perfusion pressure. In clinical settings, osmotherapy has been a common practice to decrease ICP. However, there are no guidelines on the choice of administration protocol parameters such as injection doses, infusion time and retention time. Most importantly, the effects of osmotherapy have been proven controversial since the infusion of osmotic agents can lead to a range of side effects. Here, a new Finite Element model of brain oedema and osmotherapy is thus proposed to predict treatment outcome. The model consists of three components that simulate blood perfusion, oedema, and osmotherapy, respectively. In the perfusion model (comprising arteriolar, venous, and capillary blood compartments), an anatomically accurate brain geometry is used to identify regions with a perfusion reduction and potential oedema occurrence in stroke. The oedema model is then used to predict ICP using a porous circulation model with four fluid compartments (arteriolar blood, venular blood, capillary blood, and interstitial fluid). In the osmotherapy model, the osmotic pressure is varied and the changes in ICP during different osmotherapy episodes are quantified. The simulation results of the model show excellent agreement with available clinical data and the model is employed to study osmotherapy under various parameters. Consequently, it is demonstrated how therapeutic strategies can be proposed for patients with different pathological parameters based on simulations.

Modelling collateral flow and thrombus permeability during acute ischaemic stroke.

The presence of collaterals and high thrombus permeability are associated with good functional outcomes after an acute ischaemic stroke. We aim to understand the combined effect of the collaterals and thrombus permeability on cerebral blood flow during an acute ischaemic stroke. A cerebral blood flow model including the leptomeningeal collateral circulation is used to simulate cerebral blood flow during an acute ischaemic stroke. The collateral circulation is varied to capture the collateral scores: absent, poor, moderate and good. Measurements of the transit time, void fraction and thrombus length in acute ischaemic stroke patients are used to estimate thrombus permeability. Estimated thrombus permeability ranges between 10-7 and 10-4 mm2. Measured flow rates through the thrombus are small and the effect of a permeable thrombus on brain perfusion during stroke is small compared with the effect of collaterals. Our simulations suggest that the collaterals are a dominant factor in the resulting infarct volume after a stroke.

Quantification of hypoxic regions distant from occlusions in cerebral penetrating arteriole trees.

The microvasculature plays a key role in oxygen transport in the mammalian brain. Despite the close coupling between cerebral vascular geometry and local oxygen demand, recent experiments have reported that microvascular occlusions can lead to unexpected distant tissue hypoxia and infarction. To better understand the spatial correlation between the hypoxic regions and the occlusion sites, we used both in vivo experiments and in silico simulations to investigate the effects of occlusions in cerebral penetrating arteriole trees on tissue hypoxia. In a rat model of microembolisation, 25 µm microspheres were injected through the carotid artery to occlude penetrating arterioles. In representative models of human cortical columns, the penetrating arterioles were occluded by simulating the transport of microspheres of the same size and the oxygen transport was simulated using a Green's function method. The locations of microspheres and hypoxic regions were segmented, and two novel distance analyses were implemented to study their spatial correlation. The distant hypoxic regions were found to be present in both experiments and simulations, and mainly due to the hypoperfusion in the region downstream of the occlusion site. Furthermore, a reasonable agreement for the spatial correlation between hypoxic regions and occlusion sites is shown between experiments and simulations, which indicates the good applicability of in silico models in understanding the response of cerebral blood flow and oxygen transport to microemboli.

Social media use among children and teenagers with asthma bronchiale / Asthma bronchialéban szenvedo gyermekek közösségimédia-használata

Introduction: The health behavior of patients with asthma bronchiale can be influenced by the virtual world (es., Facebook). It is often used to compensate their attachment deficits. Objective: In this study, the use of social media is analyzed among asthmatic children compared to a healthy control group. Method: 250 asthmatic and 250 healthy children were interviewed from the age of 10 to 18. The Facebook Intensity Scale, the Ten Item Personality Inventory, the Rosenberg Self-Esteem Scale, the short version of the Beck Depression Inventory and the Multidimensional Anxiety Scale for Children were used in the study. Results: Asthmatic children's social media time was significantly lower compared to that of healthy children (p<0.001). However, their feeling of being part of the Facebook community is the main motivation to use it (p<0.001). Higher scores of anxiety and depression, and the lower self-esteem compared to the healthy control group can be detected among asthmatic children (p<0.001). The increased use of Facebook can be shown in both groups of girls. The increased use of Facebook among girls is in connection with a higher score of depression and anxiety (p<0.05). Conclusion: Social media plays a very important role in the life of asthmatic children. The psychoeducation and prevention is of basic importance, because the age group of 10-18-year-old children is vulnerable to the addictive effect of social media.

In silico trials for treatment of acute ischemic stroke: Design and implementation.

An in silico trial simulates a disease and its corresponding therapies on a cohort of virtual patients to support the development and evaluation of medical devices, drugs, and treatment. In silico trials have the potential to refine, reduce cost, and partially replace current in vivo studies, namely clinical trials and animal testing. We present the design and implementation of an in silico trial for treatment of acute ischemic stroke. We propose an event-based modelling approach for the simulation of a disease and injury, where changes to the state of the system (the events) are assumed to be instantaneous. Using this approach we are able to combine a diverse set of models, spanning multiple time scales, to model acute ischemic stroke, treatment, and resulting brain tissue injury. The in silico trial is designed to be modular to aid development and reproducibility. It provides a comprehensive framework for application to any potential in silico trial. A statistical population model is used to generate cohorts of virtual patients. Patient functional outcomes are also predicted with a statistical model, using treatment and injury results and the patient's clinical parameters. We demonstrate the functionality of the event-based modelling approach and trial framework by running proof of concept in silico trials. The proof of concept trials simulate the same cohort of patients twice: once with successful treatment (successful recanalisation) and once with unsuccessful treatment (unsuccessful treatment). Ways to overcome some of the challenges and difficulties in setting up such an in silico trial are discussed, such as validation and computational limitations.

Modelling the effects of cerebral microthrombi on tissue oxygenation and cell death.

Thrombectomy, the mechanical removal of a clot, is the most common way to treat ischaemic stroke with large vessel occlusions. However, perfusion cannot always be restored after such an intervention. It has been hypothesised that the absence of reperfusion is at least partially due to the clot fragments that block the downstream vessels. In this paper, we present a new way of quantifying the effects of cerebral microthrombi on oxygen transport to tissue in terms of hypoxia and ischaemia. The oxygen transport was simulated with the Green's function method on physiologically representative microvascular cubes, which was found independent of both microvascular geometry and length scale. The microthrombi occlusions were then simulated in the microvasculature, which were extravasated over time with a new thrombus extravasation model. The tissue hypoxic fraction was fitted as a sigmoidal function of vessel blockage fraction, which was then taken to be a function of time after the formation of microthrombi occlusions. A novel hypoxia-based 3-state cell death model was finally proposed to simulate the hypoxic tissue damage over time. Using the cell death model, the impact of a certain degree of microthrombi occlusions on tissue viability and microinfarct volume can be predicted over time. Quantifying the impact of microthrombi on oxygen transport and tissue death will play an important role in full brain models of ischaemic stroke and thrombectomy.

Modelling the leptomeningeal collateral circulation during acute ischaemic stroke.

A novel model of the leptomeningeal collateral circulation is created by combining data from multiple sources with statistical scaling laws. The extent of the collateral circulation is varied by defining a collateral vessel probability. Blood flow and pressure are simulated using a one-dimensional steady state blood flow model. The leptomeningeal collateral vessels provide significant flow during a stroke. The pressure drop over an occlusion predicted by the model ranges between 60 and 85 mmHg depending on the extent of the collateral circulation. The linear transport of contrast material was simulated in the circulatory network. The time delay of peak contrast over an occlusion is 3.3 s in the model, and 2.1 s (IQR 0.8-4.0 s) when measured in dynamic CTA data of acute ischaemic stroke patients. Modelling the leptomeningeal collateral circulation could lead to better estimates of infarct volume and patient outcome.

Modelling the impact of clot fragmentation on the microcirculation after thrombectomy.

Many ischaemic stroke patients who have a mechanical removal of their clot (thrombectomy) do not get reperfusion of tissue despite the thrombus being removed. One hypothesis for this 'no-reperfusion' phenomenon is micro-emboli fragmenting off the large clot during thrombectomy and occluding smaller blood vessels downstream of the clot location. This is impossible to observe in-vivo and so we here develop an in-silico model based on in-vitro experiments to model the effect of micro-emboli on brain tissue. Through in-vitro experiments we obtain, under a variety of clot consistencies and thrombectomy techniques, micro-emboli distributions post-thrombectomy. Blood flow through the microcirculation is modelled for statistically accurate voxels of brain microvasculature including penetrating arterioles and capillary beds. A novel micro-emboli algorithm, informed by the experimental data, is used to simulate the impact of micro-emboli successively entering the penetrating arterioles and the capillary bed. Scaled-up blood flow parameters-permeability and coupling coefficients-are calculated under various conditions. We find that capillary beds are more susceptible to occlusions than the penetrating arterioles with a 4x greater drop in permeability per volume of vessel occluded. Individual microvascular geometries determine robustness to micro-emboli. Hard clot fragmentation leads to larger micro-emboli and larger drops in blood flow for a given number of micro-emboli. Thrombectomy technique has a large impact on clot fragmentation and hence occlusions in the microvasculature. As such, in-silico modelling of mechanical thrombectomy predicts that clot specific factors, interventional technique, and microvascular geometry strongly influence reperfusion of the brain. Micro-emboli are likely contributory to the phenomenon of no-reperfusion following successful removal of a major clot.

Coupling one-dimensional arterial blood flow to three-dimensional tissue perfusion models for in silico trials of acute ischaemic stroke.

An acute ischaemic stroke is due to the sudden blockage of an intracranial blood vessel by an embolized thrombus. In the context of setting up in silico trials for the treatment of acute ischaemic stroke, the effect of a stroke on perfusion and metabolism of brain tissue should be modelled to predict final infarcted brain tissue. This requires coupling of blood flow and tissue perfusion models. A one-dimensional intracranial blood flow model and a method to couple this to a brain tissue perfusion model for patient-specific simulations is presented. Image-based patient-specific data on the anatomy of the circle of Willis are combined with literature data and models for vessel anatomy not visible in the images, to create an extended model for each patient from the larger vessels down to the pial surface. The coupling between arterial blood flow and tissue perfusion occurs at the pial surface through the estimation of perfusion territories. The coupling method is able to accurately estimate perfusion territories. Finally, we argue that blood flow can be approximated as steady-state flow at the interface between arterial blood flow and tissue perfusion to reduce the cost of organ-scale simulations.

[Are we the cause of our own suffering? - Everybody depends on something].

No abstract available.

[Studying the health behavior of asthmatic children regarding the dimensions of media and internet usage and self-esteem]. / Asztmás gyermekek egészségmagatartásának vizsgálata a média- és internethasználat és az önértékelés dimenziói mentén.

INTRODUCTION: According to the literature, somatic and psychological factors are connected with asthma bronchiale. The health behavior of these patients can be influenced by the virtual world. AIM: We wish to analyze social media and internet usage, self-esteem and sociodemographic data connected to attachment. METHOD: For our research, the Facebook Intensity Scale, the Problematic Internet Usage Questionnaire, the Rosenberg Self-Esteem Scale and a socio-demographic questionnaire were used. We interviewed 175 asthmatic children from the age of 10 to 18 (92 boys, 83 girls). RESULTS: Asthmatic girls, children who went to daycare (under the age of 3) and who were not breastfed use Facebook more than boys, children who stayed at home instead of daycare and who were breastfed (p<0.01). There is no difference in their internet usage. Breastfeeding (even if it only lasted for 1-7 days) can strengthen attachment which is shown in our results regarding social media usage compared with children who were not breastfed (p<0.01). A negative relation with medium strength was found between the number of siblings (ρ = -0.400; p<0.01) and the self-esteem and Facebook usage (ρ = -0.475; p<0.01). There is a positive correlation between Facebook usage and the size of the place the children live in (ρ = 0.492; p<0.01). CONCLUSIONS: Asthmatic youth use social media more frequently which provides social feedback to compensate their self-esteem, especially by girls. As protection factors, we can emphasize the existence of human relationships and the importance of an early mother-child bond. Orv Hetil. 2018; 159(47): 1971-1980.

[Study of stutter originating from the frustrated clinging instinct and its relation to anxiety and self-esteem]. / A dadogással mint a frusztrált megkapaszkodás ösztönével összefüggo szorongás és önértékelés vizsgálata.

INTRODUCTION: The analytic and family therapeutic theories connected to the topic of stutter have to be actualized. AIM: The aim of this work was to point out connections which originate from the instinct of frustrated clinging, however, these can be interpretated in new ways these days. METHOD: Two questionnaires in 48 subjects suffering from stutter were used; Rosenberg's Self-Esteem Scale measured the children's self representation, while the Multidimensional Anxiety Scale for Children measured the degree of their anxiety. At first the subjects had to anwser the questions as themselves, for the second time they had to anwser as an ordinary person without a speech disorder. RESULTS: The hypothesis of the authors was verified: stutterers attributed a significant role to the speech disorder of the subjects in connection with their self-esteem. According to this a significant amount of their anxiety is based on their deficit. An unexpected result was that girls and boys estimated ordinary people's level of anxiety similarly. There was no significant difference between boys and girls regarding the level of other's self-esteem. CONCLUSIONS: Based on the thesis of evolutionary psychology, the adequate use of speech is more important to women who have a connecting role in the family. This results that they see stutter as a major problem.

Morphological and microcirculatory evaluation of the rat testis after detorsion with or without a capsular release with a tunica vaginalis flap.

Testicular torsion may lead to serious ischemia, and the viability depends on the duration of torsion and the effect of ischemia-reperfusion. Testicular decompression and tunica vaginalis flap application technique were introduced in 2008 by Kutikov et al. We aimed to examine the impact of this method on the testicular microcirculation and hemorheological parameters in a rat model. Six adult rats underwent bilateral scrotal exploration. Intravaginal torsion of the testis was created by 720° rotation on both sides for 2 h. After detorsion, the right testes underwent tunica albuginea incision and tunica vaginalis flap application. Testicular microcirculation was monitored and hematological parameters, erythrocyte deformability, and aggregation were determined. Measurements were performed before and after torsion, directly after detorsion, on the 1 st -2 nd and 8 th postoperative day. After the last sampling, testicles were removed to determine their volume for histological examinations. The microcirculatory parameters demonstrated slight differences between testicles. Apical zone of the left (nondecompressed) testicles had elevated compared to the middle zone (P < 0.05). On the 2 nd and 8 th day, the microcirculation of the testes normalized but not equally. The erythrocyte aggregation and deformability decreased by the 8 th day. Both testicles underwent atrophy and epithelial necrosis, but the volume of the decompressed ones was lower (1.07 ± 0.08 vs 1.25 ± 0.31). Histologically, there was no significant difference in epithelial damage score between decompressed and nondecompressed testes. In conclusion, 2-h ischemia led to alteration in testicular microcirculation, reduction in volume, changes in hemorheological parameters and serious epithelial necrosis both in decompressed and nondecompressed testicles without remarkable differences.

Correlation between the androgen receptor status of the appendix testis and the efficacy of human chorionic gonadotropin treatment in undescended testis.

PURPOSE: To compare the androgen receptor (AR) status of the appendix testis (AT) in congenital undescended and retractile testes. MATERIALS AND METHODS: Twenty-four appendix testes (AT) were removed from 21 boys to detect AR expression by immunohistochemistry and immunofluorescence staining. Group 1 (n = 3) includes ATs from three patients with unilateral and group 2 (n = 6) with bilateral congenital undescended testis. All patients with bilateral form had been previously treated with human chorionic gonadotropin (hCG) without an acceptable effect. Group 3 (n = 12) includes ATs collected from 12 boys with acquired undescended testis or retractile testicle. Group 4 (n = 3) includes ATs from three young adults who received hCG treatment for undescended testis in their childhood and underwent open testicular biopsy to investigate infertility. Further seven ATs were collected to detect AR mRNA using RT-PCR analysis. RESULTS: Both immunohistochemistry and immunofluorescence staining of ATs showed AR expression in 100 % of the cases in groups 3 and 4 (12/12 and 3/3), but there was no visible AR expression in groups 1 and 2 (0/3 and 0/6); however, RT-PCR analysis revealed mRNA expression of AR both in congenital undescended and in retractile testicles. CONCLUSIONS: The presence of AR in the epithelial cells of AT in patients with retractile testicle and its absence in patients with congenital undescended testis can be a possible cause of the effectiveness of hormonal treatment in retractile testis and its inefficacy in patients with congenital undescended testis.

Present practice of thrombosis prophylaxis of radical prostatectomy in a European country: a Hungarian multicenter study.

Venous thromboembolism is a possible fatal complication after pelvic surgery. There is a lack of trials assessing the effect of prophylactic measures in urology. The aim of the study was to evaluate the practice of thrombosis prophylaxis in a Central European country. A questionnaire of performed radical prostatectomies, way of thrombosis prophylaxis and number of experienced thrombotic events was posted to all departments of urology in Hungary. With a response rate of 59%, 506 radical prostatectomies were reported. Low molecular weight heparin was administered by 100% of the departments. Graduated support stockings were applied by 37% of the patients. Early mobilization was the most common form of mechanic prophylaxis (57%). Thrombotic events were experienced in 1.4%, 0.2% were fatal. The thrombosis prophylaxis of patients undergoing radical prostatectomy is not unified. Due to the potential mortality of thrombotic complications it should be evaluated and prophylaxis should be recommended in urological guidelines.

Leptin receptor deficient diabetic (db/db) mice are compromised in postnatal bone regeneration.

Increased fragility fracture risk with improper healing is a frequent and severe complication of insulin resistance (IR). The mechanisms impairing bone health in IR are still not fully appreciated, which gives importance to studies on bone pathologies in animal models of diabetes. Mice deficient in leptin signaling are widely used models of IR and its comorbidities. Leptin was first recognized as a hormone, regulating appetite and energy balance; however, recent studies have expanded its role showing that leptin is a link between insulin-dependent metabolism and bone homeostasis. In the light of these findings, it is intriguing to consider the role of leptin resistance in bone regeneration. In this study, we show that obese diabetic mice lacking leptin receptor (db/db) are deficient in postnatal regenerative osteogenesis. We apply an ectopic osteogenesis and a fracture healing model, both showing that db/db mice display compromised bone acquisition and regeneration capacity. The underlying mechanisms include delayed periosteal mesenchymatic osteogenesis, premature apoptosis of the cartilage callus and impaired microvascular invasion of the healing tissue. Our study supports the use of the db/db mouse as a model of IR associated bone-healing deficits and can aid further studies of mesenchymatic cell homing and differentiation, microvascular invasion, cartilage to bone transition and callus remodeling in diabetic fracture healing.