Parameter estimation to study the immediate impact of aortic cross-clamping using reduced order models.

Aortic cross-clamping is a common strategy during vascular surgery, however, its instantaneous impact on hemodynamics is unknown. We, therefore, developed two numerical models to estimate the immediate impact of aortic clamping on the vascular properties. To assess the validity of the models, we recorded continuous invasive pressure signals during abdominal aneurysm repair surgery, immediately before and after clamping. The first model is a zero-dimensional (0D) three-element Windkessel model, which we coupled to a gradient-based parameter estimation algorithm to identify patient-specific parameters such as vascular resistance and compliance. We found a 10% increase in the total resistance and a 20% decrease in the total compliance after clamping. The second model is a nine-artery network corresponding to an average human body in which we solved the one-dimensional (1D) blood flow equations. With a similar parameter estimation method and using the results from the 0D model, we identified the resistance boundary conditions of the 1D network. Determining the patient-specific total resistance and the distribution of peripheral resistances through the parameter estimation process was sufficient for the 1D model to accurately reproduce the impact of clamping on the pressure waveform. Both models gave an accurate description of the pressure wave and had a high correlation (R2 > .95) with experimental blood pressure data.

Micellar effects and analytical applications of nitro substitution in 4-Nitro-N-alkyl-1,8-naphthalimide by cysteine derivatives.

The aromatic nucleophilic substitution reactions of the nitro group of 4-Nitro-N-alkyl-1,8-naphthalimides by thiolate anions produce fluorescent derivatives and their rates are strongly accelerated by micelles of hexadecyltrimethylammonium chloride even at low pH. Acceleration factors of this reactions can reach million-fold. As the products are oxidant-insensible, this reaction allows the determination of SH- containing compounds such as cysteine, glutathione or proteins even in oxidative conditions. Limits of detection are as low as 5 × 10-7 M, ten times lower than the limit for the classic 5,5'-dithiobis-(2-nitrobenzoic) acid method. Moreover, this reaction can be developed at pHs between 6.5 and 7.5 thereby diminishing the rate of spontaneous oxidation of the thiols. In addition, we demonstrated that 4-Nitro-N-alkyl-1,8-naphthalimides can be used to evidence SH groups in peptides, proteins and living cells.

[The telemedicine as tool of management on chronic disease: the experience of ASL ROMA 3 (Italian Local Authority). Impact, outcomes and results]. / La telemedicina come strumento di presa in carico globale e per la concreta integrazione ospedale territorio: l'esperienza della ASL ROMA 3.

The increase of chronic diseases prevalence has created the need to adapt care models. Telemedicine applications play an increasingly important role in health care and provide tools that are indispensable for home health care, remote patient monitoring, disease management, and lastly are enable patients to have more control of their own well being. The paper presents an Italian Healthcare Local Authority Experience. The objective of paper was to evaluate the impact of telemedicine on patients with long-term conditions at high risk for rehospitalization or an emergency department visit, in terms of target disease control (diabetes, hypertension, heart failure, and chronic obstructive pulmonary disease). The outcomes are highly positive. They register the decrease of access to emergency care, the reduction of waiting list for the next visits and the increase of customer satisfaction.

What information can the lay public find about osteoporosis treatment? A descriptive study coding the content and quality of bisphosphonate information on the internet.

Despite its effectiveness, bisphosphonate use for osteoporosis is low. We assessed bisphosphonate information on the internet and found the most commonly listed benefits/risks were bone density loss, gastrointestinal issues, and jaw necrosis, that risk quantification was rare, and information quality varied. Findings underscore the importance of clinical communication about bisphosphonates. INTRODUCTION: The US Preventative Services Task Force recommends osteoporosis screening and treatment with bisphosphonates in high-risk populations. However, bisphosphonate use among individuals with osteoporosis remains low. The content and quality of information from outside sources may influence individuals' bisphosphonate decisions. Therefore, we sought to assess the content and quality of osteoporosis treatment information available to the public by conducting an internet search and coding available bisphosphonate information. METHODS: Eleven search terms about osteoporosis and bisphosphonates were entered into four search engines. Two raters assessed websites for information about bisphosphonates, whether and how benefits and side effects were described and quantified, contraindications, and dosing instructions. Coders also assessed website interface and slant/balance of information. RESULTS: One thousand four hundred seventy-three websites were identified. Two hundred twenty-seven websites met inclusion criteria and were coded. The most common bisphosphonate benefit described was prevention of bone density loss (77.1% of websites). The most common side effects described were gastrointestinal problems (66.1%) and jaw osteonecrosis (58.6%). Most websites did not quantify bisphosphonate benefits (78.0%) or side effects (82.4%). Complementary/integrative health websites (p < .001) and pharmaceutical litigation websites (p < .001) were more often slanted against taking bisphosphonates, compared to all websites coded. General medical knowledge websites were more balanced than other websites (p = .023). CONCLUSIONS: The quality of bisphosphonate information on the internet varies substantially. Providers counseling patients about osteoporosis treatment should inquire about patients' baseline bisphosphonate knowledge. Providers can complement accurate information and address potential bisphosphonate misconceptions.

[Diagnostic Imaging of Acute Ischemic Stroke]. / Bildgebung beim akuten ischämischen Schlaganfall.

PURPOSE OF IMAGING: Imaging plays a major role in the diagnosiss, treatment indication, and prognosis of acute ischemic stroke. RECENT STUDY RESULTS: Recent studies have proved the safety and effectiveness of thrombolysis and endovascular thrombectomy based on the individual combination of imaging and patients clinical information even beyond the classical time-windows. In these cases, magnetic resonance imaging and perfusion-imaging can provide additional and important information. STANDARD DIAGNOSTICS: Nevertheless, computed tomography with and without contrast media still represents the most available and fastest method to diagnose stroke.

[Tandem occlusions in acute ischemic stroke]. / Tandemokklusionen beim akuten Schlaganfall.

CLINICAL ISSUE: Acute strokes caused by tandem occlusions include an atherosclerotic or dissective stenosis/occlusion of the extracranial internal carotid artery (eICA) in combination with an intracranial vessel occlusion. STANDARD TREATMENT: Endovascular treatment can be technically challenging but is definitely superior to intravenous thrombolysis alone and achieves good clinical results comparable to those from solitary intracranial occlusions. LATEST STUDY RESULTS: Although there are still no prospectively randomized studies on endovascular treatment for tandem occlusions, currently available data favor acute stenting of the eACI followed by intracranial thrombectomy. PURPOSE OF THE ARTICLE: This review discusses endovascular treatment options for tandem occlusions based on currently available data.

[Chiari malformation]. / Chiari-Malformation.

Chiari malformation is one of the most common congenital anomalies involving both skeletal and neuronal structures. Magnetic Resonance Imaging(MRI) is nowadays considered the imaging technique of choice for the diagnosis of Chiari malformations. Computed Tomography (CT) scans may provide additional information about skeletal anomalies.

Project HELP: a study protocol to pilot test a shared decision-making tool about treatment options for patients with hepatitis C and chronic kidney disease.

BACKGROUND: Recent advances in treatment have given patients with chronic kidney disease (CKD) access to safer and more effective medications to treat comorbid hepatitis C virus (HCV) infection. Given the variety and complexity of treatment options that depend on patients' clinical characteristics and personal preferences, education and decision support are needed to prepare patients better to discuss treatment options with their clinicians. METHODS: Drawing on International Patient Decision Aids Standards guidelines, literature reviews, and guidance from a diverse expert advisory group of nephrologists, hepatologists, and patients, we will develop and test a HCV and CKD decision support tool. Named Project HELP (Helping Empower Liver and kidney Patients), this tool will support patients with HCV and CKD during decisions about whether, when, and how to treat each illness. The tool will (1) explain information using plain language and graphics; (2) provide a step-by-step process for thinking about treating HCV and CKD; (3) tailor relevant information to each user by asking about the individual's stage of CKD, stage of fibrosis, prior treatment, and comorbidities; (4) assess user knowledge and values for treatment choices; and (5) help individuals use and consider information appropriate to their values and needs to discuss with a clinician. A pilot study including 70 individuals will evaluate the tool's efficacy, usability, and likelihood of using it in clinical practice. Eligibility criteria will include individuals who understand and read English, who are at least 18 years old, have a diagnosis of HCV (any genotype) and CKD (any stage), and are considering treatment options. DISCUSSION: This study can identify particular characteristics of individuals or groups that might experience challenges initiating treatment for HCV in the CKD population. This tool could provide a resource to facilitate patient-clinician discussions regarding HCV and CKD treatment options.

Stakeholders' perceptions of ways to support decisions about health insurance marketplace enrollment: a qualitative study.

BACKGROUND: Approximately 29 million individuals are expected to enroll in health insurance using the Patient Protection and Affordable Care Act (ACA) Marketplace by 2022. Those seeking health insurance struggle to understand insurance options and choose a plan that best suits their needs. METHODS: We interviewed stakeholders to identify the challenges associated with the ACA Marketplace health insurance enrollment and elicited feedback about what to include in health insurance decision support tools. Interviews were transcribed and themes were identified using inductive thematic analysis. RESULTS: Stakeholders stated that consumers felt frustrated by unclear terminology, high plan costs, and complex calculations required to assess costs. Consumers felt anxious about making the wrong choice and being unable to change plans within a calendar year. Stakeholders recommended using plain language tables defining complex terms, grouping information, and using engaging graphics to communicate information about health insurance. Stakeholders thought that narratives of how others made decisions about insurance might be helpful to consumers, but recommended that they be tailored to the needs of specific consumers. CONCLUSION: Strategies that clarify health insurance terms using plain language and graphics, acknowledge concern associated with making the wrong choice, calculate and enable cost comparison, and tailor information to consumers' unique needs could benefit those enrolling in ACA Marketplace plans, Narratives developed should be simple and inclusive enough for diverse populations.

[Tumors of the posterior cranial fossa]. / Tumoren der hinteren Schädelgrube.

Various types of brain tumor can occur in the region of the posterior fossa. Brain metastases in adults are the most common malignancies at this localization. Ependymomas, medulloblastomas and pilocytic astrocytomas occur mostly in children and only rarely in adults. Other tumors that occur in the posterior fossa are meningiomas, schwannomas, hemangioblastomas, brain stem gliomas and epidermoid tumors. Due to the fact that the various tumors of the posterior fossa have different treatment approaches and prognoses, an accurate and specific diagnosis is mandatory. This review discusses the imaging aspects by computed tomography (CT) and magnetic resonance imaging (MRI) of the most frequent tumors of the posterior fossa.

[Pediatric brain tumors of neuroepithelial tissue]. / Hirntumoren des neuroepithelialen Gewebes im Kindesalter.

Tumors of neuroepithelial tissue represent the largest group of pediatric brain tumors by far and has therefore been divided into several discrete tumor subtypes each corresponding to a specific component of the neuropil. The neuropil contains several subtypes of glial cells, including astrocytes, oligodendrocytes, ependymal cells and modified ependymal cells that form the choroid plexus. This review discusses the imaging aspects of the most common pediatric tumors of neuroepithelial tissue.

Human AQP1 is a constitutively open channel that closes by a membrane-tension-mediated mechanism.

This work presents experimental results combined with model-dependent predictions regarding the osmotic-permeability regulation of human aquaporin 1 (hAQP1) expressed in Xenopus oocyte membranes. Membrane elastic properties were studied under fully controlled conditions to obtain a function that relates internal volume and pressure. This function was used to design a model in which osmotic permeability could be studied as a pressure-dependent variable. The model states that hAQP1 closes with membrane-tension increments. It is important to emphasize that the only parameter of the model is the initial osmotic permeability coefficient, which was obtained by model-dependent fitting. The model was contrasted with experimental records from emptied-out Xenopus laevis oocytes expressing hAQP1. Simulated results reproduce and predict volume changes in high-water-permeability membranes under hypoosmotic gradients of different magnitude, as well as under consecutive hypo- and hyperosmotic conditions. In all cases, the simulated permeability coefficients are similar to experimental values. Predicted pressure, volume, and permeability changes indicate that hAQP1 water channels can transit from a high-water-permeability state to a closed state. This behavior is reversible and occurs in a cooperative manner among monomers. We conclude that hAQP1 is a constitutively open channel that closes mediated by membrane-tension increments.

A counterpoint between computer simulations and biological experiments to train new members of a laboratory of physiological sciences.

When new members join a working group dedicated to scientific research, several changes occur in the group's dynamics. From a teaching point of view, a subsequent challenge is to develop innovative strategies to train new staff members in creative thinking, which is the most complex and abstract skill in the cognitive domain according to Bloom's revised taxonomy. In this sense, current technological and digital advances offer new possibilities in the field of education. Computer simulation and biological experiments can be used together as a combined tool for teaching and learning sometimes complex physiological and biophysical concepts. Moreover, creativity can be thought of as a social process that relies on interactions among staff members. In this regard, the acquisition of cognitive abilities coexists with the attainment of other skills from psychomotor and affective domains. Such dynamism in teaching and learning stimulates teamwork and encourages the integration of members of the working group. A practical example, based on the teaching of biophysical subjects such as osmosis, solute transport, and membrane permeability, which are crucial in understanding the physiological concept of homeostasis, is presented.

Water flux through human aquaporin 1: inhibition by intracellular furosemide and maximal response with high osmotic gradients.

This work studies water permeability properties of human aquaporin 1 (hAQP1) expressed in Xenopus laevis oocyte membranes, applying a technique where cellular content is replaced with a known medium, with the possibility of measuring intracellular pressure. Consequences on water transport-produced by well-known anisotonic gradients and by the intracellular effect of probable aquaporin inhibitors-were tested. In this way, the specific intracellular inhibition of hAQP1 by the diuretic drug furosemide was demonstrated. In addition, experiments imposing anisotonic mannitol gradients with a constant ionic strength showed that the relationship between water flux and the applied mannitol gradient deflects from a perfect osmometer response when the gradient is higher than 150 mosmol kg (W) (-1) . These results would indicate that the passage of water molecules through hAQP1 may have a maximum rate. As a whole, this work demonstrates the technical advantage of controlling both intracellular pressure and medium composition in order to study biophysical properties of hAQP1, and contributes information on water channel behavior under osmotic challenges and the discovery of new inhibitors.

Emerging properties of financial time series in the "Game of Life".

We explore the spatial complexity of Conway's "Game of Life," a prototypical cellular automaton by means of a geometrical procedure generating a two-dimensional random walk from a bidimensional lattice with periodical boundaries. The one-dimensional projection of this process is analyzed and it turns out that some of its statistical properties resemble the so-called stylized facts observed in financial time series. The scope and meaning of this result are discussed from the viewpoint of complex systems. In particular, we stress how the supposed peculiarities of financial time series are, often, overrated in their importance.

Stent-assisted mechanical recanalization for treatment of acute intracerebral artery occlusions.

BACKGROUND AND PURPOSE: The purpose of this study was to demonstrate a new approach to the use of a self-expanding stent in the treatment of acute ischemic stroke. METHODS: Twenty-two consecutive patients with acute intracerebral artery occlusions were treated with a self-expandable intracranial stent, which was withdrawn in its unfolded state. For this technique, we used the Solitaire AB/FR, which is the only intracranial stent that is fully recoverable. Eight patients had an occlusion of the basilar artery, 12 had a middle cerebral artery occlusion, and 2 had terminal carotid artery occlusions; 6 of these had to be treated first for an acute occlusion originating in the internal carotid artery. Recanalization results were assessed by follow-up angiography immediately after the procedure. Neurologic status was evaluated before and after treatment (90-day follow-up) according to the National Institutes of Health Stroke Scale and modified Rankin scale. RESULTS: Successful revascularization was achieved in 20 of 22 (90.9%) patients (thrombolysis in cerebral infarction [TICI] 2a/b and 3), a TICI 3 state was accomplished in 12 patients, and partial recanalization or slow distal branch filling with filling of more than two-thirds of the vessel territory was achieved in 8 patients (TICI 2b). There was immediate flow restoration in 21 of 22 (95.4%) cases after deployment of the device. The stent was removed in its unfolded state in all patients. The mean time from stroke symptom onset to recanalization was 277 minutes, with a standard deviation of 118 minutes. Mean National Institutes of Health Stroke Scale score on admission was 19.4, with a standard deviation of 5.7. Almost two-thirds of the patients (63.6%) improved by > 10 points on the National Institutes of Health Stroke Scale at discharge, and 50% showed a modified Rankin scale score of ≤ 2 at 90 days (59% with a modified Rankin scale ≤ 3). Mortality was 18.1%. In 1 case, an asymptomatic intracranial hemorrhage was detected on control computed tomography, and 2 patients had a symptomatic intracranial hemorrhage. CONCLUSIONS: Withdrawal of an unfolded, fully recoverable, intracranial stent yielded very promising angiographic and clinical results. It combines the advantages of prompt flow restoration and mechanical thrombectomy.

Pontocerebellar hypoplasia: clinical, pathologic, and genetic studies.

BACKGROUND: Mutations in genes encoding subunits of the tRNA-splicing endonuclease (TSEN) complex were identified in patients with pontocerebellar hypoplasia 2 (PCH2) and pontocerebellar hypoplasia 4 (PCH4). OBJECTIVE: We report molecular genetic findings in 12 Italian patients with clinical and MRI findings compatible with PCH2 and PCH4. METHODS: We retrospectively selected a cohort of 12 children from 9 Italian families with MRI of hypoplastic pontocerebellar structures and clinical manifestations suggesting either PCH2 or PCH4 and submitted them to direct sequencing of the genes encoding the 4 subunits of the TSEN complex, namely TSEN54, TSEN34, TSEN15, and TSEN2. RESULTS: In a cohort of 12 children, we detected the common p.A307S mutation in TSEN54 in 9/12 available patients from nine unrelated families. We also detected a novel c.1170_1183del (p. V390fs39X) in compound heterozygosity with the common p.A307S in a child with a severe PCH4 phenotype. In another severely affected patient, the second mutant allele was not identified. Two sibs without mutations in the TSEN complex were unlinked to the PCH3 locus. In addition to typical clinical and neuroradiologic features of PCH2, both children were affected by a tubulopathy resembling Bartter syndrome. CONCLUSIONS: We confirm that the common p.A307S mutation in TSEN54 is responsible for most of the patients with a PCH2 phenotype. The presence of a heterozygous in/del variant correlates with a more severe phenotype as PCH4. In addition, we describe a new clinical form of PCH in 2 sibs with clinical and MRI features of PCH2.

Paraneoplastic syndromes in patients with oral cancer.

The diagnosis of a paraneoplastic syndrome (PNS) may precede, follow or be concurrent with the diagnosis of a malignant tumor. There is increasing knowledge of association between PNS and head and neck cancers, but the relationship between oral cancer and paraneoplastic disease has not been previously investigated. PNS associated with head and neck cancer can be divided into six main groups: endocrine, cutaneous or dermatologic, hematologic, osteoarticular or rheumatologic, neurologic, and ocular syndromes. We have comprehensively reviewed the literature to evaluate the incidence of occurrence of PNS with oral cancer, and conclude that only endocrine and dermatologic PNS have been associated with oral cancer. Humoral hypercalcemia is the most frequent PNS related to oral cancer, and has a negative prognostic significance. Dermatologic PNS are less common, but when they occur, they may precede the diagnosis of the oral tumor. Awareness of these conditions is important for clinicians who deal with cancer.

[Cranial birth trauma]. / Kraniales Geburtstrauma.

Injuries to an infant that result during the birth process are categorized as birth trauma. Cranial injuries due to mechanical forces such as compression or traction include caput succedaneum, cephalhematoma, subgaleal hematoma and intracranial hemorrhaging. Hypoxic ischemic encephalopathy is the consequence of systemic asphyxia occurring during birth.

Hyperperfusion syndrome after carotid stent angioplasty.

INTRODUCTION: This study assesses the incidence and causes of hyperperfusion syndrome occurring after carotid artery stenting (CAS). MATERIALS AND METHODS: We retrospectively reviewed the clinical database of 417 consecutive patients who were treated with CAS in our department to identify patients who developed hyperperfusion syndrome and/or intracranial hemorrhage. Magnetic resonance imaging (MRI) including fluid-attenuated inversion recovery and diffusion-weighted imaging was performed before and after CAS in 269 cases. A Spearman's rho nonparametric correlation was performed to determine whether there was a correlation between the occurrence/development of hyperperfusion syndrome and the patient's age, degree of stenosis on the stented and contralateral side, risk factors such as diabetes, smoking, hypertension, adiposity, gender and fluoroscopy time, and mean area of postprocedural lesions as well as preexisting lesions. Significance was established at p < 0.05. RESULTS: Of the 417 carotid arteries stented and where MRI was also completed, we found hyperperfusion syndrome in 2.4% (ten cases). Patients who had preexisting brain lesions (previous or acute stroke) were at a higher risk of developing hyperperfusion syndrome (p = 0.022; Spearman's rho test). We could not validate any correlation with the other patient characteristics. CONCLUSION: Extensive microvascular disease may be a predictor of hyperperfusion syndrome after carotid stent placement. We believe that further studies are warranted to predict more accurately which patients are at greater risk of developing this often fatal complication.