Bilateral Giant Supraclinoid Carotid Aneurysms Causing Obstructive Hydrocephalus: Case Report and Literature Review.

Intracranial aneurysms are common conditions that are usually asymptomatic and found incidentally, yet they can rupture and lead to subarachnoid hemorrhage, in addition to causing mass effects, especially with larger aneurysms. Bilateral supraclinoid aneurysms are extremely rare and were reported in only two instances. These aneurysms can cause a range of symptoms and require careful management. We present the case of a 42-year-old man with no concomitant medical conditions who presented with a persistent headache and deteriorating visual acuity over time. Neurological examination was unremarkable. Connective tissue diseases were ruled out by clinical and laboratory testing. Bilateral large, partly thrombosed supraclinoid segment fusiform aneurysms of the internal carotid artery that are causing midbrain compression and obstructive hydrocephalus were shown by brain CT, CT angiography, MRI, and MR angiography (MRA). Both surgery and endovascular treatment were denied by the patient. However, a ventriculoperitoneal shunt was placed in an outside center and relieved the patient's symptoms. The patient is being followed up. In conclusion, bilateral giant aneurysms of the internal carotid artery present unique challenges and can lead to various clinical manifestations and effects on surrounding structures. In this case, we reported the first instance of obstructed hydrocephalus caused by the largest bilateral supraclinoid carotid aneurysms.

Reliability and concurrent validity of three-dimensional ultrasound for quantifying knee cartilage volume.

Objective: The goal of this study was to test the reliability and validity of a handheld mechanical three-dimensional (3D) ultrasound (US) device for quantifying femoral articular cartilage (FAC) against the current clinical standard of magnetic resonance imaging (MRI). Design: Bilateral knee images of 25 healthy volunteers were acquired with 3D US and 3.0 T MRI. The trochlear FAC was segmented by two raters who repeated segmentations on five cases during separate sessions. MRI and 3D US segmentations were registered using a semi-automated surface-based registration algorithm, and MRI segmentations were trimmed to match the FAC region from 3D US. Intra- (n = 5) and inter-rater (n = 25) reliabilities were assessed using intraclass correlation coefficients (ICCs) calculated from FAC volumes. Relationships between MRI and 3D US were assessed using Spearman correlation and linear regression (n = 25). Results: MRI intra-rater ICCs were 0.97 (0.79, 1.00) and 0.90 (0.25, 0.99) for each rater with an inter-rater ICC of 0.83 (0.48, 0.94). 3D US intra-rater ICCs were 1.00 (0.98, 1.00) and 0.98 (0.84, 1.00) for each rater with an inter-rater ICC of 0.96 (0.90, 0.98). Spearman correlation and linear regression revealed a strong correlation ρ = 0.884 (0.746, 0.949) and regression R2 = 0.848 (0.750, 0.950). Conclusion: These results suggest 3D US demonstrates excellent intra- and inter-rater reliabilities and strong concurrent validity with MRI when quantifying healthy trochlear FAC volume. 3D US may reduce imaging costs and greatly improve feasibility of quantifying knee cartilage volume during knee arthritis clinical trials and patient care.

Genetic Epidemiology of Glucose-6-Phosphate Dehydrogenase Deficiency in the Arab World.

A systematic search was implemented using four literature databases (PubMed, Embase, Science Direct and Web of Science) to capture all the causative mutations of Glucose-6-phosphate dehydrogenase (G6PD) deficiency (G6PDD) in the 22 Arab countries. Our search yielded 43 studies that captured 33 mutations (23 missense, one silent, two deletions, and seven intronic mutations), in 3,430 Arab patients with G6PDD. The 23 missense mutations were then subjected to phenotypic classification using in silico prediction tools, which were compared to the WHO pathogenicity scale as a reference. These in silico tools were tested for their predicting efficiency using rigorous statistical analyses. Of the 23 missense mutations, p.S188F, p.I48T, p.N126D, and p.V68M, were identified as the most common mutations among Arab populations, but were not unique to the Arab world, interestingly, our search strategy found four other mutations (p.N135T, p.S179N, p.R246L, and p.Q307P) that are unique to Arabs. These mutations were exposed to structural analysis and molecular dynamics simulation analysis (MDSA), which predicting these mutant forms as potentially affect the enzyme function. The combination of the MDSA, structural analysis, and in silico predictions and statistical tools we used will provide a platform for future prediction accuracy for the pathogenicity of genetic mutations.

A new facility for non-destructive assay using a 252Cf source.

A new laboratory facility for non-destructive analysis (NDA) using a time-tagged (252)Cf source is presented. The system is designed to analyze samples having maximum size of about 20 × 25 cm(2), the material recognition being obtained by measuring simultaneously total and energy dependent transmission of neutrons and gamma rays. The equipment technical characteristics and performances of the NDA system are presented, exploring also limits due to the sample thickness. Some recent applications in the field of cultural heritage are presented.

Lymphoscintigraphy in plastic bronchitis, a pediatric case report.

Plastic bronchitis (PB) is an uncommon, potentially fatal disease, marked by endobronchial cast formation causing variable degrees of respiratory distress. Primary and secondary pulmonary lymphatic abnormalities have been identified among the underlying mechanisms of cast formation. We present a case of PB where lymphoscintigraphy demonstrated the underlying lymphatic defect. A 6-year-old Hispanic male with congenital heart disease (CHD; post-Fontan) presented with recurrent pneumonia, respiratory distress. Bronchoscopy showed inflamed hypervascular mucosa and thick mucus plugs; no casts were seen. Later, PB was diagnosed after the patient expectorated a bronchial cast. Cast analysis showed lymphocytic aggregates with mucin and fibrin. Lymphoscintigraphy revealed abnormal lymphatic collaterals and retrograde trace reflux into the superior mediastinum, a picture consistent with thoracic duct lymph leakage into the tracheobronchial tree. The pathogenesis of PB is not fully understood, especially in patients with CHD. Chyle in bronchial casts suggests abnormal lymphatic flow. Reports of lymph flow abnormalities, especially endobronchial lymph leakage in CHD are limited. Lymphoscintigraphy in our case demonstrated clear evidence of retrograde lymph reflux and leakage into the bronchial tree. The case presented suggests that in some patients following Fontan surgery, high intrathoracic lymphatic pressure and retrograde lymph flow may contribute to recurrent cast formation. Finding the underlying lymphatic abnormality helps in specific case management. Lymphoscintigraphy is a safer and easier method than lymphangiography. Surgical lymphatic-venous shunting may be possible in select cases.

[The benefits of tension-free methods with prosthetic materials in inguinal hernia repair]. / Avantajele operatiilor tension-free cu materiale prostetice în cura herniei inghinale.

UNLABELLED: Recurrences after inguinal hernia repair represent a significant problem for both surgeons and patients. MATERIAL AND METHODS: This study tries to evaluate operations that were performed in Clinical Emergency Hospital Oradea, II-nd Surgical Department, between September 2007 and December 2009, using polypropylene meshes. The operations were performed using the Lichtenstein technique in loco-regional or general anesthesia. The follow up was performed at one month after surgery and then at 3, 6, 12 months with a compliance rate of 80%. RESULTS: were similar to the results found in literature. CONCLUSIONS: The technique is easy to learn and to perform and the benefits for patients are represented by the low recurrence rates, comfort due to low levels of postoperative pain, early discharge and early socio-professional reintegration.

[Comparative study between classical operations and Lichtenstein technique for hernia repair]. / Studiu comparativ--interventii clasice versus tehnica lichtenstein in cura herniara.

UNLABELLED: The aim of these study was to compare classical procedures in inguinal hernia repair (Postemski, Kimbarovski, Bassini, McVay) made in the Second Surgery Department of County Clinical Emergency Hospital Oradea with the operations in which was used the Lichtenstein technique in the same department, in a period of two years, with respect to recurrence rate, technical difficulty, convalescence and chronic pain. MATERIAL AND METHODS: 217 operations were performed in classic way or using the Lichtenstein technique. Follow was performed at 1 month, 3, 6 and 12 months after surgery with a compliance of 80%. RESULTS: There was no significant difference in operating time between classic operations and tension free operations. The recurrence rates were significantly lower in the group operated by the Lichtenstein technique. The chronic pain was reported in both groups as mild or moderate. CONCLUSIONS: Lichtenstein hernia repair was easy to learn took the same time and resulted in fewer recurrences. It is possible to be used successfully in a general surgical unit.

Order statistics theory of unfolding of multimeric proteins.

Dynamic force spectroscopy has become indispensable for the exploration of the mechanical properties of proteins. In force-ramp experiments, performed by utilizing a time-dependent pulling force, the peak forces for unfolding transitions in a multimeric protein (D)(N) are used to map the free energy landscape for unfolding for a protein domain D. We show that theoretical modeling of unfolding transitions based on combining the observed first (f(1)), second (f(2)), …, N(th) (f(N)) unfolding forces for a protein tandem of fixed length N, and pooling the force data for tandems of different length, n(1)

Sop-GPU: accelerating biomolecular simulations in the centisecond timescale using graphics processors.

Theoretical exploration of fundamental biological processes involving the forced unraveling of multimeric proteins, the sliding motion in protein fibers and the mechanical deformation of biomolecular assemblies under physiological force loads is challenging even for distributed computing systems. Using a C(α)-based coarse-grained self organized polymer (SOP) model, we implemented the Langevin simulations of proteins on graphics processing units (SOP-GPU program). We assessed the computational performance of an end-to-end application of the program, where all the steps of the algorithm are running on a GPU, by profiling the simulation time and memory usage for a number of test systems. The ∼90-fold computational speedup on a GPU, compared with an optimized central processing unit program, enabled us to follow the dynamics in the centisecond timescale, and to obtain the force-extension profiles using experimental pulling speeds (v(f) = 1-10 µm/s) employed in atomic force microscopy and in optical tweezers-based dynamic force spectroscopy. We found that the mechanical molecular response critically depends on the conditions of force application and that the kinetics and pathways for unfolding change drastically even upon a modest 10-fold increase in v(f). This implies that, to resolve accurately the free energy landscape and to relate the results of single-molecule experiments in vitro and in silico, molecular simulations should be carried out under the experimentally relevant force loads. This can be accomplished in reasonable wall-clock time for biomolecules of size as large as 10(5) residues using the SOP-GPU package.

Emerging ideas on the molecular basis of protein and peptide aggregation.

Several neurodegenerative diseases are associated with the unfolding and subsequent fibrillization of proteins. Although neither the assembly mechanism nor the atomic structures of the amyloid fibrils are known, recent experimental and computational studies suggest that a few general principles that govern protein aggregation may exist. Analysis of the results of several important recent studies has led to a set of tentative ideas concerning the oligomerization of proteins and peptides. General rules have been described that may be useful in predicting regions of known proteins (prions and transthyretin) that are susceptible to fluctuations, which give rise to structures that can aggregate by the nucleation-growth mechanism. Despite large variations in the sequence-dependent polymerization kinetics of several structurally unrelated proteins, there appear to be only a few plausible scenarios for protein and peptide aggregation.

Exploring the propensities of helices in PrP(C) to form beta sheet using NMR structures and sequence alignments.

Neurodegenerative diseases induced by transmissible spongiform encephalopathies are associated with prions. The most spectacular event in the formation of the infectious scrapie form, referred to as PrP(Sc), is the conformational change from the predominantly alpha-helical conformation of PrP(C) to the PrP(Sc) state that is rich in beta-sheet content. Using sequence alignments and structural analysis of the available nuclear magnetic resonance structures of PrP(C), we explore the propensities of helices in PrP(C) to be in a beta-strand conformation. Comparison of a number of structural characteristics (such as solvent accessible area, distribution of (Phi, Psi) angles, mismatches in hydrogen bonds, nature of residues in local and nonlocal contacts, distribution of regular densities of amino acids, clustering of hydrophobic and hydrophilic residues in helices) between PrP(C) structures and a databank of "normal" proteins shows that the most unusual features are found in helix 2 (H2) (residues 172-194) followed by helix 1 (H1) (residues 144-153). In particular, the C-terminal residues in H2 are frustrated in their helical state. The databank of normal proteins consists of 58 helical proteins, 36 alpha+beta proteins, and 31 beta-sheet proteins. Our conclusions are also substantiated by gapless threading calculations that show that the normalized Z-scores of prion proteins are similar to those of other alpha+beta proteins with low helical content. Application of the recently introduced notion of discordance, namely, incompatibility of the predicted and observed secondary structures, also points to the frustration of H2 not only in the wild type but also in mutants of human PrP(C). This suggests that the instability of PrP(C) proteins may play a role in their being susceptible to the profound conformational change. Our analysis shows that, in addition to the previously proposed role for the segment (90-120) and possibly H1, the C-terminus of H2 and possibly N-terminus may play a role in the alpha-->beta transition. An implication of our results is that the ease of polymerization depends on the unfolding rate of the monomer. Sequence alignments show that helices in avian prion proteins (chicken, duck, crane) are better accommodated in a helical state, which might explain the absence of PrP(Sc) formation over finite time scales in these species. From this analysis, we predict that correlated mutations that reduce the frustration in the second half of helix 2 in mammalian prion proteins could inhibit the formation of PrP(Sc).

Exploring protein aggregation and self-propagation using lattice models: phase diagram and kinetics.

Many seemingly unrelated neurodegenerative disorders, such as amyloid and prion diseases, are associated with propagating fibrils whose structures are dramatically different from the native states of the corresponding monomers. This observation, along with the experimental demonstration that any protein can aggregate to form either fibrils or amorphous structures (inclusion bodies) under appropriate external conditions, suggest that there must be general principles that govern aggregation mechanisms. To probe generic aspects of prion-like behavior we use the model of Harrison, Chan, Prusiner, and Cohen. In this model, aggregation of a structure, that is conformationally distinct from the native state of the monomer, occurs by three parallel routes. Kinetic partitioning, which leads to parallel assembly pathways, occurs early in the aggregation process. In all pathways transient unfolding precedes polymerization and self-propagation. Chain polymerization is consistent with templated assembly, with the dimer being the minimal nucleus. The kinetic effciency of R(n-1) + G --> R(n) (R is the aggregation prone state and G is either U, the unfolded state, or N, the native state of the monomer) is increased when polymerization occurs in the presence of a "seed" (a dimer). These results support the seeded nucleated-polymerization model of fibril formation in amyloid peptides. To probe generic aspects of aggregation in two-state proteins, we use lattice models with side chains. The phase diagram in the (T,C) plane (T is the temperature and C is the polypeptide concentration) reveals a bewildering array of "phases" or structures. Explicit computations for dimers show that there are at least six phases including ordered structures and amorphous aggregates. In the ordered region of the phase diagram there are three distinct structures. We find ordered dimers (OD) in which each monomer is in the folded state and the interaction between the monomers occurs via a well-defined interface. In the domain-swapped structures a certain fraction of intrachain contacts are replaced by interchain contacts. In the parallel dimers the interface is stabilized by favorable intermolecular hydrophobic interactions. The kinetics of folding to OD shows that aggregation proceeds directly from U in a dynamically cooperative manner without populating partially structured intermediates. These results support the experimental observation that ordered aggregation in the two-state folders U1A and CI2 takes place from U. The contrasting aggregation processes in the two models suggest that there are several distinct mechanisms for polymerization that depend not only on the polypeptide sequence but also on external conditions (such as C, T, pH, and salt concentration).

Protein threading by learning.

By using techniques borrowed from statistical physics and neural networks, we determine the parameters, associated with a scoring function, that are chosen optimally to ensure complete success in threading tests in a training set of proteins. These parameters provide a quantitative measure of the propensities of amino acids to be buried or exposed and to be in a given secondary structure and are a good starting point for solving both the threading and design problems.

Scoring functions in protein folding and design.

We present an analysis of the assumptions behind some of the most commonly used methods for evaluating the goodness of the fit between a sequence and a structure. Our studies on a lattice model show that methods based on statistical considerations are easy to use and can capture some of the features of protein-like sequences and their corresponding native states, but unfortunately are incapable of recognizing, with certainty, the native-like conformation of a sequence among a set of decoys. Meanwhile, an optimization method, entailing the determination of the parameters of an effective free energy of interaction, is much more reliable in recognizing the native state of a sequence. However, the statistical method is shown to perform quite well in tests of protein design.

Statistical mechanics of protein-like heteropolymers.

A strategy is outlined for obtaining the free energy of a typical designed heteropolymer. The design procedure considers the probability that the target conformation is occupied in comparison with all the other conformations that could house the given sequence. Numerical calculations on lattice heteropolymer models are presented to illustrate the key physical principles.