A rare case of supraspinatus tendon rupture

Item does not contain fulltext1 januari 201

Structural and functional relationships in the virulence-associated cathepsin L proteases of the parasitic liver fluke, Fasciola hepatica

The helminth parasite Fasciola hepatica secretes cysteine proteases to facilitate tissue invasion, migration, and development within the mammalian host. The major proteases cathepsin L1 (FheCL1) and cathepsin L2 (FheCL2) were recombinantly produced and biochemically characterized. By using site-directed mutagenesis, we show that residues at position 67 and 205, which lie within the S2 pocket of the active site, are critical in determining the substrate and inhibitor specificity. FheCL1 exhibits a broader specificity and a higher substrate turnover rate compared with FheCL2. However, FheCL2 can efficiently cleave substrates with a Pro in the P2 position and degrade collagen within the triple helices at physiological pH, an activity that among cysteine proteases has only been reported forhuman cathepsin K. The 1.4-Å three-dimensional structure of the FheCL1 was determined by x-ray crystallography, and the three-dimensional structure of FheCL2 was constructed via homology-based modeling. Analysis and comparison of these structures and our biochemical data with those of human cathepsins L and Kprovided an interpretation of the substrate-recognition mechanisms of these major parasite proteases. Furthermore, our studies suggest that a configuration involving residue 67 and the "gatekeeper" residues 157 and 158 situated at the entrance of the active site pocket create a topology that endows FheCL2 with its unusual collagenolytic activity. The emergence of a specialized collagenolytic function in Fasciola likely contributes to the success of this tissue-invasive parasite. © 2008 by The American Society for Biochemistry and Molecular Biology, Inc

Modified lateral rhinotomy for fronto-ethmoid schwannoma in a child: a case report

Schwannoma of frontoethmoid region is a rare presentation. We report a case of 11-year-old girl with a swelling at the root of nose and nasal dorsum. Based on clinical picture and radiological findings it was not possible to establish a definitive diagnosis. But the histopathological picture was suggestive of schwannoma. A novel surgical approach was adopted to facilitate complete removal of the tumor and provide best possible cosmetic results

Engineering self-organising helium bubble lattices in tungsten

The self-organisation of void and gas bubbles in solids into a superlattices is an intriguing nanoscale phenomenon. Despite the discovery of these lattices 30 years ago, the atomistics behind the ordering mechanisms responsible for the formation of these nanostructures are yet to be fully elucidated. Here we report on the direct observation via transmission electron microscopy of the formation of bubble lattices under He+ ion bombardment. By careful control of the irradiation conditions, it has been possible to engineer the bubble size and spacing of the superlattice leading to important conclusions about the significance of vacancy supply in determining the physical characteristics of the system. Furthermore, no bubble lattice alignment was observed in the directions pointing to a key driving mechanism for the formation of these ordered nanostructures being the two-dimensional diffusion of self-interstitial atoms

Transmission Heterogeneity and Control Strategies for Infectious Disease Emergence

The control of emergence and spread of infectious diseases depends critically on the details of the genetic makeup of pathogens and hosts, their immunological, behavioral and ecological traits, and the pattern of temporal and spatial contacts among the age/stage-classes of susceptible and infectious host individuals.We show that failing to acknowledge the existence of heterogeneities in the transmission rate among age/stage-classes can make traditional eradication and control strategies ineffective, and in some cases, policies aimed at controlling pathogen emergence can even increase disease incidence in the host. When control strategies target for reduction in numbers those subsets of the population that effectively limit the production of new susceptible individuals, then control can produce a flush of new susceptibles entering the population. The availability of a new cohort of susceptibles may actually increase disease incidence. We illustrate these general points using Classical Swine Fever as a reference disease.Negative effects of culling are robust to alternative formulations of epidemiological processes and underline the importance of better assessing transmission structure in the design of wildlife disease control strategies

Optimal Cerebral Perfusion Pressure in Centers With Different Treatment Protocols.

OBJECTIVES: The three centers in this study have different policies regarding cerebral perfusion pressure targets and use of vasopressors in traumatic brain injury patients. The aim was to determine if the different policies affected the estimation of cerebral perfusion pressure which optimizes the strength of cerebral autoregulation, termed "optimal cerebral perfusion pressure." DESIGN: Retrospective analysis of prospectively collected data. SETTING: Three neurocritical care units at university hospitals in Cambridge, United Kingdom, Groningen, the Netherlands, and Uppsala, Sweden. PATIENTS: A total of 104 traumatic brain injury patients were included: 35 each from Cambridge and Groningen, and 34 from Uppsala. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: In Groningen, the cerebral perfusion pressure target was greater than or equal to 50 and less than 70 mm Hg, in Uppsala greater than or equal to 60, and in Cambridge greater than or equal to 60 or preferably greater than or equal to 70. Despite protocol differences, median cerebral perfusion pressure for each center was above 70 mm Hg. Optimal cerebral perfusion pressure was calculated as previously published and implemented in the Intensive Care Monitoring+ software by the Cambridge group, now replicated in the Odin software in Uppsala. Periods with cerebral perfusion pressure above and below optimal cerebral perfusion pressure were analyzed, as were absolute difference between cerebral perfusion pressure and optimal cerebral perfusion pressure and percentage of monitoring time with a valid optimal cerebral perfusion pressure. Uppsala had the highest cerebral perfusion pressure/optimal cerebral perfusion pressure difference. Uppsala patients were older than the other centers, and age is positively correlated with cerebral perfusion pressure/optimal cerebral perfusion pressure difference. Optimal cerebral perfusion pressure was significantly lower in Groningen than in Cambridge. There were no significant differences in percentage of monitoring time with valid optimal cerebral perfusion pressure. Summary optimal cerebral perfusion pressure curves were generated for the combined patient data for each center. These summary curves could be generated for Groningen and Cambridge, but not Uppsala. The older age of the Uppsala patient cohort may explain the absence of a summary curve. CONCLUSIONS: Differences in optimal cerebral perfusion pressure calculation were found between centers due to demographics (age) and treatment (cerebral perfusion pressure targets). These factors should be considered in the design of trials to determine the efficacy of autoregulation-guided treatment

Anatomy of quantum chaotic eigenstates

The eigenfunctions of quantized chaotic systems cannot be described by explicit formulas, even approximate ones. This survey summarizes (selected) analytical approaches used to describe these eigenstates, in the semiclassical limit. The levels of description are macroscopic (one wants to understand the quantum averages of smooth observables), and microscopic (one wants informations on maxima of eigenfunctions, "scars" of periodic orbits, structure of the nodal sets and domains, local correlations), and often focusses on statistical results. Various models of "random wavefunctions" have been introduced to understand these statistical properties, with usually good agreement with the numerical data. We also discuss some specific systems (like arithmetic ones) which depart from these random models.Comment: Corrected typos, added a few references and updated some result

Enhanced Visualization of Optimal Cerebral Perfusion Pressure Over Time to Support Clinical Decision Making.

OBJECTIVE: Cerebrovascular reactivity can provide a continuously updated individualized target for management of cerebral perfusion pressure, termed optimal cerebral perfusion pressure. The objective of this project was to find a way of improving the optimal cerebral perfusion pressure methodology by introducing a new visualization method. DATA SOURCES: Four severe traumatic brain injury patients with intracranial pressure monitoring. DATA EXTRACTION: Data were collected and pre-processed using ICM+ software. DATA SYNTHESIS: Sequential optimal cerebral perfusion pressure curves were used to create a color-coded maps of autoregulation - cerebral perfusion pressure relationship evolution over time. CONCLUSIONS: The visualization method addresses some of the main drawbacks of the original methodology and might bring the potential for its clinical application closer.Marcel Aries received an unrestricted grant from the Dutch Society of Intensive Care. Joseph Donnelly is supported by a Woolf Fisher Trust Scholarship. The software for brain monitoring ICM+® (www.neurosurg.cam.ac.uk/imcplus) is licensed by the University of Cambridge (Cambridge Enterprise).This is the author accepted manuscript. It is currently embargoed pending publication by Wolters Kluwer

Microneedles: A New Frontier in Nanomedicine Delivery

This review aims to concisely chart the development of two individual research fields, namely nanomedicines, with specific emphasis on nanoparticles (NP) and microparticles (MP), and microneedle (MN) technologies, which have, in the recent past, been exploited in combinatorial approaches for the efficient delivery of a variety of medicinal agents across the skin. This is an emerging and exciting area of pharmaceutical sciences research within the remit of transdermal drug delivery and as such will undoubtedly continue to grow with the emergence of new formulation and fabrication methodologies for particles and MN. Firstly, the fundamental aspects of skin architecture and structure are outlined, with particular reference to their influence on NP and MP penetration. Following on from this, a variety of different particles are described, as are the diverse range of MN modalities currently under development. The review concludes by highlighting some of the novel delivery systems which have been described in the literature exploiting these two approaches and directs the reader towards emerging uses for nanomedicines in combination with MN

The clinical significance of serum and bronchoalveolar lavage inflammatory cytokines in patients at risk for Acute Respiratory Distress Syndrome

BACKGROUND: The predictive role of many cytokines has not been well defined in Acute Respiratory Distress Syndrome (ARDS). METHODS: We measured prospectively IL-4, IL-6, IL-6 receptor, IL-8, and IL-10, in the serum and bronchoalveolar lavage fluid (BALF) in 59 patients who were admitted to ICU in order to identify predictive factors for the course and outcome of ARDS. The patients were divided into three groups: those fulfilling the criteria for ARDS (n = 20, group A), those at risk for ARDS and developed ARDS within 48 hours (n = 12, group B), and those at risk for ARDS but never developed ARDS (n = 27, group C). RESULTS: An excellent negative predictive value for ARDS development was found for IL-6 in BALF and serum (100% and 95%, respectively). IL-8 in BALF and IL-8 and IL-10 serum levels were higher in non-survivors in all studied groups, and were associated with a high negative predictive value. A significant correlation was found between IL-8 and APACHE score (r = 0.60, p < 0.0001). Similarly, IL-6 and IL-6r were highly correlated with PaO2/FiO2 (r = -0.27, p < 0.05 and r = -0.55, p < 0.0001, respectively). CONCLUSIONS: BALF and serum levels of the studied cytokines on admission may provide valuable information for ARDS development in patients at risk, and outcome in patients either in ARDS or in at risk for ARDS