Synthesis of 1,1'-(Hexane-1,6-Diyl)Bis(5-Oxopyrrolidine-3-Carboxylic Acid) as a Monomer for a Polyanhydride Drug Delivery System

Polyanhydrides have been given much attention in the literature recently because of their desirable properties as controlled drug delivery solutions. Drug therapies could be loaded into a polyanhydride matrix and protected from denaturation and removal from the body while being slowly eluted as the polyanhydride degraded yielding a tailorable concentration profile in the bloodstream at therapeutic levels. To that end, this report discusses the synthesis of a novel monomer for polyanhydride synthesis: 1,1'-(hexane-1,6-diyl)bis(5-oxopyrrolidine-3-carboxylic acid) henceforth known as CPyH monomer for (carboxypyrrolidone)hexane monomer.

Interactions between the microbiota and the immune system

The large numbers of microorganisms that inhabit mammalian body surfaces have a highly coevolved relationship with the immune system. Although many of these microbes carry out functions that are critical for host physiology, they nevertheless pose the threat of breach with ensuing pathologies. The mammalian immune system plays an essential role in maintaining homeostasis with resident microbial communities, thus ensuring that the mutualistic nature of the host-microbial relationship is maintained. At the same time, resident bacteria profoundly shape mammalian immunity. Here, we review advances in our understanding of the interactions between resident microbes and the immune system and the implications of these findings for human health.

Homeland security: IgA immunity at the frontiers of the body

IgA is the most abundant immunoglobulin produced in mammals, and is mostly secreted across mucous membranes. At these frontiers, which are constantly assaulted by pathogenic and commensal microbes, IgA provides part of a layered system of immune protection. In this review, we describe how IgA induction occurs through both T-dependent and T-independent mechanisms, and how IgA is generated against the prodigious load of commensal microbes after mucosal dendritic cells (DCs) have sampled a tiny fraction of the microbial consortia in the intestinal lumen. To function in this hostile environment, IgA must be induced behind the 'firewall' of the mesenteric lymph nodes to generate responses that integrate microbial stimuli, rather than the classical prime-boost effects characteristic of systemic immunity.

A Comparative Study of Two Semantic Systems: Body Russian and Russian Phraseology

Grigorij Kreidlin (Russia). A Comparative Study of Two Semantic Systems: Body Russian and Russian Phraseology. Mr. Kreidlin teaches in the Department of Theoretical and Applied Linguistics of the State University of Humanities in Moscow and worked on this project from August 1996 to July 1998. The classical approach to non-verbal and verbal oral communication is based on a traditional separation of body and mind. Linguists studied words and phrasemes, the products of mind activities, while gestures, facial expressions, postures and other forms of body language were left to anthropologists, psychologists, physiologists, and indeed to anyone but linguists. Only recently have linguists begun to turn their attention to gestures and semiotic and cognitive paradigms are now appearing that raise the question of designing an integral model for the unified description of non-verbal and verbal communicative behaviour. This project attempted to elaborate lexical and semantic fragments of such a model, producing a co-ordinated semantic description of the main Russian gestures (including gestures proper, postures and facial expressions) and their natural language analogues. The concept of emblematic gestures and gestural phrasemes and of their semantic links permitted an appropriate description of the transformation of a body as a purely physical substance into a body as a carrier of essential attributes of Russian culture - the semiotic process called the culturalisation of the human body. Here the human body embodies a system of cultural values and displays them in a text within the area of phraseology and some other important language domains. The goal of this research was to develop a theory that would account for the fundamental peculiarities of the process. The model proposed is based on the unified lexicographic representation of verbal and non-verbal units in the Dictionary of Russian Gestures, which the Mr. Kreidlin had earlier complied in collaboration with a group of his students. The Dictionary was originally oriented only towards reflecting how the lexical competence of Russian body language is represented in the Russian mind. Now a special type of phraseological zone has been designed to reflect explicitly semantic relationships between the gestures in the entries and phrasemes and to provide the necessary information for a detailed description of these. All the definitions, rules of usage and the established correlations are written in a semantic meta-language. Several classes of Russian gestural phrasemes were identified, including those phrasemes and idioms with semantic definitions close to those of the corresponding gestures, those phraseological units that have lost touch with the related gestures (although etymologically they are derived from gestures that have gone out of use), and phrasemes and idioms which have semantic traces or reflexes inherited from the meaning of the related gestures. The basic assumptions and practical considerations underlying the work were as follows. (1) To compare meanings one has to be able to state them. To state the meaning of a gesture or a phraseological expression, one needs a formal semantic meta-language of propositional character that represents the cognitive and mental aspects of the codes. (2) The semantic contrastive analysis of any semiotic codes used in person-to-person communication also requires a single semantic meta-language, i.e. a formal semantic language of description,. This language must be as linguistically and culturally independent as possible and yet must be open to interpretation through any culture and code. Another possible method of conducting comparative verbal-non-verbal semantic research is to work with different semantic meta-languages and semantic nets and to learn how to combine them, translate from one to another, etc. in order to reach a common basis for the subsequent comparison of units. (3) The practical work in defining phraseological units and organising the phraseological zone in the Dictionary of Russian Gestures unexpectedly showed that semantic links between gestures and gestural phrasemes are reflected not only in common semantic elements and syntactic structure of semantic propositions, but also in general and partial cognitive operations that are made over semantic definitions. (4) In comparative semantic analysis one should take into account different values and roles of inner form and image components in the semantic representation of non-verbal and verbal units. (5) For the most part, gestural phrasemes are direct semantic derivatives of gestures. The cognitive and formal techniques can be regarded as typological features for the future functional-semantic classification of gestural phrasemes: two phrasemes whose meaning can be obtained by the same cognitive or purely syntactic operations (or types of operations) over the meanings of the corresponding gestures, belong by definition to one and the same class. The nature of many cognitive operations has not been studied well so far, but the first steps towards its comprehension and description have been taken. The research identified 25 logically possible classes of relationships between a gesture and a gestural phraseme. The calculation is based on theoretically possible formal (set-theory) correlations between signifiers and signified of the non-verbal and verbal units. However, in order to examine which of them are realised in practice a complete semantic and lexicographic description of all (not only central) everyday emblems and gestural phrasemes is required and this unfortunately does not yet exist. Mr. Kreidlin suggests that the results of the comparative analysis of verbal and non-verbal units could also be used in other research areas such as the lexicography of emotions.

Regulation of immune cell entry into the central nervous system

The central nervous system (CNS) has long been regarded as an immune privileged organ implying that the immune system avoids the CNS to not disturb its homeostasis, which is critical for proper function of neurons. Meanwhile, it is accepted that immune cells do in fact gain access to the CNS and that immune responses can be mounted within this tissue. However, the unique CNS microenvironment strictly controls these immune reactions starting with tightly controlling immune cell entry into the tissue. The endothelial blood-brain barrier (BBB) and the epithelial blood-cerebrospinal fluid (CSF) barrier, which protect the CNS from the constantly changing milieu within the bloodstream, also strictly control immune cell entry into the CNS. Under physiological conditions, immune cell migration into the CNS is kept at a very low level. In contrast, during a variety of pathological conditions of the CNS such as viral or bacterial infections, or during inflammatory diseases such as multiple sclerosis, immunocompetent cells readily traverse the BBB and likely also the choroid plexus and subsequently enter the CNS parenchyma or CSF spaces. This chapter summarizes our current knowledge of immune cell entry across the blood CNS barriers. A large body of the currently available information on immune cell entry into the CNS has been derived from studying experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis. Therefore, most of this chapter discussing immune cell entry during CNS pathogenesis refers to observations in the EAE model, allowing for the possibility that other mechanisms of immune cell entry into the CNS might apply under different pathological conditions such as bacterial meningitis or stroke.

Whole-body MRI of multiple myeloma: comparison of different MRI sequences in assessment of different growth patterns

PURPOSE: To determine sensitivity, specificity and inter-observer variability of different whole-body MRI (WB-MRI) sequences in patients with multiple myeloma (MM). METHODS AND MATERIALS: WB-MRI using a 1.5T MRI scanner was performed in 23 consecutive patients (13 males, 10 females; mean age 63+/-12 years) with histologically proven MM. All patients were clinically classified according to infiltration (low-grade, n=7; intermediate-grade, n=7; high-grade, n=9) and to the staging system of Durie and Salmon PLUS (stage I, n=12; stage II, n=4; stage III, n=7). The control group consisted of 36 individuals without malignancy (25 males, 11 females; mean age 57+/-13 years). Two observers independently evaluated the following WB-MRI sequences: T1w-TSE (T1), T2w-TIRM (T2), and the combination of both sequences, including a contrast-enhanced T1w-TSE with fat-saturation (T1+/-CE/T2). They had to determine growth patterns (focal and/or diffuse) and the MRI sequence that provided the highest confidence level in depicting the MM lesions. Results were calculated on a per-patient basis. RESULTS: Visual detection of MM was as follows: T1, 65% (sensitivity)/85% (specificity); T2, 76%/81%; T1+/-CE/T2, 67%/88%. Inter-observer variability was as follows: T1, 0.3; T2, 0.55; T1+/-CE/T2, 0.55. Sensitivity improved depending on infiltration grade (T1: 1=60%; 2=36%; 3=83%; T2: 1=70%; 2=71%; 3=89%; T1+/-CE/T2: 1=50%; 2=50%; 3=89%) and clinical stage (T1: 1=58%; 2=63%; 3=79%; T2: 1=58%; 2=88%; 3=100%; T1+/-CE/T2: 1=50%; 2=63%; 3=100%). T2w-TIRM sequences achieved the best reliability in depicting the MM lesions (65% in the mean of both readers). CONCLUSIONS: T2w-TIRM sequences achieved the highest level of sensitivity and best reliability, and thus might be valuable for initial assessment of MM. For an exact staging and grading the examination protocol should encompass unenhanced and enhanced T1w-MRI sequences, in addition to T2w-TIRM.

Total-body digital X-ray in trauma. An experience report on the first operational full body scanner in Europe and its possible role in ATLS

When patients enter our emergency room with suspected multiple injuries, Statscan provides a full body anterior and lateral image for initial diagnosis, and then zooms in on specific smaller areas for a more detailed evaluation. In order to examine the possible role of Statscan in the management of multiply injured patients we implemented a modified ATLS((R)) algorithm, where X-ray of C-spine, chest and pelvis have been replaced by single-total a.p./lat. body radiograph. Between 15 October 2006 and 1 February 2007 143 trauma patients (mean ISS 15+/-14 (3-75)) were included. We compared the time in resuscitation room to 650 patients (mean ISS 14+/-14 (3-75)) which were treated between 1 January 2002 and 1 January 2004 according to conventional ATLS protocol. The total-body scanning time was 3.5 min (3-6 min) compared to 25.7 (8-48 min) for conventional X-rays, The total ER time was unchanged 28.7 min (13-58 min) compared to 29.1 min (15-65 min) using conventional plain radiography. In 116/143 patients additional CT scans were necessary. In 98/116 full body trauma CT scans were performed. In 18/116 patients selective CT scans were ordered based on Statscan findings. In 43/143 additional conventional X-rays had to be performed, mainly due to inadequate a.p. views of fractured bones. All radiographs were transmitted over the hospital network (Picture Archiving and Communication System, PACS) for immediate simultaneous viewing at different places. The rapid availability of images for interpretation because of their digital nature and the reduced need for repeat exposures because of faulty radiography are also felt to be strengths.

Postmortem whole-body CT angiography: evaluation of two contrast media solutions

OBJECTIVE: The objective of our study was to establish a standardized procedure for postmortem whole-body CT-based angiography with lipophilic and hydrophilic contrast media solutions and to compare the results of these two methods. MATERIALS AND METHODS: Minimally invasive postmortem CT angiography was performed on 10 human cadavers via access to the femoral blood vessels. Separate perfusion of the arterial and venous systems was established with a modified heart-lung machine using a mixture of an oily contrast medium and paraffin (five cases) and a mixture of a water-soluble contrast medium with polyethylene glycol (PEG) 200 in the other five cases. Imaging was executed with an MDCT scanner. RESULTS: The minimally invasive femoral approach to the vascular system provided a good depiction of lesions of the complete vascular system down to the level of the small supplying vessels. Because of the enhancement of well-vascularized tissues, angiography with the PEG-mixed contrast medium allowed the detection of tissue lesions and the depiction of vascular abnormalities such as pulmonary embolisms or ruptures of the vessel wall. CONCLUSION: The angiographic method with a water-soluble contrast medium and PEG as a contrast-agent dissolver showed a clearly superior quality due to the lack of extravasation through the gastrointestinal vascular bed and the enhancement of soft tissues (cerebral cortex, myocardium, and parenchymal abdominal organs). The diagnostic possibilities of these findings in cases of antemortem ischemia of these tissues are not yet fully understood.

Energy harvesting from body motion using rotational micro-generation

Autonomous system applications are typically limited by the power supply operational lifetime when battery replacement is difficult or costly. A trade-off between battery size and battery life is usually calculated to determine the device capability and lifespan. As a result, energy harvesting research has gained importance as society searches for alternative energy sources for power generation. For instance, energy harvesting has been a proven alternative for powering solar-based calculators and self-winding wristwatches. Thus, the use of energy harvesting technology can make it possible to assist or replace batteries for portable, wearable, or surgically-implantable autonomous systems. Applications such as cardiac pacemakers or electrical stimulation applications can benefit from this approach since the number of surgeries for battery replacement can be reduced or eliminated. Research on energy scavenging from body motion has been investigated to evaluate the feasibility of powering wearable or implantable systems. Energy from walking has been previously extracted using generators placed on shoes, backpacks, and knee braces while producing power levels ranging from milliwatts to watts. The research presented in this paper examines the available power from walking and running at several body locations. The ankle, knee, hip, chest, wrist, elbow, upper arm, side of the head, and back of the head were the chosen target localizations. Joints were preferred since they experience the most drastic acceleration changes. For this, a motor-driven treadmill test was performed on 11 healthy individuals at several walking (1-4 mph) and running (2-5 mph) speeds. The treadmill test provided the acceleration magnitudes from the listed body locations. Power can be estimated from the treadmill evaluation since it is proportional to the acceleration and frequency of occurrence. Available power output from walking was determined to be greater than 1mW/cm³ for most body locations while being over 10mW/cm³ at the foot and ankle locations. Available power from running was found to be almost 10 times higher than that from walking. Most energy harvester topologies use linear generator approaches that are well suited to fixed-frequency vibrations with sub-millimeter amplitude oscillations. In contrast, body motion is characterized with a wide frequency spectrum and larger amplitudes. A generator prototype based on self-winding wristwatches is deemed to be appropriate for harvesting body motion since it is not limited to operate at fixed-frequencies or restricted displacements. Electromagnetic generation is typically favored because of its slightly higher power output per unit volume. Then, a nonharmonic oscillating rotational energy scavenger prototype is proposed to harness body motion. The electromagnetic generator follows the approach from small wind turbine designs that overcome the lack of a gearbox by using a larger number of coil and magnets arrangements. The device presented here is composed of a rotor with multiple-pole permanent magnets having an eccentric weight and a stator composed of stacked planar coils. The rotor oscillations induce a voltage on the planar coil due to the eccentric mass unbalance produced by body motion. A meso-scale prototype device was then built and evaluated for energy generation. The meso-scale casing and rotor were constructed on PMMA with the help of a CNC mill machine. Commercially available discrete magnets were encased in a 25mm rotor. Commercial copper-coated polyimide film was employed to manufacture the planar coils using MEMS fabrication processes. Jewel bearings were used to finalize the arrangement. The prototypes were also tested at the listed body locations. A meso-scale generator with a 2-layer coil was capable to extract up to 234 µW of power at the ankle while walking at 3mph with a 2cm³ prototype for a power density of 117 µW/cm³. This dissertation presents the analysis of available power from walking and running at different speeds and the development of an unobtrusive miniature energy harvesting generator for body motion. Power generation indicates the possibility of powering devices by extracting energy from body motion.

Body sensor network for in-home personal healthcare

A body sensor network solution for personal healthcare under an indoor environment is developed. The system is capable of logging the physiological signals of human beings, tracking the orientations of human body, and monitoring the environmental attributes, which covers all necessary information for the personal healthcare in an indoor environment. The major three chapters of this dissertation contain three subsystems in this work, each corresponding to one subsystem: BioLogger, PAMS and CosNet. Each chapter covers the background and motivation of the subsystem, the related theory, the hardware/software design, and the evaluation of the prototype’s performance.

Whole body postmortem angiography with a high viscosity contrast agent solution using poly ethylene glycol as contrast agent dissolver

Postmortem minimal invasive angiography has already been implemented to support virtual autopsy examinations. An experimental approach in a porcine model to overcome an initially described artificial tissue edema artifact by using a poly ethylene glycol (PEG) containing contrast agent solution showed promising results. The present publication describes the first application of PEG in a whole corpse angiographic CT examination. A minimal invasive postmortem CT angiography was performed in a human corpse utilizing the high viscosity contrast agent solution containing 65% of PEG. Injection was carried out via the femoral artery into the aortic root in simulated cardiac output conditions. Subsequent CT scanning delivered the 3D volume data of the whole corpse. Visualization of the human arterial anatomy was excellent and the contrast agent distribution was generally limited to the arterial system as intended. As exceptions an enhancement of the brain, the left ventricular myocardium and the renal cortex became obvious. This most likely represented the stage of centralization of the blood circulation at the time of death with dilatation of the precapillary arterioles within these tissues. Especially for the brain this resulted in a distinctively improved visualization of the intracerebral structures by CT. However, the general tissue edema artifact of postmortem minimal invasive angiography examinations could be distinctively reduced.

Wireless and passive pressure sensor system based on the magnetic higher-order harmonic field

The goal of this work is to develop a magnetic-based passive and wireless pressure sensor for use in biomedical applications. Structurally, the pressure sensor, referred to as the magneto-harmonic pressure sensor, is composed of two magnetic elements: a magnetically-soft material acts as a sensing element, and a magnetically hard material acts as a biasing element. Both elements are embedded within a rigid sensor body and sealed with an elastomer pressure membrane. Upon excitation of an externally applied AC magnetic field, the sensing element is capable of producing higher-order magnetic signature that is able to be remotely detected with an external receiving coil. When exposed to environment with changing ambient pressure, the elastomer pressure membrane of pressure sensor is deflected depending on the surrounding pressure. The deflection of elastomer membrane changes the separation distance between the sensing and biasing elements. As a result, the higher-order harmonic signal emitted by the magnetically-soft sensing element is shifted, allowing detection of pressure change by determining the extent of the harmonic shifting. The passive and wireless nature of the sensor is enabled with an external excitation and receiving system consisting of an excitation coil and a receiving coil. These unique characteristics made the sensor suitable to be used for continuous and long-term pressure monitoring, particularly useful for biomedical applications which often require frequent surveillance. In this work, abdominal aortic aneurysm is selected as the disease model for evaluation the performance of pressure sensor and system. Animal model, with subcutaneous sensor implantation in mice, was conducted to demonstrate the efficacy and feasibility of pressure sensor in biological environment.

Development of Vapor Deposited Silica Sol-Gel Particles for a Bioactive Materials System to Direct Osteoblast Behavior

Tissue engineering and regenerative medicine have emerged in an effort to generate replacement tissues capable of restoring native tissue structure and function, but because of the complexity of biologic system, this has proven to be much harder than originally anticipated. Silica based bioactive glasses are popular as biomaterials because of their ability to enhance osteogenesis and angiogenesis. Sol-gel processing methods are popular in generating these materials because it offers: 1) mild processing conditions; 2) easily controlled structure and composition; 3) the ability to incorporate biological molecules; and 4) inherent biocompatibility. The goal of this work was to develop a bioactive vaporization system for the deposition of silica sol-gel particles as a means to modify the material properties of a substrate at the nano- and micro- level to better mimic the instructive conditions of native bone tissue, promoting appropriate osteoblast attachment, proliferation, and differentiation as a means for supporting bone tissue regeneration. The size distribution, morphology and degradation behavior of the vapor deposited sol-gel particles developed here were found to be dependent upon formulation (H2O:TMOS, pH, Ca/P incorporation) and manufacturing (substrate surface character, deposition time). Additionally, deposition of these particles onto substrates can be used to modify overall substrate properties including hydrophobicity, roughness, and topography. Deposition of Ca/P sol particles induced apatite-like mineral formation on both two- and three-dimensional materials when exposed to body fluids. Gene expression analysis suggests that Ca/P sol particles induce upregulation osteoblast gene expression (Runx2, OPN, OCN) in preosteoblasts during early culture time points. Upon further modification-specifically increasing particle stability-these Ca/P sol particles possess the potential to serve as a simple and unique means to modify biomaterial surface properties as a means to direct osteoblast differentiation.

Personal experience with whole-body, low-dosage, digital X-ray scanning (LODOX-Statscan) in trauma

BACKGROUND: Lodox-Statscan is a whole-body, skeletal and soft-tissue, low-dose X-ray scanner Anterior-posterior and lateral thoraco-abdominal studies are obtained in 3-5 minutes with only about one-third of the radiation required for conventional radiography. Since its approval by the Food and Drug Administration (FDA) in the USA, several trauma centers have incorporated this technology into their Advanced Trauma Life Support protocols. This review provides a brief overview of the system, and describes the authors' own experience with the system. METHODS: We performed a PubMed search to retrieve all references with 'Lodox' and 'Stat-scan' used as search terms. We furthermore used the google search engine to identify existing alternatives. To the best of our knowledge, this is the only FDA-approved device of its kind currently used in trauma. RESULTS AND CONCLUSION: The intention of our review has been to sensitize the readership that such alternative devices exist. The key message is that low dosage full body radiography may be an alternative to conventional resuscitation room radiography which is usually a prelude to CT scanning (ATLS algorithm). The combination of both is radiation intensive and therefore we consider any reduction of radiation a success. But only the future will show whether LS will survive in the face of low-dose radiation CT scanners and magnetic resonance imaging devices that may eventually completely replace conventional radiography.

Gender-specific modulation of immune system complement gene expression in marine medaka Oryzias melastigma following dietary exposure of BDE-47

BDE-47 is one of the most widely found congeners of PBDEs in marine environments. The potential immunomodulatory effects of BDE-47 on fish complement system were studied using the marine medaka Oryzias melastigma as a model fish. Three-month-old O. melastigma were subjected to short-term (5 days) and long-term (21 days) exposure to two concentrations of BDE-47 (low dose at 290 +/- 172 ng/day; high dose at 580 +/- 344 ng/day) via dietary uptake of BDE-47 encapsulated in Artemia nauplii. Body burdens of BDE-47 and other metabolic products were analyzed in the exposed and control fish. Only a small amount of debrominated product, BDE-28, was detected, while other metabolic products were all under detection limit. Transcriptional expression of six major complement system genes involved in complement activation: C1r/s (classical pathway), MBL-2 (lectin pathway), CFP (alternative pathway), F2 (coagulation pathway), C3 (the central component of complement system), and C9 (cell lysis) were quantified in the liver of marine medaka. Endogenous expression of all six complement system genes was found to be higher in males than in females (p < 0.05). Upon dietary exposure of marine medaka to BDE-47, expression of all six complement genes were downregulated in males at day 5 (or longer), whereas in females, MBl-2, CFP, and F2 mRNAs expression were upregulated, but C3 and C9 remained stable with exposure time and dose. A significant negative relationship was found between BDE-47 body burden and mRNA expression of C1r/s, CFP, and C3 in male fish (r = -0.8576 to -0.9447). The above findings on changes in complement gene expression patterns indicate the complement system may be compromised in male O. melastigma upon dietary exposure to BDE-47. Distinct gender difference in expression of six major complement system genes was evident in marine medaka under resting condition and dietary BDE-47 challenge. The immunomodulatory effects of BDE-47 on transcriptional expression of these complement components in marine medaka were likely induced by the parent compound instead of biotransformed products. Our results clearly demonstrate that future direction for fish immunotoxicology and risk assessment of immunosuppressive chemicals must include parallel evaluation for both genders.