Standardized total tract digestibility of phosphorus in copra meal, palm kernel expellers, palm kernel meal, and soybean meal fed to growing pigs.
Sixty-six barrows (initial BW: 27.4 ± 2.8 kg) were used to determine the standardized total tract digestibility (STTD) of P in copra meal (CM), palm kernel expellers from Indonesia (PKE-IN), palm kernel expellers from Costa Rica (PKE-CR), palm kernel meal from Costa Rica (PKM), and soybean meal (SBM) without or with exogenous phytase. Pigs were housed individually in metabolism cages and allotted to 11 diets with 6 replicate pigs per diet in a generalized randomized block design. Five diets were formulated by mixing cornstarch and sugar with CM, PKE-IN, PKE-CR, PKM, or SBM. Five additional diets, which were identical to the initial 5 diets but supplemented with 800 units of phytase, were also formulated. A P-free diet was used to measure basal endogenous losses of P by the pigs. Feces were collected for 5 d using the marker to marker approach after a 5-d adaptation period. Analyzed total P in CM, PKE-IN, PKE-CR, PKM, and SBM was 0.52, 0.51, 0.53, 0.54, and 0.67%, respectively. Phytate P was 0.22, 0.35, 0.38, 0.32, and 0.44% in CM, PKE-IN, PKE-CR, PKM, and SBM, respectively. Addition of phytase increased (P < 0.05) the apparent total tract digestibility (ATTD) of P from 60.6 to 80.8, 27.3 to 56.5, 32.6 to 59.9, 48.9 to 64.1, and 41.1 to 72.2% in CM, PKE-IN, PKE-CR, PKM, and SBM, respectively. The ATTD of P in CM was greater (P < 0.05) than in any of the other ingredients. The ATTD of P in SBM and PKM was greater (P < 0.05) than in PKE-IN, with PKE-CR being intermediate. The STTD of P increased (P < 0.05) from 70.6 to 90.3, 37.6 to 66.4, 43.2 to 69.9, 57.9 to 73.5, and 49.6 to 81.1% in CM, PKE-IN, PKE-CR, PKM, and SBM, respectively, when microbial phytase was added to the diets. When expressed as a percentage of total P, phytate P concentration in the ingredient negatively affected (P < 0.05) the ATTD of P (107.09 - 1.0564 × % phytate P; R(2) = 87.1) and the STTD of P (116.3 - 1.0487 × % phytate P; R(2) = 89.4). In conclusion, microbial phytase increased P digestibility of CM, PKM, PKE-CR, PKE-IN, and SBM when fed to growing pigs, and the concentration of phytate P affects the response to microbial phytase.


Optic disc rim area is related to disc size in normal subjects.
Measurements of optic disc rim area are used to quantitatively evaluate the optic nerve head in open angle glaucoma. It has been suggested that disc rim area (neuroretinal rim area) is independent of disc size, unlike measurements of cup-disc ratio that co-vary with measurements of disc size. To test the relationships between topographic optic disc measurements and disc size, we used computerized image analysis (Rodenstock analyzer) of the optic nerve head to measure total disc area, cup area, disc rim area, and disc cup volume in 38 normal subjects. Magnification-corrected measurements of cup area, disc rim area, and cup volume were positively correlated with measurements of disc area. Measurements of disc rim area were therefore not independent of disc size in this group of normal subjects. A normal range of values for disc rim area can be predicted for an eye depending on the area of its optic disc. Sensitive predictions require further refinement based on the patient's age, race, and sex.


Enamel microhardness after in vitro demineralization and role of different restorative materials.
This study aimed to evaluate the extension of enamel demineralization around the margin of restorations after immersion in cariogenic solution, in an attempt to define the role of new restorative materials in preventing secondary caries formation. For this purpose, enamel microhardness was measured. Twelve class V restorations in human extracted third molars were prepared in vitro and immersed in a demineralizing solution (lactic acid, pH 4.5) at 37 degrees C for 3 days to simulate the formation of secondary caries and its effect on the marginal integrity of composite restorations. The restorative systems tested in the study were Scotchbond 1 + Z 250 (group A), ABF + APX (group B), Fuji IX (group C), SE Bond + APX (group D), and Scotchbond 1 + F 2000 (group E). The microhardness was measured close to the margin of restoration (marginal exposed enamel), at 2.0 mm from the margin (exposed enamel), and at approximately 4 mm from the margin in a varnish-covered enamel area (protected enamel). Five measurements were made on each site at 20, 40, 60, 80, and 100 microm depth from the external enamel surface. Exposed enamel and marginal exposed enamel were greatly affected by the cariogenic solution, as confirmed by the high rate of demineralization. The marginal exposed enamel showed a higher rate of demineralization than the exposed enamel, as demonstrated by the lowest microhardness values. The materials that claimed fluoride release did not prevent any type of enamel marginal alteration. This study revealed that enamel close to the margin of restoration may be rapidly affected by secondary caries formation when immersed in a demineralizing-cariogenic solution and that fluoride-releasing materials are unable to reduce the marginal demineralization processes. These demineralization processes may be responsible for marginal secondary caries and for restoration failures.


Cryptic-Prophage-Encoded Small Protein DicB Protects Escherichia coli from Phage Infection by Inhibiting Inner Membrane Receptor Proteins.
Bacterial genomes harbor cryptic prophages that have lost genes required for induction, excision from host chromosomes, or production of phage progeny. Escherichia coli K-12 strains contain a cryptic prophage, Qin, that encodes a small RNA, DicF, and a small protein, DicB, that have been implicated in control of bacterial metabolism and cell division. Since DicB and DicF are encoded in the Qin immunity region, we tested whether these gene products could protect the E. coli host from bacteriophage infection. Transient expression of the dicBF operon yielded cells that were ∼100-fold more resistant to infection by λ phage than control cells, and the phenotype was DicB dependent. DicB specifically inhibited infection by λ and other phages that use ManYZ membrane proteins for cytoplasmic entry of phage DNA. In addition to blocking ManYZ-dependent phage infection, DicB also inhibited the canonical sugar transport activity of ManYZ. Previous studies demonstrated that DicB interacts with MinC, an FtsZ polymerization inhibitor, causing MinC localization to midcell and preventing Z ring formation and cell division. In strains producing mutant MinC proteins that do not interact with DicB, both DicB-dependent phenotypes involving ManYZ were lost. These results suggest that DicB is a pleiotropic regulator of bacterial physiology and cell division and that these effects are mediated by a key molecular interaction with the cell division protein MinC.IMPORTANCE Temperate bacteriophages can integrate their genomes into the bacterial host chromosome and exist as prophages whose gene products play key roles in bacterial fitness and interactions with eukaryotic host organisms. Most bacterial chromosomes contain "cryptic" prophages that have lost genes required for production of phage progeny but retain genes of unknown function that may be important for regulating bacterial host physiology. This study provides such an example, where a cryptic-prophage-encoded product can perform multiple roles in the bacterial host and influence processes, including metabolism, cell division, and susceptibility to phage infection. Further functional characterization of cryptic-prophage-encoded functions will shed new light on host-phage interactions and their cellular physiological implications.


NVP-BEZ235, a novel dual PI3K-mTOR inhibitor displays anti-glioma activity and reduces chemoresistance to temozolomide in human glioma cells.
Glioblastoma multiforme (GBM) is the most frequent and most aggressive brain tumor in adults. The introduction of temozolomide (TMZ) has advanced chemotherapy for malignant gliomas. However, a considerable number of GBM cases are refractory to TMZ, the need for more effective therapeutic options is overwhelming. Mounting evidence shows that endogenous AKT (protein kinase B) activity can be activated in response to clinically relevant concentrations of TMZ. AKT activation correlated with the increased tumorigenicity, invasiveness and stemness and overexpression of an active form of AKT increases glioma cell resistance to TMZ. Previous studies also show that TMZ contributes to glioma cell apoptosis by inhibiting mTOR signaling. Thus, we hypothesized that the dual PI3K-mTOR inhibitor NVP-BEZ235 may act as antitumor agent against gliomas and potentiate the cytotoxicity of TMZ. In the present study, we found that NVP-BEZ235 treatment of glioma cell lines led to G1 cell cycle arrest, and induced apoptosis. Combination treatment with both TMZ and NVP-BEZ235 resulted in synergistically inhibited glioma cell growth and induced apoptosis (combination index CI<1) in a subset of glioma cell lines, as shown in the increased levels of Bax, and active Caspase-3, and decreased level of Bcl-2. Furthermore, NVP-BEZ235 treatment reversed p-AKT levels enhanced by TMZ. Inhibition of mTOR (p70S6K) signaling with the combination of TMZ and NVP-BEZ235 can be augmented beyond that achieved using each agent individually. In vivo xenograft models in mice, the combinatorial treatment with TMZ and NVP-BEZ235 significantly reduced tumor growth rates and prolonged median survival of tumor-bearing mice. These findings exhibit that TMZ in combination with NVP-BEZ235 act synergistically to inhibit proliferation of glioma cells by down-regulating of the PI3K-AKT-mTOR pathway, suggesting TMZ and NVP-BEZ235 combination therapy may be an option for GBM treatment.


[Spinal cord compression due to extramedullary hematopoiesis in a patient with myelofibrosis].
Development and growth of hematopoietic tissue outside of the bone marrow is termed extramedullary hematopoiesis (EMH). It occurs in patients with hematological diseases such as myelofibrosis and thalassemia. Liver and spleen are the usual sites of EMH. However, spinal cord compression caused by EMH is a rare complication. A 65-year-old man with myelofibrosis was admitted to our hospital with progressive paraparesis. Thoracic spine MRI revealed epidural masses causing cord compression. Histological examination of the epidural mass showed evidence of EMH consisting of megakaryocytic and erythroid hyperplasia. After surgical decompression and radiotherapy, lower limb weakness and sensory disturbance were significantly improved. MRI showed disappearance of the spinal cord compression. With this therapy, he had no recurrence until he died of myelofibrosis. Spinal EMH should be considered as a differential diagnosis in patients with hematological diseases presenting with paraparesis. Surgical decompression and radiotherapy are effective approaches for the treatment of paraparesis due to EMH.


Ductility and strength reduction factors for degrading structures considering cumulative damage.
The effect of cumulative damage on the strength requirements of degrading structures is assessed through the evaluation of the target ductility and corresponding strength reduction factors of simple degrading structures. While the reduction on ductility is established through the use of Park and Ang index, the suggestions given by Bojórquez and Rivera are used to model the degradation of the structural properties of the simple systems. Target ductilities and their corresponding reduced strength reduction factors are established for five sets of ground motions; most of them are recorded in California. The results given in this paper provide insight into all relevant parameters that should be considered during seismic design of earthquake-resistant structures. Finally, some recommendations to evaluate the effect of cumulative damage on seismic design are suggested.


A study of intracytoplasmic inclusions in myeloma cells from two patients with multiple myeloma.
Two cases of multiple myeloma which showed inclusions within the cytoplasma of myeloma cells were reported. One contained crystalline inclusions which were not stained by May-Grünwald and Giemsa, and the other contained Auer rod-like spindle shaped inclusions which were stained by May-Grünwald and Giemsa and PAS. Both cases were stained intensively by acid phosphatase but they were not stained by Congo red or by thioflavine-T. Moreover, they reacted only with anti-kappa sera in the immunofluorescent study and showed the same structure on electron microscopic observation. Although they showed different staining behaviors according to their compositions, they were considered to be essentially the same. It appears that light chains produced in excess are concentrated and form inclusions through the addition of sugar or digestion by lysosomal enzymes.


The Breathing Cell: Cyclic Intermembrane Distance Variation in Reverse Electrodialysis.
The breathing cell is a new concept design that operates a reverse electrodialysis stack by varying in time the intermembrane distance. Reverse electrodialysis is used to harvest salinity gradient energy; a rather unknown renewable energy source from controlled mixing of river water and seawater. Traditionally, both river water and seawater compartments have a fixed intermembrane distance. Especially the river water compartment thickness contributes to a large extent to the resistance of the stack due to its low conductivity. In our cyclic approach, two stages define the principle of the breathing concept; the initial stage, where both compartments (seawater and river water) have the same thickness and the compressed stage, where river water compartments are compressed by expanding the seawater compartments. This movement at a tunable frequency allows reducing stack resistance by decreasing the thickness of the river water compartment without increasing permanently the pumping losses. The breathing stacks clearly benefit from the lower resistance values and low pumping power required, obtaining high net power densities over a much broader flow rate range. The high frequency breathing stack (15 cycles/min) shows a maximum net power density of 1.3 W/m2. Although the maximum gross and net power density ever registered (2.9 W/m2 and 1.5 W/m2, respectively) is achieved for a fixed 120 μm intermembrane distance stack (without movement of the membranes), it is only obtained at a very narrow flow rate range due to the high pressure drops at small intermembrane distance. The breathing cell concept offers a unique feature, namely physical movement of the membranes, and thus the ability to adapt to the operational conditions and water quality.


Stress-induced biosynthesis of dicaffeoylquinic acids in globe artichoke.
Leaf extracts from globe artichoke ( Cynara cardunculus L. var. scolymus) have been widely used in medicine as hepatoprotectant and choleretic agents. Globe artichoke leaves represent a natural source of phenolic acids with dicaffeoylquinic acids, such as cynarin (1,3-dicaffeoylquinic acid), along with its biosynthetic precursor chlorogenic acid (5-caffeoylquinic acid) as the most abundant molecules. This paper reports the development of an experimental system to induce caffeoylquinic acids. This system may serve to study the regulation of the biosynthesis of (poly)phenolic compounds in globe artichoke and the genetic basis of this metabolic regulation. By means of HPLC-PDA and accurate mass LC-QTOF MS and MS/MS analyses, the major phenolic compounds in globe artichoke leaves were identified: four isomers of dicaffeoylquinic acid, three isomers of caffeoylquinic acid, and the flavone luteolin 7-glucoside. Next, plant material was identified in which the concentration of phenolic compounds was comparable in the absence of particular treatments, with the aim to use this material to test the effect of stress application on the regulation of biosynthesis of caffeoylquinic acids. Using this material, the effect of UV-C, methyl jasmonate, and salicylic acid treatments on (poly)phenolic compounds was tested in different globe artichoke genotypes. UV-C exposure consistently increased the levels of dicaffeoylquinic acids in all genotypes, whereas the effect on compounds from the same biosynthetic pathway, for example, chlorogenic acid and luteolin-7-glucoside, was much less pronounced and was not statistically significant. No effect of methyl jasmonate or salicylic acid was found. Time-response experiments indicated that the level of dicaffeoylquinic acids reached a maximum at 24 h after UV radiation. On the basis of these results a role of dicaffeoylquinic acids in UV protection in globe artichoke is hypothesized.


Macrophages Respond Rapidly to Ototoxic Injury of Lateral Line Hair Cells but Are Not Required for Hair Cell Regeneration.
The sensory organs of the inner ear contain resident populations of macrophages, which are recruited to sites of cellular injury. Such macrophages are known to phagocytose the debris of dying cells but the full role of macrophages in otic pathology is not understood. Lateral line neuromasts of zebrafish contain hair cells that are nearly identical to those in the inner ear, and the optical clarity of larval zebrafish permits direct imaging of cellular interactions. In this study, we used larval zebrafish to characterize the response of macrophages to ototoxic injury of lateral line hair cells. Macrophages migrated into neuromasts within 20 min of exposure to the ototoxic antibiotic neomycin. The number of macrophages in the near vicinity of injured neuromasts was similar to that observed near uninjured neuromasts, suggesting that this early inflammatory response was mediated by "local" macrophages. Upon entering injured neuromasts, macrophages actively phagocytosed hair cell debris. The injury-evoked migration of macrophages was significantly reduced by inhibition of Src-family kinases. Using chemical-genetic ablation of macrophages before the ototoxic injury, we also examined whether macrophages were essential for the initiation of hair cell regeneration. Results revealed only minor differences in hair cell recovery in macrophage-depleted vs. control fish, suggesting that macrophages are not essential for the regeneration of lateral line hair cells.


Myeloperoxidase oxidation states involved in myeloperoxidase-oxidase oxidation of thiols.
The changes in the oxidation state of the leucocyte enzyme myeloperoxidase, induced by buffer and thiols, were studied with visible-light-absorption spectroscopy. It was concluded that phosphate buffer contains small amounts of H2O2 and that thiols, when added to buffer, induce the generation of minute amounts of superoxide radical anion. These minute amounts of reduced oxygen species are suggested to account for the initiation of myeloperoxidase-oxidase oxidation of thiols. Myeloperoxidase was found to be in its Compound III oxidation state during myeloperoxidase-oxidase oxidation of thiols. However, myeloperoxidase-mediated oxidation of thiols with concomitant O2 consumption can also occur with myeloperoxidase in its Compound II oxidation state. These studies indicate that the ferro and Compound III oxidation states may not be essential intermediates in myeloperoxidase-oxidase oxidation of thiols, but rather that the formation of the Compound III oxidation state retards the reaction.


Tofacitinib suppresses disease activity and febrile attacks in a patient with coexisting rheumatoid arthritis and familial Mediterranean fever.
Familial Mediterranean fever (FMF) is the most common hereditary auto-inflammatory (periodic fever) syndrome, and usually successfully treated with colchicine. However, nearly 5-10% of FMF cases are resistant or intolerant to colchicine and treatment options are highly restricted in these cases. Biologics including anakinra, canakinumab, rilonacept, etanercept, infliximab, interferon-alpha, and tocilizumab are shown to have efficacy to control FMF attacks. Tofacitinib, a Janus kinase (JAK) inhibitor, is an orally administered non-biologic disease modifying anti-rheumatic drug for the treatment of rheumatoid arthritis (RA). Herein we report a female patient with coexisting RA and colchicine resistant FMF whose FMF attacks and disease activity were completely controlled after treatment with tofacitinib, a small-molecule JAK3 inhibitor.


Food Microstructure and Fat Content Affect Growth Morphology, Growth Kinetics, and Preferred Phase for Cell Growth of Listeria monocytogenes in Fish-Based Model Systems.
Food microstructure significantly affects microbial growth dynamics, but knowledge concerning the exact influencing mechanisms at a microscopic scale is limited. The food microstructural influence on Listeria monocytogenes (green fluorescent protein strain) growth at 10°C in fish-based food model systems was investigated by confocal laser scanning microscopy. The model systems had different microstructures, i.e., liquid, xanthan (high-viscosity liquid), aqueous gel, and emulsion and gelled emulsion systems varying in fat content. Bacteria grew as single cells, small aggregates, and microcolonies of different sizes (based on colony radii [size I, 1.5 to 5.0 μm; size II, 5.0 to 10.0 μm; size III, 10.0 to 15.0 μm; and size IV, ≥15 μm]). In the liquid, small aggregates and size I microcolonies were predominantly present, while size II and III microcolonies were predominant in the xanthan and aqueous gel. Cells in the emulsions and gelled emulsions grew in the aqueous phase and on the fat-water interface. A microbial adhesion to solvent assay demonstrated limited bacterial nonpolar solvent affinities, implying that this behavior was probably not caused by cell surface hydrophobicity. In systems containing 1 and 5% fat, the largest cell volume was mainly represented by size I and II microcolonies, while at 10 and 20% fat a few size IV microcolonies comprised nearly the total cell volume. Microscopic results (concerning, e.g., growth morphology, microcolony size, intercolony distances, and the preferred phase for growth) were related to previously obtained macroscopic growth dynamics in the model systems for an L. monocytogenes strain cocktail, leading to more substantiated explanations for the influence of food microstructural aspects on lag phase duration and growth rate.IMPORTANCEListeria monocytogenes is one of the most hazardous foodborne pathogens due to the high fatality rate of the disease (i.e., listeriosis). In this study, the growth behavior of L. monocytogenes was investigated at a microscopic scale in food model systems that mimic processed fish products (e.g., fish paté and fish soup), and the results were related to macroscopic growth parameters. Many studies have previously focused on the food microstructural influence on microbial growth. The novelty of this work lies in (i) the microscopic investigation of products with a complex composition and/or structure using confocal laser scanning microscopy and (ii) the direct link to the macroscopic level. Growth behavior (i.e., concerning bacterial growth morphology and preferred phase for growth) was more complex than assumed in common macroscopic studies. Consequently, the effectiveness of industrial antimicrobial food preservation technologies (e.g., thermal processing) might be overestimated for certain products, which may have critical food safety implications.


A parametric study of the hydrodynamic roughness produced by a wall coating layer of heavy oil.
In water-lubricated pipeline transportation of heavy oil and bitumen, a thin oil film typically coats the pipe wall. A detailed study of the hydrodynamic effects of this fouling layer is critical to the design and operation of oil-water pipelines, as it can increase the pipeline pressure loss (and pumping power requirements) by 15 times or more. In this study, a parametric investigation of the hydrodynamic effects caused by the wall coating of viscous oil was conducted. A custom-built rectangular flow cell was used. A validated CFD-based procedure was used to determine the hydrodynamic roughness from the measured pressure losses. A similar procedure was followed for a set of pipe loop tests. The effects of the thickness of the oil coating layer, the oil viscosity, and water flow rate on the hydrodynamic roughness were evaluated. Oil viscosities from 3 to 21300 Pa s were tested. The results show that the equivalent hydrodynamic roughness produced by a wall coating layer of viscous oil is dependent on the coating thickness but essentially independent of oil viscosity. A new correlation was developed using these data to predict the hydrodynamic roughness for flow conditions in which a viscous oil coating is produced on the pipe wall.


The Effects of Progesterone on Glial Cell Line-derived Neurotrophic Factor Secretion from C6 Glioma Cells.
Progesterone is a steroid hormone whose biology has been greatly studied within the confines of reproductive function. In recent years, the neuroprotective effects of progesterone have attracted growing interest. Glial cell line-derived neurotrophic factor (GDNF), is a neurotrophic factor which plays a crucial role in the development and maintenance of distinct sets of central and peripheral neurons. In the present study, we investigated the potential implication of GDNF in the neuroprotective action of progesterone. Cultured rat C6 glioma cells were treated with progesterone (100 nm, 1 µM, and 10 µM) or its vehicle. After 24, 36, 48 and 72 hr, GDNF protein levels were measured in the cell-conditioned media and cell lysates using a GDNF ELISA kit. Cell numbers were determined by a cell-counting assay kit. Forty-eight hr treatment with progesterone (10 µM) resulted in a significant elevation of GDNF secretion from C6 glioma cells that remained elevated up to 72 hr. The intracellular content of GDNF and cell numbers were not affected by progesterone treatment. Stimulation of GDNF release from glial cells appears as a potential mechanism through which progesterone exerts its neuroprotective effects.


Involvement of Ngn2, Tbr and NeuroD proteins during postnatal olfactory bulb neurogenesis.
Postnatal neurogenesis takes place in two brain regions, the hippocampus and the subventricular zone (SVZ). The transcriptional cascade controlling hippocampal neurogenesis has been described in detail; however, the transcriptional control of olfactory bulb neurogenesis is still not well mapped. In this study, we provide insights into the molecular events controlling postnatal olfactory bulb neurogenesis. We first show the existence of diverse neural stem cell/progenitor populations along the SVZ-rostral migratory stream (RMS) axis, focusing on those expressing the basic helix-loop-helix (bHLH) transcription factor Mash1. We provide evidence that Mash1-derived progenies generate oligodendrocytic and neuronal precursors through the transient expression of the bHLH transcription factors Olig2 and neurogenin2 (Ngn2), respectively. Furthermore, we reveal that Ngn2-positive progenies express the T-box transcription factors Tbr2 and Tbr1, which are usually present during cortical and hippocampal glutamatergic neuronal differentiation. We also highlight a cell population expressing another bHLH transcription factor, neuroD1 (ND1). The ND1-positive cells are located in the SVZ-RMS axis and also co-express Tbr2, Tbr1 and neuroD2. The observations that these cells incorporate bromodeoxyuridine and express both doublecortin and polysialylated form of neural cell adhesion molecule suggest that they are newborn neurons. Finally, using an in vitro assay, we demonstrate that Ngn2 and ND1 equally and exclusively direct differentiation of Mash1-expressing precursors into calbindin-expressing and calretinin-expressing neurons, which are both neuronal subtypes normally found in the olfactory bulb. Taken together, our data illustrate that Ngn2, neuroD and Tbr transcription factors are involved in postnatal neurogenesis in the olfactory bulb.


Dealing with grief related to loss by death and chronic pain: suggestions for practice. Part 2.
This paper, the second of two, represents a theoretical framework for interventions related to loss by death of someone close, or chronic pain. This work is based on our previous understanding where grief is considered an integrated experience which involves movements on several continua. We have performed a comparison between two interventions dealing with grief and chronic pain using different designs. Interrelated experiences and processes were identified. Life phenomena like grief and loss caused by death and chronic pain, seem to have many qualities in common and may overlap each other. A common core containing emptiness, vulnerability and exhaustion is identified. Despite advances in research and thinking in recent years, several issues related to grief caused by death or chronic pain remain a challenge in clinical settings and research. When preparing interventions, we must pay attention to the relearning process, the common core and the interplay between these bodily expressions. We believe there is a value in future research and practice to consider losses caused by death and chronic pain, together as well as separately. Our comprehensive approach indicates that understanding the processes involved in one sort of grief may help understand the processes involved in the other.


EASTERN EUROPE: Help Needed to Rebuild Science in Yugoslavia.
The Yugoslavian scientific community has withered in the past decade, crippled by a massive brain drain and starved for resources. Now the promise of democratic rule in Yugoslavia has rekindled scientists' hopes that their careers will eventually get back on track and that scientific cooperation between the former Yugoslav republics can be reestablished. But the losses have been so great that the comeback of Yugoslavian science depends largely on how much assistance Western countries and expatriate scientists provide.


[Rheology, hemolysis and peripheral blood indices in macaccus rhesus monkeys in health and posthemorrhagic period].
Twenty monkeys (macaccus rhesus) were examined by the following parameters: deformability of erythrocytes and mononuclear leukocytes, hemolytic activity of the serum, free hemoglobin of the serum and viscosity of plasma. The data obtained are accepted as standard because literature data on hemorrheology of monkeys are absent. Compared to relevant indices in humans, monkeys have increased hematocrit, serum hemolytic activity, erythrocytic rigidity index. Seven monkeys were used as the model of "donor" (6-8% blood loss). The above indices were measured before exfusion and on days 2, 7, 14 and 21 after exfusion. Maximal changes in rheology and hemolysis were observed on day 2 and 7 after blood loss which correlated with deviations of the red sprout of hemogeny.


Pop hole use by hens with different keel fracture status monitored throughout the laying period.
The aim of this work was to study the effect of keel fractures on the extent to which free-range hens access the range through pop holes. Over two consecutive laying periods (two production years) a total of 1100 individual birds from one half of a house, divided into four separated flocks, were caught at 25, 35, 45, 55 and 65 weeks, palpated to assess the prevalence and severity of keel fractures and tagged with RFID transponders. Their use of pop holes was subsequently monitored in some cases from week 25 to end of lay at 68 to 70 weeks. At regular intervals (every 10 weeks), the tagged birds were re-caught to assess changes in keel fracture prevalence and severity. The average percentage of birds with fractured keels at 25, 35, 45, 55, 65 and at end of lay (68 to 70 weeks of age) was 5.5, 25.5, 49, 63, 66.5 and 78.5, respectively, across both production years. The effect of keel score on pop hole use was modelled statistically, adjusting for weather conditions and age of the birds. There were significant effects of most of the weather variables recorded, as well as age of the bird, on use of pop holes and also a significant effect of keel score. Higher keel scores resulted in a reduction in pop hole use. A significant statistical interaction between keel score and ambient temperature revealed an accelerated reduction in use as the temperature decreased and keel score increased. It is concluded that the occurrence of keel fractures may affect the birds' ability or willingness to utilise the outdoor range provided by free-range housing systems, thereby reducing the potential welfare advantages of this type of housing.


Differential Effects of Estrogen on Corticosteroid-Binding Globulin Forms Suggests Reduced Cleavage in Pregnancy.
Corticosteroid-binding globulin (CBG) is secreted as high-affinity CBG (haCBG), which may be cleaved by tissue proteases to low-affinity CBG (laCBG), releasing free cortisol. Pregnancy and the estrogen-based combined oral contraceptive pill (COCP) increase CBG concentrations twofold to threefold. The relative effects of these two hyperestrogenic states on the CBG affinity forms are unknown. We performed an observational study in 30 pregnant women, 27 COCP takers and 23 controls. We analyzed circulating total CBG, haCBG, laCBG, and free and total cortisol concentrations. In pregnancy, total CBG and haCBG were increased compared to controls (both P < 0.0001); however, laCBG concentrations were similar. In COCP takers, total CBG and haCBG were increased [802 ± 41 vs compared to controls (both P < 0.0001)], but laCBG was also increased (P = 0.03). Pregnancy and use of COCP were associated with a comparable rise in haCBG, but laCBG was lower in pregnancy (P < 0.0001). These results were consistent with an estrogen-mediated increase in CBG synthesis in both hyperestrogenemic states but with reduced CBG cleavage in pregnancy relative to the COCP, perhaps due to pregnancy-induced CBG glycosylation. Speculatively, increased circulating haCBG concentrations in pregnancy may provide an increased reservoir of CBG-bound cortisol to prepare for the risk of puerperal infection or allow for cortisol binding in the face of competition from increased circulating progesterone concentrations.


Benefits of music training are widespread and lifelong: a bibliographic review of their non-musical effects.
Recent publications indicate that musical training has effects on non-musical activities, some of which are lifelong. This study reviews recent publications collected from the Performing Arts Medicine Association bibliography. Music training, whether instrumental or vocal, produces beneficial and long-lasting changes in brain anatomy and function. Anatomic changes occur in brain areas devoted to hearing, speech, hand movements, and coordination between both sides of the brain. Functional benefits include improved sound processing and motor skills, especially in the upper extremities. Training benefits extend beyond music skills, resulting in higher IQs and school grades, greater specialized sensory and auditory memory/recall, better language memory and processing, heightened bilateral hand motor functioning, and improved integration and synchronization of sensory and motor functions. These changes last long after music training ends and can minimize or prevent age-related loss of brain cells and some mental functions. Early institution of music training and prolonged duration of training both appear to contribute to these positive changes.


Requirement of Gbetagamma and c-Src in D2 dopamine receptor-mediated nuclear factor-kappaB activation.
The D2 dopamine receptor (D2R) was examined for its ability to mediate nuclear factor-kappaB (NF-kappaB) activation through G proteins. Stimulation of D2R-transfected HeLa cells with its agonist quinpirole induced the expression of a NF-kappaB luciferase reporter and formation of NF-kappaB-DNA complex. This response was blocked by pertussis toxin, and by the Gbetagamma scavengers transducin and beta-adrenergic receptor kinase 1 carboxyl-terminal fragment. Unlike Gi-coupled chemoattractant receptors, D2R activated NF-kappaB without an increase in phospholipase C-beta activity, and the response was only slightly affected by the phosphoinositide 3-kinase inhibitor 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002). In contrast, treatment with genistein and 4-amino-1-tert-butyl-3-(p-methylphenyl)pyrazolo[3,4-d] pyrimidine abolished the induced NF-kappaB activation, suggesting involvement of protein tyrosine kinases. Activation of D2R led to phosphorylation of c-Src at Tyr-418, and expression of a kinase-deficient c-Src inhibited D2R-mediated NF-kappaB activation. The D2R-mediated NF-kappaB activation was not dependent on epidermal growth factor (EGF) receptor transactivation since 4-(3'-chloroanilino)-6,7-dimethoxyquinazoline (AG1478), an EGF receptor-selective tyrphostin used at 1 microM, blocked EGF-induced NF-kappaB activation but not the quinpirole-induced response. In addition, the D2R-mediated NF-kappaB activation was enhanced by over-expression of beta-arrestin 1. These results suggest that D2R-mediated NF-kappaB activation requires Gbetagamma and c-Src, and possibly involves beta-arrestin 1.


Long-term health effects of harness-mounted radio transmitters in red kites (Milvus milvus) in England.
In 1989, the Nature Conservancy Council and the Royal Society for the Protection of Birds commenced reintroduction of the red kite (Milvus milvus) according to International Union for Conservation of Nature criteria. Following 22 years of intensive effort, the red kite reintroduction programme has been a success with an estimated 1000 pairs now breeding in England. Post-release health surveillance is ongoing and has been achieved through radio-tracking, monitoring breeding at nest sites and pathological examinations of any red kites found dead. Tail-mounted radio transmitters were fitted from 1989 with harness-mounted radio transmitters being preferentially used since 2000. Since 2000, 180 individuals have been recovered for postmortem examination. Eighteen of these birds had previously had a harness-mounted radio transmitter fitted and four of these (22 per cent) had moderate to severe lesions associated with the presence of the harness and radio transmitter including chronic necrogranulomatous inflammation, deep muscular exposure and distorted muscular conformation. Failure to breed was also reported in two of these individuals over the preceding year(s), although it is not known whether the presence of the harness contributed to this failure. Duration of deployment may have been a significant factor in the formation of these lesions as those with lesions (n=4) had a statistically significant (P=0.009) longer duration of deployment compared to those without lesions (n=14). No lesions were reported in those red kites fitted with tail-transmitters.


Between facets and domains: 10 aspects of the Big Five.
Factor analyses of 75 facet scales from 2 major Big Five inventories, in the Eugene-Springfield community sample (N=481), produced a 2-factor solution for the 15 facets in each domain. These findings indicate the existence of 2 distinct (but correlated) aspects within each of the Big Five, representing an intermediate level of personality structure between facets and domains. The authors characterized these factors in detail at the item level by correlating factor scores with the International Personality Item Pool (L. R. Goldberg, 1999). These correlations allowed the construction of a 100-item measure of the 10 factors (the Big Five Aspect Scales [BFAS]), which was validated in a 2nd sample (N=480). Finally, the authors examined the correlations of the 10 factors with scores derived from 10 genetic factors that a previous study identified underlying the shared variance among the Revised NEO Personality Inventory facets (K. L. Jang et al., 2002). The correspondence was strong enough to suggest that the 10 aspects of the Big Five may have distinct biological substrates.


Assessment of Explicitly Stated Interval Change on Noncontrast Head CT Radiology Reports.
Consistent and standardized reporting of interval change for certain diagnoses may improve the clinical utility of radiology reports. The purpose of this study was to assess explicitly stated interval change of various findings in noncontrast head CT reports. A retrospective review was performed on successive noncontrast head CT radiology reports from the first 2 weeks of January 2014. Reports with at least 1 prior comparison CT scan were included. Reports with normal examination findings and those that made comparison with only other types of examinations (eg, MR imaging) were excluded. Descriptive and subgroup statistical analyses were performed. In total, 200 patients with 230 reports and 979 radiographic findings were identified. The average interval between reports was 344.9 ± 695.9 days (range, 0-3556 days). Interval change was mentioned 67.3% (n = 659) of the time for all findings (n = 979). Explicitly stated interval change was significantly associated with nonremote findings (P < .001) and generalized statements of interval change (P < .001). The proportion of interval change reported ranged from 95.3% of the time for hemorrhagic to 36.4% for soft-tissue/osseous categorizations. Interval change reporting was variable, mentioned for 67.3% of noncontrast head CT report findings with a prior comparison CT scan. Structured radiology reports may improve the consistent and clear reporting of interval change for certain findings.


Deep UV light induced, fast reconfigurable and fixed waveguides in Mg doped LiTaO(3).
Dynamic waveguides are induced beneath the surface of magnesium doped near-stoichiometric lithium tantalate by deep UV light at lambda = 257 nm using the interband photorefractive effect. The waveguides can be reconfigured in 10 ms at UV intensities of 100 mW/cm(2). We show the importance of the background illumination for the build-up of dynamic optical waveguides. We also present a new fixing process of the light-induced waveguide structures when the background light is absent. These quasi-fixed structures with dark decay times of several days are due to charges trapped in deep traps.


Heuristic and linear models of judgment: matching rules and environments.
Much research has highlighted incoherent implications of judgmental heuristics, yet other findings have demonstrated high correspondence between predictions and outcomes. At the same time, judgment has been well modeled in the form of as if linear models. Accepting the probabilistic nature of the environment, the authors use statistical tools to model how the performance of heuristic rules varies as a function of environmental characteristics. They further characterize the human use of linear models by exploring effects of different levels of cognitive ability. They illustrate with both theoretical analyses and simulations. Results are linked to the empirical literature by a meta-analysis of lens model studies. Using the same tasks, the authors estimate the performance of both heuristics and humans where the latter are assumed to use linear models. Their results emphasize that judgmental accuracy depends on matching characteristics of rules and environments and highlight the trade-off between using linear models and heuristics. Whereas the former can be cognitively demanding, the latter are simple to implement. However, heuristics require knowledge to indicate when they should be used.


Optical interconnection networks for high-performance computing systems.
Enabled by silicon photonic technology, optical interconnection networks have the potential to be a key disruptive technology in computing and communication industries. The enduring pursuit of performance gains in computing, combined with stringent power constraints, has fostered the ever-growing computational parallelism associated with chip multiprocessors, memory systems, high-performance computing systems and data centers. Sustaining these parallelism growths introduces unique challenges for on- and off-chip communications, shifting the focus toward novel and fundamentally different communication approaches. Chip-scale photonic interconnection networks, enabled by high-performance silicon photonic devices, offer unprecedented bandwidth scalability with reduced power consumption. We demonstrate that the silicon photonic platforms have already produced all the high-performance photonic devices required to realize these types of networks. Through extensive empirical characterization in much of our work, we demonstrate such feasibility of waveguides, modulators, switches and photodetectors. We also demonstrate systems that simultaneously combine many functionalities to achieve more complex building blocks. We propose novel silicon photonic devices, subsystems, network topologies and architectures to enable unprecedented performance of these photonic interconnection networks. Furthermore, the advantages of photonic interconnection networks extend far beyond the chip, offering advanced communication environments for memory systems, high-performance computing systems, and data centers.


Systemic low-grade inflammation and risk of coronary heart disease: results from the MONICA/KORA Augsburg cohort studies.
Atherosclerosis is characterised by a non-specific local inflammatory process accompanied by a systemic response. A number of prospective studies in initially healthy subjects and in patients with manifest atherosclerosis have now convincingly demonstrated a strong and independent association between even slightly elevated concentrations of various systemic markers of inflammation (plasma viscosity, C-reactive protein [CRP], and other acute phase reactants) and a number of cardiovascular endpoints. Presently, CRP, the classical acute phase protein, seems to be the marker of choice for the clinical situation. Initial evidence suggests that measurement of CRP adds to global risk assessment based on the Framingham risk score. The recent AHA/CDC consensus report recommends the measurement of CRP in asymptomatic subjects at intermediate risk for future coronary events (10-year risk of 10-20 %) and in selected patients after an acute coronary syndrome. Whether CRP shall alter treatment strategies in subjects without clinically manifest atherosclerosis is presently being tested in a large randomised clinical trial. In addition, recent research has suggested that CRP may not only be a risk marker, but may be directly involved in the pathogenesis of atherothrombosis. However, there are other emerging biomarkers. Lipoprotein-associated phospholipase A (2) (Lp-PLA (2)), an enzyme produced by monocytes/macrophages, T-cells and mast cells was found to generate proinflammatory and proatherogenic molecules from oxidised LDL. We tested the association of these new biomarkers with traditional risk factors and their ability to predict incident coronary events, using the MONICA/KORA database.


Repeated mild brain injuries result in cognitive impairment in B6C3F1 mice.
Experimental investigations of single mild brain injury (SMI) show relatively little resultant cognitive impairment. However, repeated mild brain injuries (RMI), as those sustained by athletes (e.g., football, hockey, and soccer players) may have cumulative effects on cognitive performance and neuropathology. Numerous clinical studies show persistent, latent, and long-term consequences of RMI, unlike the episodic nature of SMI. The nature of repeated traumatic brain injury (TBI) introduces confounding factors in invasive and even semiinvasive animal models of brain injury (e.g., scar formation). Thus, the present study characterizes SMI and RMI in a noninvasive mouse weight drop model and the cumulative effects of RMI on cognitive performance. Investigation of drop masses and drop distances revealed masses of 50, 100, and 150 g dropped from 40 cm resulted in 0% mortality, no skull fracture, and no difference in acute neurological assessment following sham injury, SMI, or RMI. Cumulative effects of RMI were examined following four mild brain injuries 24 h apart induced by 50-, 100-, or 150-g masses dropped from 40 cm through histological measures, mean arterial pressure, and measures of complex/spatial learning. RMI produced no overt cell death within the cortex or hippocampus, no evidence of blood-brain barrier compromise, and no significant change in mean arterial pressure. Following testing in the Morris water maze (MWM) on days 7-11 after initial injury, mice in the RMI 100-g and RMI 150-g groups had significantly longer MWM goal latencies compared to sham, SMI 150-g, and RMI 50-groups. Additionally, the evident cognitive deficit manifested in the absence of observed cell death. This is the first study to show complex/spatial learning deficits following RMI, similar to the visual/spatial perception and planning deficits observed in clinical studies.


PEDOT-Based Conducting Polymer Actuators.
Conducting polymers, particularly poly(3,4-ethylenedioxythiophene) (PEDOT) and its complex with poly(styrene sulfonate) (PEDOT:PSS), provide a promising materials platform to develop soft actuators or artificial muscles. To date, PEDOT-based actuators are available in the field of bionics, biomedicine, smart textiles, microactuators, and other functional applications. Compared to other conducting polymers, PEDOT provides higher conductivity and chemical stability, lower density and operating voltages, and the dispersion of PEDOT with PSS further enriches performances in solubility, hydrophility, processability, and flexibility, making them advantageous in actuator-based applications. However, the actuators fabricated by PEDOT-based materials are still in their infancy, with many unknowns and challenges that require more comprehensive understanding for their current and future development. This review is aimed at providing a comprehensive understanding of the actuation mechanisms, performance evaluation criteria, processing technologies and configurations, and the most recent progress of materials development and applications. Lastly, we also elaborate on future opportunities for improving and exploiting PEDOT-based actuators.


The dynamics of residential aged care in Australia: 8-year trends in admission, separations and dependency.
The aims of this paper are to analyse changes in dependency of residents in residential aged care homes consequent upon the passing of the Commonwealth Aged Care Act in late 1997, and to establish the extent of resultant changes in the dynamics of residential aged care. The paper outlines the major changes brought by the Aged Care Act, and evidence for the effects of these changes is examined to test the hypothesis that changes in dependency generated changes in turnover and length of stay. The findings show that the proportion of admissions classified at higher categories of the Resident Classification Scale has increased over time, and that the trend to higher classification is even more pronounced by the time residents separate. As funding of residential aged care is based on resident dependency, change in dependency and in the dynamics of the aged care system have potentially significant consequences for Commonwealth funding of providers to ensure care can be provided commensurate with resident needs. The conclusions take up a number of implications of the findings for future policy in relation to planning and funding of residential aged care as a new resident funding system based on the Aged Care Funding Instrument (ACFI) is phased in from mid 2007.


Influence of laboratory-related and endoscopy-related factors on the assessment of serum pepsinogens and gastrin-17.
Serum pepsinogen I (PGI) and pepsinogen II (PGII) are noninvasive parameters in the detection of atrophic gastritis. The diagnostic add-on value of serum gastrin-17 (G-17) remains uncertain. The aim of this study was to assess the stability of these serum parameters over time and to evaluate the influence of clinical factors, such as upper gastrointestinal (GI) endoscopy and bowel cleansing, on serum PGI, PGII, and G-17 assessment. A prospective study was carried out in healthy individuals and patients. For the stability analyses, the plasma and serum samples from 23 individuals were processed at different time points with and without the addition of a stabilizer. Ten patients were included to evaluate the influence of upper GI endoscopy and 18 patients to evaluate the effect of bowel cleansing before colonoscopy. PGI, PGII, and G-17 levels were not statistically different in the serum and plasma. PGI and PGII serum levels were stable over time. G-17 is associated with time-dependent degradation (P=0.0001). The addition of the G-17 stabilizer showed no improvement in stability. Upper GI endoscopy and bowel preparation before colonoscopy were associated with minimal variations in PGI and PGII, whereas G-17 showed patient-specific alterations. PGI and PGII serum levels are stable over time. However, G-17 stability is strongly dependent on the time of processing and storage; therefore, samples for G-17 analysis need to be processed no later than 6 h after blood collection. Upper GI endoscopy and colonoscopy preparation lead to minimal nonsignificant changes in basal PGI, PGII, and G-17 levels.


Manipulation of Electrode Composition for Effective Water Management in Fuel Cells Fed with an Electrically Rechargeable Liquid Fuel.
The liquid fuel cell, with its high energy density and ease of fuel handling, has attracted great attention worldwide. However, its real application is still being greatly hindered by its limited power density. Hence, the recently proposed and demonstrated fuel cell, using an electrically rechargeable liquid fuel (e-fuel), is believed to be a candidate with great potential due to its significant performance advancement. Unlike the conventional alcoholic liquid fuels, the e-fuel possesses excellent reactivity, even on carbon-based materials, which therefore allows the e-fuel cell to achieve superior performance without any noble metal catalysts. However, it is found that, during the cell operation, the water generated at the cathode following the oxygen reduction reaction could lead to a water flooding problem and further limit the cell performance. To address this issue, in this work, by manipulating the cathode composition, a blended binder cathode using both Nafion and polytetrafluoroethylene as binding agents is fabricated and demonstrated its superiority in the fuel cell to achieve an enhanced water management and cell performance. Furthermore, using the developed cathode, a fuel cell stack is designed and fabricated to power a 3D-printed toy car, presenting this system as a promising device feasible for future study and real applications.


Transplantation immunology: solid organ and bone marrow.
Development of the field of organ and tissue transplantation has accelerated remarkably since the human MHC was discovered in 1967. Matching of donor and recipient for MHC antigens has been shown to have a significant positive effect on graft acceptance. The roles of the different components of the immune system involved in the tolerance or rejection of grafts and in graft-versus-host disease have been clarified. These components include antibodies, antigen-presenting cells, helper and cytotoxic T-cell subsets, immune cell-surface molecules, signaling mechanisms, and cytokines. The development of pharmacologic and biological agents that interfere with the alloimmune response has had a crucial role in the success of organ transplantation. Combinations of these agents work synergistically, leading to lower doses of immunosuppressive drugs and reduced toxicity. Reports of significant numbers of successful solid-organ transplantations include those of the kidneys, liver, heart, and lung. The use of bone marrow transplantation for hematologic diseases, particularly hematologic malignancies and primary immunodeficiencies, has become the treatment of choice in many of these conditions. Other sources of hematopoietic stem cells are also being used, and diverse immunosuppressive drug regimens of reduced intensity are being proposed to circumvent the mortality associated with the toxicity of these drugs. Gene therapy to correct inherited diseases by means of infusion of gene-modified autologous hematopoietic stem cells has shown efficacy in 2 forms of severe combined immunodeficiency, providing an alternative to allogeneic tissue transplantation.


Etiology, Epidemiology, and Disparities in the Burden of Diabetic Foot Ulcers.
Diabetic foot ulcers (DFU) are a major source of preventable morbidity in adults with diabetes. Consequences of foot ulcers include decline in functional status, infection, hospitalization, lower-extremity amputation, and death. The lifetime risk of foot ulcer is 19% to 34%, and this number is rising with increased longevity and medical complexity of people with diabetes. Morbidity following incident ulceration is high, with recurrence rates of 65% at 3-5 years, lifetime lower-extremity amputation incidence of 20%, and 5-year mortality of 50-70%. New data suggest overall amputation incidence has increased by as much as 50% in some regions over the past several years after a long period of decline, especially in young and racial and ethnic minority populations. DFU are a common and highly morbid complication of diabetes. The pathway to ulceration, involving loss of sensation, ischemia, and minor trauma, is well established. Amputation and mortality after DFU represent late-stage complications and are strongly linked to poor diabetes management. Current efforts to improve care of patients with DFU have not resulted in consistently lower amputation rates, with evidence of widening disparities and implications for equity in diabetes care. Prevention and early detection of DFU through guideline-directed multidisciplinary care is critical to decrease the morbidity and disparities associated with DFU. This review describes the epidemiology, presentation, and sequelae of DFU, summarizes current evidence-based recommendations for screening and prevention, and highlights disparities in care and outcomes.


Cohen syndrome in the Ohio Amish.
We describe eight members from two large Amish kindreds who share a phenotype characterized by early-onset pigmentary retinopathy and myopia, global developmental delay and mental retardation, microcephaly, short stature, hypotonia, joint hyperextensibility, small hands and feet, common facial appearance, and friendly disposition. Several of the children had intermittent granulocytopenia. The phenotypic occurrence in three siblings coupled with the increased coefficient of inbreeding in the Amish suggested that this disorder is autosomal recessive and due to a single founder allele. Despite similarity to the clinical features of Cohen syndrome, experienced dysmorphologists attending the 23rd David W. Smith Workshop suggested the facial gestalt of the Amish children was inconsistent with this diagnosis. We mapped the locus responsible for these individuals' phenotype to chromosome 8q22-q23, which contains the recently discovered Cohen syndrome gene, COH1. Complete sequencing of the COH1 gene identified a likely disease-causing frameshift mutation and a missense mutation in the Amish patients. A comparison of features among different Cohen syndrome populations with shared linkage to the COH1 locus or known COH1 gene mutations may allow for the determination of improved clinical criteria on which to suspect the diagnosis of Cohen syndrome. We conclude that facial gestalt seems to be an unreliable indicator of Cohen syndrome between ethnic populations, although it is quite consistent among affected individuals within a particular ethnic group. Other features common to almost all individuals with proven COH1 mutations, such as retinal dystrophy, myopia, microcephaly, mental retardation, global developmental delay, hypotonia, and joint hyperextensibility appear to be better clinical indicators of this disorder.


Efficient processing of the immunodominant, HLA-A*0201-restricted human immunodeficiency virus type 1 cytotoxic T-lymphocyte epitope despite multiple variations in the epitope flanking sequences.
Immune escape from cytotoxic T-lymphocyte (CTL) responses has been shown to occur not only by changes within the targeted epitope but also by changes in the flanking sequences which interfere with the processing of the immunogenic peptide. However, the frequency of such an escape mechanism has not been determined. To investigate whether naturally occurring variations in the flanking sequences of an immunodominant human immunodeficiency virus type 1 (HIV-1) Gag CTL epitope prevent antigen processing, cells infected with HIV-1 or vaccinia virus constructs encoding different patient-derived Gag sequences were tested for recognition by HLA-A*0201-restricted, p17-specific CTL. We found that the immunodominant p17 epitope (SL9) and its variants were efficiently processed from minigene expressing vectors and from six HIV-1 Gag variants expressed by recombinant vaccinia virus constructs. Furthermore, SL9-specific CTL clones derived from multiple donors efficiently inhibited virus replication when added to HLA-A*0201-bearing cells infected with primary or laboratory-adapted strains of virus, despite the variability in the SL9 flanking sequences. These data suggest that escape from this immunodominant CTL response is not frequently accomplished by changes in the epitope flanking sequences.


Identification of 167 polymorphisms in 88 genes from candidate neurodegeneration pathways.
Catalogs of intra-gene polymorphisms are needed to facilitate wide-ranging candidate gene-based association studies in common complex diseases. With this in mind, we have scanned multiple alignments of expressed sequence tags and of genomic DNA sequences (PCR products from four to eight unrelated individuals) to find polymorphisms in 195 genes putatively involved in neurodegenerative illness (including components of oxidative stress, excitotoxicity, inflammation, apoptosis and aging). This led to the discovery of 167 polymorphisms in 88 genes. These comprised 163 single nucleotide polymorphisms, one insertion/deletion, and three other variations involving more than one base pair. The polymorphisms were distributed in the exons (87), introns (70), and gene flanking regions (10). Of the exonic polymorphisms, 17 would give rise to non-synonymous amino acid substitutions. These findings now provide a valuable resource for association studies in neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease.


Worsening calcification propensity precedes all-cause and cardiovascular mortality in haemodialyzed patients.
A novel in-vitro test (T50-test) assesses ex-vivo serum calcification propensity which predicts mortality in HD patients. The association of longitudinal changes of T50 with all-cause and cardiovascular mortality has not been investigated. We assessed T50 in paired sera collected at baseline and at 24 months in 188 prevalent European HD patients from the ISAR cohort, most of whom were Caucasians. Patients were followed for another 19 [interquartile range: 11-37] months. Serum T50 exhibited a significant decline between baseline and 24 months (246 ± 64 to 190 ± 68 minutes; p < 0.001). With serum Δ-phosphate showing the strongest independent association with declining T50 (r = -0.39; p < 0.001) in multivariable linear regression. The rate of decline of T50 over 24 months was a significant predictor of all-cause (HR = 1.51 per 1SD decline, 95% CI: 1.04 to 2.2; p = 0.03) and cardiovascular mortality (HR = 2.15; 95% CI: 1.15 to 3.97; p = 0.02) in Kaplan Meier and multivariable Cox-regression analysis, while cross-sectional T50 at inclusion and 24 months were not. Worsening serum calcification propensity was an independent predictor of mortality in this small cohort of prevalent HD patients. Prospective larger scaled studies are needed to assess the value of calcification propensity as a longitudinal parameter for risk stratification and monitoring of therapeutic interventions.


Adverse drug reaction monitoring of antidepressants in the psychiatry outpatients department of a tertiary care teaching hospital.
Depression is a prevalent mental disorder and the 4(th) leading cause of disability in the world as per the World Health Organization (WHO). The adverse Drug Reactions (ADRs) to antidepressants are common and they can lead to a non compliance or even a discontinuation of the therapy. This study entitled us to monitor the ADR profile of the antidepressants in a tertiary care teaching hospital. A longitudinal, observational study was conducted in the Outpatients Department of Psychiatry in S.C.B. Medical College and Hospital l in collaboration with the I.M.S and SUM Hospital. A total of 160 cases were studied for ADRs by using a predesigned CDSCO form. The patients who were on TCAs, SSRIs and newer antidepressants (SNRIs/NDRIs) were assessed by doing physical examinations, neurological examinations and relevant lab tests. The causalities were assessed by the criteria of the WHO-UMC. The analysis of ADRs was done by using the Chi square test. Among the 160 patients who took antidepressants, 26.87% reported ADRs, with at least one possible causality.None were labeled as certain, as a rechallenge was not performed.ADRs were mostly observed in polytherapy (14.37%) and with antidepressants like TCAs (58.84%). Agitation, anxiety and insomnia were the common ADRs which were associated with the use of antidepressants. This study offers a representative profile of the ADRs which can be expected in the Psychiatry Outpatients Department and due care must be taken to avoid these ADRs.


Damage formation and repair efficiency in the p53 gene of cell lines and blood lymphocytes assayed by multiplex long quantitative polymerase chain reaction.
We examined ultraviolet (UV) irradiation and cisplatin treatment damage formation and repair efficiency in the p53 tumor suppressor gene of various cultured cell lines and lymphocytes using a nonradioactive multiplex long quantitative polymerase chain reaction (QPCR) assay, which amplified a 7-kb fragment of the target gene and a 500-bp fragment of the template control to successfully increase the sensitivity and reliability of the assay. The multiplex long QPCR detected a lesion frequency of 0.63 lesions/10kb/10J/m(2) in the p53 gene of fibroblast cells. In addition, the multiplex long QPCR assay detected pronounced differences in the repair of UV damage in the p53 gene among repair-proficient CRL-1475 cells and repair-deficient XP-A and XP-C cells. The multiplex long QPCR assay was also evaluated as a sensitive assay for the detection of DNA damage induced by cisplatin. The data indicated that the lesion frequency in the p53 gene was 1.27-1.75 times higher in the H23 cisplatin-sensitive cell than in the H1435 cisplatin-resistant cell at the IC(70) dose. After 8-h and 24-h repair periods, only 13 and 75% of cisplatin-induced damage had been removed in the H23 cells, whereas these values were 92 and 100% in the H1435 cells. In addition, our data indicate that multiplex long QPCR is a sensitive method for validly estimating repair in freshly isolated lymphocytes. The results suggest that the current protocol of the multiplex long QPCR method can be used to assess the damage formation and repair efficiency of various agents at biologically relevant doses and to allow a more precise determination of gene-specific repair in disease susceptibility and drug resistance in epidemiological studies.


Local production of rotavirus specific IgA in breast tissue and transfer to neonates.
Rotavirus specific IgA, secretory component, and IgG were measured by enzyme linked immunosorbent assay in 20 pairs of mothers and babies to estimate antibody transfer from the mother, particularly from breast milk to neonatal faeces. Colostrum contained high titres of specific IgA and secretory component, which decreased gradually. Faeces after breast feeding for three days showed detectable titres of IgA and secretory component, with further increases by seven days. There was a positive correlation between titres of secretory component in breast milk and in faeces. To clarify the mechanism of high anti-rotavirus activity in breast milk, ratios of rotavirus specific IgA in maternal serum samples to breast milk were calculated and compared with those that were herpes simplex virus specific. Significantly higher concentrations were obtained for the herpes simplex virus specific samples, indicating that anti-rotavirus IgA is selectively produced in breast tissue.


External irradiation versus external irradiation plus endobronchial brachytherapy in inoperable non-small cell lung cancer: a prospective randomized study.
No randomized studies are available on the additional value of endobronchial brachytherapy (EBB) to external irradiation (XRT) regarding palliation of respiratory symptoms (RS). A prospective randomized study was initiated to test the hypothesis that the addition of EBB to XRT provides higher levels of palliation of dyspnea and other RS and improvement of quality of life (QoL) in patients with non-small cell lung cancer (NSCLC) with endobronchial tumour. Patients with previously untreated NSCLC, stages I-IIIb, WHO-performance status of 0-3 and with biopsy proven endobronchial tumour in the proximal airways were eligible. EBB consisted of two fractions of 7.5 Gy at 1 cm on day 1 and 8. XRT started at day 2. The XRT dose was 30 Gy (2 weeks) or 60 Gy (6 weeks). The EORTC QLQ-C30 and QLQ-LC13 were assessed before treatment and 2 weeks, 6 weeks, 3, 6 and 12 months after treatment. Re-expansion of collapsed lung was tested by the inspiratory vital capacity (IVC) and CT scan of the chest. Ninety-five patients were randomized between arm 1 (XRT alone) (n=48) or arm 2 (XRT+EBB) (n=47). The arms were well balanced regarding pre-treatment characteristics and QoL scores. The compliance for QoL-assessment was >90% at all times. No significant difference between the trial arms was observed with respect to response of dyspnea. However, a beneficial effect of EBB was noted concerning the mean scores of dyspnea over time (P=0.02), which lasted for 3 months. This benefit was only observed among patients with an obstructing tumour of the main bronchus. A higher rate of re-expansion of collapsed lung was observed in arm 2 (57%) compared to arm 1 (35%) (P=0.01). The inspiratory vital capacity (IVC) assessed 2 weeks after radiotherapy improved with 493 cm(3) in arm 2 and decreased 50 cm(3) in arm 1 (P=0.03). No difference was noted regarding the incidence of massive haemoptysis (13 vs. 15%). The addition of EBB to XRT in NSCLC is safe and provides higher rates of re-expansion of collapsed lung resulting in a transient lower levels of dyspnea. This beneficial effect was only observed among patients with obstructing tumours in the main bronchus.


Native oligodeoxynucleotides specifically active against human immunodeficiency virus type 1 in vitro: a G-quartet-driven effect?
Among a series of unmodified phosphodiester (PO)-oligodeoxynucleotides (PO-ODNs) complementary to some of the human immunodeficiency virus type 1 (HIV-1) regulatory genes, several PO-ODN sequences complementary to the vpr gene (PO-ODNs-a-vpr, where a-vpr is the antisense vpr sequence) emerged as potent inhibitors (at concentrations of 0.8 to 3.3 microM) of HIV-1 multiplication in de novo infected MT-4 cells, while they showed no cytotoxicity for uninfected cells at concentrations up to 100 microM. Unlike phosphorothioate counterparts, PO-ODN-a-vpr sequences were not inhibitory to HIV-2 multiplication in de novo infected C8166 cells and neither prevented the fusion between chronically infected and bystander CD4+ cells nor inhibited the activity of the HIV-1 reverse transcriptase in enzyme assays. Moreover, they were not inhibitory to HIV-1 multiplication in chronically infected cells. Delayed addition experiments showed that PO-ODNs-a-vpr inhibit an event in the HIV-1 replication cycle following adsorption to the host cell, but preceding reverse transcription. Structure-activity relationship studies indicated that the antiviral activity of the test PO-ODN-a-vpr sequences is not related to an antisense mechanism but to the presence, within the active sequences, of contiguous guanine residues. Physical characterization of the test PO-ODNs suggested that the active structure is a tetramer stabilized by G quartets (i.e., four G residues connected by eight hydrogen bonds).


World health organisation-international society of hypertension (WHO/ISH) hypertension guidelines.
Hypertension is now recognised as a very major contributor to disease burden globally. The close working relationship between the World Health Organisation (WHO) and the International Society of Hypertension (ISH) has existed for several decades and led to the production of a number of guidelines and statements. Since the publication of the 1999 WHO/ISH Guidelines for the Management of Hypertension, WHO determined in 2000 that in future the evidence base for all of its guidelines will be explicitly documented according to a defined methodology. In 2002 the World Health Report on Reducing Risks and Promoting Health Life documented the burden of disease (4.5%) related to blood pressure, and subsequently decided to establish comprehensive guidelines to help bring about a paradigm shift to a holistic multiple risk factor approach and facilitate policy development for implementation of population based strategies. ISH will be part of this process. The 2003 WHO/ISH Statement on Management of Hypertension focuses on key areas where new information has become available since the 1999 Guidelines, including establishment of thresholds and goals, treatment strategies and cost-effectiveness. It will be published in the Journal of Hypertension during 2003.


Advancing children's rights to be heard and protected: The model representation of children in abuse, neglect, and custody proceedings act.
Litigation surrounding family matters can have a significant impact on children well into their adult years. Because their interests may differ from those of their parents or other caretakers, it is crucial that the legal system provide a mechanism to ensure that children's interests are both protected by and appropriately communicated to the family court. The legal community has not reached a consensus regarding how children's interests can best be protected--or the appropriate role for attorneys involved in such cases. In fact, a number of professional organizations have proposed standards that impose differing obligations upon attorneys. In this article, the strengths and limitations of various practice standards are compared and contrasted, with the focus being on how children's interests can best communicated to, and protected by, the court.


A Pilot Study for Investigation of Plasma Amino Acid Profile in Neurofibromatosis Type 1 Patients.
Neurofibromatosis, also known as Von Recklinghausen disease, is a systemic and progressive genetic disease that primarily affects the skin, eyes, nervous system, and bones. The disease can occur in a variety of ways and can vary in individuals. Metabolomic-based research using blood samples has enabled new diagnostic methods to be used in the diagnosis of various diseases, especially cancer. Among the metabolites, profiling of plasma free amino acids (PFAA) is a promising approach because PFAAs bind all organ systems and play an important role in the metabolism. This study aimed to determine the characteristics of PFAA profiles in neurofibromatosis patients and the possibility of using them for early detection and treatment of the disease. Patients with a diagnosis of Neurofibromatosis Type I confirmed by genetic analysis and healthy individuals of the same age group without any disease were included in the study. We analysed the nineteen plasma free amino acids (phenylalanine, proline, threonine, arginine, asparagine, cystine, valine, glutamate, tyrosine, serine, glutamine, glycine, tryptophane, leucine, lysine, methionine, isoleucine, aspartate and alanine) from neurofibromatosis Type I patients and control group by liquid chromatography tandem mass spectrometry (LC-MS/MS) in Metabolism Laboratory of Harran University Research and Application Hospital. The results of the plasma free amino acid levels were divided into 3 groups as essential, semi-essential, and non-essential. The differences in amino acid levels between groups were determined. The levels of eight amino acids (methionine, arginine, cystine, glutamine, proline, asparagine, serine, aspartate) were significantly altered in patients with neurofibromatosis type 1. In essential amino acids, methionine levels were significantly higher in the patient group than control group. While the levels of arginine and glutamine in semi-essential amino acids were statistically significantly higher in the patient group, a significant decrease was observed in cystine and proline levels compared to the control group's amino acid levels. In the non-essential amino acids group, asparagine, serine and aspartate amino acid levels were significantly higher in the patient group compared to the control group. The current research predicates that eight amino acids, namely methionine, arginine, cystine, glutamine, proline, asparagine, serine, aspartate can be considered to be valuable biomarkers for neurofibromatosis type I. This present study is the first to build models for neurofibromatosis Type I screening using plasma free amino acids and the amino acid profile will be able to guide the prediction of the complications that may occur during the course of the disease.


A colloid model system for interfacial sorption kinetics.
Particle adsorption to an interface may be a complicated affair, motivating detailed measurements of various processes involved, to discover better understanding of the role of particle characteristics and solution conditions on adsorption coverage and rate. Here we use micron size colloids with a weak interfacial interaction potential as a model system to track particle motion and measure the rates of desorption and adsorption. The colloid-interface interaction strength is tuned to be less than 10 kBT so that it is comparable to many nanoscale systems of interest such as proteins at interfaces. The tuning is accomplished using a combination of depletion, electrostatic, and gravitational forces. The colloids transition between an entropically trapped adsorbed state and a desorbed state through Brownian motion. Observations are made using an light-emitting diode (LED)-based total internal reflection microscopy (TIRM) setup. The observed adsorption and desorption rates are compared to theoretical predictions based on the measured interaction potential and near-wall particle diffusivity. The results demonstrate that diffusion dynamics play a significant role when the barrier energy is small. This experimental system will allow for the future study of more complex dynamics such as nonspherical colloids and collective effects at higher concentrations.


Determination of proper band size for stainless steel crowns of primary second molars: A cross-sectional study.
Fixed space maintainers are often used following primary tooth loss. In this process, selection of a proper band size for stainless steel crowns (SSCs) is often performed by trial and error, which increases the chairside time and risk of contamination of the tried bands with saliva, blood, and gingival crevicular fluid, necessitating their subsequent sterilization. This study is aimed at determining the proper size of prefabricated bands for all SSCs of primary second molars. In this cross-sectional study, seven examiners, including three orthodontists and four pediatric dentists attempted to select the proper band size for 24 primary second molar SSCs (3M). They selected the proper band size for each size of SSC six times in three sessions. The significance of all selected choices was carried out using the test of proportions. The most commonly selected bands for EU2, EU3, EU4, EU5, EU6, and EU7 SSCs were sizes 31+, 32+, 34, 35+, 37, and 38, respectively, and the proper bands for EL2, EL3, EL4, EL5, EL6, and EL7 SSCs were sizes 30, 31+, 32+, 33+, 35 and 36+, respectively. The difference in the frequency ratio of different choices for all sizes of SSCs was significant (P < 0.05). The current study determined the proper band size for all SSCs of primary maxillary and mandibular second molars. This information can help dental clinicians in selecting the proper band size for SSCs without trial and error.


Recombinant DNA techniques. Basic concepts and practical applications in oral biology.
Advances in molecular biology and recombinant DNA technology, in particular, have provided researchers and diagnostic laboratories with powerful new tools enhancing understanding of biological events and aiding clinical laboratory diagnosis of many diseases (both genetic and those caused by infectious agents). The main applications of recombinant DNA technology at the moment include diagnosis of genetic disorders and microbiological infections, assessment of normal cell differentiation, and the molecular biology of tumours. In future, extensive correlation analyses of gene structure and expression with tissue morphology, clinical presentation and prognosis will also improve abilities to diagnose diseases of the oral cavity.


Physical fitness of secondary school adolescents in relation to the body weight and the body composition: classification according to Bioelectrical Impedance Analysis. Part II.
Underweight and obesity are important factors affecting the level of physical fitness. The aim of this study was to assess physical fitness of lower secondary school adolescents in relation to BMI. Two-hundred students, aged 14-16, were examined. Respondents were divided into 4 groups according to BMI classification. The body height and weight were determined. Physical fitness was assessed on the basis Zuchora's ISF tests. The body weight deficiency occurred in 3% of girls and 5% of boys, overweight was noted in 14% of both groups, and obesity in 6% and 12% accordingly. Statistically significant differences were determined in the components of physical fitness. They were noted in both genders between the group of children with standard body weight and overweight as well as obese children. Significant negative correlations were determined between and the components of physical fitness. More significant correlations giving evidence to the decrease of Zuchora's ISF score along with the increase of BMI were more significant in girls. Statistically significant differences between the boys and girls were determined in all five Zuchora's tests. The highest scores in physical fitness were achieved by the boys and girls with weight deficiency.


SARS-CoV-2 and human milk: What is the evidence?
The novel coronavirus SARS-CoV-2 has emerged as one of the most compelling and concerning public health challenges of our time. To address the myriad issues generated by this pandemic, an interdisciplinary breadth of research, clinical and public health communities has rapidly engaged to collectively find answers and solutions. One area of active inquiry is understanding the mode(s) of SARS-CoV-2 transmission. Although respiratory droplets are a known mechanism of transmission, other mechanisms are likely. Of particular importance to global health is the possibility of vertical transmission from infected mothers to infants through breastfeeding or consumption of human milk. However, there is limited published literature related to vertical transmission of any human coronaviruses (including SARS-CoV-2) via human milk and/or breastfeeding. Results of the literature search reported here (finalized on 17 April 2020) revealed a single study providing some evidence of vertical transmission of human coronavirus 229E; a single study evaluating presence of SARS-CoV in human milk (it was negative); and no published data on MERS-CoV and human milk. We identified 13 studies reporting human milk tested for SARS-CoV-2; one study (a non-peer-reviewed preprint) detected the virus in one milk sample, and another study detected SARS-CoV-2 specific IgG in milk. Importantly, none of the studies on coronaviruses and human milk report validation of their collection and analytical methods for use in human milk. These reports are evaluated here, and their implications related to the possibility of vertical transmission of coronaviruses (in particular, SARS-CoV-2) during breastfeeding are discussed.


Generation of a membrane potential by one of two independent pathways for nitrite reduction by Escherichia coli.
A set of four isogenic Escherichia coli strains has been constructed in which all possible combinations of NADH- and formate-dependent nitrite reductases are active or inactive. Each pathway can be inactivated genetically without a corresponding loss in the other activity: the two pathways are therefore biochemically independent. The generation of a membrane potential during nitrite reduction by formate has been demonstrated using an ion-selective electrode specific for a lipophilic cation. The observed energy conservation results, at least in part, from the ability of formate dehydrogenase in E. coli to pump protons.


Suppression of pro-inflammatory T-cell responses by human mesothelial cells.
Human γδ T cells reactive to the microbial metabolite (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP) contribute to acute inflammatory responses. We have previously shown that peritoneal dialysis (PD)-associated infections with HMB-PP producing bacteria are characterized by locally elevated γδ T-cell frequencies and poorer clinical outcome compared with HMB-PP negative infections, implying that γδ T cells may be of diagnostic, prognostic and therapeutic value in acute disease. The regulation by local tissue cells of these potentially detrimental γδ T-cell responses remains to be investigated. Freshly isolated γδ or αβ T cells were cultured with primary mesothelial cells derived from omental tissue, or with mesothelial cell-conditioned medium. Stimulation of cytokine production and proliferation by peripheral T cells in response to HMB-PP or CD3/CD28 beads was assessed by flow cytometry. Resting mesothelial cells were potent suppressors of pro-inflammatory γδ T cells as well as CD4+ and CD8+ αβ T cells. The suppression of γδ T-cell responses was mediated through soluble factors released by primary mesothelial cells and could be counteracted by SB-431542, a selective inhibitor of TGF-β and activin signalling. Recombinant TGF-β1 but not activin-A mimicked the mesothelial cell-mediated suppression of γδ T-cell responses to HMB-PP. The present findings indicate an important regulatory function of mesothelial cells in the peritoneal cavity by dampening pro-inflammatory T-cell responses, which may help preserve the tissue integrity of the peritoneal membrane in the steady state and possibly during the resolution of acute inflammation.


Nutrition in Patients with Lactose Malabsorption, Celiac Disease, and Related Disorders.
Lactose malabsorption (LM), celiac disease (CD), non-celiac gluten sensitivity (NCGS), and irritable bowel syndrome (IBS) are conditions associated with food triggers, improvement after withdrawal, treatment with dietary restriction, and subsequent nutritional detriments. LM occurs when there is incomplete hydrolysis of lactose due to lactase deficiency and frequently produces abdominal symptoms; therefore, it can cause lactose intolerance (LI). A lactose-restricted diet is frequently recommended, although it can potentially lead to nutrient deficiencies. Furthermore, lactose is an essential component of fermentable oligo-, di-, and monosaccharides and polyols (FODMAPs) and is subsequently associated with intolerance to these compounds, especially in IBS. LM commonly presents in CD. Nutritional deficits are common in CD and can continue even on a gluten-free diet (GFD). Conditions triggered by gluten are known as gluten-related disorders (GRDs), including CD, wheat allergy, and NCGS. IBS can also be associated with a gluten sensitivity. A GFD is the treatment for CD, GRDs, and gluten sensitive IBS, although compliance with this restricted diet can be difficult. Strict dietary therapies can have a negative effect on quality of life. This review aims to provide an overview of the difficult nutritional elements of these disorders, which are critical for medical providers to recognize when managing these patients.


Embolization of a ruptured pseudoaneurysm with massive hemorrhage following pancreas transplantation: a case report.
Pseudoaneurysm associated with an arterioenteric fistula is rare, but its clinical manifestations may represent a dramatic event that involves diagnostic and therapeutic problems. We report a case of an arterioduodenal fistula related to a ruptured pseudoaneurysm after simultaneous pancreas-kidney transplantation (SPK) with massive gastrointestinal hemorrhage treated by embolization of the Y graft. A 51-year-old man with type I diabetes and end-stage renal disease underwent SPK. No rejection episodes were documented; the patient was discharged with normal pancreatic and renal function. Two months later the patient was readmitted for an episode of massive lower digestive bleeding and hypotension. The Y-graft was embolized in order to obtain a prompt arrest of the bleeding. The procedure was successful and the patient progressively recovered. Once the hypovolemia was completely corrected, the graft was removed. An arterioenteric fistula between donor mesenteric artery and duodenum was confirmed. Few reports exist in the literature regarding the development of a pseudoaneurysm after pancreas transplantation. To our best knowledge only one case of pseudoaneurysm rupture into donor duodenum has been recently published. In our case angiography recognized the site of the pseudoaneurysm and its rupture into donor duodenum. Embolization of the Y-graft appeared the most rapid, simple, and safe approach to obtain the prompt arrest of the massive bleeding. Embolization of the Y-graft may represent a valid option in the presence of life-threatening hemorrhage.


The role of iron and myelin in orientation dependent R2* of white matter.
Brain myelin and iron content are important parameters in neurodegenerative diseases such as multiple sclerosis (MS). Both myelin and iron content influence the brain's R2* relaxation rate. However, their quantification based on R2* maps requires a realistic tissue model that can be fitted to the measured data. In structures with low myelin content, such as deep gray matter, R2* shows a linear increase with increasing iron content. In white matter, R2* is not only affected by iron and myelin but also by the orientation of the myelinated axons with respect to the external magnetic field. Here, we propose a numerical model which incorporates iron and myelin, as well as fibre orientation, to simulate R2* decay in white matter. Applying our model to fibre orientation-dependent in vivo R2* data, we are able to determine a unique solution of myelin and iron content in global white matter. We determine an averaged myelin volume fraction of 16.02 ± 2.07% in non-lesional white matter of patients with MS, 17.32 ± 2.20% in matched healthy controls, and 18.19 ± 2.98% in healthy siblings of patients with MS. Averaged iron content was 35.6 ± 8.9 mg/kg tissue in patients, 43.1 ± 8.3 mg/kg in controls, and 47.8 ± 8.2 mg/kg in siblings. All differences in iron content between groups were significant, while the difference in myelin content between MS patients and the siblings of MS patients was significant. In conclusion, we demonstrate that a model that combines myelin-induced orientation-dependent and iron-induced orientation-independent components is able to fit in vivo R2* data.


Proteomic profiling of yeast- and hyphal-specific responses of Candida albicans to the antifungal agent, HWY-289.
Virulence of Candida albicans is attributable to its unique dimorphic transition from nonpathogenic yeast cells to pathogenic hyphal cells. We previously discovered a novel antifungal agent, known as HWY-289. To characterize the mechanism underlying HWY-289 antifungal activity, we performed 2-DE to identify proteins that were differentially expressed during yeast-to-hyphal transition and in response to HWY-289. Twenty-four differentially expressed protein spots were identified in HWY-289-treated yeast. Most differentially expressed proteins were involved in carbohydrate-derived energy metabolism, cellular detoxification, and antioxidant defenses. Two proteins were involved in cell cycle regulation and DNA processing, and both were downregulated by HWY-289, suggesting that this agent might promote cell death by weakening cellular defense systems. HWY-289 inhibited yeast-to-hyphal transition in a dose-dependent manner. 2-DE analysis of hyphae uncovered several proteins that were induced during yeast-to-hyphal transition. Of these, aconitase and phosphatidylinositol transfer protein were downregulated by HWY-289, suggesting that they mediate the antifungal effects of HWY-289. Finally, RT-PCR analysis revealed that HWY-289 induced expression of three RAS-related genes (CcCST20, CaHST7, and CaCPH1) in yeast cells, but suppressed their expression in hyphae. Thus, the antifungal action of HWY-289 may be attributable to its ability to disrupt prohyphal RAS signaling.


Non-Invasive Imaging of Normalized Solid Stress in Cancers in Vivo.
The solid stress (SSg) that develops inside a cancer is an important marker of cancer's growth, invasion and metastasis. Currently, there are no non-invasive methods to image SSg inside tumors. In this paper, we develop a new, non-invasive and cost-effective imaging method to assess SSg inside tumors that uses ultrasound poroelastography. Center to the proposed method is a novel analytical model, which demonstrates that SSg and the compression-induced stress (SSc) that generates inside the cancer in a poroelastography experiment have the same spatial distribution. To show the clinical feasibility of the proposed technique, we imaged and analyzed the normalized SSg inside treated and untreated human breast cancers in a small animal model. Given the clinical significance of assessing SSg in cancers and the advantages of the proposed ultrasonic methods, our technique could have a great impact on cancer diagnosis, prognosis and treatment methods.


A system for cost and reimbursement control in hospitals.
This paper approaches the design of a regional or statewide hospital rate-setting system as the underpinning of a larger system which permits a regulatory agency to satisfy the requirements of various public laws now on the books or in process. It aims to generate valid interinstitutional monitoring on the three parameters of cost, utilization, and quality review. Such an approach requires the extension of the usual departmental cost and budgeting system to include consideration of the mix of patients treated and the utilization of various resources, including patient days, in the treatment of these patients. A sampling framework for the application of process-based quality studies and the generation of selected performance measurements is also included.


Cecropins contribute to Drosophila host defense against a subset of fungal and Gram-negative bacterial infection.
Cecropins are small helical secreted peptides with antimicrobial activity that are widely distributed among insects. Genes encoding Cecropins are strongly induced upon infection, pointing to their role in host defense. In Drosophila, four cecropin genes clustered in the genome (CecA1, CecA2, CecB, and CecC) are expressed upon infection downstream of the Toll and Imd pathways. In this study, we generated a short deletion ΔCecA-C removing the whole cecropin locus. Using the ΔCecA-C deficiency alone or in combination with other antimicrobial peptide (AMP) mutations, we addressed the function of Cecropins in the systemic immune response. ΔCecA-C flies were viable and resisted challenge with various microbes as wild-type. However, removing ΔCecA-C in flies already lacking 10 other AMP genes revealed a role for Cecropins in defense against Gram-negative bacteria and fungi. Measurements of pathogen loads confirm that Cecropins contribute to the control of certain Gram-negative bacteria, notably Enterobacter cloacae and Providencia heimbachae. Collectively, our work provides the first genetic demonstration of a role for Cecropins in insect host defense and confirms their in vivo activity primarily against Gram-negative bacteria and fungi. Generation of a fly line (ΔAMP14) that lacks 14 immune inducible AMPs provides a powerful tool to address the function of these immune effectors in host-pathogen interactions and beyond.


An optical method for serum calcium and phosphorus level assessment during hemodialysis.
Survival among hemodialysis patients is disturbingly low, partly because vascular calcification (VC) and cardiovascular disease are highly prevalent. Elevated serum phosphorus (P) and calcium (Ca) levels play an essential role in the formation of VC events. The purpose of the current study was to reveal optical monitoring possibilities of serum P and Ca values during dialysis. Twenty-eight patients from Tallinn (Estonia) and Linköping (Sweden) were included in the study. The serum levels of Ca and P on the basis of optical information, i.e., absorbance and fluorescence of the spent dialysate (optical method) were assessed. Obtained levels were compared in means and SD. The mean serum level of Ca was 2.54 ± 0.21 and 2.53 ± 0.19 mmol/L; P levels varied between 1.08 ± 0.51 and 1.08 ± 0.48 mmol/L, measured in the laboratory and estimated by the optical method respectively. The levels achieved were not significantly different (p = 0.5). The Bland-Altman 95% limits of agreement between the two methods varied from -0.19 to 0.19 for Ca and from -0.37 to 0.37 in the case of P. In conclusion, optical monitoring of the spent dialysate for assessing the serum levels of Ca and P during dialysis seems to be feasible and could offer valuable and continuous information to medical staff.