Effect of Bromelain-Based Enzymatic Debridement on Skin Cells.
Several reports have concluded that enzymatic debridement based on Bromelain (NX) is selective and efficient. Although clinical trials showed that viable tissue is not damaged at the macroscopic level, the effect on the cellular level is largely unknown. The current study is meant to close this gap by evaluating whether NX has an effect on vital cells of the human dermis on a cellular level. In an experimental in vitro study design, the effect of NX on human keratinocytes, fibroblasts, and macrophages was analyzed. Enzymatic treatment was performed for 4 hours by using either cell culture medium or phosphate-buffered saline as diluting agent for NX. Cell viability and relative cell number in relation to untreated control cells were determined using a resazurin-based assay. In addition, the development of enzyme activity during clinical treatment was analyzed: wound fluid collected from a burn wound at different points of debridement was applied on collagen-elastin disks to prove enzymatic digestion activity. Both keratinocytes and fibroblasts were damaged by NX even at low concentrations. Both cell types showed improved survival when a medium was used for dissolving NX. Macrophages appeared to resist NX treatment more efficiently than the other cell types. In the clinical trial, NX activity in the wound fluid decreased clearly following 4 hours of enzymatic debridement. NX induces toxicity of vital skin cells in vitro. However, macrophages appear to be more resistant against NX treatment in vitro. The inflammatory responses of vital cells in the burn wound itself are likely to inhibit NX activity. The effect of this inflammatory process on NX activity will have to be investigated in future studies.


Lichen planopilaris presenting as truncal alopecia: a case presentation and review of the literature.
Lichen planopilaris is an inflammatory condition of unknown etiology, characterized by violaceous folliculocentric papules and hair loss. Some clinicians consider lichen planopilaris to be a variant of lichen planus, but others believe it to be a separate disease entity. Many treatment modalities have been utilized, with varying degrees of success. We describe the case of a 63-year-old man who presented with widespread alopecia of the trunk and extremities and was subsequently diagnosed with lichen planopilaris.


Development of the M-SACRAH, a modified, shortened version of SACRAH (Score for the Assessment and Quantification of Chronic Rheumatoid Affections of the Hands).
The Score for the Assessment and Quantification of Chronic Rheumatoid Affections of the Hands (SACRAH) is a self-administered questionnaire assessing functional status, stiffness and pain in patients suffering from hand osteoarthritis (HOA) as well as rheumatoid arthritis (RA) of the hand. It consists of 23 questions in three domains, to be answered on 100 mm visual analogue scales (VAS). Our goal was to shorten the original SACRAH by elimination of redundant questions in order to make it easier to use for patients and physicians. Following an arbitrary procedure employing high intervariable correlations, redundant questions were eventually eliminated. To validate the shortened version, 60 patients with HOA, recruited at four rheumatological centres in Austria, completed the original SACRAH as well as the shortened version. Fifty-five patients suffering from RA of the hands treated at the Second Department of Medicine, Humanis Klinikum Stockerau, also completed both questionnaires. A total of 11 questions (nine from the function domain and two from the pain domain) were eliminated, leading to the modified score consisting of 12 questions. Comparing the results of SACRAH and M-SACRAH, as well as the domain scores in individual patients, correlation coefficients were r = 0.978 for HOA patients (P < 0.0001) and r = 0.986 for RA patients (P < 0.0001). M-SACRAH, the shortened and simplified version of the original SACRAH questionnaire, proved to be as reliable and as representative as SACRAH for hand status in individual HOA and RA patients.


Regulation of the choline, ethanolamine and serine base exchange enzyme activities of rat brain microsomes by phosphorylation and dephosphorylation.
The base exchange enzyme activities of rat brain microsomes were estimated subsequent to preincubations under conditions for either protein phosphorylation or dephosphorylation. Quantitatively the choline base exchange activity was most affected by these treatments. Exposure of the microsomes to alkaline phosphatase resulted in a decrease of all three base exchange activities. Pretreatment with a cAMP-dependent protein kinase resulted in increases of all 3 enzyme activities. Conditions favoring protein kinase C phosphorylation resulted in stimulation of the choline base exchange activity.


[Animal experiment study on intracranial pressure, after ketamine administration].
The action of ketamine on intracranial pressure in the presence of haemorrhagic shock, at both the dosage levels used for emergency cases and for in-patient treatment, was investigated using an animal model. Haemodynamically stable animals with a normal or raised intracranial pressure served as a control group. All animals were normoventilated. No rise in intracranial pressure was observed with either 0.5 or 2.0 mg/kg body weight of ketamine in those animals with normal, or in those with a raised pressure. This applied to both the haemodynamically stable animals, and to those in haemorrhagic shock. This finding is probably due to the fact that PCO2 levels did not rise under the controlled ventilation.


Overexpression of trypanosomal triosephosphate isomerase in Escherichia coli and characterisation of a dimer-interface mutant.
In this paper, the successful expression of trypanosomal triosephosphate isomerase (TIM) from Trypanosoma brucei brucei to high yield in Escherichia coli, using a T7-polymerase-based expression system, is described. Overexpressed trypanosomal TIM is fully active. The measured physicochemical properties of this recombinant TIM and TIM purified from trypanosomes are indistinguishable. Crystals of recombinant TIM have been grown in the presence of 2.4 M ammonium sulphate under the same conditions as for trypanosomally expressed TIM. The recombinant TIM crystal structure has been refined at 0.23 nm resolution; no differences were detected between this structure and the original crystal structure. A TIM mutant was made in which a unique dimer-interface histidine residue (His47) was changed into an asparagine. This variant ([H47N]TIM) could be expressed and purified to homogeneity by a procedure which was somewhat different from the purification of recombinant wild-type TIM. It is shown that the [H47N]TIM dimer is considerably less stable than wild-type trypanosomal TIM. The catalytic activity of [H47N]TIM is concentration dependent. The dilution-dependent inactivation is reversible. His47 is involved in a water-mediated hydrogen bond with Asp385 of the other subunit. The lower stability of the [H47N]TIM dimer implies that this water-mediated hydrogen bond is important for the stability of the TIM dimer.


Modulation of microtubule dynamics by the microtubule-associated protein 1a.
Structural microtubule-associated proteins (MAPs) interact with microtubules to regulate the various dynamic stages of microtubules. The purpose of this study was to measure the impact of myc-tagged MAP1a fragments on microtubule dynamic phases in vivo. Cells from an epithelial kidney cell line (LLCPK1) that had been permanently transfected with human green fluorescent protein (GFP)-alpha-tubulin were transiently transfected with myc-tagged MAP1a fragments. Cells expressing MAP1a fragments were used to make direct observations of microtubule dynamics in living cells using fluorescence microscopy. All truncated MAP1a heavy chain fragments that contained the microtubule-binding domain were shown to associate with microtubules. Truncated fragments containing different regions of the projection domain of MAP1a demonstrated variations in their impact on microtubule dynamic events by promoting growth or inhibition of shortening phases. In contrast to MAP1a, MAP2c bundled microtubules and resulted in a complete arrest of microtubule motility. Results from the present study suggest that MAP1a promotes slow, stable growth of microtubules. This type of growth may be important in the maintenance and restructuring of adult neurons.


Flow perfusion culture of human fetal bone cells in large beta-tricalcium phosphate scaffold with controlled architecture.
One unsolved problem in bone tissue engineering is how to enable the survival and proliferation of osteoblastic cells in large scaffolds. In this work, large beta-tricalcium phosphate scaffolds with tightly controlled channel architectures were fabricated and a custom-designed perfusion bioreactor was developed. Human fetal bone cells in third passage were seeded onto the scaffolds and cultured in static or flow perfusion conditions for up to 16 days. Compared with nonperfused constructs, flow perfused constructs demonstrated improved cells proliferation and differentiation according to cell viability, glucose consumption, alkaline phosphatase activity, and osteopontin. Moreover, after 16 days of perfusion culture, a homogenous layer composed of cells and mineralized matrix throughout the whole scaffold was observed by scanning electron microscopy and histological study. In contrast, cells were located only along the scaffold perimeter in static culture. These results demonstrated the feasibility and benefit of perfusion culture in conjunction with well-defined three-dimensional environment for large bone graft construction. Porous scaffold with controlled architecture can be a potential tool to evaluate the effects of scaffold specific geometry on fluid flow configuration and cell behavior under perfusion culture.


Open exchange as a model for continuing education.
The Global Nursing Exchange is a unique, annual opportunity for a select group of nurses to confer with each other and learn in an unstructured, nonrestrictive forum for free uncensored exchange of ideas. It is an unusual "conference" in that both the structure and process have been designed to encourage spontaneity, creativity, and group sharing. Relaxation and work comingle. Networking, dialog, and inclusiveness are operating themes at all times. Started in 1988 by 9 nurses with a mix of backgrounds and experience, the Global Nursing Exchange has expanded to include international participants. In 2003, over 60 nurses joined in celebrating the 15th year of this group gathering. Examples of outcomes that have resulted from this unique "conferencing" experience are described.


AIRE's CARD revealed, a new structure for central tolerance provokes transcriptional plasticity.
Developing T cells encounter peripheral self-antigens in the thymus in order to delete autoreactive clones. It is now known that the autoimmune regulator protein (AIRE), which is expressed in thymic medullary epithelial cells, plays a key role in regulating the thymic transcription of these peripheral tissue-specific antigens. Mutations in the AIRE gene are associated with a severe multiorgan autoimmune syndrome (APECED), and autoimmune reactivities are manifest in AIRE-deficient mice. Functional AIRE protein is expressed as distinct nuclear puncta, although no structural basis existed to explain their relevance to disease. In addressing the cell biologic basis for APECED, we made the unexpected discovery that an AIRE mutation hot spot lies in a caspase recruitment domain. Combined homology modeling and in vitro data now show how APECED mutations influence the activity of this transcriptional regulator. We also provide novel in vivo evidence for AIRE's association with a global transcription cofactor, which may underlie AIRE's focal, genome-wide, alteration of the transcriptome.


Langmuir-Blodgett Thin Films of Diketopyrrolopyrrole-Based Amphiphiles.
We report on two π-conjugated donor-acceptor-donor (D-A-D) molecules of amphiphilic nature, aiming to promote intermolecular ordering and carrier mobility in organic electronic devices. Diketopyrrolopyrrole was selected as the acceptor moiety that was disubstituted with nonpolar and polar functional groups, thereby providing the amphiphilic structures. This structural design resulted in materials with a strong intermolecular order in the solid state, which was confirmed by differential scanning calorimetry and polarized optical microscopy. Langmuir-Blodgett (LB) films of ordered mono- and multilayers were transferred onto glass and silicon substrates, with layer quality, coverage, and intermolecular order controlled by layer compression pressure on the LB trough. Organic field-effect transistors and organic photovoltaics devices with active layers consisting of the amphiphilic conjugated D-A-D-type molecules were constructed to demonstrate that the LB technique is an effective layer-by-layer deposition approach to fabricate self-assembled, ordered thin films.


Simultaneous detection of human bocavirus and adenovirus by multiplex real-time PCR in a Belgian paediatric population.
Since the discovery of human bocavirus (hBoV), the virus has been detected worldwide in respiratory tract samples from young children by various polymerase chain reaction (PCR) assays and real-time PCRs (Q-PCR). Until now, no data have been reported on the presence of hBoV in Belgium and the detection of hBoV in a multiplex Q-PCR setting has not been described. The aim of this study was to develop a fast and reliable multiplex Q-PCR for the simultaneous detection of hBoV DNA and adenovirus (AdV) DNA. During the winter of 2004-2005, 445 nasopharyngeal aspirates (NPAs) were analysed from 404 Belgian children up to 5 years old with acute respiratory tract infections (ARTIs). (Co)infections with hBoV, AdV, respiratory syncytial virus (RSV), human metapneumovirus (hMPV) and influenza A virus were investigated. A viral agent was detected in 61% (n = 272/445) of the NPAs. Multiplex Q-PCR found a prevalence of 11% (n = 51/445) hBoV and 13% (n = 58/445) AdV. Coinfections were more frequently found with AdV (62%; n = 36/58) than with hBoV (49%; n = 25/51). Follow-up samples were available from 22 patients with ARTIs. In three patients, hBoV DNA persisted for one month. Multiplex Q-PCR may help in closing the diagnostic gap by addressing a broader range of potential respiratory pathogens.


Clinical development of the STn-KLH vaccine (Theratope).
The development of active specific immunotherapy depends on the identification of altered cancer cell-specific molecules or epitopes that are immunogenic. Many cancer-specific peptide or glycoprotein target antigens have been identified. Tumors carrying aberrant epitopes as a result of underglycosylation of mucins are associated with poor prognosis in many epithelial cancers. The aberrant mucin sialyl-Tn (STn) epitope, in addition to being a predictor of poor prognosis when expressed in tumors, is associated with increased aggressiveness and metastatic potential, making it a promising target for immunotherapy. The STn-keyhole limpet hemocyanin (KLH) vaccine (Theratope) is an investigational active specific immunotherapy consisting of a synthetic STn epitope conjugated to a high molecular weight protein carrier, KLH. The immune response generated by the STn-KLH vaccine is both humoral and cellular. More than 1000 breast cancer patients with metastatic disease are currently enrolled in a phase III clinical trial to assess the safety and efficacy of the STn-KLH vaccine. Interim analysis from a current phase III trial has confirmed the safety of the STn-KLH vaccine, and the clinical outcome awaits the final analysis expected in 2003.


Persistence of Escherichia coli O157:H7 during pilot-scale processing of iceberg lettuce using flume water containing peroxyacetic acid-based sanitizers and various organic loads.
In order to minimize cross-contamination during leafy green processing, chemical sanitizers are routinely added to the wash water. This study assessed the efficacy of peroxyacetic acid and mixed peracid against E. coli O157:H7 on iceberg lettuce, in wash water, and on equipment during simulated commercial production in a pilot-scale processing line using flume water containing various organic loads. Iceberg lettuce (5.4kg) inoculated to contain 106CFU/g of a 4-strain cocktail of non-toxigenic, GFP-labeled, ampicillin-resistant E. coli O157:H7, was shredded using a commercial shredder, step-conveyed to a flume tank, washed for 90s using water alone or two different sanitizing treatments (50ppm peroxyacetic acid or mixed peracid) in water containing organic loads of 0, 2.5, 5 or 10% (w/v) blended iceberg lettuce, and then dried using a shaker table and centrifugal dryer. Thereafter, three 5.4-kg batches of uninoculated iceberg lettuce were identically processed. Various product (25g) and water (50ml) samples collected during processing along with equipment surface samples (100cm2) from the flume tank, shaker table and centrifugal dryer were then assessed for numbers of E. coli O157:H7. Organic load rarely impacted (P>0.05) the efficacy of either peroxyacetic acid or mixed peracid, with typical reductions of >5logCFU/ml in wash water throughout processing for all organic loads. Increases in organic load in the wash water corresponded to changes in total solids, chemical oxygen demand, turbidity, maximum filterable volume, and oxidation/reduction potential. After 90s of exposure to flume water, E. coli O157:H7 reductions on inoculated lettuce ranged from 0.97 to 1.74logCFU/g using peroxyacetic acid, with an average reduction of 1.35logCFU/g for mixed peracid. E. coli O157:H7 persisted on all previously uninoculated lettuce following the inoculated batch, emphasizing the need for improved intervention strategies that can better ensure end-product safety.


Is it Safe to Reduce Water Intake in the Overactive Bladder Population? A Systematic Review.
Overactive bladder imposes a significant socioeconomic burden on the health care system. It is a commonly held belief that increased fluid intake (8 glasses of water per day) is beneficial for health. However, increased fluid intake exacerbates overactive bladder symptoms. Thus, it is imperative that clinicians appropriately educate patients for whom increased water intake may be detrimental (women with overactive bladder), in contrast to patients with comorbidities that necessitate increased water intake (nephrolithiasis). We systematically reviewed the literature to determine the potential health advantages of increased water intake and identify specific subpopulations that need increased hydration. We systematically reviewed published articles from 1972 through 2017 on PubMed® and the Cochrane Library. The data were reviewed independently by 2 individuals. Studies were included if they explored water intake in relation to the risk of a particular disease. Level 1 evidence supported increased fluid intake in patients with nephrolithiasis. There was no available evidence to support increased fluid intake in patients with cardiovascular disease, constipation, venous thromboembolism, headaches, cognitive function or bladder cancer. Dehydration may exacerbate some conditions, specifically chronic constipation and headache intensity. Increased fluid intake may have a role in preventing stroke recurrence but not in preventing primary stroke. The available reviewed literature suggests no benefit to drinking 8 glasses of water per day in patients without nephrolithiasis. Also, excess fluid intake can exacerbate symptoms of overactive bladder.


[Dysenteric rheumatism. What remains in 1976?].
Joint manifestations that occur during or after an episode of dysentery, grouped under the name of dysenteric rheumatism, have been known since antiquity, and have been mainly found in military circles, in camps, or during military campaigns. After reviewing the principal epidemics of rheumatism complicated by joint manifestations, the authors show that the only different feature about what is called dysenteric rheumatism is the particular character of the joint manifestations which may be isolated or associated with other manifestations, notably ocular or urethral, forming then what is called the Fiessinger-Leroy-Reiter syndrome. The role of the dysentery bacillus in the genesis of the joint lesions is not clear. Although it may been suspected on the basis of epidemiological or bacteriological arguments in some cases, it has never been formally demonstrated and is often non-existent. The term dysenteric rheumatism is too restrictive and should henceforth be abandoned.


Binding and dissociation of cytochrome c to and from membranes containing acidic phospholipids.
Membrane association and detachment of cytochrome c (cyt c) in millisecond to second time domain were investigated by stopped-flow fluorescence spectroscopy monitoring the efficiency of energy transfer from a pyrene-fatty acid containing phospholipid derivative, 1-palmitoyl-2-[10-(pyren-1-yl)-decanoyl]-sn-glycero-3-phosphoglyce rol (PPDPG, mole fraction X = 0.01) to the heme of the cyt c. Large unilamellar liposomes composed of egg phosphatidylcholine (eggPC) with varying content of the acidic phospholipid phosphatidylglycerol (eggPG) were employed. Unexpectedly, the rate of binding of cyt c to membranes was attenuated upon increasing the mole fraction of the acidic phospholipid (XPG). For example, at 50 microM phospholipid and 5 microM cyt c, when XPG was increased from 0.20 to 0.40 the half-time for the single-exponential decay in fluorescence increased from 4.7 to 8.6 ms. A similar observation was made for the membrane binding of another cationic protein, histone H1. We suggest that the formation of cooperative hydrogen-bonded networks by deprotonated and protonated PG in the vesicle surface retards the binding of cyt c to the liposome surface. However, once formed, the complex of cyt c with acidic phospholipids is stabilized by increasing XPG. Accordingly, significantly prolonged half-times of dissociation of cyt c from liposomes by NaCl, ATP, and different cationic proteins are measured upon increasing XPG. Differences between the latter cationic membrane binding ligands most likely reflect the varying relative contributions of hydrophobicity and Coulombic forces to their attachment to liposomes. Our data on the release and binding of cyt c to liposomes as a function of XPG and in the presence of ATP also provide the first direct experimental evidence for multiple lipid binding sites in cyt c.


Drug resistance caused by reversion mutation.
Cells carrying mutated BRCA1 or BRCA2 genes are defective in DNA repair by homologous recombination and, as a consequence, are highly sensitive to inhibitors of poly (ADP-ribose) polymerase (PARP). This provides the basis for a novel "synthetic lethal" approach to cancer therapy. We have recently shown that this sensitivity can be reversed, and resistance to PARP inhibition can be acquired by deletion of a mutation in BRCA2. Furthermore, a similar mechanism seems to be associated with carboplatin resistance in some BRCA2 mutation carriers with ovarian cancer.


Case study: getting boards on board at Allen Memorial Hospital, Iowa Health System.
In 2005, the board of Allen Memorial Hospital, located in Waterloo, Iowa, in association with the leadership and medical staff, committed itself to the Institute of Health Care Improvement's 5 Million Lives Campaign interventions--Six Things All Boards Should Do to Improve Quality and Reduce Harm. (1) Setting an Aim; (2) Getting Data and Hearing Stories; (3) Establishing and Monitoring System-Level Measures; (4) Changing the Environment, Policies, and Culture; (5) Learning... Starting with the Board; and (6) Establishing Executive Accountability. For example, for intervention 3, the Allen board approved 10 clinical, evidence-based standards of care and 27 measures for monthly administrative and quarterly board review. A scorecard of these measures was developed to be presented as a handout at the meetings and to be displayed in poster size in each unit on a monthly basis. To make strides on these measures, rapid improvement teams were implemented, led by both a physician champion and a frontline clinical champion. Allen's rapid improvement teams have generated measurable success in quality and patient safety. The drive to excellence in clinical care was beginning to be "hard wired" into standard processes, monitoring systems, and periodic reviews. Processes were established to review every process failure and concern of the involved staff.


Hyperplasia and hypertrophy of chicken cardiac myocytes during posthatching development.
For characterization of the growth pattern of cardiac myocytes during posthatching development, cardiac myocytes were enzymatically isolated from the ventricles of 1-, 15-, 29-, and 42-day-old chickens for measurement of myocyte nucleation, length, width, volume, and number, and for immunolabeling of cytoskeletal proteins. Ventricular myocyte number increased 156% from day 1 to day 42. Average cell volume increased more than 400%, and myocytes lengthened 125%, but cell width only increased 53% during this period. All myocytes were mononucleated at day 1. At day 15, 18% of myocytes became binucleated with < 1% of myocytes containing more than two nuclei. Interestingly, binucleated myocytes were able to divide with two nuclei going through mitosis at the same time. As demonstrated by staining with tubulin and alpha-actinin antibodies, two mitotic spindles and two cleavage furrows were formed in dividing binucleated myocytes. At day 42, binucleated myocytes increased to 44% with 11% of myocytes containing more than two nuclei. Sarcomeric alpha-actinin was partially disassembled in prometaphase and was reorganized into regular Z lines of sarcomeres in telophase. Desmin was disassembled in prophase and was reassembled during late telophase. These results suggest that chicken myocytes undergo hypertrophy and continue to proliferate during posthatching maturation, although it is currently believed that myocytes of all vertebrates withdraw from the cell cycle shortly after birth. We provide direct evidence for the first time of in vivo myocyte division in 6-wk-old chicken hearts.


Characterization and functional analysis of a pollen-specific gene st901 in Solanum tuberosum.
A pollen-specific gene, sb401, which was isolated from a cDNA library of in vitro geminated pollen of the diploid potato species Solanum berthaultii, belongs to the class of genes expressed late during pollen development. Using sb401 as a probe, a pollen-specific gene st901 was isolated from the genomic library of a potato species Solanum tuberosum cv. Desiree. Sequencing and RT-PCR analysis showed that the st901 genomic gene is 2,889 bp long, contains three exons and two introns, and encodes a putative polypeptide of 217 residues. The predicted protein sequence contains four imperfect repeated motifs of V-V-E-K-K-N/E-E; the core sequence of the repeats (K-K-N/E-E) resembles a microtubule-binding domain of the microtubule-associated protein MAP1B from mouse. The examination of a promoter-reporter construct in transgenic potato plants revealed that the st901 is expressed exclusively in mature pollen grains, which is consistent with the results of Northern blot and RT-PCR. For analysis of the function of st901, transgenic plants harboring antisense copies of st901 cDNA driven by a native st901 promoter were generated. Suppression of st901 gene in potato resulted in aberrant pollen at maturation and pollen viability of transgenic plants ranged from 4.4 to 14.8%, while that of control plants were more than 90%. These results strongly suggest that st901 has an essential role in pollen development.


Blocked Ras activation in anergic CD4+ T cells.
T cell anergy is a state of functional unresponsiveness characterized by the inability to produce interleukin-2 (IL-2) upon T cell receptor stimulation. The mitogen-activated protein kinases ERK-1 and ERK-2 and the guanosine triphosphate-binding protein p21ras were found to remain unactivated upon stimulation of anergic murine T helper cell 1 clones. The inability to activate the Ras pathway did not result from a defect in association among Shc, Grb-2, and murine Son of Sevenless, nor from a defect in their tyrosine phosphorylation. This block in Ras activation may lead to defective transactivation at activator protein 1 sites in anergic cells and may enable T cells to shut down IL-2 production selectively during anergy.


The rise and fall of triple nucleoside reverse transcriptase inhibitor (NRTI) regimens.
Triple nucleoside reverse transcriptase inhibitor (NRTI) regimens have attracted much interest due to their potential to (1) simplify dosing, with potential gains in adherence to treatment, and (2) reduce or even reverse dyslipidaemia associated with protease inhibitor (PI) therapy. A variety of triple NRTI combinations have been investigated, in both antiretroviral-naive and antiretroviral-experienced HIV-infected patients. Many of these trials have generated disappointing results, and some have been prematurely discontinued due to poor efficacy. This article reviews the background to the development of triple NRTI regimens, and the mounting evidence that this approach is suboptimal for antiretroviral-naive patients. Indeed, some triple NRTI regimens should never be used in this population. A role for triple NRTI combinations as a simplification strategy in treatment-experienced patients whose HIV is well controlled has been suggested, but emerging evidence indicates that such an approach can, under adequate selection pressure, lead to the emergence of mutations and viral load rebound. This commentary discusses the factors that appear to influence patients' responses to triple NRTI therapy, and their implications for patient selection.


Surgical decompression for traumatic atlantoaxial subluxation in a weanling filly.
A filly with ataxia and splinting and crepitation in the neck was found to have atlantoaxial subluxation. Radiographic diagnosis was based on the same criteria as those used in other species, ie, increased distance between the atlas and spine of the axis and increased distance between the dens and floor of the atlas. Extensive hemilaminectomy was performed to decompress the spinal cord. Stabilization was not attempted. Immediate postoperative response was encouraging, but the untimely death of the filly prevented further evaluation of the procedure.


Serological surveillance of plague in dogs and cats, California, 1979-1991.
Following natural infection both cats and dogs develop antibodies to plague which can be measured for several months after infection. Besides being helpful in the diagnosis of plague in domestic carnivores, the antibody titer has important implications in outbreak investigation and surveillance programs. We report the first serological survey for plague in domestic carnivores conducted in California between 1979 and 1991 in five different settings or programs. A total of 4115 dogs and 466 cats were tested for plague antibody by the passive hemagglutination test. 86 dogs (2.09%) and 15 cats (3.22%) had plague antibody titers > or = 1:16. The percentage of positive dogs and cats were respectively 3.96% and 0% on reservations, 3.27% and 1.39% on military bases, 0.74% and 1.25% in Los Angeles County and 0% and 4.61% in veterinary clinics, but 41.38% and 41.2% from outbreak investigations. Titers ranged from 1:16 to 1:4096 in dogs and cats, but were low in dogs and cats in the Los Angeles County survey and on the military bases. Serologic testing of pets during human case investigation or increased rodent mortality should be regularly implemented, as well as dog surveys on reservations. Surveys of pet dogs in veterinary clinics did not appear worthwhile, even if selected from plague endemic regions. Veterinarians should report suspect cases in cats to public health authorities, that will improve plague surveillance and reduce the risk of humans contracting the disease from their pets.


Preoperative colour-coded duplex examination of the saphenopopliteal junction in recurrent varicosis of the short saphenous vein.
Undetected anatomical variations of the short saphenous vein are a major contributing factor to recurrent varicose veins in the saphenous vein area. Perioperative venography and varicography of the short saphenous vein have been proposed as a means of exact localization of its termination. The present study evaluated whether colour-coded duplex examination constituted a reliable alternative for localization of the saphenopopliteal junction. Between 1989 and 1990, 12 patients were reoperated on after previous classical ligation of the short saphenous vein. Preoperative colour-coded duplex examination revealed an abnormally high saphenopopliteal junction with persistent reflux in 11 patients and a Giacomini vein in one. When comparing these results with venographic and operative findings an accuracy of 100% was reached in these specific cases. It is concluded that for patients with recurrent varicosis of the short saphenous vein, preoperative colour-coded duplex examination provides a reliable non-invasive alternative to venography in the exact localization of the saphenopopliteal junction.


[Immunosenescence. Current status and molecular mechanisms].
One of the most important biological changes occurring during human aging is termed 'immunosenescence' characterized by a functional decline in immunity leading to a progressive immunodeficiency. Regulatory mechanisms also are diminished, leading to an inefficient and poorly controlled pro-inflammatory activation of the immune response. This increases the risk for disorders such as infectious, autoimmune, neoplastic, cardiovascular and neurodegenerative disease. Many of these entities are quite relevant for dermatology. Hence, immunosenescence constitutes a pathologic process contributing to morbidity and mortality of important clinical relevance in an aging population. Investigation of the underlying pathomechanisms and the application of modern mechanism-directed therapy offer many opportunities for a targeted modulation and "rejuvenation", thus indicating possible targets for the reduction of age-associated morbidity and mortality. Some promising targeted 'molecular' therapies are already currently being used in the context of other diseases, also in the field of dermatology.


Voice parade procedures: optimising witness performance.
Unfamiliar voice identification is error-prone. Whilst the investigation of system variables may indicate ways of boosting earwitness performance, this is an under-researched area. Two experiments were conducted to investigate how methods of presenting voices during a parade affect accuracy and self-rated confidence. In each experiment participants listened to a target voice, and were later asked to identify that voice from a nine-person target present or target absent parade. In Experiment 1, accuracy did not vary across parades comprising 15 or 30 s sample durations. Overall, when the target was present, participants correctly identified the target voice with 39% accuracy. However, when the target was absent, participants correctly rejected the parade 6% of the time. There was no relationship between accuracy and confidence. In Experiment 2, performance with a serial procedure, in which participants responded after hearing all nine voices, was compared with a sequential procedure, in which participants made a decision after listening to each voice. Overall accuracy was higher with the sequential procedure. These results highlight the importance of system variable research in voice identification. Different methods of presenting voices have the potential to support higher levels of accuracy than the procedure currently recommended in England and Wales.


The molecular interactions of organic compounds with tire crumb materials differ substantially from those with other microplastics.
Tire materials are the most commonly found elastomers in the environment and they account for a significant fraction of microplastic pollution. In the discussions on the environmental impact of microplastics tire materials and their sorption properties have been largely overlooked. In this study we used experimental sorption data from six organic probe sorbates sorbing to two tire materials and their major components, styrene butadiene rubber and carbon black, to gain a better understanding of the underlying sorption processes of tire materials. Commonly applied models used to describe non-linear sorption processes were unable to fully explain sorption to tire materials but showed that absorption into the rubber fraction dominated the sorption process. Hydrophobicity was approximated using the hexadecane-water partitioning constant, which correlated very well with the distribution data obtained for styrene rubber, whereas the correlations between hydrophobicity of sorbates and the sorption data to the tire materials were poor. Although hydrophobicity plays an important role in sorption to tire materials, additional interactions must be taken into account. Overall, the processes involved in sorption to tire materials differed significantly from those governing sorption to other microplastics.


Progress in the Use of Autologous Regenerative Platelet-based Therapies in Implant Dentistry.
The field of medicine is rapidly moving towards the development of personalized treatments and non-invasive tools to achieve a more predictable and optimal tissue regeneration. In this sense, the goal of periodontal healing is to arrest disease progression and functionally regenerate all the tissues that comprise the periodontium. The latter implies a well-orchestrated interaction among oral cells, growth factors and extracellular matrix. Although several procedures are performed in an attempt to regenerate lost periodontal tissue, outcomes are not always predictable. Growth factors represent a class of biologically active polypeptides that have a critical role in the healing process. Their use provides a new paradigm to understand the regenerative medicine. The use of platelet- rich plasma (PRP) products as a local source and delivery system of autologous growth factors has emerged recently. Among them, PRGF stands for its remarkable stimulatory effect on oral tissue regeneration, making it a very safe and successful tool with a great value in Dentistry.


HIFU for Palliative Treatment of Pancreatic Cancer.
Pancreatic cancer is one of the deadliest malignancies, with only a 6 % 5-year survival rate and over 50 % of patients being diagnosed at the advanced stage. Current therapies are ineffective, and the treatment of patients with advanced disease is palliative. In the past decade, HIFU ablation has emerged as a modality for palliative treatment of pancreatic tumors. Multiple preclinical and non-randomized clinical trials have been performed to evaluate the safety and efficacy of this procedure. Substantial tumor-related pain reduction was achieved in most cases after HIFU treatment and few significant side effects were observed. In addition, some studies indicate that combination of HIFU ablation with chemotherapy may provide a survival benefit. This chapter summarizes the pre-clinical and clinical experience obtained to date in HIFU treatment of pancreatic tumors and discusses the challenges, limitations and new approaches in this modality.


An unusual case of undifferentiated carcinoma in situ with osteoclast-like giant cells of the pancreas.
We report an unusual case of undifferentiated carcinoma in situ with osteoclast-like giant cells (UC with OGCs) in a 68-year-old Japanese woman. Preoperative examinations revealed an unidentifiable mass lesion within the main pancreatic duct (MPD) in the pancreatic head, accompanied by a dilated MPD distal to the mass lesion, which was suspected to be an intraductal papillary-mucinous neoplasm of the main-duct type with acute pancreatitis because of an increased serum amylase level. A pancreaticoduodenectomy was performed. A pencil-like tumor occupied the lumen of the MPD of the pancreatic head without a visible pancreatic parenchymal mass. The intraductal tumor included a sheet of spindle cells intermingled with scattered OGCs and pleomorphic giant cells. A poorly developed glandular pattern was occasionally observed at the tumor periphery. These findings were consistent with conventional UC with OGCs. However, extraductal invasion was not found in an extensive histopathologic examination, although focal intraductal spreading into the epithelium of the first branch of the MPD was observed. Undifferentiated carcinoma with OGCs usually exhibits an invasive tumor at diagnosis and is associated with a poor outcome, but the patient is alive without recurrence 22 months after surgery. To our knowledge, this is the first reported case of UC in situ without evident extraductal invasion in English literature.


A novel type of PTD, common helix-loop-helix motif, could efficiently mediate protein transduction into mammalian cells.
Protein transduction domains (PTDs), such as HIV TAT PTD, have been widely used as delivery tools into living cells. Here we reported for the first time that the helix-loop-helix (HLH) domain of basic helix-loop-helix (bHLH) family was a novel type of PTD. Efficient internalization has been obtained with HLH domains derived from bHLH proteins, NeuroD/BETA2, Neurogenin3, and Mitf, in various cell types including stable cell lines and primary cells. Cellular uptake of HLH PTD was barely or slightly inhibited by the metabolic, phagocytosis, clathrin- or caveolar-endocytosis formation inhibitors, but significantly and substantially reduced by heparin and macropinocytosis inhibitor, which suggested important roles of cell surface glycosaminoglycans and macropinocytosis during the protein transduction. Furthermore, NeuroD proteins still preserved transcription activation after internalized into cells. Our results demonstrated a new motif of PTD different from previous models as cationic residues cluster or amphipathic helix. The HLH domain is also the characteristic of the bHLH family, which implied a large number of PTDs could be discovered in this family to fit different purposes, and some of them could be directly recruited to penetrate cell membrane according to their crucial roles in development such as NeuroD and Ngn3.


The Digital Cytocochleogram.
The Mouse Cochlea Database (MCD) is a collection of resources that include digital images and bibliographic information on the mouse cochlea and is available at: http://mousecochlea.ccgb.umn.edu. The purpose of this communication is to report on the development of one MCD resource: the Digital Cytocochleogram. A cytocochleogram is a graphic representation of the anatomical state of the hair cells along the complete width and length of the organ of Corti. The Digital Cytocochleogram provides Internet users with a complete collection of digital images of one or more surface preparations of the mouse organ of Corti from which morphometric information can be obtained. By moving a mouse driven, screen cursor over a digital image, the location and approximate frequency region of the anatomical structure is displayed. Users can also measure the straight-line distance between any two structures on the image. The Digital Cytocochleogram resource uses two software programs, the Coordinate Finder and Viewer, which are written as CGI scripts. The Coordinate Finder program maps each digital image to an X,Y coordinate system. The total length of the organ of Corti from all tissue segments is computed using an arc-distance approximation formula, with the lateral border of the inner pillar cell headplates serving as a trace line or reference location. After all of the digital images of the tissue segments are mapped, they are placed on the MCD Website where users can use the Viewer program to view and morphometrically assess structures using a web browser. A single, complete surface preparation from a normal mouse is presently available on the MCD website. As the MCD grows, additional images of surface preparations at different magnifications from normal, mutant, and experimentally altered mouse cochleas will become available.


Evidence for capitation reform in a New Rural Cooperative Medical Scheme in Pudong New Area, Shanghai: A longitudinal study.
Currently, China has been experiencing rapid growth of medical costs, serious waste of medical resources, increasing disease burden for residents, and a medical insurance fund deficit. Therefore, an urgent problem that needs to be solved is to choose a rational payment for the insurance system. To empirically evaluate the long-term effects of capitation reform in a New Rural Cooperative Medical Scheme in Pudong New Area, we collected and analysed data regarding financing, fund operation, medical service cost, and medical care-seeking behaviour from 2011 to 2015, a duration that includes data before and after reform. The data for financing and behaviours were compared year by year, and the monthly data for inpatient and outpatient costs were evaluated in a retrospective time series study. The capitation reform in Pudong New Area showed strong evidence of the power of medical cost control in the long run, while it was weak in reversing the number of patients flowing into secondary and tertiary hospitals. To make the payment of capitation play a bigger role in cost control in China, a tighter alignment of capitation with the general practitioner system and achieving dual referral is critical for future studies.


Long-term therapy with rifampin and the secondary antibody response to killed influenza vaccine.
The secondary antibody response was studied in 22 patients with tuberculosis, 11 of whom were taking rifampin as part of their antituberculous regimen. The mean duration of rifampin therapy was 12.7 months. Hemagglutination-inhibiting antibody titers to bivalent influenza vaccine were determined before, and 4 and 8 weeks after, vaccination. There was no significant difference in the number of patients who developed a 4-fold or greater increase in titer, or in the level of titer response between the rifampin and control groups. Long-term therapy with rifampin was not found to suppress the secondary antibody response to influenza vaccination.


A Fully Implantable Stimulator With Wireless Power and Data Transmission for Experimental Investigation of Epidural Spinal Cord Stimulation.
Epidural spinal cord stimulation (ESCS) combined with partial weight-bearing therapy (PWBT) has been shown to facilitate recovery of functional walking for individuals after spinal cord injury (SCI). The investigation of neural mechanisms of recovery from SCI under this treatment has been conducted broadly in rodent models, yet a suitable ESCS system is still unavailable. This paper describes a practical, programmable, and fully implantable stimulator for laboratory research on rats to explore fundamental neurophysiological principles for functional recovery after SCI. The ESCS system is composed of a personal digital assistant (PDA), an external controller, an implantable pulse generator (IPG), lead extension, and stimulating electrodes. The stimulation parameters can be programmed and adjusted through a graphical user interface on the PDA. The external controller is placed on the rat back and communicates with the PDA via radio-frequency (RF) telemetry. An RF carrier from the class-E power amplifier in the external controller provides both data and power for the IPG through an inductive link. The IPG is built around a microcontroller unit to generate voltage-regulated pulses delivered to the bipolar electrode for ESCS in rats. The encapsulated IPG measures 22 mm × 23 mm × 7 mm with a mass of ∼ 3.78 g. This fully implantable batteryless stimulator provided a simplified and efficient method to carry out chronic experiments in untethered animals for medical electro-neurological research.


General practice supervision at a distance--is it remotely possible?
The Remote Vocational Training Scheme (RVTS) trains GPs while in solo rural or remote practice. General practice registrars choose an experienced rural or remote practitioner as their distant supervisor. During a teacher training telephone tutorial series RVTS general practice supervisors discussed the unique features of this model of general practice training, and shared their perspectives on how to make this distance supervision effective. This paper outlines the unique qualities of general practice registrars, the registrar-supervisor relationship and the content of tutorials, in the context of remote supervision. This paper suggests ways to provide educational support despite geographical distance. Experienced rural and remote GPs can provide effective supervision at a distance. The RVTS provides an innovative, alternative model for training GPs for rural and remote practice. Further qualitative research on this topic is required.


Hydrothermally synthesized Copper Oxide (CuO) superstructures for ammonia sensing.
According to environmental protection agencies (EPA), the emission threshold of NH3 in air is 1000kg/yr which is now about 20Tg/yr. Hence, there is a rapid increase in need of NH3 sensors to timely detect and control NH3 emissions. Metal oxide nanostructures such as CuO with special features are potential candidates for NH3 sensing. In the present study, morphology controlled 3-dimensional CuO superstructures were synthesized by surfactant-free hydrothermal method for NH3 detection. In addition to conventional hydrothermal method where water as solvent, a modified approach using a mixture of water and ethylene glycol (EG) was used as solvent to control the growth process. Hierarchical superstructures namely, snowflake-like, flower-like, hollow-sphere-like and urchin-like feature with particle dimensions ranging from 0.3 to 1μm were obtained by varying water/EG ratio and reaction temperature. The synthesized nanostructures exhibited morphology dependent luminescence and gas sensing properties. The surface area and pore distribution determined by BET surface analysis also largely influenced by the presence of EG in the reaction system. The average pore diameter enhanced from 6nm to 14nm by the addition of 10ml EG as solvent. The room temperature ammonia sensing behavior of all samples was studied using an indigenous gas sensing set-up. It was found that hollow-sphere like CuO nanostructures showed a maximum sensitivity of 150% towards 600ppm ammonia with a response and recovery time of 6min. The hydrothermal synthesis strategy reported here has the advantage of producing shape controlled hierarchical materials are highly suitable for various technological applications.


Solving DNA structures by MERLOT.
MERLOT, a molecular replacement computer package, has been successfully used for the determination of initial phases for five different oligonucleotide structures. Two of these, CCGG and CGCGCGTTTTCGCGCG, with 316 and 323 non-H atoms respectively in the asymmetric unit, have been solved ab initio using the MERLOT package. The rest are re-examinations of previously solved DNA oligomer structures, ioCCGG, CGCGAATTCGCG and CGCGAATTbrCGCG, with 160, 486 and 488 non-H atoms in the asymmetric unit respectively. Problems involved in applying the molecular-replacement technique to DNA structures, and their possible solutions, are discussed.


Improving access to pediatric health care in Mississippi.
Working under the Mississippi Postneonatal Death Impact Project, the Mississippi Chapter of the American Academy of Pediatrics, in conjunction with the State Department of Health, helped improve access to pediatric health care in Mississippi. This was accomplished by developing a statewide telephone information and referral service (telephone case management), enlisting primary care physicians to treat a limited number of children without specific compensation and staging a public awareness campaign. System barriers encountered were identified and interagency coordination and cooperation suggested. This effort could be easily replicated and expanded.


Effect of chronicity of infection on the sensitivity of the In-111-labeled leukocyte scan.
This study was undertaken to determine the effect of chronicity of infection on the sensitivity of In-111-labeled leukocyte scanning. A total of 332 scans on 290 patients were reviewed retrospectively. The diagnosis of infection was based on culture results and other laboratory data, autopsy findings, radiographic studies, and clinical course. Duration of infection at the time of scanning was determined by the date of onset of fever and symptoms, elevation of white cell count, positive cultures, and abnormal findings on radiographic studies. Sensitivity of leukocyte scanning was 90% for 69 patients who had infections for 0-14 days and 86% for 86 who had infections for 15 days or longer. This difference is not statistically significant.


[Screening for low-density lipoprotein receptor gene mutations in familial hypercholesterolemia Chinese].
To screen the mutations of low-density lipoprotein receptor (LDLR) gene in Chinese familial hypercholesterolemia (FH) patients. 7 patients with clinical phenotype of homozygous FH and their parents were investigated for mutations in all the eighteen exons of LDLR gene. Screening was carried out using PCR-SSCP and direct DNA sequencing and LDLR gene mutation database was searched to identify the alteration. In addition, the apolipoprotein B gene (apo B) was screened for known mutations (R3500Q) that caused familial defective apo B100 (FDB) with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Nine mutations in the LDLR gene were identified in the FH patients. All the mutations except C255R have not been published in the LDLR gene mutation database. No mutation of apo B100 (R3500Q) was observed. Chinese FH patients may have specific spectrum and regional difference of LDLR gene mutations. Apolipoprotein B-100 gene mutation might not be the main cause of hypercholesterolemia patients in China.


Molecular dynamics simulation of the LOV2 domain from Adiantum capillus-veneris.
The mechanism for signal transduction from the LOV-domains toward the kinase region of phototropin is still not well understood. We have performed molecular dynamics (MD) simulations and CONCOORD calculations on the LOV2 domain of Adiantum capillus-veneris, with the goal to detect possible differences between the two forms of the LOV domain which may not show up in the static crystal structures. Since no such clear differences are found in the MD simulations also, we suggest that the real, biologically active conformation of the LOV domain within the whole phototropin is different from the crystal structure of the isolated LOV domains. The MD simulations do offer, however, insight into details of the dynamics of the dark and illuminated LOV domains, which are discussed in the light of recent experiments.


Bariatric surgery, hyperoxaluria, and nephrolithiasis: a plea for close postoperative management of risk factors.
Hyperoxaluria contributes significant risk for kidney stone development. It can result from disordered metabolism, excessive intake of oxalate or other nutrients, or alterations of bowel flora and function. Sinha et al. show that individuals undergoing Roux-en-Y bypass have high rates of stone disease, both before and after their procedure. Whether or not the incidence of stone events is increased after surgery, hyperoxaluria should be addressed. After Roux-en-Y, it is important for patients to maintain high urine outputs, to limit fat intake, and to ingest adequate amounts of calcium.


Characterization of the cytopathic effect of Haemophilus ducreyi.
Haemophilus ducreyi is the etiologic agent of chancroid, which is a genital ulcer disease that increases the risk of acquiring and transmitting HIV. The pathogenesis of H. ducreyi is not well understood. The goal of this study was to use a quantitative tetrazolium-based XTT assay to characterize the cytopathic effect of H. ducreyi on human foreskin fibroblasts. Haemophilus ducreyi strains 35000, R018, A77 and CIP542 were evaluated using the XTT assay. The role of attachment on resultant CPE was assessed using a wash step 2 hours post-infection. Internalization was evaluated by the gentamicin kill assay. Secreted exotoxin was studied using permeable inserts to separate the bacteria from the HFF monolayer. HFF cell damage did not appear to be mediated by a secreted H. ducreyi cytotoxin. Direct contact of viable H. ducreyi with HFF cells was required for cell damage. H. ducreyi strains that attached poorly could be readily removed by a wash step. This reduced their capacity to damage HFF cells significantly. Although some H. ducreyi strains attach to high levels within 4 hours, no HFF cell damage was detected by the XTT assay. However, once HFF cell damage was detected by 24 hours, it was not easily reversible, despite antibiotic treatment that eradicated H. ducreyi. Internalization of H. ducreyi by HFF cells apparently did not occur to a significant degree. This study indicates that classic "soluble exotoxins" are not likely the key component in H. ducreyi pathogenesis. Attachment or direct contact with HFF cells are required for H. ducreyi to cause a CPE.


Using the protein chip interface with quadrupole time-of-flight mass spectrometry to directly identify peaks in SELDI profiles--initial evaluation using low molecular weight serum peaks.
Mass spectrometric profiling, particularly in the form of SELDI, has been used in many studies, particularly in attempts to generate diagnostic serum profiles. Several studies have generated promising results but one of the limitations is the inability to identify easily potential discriminatory peaks. This may enable specific assays to be developed and increased biological insight. We describe the first systematic technical evaluation of the ProteinChip interface coupled to a tandem mass spectrometer which allows direct sequencing of peptides <6000 Da, and describe the direct sequence identification of 21 peaks commonly observed in serum samples. Additionally we describe for the first time the use of on-chip acetylation to assist in the validation of sequence identification.


In vitro activity of three new triazoles and one echinocandin against Candida bloodstream isolates from cancer patients.
The in vitro activities of voriconazole, posaconazole, ravuconazole and micafungin were compared with those of fluconazole, itraconazole, ketoconazole, flucytosine and amphotericin B against 164 candidaemia isolates recovered from cancer patients in two Canadian centres. The MIC(50) results for ravuconazole, voriconazole, posaconazole and micafungin were 0.01, 0.03, 0.12 and 0.25 mg/L, respectively. The new antifungal agents showed substantial activity against isolates demonstrating in vitro resistance to fluconazole and itraconazole. These results suggest that the newer antifungal agents possess promising activity against invasive Candida isolates, particularly against those with reduced susceptibility to fluconazole and itraconazole.


Factors determining the blood pressure response to enalapril and nifedipine in hypertension associated with NIDDM.
To examine the factors that determine the blood pressure response to enalapril and nifedipine monotherapy in the treatment of hypertension associated with non-insulin-dependent diabetes mellitus (NIDDM). After a 6-week placebo baseline period, 102 hypertensive NIDDM patients were randomly assigned, double-blindly, to treatment with nifedipine retard (slow release) (n = 52) or enalapril (n = 50). The daily dosage of enalapril was increased, if required, from 10 to 20 to 40 mg and that of nifedipine from 40 to 60 to 80 mg at 4-week intervals during the 12-week titration period. Blood pressure, 24-h urinary albumin excretion (UAE), biochemical data, and serum angiotensin-converting enzyme (ACE) activity were measured at weeks -6, -4, 0, 4, 8, and 12. At week 0, venous blood was also sampled for baseline plasma atrial natriuretic peptide, renin, aldosterone, and serum insulin concentrations. At week 12, the mean daily dose of enalapril was 35 +/- 11.4 mg, and 27 (57%) patients were receiving the maximum daily dose of 40 mg. In the nifedipine group, the mean daily drug dose was 50 +/- 12.9 mg, and 4 (8%) were receiving the maximum daily dose of 80 mg. Despite a dose-dependent fall in the serum ACE activity in the enalapril group, the mean arterial pressure (MAP) was reduced by only 8 mmHg throughout the 12-week titration period compared to a decline of 15, 18, and 19 mmHg at weeks 0, 4, and 12, respectively, in the nifedipine group (P = 0.01 between groups). In the enalapril group, changes in MAP between weeks 0 and 12 correlated significantly with baseline plasma glucose (r = 0.45, P = 0.001) and aldosterone concentrations (r = -0.32, P = 0.02) and UAE (r = 0.3, P = 0.04). There was no statistically significant correlation between the changes in MAP and baseline plasma renin concentration. On multivariate analysis, the baseline renal function, glycemic control, and plasma aldosterone and serum insulin concentrations were all independently related to the changes in blood pressure in the enalapril-treated patients. No such statistical associations were observed in the nifedipine group. In hypertensive NIDDM patients, the activity of the renin-angiotensin-aldosterone system, the level of serum insulin, glycemic control, renal function, and proteinuria may be important determinants of the blood pressure response to ACE inhibition. Good glycemic control may optimize the antihypertensive efficacy of concomitant ACE inhibitor therapy.


Sulfated galactans from Australian specimens of the red alga Phacelocarpus peperocarpos (Gigartinales, Rhodophyta).
Polysaccharides from the red alga Phacelocarpus peperocarpos were extracted with hot water, clarified, and precipitated with 2-propanol. The native preparation was highly sulfated (36.2% w/w). Alkali modification decreased the sulfate content by 2.0% w/w. The alkali-modified polysaccharide is composed mostly of galactose (Gal. 51 mol%) and 3,6-anhydrogalactose (AnGal, 41 mol%), with minor amounts of a mono-O-methylgalactose (MeGal, 1 mol%), xylose (Xyl, 6 mol%), and glucose (Glc, 1 mol%). The FTIR spectrum of the alkali-modified polysaccharide resembled kappa-carrageenan with absorption at 930 cm-1 (indicative of AnGal) and 850 cm-1 (Gal 4-sulfate). However, an additional, major band of absorption occurred sulfate ester substitution at O-6 of at 820 cm-1, indicating the presence of equatorial sulfate ester substitution at O-6 of Gal residues. A combination of linkage and 13C NMR spectroscopic analyses showed that the polysaccharide was composed predominantly of a novel repeating-unit, O-beta-D-galactopyranosyl 4,6-disulfate)-(1-->4)-3,6-anhydro-alpha-D-galactopyranose. Minor structural variations also occurred, including alternative patterns of sulfation and the presence of terminal Xylp. The location of the terminal Xylp residues was not certain but evidence supported their attachment at O-3 of some 4-linked Galp residues. The cell-wall galactans remain unchanged during the life cycle of the alga.


Nonenriched PCR Versus Mutant-Enriched PCR in Detecting Selected Epidermal Growth Factor Receptor Gene Mutations Among Nonsmall-Cell Lung Cancer Patients.
Biopsies obtained from lung cancers contain a mixture of cancerous and healthy tissues. The mutant-enriched polymerase chain reaction (ME-PCR) identifies low-level somatic DNA mutations within an excess wild-type sample. This study aimed at comparing nonenriched PCR (NE-PCR) versus ME-PCR for the detection of two epidermal growth factor receptor (EGFR) gene mutations among nonsmall cell lung cancer patients. Fifty lung tissue biopsies were screened for inframe TTAA deletions in exon-19 and the L858R point mutation in exon-21, using ME-PCR and NE-PCR, followed by capillary electrophoresis. Only exon-19 deletions were detected in 22% and 18% of cases using ME-PCR and NE-PCR, respectively. Diagnostic performance of the NE-PCR versus the ME-PCR serving as a "gold standard" revealed a sensitivity of 82%, and a specificity of 100%, with positive and negative predictive values of 100% and 95%, respectively, and an overall accuracy of 96%. Despite a strong agreement shown between the two assays (K=0.875), the NE-PCR showed an 18% false-negative rate in bronchoscopically obtained biopsies compared to ME-PCR. The false negativity encountered with NE-PCR in bronchoscopically obtained samples makes ME-PCR the technique of choice in such situations.


Intra-cardiac echocardiography guided trans-septal puncture in patients with dilated left atrium undergoing percutaneous transvenous mitral commissurotomy.
Percutaneous transvenous mitral commissurotomy (PTMC) is an effective treatment for mitral stenosis, but trans-septal puncture carries a certain risk of complications. There have been few reports on phase-array intra-cardiac echocardiography (ICE) guidance in trans-septal puncture for PTMC, especially in patients with dilated left atrium or distorted anatomy. Herein, we report our preliminary experience with ICE-guided trans-septal puncture in patients with dilated left atrium (>or=5.5 cm) who underwent PTMC. From June 2005 to March 2006, there were nine consecutive patients with symptomatic mitral stenosis and left atrium size larger than 5.5 cm who underwent trans-septal puncture for PTMC with the ICE guidance in this institution by a same operator. The procedural and catheterization results were analyzed. Using ICE guidance, the success rate for trans-septal puncture was 100% for all patients with dilated left atrium (>or=5.5 cm). The trans-septal procedures were free of major and minor complications and the patients were not exposed to contrast medium. Mitral valve area increased significantly from 1.0+/-0.2 cm(2) to 1.9+/-0.2 cm(2). Our preliminary result showed that ICE safely and effectively guided trans-septal puncture for PTMC in patients with dilated left atrium (>or=5.5 cm), thus eliminating contrast medium usage and avoiding unnecessary longer X-ray exposure.


[Prognosis of the reproduction health care in the Czech Republic until 2010: II. Planned parenthood].
To prepare a prognosis of development of contraception, artificial termination of pregnancy and asisted reproductive technologies until 2010, based on the trend in their indicators in the previous years. A retrospective epidemiological study to be used as a basis for the prognosis Mother and Child Care Institute, Prague - Podolí For outlining the probable trend in the use of various types of contraceptives (IUD) as well as for artificial termination of pregnancy, evaluated according to their internationally recognised indicators, the extrapolation of the trends in these criteria prevalent in the period 1995-2002 was used. The prognosis of increase in the number of female users of hormonal contraception at the expense of IUD as well as the decrease in the number of women solving their problem with unwanted pregnancy by artificial termination of pregnancy (ATP), based on the said extrapolation of their indicators with a prospect until 2010, is probably overly optimistic. Due to probable changes in the political, social and economic circumstances as well as in the women's attitudes, it is expected that this trend will slow down. This is why it is expected that the number of female users of hormonal contraception will increase merely to 500 and that the women using IUD will decrease to 50 per 1,000 fertile women. Also, as concerns the number of ATPs, it is expected that it will decrease merely just below 10 for every 1,000 fertile women and to 20 for every 100 births. Even if the trends of all these indicators slow down, it can be expected that they will reach the average levels reported in the countries of Western Europe. As for the trend in asisted reproductive technologies (ART), whose share in the total number of births will rise, the main emphasis will be put on consistent nationwide registration, amendments to legislation and research mainly in the area of psycho-neurological development of these children, as recommended by the WHO. The expected rate of growth of the number of female users of effective contraception and the expected rate of decline of the number of ATPs, corresponding to the trend of the recent years, will probably decrease by 2010 but the average levels reported by the countries of Western Europe will still be reached. According to the recommendation of the WHO, the trend in some forms of ART will require research in the field of psycho-neurological development of the children from these pregnancies until they reach adulthood as well as some amendments to legislation.


Lipid lowering drug therapy in patients with coronary heart disease from 24 European countries--Findings from the EUROASPIRE IV survey.
Since dyslipidaemia is one of the most important risk factors for coronary heart disease (CHD), lowering of LDL-cholesterol (LDL-C) causes significant reduction in morbidity and mortality, particularly in patients with established CHD. The aim of this survey was to assess how statins were prescribed in CHD patients at discharge after a coronary event from hospitals throughout Europe and how the intake of these drugs was reported by the patients when they were seen more than one year later in relationship with their achieved LDL-C levels. 6648 CHD patients' data from centres in 24 European countries were gathered using standardized methods. Lipid measurements were performed in one central laboratory. Patients were divided in three groups: high-intensity statin therapy, moderate or low intensity statin therapy and no statin therapy at all. 90.4% CHD patients were on statin therapy at the time of discharge from the hospital which decreased to 86% one year later. Only 37.6% of these patients were prescribed a high-intensity statin at discharge which even decreased to 32.7% later. In only 6 countries (all of them high-income countries) the number of patients on a high-intensity statin therapy increased substantially after the hospital discharge. It is worrying that statin therapy was discontinued in 11.6% and that only 19.3% of all CHD patients achieved target values of LDL-C < 1.8 mmol/L at the time of interview. Too many CHD patients with dyslipidaemia are still inadequately treated and most of these patients on statin therapy are not achieving the treatment targets. Therapeutic control of LDL-C is clearly related to the intensity of lipid lowering drug regimen after the CHD event indicating that a considerable potential still exists throughout Europe to reduce CHD mortality and morbidity rates through more efficient LDL-C lowering.


Femoral Traction Splints in Mountain Rescue Prehospital Care: To Use or Not to Use? That Is the Question.
To determine the incidence of femur fractures in mountain rescue in England and Wales. To investigate the attitudes of rescuers toward the use of femoral traction splints. To review the literature for evidence on the use of traction splints in prehospital medicine and test the hypothesis that femoral traction splints reduce morbidity and mortality in patients with a fractured femur. The Mountain Rescue England and Wales database was searched for cases of suspected fractured femur occurring between 2002 and 2012, a questionnaire was sent to all mountain rescue teams in England and Wales, and a literature review was performed. Relevant articles were critically reviewed to identify the evidence base for the use of femoral traction splints. Femur fractures are uncommon in mountain rescue, with an incidence of suspected femur fractures on scene at 9.3 a year. Traction splints are used infrequently; 13% of the suspected femur fractures were treated with traction. However, rescuers have a positive attitude toward traction splints and perceive few disadvantages to their use. No trials demonstrate that traction splints reduce morbidity or mortality, but a number describe complications resulting from their use. Femur fractures are rare within mountain rescue. Traction splints may be no more effective than other methods of splinting in prehospital care. We failed to identify evidence that supports the hypothesis that traction splints reduce morbidity or mortality. We advocate the use of a femoral traction splints but recognize that other splints may also be appropriate in this environment.


[DRESS syndrome or reaction to drugs with eosinophilia and systemic symptoms associated to anti-tuberculosis drugs].
Tuberculosis has increased all over the world. This paper reports the case of a male patient with tuberculous meningitis, spinal tuberculosis (Pott's disease) and severe adverse reactions to antituberculosis drugs. He had skin rash, hepatitis, eosinophilia and fever; all these signs make the diagnosis of DRESS syndrome. This syndrome is caused by a severe hypersensitivity reaction to different drugs. It is usually caused by anticonvulsants, sulfonamides and some antiviral drugs, among other drugs. Anti-tuberculosis drugs can also cause this potentially fatal syndrome. The importance of surveillance for early detection and treatment of adverse drug reactions is emphasized.


Optically detected cross-relaxation spectroscopy of electron spins in diamond.
The application of magnetic resonance spectroscopy at progressively smaller length scales may eventually permit 'chemical imaging' of spins at the surfaces of materials and biological complexes. In particular, the negatively charged nitrogen-vacancy (NV(-)) centre in diamond has been exploited as an optical transducer for nanoscale nuclear magnetic resonance. However, the spectra of detected spins are generally broadened by their interaction with proximate paramagnetic NV(-) centres through coherent and incoherent mechanisms. Here we demonstrate a detection technique that can resolve the spectra of electron spins coupled to NV(-) centres, in this case, substitutional nitrogen and neutral nitrogen-vacancy centres in diamond, through optically detected cross-relaxation. The hyperfine spectra of these spins are a unique chemical identifier, suggesting the possibility, in combination with recent results in diamonds harbouring shallow NV(-) implants, that the spectra of spins external to the diamond can be similarly detected.


Brønsted acidic ionic liquids and their zwitterions: synthesis, characterization and pKa determination.
Imidazolium chlorides with one or two carboxylic acid substituent groups, 1-methyl-3-alkylcarboxylic acid imidazolium chloride, [Me[(CH2)nCOOH]im]Cl (n=1, 3), and 1,3-dialkylcarboxylic acid imidazolium chloride, [[(CH2)nCOOH]2im]Cl (n=1, 3), have been synthesized via their corresponding acid esters. Deprotonation of the carboxylic acid functionalized imidazolium chlorides with triethylamine affords the corresponding zwitterions [Me[(CH2)nCOO]im] (n=1, 3) and [[(CH2)nCOOH][(CH2)nCOO]im] (n=1, 3). Subsequent reaction of the zwitterions with strong acids gives the new imidazolium salts [Me[(CH2)nCOOH]im]X (n=1, 3; X=BF4, CF3SO3) and [[(CH2)nCOOH]2im]X (n=1, 3; X=BF4, CF3SO3), which exhibit melting points as low as -61 degrees C. The solid-state structures of two of the carboxylic acid functionalized imidazolium salts have been determined by single-crystal X-ray diffraction analysis. Extensive hydrogen bonding is present between the chloride and the imidazolium, with eight Cl.H interactions below 3 A. The pK(a) values of all the salts, determined by potentiometric titration, lie between 1.33 and 4.59 at 25 degrees C.


Effectiveness of fluticasone propionate in patients with moderate asthma: a dose-ranging study.
This study was undertaken to evaluate the efficacy and safety of fluticasone propionate, an inhaled corticosteroid, in adolescents and adults with moderate asthma who were previously taking inhaled corticosteroids. After a 2-week, open-label screening period, a double-masked, randomized, parallel-group, dose-ranging study was conducted over 12 weeks in 21 outpatient centers throughout the United States. Patients (N = 304) > or = 12 years of age with moderate asthma previously treated with inhaled corticosteroids and beta-sympathomimetic bronchodilators were enrolled. Patients were assigned to receive placebo or fluticasone propionate 100, 250, or 500 micrograms twice daily via a metered-dose inhaler without a spacer device. These doses refer to the amount of fluticasone propionate released from the valve of the metered-dose inhaler; the corresponding doses released from the activator of the metered-dose inhaler are 88 micrograms, 220 micrograms, and 440 micrograms, respectively. Between baseline and end point, mean values of forced expiratory volume in 1 second decreased 0.31 L in the placebo group and improved 0.39 L, 0.30 L, and 0.43 L in patients receiving 100-micrograms, 250-micrograms, and 500-micrograms fluticasone propionate, respectively. The differences between placebo and all treatment groups were statistically significant. More patients were withdrawn from placebo (72%) than from fluticasone propionate (13% to 16%) because of failure to meet predetermined asthma stability criteria. Differences in baseline-to-end point changes in morning peak expiratory flow rate, physician overall assessments and patient-rated assessment of symptoms, and albuterol use for symptom control also significantly favored each fluticasone propionate group over placebo. There were essentially no differences in efficacy among the three fluticasone propionate groups. Treatment-related adverse events occurred in 8% of placebo-treated patients and 13% to 15% of fluticasone propionate-treated patients; these events were mainly localized to the oropharynx/ larynx. A 12-week course of fluticasone propionate (100, 250, and 500 micrograms twice daily) was well tolerated and more effective than placebo based on maintenance of asthma stability, pulmonary function tests, physician and patient assessments, and rescue bronchodilator use. No dose-related effects were observed with the dosages of fluticasone propionate used in this study.


Enzymatic synthesis of novel fructosyl and oligofructosyl trehaloses by Aspergillus sydowi beta-fructofuranosidase.
An intracellular beta-D-fructofuranosidase produced by Aspergillus sydowi IAM 2544 was purified by Q-Sepharose and Alkyl-Sepharose chromatographies. The molecular mass was 50 kDa by SDS-PAGE analysis. The optimum pH and temperature of sucrose hydrolyzing activity of the enzyme were 5.5 and 75 degrees C, respectively, but those of fructosyl transferase activity were 5.2 and 55 degrees C, respectively. The enzyme efficiently transferred the fructose residue of sucrose as a donor to trehalose as an acceptor. And the amount of fructosyl and oligofructosyl trehaloses produced was changed by the molar ratio of trehalose as an acceptor to sucrose as a donor used. The most efficient production of the transferred products was achieved at the reaction conditions in the range of molar ratios of 1:1 to 3:1 (trehalose:sucrose). The chemical structures of these new kinds of resulting series of fructosyl and oligofructosyl trehaloses produced were identified as O-beta-D-Fru-(2-->6)-alpha-D-Glc-(1-->1)-alpha-D-glucopyranoside, O-beta-D-Fru-(2-->6)-alpha-D-Glc-(1-->1)-alpha-D-glucopyranoside, and O-beta-D-Fru-(2-->1)-O-beta-D-Fru-(2-->1)-O-beta-D-Fru-(2-->6)-alpha-D-G lc- (1-->1)-alpha-D-glucopyranoside. These results indicate that beta-fructofuranosidase from Aspergillus sydowi specifically transferred the fructose residue of sucrose to the C6-OH position of the glucose residue of trehalose at the early stage of the reaction, following the elongation of the fructose residue by the transfructosylation of the enzyme to form oligofructosyl trehalose of a longer fructose chain.


Contamination of table salts from Turkey with microplastics.
Microplastics (MPs) pollution has become a problem that affects all aquatic, atmospheric and terrestial environments in the world. In this study, we looked into whether MPs in seas and lakes reach consumers through table salt. For this purpose, we obtained 16 brands of table salts from the Turkish market and determined their MPs content with microscopic and Raman spectroscopic examination. According to our results, the MP particle content was 16-84 item/kg in sea salt, 8-102 item/kg in lake salt and 9-16 item/kg in rock salt. The most common plastic polymers were polyethylene (22.9%) and polypropylene (19.2%). When the amounts of MPs and the amount of salt consumed by Turkish consumers per year are considered together, if they consume sea salt, lake salt or rock salt, they consume 249-302, 203-247 or 64-78 items per year, respectively. This is the first time this concerning level of MPs content in table salts in the Turkish market has been reported.


Early research on human genetics using the twin method: who really invented the method?
The twin method consists of a formal comparison between the resemblance between identical (monozygotic, MZ) twins and the resemblance between fraternal (dizygotic, DZ) twins for some trait of interest. It was developed between 1900 and about 1940, as more accurate tools for diagnosis of zygosity and for statistically analyzing the resemblance between relatives were built. Its early use was in the demonstration that a trait was inherited or that part of the causation of a trait was genetical, but it has now evolved to the point that twin registries constitute an important resource for the identification of specific genes and their interactions both with other genes and with the internal and external environment. Who really invented the method is still an unsettled question, which this article explores.


Anaemia in women of reproductive age in Dar-es-Salaam, Tanzania.
Anaemia is among the greatest health problems in reproductive age women in developing countries. To estimate the prevalence of anaemia among non-pregnant parous women, and to investigate the main underlying cause for the anaemia. A sub-urban Maternal and Child Health Clinic (MCH) in Dar es Salaam. Cross-sectional. Consecutive parous non-pregnant women who had brought their children for vaccination and/or had come for family planning to Mbagala MCH clinic were invited to participate in the study. Obstetric and social history was recorded, and their height and weight were checked. Haemoglobin was measured using HemoCue hemoglobinometer. Anaemic women were further investigated to determine the cause of anaemia by haematological and biochemical tests. Five hundred and four parous non-pregnant women were screened, 49% were anaemic (Hb <12 g/dl) and 1.6% severely anaemic (Hb <7 g/dl). Anaemia was not related to socio-demographic and obstetric history characteristics, but decreased significantly with increasing Body Mass Index (BMI) (p=0.042). The prevalence of anaemia was significantly lower in women using hormonal contraceptives, compared to non-users (36% vs 54%) (p=0.04). Eighty-seven percent of the anaemic women were iron deficient and 8.7% had elevated serum C-reactive protein indicating undiagnosed infections. Nutritional deficiencies in women have to be corrected before and between pregnancies and all contacts women have with the health system should be utilised for anaemia control interventions, in addition to long-term community approaches. To improve maternal health calls for a broader agenda and a change of approach in the MCH-clinics.


Engineering the chloroplast genome for hyperexpression of human therapeutic proteins and vaccine antigens.
The chloroplast genome is ideal for engineering because it offers a number of attractive advantages, including high-level gene expression, the feasibility of expressing multiple genes or pathways in a single transformation event, and transgene containment due to lack of pollen transmission. The chloroplast-based expression system is suitable for hyperexpression of foreign proteins, oral delivery of vaccine antigens and therapeutic proteins, via both leaves and fruits. Through the refinement of expression vectors and use of chaperones, chloroplasts produce up to 47% of foreign protein in the total cellular protein in transgenic tissues. This chapter describes various techniques for creating chloroplast transgenic plants and their biochemical and molecular characterization. Suitable examples for application of chloroplast genetic engineering in human medicine are provided.


[Criteria of early diagnosis of postoperative peritonitis in abdominal injuries].
The article deals with 221 relaparotomies in abdominal injuries. It was undertaken for postoperative peritonitis in 136 (61.5%) patients. It was established that signs of intoxication are the early diagnostic criteria of peritonitis which determine the indications for laparotomy in injuries to the abdomen. Signs of peritoneal irritation are less informative. The diagnosis of postoperative peritonitis can be made sufficiently objectively on the grounds of a diagnostic index suggested by the authors.


A novel, single nucleotide polymorphism-based assay to detect 22q11 deletions.
Velocardiofacial syndrome, DiGeorge syndrome, and conotruncal anomaly face syndrome, now collectively referred to as 22q11deletion syndrome (22q11DS) are caused by microdeletions on chromosome 22q11. The great majority ( approximately 90%) of these deletions are 3 Mb in size. The remaining deleted patients have nested break-points resulting in overlapping regions of hemizygosity. Diagnostic testing for the disorder is traditionally done by fluorescent in situ hybridization (FISH) using probes located in the proximal half of the region common to all deletions. We developed a novel, high-resolution single-nucleotide polymorphism (SNP) genotyping assay to detect 22q11 deletions. We validated this assay using DNA from 110 nondeleted controls and 77 patients with 22q11DS that had previously been tested by FISH. The assay was 100% sensitive (all deletions were correctly identified). Our assay was also able to detect a case of segmental uniparental disomy at 22q11 that was not detected by the FISH assay. We used Bayesian networks to identify a set of 17 SNPs that are sufficient to ascertain unambiguously the deletion status of 22q11DS patients. Our SNP based assay is a highly accurate, sensitive, and specific method for the diagnosis of 22q11 deletion syndrome.


3-Deoxyglucosone: metabolism, analysis, biological activity, and clinical implication.
3-Deoxyglucosone (3-DG) is synthesized via the Maillard reaction and the polyol pathway, and is detoxified to 3-deoxyfructose and 2-keto-3-deoxygluconic acid. 3-DG rapidly reacts with protein amino groups to form advanced glycation end products (AGEs) such as imidazolone, pyrraline, N'-(carboxymethyl)lysine and pentosidine, among which imidazolone is the AGE most specific for 3-DG. As demonstrated by using gas chromatography-mass spectrometry or high-performance liquid chromatography, plasma 3-DG levels are markedly increased in diabetes and uremia. Although the plasma 3-DG levels had been controversial, it was clearly demonstrated that its plasma level depends on the deproteinization method by which either free or total 3-DG, presumably bound to proteins, is measured. In diabetes, hyperglycemia enhances the synthesis of 3-DG via the Maillard reaction and the polyol pathway, and thereby leads to its high plasma and erythrocyte levels. In uremia, however, the decreased catabolism of 3-DG, which may be due to the loss of 3-DG reductase activity in the end-stage kidneys, may lead to high plasma 3-DG level. The elevated 3-DG levels in plasma and erythrocytes may promote the formation of AGEs such as imidazolone, as demonstrated by immunohistochemistry and immunochemistry using an anti-imidazolone antibody. Although AGE-modified proteins prepared in vitro exhibit a variety of biological activities, known AGE structures have not yet been demonstrated to show any biological activities. Because 3-DG is potent in the formation of AGEs and has some biological activities, such as cellular toxicity, it may be more important in the development of diabetic and uremic complications than the known AGE structures. By demonstrating that treatment with an aldose reductase inhibitor reduces the erythrocyte levels of 3-DG and AGEs, such as imidazolone, light is shed on the mystery of how aldose reductase inhibitors may prove beneficial in diabetic complications. These evidences suggest that 3-DG plays a principal role in the development of diabetic and uremic complications.


Barriers to effective screening for domestic violence by registered nurses in the emergency department.
Triage nurses in the emergency department are in a unique position to screen for domestic violence. This study, using Orlando's theory with a focus on two of her five major concepts, identifies barriers that prevent effective screening for domestic violence. A quantitative survey was distributed to 101 registered nurses employed in a large emergency department. Results identified three major barriers and a relationship between age and inservice attendance on domestic violence. Education on abuse and resources should be essential in nursing school curricula. Policy development and review should be part of an annual, mandatory inservice for all emergency nurses.


Skill transfer from virtual reality to a real laparoscopic task.
To validate the usefulness of virtual reality surgical simulators, we investigated the transfer of skills achieved by their use to real tasks. Thirty medical students underwent a pretest using a real laparoscopic trainer. They were then randomized to the following three groups: group I received no training; group II received training using the Minimal Invasive Surgical Trainer in Virtual Reality (MIST-VR); and group III received training using conventional training exercises. Each group then underwent a posttest. Using the Imperial College Surgical Assessment Device (ICSAD), scores were generated for time taken, distance traveled, number of movements made, and speed of instrument movement. Significant changes between the MIST-VR group (group II) and the conventionally trained group (group III), were observed in the speed of movement of the left hand and the numbers of movements taken by each hand, when compared to the untrained group (group I). The training of novices using MIST-VR yields quantifiable changes in skill that are transferable to a simple real task and are similar to the results achieved with conventional training.


Salary survey 2005.
Nursing Management's seventh annual salary survey offers nationwide data on nurse leaders' earnings and provides insight into compensation issues and retention incentives.


Meta analysis of the relationship between tuberous sclerosis complex and renal cell carcinoma.
The association of angiomyolipoma with tuberous sclerosis complex (TSC) patients is well recognised. Some literature has suggested that patients with TSC are at increased risk of renal neoplasm, particularly since angiomyolipomas can be locally invasive and demonstrate tumor like neovascularity on angiography. In an attempt to place in context one case of metastatic renal cell carcinoma in a patient with TSC a meta analysis of the literature was performed. One pediatric patient with TSC and metastatic renal cell carcinoma was evaluated. Reviews and case reports of TSC and renal cell carcinoma and related imaging findings were identified by searching the MEDLINE database, the 'bibliography of reviews' in Index Medicus, personal files and the reference lists from all identified reviews. Individual cases suitable for review in the available literature from 1922 through 1993 comprised the data base. The data base was analysed with the method of proportions and unpaired two-tailed Student's t-test for different populations. A cumulative summary of the literature amassed 107 additional cases from 62 reports over 71 years. Our case is the 17th case, to our knowledge, of renal cell carcinoma in TSC. Analysis of the distribution of characteristics and incidence of; renal cysts, renal cell carcinoma, and lymph node involvement demonstrate no increased risk of renal cell carcinoma in patients with TSC (P = NS). Though anecdotal evidence has suggested a relationship between TSC and renal cell carcinoma, meta analysis of cases of coincident TSC renal complex, cystic changes, angiomyolipoma and renal cell carcinoma implies an identical, though small, risk of malignancy in TSC patients as compared with the normal population.


Components of asymmetrical visual encoding of geometrically transformed scripts.
Austrian and Israeli subjects were presented tachistoscopically with geometrically transformed numbers, nonsense syllables in Latin letters and Hebrew words (only the Israeli). Opposite reading and writing habits and different hand dominance were used as experimental variables. Criteria for evaluating the data were scanning pattern (voluntary preferred reading direction) and reading performance. A difference in reading pattern was found between Austrian right- and left-handed subjects but no difference in their reading performance. Also between Austrian and Israeli right-handed subjects a difference in the reading pattern appeared as well as in reading performance. Furthermore, the scanning pattern used by Austrian right-handed subjects in reading geometrically transformed numbers was different from their pattern in reading syllables. Distinguished were two sources of asymmetries, an intrinsic in visual mechanisms and a structural one in the stimulus itself.


Pharmacokinetics and pharmacodynamics of docetaxel with or without ketoconazole modulation in chemonaive breast cancer patients.
We previously found 70 mg flat-dose docetaxel coadministered with ketoconazole to modulate CYP3A4 to be the maximum tolerated dose that resulted in comparable docetaxel area under the plasma concentration-time curve (AUC) as 75-100 mg/m² docetaxel. We compared cycle 1 docetaxel pharmacokinetics and pharmacodynamics between ketoconazole-modulated (70 mg flat-dose docetaxel, n = 31) and conventional-dosed docetaxel (75 mg/m², n = 51) in chemonaive breast cancer patients in two sequential phase II studies. Ketoconazole-modulated docetaxel resulted in reduced docetaxel clearance (22.05 ± 8.29 versus 36.52 ± 13.39 l/h, P < 0.001), similar docetaxel AUC (3.93 ± 2.77 versus 3.77 ± 2.70 mg/l·h, P = 0.794) and tumor efficacy (cycle 1 responder 52% versus 55%) and less day 8 neutrophil suppression (1.24 ± 1.02 × 10⁹/l versus 0.47 ± 0.56 × 10⁹/l, P < 0.001), grade 4 neutropenia (32.3% versus 72.0%, P < 0.001) and febrile neutropenia (3.2 versus 23.5%, P = 0.015), compared with conventional-dosed docetaxel. Chinese had the lowest docetaxel clearance, highest AUC and most myelosuppression, followed by Malays and Indians, in response to ketoconazole-modulated docetaxel, while no significant interethnic differences were observed with conventional-dosed docetaxel. Ketoconazole-modulated docetaxel achieved similar docetaxel AUC and tumor efficacy but reduced neutrophil suppression and febrile neutropenia at ∼40% reduced dose, representing a feasible alternative to conventional-dosed docetaxel. Interethnic differences in CYP3A4 inhibition by ketoconazole exist and are important when evaluating the impact of concomitant medications.


Microsporidial infections in humans: current practice and developments in laboratory diagnosis.
Microsporidia are small, intracellular parasites that infect a wide range of hosts, including vertebrates, invertebrates and fish. They were discovered more than a century ago. The first well documented human case, however, was not reported until 100 years later. Since the first case of intestinal microsporidiosis was reported in 1985, numerous cases of microsporidiosis have been reported in immunocompromised patients, especially those in the later stages of human immunodeficiency virus (HIV) infection. Microsporidia also have been described in various other clinical conditions, including keratoconjunctivitis, sinusitis, peritonitis and myositis. The numbers of cases reported have risen dramatically since 1985, which can be explained partly by the acquired immune deficiency syndrome (AIDS) pandemic and partly by increased laboratory awareness. Some studies have shown that up to 50% of selected AIDS patients are infected with microsporidia. Diagnosis depended initially on the use of invasive techniques, namely histological examination of biopsy material. Since then, however, there have been important advances in the detection of microsporidial spores in clinical samples. Recent developments in the diagnosis of microsporidiosis are described, including light microscopy staining methods, fluorescent staining, electron microscopy and molecular techniques.