A clinical audit cycle of post-operative hypothermia in dogs.
Use of clinical audits to assess and improve perioperative hypothermia management in client-owned dogs. Two clinical audits were performed. In Audit 1 data were collected to determine the incidence and duration of perioperative hypothermia (defined as rectal temperatures <37·0°C). The results from Audit 1 were used to reach consensus on changes to be implemented to improve temperature management, including re-defining hypothermia as rectal temperature <37·5°C. Audit 2 was performed after 1 month with changes in place. Audit 1 revealed a high incidence of post-operative hypothermia (88·0%) and prolonged time periods (7·5 hours) to reach normothermia. Consensus changes were to use a forced air warmer on all dogs and measure rectal temperatures hourly post-operatively until temperature ≥37·5°C. After 1 month with the implemented changes, Audit 2 identified a significant reduction in the time to achieve a rectal temperature of ≥37·5°C, with 75% of dogs achieving this goal by 3·5 hours. The incidence of hypothermia at tracheal extubation remained high in Audit 2 (97·3% with a rectal temperature <37·5°C). Post-operative hypothermia was improved through simple changes in practice, showing that clinical audit is a useful tool for monitoring post-operative hypothermia and improving patient care. Overall management of perioperative hypothermia could be further improved with earlier intervention.


Non-secretory multiple myeloma with multinucleated giant plasma cells.
We report a case of non-secretory multiple myeloma with unusual cytological features. The plasma cells were multinucleated and contained up to forty nuclei. All nuclei had regular outlines without multilobulated and convoluted slopes. DNA content measurement demonstrated that all nuclei of uni- and multinucleated cells were diploid. All plasma cells contained cytoplasmic alpha chain but light chains and their corresponding transcripts were absent. There is no clear explanation concerning multinuclearity. In addition, hypotheses regarding non-secretion of immunoglobulin in non-secretory multiple myeloma and in other B-cell neoplasias are discussed.


[Hodgkin's lymphoma].
During the past 2 decades, major medical advances have resulted in dramatic improvements in cure rates for the majority of children with cancer, including those with Hodgkin's disease. Long-term data from different Institutions reveal actuarial 5, 10 and 15 year survival rates of 90, 80 and 70% and corresponding freedom from relapse rates of 75, 66 and 66% respectively. The prices that are paid to achieve these results are high in term of growth and development, sterility and second malignant tumor. The present challenge in the treatment of children with Hodgkin's disease is to delineate a therapeutic program which will insure continuation of the excellent survival and disease-free survival which are now being achieved while minimizing the risks of complications from treatment. At present it appears that the combination of low dose irradiation and chemotherapy (alternating non-cross-resistant drug combinations: MOPP/ABVD) is successful in affording optimistic cure rate with minimal morbidity. However, there are many questions which require a specific answer in the future: to define the risk/benefit ratio of therapy and to establish the role of surgical staging in the pediatric population.


Distraction Osteogenesis of Severely Resorbed Mandible.
Edentulous patients require an adequate rehabilitation so that the alveolar ridge in the interforaminal region be restored for subsequent implant-supported overdentures. The ultimate goal of distraction is to reconstruct the alveolar ridge to a suitable height and width compatible with Atwood class 2 in an appropriate direction allowing the sagittal interalveolar relation to be normally restored. Methods. A 65-year-old man presented with a grade 4 Mandibular atrophy as per Atwood classification which resulted in unsatisfactory treatment with full dentures. Endo-Distractor Krenkel® device was used for anterior mandibular vertical distraction osteogenesis. Four mandibular implants (ITI Straumann, Basel, Switzerland) measuring diameter Ø = 4.1 mm and length L = 16 mm were inserted after the required retention period. Standardized prosthetic treatment was completed with titanium bar retained over dentures. Results. A distraction of 11 mm was achieved within 18 days followed by a retention period of 4 months. No signs of infection nor distractor anchorage loosening were detected, and minimal lingual tilting has occurred. Conclusion. Distraction is possible on severely atrophic mandibles. The quality of bone reconstruction is satisfactory for both functional and esthetic results.


[High-intensity transcranial Doppler signals in patients wearing heart valve prostheses: a prospective study].
Transcranial Doppler sonography (TCD) of the middle cerebral arteries in patients with prosthetic heart valves reveals high-intensity transient signals (HITS) and can detect asymptomatic cerebrovascular microemboli. Both the nature of the underlying embolic material (either gaseous or corpuscular) and its clinical significance remain uncertain. Seventy-one patients undergoing heart valve replacement (n = 63) or repair (n = 8) from June 1996 to June 1998 were prospectively evaluated preoperatively and one week, 3 months and 12 months after valve replacement using TCD. At each follow-up interval, clinical assessment was aimed at detecting neurological events. Furthermore, continuous echo-Doppler study of the carotid arteries and TCD of the middle cerebral arteries for a 30-minute period during each following visit was carried out. No HITS were recorded preoperatively in any patient. At one week, HITS were detected in 25 patients (35%): 22 (65%) of these had received a mechanical prosthesis and three (10%) a bioprosthesis. No HITS were recorded in patients with mitral repair. HITS were subsequently detected only in patients with mechanical prosthesis with a positive TCD at one week, the mean number of HITS per patient being 7 +/- 18 at 3 months and 8 +/- 24 at 12 months. No neurological symptoms were evident in any patients during the postoperative evaluation. Multivariate analysis showed mechanical prosthetic valve to be the only independent predictive risk factor for HITS development. The role of a mechanical prosthetic valve as a risk factor in the pathogenesis of HITS appears evident. However, HITS appear to be unrelated to possible postoperative neurological events. TCD could have more specific clinical applications if associated with methods that would make it possible to ascertain the nature of various embolic materials.


Using a logical information model-driven design process in healthcare.
A hybrid standards-based approach has been adopted in Singapore to develop a Logical Information Model (LIM) for healthcare information exchange. The Singapore LIM uses a combination of international standards, including ISO13606-1 (a reference model for electronic health record communication), ISO21090 (healthcare datatypes), SNOMED CT (healthcare terminology) and HL7 v2 (healthcare messaging). This logic-based design approach also incorporates mechanisms for achieving bi-directional semantic interoperability.


Structure and orientation of the surfactant-associated protein C in a lipid bilayer.
The secondary structure of native and depalmitoylated porcine surfactant-associated protein C (SP-C) was studied by attenuated total reflection Fourier-transform infrared spectroscopy. Both forms of porcine SP-C adopt mainly an alpha-helical conformation. These two forms of the protein were reconstituted in a lipid bilayer. The insertion of the protein in a membrane is associated with an increase of the alpha-helical content. Dichroic measurements show that, in both cases, the long axis of the alpha-helix is oriented parallel to the lipid acyl chains.


Enantioselective Total Synthesis of Cepharatines via Bioinspired Ring Reconstruction.
We describe enantioselective total syntheses of cepharatines A-D, members of the hasubanan alkaloid family, which feature an unusual tetracyclic skeleton including an azabicyclo[3.3.1]nonane motif. A key reaction is a regio-divergent oxidative phenolic coupling reaction that affords the tricyclic core structure of hasubanan with different substitution patterns on the A-ring, including the all-carbon quaternary stereogenic center at C13, in a single step. The characteristic tetracyclic azabicyclo[3.3.1]nonane motif was constructed by means of a bioinspired cascade reaction involving the retro-aza-Michael reaction/hemiaminal formation.


Reflective correctors for the Hubble Space Telescope axial instruments.
Reflective correctors to compensate the spherical aberration in the Hubble Space Telescope are placed in front of three of the axial scientific instruments (a camera and two spectrographs) during the first scheduled refurbishment mission. The five correctors required are deployed from a new module that replaces the fourth axial instrument. Each corrector consists of a field mirror and an aspherical, aberration-correcting reimaging mirror. In the camera the angular resolution capability is restored, be it in reduced fields, and in the spectrographs the potential for observations in crowded areas is regained along with effective light collection at the slits.


Effects of SK-951, a benzofuran derivative, as a prokinetic agent in rats and dogs.
The gastrokinetic activity of SK-951 ((-)4-amino-N-[2-(1-azabicyclo[3.3.0]octan-5-yl)ethyl]-5-chloro-2,3-dihy dro-2-methylbenzo[b]furan-7-carboxamide hemifumarate), a benzofuran derivative with 5-hydroxytryptamine (5-HT)4-receptor agonist activity, was studied in rats and dogs. The effects of SK-951 were also investigated in a model of vagotomy-induced gastroparesis in comparison with cisapride. In rats, both SK-951 and cisapride enhanced gastric emptying of liquids (phenol red) at a dose of 1-100 mg/kg, p.o. Gastric emptying of liquid (acetaminophen) in fasted beagle dogs was enhanced significantly by SK-951 (1.0 mg/kg, i.v.), whereas the effect of cisapride (0.2-1.0 mg/kg, i.v.) was not statically significant. Similar results were found when radiopaque markers were given with standard meal to dogs with vagotomy-induced gastroparesis. The delayed gastric emptying of radiopaque markers by vagotomy was reversed by SK-951 (1.0 mg/kg, i.v.), whereas cisapride showed no effect at doses from 0.1 to 1.0 mg/kg, i.v. These results indicated that oral and intravenous administration of SK-951 accelerates gastric emptying of both liquids and solids in animal models. Thus, SK-951 may be a highly potent and useful prokinetic agent in comparison to cisapride.


Development of spatial preferences for counting and picture naming.
The direction of object enumeration reflects children's enculturation but previous work on the development of such spatial preferences has been inconsistent. Therefore, we documented directional preferences in finger counting, object counting, and picture naming for children (4 groups from 3 to 6 years, N = 104) and adults (N = 56). We found a right-side preference for finger counting in 3- to 6-year-olds and a left-side preference for counting objects and naming pictures by 6 years of age. Children were consistent in their special preferences when comparing object counting and picture naming, but not in other task pairings. Finally, spatial preferences were not related to cardinality comprehension. These results, together with other recent work, suggest a gradual development of spatial-numerical associations from early non-directional mappings into culturally constrained directional mappings.


Propofol-induced alterations in the microcirculation of hamster striated muscle.
To investigate the effects of propofol on small vessels, we have measured changes in diameter and blood flow in microcirculatory venules and arterioles. Studies were carried out in the dorsal skinfold chamber of hamsters by intravital fluorescence microscopy. A bolus injection of propofol 25 mg kg-1 dilated small and collecting venules by a mean value of 18% and arterioles by 13%. Blood flow in venules increased by up to 69%. Intralipid dilated arterioles and post-capillary venules by 26% and 30%, respectively. After 4 h of continuous infusion (0.2-0.8 mg kg-1), only blood flow in post-capillary venules increased (66% propofol and 92% Intralipid). Post-capillary and collecting venules dilated in both groups. Therefore, propofol and Intralipid induced venodilatation and enhanced blood flow after bolus administration. After 4 h, despite dilatation in both groups, only post-capillary venules showed enhanced blood flow. These observations suggest redistribution of blood flow after prolonged administration of propofol.


miRNA Dysregulation in the Development of Non-Alcoholic Fatty Liver Disease and the Related Disorders Type 2 Diabetes Mellitus and Cardiovascular Disease.
According to the World Health Organization, the continuing surge in obesity pandemic creates a substantial increase in incidences of metabolic disorders, such as non-alcoholic fatty liver disease (NAFLD), type 2 diabetes mellitus, and cardiovascular disease. MicroRNAs (miRNAs) belong to an evolutionarily conserved class of short (20-22 nucleotides in length) and single-stranded non-coding RNAs. In mammals, miRNAs function as critical post-transcriptional negative regulators involved not only in many biological processes but also in the development of many diseases such as NAFLD and comorbidities. More recently, it has been described that cells can secrete miRNAs in extracellular vesicles, transported by body fluids, and uptaken by other tissues regulating gene expression. Therefore, this could be a mechanism of signaling involved not only in physiological pathways but also in the development of diseases. The association of some miRNA expression profiles with certain disorders has made them very interesting molecules for diagnosis, prognosis, and disease management. The finding of specific miRNA signatures to diagnose NAFLD and related diseases could anticipate the risk of development of related complications and, actually, it is the driving force of present health strategies worldwide. In this review, we have included latest advances in knowledge about the miRNAs involved in the development of NAFLD and related diseases and examined how this knowledge could be used to identify new non-invasive biomarkers and new pharmacological interventions.


Medical management of carotid stenosis.
Stroke is a leading cause of morbidity and mortality in the developed world. Although the rates of stroke have decreased in North America, there are significant areas of risk stratification and management that can be improved. Hypertension is the most significant and perhaps most modifiable risk factor for stroke. Carotid atherosclerotic disease is associated with 15% of ischemic strokes. Although carotid endarterectomy (CEA) remains a recommendation for significant symptomatic carotid stenosis, controversy continues in the management of asymptomatic and recurrent carotid stenosis. Medical management options and effectiveness has significantly improved since the early CEA trials were published. Optimal medical management now must incorporate aggressive risk factor reduction measures, particularly with antihyperlipidemic therapy. Improved understanding of the natural history of carotid atherosclerosis is necessary to improve the application of management strategies.


Clients' pretreatment role expectations, the therapeutic alliance, and clinical outcomes in outpatient therapy.
The present study examined the associations between pretreatment role expectations, working alliance, and therapy outcome. A mediational model was hypothesized wherein the therapeutic alliance mediates the relationship between clients' pretreatment role expectations and psychotherapy outcome. Sixty-eight clients completed the Expectations About Counseling-Brief Form at pretreatment, the Working Alliance Inventory-Short Form Revised after Session 3, and the Outcome Questionairre-45 at both pretreatment and the final session. All 3 expectations factors (Personal Commitment, Facilitative Conditions, Counselor Expertise) were related to the alliance. However, only expectations for Counselor Expertise were related to outcome, although this relationship did not appear to be mediated by the alliance. Suggested research directions, clinical implications, and study limitations are discussed.


[Pharmacodynamics of vecuronium in infants during intravenous induction of anesthesia with ketamine].
The pharmacodynamic effects of vecuronium in children aged 1 to 6 years were investigated after intravenous induction of anaesthesia with ketamine, using an initial dose of vecuronium of 0.08 mg/kg body wt. 0.1 mg/kg body wt. The degree of neuromuscular blockade was determined by measuring the contraction force of the m. adductor pollicis after supramaximal stimulation of the ulnar nerve using an electromechanical device. The results (median, chi min and chi max) were as follows. For the initial dose 0.08 mg/kg body wt., the onset time was 150 s (110-360 s); total blockade: 5 of 9 children, D25 (duration of 25% recovery) 13 min (10-31); RI (recovery index): 8.5 min (6.0-14.5); D90 (duration of 90% recovery): 27 min (20-44). For the initial dose of 0.1 mg/kg body wt., the onset time was 135 s (80-300); total blockade: all children, D25: 19.5 min (12-32.5); RI: 8.75 min (6.5-13.5); D90 35 min (22-45). Only the D25 was significantly shorter using an initial dose of 0.08 mg/kg body wt. For a total blockade, a higher dose of vecuronium is necessary using intravenous induction of anaesthesia compared with previously described inhalation techniques. Even with the high dosage, recovery from neuromuscular blockade is so rapid in this age group that it can be used even for short operations without reversal.


Psychoeducational Interventions for Adults With Level 3 Autism Spectrum Disorder: A 50-Year Systematic Review.
There is face validity to the expectation that adults with level 3 autism spectrum disorder (ASD-3) will benefit from a range of psychoeducational interventions. This paper reviews the empirical evidence supporting the effectiveness of these interventions, many of which are currently used in clinical settings. We reviewed 56 peer-reviewed studies of psychoeducational interventions for adults with ASD-3, written in English and since 1968, that met our criteria. The reviewing team included educators, clinicians, researchers, and a biostatistician. The available literature was limited, and most, if not all, of the studies presented some significant methodological limitations. When using Cochrane's criteria to assess seven key outcome domains-activities of daily living, aggressive/destructive behaviors, emotional functioning, language/communication skills, self-injurious behaviors, stereotypy/mannerisms, and vocational skills-we found only moderately reliable evidence to support the effectiveness of interventions designed to improve emotional functioning in adults with ASD-3. The reliability of evidence relevant to the six other outcome domains was rated as low or very low. Based on this review, we suggest directions for future study of interventions for adults with ASD-3, including topics, subpopulations, and approaches that should be explored. We also propose some crucial changes in how future studies regarding this population should be designed, analyzed, and documented, while balancing clinical considerations with scientific/educational utility.


Effect of mammalian cell differentiation on response to exogenous 5-aminolevulinic acid.
Many different types of mammalian cells accumulate fluorescing and photosensitizing concentrations of protoporphyrin IX (PpIX) when exposed to exogenous 5-aminolevulinic acid (ALA) in vivo or in vitro. Most types of malignant cells accumulate substantially more ALA-induced PpIX than do the normal cells from which they arose. Most types of malignant cells also are less differentiated than their normal counterparts. We therefore considered the possibility that malignant cells demonstrate a malignant ALA phenotype (accumulate abnormally large amounts of PpIX when exposed to exogenous ALA) as a direct consequence of their less differentiated state. Human promyelocyte cell line HL-60 and mouse preadipocyte cell line 3T3 L1 were induced to differentiate by exposing them to inducing agents in vitro. The HL-60 cells accumulated less ALA-induced PpIX when differentiated, but the 3T3 L1 cells accumulated more. It appears then that changes in the ALA phenotype with changes in the state of differentiation are cell-type specific. The decreased accumulation of ALA-induced PpIX that accompanied differentiation of the promyelocytic leukemia cells may have clinical application for rapid quantitation of the response of myelocytic leukemia patients to differentiation therapy.


Reciprocal regulation of calcium dependent and calcium independent cyclic AMP hydrolysis by protein phosphorylation.
The hydrolysis of cyclic nucleotide second messengers takes place through multiple cyclic nucleotide phosphodiesterases (PDEs). The significance of this diversification is not fully understood. Here we report the differential regulation of low K(m) Ca2+-activated (PDE1C) and Ca2+-independent, rolipram-sensitive (PDE4) PDEs by protein phosphorylation in the neuroendocrine cell line AtT20. Incubation of cells with 8-(4-chlorophenylthio)-cyclic AMP (CPT-cAMP) enhanced PDE4 and reduced PDE1C activity. These effects were blocked by H89 indicating mediation by cAMP-dependent protein kinase (PKA), furthermore in broken cell preparations PKA produced the same reciprocal changes of PDE activities. Calyculin A, an inhibitor of protein phosphatases 1 and 2 A, stimulated PDE4 and enhanced the inhibitory effect of CPT-cAMP on PDE1C. The reduction of PDE1C activity was characterized by a marked attenuation of the activation by Ca2+/calmodulin. Stimulation of PDE4 activity by CPT-cAMP or calyculin A was attributable to PDE4D3 and these effects could also be reproduced in human embryonic kidney cells expressing epitope-tagged PDE4D3. Together, these data show reciprocal regulation of PDE1C and PDE4D by PKA, which represents a novel scheme for plasticity in intracellular signalling.


Isolation and characterization of mutants corresponding to the MENA, MENB, MENC and MENE enzymatic steps of 5'-monohydroxyphylloquinone biosynthesis in Chlamydomonas reinhardtii.
Phylloquinone (PhQ), or vitamin K1 , is an essential electron carrier (A1 ) in photosystem I (PSI). In the green alga Chlamydomonas reinhardtii, which is a model organism for the study of photosynthesis, a detailed characterization of the pathway is missing with only one mutant deficient for MEND having been analyzed. We took advantage of the fact that a double reduction of plastoquinone occurs in anoxia in the A1 site in the mend mutant, interrupting photosynthetic electron transfer, to isolate four new phylloquinone-deficient mutants impaired in MENA, MENB, MENC (PHYLLO) and MENE. Compared with the wild type and complemented strains for MENB and MENE, the four men mutants grow slowly in low light and are sensitive to high light. When grown in low light they show a reduced photosynthetic electron transfer due to a specific decrease of PSI. Upon exposure to high light for a few hours, PSI becomes almost completely inactive, which leads in turn to lack of phototrophic growth. Loss of PhQ also fully prevents reactivation of photosynthesis after dark anoxia acclimation. In silico analyses allowed us to propose a PhQ biosynthesis pathway in Chlamydomonas that involves 11 enzymatic steps from chorismate located in the chloroplast and in the peroxisome.


Role of heat shock protein and cytokine expression as markers of clinical outcomes with glutamine-supplemented parenteral nutrition in surgical ICU patients.
Nutrients, such as glutamine (GLN), have been shown to effect levels of a family of protective proteins termed heat shock proteins (HSPs) in experimental and clinical critical illness. HSPs are believed to serve as extracellular inflammatory messengers and intracellular cytoprotective molecules. Extracellular HSP70 (eHSP70) has been termed a chaperokine due to ability to modulate the immune response. Altered levels of eHSP70 are associated with various disease states. Larger clinical trial data on GLN effect on eHSP expression and eHSP70's association with inflammatory mediators and clinical outcomes in critical illness are limited. Explore effect of longitudinal change in serum eHSP70, eHSP27 and inflammatory cytokine levels on clinical outcomes such as pneumonia and mortality in adult surgical intensive care unit (SICU) patients. Further, evaluate effect of parenteral nutrition (PN) supplemented with GLN (GLN-PN) versus GLN-free, standard PN (STD-PN) on serum eHSP70 and eHSP27 concentrations. Secondary observational analysis of a multicenter clinical trial in 150 adults after cardiac, vascular, or gastrointestinal surgery requiring PN support and SICU care conducted at five academic medical centers. Patients received isocaloric, isonitrogenous PN, with or without GLN dipeptide. Serum eHSP70 and eHSP27, interleukin-6 (IL-6), and 8 (IL-8) concentrations were analyzed in patient serum at baseline (prior to study PN) and over 28 days of follow up. eHSP70 declined over time in survivors during 28 days follow-up, but non-survivors had significantly higher eHSP70 concentrations compared to survivors. In patients developing pneumonia, eHSP70, eHSP27, IL-8, and IL-6 were significantly elevated. Adjusted relative risk for hospital mortality was reduced 75% (RR = 0.25, p = 0.001) for SICU patients with a faster decline in eHSP70. The area under the receiver operating characteristic curve was 0.85 (95% CI: 0.76 to 0.94) for the final model suggesting excellent discrimination between SICU survivors and non-survivors. GLN-PN did not alter eHSP70 or eHSP27 serum concentrations over time compared to STD-PN. Our results suggest that serum HSP70 concentration may be an important marker for severity of illness and likelihood of recovery in the SICU. GLN-supplemented-PN did not increase eHSP70.


Cerebrovascular damage in late-life depression is associated with structural and functional abnormalities of subcutaneous small arteries.
Late-life depression is increasingly viewed as a vascular illness because of patients exhibiting characteristic white matter brain lesions and in vivo large artery endothelial dysfunction. However, the "vascular depression" hypothesis pertains to the microvasculature, and this circulation has not been studied in this context. Our objective was to examine structure and function of small subcutaneous arteries in patients with late-life depression. Thus, 16 patients aged 71.8±4.0 years with late-life depression were compared with 15 control participants aged 72.1±5.9 years. There were similar cardiovascular profiles between the 2 groups. All of the participants underwent MRI brain scans and subcutaneous gluteal fat biopsy from which small arteries were isolated and studied using pressure myography. Cerebral microvascular damage in depressed patients was confirmed by assessment of basal ganglia Virchow-Robin space scores (depressed patients 3.9±1.7 versus controls: 2.5±1.6; P=0.01). Contractility to norepinephrine was equivalent in both groups, but relaxation of the small arteries to acetylcholine was significantly reduced in depressed patients (84.0±4.0%) compared with control participants (96.0±1.4%; P=0.012). This difference in arterial relaxation was reduced but not entirely eliminated when NO synthase was inhibited. Depressed patients also exhibited hypertrophic wall growth with an increase in medial cross-sectional area (P=0.035, multiple ANOVA and wall thickness; P=0.04, multiple ANOVA). In conclusion, despite similar cardiovascular profiles, depressed patients with cerebral microvascular damage show abnormalities of subcutaneous small artery structure and function.


Cutting edge: cell surface expression and lipopolysaccharide signaling via the toll-like receptor 4-MD-2 complex on mouse peritoneal macrophages.
The human MD-2 molecule is associated with the extracellular domain of human Toll-like receptor 4 (TLR4) and greatly enhances its LPS signaling. The human TLR4-MD-2 complex thus signals the presence of LPS. Little is known, however, about cell surface expression and LPS signaling of the TLR4-MD-2 complex in vivo. We cloned mouse MD-2 molecularly and established a unique mAb MTS510, which reacted selectively with mouse TLR4-MD-2 but not with TLR4 alone in flow cytometry. Mouse MD-2 expression in TLR4-expressing cells enhanced LPS-induced NF-kappaB activation, which was clearly inhibited by MTS510. Thioglycolate-elicited peritoneal macrophages expressed TLR4-MD-2, which was rapidly down-regulated in the presence of LPS. Moreover, LPS-induced TNF-alpha production by peritoneal macrophages was inhibited by MTS510. Collectively, the TLR4-MD-2 complex is expressed on macrophages in vivo and senses and signals the presence of LPS.


Effects of human chorionic gonadotropin, androgens, adrenocorticotropin hormone, dexamethasone and hyperprolactinemia on plasma sex steroid-binding protein.
This presentation reports the effects of androgens, glucocorticoids and some pituitary hormones on plasma sex steroid-binding protein (SBP). The latter was measured by a solid phase method after desteroidation of the plasma. An hCG test (1500 I.U. every other day X 7) was given to 60 boys. In the children with a normal testosterone (T) rise, plasma SBP decreased (% of basal values) either significantly (38.3 +/- 9.3%, group A; n = 29), or moderately (13.4 +/- 4.4%, group B; n = 9) or did not change (-1.6 +/- 6.4%, group C; n = 10). In the 3 infants tested at an age when SBP normally rise sharply, hCG partially prevented this rise. The administration of either fluoxymesterone (10 mg/m2 for 10 days) or depot-T (4 I.M. injections of 100 mg/m2 every 2 weeks) induced a significant drop (about 2-fold) in plasma SBP in a control group of infants or children, but did not change SBP in 3 infants with the androgen insensitivity syndrome. A single injection of 0.25 mg of ACTH did not significantly alter SBP levels. In contrast, at the end of a 3-day ACTH test (0.5 mg/m2 12 hourly X 6) SBP levels had significantly decreased (mean 35% fall) with no age or sex differences, and with no correlation with the cortisol levels reached. However, the lowering effect of ACTH on SBP levels is likely mediated by glucocorticoids, since its effect was reproduced by high doses (8 mg/day for 3 days) of dexamethasone given at once or after 3 days of treatment at lower dose (20 micrograms/kg BW). It would appear that the depressive effect of ACTH and/or dexamethasone is observed for a threshold dose of glucocorticoids (greater than 5-fold physiological levels) and a certain time (greater than or equal to 3 days) of exposure. The mechanism by which androgens and glucocorticoids lower SBP levels in vivo is not yet understood. From recent experiments, showing that both stimulate the secretion of SBP in hepatoma cells in vitro, it would appear that both hormones may alter SBP metabolism. In a selected population of hyperprolactinemic women, with normal weight and no hirsutism, plasma SBP levels were found in the normal female range. The discrepancy with previous studies in the literature may be explained by differences in the degree of hyperprolactinemia and/or associated hyperandrogenim. This study further documents the multifactorial and intricated hormonal influences involved in the regulation of plasma SBP in vivo.


Wisconsin trends in pneumonia and influenza mortality, 1980-2003.
Mortality due to pneumonia and influenza continues to be a serious public health threat, especially among those aged > or = 65. Continued monitoring of these high-risk populations is necessary for evaluating the impact of public health prevention activities, determining vaccine distribution policies, and ensuring that existing guidelines reflect the populations at risk. We characterized pneumonia and influenza mortality in Wisconsin from 1980 to 2003, including trend analysis, identification of high risk populations, and assessment of Wisconsin's progress toward state and national goals for vaccination. We examined mortality trends for pneumonia and influenza as underlying causes of death among all Wisconsin residents who died in the state from 1980 to 2003. The pneumonia and influenza (P&I) mortality rate increased from 27/100,000 to 38/100,000 during 1980 through 1988, and then decreased to 26/100,000 through 2003. The decline in the mortality rate after 1988 was temporally associated with improving pneumococcal and influenza vaccination among those > or = 65. By 2003, all age groups except those aged > or = 85 had lower P&I mortality than in 1980. In Wisconsin, the increase in pneumonia and influenza mortality demonstrated during the 1980s was reversed. However, there was relatively little change in mortality among those aged 65-84 and rates among those > or = 85 years have increased. Novel improvements in public health interventions are needed to improve the focus on the elderly, including efforts to increase vaccination, prevent pneumococcal disease, and explore other evidence-based strategies to reduce pneumonia and influenza mortality.


Endothelial versus pronephron fate decision is modulated by the transcription factors Cloche/Npas4l, Tal1, and Lmo2.
Endothelial specification is a key event during embryogenesis; however, when, and how, endothelial cells separate from other lineages is poorly understood. In zebrafish, Npas4l is indispensable for endothelial specification by inducing the expression of the transcription factor genes etsrp, tal1, and lmo2. We generated a knock-in reporter in zebrafish npas4l to visualize endothelial progenitors and their derivatives in wild-type and mutant embryos. Unexpectedly, we find that in npas4l mutants, npas4l reporter-expressing cells contribute to the pronephron tubules. Single-cell transcriptomics and live imaging of the early lateral plate mesoderm in wild-type embryos indeed reveals coexpression of endothelial and pronephron markers, a finding confirmed by creERT2-based lineage tracing. Increased contribution of npas4l reporter-expressing cells to pronephron tubules is also observed in tal1 and lmo2 mutants and is reversed in npas4l mutants injected with tal1 mRNA. Together, these data reveal that Npas4l/Tal1/Lmo2 regulate the fate decision between the endothelial and pronephron lineages.


Molecular mechanism of remodeling of autologous artery graft interposed to vein in rabbit.
Our previous study found that the artery interposed to vein did not develop atherosclerosis but rather underwent atrophic remodeling in hyperlipidemic rabbits, suggesting that local hemodynamic load was another important determinant for the development of atherosclerosis. This study focused on the cellular and molecular changes in autologous artery grafts derived from rabbits fed with high lipid diet for 1, 2, 4, 8, and 12 weeks. Thickness, area of vessel wall, and lumen area were measured and analyzed on the grafted common carotid artery (GCCA) interposed to vein and on the right common carotid artery. Apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling. Both elastin and collagen of GCCA were identified by the method of double stains of elastin and collagen. Reverse transcription polymerase chain reaction was used to observe matrix metalloproteinases (MMPs) mRNA expression changes in the examined arteries. The lumen area increased gradually in control common carotid artery and remained unchanged in GCCA 3 months later, since the surgery and the start of high lipid diet, while significantly increased apoptosis was evidenced from inner to outer part of GCCA. Collagen content decreased gradually and elastic fibers remained unchanged in GCCA. At 1 week after operation, the mRNA expression of MMP(2) and MMP(9) increased significantly and returned to baseline thereafter. The artery interposed to a vein underwent atrophy, characterized by increased apoptosis in the vessel wall from intima to adventitia, possibly due to low shear stress circumference and reduced vessel collagen resulting from postsurgical upregulated MMP(2) and MMP(9) expression.


Expression of sialyl Lewis(x) and Lewis(x) defines distinct stages of chicken B cell maturation.
Commitment of cells to the B lineage in chickens occurs only during a brief period of embryogenesis. B cell progenitors then progress through discrete developmental stages resulting in the production of mature B cells that are competent to form a functioning humoral immune system in the adult bird. During embryogenesis, chicken B cell precursors undergo tissue and developmental stage-specific changes in cell-surface glycosylation. Immature B cell progenitors that migrate to the bursa of Fabricius express the carbohydrate epitope sialyl Lewis(x). Such cells undergo initial clonal expansion within the bursa without undergoing gene conversion. Beginning between days 15 and 17 of embryogenesis, B cells in the bursa undergo a tissue specific change in surface glycosylation that results in the loss of sialyl Lewis(x) expression and the acquisition of the related carbohydrate structure Lewis(x). Expression of Lewis(x) identifies B lymphocytes that have begun to undergo gene conversion. Before emigration from the bursa, bursal lymphocytes undergo another phenotypic switch in glycosylation and down-regulate Lewis(x) expression. Therefore, developmental switches in glycosylation allow us to distinguish three populations of B cells in the bursa of Fabricius at defined stages of development and suggest that regulation of cell-surface glycosylation plays a role in B cell development in the chicken.


Combination of antiretroviral drugs as microbicides.
Tenofovir, a highly prescribed drug for the treatment of HIV/AIDS infections, has recently also shown its effectiveness as a potential topical microbicide drug in the prevention of HIV transmission. Here, we discuss the combination of tenofovir with various other antiretrovirals (ARV) highlighting the large class of carbohydrate-binding agents (CBAs) targeting the glycans on the viral envelope gp120 for their anti-HIV activity and their favorable combinatory potential. The tenofovir/CBA and several other ARV combinations consistently showed synergistic antiviral activities. Also combinations of other classes of ARV such as receptor (i.e. CD4, CXCR4 and CCR5) inhibitors, various monoclonal antibodies (mAbs) directed against the HIV envelope gp120 and HIV gp41 inhibitors were demonstrated to have synergistic anti-HIV effects. Moreover, certain antimetabolite drugs that show limited, if any, anti-HIV activity when administered as a single drug, can potentiate the antiviral activity of anti-HIV nucleoside analogues (NRTIs) by creating a beneficial metabolic and/or competitive advantage for the combined NRTIs. Thus, well-defined combinations of ARV may synergize and/or enhance the antiviral potency of the individual drugs and should be envisioned in the design of future microbicide studies. Recently, drugs such as tenofovir and acyclovir were demonstrated to be endowed with a dual (concomitant) antiviral (i.e. anti-HIV/HSV) activity in different in vitro, ex vivo and animal models. They also deserve special attention for their potential to prevent HIV transmission and to concomitantly suppress co-pathogens of HIV such as herpes viruses.


Substantial reduction of platelet adhesion by heparin-coated stents.
Although optimized antiplatelet medication has improved the clinical outcome after coronary stenting, vessel occlusion and restenosis still remain a relevant clinical problem. Platelets play a key role in this process. Therefore, the authors compared the platelet adhesion on different stent surface modifications (electropolished without coating or coated with carbon, carbon and additional heparin, silicon carbide, or heparin alone) to investigate their role in reducing platelet adhesion. All stents and additional stainless steel plates were incubated in heparinized whole blood with radiolabeled platelets. After washing the stents and plates four times, radioactivity caused by the adhesion of radiolabeled platelets was measured. The adhesion of radiolabeled platelets, compared to uncoated, electropolished stents, was reduced through silicon carbide coating to 58.6%, by carbon coating with additional heparin to 32.9%, and heparin coating alone to 7.7%. Stent coating with heparin is the most effective among the examined coatings in reducing platelet adhesion in vitro.


Association between body composition and bone mineral density in healthy, non-obese, young Romanian adults and effects of menopause.
The link between bone mass and body composition is widely recognized, but the mechanism remains unclear. Most studies enrolled subjects irrespective of their body weight and only few works were selectively performed on healthy subjects with body mass index (BMI) within normal limits. We aimed to determine the relevance of body composition parameters to bone mass in healthy, young and non-obese Romanian volunteers (n=42) and in postmenopausal women (n=20) and to establish the effects of menopausal transition. Both bone mineral density (BMD) and body composition were assessed using whole-body dual X-ray absorptiometry (DXA). Despite normal mean BMI, large variability of the whole-body fat mass (FM) content was noted, ranging between 18.6-49.7% in women and 22-40.3% in men. Fat mass was not related to bone density; in contrast, BMD at all sites was positively associated to fat-free mass (FFM) in young non-obese women (r=0.34-0.53). In women, the trunk fat mass/leg fat mass ratio was significantly predicted by age (p=0.001), explaining about 20% of the pattern variability. Menopausal status appeared not to significantly influence whole-body fat or FM distribution. A tendency towards a higher trunk FM/legs FM ratio was observed after menopause, but lost after age-adjustment. In non-obese subjects, even of young age, the FM content and distribution is highly variable. FFM mass appears to be the main composition contributor to bone mass, at least in young, healthy, non-obese women. Menopause is not associated to major changes of whole-body fat and trunk adipose tissue, although a significant decrease in peripheral FM content and a tendency towards an age-dependent central redistribution of adiposity is noticed.


A dialyzer-based flow system for validating dynamic contrast enhanced MR image acquisition.
Dynamic contrast enhanced magnetic resonance imaging (MRI) has proven to be quite sensitive for the characterization of masses and early response to therapy. However, it is fraught with a number of procedural challenges as well as a lack of standardization. In this article, we describe the use of a simple dialyzer-based flow system to evaluate reproducibility of dynamic contrast enhanced MRI under active flow conditions. The MR signal during a bolus injection of Gd-DTPA was analyzed to test the precision and variability of contrast agent kinetics during a typical dynamic contrast enhanced MRI sequence. A simple model allows an estimation of the washout rate constant of Gd-DTPA through the polysulfone tubules of the dialyzer. The simple flow phantom described here provided reproducible measurements of the washout rate constants. The washout rate increased from 0.20 ± 0.005 min(-1) to 0.25 ± 0.008 min(-1) over 32 weeks. Measurements were also made at week 24 using dynamic computed tomography and found to be 0.27 ± 0.006 min(-1) . Overall, the computed tomography derived rate constants results were found be ∼12% higher than the corresponding MRI values. In this study, we show that a simple dialyzer-based flow phantom can be used for testing dynamic contrast enhanced MRI pulse sequences and also allows for short-term reproducibility testing of rate constants.


Malaria control in South Sudan, 2006-2013: strategies, progress and challenges.
South Sudan has borne the brunt of years of chronic warfare and probably has the highest malaria burden in sub-Saharan Africa. However, effective malaria control in post-conflict settings is hampered by a multiplicity of challenges. This manuscript reports on the strategies, progress and challenges of malaria control in South Sudan and serves as an example epitome for programmes operating in similar environments and provides a window for leveraging resources. To evaluate progress and challenges of the national malaria control programme an in-depth appraisal was undertaken according to the World Health Organization standard procedures for malaria programme performance review. Methodical analysis of published and unpublished documents on malaria control in South Sudan was conducted. To ensure completeness, findings of internal thematic desk assessments were triangulated in the field and updated by external review teams. South Sudan has strived to make progress in implementing the WHO recommended malaria control interventions as set out in the 2006-2013 National Malaria Strategic Plan. The country has faced enormous programmatic constraints including infrastructure, human and financial resource and a weak health system compounded by an increasing number of refugees, returnees and internally displaced people. The findings present a platform on which to tailor an evidence-based 2014-2018 national malaria strategic plan for the country and a unique opportunity for providing a model for countries in a post-conflict situation. The prospects for effective malaria control and elimination are huge in South Sudan. Nevertheless, strengthened coordination, infrastructure and human resource capacity, monitoring and evaluation are required. To achieve all this, allocation of adequate local funding would be critical.


Compendium of psittacosis (chlamydiosis) control, 1997. Centers for Disease Control and Prevention.
Infection with Chlamydia psittaci, often referred to as avian chlamydiosis (AC), is an important cause of systemic illness in companion birds (i.e., birds kept by humans as pets) and poultry. Infection can be transmitted from infected birds to humans. In humans, infection caused by C. psittaci is referred to as psittacosis, which can result in fatal pneumonia. This compendium provides information on AC (also known as psittacosis, ornithosis, and parrot fever) and psittacosis (also known as parrot disease, parrot fever, and chlamydiosis) to public health officials, veterinarians, physicians, the companion-bird industry, and others concerned with control of the disease and protection of public health. These recommendations provide effective, standardized disease control procedures for AC in companion birds and will be reviewed and revised as necessary.


Prevalence of Helicobacter pylori infection in patients with peptic ulcer diseases.
To determine the prevalence of Helicobacter pylori (H. pylori) infection among patients presenting with peptic ulcer disease (PUD) and to establish the relationship between H. pylori infection and its diverse pathology. Secondly, we aimed to examine the effect of age, gender, and geographical distribution on the prevalence of the disease. The study included patients with PUD who underwent upper gastrointestinal endoscopy at Hera General Hospital, Makkah, Kingdom of Saudi Arabia between January 2003 and February 2004. We tested the biopsies for the detection of H. pylori by Campylobacter like organism (CLOTM) test, histopathology, immunoglobulin G (IgG) antibodies, culture, and antimicrobial susceptibility testing. The overall prevalence rate of H. pylori infection among 132 patients with PUD was 63%, while it was high among females (70%) as compared with males (58%). The H. pylori were mainly found in chronic active gastritis (89%) and severe active gastritis (96%). Helicobacter pylori were documented by CLOTM test in 73 (55.3%) cases, histopathology in 69 (52.3%) cases, microbiological culture in 59 (44.7%) cases, and IgG antibodies in 61 (46.2%) cases. The highest resistance (31%) was found in metronidazole, while lowest the (3%) in tetracycline and erythromycin. The highest prevalence of H. pylori was found in the younger age group with female preponderance. The leading causes of multifocal pathology were chronic and severe active gastritis secondary to H. pylori infection.


Medullary raphe neuron activity is altered during fictive cough in the decerebrate cat.
Chemical lesions in the medullary raphe nuclei region influence cough. This study examined whether firing patterns of caudal medullary midline neurons were altered during cough. Extracellular neuron activity was recorded with microelectrode arrays in decerebrated, neuromuscular-blocked, ventilated cats. Cough-like motor patterns (fictive cough) in phrenic and lumbar nerves were elicited by mechanical stimulation of the intrathoracic trachea. Discharge patterns of respiratory and nonrespiratory-modulated neurons were altered during cough cycles (58/133); 45 increased and 13 decreased activity. Fourteen cells changed firing rate during the inspiratory and/or expiratory phases of cough. Altered patterns in 43 cells were associated with the duration of, or extended beyond, the cough episodes. The different response categories suggest that multiple factors influence the discharge patterns during coughing: e.g., respiratory-modulated and tonic inputs and intrinsic connections. These results suggest involvement of midline neurons (i.e., raphe nuclei) in the cough reflex.


AFLP protocol comparison for microbial diversity fingerprinting.
Over the last decade, several methods based on genomic DNA have been developed for the identification and genotyping of prokaryotic and eukaryotic organisms. These genomic methods differ regarding taxonomic range, discriminatory power, reproducibility, and ease of interpretation and standardization. The amplified fragment length polymorphism (AFLP) technique is a very powerful DNA fingerprinting technique for DNA of any source or complexity, varying in both size and base composition. In addition, this method shows high discriminatory power and good reproducibility allowing it to be efficient in discriminating at both the species and strain levels. The development and application of AFLP have allowed significant progress in the study of biodiversity and taxonomy of microorganisms. In the last years, the Applied Biosystems AFLP Microbial Fingerprinting Kit, now out of production, was widely used in various studies to perform AFLP characterization of selected bacteria strains (described by Vos et al. (Nucleic Acids Res 23(21):4407-4414, 1995)). Its replacement gives the possibility for laboratories to continue the use of the previous AFLP data as a reference for bacteria genetic fingerprinting analysis in biodiversity studies. To overcome this issue a result comparison, by using an improved AFLP protocol and the AFLP commercial kit, was performed. In particular, previous results on different species (Listeria monocytogenes, Lactobacillus plantarum, and Streptococcus thermophilus) obtained with the commercial kit were compared with the improved AFLP procedure to validate the protocol. When compared with the AFLP Microbial Fingerprinting Kit, the improved protocol shows high reproducibility, resolution, and overall, is a faster method with lower costs.


Laser ablation-miniature mass spectrometer for elemental and isotopic analysis of rocks.
A laser ablation-miniature mass spectrometer (LA-MMS) for the chemical and isotopic measurement of rocks and minerals is described. In the LA-MMS method, neutral atoms ablated by a pulsed laser are led into an electron impact ionization source, where they are ionized by a 70 eV electron beam. This results in a secondary ion pulse typically 10-100 μs wide, compared to the original 5-10 ns laser pulse duration. Ions of different masses are then spatially dispersed along the focal plane of the magnetic sector of the miniature mass spectrometer (MMS) and measured in parallel by a modified CCD array detector capable of detecting ions directly. Compared to conventional scanning techniques, simultaneous measurement of the ion pulse along the focal plane effectively offers a 100% duty cycle over a wide mass range. LA-MMS offers a more quantitative assessment of elemental composition than techniques that detect ions directly generated by the ablation process because the latter can be strongly influenced by matrix effects that vary with the structure and geometry of the surface, the wavelength of the laser beam, and the not well characterized ionization efficiencies of the elements in the process. The above problems attendant to the direct ion analysis has been minimized in the LA-MMS by analyzing the ablated neutral species after their post-ionization by electron impaction. These neutral species are much more abundant than the directly ablated ions in the ablated vapor plume and are, therefore, expected to be characteristic of the chemical composition of the solid. Also, the electron impact ionization of elements is well studied and their ionization cross sections are known and easy to find in databases. Currently, the LA-MMS limit of detection is 0.4 wt.%. Here we describe LA-MMS elemental composition measurements of various minerals including microcline, lepidolite, anorthoclase, and USGS BCR-2G samples. The measurements of high precision isotopic ratios including (41)K/(39)K (0.077 ± 0.004) and (29)Si/(28)Si (0.052 ± 0.006) in these minerals by LA-MMS are also described. The LA-MMS has been developed as a prototype instrument system for space applications for geochemical and geochronological measurements on the surface of extraterrestrial bodies.


Biological X-ray absorption spectroscopy and metalloproteomics.
In the past seven years the size of the known protein sequence universe has been rapidly expanding. At present, more then five million entries are included in the UniProtKB/TrEMBL protein database. In this context, a retrospective evaluation of recent X-ray absorption studies is undertaken to assess its potential role in metalloproteomics. Metalloproteomics is the structural and functional characterization of metal-binding proteins. This is a new area of active research which has particular relevance to biology and for which X-ray absorption spectroscopy is ideally suited. In the last three years, biological X-ray absorption spectroscopy (BioXAS) has been included among the techniques used in post-genomics initiatives for metalloprotein characterization. The emphasis of this review is on the progress in BioXAS that has emerged from recent meetings in 2007-2008. Developments required to enable BioXAS studies to better contribute to metalloproteomics throughput are also discussed. Overall, this paper suggests that X-ray absorption spectroscopy could have a higher impact on metalloproteomics, contributing significantly to the understanding of metal site structures and of reaction mechanisms for metalloproteins.


Identification of the mechanism of enhanced exciton interaction in rigidly linked naphthalene dimers.
Recently we characterized the low-lying electronic excitations of H-aggregated perylene bisimide (PBI) dyes using the time-dependent long-range-corrected density functional theory (TD-LRC-DFT) and the mixed intramolecular Frenkel exciton (FE) and the intermolecular charge-transfer exciton (CTE) model (F. Pan, F. Gao, W. Z. Liang and Y. Zhao, J. Phys. Chem. B, 2009, 113, 14581.). We found that the dimer absorption follows closely the spectra of PBI aggregates in solution, and demonstrates strong mixing of two kinds of excitons. Here we implement the theoretical approaches to study the electronic excitations of a family of bridged naphthalene dimers. It is found that TD-LRC-DFT reproduces all experimentally observed trends in the absorption profiles. By comparing the results obtained from the popular hybrid exchange-correlation functionals with these from LRC-DFT, we display how the experimentally measured dipole-allowed mixed exciton states of systems are formed. The major terms which contribute to the experimentally measured dimeric splitting are qualitatively identified. Three-dimensional plots of transition charge density help visualize how the excitons couple.


Anticoagulation control of pharmacist-managed collaborative care versus usual care in Thailand.
There has been a lack of evidence of the effects of pharmacist-managed warfarin therapy (PMWT) in developing countries (e.g. Southeast Asian countries) where the patients' characteristics, genetic make-up, clinical practice and healthcare system are different from the Western world. This study aimed to compare the anticoagulation control and clinical outcomes associated with warfarin therapy provided by PMWT to usual care (UC) in the Thai population. A 1,000-bed tertiary-care hospital in Nakornratchasima province of Thailand. A quasi-experimental study comparing PMWT and UC in patients receiving long-term warfarin therapy. For PMWT group, clinical pharmacists optimised the warfarin therapy and suggested recommendations (e.g. dose adjustment, safer alternative drugs, and follow-up time) to physicians. The UC group received the standard care. Time in therapeutic range (TTR), both actual- and expanded-TTR, bleeding and thromboembolic complications, and physician' acceptance of pharmacist suggestions. Of 433 patients enrolled, 220 and 213 were in the PMWT and UC groups respectively. At baseline, patient's characteristics of both groups were comparable. At the end of follow-up period, patients in the PMWT group had significantly higher actual-TTR (48.3% vs. 40.1%; P < 0.001) and expanded-TTR (62.7% vs. 53.9%; P < 0.001) compared to those in the UC group. Rates of major bleeding were 4.4 vs 4.5 events per 100 person-years for the PMWT and UC groups, respectively. Pharmacists performed 284 interventions with an acceptance rate of 80.3% from physicians. Pharmacist-managed warfarin therapy resulted in a significantly better anticoagulation control. This study showed that a collaborative approach in anticoagulation management can be successfully implemented in a developing country. Implementation of such care model in other developing countries should be considered.


Observation of traveling thermoacoustic shock waves (L).
Shock waves were explored in the thermoacoustic spontaneous gas oscillations occurring in a gas column with a steep temperature gradient. The results show that a periodic shock occurs in the traveling wave mode in a looped tube but not in the standing wave mode in a resonator. Measurements of the harmonic components of the acoustic intensity reveal a clear difference between them. The temperature gradient acts as an acoustic energy source for the harmonic components of the shock wave in the traveling wave mode but as an acoustic energy sink of the second harmonic in the standing wave mode.


The relationship between left ventricular shape and QT interval dispersion.
Left ventricular geometry is suspected to affect heterogeneity of myocardial repolarization; therefore, it is plausible but unproven that increased sphericity of the left ventricle is associated with greater QT interval dispersion. In 60 patients with dilated cardiomyopathy with left ventricular ejection fraction < or = 30%, we found that spherical distortion of the left ventricle was associated with increased QT dispersion, implying increased heterogeneity of myocardial repolarization.


Clinical outcome following DIAM implantation for symptomatic lumbar internal disk disruption: a 3-year retrospective analysis.
Internal disk disruption (IDD), an early event of lumbar disk degeneration, is the most common cause of low back pain. Since increased intradiskal pressure (IDP) is associated with symptoms and progression of disk degeneration, unloading a painful disk with an interspinous process device (IPD) is a rational treatment option. The goal of this study was to evaluate the effectiveness of dynamic stabilization with an IPD in the treatment of symptomatic IDD of the lumbar spine. Patients with symptomatic IDD were treated with implantation of an IPD, the device for intervertebral assisted motion (DIAM). Diagnosis of IDD was based on typical MRI finding of posterior annular high-intensity zone and positive provocative test on discography. IDP was analyzed intraoperatively. Axial back and leg pain was evaluated with visual analog scale, functional status with Oswestry Disability Index, and final clinical outcomes with Odom criteria. Data from 34 patients followed up for at least 3 years were collected. DIAM implantation significantly reduced IDP (n=11, P<0.0001). All 34 patients reported symptom relief. Thirty-one patients (91%) remained symptom free until the last followups. Three patients (9%) experienced recurrence of pain, of which the causes were unrelated to the IDD or surgery. Disk status at the DIAM-implanted segments remained stable. Segmental flexion/extension mobility was preserved in 27 of 30 patients with preoperative mobility. No proximal or distal adjacent segment degeneration was observed. The final clinical outcomes were excellent/good in 31 and fair/poor in three patients. For patients with symptomatic IDD, dynamic stabilization with DIAM provides pain relief and functional improvement. The implantation maintains disk status and prevents progression of disk degeneration, without compromising segmental flexion/extension mobility or causing adjacent segment degeneration.


Selenoprotein P and selenoprotein M block Zn2+ -mediated Aβ42 aggregation and toxicity.
Aggregation and cytotoxicity of the amyloid-β (Aβ) peptide with transition metal ions in neuronal cells have been suggested to be involved in the progression of Alzheimer's disease (AD). A therapeutic strategy to combat this incurable disease is to design chemical agents to target metal-Aβ species. Selenoproteins are a group of special proteins that contain the 21st amino acid Sec in their sequence. Due to the presence of Sec, studies of this group of proteins are basically focused on their roles in regulating redox potential and scavenging reactive oxygen species. Here, we reported that the His-rich domain of selenoprotein P (SelP-H) and the Sec-to-Cys mutant selenoprotein M (SelM') are capable of binding transition metal ions and modulating the Zn(2+)-mediated Aβ aggregation, ROS production and neurotoxicity. SelM' (U48C) and SelP-H were found to coordinate 0.5 and 2 molar equivalents of Zn(2+)/Cd(2+) with micromolar and submicromolar affinities, respectively. Metal binding induced the structural changes in SelP-H and SelM' according to the circular dichorism spectra. Zn(2+) binding to Aβ42 almost completely suppressed Aβ42 fibrillization, which could be significantly restored by SelP-H and SelM', as observed by thioflavin T (ThT) fluorescence and transmission electron microscopy (TEM). Interestingly, both SelP-H and SelM' inhibited Zn(2+)-Aβ42-induced neurotoxicity and the intracellular ROS production in living cells. These studies suggest that SelP and SelM may play certain roles in regulating redox balance as well as metal homeostasis.


Fluorescent Copper Nanomaterials for Sensing NO2 - and Temperature.
In this work, highly fluorescent copper nanomaterials were synthesized by using ascorbic acid as a ligand. The excitation wavelength of copper nanomaterials is 367 nm, and the emission wavelength is 420 nm. The size range is 5-6 nm. Nitrite can selectively quench the fluorescence of copper nanomaterials. Therefore, copper nanomaterials can be used to selectively detect nitrite ions. The linear equation is F = -32.94 c (NO2 -) + 8,455, and the correlation coefficient is 0.9435. At the same time, we found that the fluorescence intensity of copper nanomaterials has a good correlation with temperature (20-60°C), which shows that they have great potential in the application of nanothermometers.


CNS involvement in CMTX1 caused by a novel connexin 32 mutation: a 6-year follow-up in neuroimaging and nerve conduction.
X-linked Charcot-Marie-Tooth disease, type 1 (CMTX1) is one of the most common inherited neurological disorders. Obvious CNS involvement is relatively rare in CMTX1 patients. A 24-year-old male with CMTX1 presented with three transient stroke-like attacks, and was followed up regularly for 6 years with brain MRI and electrophysiological examination. Transient symmetrical high signals on T2 imaging and restricted diffusion were found in bilateral deep white matter. Electrophysiological measurement revealed a sensorimotor peripheral neuropathy with slightly reduced nerve conduction velocities. A novel thymine to cytosine mutation at nucleotide position 445 in the connexin 32 allele of the GJB1 gene was identified. During the 6-year longitudinal study, patient's motor and sensory function did not worsen; radiological abnormalities correlated with episodes of CNS dysfunction and resolved after clinical recovery; electrophysiological records showed no obvious change. Little change in the patient's clinical, radiological and electrophysiological results over the follow-up reflected a slow disease progression.


[Study on the active life expectancy of the elderly and its longitudinal transition in Beijing].
Focus on the Active Life Expectancy (ALE) of elderly in Beijing and the transition in recent years. A representative sample of 3257 elderly people who lived in the urban, suburban and rural communities in Beijing that had been followed up for 12 years. Their health and survival status had been surveyed every 2-3 years. Activity Daily Living scale (ADL), recommended by WHO was used to evaluate the physical function capability of the elderly. IMaCH 0.8 was used to estimate life expectancy (LE) and active life expectancy (ALE) for both periods while age, sex and rural/urban residence areas were adjusted. Longitudinally, data showed that the main characters remained unchange throughout the two periods including 1) LE, ALE, ALE/LE of elderly living in urban area were higher than those living in rural area; 2) LE seemed longer in women than men, but ALE/LE was less in women. The transition between two period showed that 1) LE increased modestly in all groups but less prominent in urban residents and in females; 2) ALE was not significantly changed in the rural elderly but declined markedly in women living in the urban area; 3) ALE/LE of the elderly declined in all groups, especially in urban and oldest old groups. In Beijing, elderly AL-E did not increase in parallel with the increase of LE while ALE/LE of the elderly declined significantly in recent years. In order to improve quality of life of the elderly and to increase their ALE, emphasis should be given to prevention of cardiovascular, cerebrovascular and other chronic diseases while reducing the occurrence of physical disability and strengthening on rehabilitation would be the basic health care measures.


Serous retinal detachment and cystoid macular edema in a patient with Wyburn-Mason syndrome.
Wyburn-Mason syndrome is a rare phacomatosis characterized by unilateral arteriovenous malformations (AVMs) involving the brain, retina, and (rarely) the skin. The diagnosis is concluded with dilated fundus examination and markedly dilated tortuous vascular loops with arteriovenous communications on fluorescent angiography. We present a 14-year-old male patient with Wyburn-Mason syndrome who developed serous macular neuroretinal detachment, cystoid macular edema (CME), and consequent visual deterioration in the left eye. To the best of our knowledge, this is the first report of a patient with Wyburn-Mason syndrome who developed serous retinal detachment and CME.


Twin-arginine translocation of active human tissue plasminogen activator in Escherichia coli.
When eukaryotic proteins with multiple disulfide bonds are expressed at high levels in Escherichia coli, the efficiency of thiol oxidation and isomerization is typically not sufficient to yield soluble products with native structures. Even when such proteins are secreted into the oxidizing periplasm or expressed in the cytoplasm of cells carrying mutations in the major intracellular disulfide bond reduction systems (e.g., trxB gor mutants), correct folding can be problematic unless a folding modulator is simultaneously coexpressed. In the present study we explored whether the bacterial twin-arginine translocation (Tat) pathway could serve as an alternative expression system for obtaining appreciable levels of recombinant proteins which exhibit complex patterns of disulfide bond formation, such as full-length human tissue plasminogen activator (tPA) (17 disulfides) and a truncated but enzymatically active version of tPA containing nine disulfides (vtPA). Remarkably, targeting of both tPA and vtPA to the Tat pathway resulted in active protein in the periplasmic space. We show here that export by the Tat translocator is dependent upon oxidative protein folding in the cytoplasm of trxB gor cells prior to transport. Whereas previous efforts to produce high levels of active tPA or vtPA in E. coli required coexpression of the disulfide bond isomerase DsbC, we observed that Tat-targeted vtPA and tPA reach a native conformation without thiol-disulfide oxidoreductase coexpression. These results demonstrate that the Tat system may have inherent and unexpected benefits compared with existing expression strategies, making it a viable alternative for biotechnology applications that hinge on protein expression and secretion.


Quantitation of free glycation compounds in saliva.
In the course of the Maillard reaction, which occurs during heating of food but also under physiological condition, a broad spectrum of reaction products is formed. Among them, the advanced glycation endproducts (AGEs) Nε-carboxymethyllysine (CML), pyrraline (Pyr), methylglyoxal-derived hydroimidazolone 1 (MG-H1) and Nε-carboxyethyllysine (CEL) are the quantitatively dominating compounds during later reaction stages. Those dietary glycation compounds are under discussion as to be associated with chronic inflammation and the pathophysiological consequences of diseases such as diabetes. In the present study, the concentration of individual glycation compounds in saliva was monitored for the first time and related to their dietary uptake. Fasting saliva of 33 metabolically healthy subjects was analyzed with HPLC-MS/MS. The observed levels of individual glycation compounds ranged from 0.5 to 55.2 ng/ml and differed both intra- and interindividually. Patterns did not correlate with subject-related features such as vegetarianism or sports activities, indicating that dietary intake may play an important role. Therefore, six volunteers were asked to eat a raw food diet free of glycation compounds for two days. Within two days, salivary Pyr was lowered from median 1.7 ng/ml to a minimum level below the limit of detection, and MG-H1 decreased from 3.6 to 1.7 ng/ml in in a time-dependent manner after two days. Salivary CML and CEL concentrations were not affected. Therefore, measuring Pyr and MG-H1 in saliva is a suitable diagnostic tool to monitor the dietary intake and metabolic transit of glycation compounds present in heated foods.


Isolation and culture of adult Sertoli cells and their effects on the function of co-cultured allogeneic islets in vitro.
Globally, 180 million people suffer from diabetes mellitus. Islet transplantation is believed to be an almost ideal therapy for insulin-dependent patients. How to maintain the viability and the function of isolated human islets is a challenge in clinical practice. Sertoli cells are considered 'nurse cells' in the seminiferous tubules and have been used in cell graft protocols for neurodegenerative diseases and diabetes in many studies. Many researchers have used immature murine testes as the primarily source of Sertoli cells in islet transplantation because they are easily purified. Mature human Sertoli cells have been seldom investigated. In the present study, we developed a method for the isolation and culture of Sertoli cells derived from adult human testes, and investigated their effects on the function of allogeneic islets when they were cultured together in vitro. Adult Sertoli cells were prepared successfully by two-step enzyme digestion with trypsin, collagenase and hyaluronidase. They were identified by morphological characteristics and their activity was determined by MTT colorimetry over a 28-day culture time in vitro. A glucose-stimulated insulin secretion test was performed to detect the effects of Sertoli cells on allogeneic islets' function when they were co-cultured for 21 days in vitro. In cultured cells, mature human Sertoli cells accounted for more than 90% of total cells. The activity of Sertoli cells reached 95% and they remained highly cytoactive for a long time in vitro (P > 0.05). Compared with the islets cultured alone, the co-cultured islets with allogeneic Sertoli cells maintained higher sensitivity to glucose stimulation for the duration of the experiment (P < 0.01). A method of isolation and culture of Sertoli cells from adult testes has been established. Sertoli cells could enhance allogeneic islets' function when they were co-cultured in vitro. They could be a helper cell in islet transplantation.


The role of NAD(P)H: quinone reductase (EC 22.214.171.124, DT-diaphorase) in the reductive bioactivation of the novel indoloquinone antitumor agent EO9.
EO9 [3-hydroxymethyl-5-aziridinyl-1-methyl-2-(H-indole-4, 7-indione)-propenol] is a novel indoloquinone structurally related to mitomycin C, a quinone anticancer drug that requires reductive bioactivation. NAD(P)H: (quinone-acceptor) oxidoreductase (quinone reductase, DT-diaphorase, EC 184.108.40.206) is an obligate 2-electron donating enzyme that can reduce a variety of quinones resulting either in bioactivation or bioprotection. Using quinone reductase (QR) preparations from rat Walker 256 mammary tumor cells and human HT29 colon carcinoma cells, we have characterized the role of this enzyme in EO9 reductive metabolism. QR activity was assayed under optimal conditions by following cytochrome c reduction at 550 nm in the presence of enzyme, quinone substrate, NADH, and bovine albumin, and confirmed by loss of EO9 absorbance at 550 nm. Both the rat and human tumor cell enzymes catalyzed reduction of the benchmark quinone menadione with a similar Km of 1.4-3.1 microM, although the Vmax was 7 to 8-fold lower for the human preparation. EO9 was readily reduced by the rat Walker QR. The mean Km was about 5-fold higher than for menadione at around 15 microM and the Vmax was 6-fold lower at around 2.5 mumol of cytochrome c reduced mg-1 of protein. EO9 was also metabolized by QR from HT29 human colon carcinoma cells but rather less efficiently than by the rat tumor enzyme. For example, the rate was 6-fold lower than that for the Walker tumor enzyme at 100 microM substrate concentration after correcting for the 7- to 8-fold difference in specific activity for the two preparations.(ABSTRACT TRUNCATED AT 250 WORDS)


Integrative Analyses Reveal Tstd1 as a Potential Modulator of HDL Cholesterol and Mitochondrial Function in Mice.
High-density lipoprotein (HDL) cholesterol levels are closely associated with human health and diseases. To identify genes modulating plasma HDL levels, we integrated HDL measurements and multi-omics data collected from diverse mouse cohorts and combined a list of systems genetics methods, including quantitative trait loci (QTL) mapping analysis, mediation analysis, transcriptome-wide association analysis (TWAS), and correlation analysis. We confirmed a significant and conserved QTL for plasma HDL on chromosome 1 and identified that Tstd1 liver transcript correlates with plasma HDL in several independent mouse cohorts, suggesting Tstd1 may be a potential modulator of plasma HDL levels. Correlation analysis using over 70 transcriptomics datasets in humans and mice revealed consistent correlations between Tstd1 and genes known to be involved in cholesterol and HDL regulation. Consistent with strong enrichment in gene sets related to cholesterol and lipoproteins in the liver, mouse strains with high Tstd1 exhibited higher plasma levels of HDL, total cholesterol and other lipid markers. GeneBridge using large-scale expression datasets identified conserved and positive associations between TSTD1/Tstd1 and mitochondrial pathways, as well as cholesterol and lipid pathways in human, mouse and rat. In summary, we identified Tstd1 as a new modulator of plasma HDL and mitochondrial function through integrative systems analyses, and proposed a new mechanism of HDL modulation and a potential therapeutic target for relevant diseases. This study highlights the value of such integrative approaches in revealing molecular mechanisms of complex traits or diseases.


Tumor necrosis factor alpha (TNF-alpha)-induced prostaglandin E2 release is mediated by the activation of cyclooxygenase-2 (COX-2) transcription via NFkappaB in human gingival fibroblasts.
Nuclear factor kappaB (NFkappaB) is a transcription factor and plays a key role in the expression of several genes involved in the inflammatory process. Cyclooxygenase (COX) is the key regulatory enzyme of the prostaglandin/eicosanoid synthetic pathway. COX-2 is a highly inducible enzyme by proinflammatory cytokines, of which gene expression is regulated by NFkappaB. TNF-alpha is a pro-inflammatory cytokine. In this paper, we investigated the involvement of NFkappaB on TNF-alpha-mediated prostaglandin E2 (PGE2) release and COX-2 gene expression in human gingival fibroblasts (HGF). TNF-alpha-induced PGE2 release and COX-2 mRNA accumulation in a time- and concentration-dependent manner in HGF. The results of transient transfection assays using a chimeric construct of the human COX-2 promoter (nts -1432 approximately +59) ligated to a luciferase reporter gene indicated that TNF-a stimulated the transcriptional activity approximately 1.4-fold. Gel mobility shift assays with a radiolabelled COX-2-NFkappaB oligonucleotide (nts -223 to -214) revealed an increase in the binding of nuclear proteins from TNF-alpha-stimulated HGF. The COX-2-NFKB DNA-protein complex disappeared after treatment with pyrrolidine dithiocarbamate (PDTC; an antioxidant) or herbimycin A (a tyrosine kinase inhibitor). PDTC and herbimycin A attenuated TNF-alpha-stimulated PGE2 release. These results suggest that NFkappaB transcription factor is a key regulator of COX-2 expression in TNF-alpha-induced PGE2 production, which is mediated through a tyrosine kinase pathway in HGF.


Ezrin Is Associated with Disease Progression in Ovarian Carcinoma.
Ezrin and p130Cas are structural proteins with an important role in signaling pathways and have been shown to promote cancer dissemination. We previously reported on overexpression of both ezrin and p130Cas in breast carcinoma effusions compared to primary carcinomas. Since ovarian and breast carcinomas share the ability to disseminate by forming malignant effusions, we sought to study the role of these molecules in ovarian carcinoma (OC). OC cell lines were cultured in two different 3-dimensional conditions, on alginate scaffolds and as spheroids, which served as models for solid tumor and malignant effusions, respectively. shRNA was used to reduce protein expression in the cells. The malignant potential was evaluated by chemo-invasion assay, branching capacity on Matrigel and rate of proliferation. Subsequently, clinical specimens of high-grade serous carcinoma effusions, ovarian tumors and solid metastases were analyzed for ezrin and p130Cas expression. Higher ezrin expression was found in cells composing the spheroids compared to their counterparts cultured on alginate scaffold and in clinical samples of malignant effusions compared to solid tumors. In addition, reduced Ezrin expression impaired the invasion ability and the branching capacity of OC cells to a greater extent than reduced p130Cas expression. However, ezrin and p130Cas expression in effusions was unrelated to clinical outcome. The 3-dimensional cell cultures were found to mimic the different tumor sites and be applicable as a model. The in vitro results concur with the clinical specimen analysis, suggesting that in OC, the role of ezrin in disease progression is more pronounced than that of p130Cas.


[Structure of eyes in trombidioid mites (Acariformes: Trombidioidea)].
The eyes or ocelli of trombidioid mite larvae of Euschoengastia rotundata, Hirszutiella zachvatkini and Camerotrombidium pexatum, and larvae and adults of Platytrombidium fasciatum were studied by means of transmission electron microscopy. These species together with larvae of Odontacarus efferus, Ericotrombidium hasgelum, Walchia chinensis and adult E. rotundata and H. zachvatkini were also studied under scanning electron microscope. The eyes of larvae are not inverted and characterized by an epicuticular lamellar lens. The group of phoreceptor cells with rhabdomeres arranged typically of Chelicerata is underlaid by a pigment cup. The eyes of adult mites are inverted, perikarions of photoreceptor cells are situated between the lens and rhabdomeres; tapetum occupies the space between the pigment cup and rhabdomeres. Sensitivity of eyes to light is similar to that of primary eyes of spiders dwelling on soil surface.


Translational analysis of mouse and human placental protein and mRNA reveals distinct molecular pathologies in human preeclampsia.
Preeclampsia (PE) adversely impacts ~5% of pregnancies. Despite extensive research, no consistent biomarkers or cures have emerged, suggesting that different molecular mechanisms may cause clinically similar disease. To address this, we undertook a proteomics study with three main goals: (1) to identify a panel of cell surface markers that distinguish the trophoblast and endothelial cells of the placenta in the mouse; (2) to translate this marker set to human via the Human Protein Atlas database; and (3) to utilize the validated human trophoblast markers to identify subgroups of human preeclampsia. To achieve these goals, plasma membrane proteins at the blood tissue interfaces were extracted from placentas using intravascular silica-bead perfusion, and then identified using shotgun proteomics. We identified 1181 plasma membrane proteins, of which 171 were enriched at the maternal blood-trophoblast interface and 192 at the fetal endothelial interface with a 70% conservation of expression in humans. Three distinct molecular subgroups of human preeclampsia were identified in existing human microarray data by using expression patterns of trophoblast-enriched proteins. Analysis of all misexpressed genes revealed divergent dysfunctions including angiogenesis (subgroup 1), MAPK signaling (subgroup 2), and hormone biosynthesis and metabolism (subgroup 3). Subgroup 2 lacked expected changes in known preeclampsia markers (sFLT1, sENG) and uniquely overexpressed GNA12. In an independent set of 40 banked placental specimens, GNA12 was overexpressed during preeclampsia when co-incident with chronic hypertension. In the current study we used a novel translational analysis to integrate mouse and human trophoblast protein expression with human microarray data. This strategy identified distinct molecular pathologies in human preeclampsia. We conclude that clinically similar preeclampsia patients exhibit divergent placental gene expression profiles thus implicating divergent molecular mechanisms in the origins of this disease.


Automatic Atrial Fibrillation detection: A novel approach using discrete wavelet transform and heart rate variability.
Early detection of Atrial Fibrillation (AF) is crucial in order to prevent acute and chronic cardiac rhythm disorders. In this study, a novel method for robust automatic AF detection (AAFD) is proposed by combining atrial activity (AA) and heart rate variability (HRV), which could potentially be used as a screening tool for patients suspected to have AF. The method includes an automatic peak detection prior to the feature extraction, as well as a noise cancellation technique followed by a bagged tree classification. Simulation studies on the MIT-BIH Atrial Fibrillation database was performed to evaluate the performance of the proposed method. Results from these extensive studies showed very promising results, with an average sensitivity of 96.51%, a specificity of 99.19%, and an overall accuracy of 98.22%.


Phospholipase A2 (PLA2) as an Early Indicator of Envenomation in Australian Elapid Snakebites (ASP-27).
Early diagnosis of snake envenomation is essential, especially neurotoxicity and myotoxicity. We investigated the diagnostic value of serum phospholipase (PLA2) in Australian snakebites. In total, 115 envenomated and 80 non-envenomated patients were recruited over 2 years, in which an early blood sample was available pre-antivenom. Serum samples were analyzed for secretory PLA2 activity using a Cayman sPLA2 assay kit (#765001 Cayman Chemical Company, Ann Arbor MI, USA). Venom concentrations were measured for snake identification using venom-specific enzyme immunoassay. The most common snakes were Pseudonaja spp. (33), Notechis scutatus (24), Pseudechis porphyriacus (19) and Tropidechis carinatus (17). There was a significant difference in median PLA2 activity between non-envenomated (9 nmol/min/mL; IQR: 7-11) and envenomated patients (19 nmol/min/mL; IQR: 10-66, p < 0.0001) but Pseudonaja spp. were not different to non-envenomated. There was a significant correlation between venom concentrations and PLA2 activity (r = 0.71; p < 0.0001). PLA2 activity was predictive for envenomation; area under the receiver-operating-characteristic curve (AUC-ROC), 0.79 (95% confidence intervals [95%CI]: 0.72-0.85), which improved with brown snakes excluded, AUC-ROC, 0.88 (95%CI: 0.82-0.94). A cut-point of 16 nmol/min/mL gives a sensitivity of 72% and specificity of 100% for Australian snakes, excluding Pseudonaja. PLA2 activity was a good early predictor of envenomation in most Australian elapid bites. A bedside PLA2 activity test has potential utility for early case identification but may not be useful for excluding envenomation.


Microscopic anatomy of the human vertebro-basilar system.
Concerning the structure of connective-muscular components the authors studied the walls of the terminal segments of the vertebral arteries as well as the basilar artery, utilizing the following staining methods: Azan modified by Heidenheim, Weigert's resorcin-fuchsin, and Weigert modified by van Gieson. It was established that wall of the vertebro-basilar system exhibits a mixed structure, muscular and elastic, by means of which the vessels are adjusted to the specific blood circulation conditions. Thus, vertebral arteries show in the most external layer of tunica media an evident external elastic lamina. In contrast, in the basilar artery the elastic tissue is localized mainly in the tunica media, and is distributed heterogeneously. In its caudal segment the elastic fibers are situated in the most internal layer of tunica media, and in the cranial segment the elastic component is homogeneously distributed in the whole of tunica media.


Structure of quasi-one-dimensional ribbon colloid suspensions.
We report the results of an experimental study of a colloid fluid confined to a quasi-one-dimensional (q1D) ribbon channel as a function of channel width and colloid density. Our findings confirm the principal predictions of previous theoretical studies of such systems. These are (1) that the density distribution of the liquid transverse to the ribbon channel exhibits stratification; (2) that even at the highest density the order along the strata, as measured by the longitudinal pair correlation function, is characteristic of a liquid; and (3) the q1D pair correlation functions in different strata exhibit anisotropic behavior resembling that found in a Monte Carlo simulation for the in-plane pair correlation function of a hard sphere fluid in a planar slit.


Human papillomavirus absence predicts normal cervical histopathologic findings with abnormal papanicolaou smears: a study of a university-based inner city population.
We studied the role of human papillomavirus (HPV) typing in predicting cervical dysplasia in women with abnormal Papanicolaou (Pap) test results. A university colposcopy clinic-based consecutive sample of 179 women completed a questionnaire and underwent colposcopy, HPV typing (Hybrid Capture System HPV DNA Assay II; Digene Diagnostics, Gaithersburg, MD, USA), and biopsy (if indicated). No severe dysplasia was observed in women with low-risk HPV or in women with negative HPV test results who had a low-grade abnormality on the Pap test. High-risk (HR) HPV was present in every case of severe dysplasia on biopsy. The cumulative odds risk for cervical dysplasia was 1.11 in HIV(+) women with low-grade squamous intraepithelial lesion on the Pap test who were older than 21 years of age and HPV-HR(+). In the population studied, HPV typing is a valuable adjunct to a low-grade abnormality on the Pap test in predicting the absence of cervical dysplasia on biopsy. Larger prospective population-based studies are needed to study the role of HPV as a negative predictor of disease in cervical dysplasia.


Structure determination and activity manipulation of the turfgrass ABA receptor FePYR1.
Turfgrass are widely cultivated ornamental plants that have important ecological, societal and economical values. However, many turfgrass species are susceptible to drought and demand frequent irrigation thus consuming large amounts of water. With the ultimate goal of improving drought resistance in turfgrass, we identified several ABA receptors in turfgrass that are important to mediate ABA signaling and drought stress response. The ABA receptor FePYR1 from turfgrass Festuca elata was demonstrated to bind ABA as a monomer. Crystal structure analysis revealed that FePYR1 recognizes and binds ABA by the common gate-latch-lock mechanism resembling the Arabidopsis ABA receptors, but the ABA binding pocket in FePYR1 shows discrepant residues resulting in different binding affinity to ABA. Structure-guided alterations of amino acid residues in FePYR1 generated ABA receptor variants with significantly increased ABA binding affinity. Expression of FePYR1 in Arabidopsis conferred enhanced drought resistance in the transgenic plants. These findings provided detailed information about FePYR1 and demonstrated that structure-assisted engineering could create superior ABA receptors for improving plant drought resistance. The detailed structural information of FePYR1 would also assist future rational design of small molecules targeting specific ABA receptors in economically important plant species.


Diffractographic dimensional measurement. Part 2: profile measurement.
Part 1 of this paper discussed a "diffractographic" method by which changes in separation between two objects could be measured using changes in the diffraction pattern of the slit-type aperture formed between them. A unique line measurement capability was demonstrated. In this part we discuss profile measurement whereby the diffraction pattern formed is used to indicate changes in separation between adjacent sets of opposite points, rather than changes between the points themselves. Positions of points on one object are usually known, in order to test the profile of the second. The method offers many interesting advantages in those applications where it may be used, particularly due to the speed, accuracy, and easily automated nature of the process.


BPF-Based Thermal Sensor Circuit for On-Chip Testing of RF Circuits.
A new sensor topology meant to extract figures of merit of radio-frequency analog integrated circuits (RF-ICs) was experimentally validated. Implemented in a standard 0.35 μm complementary metal-oxide-semiconductor (CMOS) technology, it comprised two blocks: a single metal-oxide-semiconductor (MOS) transistor acting as temperature transducer, which was placed near the circuit to monitor, and an active band-pass filter amplifier. For validation purposes, the temperature sensor was integrated with a tuned radio-frequency power amplifier (420 MHz) and MOS transistors acting as controllable dissipating devices. First, using the MOS dissipating devices, the performance and limitations of the different blocks that constitute the temperature sensor were characterized. Second, by using the heterodyne technique (applying two nearby tones) to the power amplifier (PA) and connecting the sensor output voltage to a low-cost AC voltmeter, the PA's output power and its central frequency were monitored. As a result, this topology resulted in a low-cost approach, with high linearity and sensitivity, for RF-IC testing and variability monitoring.


Generalized cortical dysplasia. Clinical and pathologic aspects.
Three children with profound mental retardation and intractable seizures died at ages 10 months, 3 years, and 7 years, respectively. Complete examination of their brains showed generalized cortical dysplasia, without any major malformation of the external gyral pattern. The neuropathologic features of cortical dysplasia include abnormally thickened cortex with indistinct demarcation of the gray-white matter junction. In many areas, the cortex contained increased numbers of large neurons with disordered cortical lamination. Heterotopic neurons were scattered throughout the white matter with decreased myelination of the underlying white matter. To our knowledge, these cases represent the first fully detailed neuropathologic study of diffuse cortical dysplasia--a newly recognized entity of abnormal neuronal migration.


Qualitative Assessment of Bad News Delivery Practices during Miscarriage Diagnosis.
Miscarriage is one of the most common pregnancy complications health care providers discuss with patients. Previous research suggests that women's distress is compounded by ineffective communication with providers, who are usually not trained to deliver bad news using patient-centered dialogue. The purpose of this study was to use a patient-centered approach to examine women's experiences with and perspectives of communication during a miscarriage to assist in the development of communication training tools for health care providers. During focus groups, 22 women who had experienced miscarriage discussed video-recorded standardized patient-provider interactions and recalled communication during their own miscarriages. Results of a pragmatic iterative analysis of the transcripts suggest training techniques and communication behaviors that should guide education for providers to deliver the diagnosis of and treatment options for early pregnancy loss, such as demonstrating empathy, creating space for processing, checking for understanding, and avoiding medical jargon and emotionally charged language.


Broadband terahertz transmission within the symmetrical plastic film coated parallel-plate waveguide.
We report on the broadband terahertz (THz) transmission within a symmetrical plastic film coated parallel-plate waveguide. We theoretically study the antiresonant reflecting mechanism of the waveguide, and we find that the broadband THz wave can transmit in this waveguide with ultralow loss. The loss of the TM mode in this waveguide can be 4 orders of magnitude lower than the uncoated parallel-plate waveguide. The transmission bandwidth of this waveguide is up to 5.12 THz. We further show the mode field distributions which explain the loss mechanism.


Design and structural analysis of hairpin-TFO for transcriptional activation of genes in S. cerevisiae.
Triplex forming oligonucleotides (TFOs) have the potential to modulate gene expression. While most of the experiments are directed towards triplex mediated inhibition of gene expression the strategy potentially could be used for gene specific activation. In an attempt to design a strategy for gene specific activation in vivo applicable to a large number of genes we have designed a TFO based activator-target system which may be utilized in Saccharomyces cerevisiae or any other system where Gal4 protein is ectopically expressed. The total genome sequence of Saccharomyces cerevisiae and expression profiles were used to select the target genes with upstream poly (pu/py) sequences. We have utilized the paradigm of Gal4 protein and its binding site. We describe here the selection of target genes and design of hairpin-TFO including the targeting sequences containing polypurine stretch found in the upstream promoter regions of weakly expressed genes. We demonstrate, the formation of hairpin-TFO, its binding to Gal4 protein, its ability to form triplex with the target duplex in vitro, the effect of polyethylenimine on complex formation and discuss the implication on in vivo transcription activation.