5-type HPV mRNA versus 14-type HPV DNA test: test performance, over-diagnosis and overtreatment in triage of women with minor cervical lesions.
Repeat cytology and HPV testing is used in triage of women with minor cytological lesions. The objective of this study was to evaluate 14-type HPV DNA and 5-type HPV mRNA testing in delayed triage of women with ASC-US/LSIL. We compared a DNA test (Roche Cobas 4800) and an 5-type mRNA test (PreTect HPV-Proofer). In total 564 women were included in the study. The sensitivity among solved cases for CIN3+ were 100 % (15/15) for both tests. The sensitivity for CIN2+ of the HPV DNA test was 100 % (38/38) relative to 79 % (30/38) for the 5-type HPV mRNA test. The corresponding estimates of specificity for CIN2+ among solved cases were 84 % (393/466; 95 % CI: 81-88) and 91 % (451/498; 95 % CI: 88-93). The positive predictive values for CIN3+ were 13.5 % (15/111) for DNA+ and 19.5 % (15/77) for 5-type mRNA+. Significantly more women screened with 5-type mRNA than DNA returned to screening (81 % vs 71 %, p < 0.01). Subsequently, significantly fewer women were referred for colposcopy/biopsies/treatment (19 % (105/564) vs 29 % (165/564), p < 0.01). 5-type HPV mRNA is more specific than 14-type HPV DNA in delayed triage of women with ASC-US/LSIL. The referral rate for colposcopy was 57 % higher for DNA+ relative to mRNA+ cases (165 vs 105), with the same detection rate of CIN3+, but the 5-type mRNA test had lower sensitivity for CIN2+. It is important to consider the trade-off between sensitivity and specificity of the diagnostic test when designing screening algorithms.


Medical conditions associated with venous leg ulcers.
In patients who have a venous leg ulcer, very little is known about the frequency of their concomitant medical conditions. To evaluate the frequency that other medical conditions are associated with a new venous leg ulcer. We studied a 10% random sample of elderly patients registered in the General Practice Research Database between 1988 and 1996. We describe the frequency of medical conditions using simple percentages. In order to assess the associations between medical conditions and the onset of a venous leg ulcer, we used logistic regression models. Several medical conditions occur commonly in patients who develop venous leg ulcers, including anaemia, angina, asthma, cellulitis of the lower extremity, depression, diabetes, limb oedema, hypertension, osteoarthritis, pneumonia and urinary tract infection. After statistical adjustment many medical conditions were significantly associated with those who had recent onset of a venous leg ulcer, including asthma, cellulitis of the lower extremity, congestive heart failure, diabetes, deep venous thrombosis, lower limb oedema, osteoarthritis, peripheral vascular arterial disease of the lower extremity, rheumatoid arthritis, history of hip surgery, and history of venous surgery/ligation. Unexpectedly, some illnesses were inversely associated with those that had recent onset of a venous leg ulcer, including angina, cerebral vascular accident, depression, malignancy, myocardial infarction, pneumonia and urinary tract infection. Physicians caring for individuals with venous leg ulcers need to be aware that it is likely that these individuals may have one of the comorbid illnesses listed above.


Trend of contrast detection threshold with and without localization.
Published information on contrast detection threshold is based primarily on research using a location-known methodology. In previous work on testing the Digital Imaging and Communications in Medicine (DICOM) Grayscale Standard Display Function (GSDF) for perceptual linearity, this research group used a location-unknown methodology to more closely reflect clinical practice. A high false-positive rate resulted in a high variance leading to the conclusion that the impact on results of employing a location-known methodology needed to be explored. Fourteen readers reviewed two sets of simulated mammographic background images, one with the location-unknown and one with the location-known methodology. The results of the reader study were analyzed using Reader Operating Characteristic (ROC) methodology and a paired t test. Contrast detection threshold was analyzed using contingency tables. No statistically significant difference was found in GSDF testing, but a highly statistical significant difference (p value <0.0001) was seen in the ROC (AUC) curve between the location-unknown and the location-known methodologies. Location-known methodology not only improved the power of the GSDF test but also affected the contrast detection threshold which changed from +3 when the location was unknown to +2 gray levels for the location-known images. The selection of location known versus unknown in experimental design must be carefully considered to ensure that the conclusions of the experiment reflect the study's objectives.


A novel approach to tricuspid valve replacement: the upside down stentless aortic bioprosthesis.
Tricuspid valve replacement (TVR) is a rarely needed operation. Choices between mechanical and biological prosthesis still generate controversy. We present our initial clinical experience with a stentless aortic root placed inverted in the tricuspid annulus. Between August 2000 and September 2003, TVR for severe tricuspid insufficiency was performed in 8 patients. Indications were infective endocarditis (7) and iatrogenic damage (1). Mean age was 42.2 years old (20 to 58 years old). Five patients were male and 3 patients had a concomitant procedure (mitral valvuloplasty, coronary bypass grafting, and aortic valve replacement). A stentless aortic root, size 27 mm (n = 5) or 29 mm (n = 3) was placed inverted in the tricuspid position after the valsalva sinuses were scalloped. Interrupted 4-0 polypropylene sutures were used between the tricuspid valve annulus and the sewing ring. The struts equivalent on the stentless valve were anchored to the septal, anterior and posteroinferior wall of the right ventricle using 5-0 PTFE pledgeted sutures. Hospital survival was 100% and mean hospital stay was 12.5 days (3 to 18 days). Intraoperative and follow-up echocardiograms revealed no stenosis or insufficiency. Mean follow-up was 17.2 months (1-38 months). There were 3 late deaths due to continued IV drug use (n = 2) and end-stage renal failure (n = 1). This is a novel surgical alternative for a very high risk population. Potential advantages over current options include minimization of blood contact with nonbiological surfaces, preservation of annular motion, freedom from anticoagulation, and a theoretical lower rate of calcification.


Early maternal relational traumatic experiences and psychopathological symptoms: a longitudinal study on mother-infant and father-infant interactions.
Early maternal relational traumas and psychopathological risk can have an impact on mother-infant interactions. Research has suggested the study of fathers and of their psychological profiles as protection or risk factors. The aim of the paper is to assess the quality of parental interactions during feeding in families with mothers with early traumatic experiences. One hundred thirty-six (N = 136) families were recruited in gynecological clinics: Group A included families with mothers who experienced early sexual/physical abuse; Group B was composed of families with mothers who experienced early emotional abuse or neglect; and Group C comprised healthy controls. The subjects participated in a 10-month longitudinal protocol [at the fourth month of pregnancy (T0), 3 months after child birth (T1), and 6 months after child birth (T2)] that included an observation of mother-infant and father-infant interactions during feeding (Scala di Valutazione dell'Interazione Alimentare [SVIA]) and a self-reporting 90-item Symptom Checklist-Revised (SCL-90-R). Maternal higher rates of depression and early traumatic experiences of neglect and emotional abuse predicted more maladaptive scores on the affective state of the dyad SVIA subscale. Paternal anxiety predicted more severe levels of food refusal in the child during feeding.


Habitat variations affect morphological, reproductive and some metabolic traits of Mediterranean Centaurea glomerata Vahl populations.
Centaurea glomerata Vahl is an annual, monoecious and herbaceous member of Asteraceae, found in some localities of different topographic features/habitat conditions along the Mediterranean coastal region of Egypt. This study aimed to investigate some environmental gradients including edaphic and climate criteria on morphological, reproductive traits as well as phenolic and flavonoid metabolites in this species. Three distinct populations were selected. Two of them were located in coastal sand dunes (found in Rosetta region in Egypt); one was located on flat sand dunes, whereas the other grown on sloping ones. Meanwhile, the third population was represented in the rocky hillside of Burg El Arab region. The population detected in the sloping sand dunes showed best morphological and reproductive features, whilst the opposite was true for that represented on the rocky hillside. Moreover, the free phenolic and flavonoid compounds prevailed in the later. The meteorological data revealed that the rocky hillside received relatively lower minimum temperature and higher solar irradiance, while the sand dunes of Rosetta showed more warmer conditions. Light intensity and wind speed were reduced on the sloping sand dunes. The Canonical Correspondence Analysis (CCA) exhibited a clear correlation between most of metabolites detected and the population found on the rocky hillside along with higher solar irradiance prevails. The morpho-reproductive traits were related to climatic gradients and some soil criteria. These results revealed that the changes in micro-topography, that may lead to change in soil and climate variables, is the most important environmental gradient that controls the morphological and biochemical features of C. glomerata. Solar irradiance and/or light intensity are key factors playing a role influencing the measured traits of this species. These findings suggest that accumulation of secondary metabolites could be a biochemical strategy and an adaptational criterion for such species under stress conditions.


LncRNA TTN-AS1 confers tamoxifen resistance in breast cancer via sponging miR-107 to modulate PI3K/AKT signaling pathway.
Tamoxifen resistance of breast cancer (BC) is a significant hindrance in clinical therapy. The long-noncoding RNA (lncRNA) TTN-AS1 has been reported as a crucial tumor promoting factor in various cancers. In this study, we set out to discover the specific pathologic regulatory mechanisms of tamoxifen-resistance in breast cancer. MTT assay was conducted to evaluate the cell viability of the breast cancer cell lines MCF-7 and MCF-7/TAM. QRT-PCR and western blot assay were performed to estimate the expression of TTN-AS1, miR-107 and related proteins. Flow cytometry was conducted to identify degree of apoptosis and cell cycle. The invasive ability was estimated by transwell chamber assay. Our findings revealed that TTN-AS1 can enhance tamoxifen-resistance in BC cells and augment the invasive ability of tamoxifen-resistant breast cancer cells by down-regulating miR-107, and thereby encourage the development of drug-resistant BC. Further investigation indicates that lncRNA TTN-AS1 worsens the course of tamoxifen-resistant BC by regulating zinc and ring finger 2 (ZNRF2) via miR-107 and activating the PI3K/AKT pathway. Our findings suggest that the lncRNA TTN-AS1 can encourage tamoxifen-resistance in BC by modulating the miR-107/ZNRF2 axis and stimulating the PI3K/AKT pathway.


In vitro antifungal assay of traditional Argentine medicinal plants.
Methanol extracts from 11 traditionally used Argentine medicinal plants were assayed in vitro for antifungal activity against yeasts, hialohyphomycetes as well as dermatophytes with the microbroth dilution method. Among them, the strongest effect was presented by Eupatorium buniifolium and Terminalia triflora, Trichophyton mentagrophytes and Trichophyton rubrum being the most susceptible species with MICs ranging from 100 to 250 microg/ml. Lithrea molleoides showed the broadest spectrum of action inhibiting all of the tested dermatophytes with MIC=250 microg/ml.


Classification and staging of hepatocellular carcinoma: an aid to clinical decision-making.
Classification and staging of hepatocellular carcinoma in a way that allows optimal treatment selection is challenging. This article summarizes some of the classification and staging schemes and discusses the conceptual framework that guides optimal treatment selection for each patient. The article does not exhaustively discuss each staging system proposed in the last three decades, but rather reviews the most commonly used staging systems, evaluates the rationale behind some of the newer staging systems, and compares them focusing on their use in clinical decision-making, notably choice of therapy.


Biomarkers of endothelial dysfunction are elevated and related to prognosis in chronic heart failure patients with diabetes but not in those without diabetes.
Biomarkers of endothelial dysfunction, such as soluble E-selectin, and von Willebrand factor (vWf) are elevated in patients with chronic heart failure (CHF). The impact of diabetes mellitus (DM) on these biomarkers, and their relation to prognosis remains unknown. to investigate the impact of DM on plasma levels and the prognostic value of E-selectin and vWf in patients with CHF. Plasma levels of E-selectin and vWf were measured in 195 CHF patients with (n=48, 24.5%), and without DM, and in 116 age-matched healthy controls. Compared with controls, median plasma E-selectin levels were higher in CHF patients with DM (P=0.012), but not in CHF patients without DM (P=0.45); vWf levels were also higher in CHF patients with DM (P<0.001), but not without DM (P=0.108). E-selectin was associated with risk of recurrent ischaemic cardiovascular events among CHF patients with DM (HR 2.60; P=0.009), but not among patients without DM (HR 1.09; P=0.60) per 1 SD increment in log transformed variable. vWf was not related with outcome in CHF patients with or without DM. Plasma levels of E-selectin and vWf are elevated in CHF patients with DM but not in those without DM. High E-selectin levels may be associated with ischaemic events in patients with DM.


Mild emphysema: a novel method using formalin-fixed lungs for computed tomography and pathological analyses.
We evaluated a novel method of computed tomography (CT) analysis using formalin-fixed lungs of autopsy cases with mild emphysema. Eight formalin-inflated lungs (FILs) obtained at autopsy were examined using CT after draining off the formalin and air inflation with an air pump, and subjected to pathological study including pathological scoring of emphysema and microscopic image analysis (MIA). Satisfactory CT examination was carried out within 5 h of lung fixation. The mean alveolar area determined by MIA correlated highly with the lung volume (r = 0.845) and CT score (r = 0.722). This method is simple compared with conventional polyethylene glycol fixation for CT and enables CT examination of resected lungs without anxiety about biohazards, Mild emphysema can be detected by MIA.


An immunohistochemical study of seasonal changes in luteinizing hormone-releasing hormone and vasotocin in the forebrain and the neurohypophysis of the toad, Bufo japonicus.
Seasonal changes in luteinizing hormone-releasing hormone (LH-RH) and arginine vasotocin (AVT) were examined immunohistochemically in the toad forebrains and neurohypophyses. Strongly immunoreactive (ir-) LH-RH perikarya, from which dense ir-LH-RH fibers project to the median eminence, were localized in the medial septal nucleus and the nucleus of the diagonal band of Broca in the animals captured in the spring and the autumn. While, in the animals collected in the summer, ir-LH-RH perikarya and fibers were sparse, and immunoreactivity in the median eminences was weak. Artificially induced hibernation decreased the density of ir-LH-RH in the median eminence, in contrast with strong immunoreactivity in the control animals kept at room temperature. The amounts of ir-LH-RH in the median eminences of hibernating toads which were captured shortly before the breeding period varied conspicuously among individuals. The median eminences in migrating toads showed relatively weak LH-RH immunoreactivity. After the breeding, the immunoreactivity returned to the strong level that was observed in the spring and the autumn. These seasonal changes in ir-LH-RH seem to correspond to seasonal reproductive activity in this species. However, significant seasonal variations were not found in ir-AVT.


The localization of intrarenal calculi during surgery.
This is a summary review of past and present technology for accurate anatomical localization of calculi within the surgically exposed kidney. The methodology is applicable to reconstructive renal surgery for pathological processes other than calculi.


Techniques for isolation of brush-border and basolateral membrane vesicles from dog kidney cortex.
Two methods are reported for renal membrane preparation from the dog kidney cortex. One method is a simultaneous preparation of brush-border (BBMV) and basolateral (BLMV) membranes. Using readily available laboratory equipment, differential centrifugation produced a supernatant which was treated with Mg2+. The Mg2+ treatment produced a pellet (crude BLMV) which was added to Percoll and centrifuged to produce purified BLMV. The supernatant after Mg2+ treatment eventually yielded pure BBMV after additional Mg2+ precipitations. The second method used an acidic medium in conjunction with divalent-cation precipitation to prepare BBMV. Whichever method was used, BBMV and BLMV showed appropriate enzyme and transport activities.


Brain temperature affects quantitative features of hippocampal sharp wave ripples.
Biochemical mechanisms are temperature dependent. Brain temperature shows wide variations across brain states, and such changes may explain quantitative changes in network oscillations. Here, we report on the relationship between various hippocampal sharp wave ripple features to brain temperature. Ripple frequency, occurrence rate, and duration correlated with temperature dynamics. By focal manipulation of the brain temperature in the hippocampal CA1 region, we show that ripple frequency can be increased and decreased by local heating and cooling, respectively. Changes of other parameters, such as the rate of sharp wave-ripple complex (SPW-R) and ripple duration were not consistently affected. Our findings suggest that brain temperature in the CA1 region plays a leading role in affecting ripple frequency, whereas other parameters of SPW-Rs may be determined by mechanisms upstream from the CA1 region. These findings illustrate that physiological variations of brain temperature exert important effects on hippocampal circuit operations.NEW & NOTEWORTHY During physiological conditions, brain temperature fluctuates approximately 3°C between sleep and active waking. Here, we show that features of hippocampal ripples, including the rate of occurrence, peak frequency, and duration are correlated with brain temperature variations. Focal bidirectional manipulation of temperature in the hippocampal CA1 region in awake rodents show that ripple frequency can be altered in the direction expected from the correlational observations, implying that temperature plays a significant role.


BDNF/TrkB Signaling as a Potential Novel Target in Pediatric Brain Tumors: Anticancer Activity of Selective TrkB Inhibition in Medulloblastoma Cells.
Medulloblastoma (MB) is the most common malignant pediatric brain tumor. Deregulation of brain-derived neurotrophic factor (BDNF)/tropomyosin-related kinase B (TrkB) signaling has been associated with increased proliferative capabilities, invasiveness, and chemoresistance in several types of cancer. However, the relevance of this pathway in MB remains unknown. Here, we show that the selective TrkB inhibitor N-[2-[[(hexahydro-2-oxo-1H-azepin-3-yl)amino]carbonyl]phenyl]-benzo[b]thiophene-2-carboxamide (ANA-12) markedly reduced the viability and survival of human cell lines representative of different MB molecular subgroups. These findings provide the first evidence supporting further investigation of TrkB inhibition as a potential novel strategy for MB treatment.


Carbon, nitrogen, and phosphorus dynamics in China's lakes: climatic and geographic influences.
Given the differences in geomorphology, climate, hydrology, and human activities in various regions, lake chemometrics may also vary. However, the spatial distribution of lake chemistry and the factors affecting such pattern are still unclear. Here, we collected data for carbon, nitrogen, and phosphorus from published literature and databases in 224 lakes and calculated the trophic status index to represent the nutrient classification state of lakes. We found that lakes with high carbon concentrations were located in the Tibet-Qinghai Limnetic Region of western China, whereas lakes with high nitrogen and phosphorus concentrations were located in the Inner Mongolia-Xinjiang Limnetic Region and Northeast Limnetic Region of northern China. Areas with larger cropland and urban residential land (such as the junction of the three lake regions, i.e., the Northeast Limnetic Region, East Limnetic Region, and Inner Mongolia-Xinjiang Limnetic Region) tended to have lakes with high nitrogen and phosphorus concentrations. Our analysis suggested that spatial distribution of carbon, nitrogen, and phosphorus concentrations reflect the effect of climate, geomorphology, and land use in each lake region and nationwide.


Hepatocyte growth factor activator is a potential target proteinase for Kazal-type inhibitor in turkey (Meleagris gallopavo) seminal plasma.
A peculiar characteristic of turkey seminal plasma is the increased activity of serine proteinases. It is of interest if the single-domain Kazal-type inhibitor controls the activity of turkey seminal plasma proteinases. Pure preparations of the Kazal-type inhibitor and anti-Kazal-type inhibitor monospecific immunoglobulin Gs were used as ligands in affinity chromatography for proteinase isolation from turkey seminal plasma. Gene expression and the immunohistochemical detection of the single-domain Kazal-type inhibitor in the reproductive tract of turkey toms are described. The hepatocyte growth factor activator (HGFA) was identified in the binding fraction in affinity chromatography. Hepatocyte growth factor activator activity was inhibited by the Kazal-type inhibitor in a dose-dependent manner. This protease was a primary physiological target for the single-domain Kazal-type inhibitor. Numerous proteoforms of HGFA were present in turkey seminal plasma, and phosphorylation was the primary posttranslational modification of HGFA. In addition to HGFA, acrosin was a target proteinase for the single-domain Kazal-type inhibitor. In seminal plasma, acrosin was present only in complexes with the Kazal-type inhibitor and was not present as a free enzyme. The single-domain Kazal-type inhibitor was specific for the reproductive tract. The germ cell-specific expression of Kazal-type inhibitors in the testis indicated an important function in spermatogenesis; secretion by the epithelial cells of the epididymis and the ductus deferens indicated that the Kazal-type inhibitor was an important factor involved in the changes in sperm membranes during maturation and in the maintenance of the microenvironment in which sperm maturation occurred and sperm was stored. The role of HGFA in these processes remains to be established.


Gastric related properties of rat paraventricular neurons.
Central control of gastric acid secretion (GAS) was formerly attributed to specific neurons in the lateral hypothalamus (LHA), but the rostral part of the paraventricular nucleus (r-PVN) of the hypothalamus was shown to be another site that modulates central control of GAS. In the present study, the characteristics of 145 spontaneously firing r-PVN neurons were investigated in 22 rats. Discharges were: high frequency regular or irregular, low frequency regular or irregular. About half of the regular discharges were phasic. Electrical stimulation in the r-PVN evoked responses in 407 LHA units. Response latencies ranged from 4.7 to 78.1 msec; indicating mono- and polysynaptic, and myelinated and nonmyelinated fiber connections. Gastric related and non-related r-PVN neurons were observed. It was also shown, for the first time, that electrophoretic application of various chemicals, especially glucose, affected chemosensitive neurons in the r-PVN. PVN neuron responses to LHA repetitive stimulation were classified as excitatory (E), excitatory-inhibitory (E-I), I and I-E. PVN neuronal discharges might be modulated by gastric type LHA neurons. Electrophoretically applied norepinephrine (NE) increased PVN neuronal activity and suppressed GAS. Results suggest that rostral PVN neurons might affect LHA control of GAS, with NE as the probable transmitter or modulator.


Physical and information workflow mapping of vancomycin therapeutic drug management: A single site case study revealing potential gaps in the process.
Vancomycin is one of the most prescribed antibiotics in pediatric intensive care units (PICU) in US hospitals. However, a detailed understanding of workflow and information flow among various stakeholders regarding vancomycin treatment processes in clinical settings is lacking. We conducted direct observations and informant interviews to develop the mapping of key processes and information flow for vancomycin treatment, with an emphasis on therapeutic drug monitoring (TDM) dose adjustment decision-making. A health information technology (HIT) sociotechnical framework was used to identify EHR related safety concerns. A total of 27 vancomycin treatment activities were observed over a 60-h duration including infusion administration, infusion completion, trough concentration blood draw and therapeutic decision making processes. Workflow and information flow mappings revealed (1) deviations between the documented timestamp used for TDM decision making and the actual time the tasks executed and (2) the lack of information flow regarding infusion completion and interruption. Missing features, insufficient usability and lack of integration with workflow and communication in the EHR were deemed safety gaps that may affect the accuracy of therapeutic decisions. Our case study identified gaps in information flow among clinical team members via EHR in TDM processes to provide insights for the improvement of the EHR system for antibiotic treatment purposes. In particular, the potential harm of the missing, uncertain, and inaccurate documented TDM task times warrant further investigations.


Retinal vein occlusion and factor V Leiden and prothrombin 20210 G:A mutations.
The aim of this study was to establish whether the factor V Leiden mutation and the prothrombin 20210 G:A mutation were risk factors for retinal vein occlusion. Blood samples were obtained from 40 patients with retinal vein occlusion and from 50 healthy normal volunteers as controls. Polymerase chain reaction assays were done to detect factor V Leiden and prothrombin 20210 G:A mutations, and the two groups were compared. Two (5%) of 40 patients with retinal vein occlusion and three (6%) of 50 controls were heterozygous for factor V Leiden (p=0.84). None of the individuals in either group had the prothrombin 20210 G:A mutation. There was no significant association between retinal vein occlusion and the factor V Leiden mutation.


The molecular basis for the differential sensitivity of B and T lymphocytes to growth inhibition by thymidine and 5-fluorouracil.
Cultured leukemic lymphocytes originating from patients with T, B and non-T, non-B (null) leukemia were tested for their sensitivity to thymidine and 5-fluorouracil. T cells were found to be 5-7 fold more sensitive to thymidine growth inhibition than B-cells. At 10(-3) M concentration of thymidine, T cells showed a progressive (up to 75%) decline in the populating trypan blue-excluding cells, after 72 h. At this concentration of thymidine B cells showed slight inhibition at 24 and 48 h, then at 72 h the surviving cell level returned almost to the level of unperturbed cells. Thymidine at 10(-5) M concentration, caused 40% cell growth inhibition of T cells, however, at this concentration it had little or no effect on B cells. 5-fluorouracil effects on B and T lymphocytes are opposite to that of thymidine. B cells were on an average 5-7 times more sensitive to 5-FU than T cells. 5-FU at 10(-6) M caused up to 45% inhibition of B-cell growth but at this concentration it had no effect on the growth of T cells. B-, T- and null-lymphocytes sensitivity to thymidine and 5-FU was correlated with the level of the catabolic enzyme thymidine phosphorylase. B cells had, on average, 5-fold more thymidine phosphorylase than T or null cells. Furthermore, the enzyme from the B-cell line (HR1K) chromatographed differently on DEAE-Sephadex than the normal peripheral blood lymphocytes enzyme. The normal enzyme from peripheral blood lymphocytes when adsorbed to DEAE-Sephadex was eluted at a salt concentration of 0.3 M KCI, Enzyme activities of HR1K did not adsorb to the DEAE-Sephadex column but were adsorbed to a phosphocellulose column. Enzyme from normal and leukemic lymphocytes showed similar molecular weights of 130,000 dalton as determined by gel filtration.


Skin disease symptoms and related risk factors among young workers in high-risk jobs.
Occupational skin diseases are the one of the most frequent diseases in many industrialized countries. The studies about skin disease (SD) on young workers were limited. In this study, we aim to evaluate the prevalence of SD symptoms and related risk factors among young workers in high-risk occupations. This cross-sectional study was undertaken between 2011 and 2012 in two vocational training centres. We included 455 young workers who were working as hairdressers, jewellers, or car mechanics. Data were collected with the Nordic Occupational Skin Questionnaire, which was adapted to Turkish for young workers. The average age of the young workers was 17.9 ± 1.7 years. Of the 455 young workers, 52.7% were female and 47.3% were male. During the previous 12 months, the prevalences of the total SD symptoms, hand/forearm eczema symptoms and urticaria symptoms were 49.7%, 44.4%, and 13.4%, respectively. Those who worked as car mechanics were 5.8 times more likely [odds ratio (OR) 5.81, 95%CI: 2.58-13.10) to have a dry skin type, 2.9 times more likely (OR 2.86, 95%CI: 1.72-4.75) to work for >12 h daily, 2.6 times more likely (OR 2.59, 95%CI: 1.25-5.35) to have worked for >5 years, and 3.0 times more likely (OR 3.05, 95%CI: 1.14-8.14) to have SD symptoms. The results indicate that young workers in high-risk jobs have a high frequency of skin symptoms. These results could provide a basis for occupational health professionals to plan prevention programmes for young workers.


Noncoordinate expression of SV40-induced transformation and tumorigenicity in mouse cell hybrids.
Somatic mouse cells hybrids formed by fusion of nontumorigenic 3T3 closely related SV40-transformed SVT2 cells were analyzed in a study designed to probe the genetic basis of the multiple phenotypic changes induced by SV40 transformation. These hybrids showed noncoordinate expression of the transformation phenotype. Although they cloned at high efficiency in medium with low serum and expressed the SV40 T-antigen of the SVT2 parent, hybrid cells grew poorly without anchorage and exhibited a cell and colony morphology intermediate between that of the parents. Tumorigenicity was assayed quantitatively by subcutaneous coinjection into athymic nude mice of serial dilutions of 10(2) to 10(5) hybrid cells with 10(7) lethally irradiated 3T3 cells. The results showed that 100--1000 times more hybrid cells had to be injected for tumor formation than were required with SVT2. These and other observations show that most 3T3/SVT2 hybrid cells are not tumorigenic but that each population contains a rare subset of tumorigenic cells.


Colonoscopy Findings in FIT+ and mt-sDNA+ Patients versus in Colonoscopy-only Patients: New Hampshire Colonoscopy Registry Data.
Few studies compare fecal immunochemical test (FIT) and multi-target stool DNA (mt-sDNA) outcomes in practice. We compared colonoscopy yield following FIT+ or mt-sDNA+ tests to colonoscopies without preceding stool tests in the comprehensive population-based New Hampshire Colonoscopy Registry (NHCR). Outcomes were any neoplasia and an ordered outcome: adenocarcinoma, advanced neoplasia (adenoma/serrated polyp ≥ 1 cm/villous/high-grade dysplasia), nonadvanced neoplasia, or normal. Our total sample included 306 mt-sDNA+ (average age ± SD 67.0 ± 7.9), 276 FIT+ (66.6 ± 8.7), and 50,990 colonoscopy-only patients (61.8 ± 8.1). Among average-risk patients (N = 240 mt-sDNA+, N = 194 FIT+, N = 26,221 colonoscopy only), mt-sDNA+ patients had a higher risk for any neoplasia (67.1%) compared with FIT+ (54.6%, P = 0.00098) or colonoscopy (40.8%, P < 0.0001). Severity of findings and histology subtypes differed across the three groups (P < 0.0001 for both), with a higher yield of advanced findings in mt-sDNA+ patients. In particular, clinically relevant serrated polyps (hyperplastic polyps ≥10 mm/traditional serrated adenomas/sessile serrated polyps) were detected at a higher frequency in mt-sDNA+ patients as compared with FIT+ or colonoscopy-only patients. Even after adjustment, patients with positive mt-sDNA [OR = 2.82; 95% confidence interval (CI), 2.00-4.02] or FIT+ tests (OR = 1.67; 95% CI, 1.19-2.36) were more likely to have histologically more advanced findings than colonoscopy alone. At follow-up colonoscopy, mt-sDNA+ tests were more likely to predict neoplasia than FIT+, largely due to increased detection of serrated polyps. Prevention Relevance: Colorectal cancer screening options include colonoscopy and stool-based tests, including the fecal immunochemical test (FIT) and the multi-target stool DNA (mt-sDNA) test which, if positive, must be followed by a colonoscopy. Assessing "real-world" outcomes of colonoscopies following positive stool tests can inform their clinical use. See related Spotlight, p. 417.


Outcome of gamma knife radiosurgery for metastatic brain tumors derived from non-small cell lung cancer.
The purpose of this study was to analyze outcomes in patients treated with gamma knife radiosurgery (GKS) for brain metastases from non-small cell lung cancer (NSCLC). We retrospectively reviewed the medical records of 817 patients who underwent GKS for brain metastases from NSCLC between January 2002 and December 2012. A total of 1363 GKS procedures were performed for 2970 lesions. The median overall survival time from the initial GKS was 13 months and the salvage treatment-free survival from the first GKS was 6.5 months. Younger age (≤65 years), female sex, better RPA class, higher DS-GPA score, adenocarcinoma, synchronous onset, and lower integrated value of the "numbers and cumulative volume of tumors" were associated with better outcomes. Among the 601 patients with an available follow up image, the pattern of the first progression after initial GKS was the development of new lesions in 356 patients (59.2 %), regrowth of treated lesions in 106 patients (17.6 %), and leptomeningeal seeding (LMS) in 51 patients (8.5 %). Among the deceased, the last MRI performed prior to death was evaluated in 409 patients and showed progression in 263 patients (64.3 %), despite multiple salvage treatments. LMS was identified in 63 patients (15.4 %); a rate much higher than the incidence at first progression. Intracranial tumor burden, defined as the integrated value of the "number of the lesions and cumulative tumor volume", is a new prognostic factor of greater significance than tumor volume or number alone when analyzed as separate factors. Although the cause of death was not progression of brain lesions in the majority of patients, the brain lesions tended to have been persistently progressive in most patients, despite repeated salvage treatment. LMS is an important pattern of treatment failure, in addition to local progression or development of new lesions, particularly in the terminal phase of the disease.


Strategic Planning: Moving From Plan to Implementation.
Successful organizations depend on strategic thinkers who understand strategic planning and strategic management. These strategic leaders can proactively manage the constant environmental changes to position their organizations for a competitive advantage and avoid acting in a reactive and defensive manner. However, while organizations are often adept at developing extensive strategic plans, implementation of the plan is often poor or without a definitive strategy. This article addresses key strategies for successful implementation of changes to bring about sustainable cultural change in an organization to meet the organization's overall strategic goals, specifically through the use of implementation science.


Left-right asymmetry in Drosophila.
Seminal studies of left-right (L/R) patterning in vertebrate models have led to the discovery of roles for the nodal pathway, ion flows and cilia in this process. Although the molecular mechanisms underlying L/R asymmetries seen in protostomes are less well understood, recent work using Drosophila melanogaster as a novel genetic model system to study this process has identified a number of mutations affecting directional organ looping. The genetic analysis of this, the most evolutionary conserved feature of L/R patterning, revealed the existence of a L/R pathway that involves the actin cytoskeleton and an associated type I myosin. In this review, we describe this work in the context of Drosophila development, and discuss the implications of these results for our understanding of L/R patterning in general.


α-Hispanolol sensitizes hepatocellular carcinoma cells to TRAIL-induced apoptosis via death receptor up-regulation.
Hispanolone derivatives have been previously described as anti-inflammatory and antitumoral agents. However, their effects on overcoming Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) resistance remain to be elucidated. In this study, we analyzed the cytotoxic effects of the synthetic hispanolone derivative α-hispanolol (α-H) in several tumor cell lines, and we evaluated the induction of apoptosis, as well as the TRAIL-sensitizing potential of α-H in the hepatocellular carcinoma cell line HepG2. Our data show that α-H decreased cell viability in a dose-dependent manner in HeLa, MDA-MB231, U87 and HepG2 cell lines, with a more prominent effect in HepG2 cells. Interestingly, α-H had no effect on non-tumoral cells. α-H induced activation of caspase-8 and caspase-9 and also increased levels of the proapoptotic protein Bax, decreasing antiapoptotic proteins (Bcl-2, X-IAP and IAP-1) in HepG2 cells. Specific inhibition of caspase-8 abrogated the cascade of caspase activation, suggesting that the extrinsic pathway has a critical role in the apoptotic events induced by α-H. Furthermore, combined treatment of α-H with TRAIL enhanced apoptosis in HepG2 cells, activating caspase-8 and caspase-9. This correlated with up-regulation of both the TRAIL death receptor DR4 and DR5. DR4 or DR5 neutralizing antibodies abolished the effect of α-H on TRAIL-induced apoptosis, suggesting that sensitization was mediated through the death receptor pathway. Our results demonstrate that α-H induced apoptosis in the human hepatocellular carcinoma cell line HepG2 through activation of caspases and induction of the death receptor pathway. In addition, we describe a novel function of α-H as a sensitizer on TRAIL-induced apoptotic cell death in HepG2 cells.


The intraoperative use of the artificial urinary stream in hypospadias surgery.
Attainment of a single, compact, directable urinary stream is one of the goals of hypospadias surgery. A technique that can be used intraoperatively to evaluate the urinary stream is described and its clinical application is discussed.


Portal blood flow-dependent NO-mediated lymph formation in rat jejunum.
The higher permeability of the venules in jejunal microcirculation to albumin contributes to the increased mesenteric lymph formation. Recently, we demonstrated that water intake induced serotonin release from enterochromaffin cells in rat jejunum, serotonin of which circulated through the portal vein into blood circulation and then increased the mesenteric lymph formation. The mode of action of serotonin remains unclear. Therefore, we aimed to clarify the mechanisms involved in the regulation of the jejunal lymph formation with permeant albumin in in vivo rat experiments. We investigated the effects of intravenous administration of serotonin or water intake on the jejunal-originated lymph volume and the concentration of albumin in the lymph in the presence or absence of L-NAME. The effects of intravenous administration of L-NAME, nicardipine, A23187, and ML-7 on the lymph formation with permeant albumin were also evaluated. Serotonin or water intake significantly increased the mesenteric lymph volume with permeant albumin in the jejunal microcirculation. The serotonin- and water intake-mediated responses were significantly reduced by the pretreatment with intravenous administration of L-NAME. Intravenous administration of L-NAME itself also decreased significantly the jejunal lymph formation. Administration of A23187 and ML-7 significantly reduced the jejunal lymph formation with permeant albumin. In contrast, administration of nicardipine significantly increased the lymph formation. In conclusion, portal venous blood flow- or serotonin-mediated NO release from venular endothelial cells plays physiologically key roles in the lymph formation in rat jejunum via the extrusion of calcium ions and inactivation of MLCK in endothelial cells.


Antioxidant activity and structural features of Cinnamomum zeylanicum.
The antioxidants in food materials have recently attracted researchers' attention because many reports have shown that the oxidative stress is closely related to the aging process of the cells and acts as a trigger to various diseases including cancer. Since reactive oxygen species (ROS) is involved in initiating and promoting several diseases such as cancer and cardiovascular events, this study was designed to evaluate the antioxidant capacity of pectic polysaccharides extracted from the bark of Cinnamomum zeylanicum, locally known as Daruchini. An arabinogalactan (A), one partly methyl esterified galacturonic acid (B) and a neutral glucan (C) were isolated. The glucan is made up of β-(1 → 3)-linked glucopyranosyl residues and has a molecular mass of 7 kDa. The arabinogalactan is highly branched and has an average molecular mass of 40 kDa. The in vitro antioxidant capacity of the fractions was studied by ferric reducing antioxidant power (FRAP) and 1,1-diphenyl-2-picrylhydrazyl (DPPH) assays. The arabinogalactan (A) showed the highest potential followed by the uronic acid (B) and glucan (C). Taken together, these findings demonstrate that these polysaccharides could be used as natural antioxidants by the food industry.


Changes of diesel particle diameter and surface area distributions by non-thermal plasma.
A wide literature has demonstrated that internal combustion engines are the main responsible for the emission of fine particles in urban areas. Within this scope, ultrafine particles within diesel exhausted gas have been widely proven to exert a significantly harmful impact on human health and environment. This scenario has led the research community to turn the attention from particle mass to diameter and surface area. In this paper, non-thermal plasma (NTP) technology was applied to a heavy duty diesel engine. Chemical reactions of diesel particles in plasma zone were analyzed. Additionally, variation in diesel particles' number and surface area distributions, engendered by above reactions, were thoroughly investigated. The results showed that diesel exhausted particles experienced oxidation, aggregation, and crush because of enhanced plasma transports and active species in plasma zone. NTP presents excellent reduction effectiveness of diesel particles covering different sizes. Being more than 50%, the most considerable surface area concentration drop was found in correspondence of 1800 RPM. Differently, the lowest drop of surface area concentration was seen at 1200 RPM. As a result of the NTP actions, surface area concentration distributions were almost the same for diameters being larger than 0.5 μm at different engine modes, except at 900 RPM. This research made a foundation of dropping particle emissions and evaluating the effectiveness of NTP dropping particle harms to human health.


A comparison of shear bond strengths of metal and ceramic brackets.
The study measures and compares shear bond strength data obtained from metal, ceramic, and ceramic-filled plastic brackets bonded to human incisor teeth with a heavily filled composite resin. The mean values for groups of different types of brackets were not statistically significant. The site of failure was commonly at the resin/bracket interface except for the ceramic-filled plastic brackets, which frequently showed failure of the bracket itself. One group of ceramic brackets that used no mechanical retention often showed failure to the extent that the bulk of resin remained on the bracket. The findings strongly suggest that ceramic brackets should offer a viable alternative to their metal counterparts because they combine esthetics with a bond strength that is comparable to and as reliable as their metal counterparts.


Morphology and electrochemical behavior of Ag-Cu nanoparticle-doped amalgams.
The aim of this study was to introduce Ag-Cu phase nanopowder as an additive to improve the corrosion behavior of dental amalgams. A novel Ag-Cu nanopowder was synthesized by the precipitation method. An amalgam alloy powder (World-Cap) was added and mixed with 5 wt.% and 10 wt.% of Ag-Cu nanopowders, respectively, to form experimental amalgam alloy powders. The original alloy powder was used as a control. Alloy powders were examined using X-ray diffraction, transmission electron microscopy (TEM), scanning electron microscopy and electron probe microanalysis. Amalgam disk specimens of metallurgically prepared were tested in 0.9% NaCl solution using electrochemical methods. The changes in the corrosion potential and anodic polarization characteristics were determined. Corrosion potential data were analyzed statistically (n=3, analysis of variance, Tukey's test, p<0.05). The diameters of lamellar structure Ag-Cu nanoparticles were measured to be approximately 30 nm. The composition of the Ag-Cu nanoparticles determined by TEM-energy-dispersive spectroscopy was 56.28 at.% Ag-43.72 at.% Cu. A light-shaded phase was found mixing with dark Cu-Sn reaction particles in the reaction zones of Ag-Cu nanoparticle-doped amalgams. The Ag-Cu nanoparticle-doped amalgams exhibited zero current potentials more positive than the control (p<0.05) and no current peak was observed at -325mV that related to Ag-Hg phase and Cu6Sn5 phase in anodic polarization curves. The results indicated that the corrosion resistance of high-copper single-composition amalgam could be improved by Ag-Cu nanoparticle-doping.


Externally controllable glycan presentation on nanoparticle surfaces to modulate lectin recognition.
Nature dynamically controls carbohydrate expression on cells rather than static presentation. Here we report synthetic glycosylated nanoparticles that contain polymeric 'gates' to enable external control (via temperature changes) of glycan surface expression, as an alternative to enzymatic control in nature. This approach offers a new dynamic multivalent scaffold for glycan recognition.


IL-33/ST2 axis is involved in disease progression in the spleen during Leishmania donovani infection.
During infection with Leishmania donovani, parasite control is linked to the systemic Th1 immune response, but in infected organs (liver, spleen and bone marrow), the response differs according to the micro-environment. The pleiomorphic cytokine interleukin-33 (IL-33) exerts various roles during infection, either protective or detrimental. In this study, we explored the role of IL-33 in the outcome of Leishmania infection in the spleen. We used several mouse models, on BALB/c and C57BL/6 (B6) backgrounds, infected with L. donovani and sacrificed at 15, 30 or 60 days after infection and characterized mRNA expression of immune markers, immune cell populations, histological response, and parasite loads. During infection IL-33 and ST2 mRNA increased in parallel in the spleen of wild type (wt) animals and paralleled the immunodetection of ST2+ and IL-33+ cells; their expression was twice as high in BALB/c, compared to B6 mice. Mice treated with twice-weekly injections of rIL-33 had higher splenic parasite burdens on D15 (BALB/c) or on D60 (B6). In BALB/c, IL-33 treatment led to immune exhaustion with abolition of Th1 cytokine expression (IFN-γ and IL-12) in the spleen and higher serum levels of Th2 cytokines (IL-4, IL-5 and IL-13). In B6, IL-33 treatment induced the Treg cell pathway with a dramatic increase of FoxP3 mRNA induction and expression on tissue sections. IL-33-KO mice had lower parasite loads and a higher Th1 response than their wt counterparts. IL-33 appears as a factor of aggravation of the disease in the spleen tissue of mice infected with L. donovani.


A new ganglion in male Moniliformis moniliformis (Acanthocephala).
A new ganglion identified as the bursal ganglion is described from male Moniliformis moniliformis. This ganglion is located adjacent to the pseudocoel and longitudinal muscle fibers and medial to the dorsal lacunar canal about 1 mm from the posterior end of males with non-everted bursa. The ganglion consists of four large club-shaped cells with single nuclei and bipolar neurons. The ganglion cells are paired with one neuron from each cell innervating the opposite side of the worm.


In situ approach induced growth of highly monodispersed Ag nanoparticles within free standing PVA/PVP films.
Ag nanoparticles supported within polyvinyl alcohol (PVA)/polyvinyl pyrrolidone (PVP) films have been successfully synthesized using novel in situ method. PVA and PVP acted as stabilizer and polyol reductant, respectively. The successful incorporation of silver nanoparticles in PVA/PVP matrix was confirmed by UV-Vis spectroscopy, X-ray diffraction (XRD), transmission electron microscope (TEM) and Fourier transform infrared (FTIR) spectroscopy. It was found that PVA/PVP-stabilized silver nanocomposite film revealed the presence of well-dispersed and spherical silver nanoparticles with an average diameter of 30 nm, while the particle sizes were reduced as the PVP percentage increased. A possible formation mechanism of Ag nanoparticles is also proposed in this article.


Distribution of Tryptophan Hydroxylase Immunoreactivity in the Spiral Ganglion Neurons of Mouse Cochlea.
Serotonin, also known as 5-hydroxytryptamine, is an important neurotransmitter and neuromodulator in the nervous system. Spiral ganglion neurons (SGNs) are the first station of the peripheral afferent auditory nervous system. We have previously demonstrated positive serotonin immunoreactivity in mouse SGNs. Whether serotonin in the SGNs is absorbed from the circumstances, or is synthesized by the neurons themselves is unknown. The purpose of this study was to find out the source of serotonin in the SGNs. Tryptophan hydroxylase is the rate-limiting enzyme in the process of serotonin biosynthesis. We detected tryptophan hydroxylase in the mouse SGNs using immunohistochemistry. The positive immunostaining of tryptophan hydroxylase was observed in the cytoplasm of SGNs. The cytoplasm of the SGNs was not get stained in the negative control group. Our results suggest that SGNs can synthesize serotonin themselves, and they may serve as an additional source of serotonin in the cochlea. The SGNs are serotonergic neurons. The receptors of serotonin on the membrane of SGNs interact with serotonin as auto-receptors. Serotonin in these neurons plays its physiological role in an autocrine/paracrine way.


Physical activity as a correlate of symptoms, quality of life, comorbidity, and disability status in Hispanics with multiple sclerosis.
Hispanics with multiple sclerosis (MS) experience disproportionate rates of mobility disability compared to non-Hispanic Whites with MS. Physical activity (PA) is highlighted as a potential adjuvant therapy for improving MS symptoms and disease progression, however less than 30% of Hispanics with MS report sufficient levels of PA. The current study aimed to examine the correlates of PA behavior among Hispanics with MS in the North American Research Committee on Multiple Sclerosis Registry (NARCOMS). In Spring 2015, 136 NARCOMS participants identified as Hispanic and completed the International Physical Activity Questionnaire (IPAQ). IPAQ scores were converted to Health Contribution Scores (HCS) for estimating PA. The association between the HCS scores and MS symptoms (i.e., mobility, cognition, fatigue, spasticity, hand function, bowel/bladder, sensory, tremors, depression, and pain), quality of life (QOL), comorbid conditions, and disability status were evaluated using Pearson or Spearman correlation coefficients with follow-up multivariable regression analyses. The mean age among participants was 58 years and 79% identified as female. The mean MS disease duration was 20 years and 68% reported relapsing disease course. The mean HCS score among participants was 15.6 ± 20.9. HCS was moderately associated with disability status (rs = -0.39), mobility (rs = -0.37), bowel/bladder function (rs = -0.33), and physical health related QOL (r = 0.32). There were small associations between HCS and hand function (rs = -0.29), fatigue (rs = -0.20), and tremor (rs = -0.25). Multivariable regression analyses indicated that disability status, mobility, bowel/bladder function, and physical health related QOL were all associated with HCS but did not independently contribute to the models when controlling for age, sex, and employment. This study highlights correlates of PA behavior among Hispanics with MS. Researchers and clinicians may consider disability status, mobility, and physical health related QOL in future studies examining PA among Hispanics with MS.


Analytical evaluation of the novel soluble fms-like tyrosine kinase 1 and placental growth factor assays for the diagnosis of preeclampsia.
Performance evaluation of the novel BRAHMS KRYPTOR soluble fms-like tyrosine kinase 1 (sFlt-1) and placental growth factor (PlGF) assays. Intra- and inter-assay imprecision, functional sensitivity, linearity in dilution, method comparison, and diagnostic capacity were evaluated. Intra-assay coefficient of variations (CVs) were between 1.1% and 5.3% and inter-assay CVs between 3.9% and 11.1%. Functional sensitivity was 6.7ng/L for PlGF and 34ng/L for sFlt-1, respectively. The linearity in dilution was excellent (r>0.995) in the assay-specific relevant range of concentration. The KRYPTOR assay correlated well with the Elecsys sFlt-1 (r=0.996), Elecsys PlGF (r=0.990) and the Elecsys sFlt-1/PlGF ratio (r=0.947) with partially high mean bias values. The optimal cut points for diagnosis of preeclampsia were calculated for KRYPTOR assays at: 60.5ng/L (PlGF), 4725ng/L (sFlt-1), and 99.2 (sFlt-1/PlGF ratio) which were different with the corresponding Elecsys cut points. Nevertheless, the sensitivity, specificity, positive predictive values (PPVs), negative predictive values (NPVs), and areas under the curves (AUCs) were completely comparable in both assay platforms, even when applying the standard cut-off of 85 for sFlt-1/PlGF ratio or gestational age specific "rule in-rule-out" cut-offs for early and late onset preeclampsia. The new BRAHMS KRYPTOR sFlt-1 and PlGF immunoassay show excellent precision and reliability. The assay results and the diagnostic capacity were highly comparable to established fully automated immunoassays (Elecsys). Hence, sFlt-1/PlGF ratio generated on KRYPTOR immunoassay platform should be suitable for diagnosing preeclampsia in clinical routine laboratory.


Screening for pre-eclampsia and fetal growth restriction by uterine artery Doppler at 11-14 weeks of gestation.
To examine the value of uterine artery Doppler at 11-14 weeks of gestation in the identification of women at risk of developing pre-eclampsia and fetal growth restriction. Uterine artery Doppler was carried out at 11-14 weeks in 3324 consecutive singleton pregnancies attending for routine care in three London hospitals. The right and left uterine arteries were identified using color flow mapping and velocity waveforms were obtained using pulsed Doppler. The mean pulsatility index of the two arteries was determined and the predictive value of a mean pulsatility index > the 95th centile in the prediction of pre-eclampsia and/or fetal growth restriction was calculated. Satisfactory flow velocity waveforms were obtained from both uterine arteries in 3195 (96.1%) of the 3324 pregnancies examined and complete outcome information was obtained for 3045 (95.3%) of these women. The 95th centile of the uterine artery mean pulsatility index was 2.35 and did not change significantly with gestational age. The pregnancy was complicated by pre-eclampsia in 63 (2.1%) cases and by fetal growth restriction in 290 (9.5%) cases. The sensitivity of a mean pulsatility index > 2.35 for pre-eclampsia (with or without fetal growth restriction) was 27.0% but for fetal growth restriction alone it was 11.7%. The respective sensitivities for these complications requiring delivery before 32 weeks of gestation were 60.0% and 27.8%, respectively. Uterine artery Doppler at 11-14 weeks of gestation identifies a high proportion of women who develop severe pre-eclampsia and/or fetal growth restriction.


Effect of calcium ions on the density of lecithin and its effective molecular volume in lecithin-water dispersions.
As the packing structure of lipid molecules in the liposomes will vary in the presence of ions, it is expected that the density of lipid and the effective volume of lipid molecules in the dispersions will also vary, albeit minutely. Density measurements of lipid-water dispersions with the addition of Ca(2+) ions were determined accurately. The effect of Ca(2+) ions on the molecular packing structure of the liposomes was elucidated from the results obtained. The results for the density of the lecithin in the dispersions with and without the addition of Ca(2+) ions are, respectively, 1.0782 and 1.0579 g cm(-3) at 25 degrees C; and 1.0048 and 0.9961 g cm(-3) at 50 degrees C. The average values of the effective molecular volume of lecithin in the dispersions with and without the addition of Ca(2+) ions are, respectively, 1.131E-21 and 1.152E-21 cm(3) at 25 degrees C; and 1.213E-21 and 1.224E-21 cm(3) at 50 degrees C.


Successful transcatheter retrieval of embolized Amplatz Canine Duct Occluders in two dogs.
Transcatheter occlusion of patent ductus arteriosus (PDA) using an Amplatz® Canine Duct Occluder (ACDO) is routinely performed in dogs. Pulmonary embolization of the device is a rarely reported complication of this procedure. We report here the first two cases of successful transcatheter retrieval of an embolized ACDO. An 8-month-old, 21-kg, German shepherd (case 1) was referred for pulmonary edema secondary to a large PDA with left-to-right shunting. After medical stabilization, an emergency procedure for PDA closure was recommended. An 8-mm ACDO was deployed under general anesthesia. The device was released after confirming its stability with a gentle tug test but migrated into the pulmonary trunk. A 10-mm ACDO was subsequently successfully deployed and released. Vascular access was then obtained from the right jugular vein so that a vascular snare could be used to capture the ACDO waist and pull it back toward the right ventricle and then the right atrium. It was then removed through the jugular vein. The dog recovered uneventfully and was discharged after confirmation of complete ductal occlusion. The same complication occurred in a second case (case 2, asymptomatic 6-month-old, 7.9-kg, cocker spaniel), and a similar procedure was used to successfully retrieve the embolized device. Both dogs are still doing well 9 and 21 months, respectively, after the procedure. These cases illustrate that transcatheter retrieval of ACDO devices embolized in the pulmonary artery using vascular snares is technically feasible in the dog.


The effect of progesterone on hemoglobin synthesis in suspension cultures of fetal erythroid cells from calf liver.
When fetal calf liver erythroid cells were incubated in the presence of small amounts of progesterone (10(-7)-10(-8) M), the hemoglobin synthesis in these cells was significantly increased. The increase in the amount of radioactivity in de novo synthesized hemoglobins could be demonstrated when techniques such as isoelectric focusing, chromatography on DEAE-cellulose and gel chromatography on Sephadex G-100 were used to isolate the hemoglobin fraction. Using the latter technique, it was shown that the synthesis of cytoplasmic non-hemoglobin proteins in erythroid-cell lysates was also stimulated by progesterone. The presence of hepatocytes in culture nullified the hormone action. It was necessary that progesterone was present during the first hours of culture. Delayed addition of the steroid to the cells had no effect on hemoglobin synthesis. Erythropoietin was necessary to obtain stimulation by progesterone. These results suggest that the target cell of the hormone is an erythropoietin-sensitive cell. High concentrations of progesterone (10(-4) M) strongly inhibited hemoglobin synthesis in fetal calf erythroid cells. Culture of cells under this condition, however, gives rise to a cell population that preferentially synthesizes adult hemoglobin. Our results suggest that in the erythropoietic calf liver, high concentrations of progesterone may preferentially stimulate adult hemoglobin synthesis, or that those cells which have a high capacity to synthesize adult hemoglobins are less sensitive to toxic concentrations of the hormone. The effects of stimulation of hemoglobin synthesis in fetal calf erythroid cells occur at hormone concentrations that suggest a possible physiological role of progesterone in fetal, and eventually also in maternal, erythropoiesis.


The results of modipin monotherapy in coronary heart disease patients with arterial hypertension (secondary coronary prevention).
The goal of the present study was to evaluate the safety and efficacy of the third generation calcium antagonist -- modipin (amlodipin, Asfarma, Turkey) in 29 patients with coronary atherosclerosis and arterial hypertension. In addition, some pleiotropic actions were examined. On the background of 5-10 mg/day modipin monotherapy during the 3-month study period the target systolic and diastolic blood pressure were achieved in 64 and 51% of cases. Modipin revealed some antiatherogenic efficacy as well. Pleiotropic effects of the drug were particularly expressed in restoring endothelial function reducing degree of hyperlipoperoxidemia and inhibition of platelet aggregation. There were positive changes in functional class of angina. Clinical safety was good. Consequently the present trial supports the use of modipine in all coronary artery disease patients with moderate or severe arterial hypertension.


Different expression of estrogen receptors alpha and beta in human myometrium and leiomyoma during the proliferative phase of the menstrual cycle and after GnRHa treatment.
Uterine leiomyomas (uterine fibroids) are sex-steroid dependent benign tumors. Limited knowledge is available regarding the role of estrogen and their receptors in the regulation of fibroids in premenopausal women, and in their shrinkage after treatment with a gonadotropin-releasing hormone analogue (GnRHa). The expression of the two subtypes of the estrogen receptor (ER), ER alpha and ER beta, was studied in leiomyoma and homologous myometrium from women in the proliferative phase of the menstrual cycle and from women treated with GnRHa. The mRNA levels of ER alpha and ER beta were monitored by solution hybridization and in situ hybridization, and receptor proteins were detected and localized by immunohistochemistry. Both ER alpha and ER beta were present in the leiomyomas and homologous myometrium. The ER alpha mRNA level in the leiomyomas was higher than in the surrounding myometrium. The ER beta mRNA level was lower than that of ER alpha in both groups. ER beta immunoreactivity was lower in leiomyomas when compared with the myometrium after GnRHa treatment, while ER alpha was higher in the leiomyomas. The present results imply that the increased ratio of ER alpha/ER beta observed in the fibroids after GnRHa treatment could reflect or be the cause of the shrinkage of the leiomyoma, which is the clinical outcome of this treatment.


Pro-apoptotic effect of the hepatitis B virus X gene.
The hepatitis B virus (HBV) is a common human pathogen that causes acute and chronic liver disease. Persistent HBV infection is strongly associated with the development of hepatocellular carcinoma. The contribution of the viral regulatory protein HBx in liver oncogenesis has been supported by our recent studies in a transgenic mouse model, showing that HBx cooperates with c-myc by accelerating the onset of primary liver tumors. Here we show that liver expression of HBx is associated with increased rates of spontaneous apoptosis in liver cells from two different transgenic lines. In transient transfection assays, overexpression of HBx in the established hepatocyte cell line MMHD3 and in human hepatoma cells HepG2 was found to induce apoptosis in a dose-dependent manner. These data suggest that HBx might trigger an apoptotic process in HBV-infected hepatocytes, in turn possibly favoring liver regeneration and accumulation of genetic alterations, ultimately leading to liver cell transformation in chronically infected patients.


The influence of surface topography of a porous perfluoropolyether polymer on corneal epithelial tissue growth and adhesion.
Design principles for corneal implants are challenging and include permeability which inherently involves pore openings on the polymer surface. These topographical cues can be significant to a successful clinical outcome where a stratified epithelium is needed over the device surface, such as with a corneal onlay or corneal repair material. The impact of polymer surface topography on the growth and adhesion of corneal epithelial tissue was assessed using porous perfluoropolyether membranes with a range of surface topography. Surfaces were characterised by AFM and XPS, and the permeability and water content of membranes was measured. Biological testing of membranes involved a 21-day in vitro tissue assay to evaluate migration, stratification and adhesion of corneal epithelium. Similar parameters were monitored in vivo by surgically implanting membranes into feline corneas for up to 5 months. Data showed optimal growth and adhesion of epithelial tissue in vitro when polymer surface features were below a 150 nm RMS value. Normal processes of tissue growth and adhesion were disrupted when RMS values approached 300 nm. Data from the in vivo study confirmed these findings. Together, outcomes demonstrated the importance of surface topography in the design of implantable devices that depend on functional epithelial cover.


Omnidirectional guided wave inspection of large metallic plate structures using an EMAT array.
The design of an electromagnetic acoustic transducer (EMAT) array device for the inspection of large areas of metallic plate-like structures using the S0 guided wave mode is described. The reasons for using the S0 mode are discussed and it is shown how the choice of mode determines the nature of the EMAT array elements. A novel array construction technique is shown to be necessary whereby the EMAT coils for adjacent elements are overlapped in order to achieve the required element density. Results are presented that illustrate the operation of the device on steel and aluminum plate specimens in the thickness range from 5 to 10 mm. An area of at least 10 m2 can be inspected from a single location. Spurious signals in the results are caused both by the unwanted A0 mode and by S0 sidelobes, the latter occurring at the same radial distance from the array as the genuine S0 signal from a reflector, but in the wrong direction. The signal-to-coherent noise performance of the complete system is determined by the amplitude ratio of the largest genuine S0 signal to the largest spurious signal. This is typically around 30 dB. The sensitivity of the device to artificial defects and genuine corrosion patches is demonstrated and the limitations of its operation are discussed. The feasibility of using the device with the S1 guided wave mode to inspect a 20 mm thick plate is also demonstrated.


[Current treatment for Gaucher's disease and new prospects].
Two new useful enzymes have recently undergone clinical trials for the treatment of Gaucher's disease (GD): velaglucerase alpha and taliglucerase alpha were both approved for early access programs as of the June 2009 shortage in Imiglucerase supply. Velaglucerase has been approved by both, Food and Drug Administration and European Medicines Agency. The Phase I/II trial of velaglucerase is in its 8th year: There were no drug-related serious adverse events or withdrawals, and no antibodies. Statistically significant improvements (p<0.004) were noted in mean percent change from baseline to nine months and baseline to 48 months for hemoglobin (19.2% and 21.7%, respectively), platelet counts (67.6% and 157.8%, respectively), normalized liver volume (<18.2% and <42.8%, respectively), and normalized spleen volume (<49.5% and <79.3%, respectively). Within 2 years of initiation of therapy, all patients achieved normalization of hemoglobin level, all but one patient achieved platelet counts of greater than 100×10(9)/L, all patients achieved near normalization in liver volumes, and all patients but one exhibited a reduction of more than 50% in spleen volume. At present, velaglucerase alpha is indicated in type 1 GD symptomatic patients (children or adults) and is accepted as an orphan drug by the EMA with similar cost to imiglucerase. Taliglucerasa alpha, obtained from transfected plant cell cultures, is pending to approval.


Understanding breast cancer stories via Frank's narrative types.
While breast cancer narratives have become prevalent in Western culture, few researchers have explored the structure of such narratives, relying instead on some form of thematic analysis based upon content. Although such analyses are valuable, Arthur Frank (The Wounded Storyteller, The University of Chicago Press, Chicago, 1995) provides researchers with an additional means of studying stories of illness, through the examination of their structures. In this article, the author applies Frank's work to a phenomenological study of embodiment after breast cancer. Frank's three narrative types are used to enhance understanding of the ways in which stories are culturally constructed, using data collected through one focus group discussion and two in-depth interviews with each of 12 women who had experienced breast cancer. The author then conveys the significance of this form of analysis for future research.


Voluntary intake, chemical composition and in vitro digestibility of fresh forages fed to guinea pigs in periurban rearing systems of Kinshasa (Democratic Republic of Congo).
The daily voluntary intake (DVI) of Guinea pigs (GP) fed 15 fresh forages used in periurban rearing systems of Kinshasa (Democratic Republic of Congo) was investigated. In order to determine the best forages combination for GP diet, DVI was compared to their nutritional value measured in vitro using (1) a pepsin-pancreatin hydrolysis, (2) an gas fermentation test on the hydrolysed residues with an inoculum prepared from GP faeces, and (3) the chemical composition of the offered feeds and the hydrolysis residues. The forages ranking based on the DVI was correlated to the NDF content, but not to their nutritional values determined in vitro. According to their high DVI (from 4.23 to 7.75 g/kg liveweigth), and their valuable in vitro nutritional values (crude protein ranging from 261 to 279 g crude protein kg(-1) DM, pepsin-pancreatin digestibilities of the dry matter from 0.55 to 0.59 and final gas production from 170 to 196 1 kg(-1) DM), Desmodium intortum, Euphorbia heterophylla or Amaranthus hybridus, can be suggested to the farmers to complement the usual diet distributed to the GP based on Panicum maximum.


Impact of emotion dysregulation and cognitive insight on psychotic and depressive symptoms during the early course of schizophrenia spectrum disorders.
Emotion dysregulation is relevant to the aetiology of schizophrenia spectrum disorders (SSD). While most studies have focused on the chronic phase of SSD, little is known about the effects of emotion dysregulation and associated cognitive risk factors during the early phase of the illness, with negative implications for early intervention. The purpose of this study is to examine the impact of maladaptive cognitive emotion regulation strategies, global emotion dysregulation, and cognitive insight on psychotic and comorbid depressive symptoms in patients with early SSD. Participants included 150 newly diagnosed outpatients with SSD who were seeking treatment at the Early Psychosis Intervention Program. All participants completed the Cognitive Emotion Regulation Questionnaire, Difficulties with Emotion Regulation Scale, and Beck Cognitive Insight Scale. Severity of psychotic and depressive symptoms were rated on the Brief Psychiatric Rating Scale. Multivariate regression adjusting for gender and psychiatric comorbidity revealed that global emotion dysregulation was associated with more severe positive and depressive symptoms. Further moderation analyses revealed a significant interaction between global emotion dysregulation and cognitive insight (self-certainty) on depression such that for patients with high self-certainty, greater global emotion dysregulation was associated with increased severity of depressive symptoms. There was no interaction between global emotion dysregulation and cognitive insight on positive symptoms. Our findings provide preliminary support for the associations between emotion dysregulation and psychopathology in early SSD. Further research is needed to examine the transdiagnostic role of emotion dysregulation in the aetiology and treatment of a wider range of psychotic disorders.


Hormonal and inflammatory signatures of different mood episodes in bipolar disorder: a large-scale clinical study.
Bipolar disorder (BD) is characterized by intensive mood fluctuations. While hormones imbalance plays important role in the mood swings, it is unknown whether peripheral hormones profiles could differentiate the manic and depressive mood episodes in BD. In this study, we investigated the changes of various hormones and inflammatory markers across distinct mood episodes of BD in a large clinical study to provide mood episode-specific peripheral biomarkers for BD. A total of 8332 BD patients (n = 2679 depressive episode; n = 5653 manic episode) were included. All patients were in acute state of mood episodes and need hospitalization. A panel of blood tests were performed for levels of sex hormones (serum levels of testosterone, estradiol, and progesterone), stress hormones (adrenocorticotropic hormone and cortisol), and an inflammation marker (C-reactive protein, CRP). A receiver operating characteristic (ROC) curve was used to analyze the discriminatory potential of the biomarkers for mood episodes. In overall comparison between mood episodes, the BD patients expressed higher levels of testosterone, estradiol, progesterone, and CRP (P < 0.001) and lower adrenocorticotropic hormone (ACTH) level (P < 0.001) during manic episode. The episode-specific changes of testosterone, ACTH, and CRP levels remained between the two groups (P < 0.001) after correction for the confounding factors including age, sex, BMI, occupation, marital status, tobacco use, alcohol consumption, psychotic symptoms, and age at onset. Furthermore, we found a sex- and age-specific impact of combined biomarkers in mood episodes in male BD patients aged ≥ 45 years (AUC = 0.70, 95% CI, 0.634-0.747), not in females. While both hormone and inflammatory change is independently associated with mood episodes, we found that the combination of sex hormones, stress hormones and CRP could be more effective to differentiate the manic and depressive episode. The biological signatures of mood episodes in BD patients may be sex- and age-specific. Our findings not only provide mood episode-related biological markers, but also better support for targeted intervention in BD treatments.


The effects of exercise and diet program in overweight people - Nordic walking versus walking.
Nordic walking (NW) has been recommended as a form of exercise for clinical populations. Despite intervention programs designed to face a clinical status may last several months, no longitudinal studies have compared the effect of NW to another usual form of exercise, like walking (W). We evaluated the effects of diet combined with a long-supervised NW versus W training on body composition, aerobic capacity and strength in overweight adults. Thirty-eight participants, randomized into a NW (n=19, 66±7 years, body mass index (BMI) 33±5)) and a W (n=19, 66±8 years, BMI 32±5) group, followed a diet and a supervised training routine 3 times/week for 6 months. The variables assessed at baseline, after 3 and 6 months were: anthropometric indexes (ie, BMI and waist circumference (WC)), body composition, aerobic capacity (oxygen consumption (VO2peak), peak power output (PPO), 6-min walking test (6MWT)) and strength (maximal voluntary contraction of biceps brachialis (MVCBB) and quadriceps femoris (MVCQF), chair stand and arm curl (AC)). After 6 months both NW and W group decreased significantly BMI (6% and 4%, respectively) and WC (8% and 4%, respectively), but only the NW group reduced (P<0.05) total body fat (8%), android fat (14%) and leg fat (9%). After 6 months, PPO increased (P<0.05) in both groups, but VO2peak improved (P<0.05) only in the NW group (8%). After 6 months, 6MWT increased (P<0.001) in both groups and only the NW group improved (P<0.05) in MVCBB (14%), MVCQF (17%) and AC (35%). Our results suggest that NW can give in some relevant health parameters, greater and faster benefits than W. Thus, NW can be a primary tool to counteract the obesity and overweight state in middle-aged adults.


Hybrid-architectured double-promoter expression systems enhance and upregulate-deregulated gene expressions in Pichia pastoris in methanol-free media.
Double-promoter expression system (DPES) design as de novo metabolic engineering strategy enables fine-tuned and enhanced gene expression. We constructed a collection of monodirectional hybrid-architectured DPESs with engineered promoter variants PADH2-Cat8-L2 and PmAOX1 and with the naturally occurring promoter PGAP to enhance and upregulate-deregulated gene expressions in Pichia pastoris in methanol-free media. Reporter red fluorescent protein (mApple) and enhanced green fluorescent protein (eGFP) were expressed under PADH2-Cat8-L2 and PmAOX1 or PGAP, respectively, enabling the determination of the transcription period and strength of each constituent in the DPESs. We determined fluorescent protein expressions in batch cultivations on 2% (v/v) ethanol, excess glucose, and excess glycerol, and compared them with single-promoter expression systems constructed with PADH2-Cat8-L2, PmAOX1, and PGAP. The transcription- and expression-upregulation power of bifunctional DPESs was higher than that of twin DPESs (two-copy expression systems). Our findings answer long-standing questions regarding the high- (or multi-) copy clone results in the literature. Our first conclusion is that increasing identical components in the DPES architectures linearly increases the concentrations of cis-acting DNA sites and increases the demand for key transcription factors (TFs) that perturb their good coupling of supply and demand. The next is that the synthesis of some amino acids may create bottleneck(s) as rate-limiting amino acid(s) in recombinant protein synthesis. With bifunctional DPESs, each constituent upregulated the transcription and increased the expression and reduced the demand for the same TF(s) in the generation of novel regulatory circuits, due to the increased number of nonidentical cis-acting DNA sites. We tested superior DPES performances in extracellular human growth hormone (rhGH) production. Thereby, the indications related to the rate-limiting amino acids were verified. Compared with its constituents PADH2-Cat8-L2 and PmAOX1, the bifunctional DPES4 enhanced rhGH production by 1.44- and 2.02-fold, respectively. The DPES design method, with its constraint and parameters, enables the generation of promising r-protein production platforms with high impact on industrial-scale production processes and opens up new avenues for research in yeasts. KEY POINTS: • Design method with the constraint and parameters for the construction of the DPESs is presented. • Hybrid-architectured de novo DPESs are designed to enhance and fine-tune gene expression. • Bifunctional DPESs demonstrate enhanced transcription and expression. • Twin DPESs linearly increase cis-acting DNA sites and consequently increase the demand for the same TFs. • Bifunctional DPESs enable good coupling of supply and demand to bind with TFs. • Ethanol-controlled Snf1 pathway and crosstalk enable fine-tuned transcription and enhanced expression.


Effects of calcium-channel blocking agents on left ventricular diastolic function in hypertrophic cardiomyopathy and in coronary artery disease.
Abnormal left ventricular (LV) diastolic performance is a characteristic feature of hypertrophic cardiomyopathy (HC) and an important contributor to the development of symptoms. Impaired diastolic filling of the hypertrophied left ventricle results from both diminished distensibility and prolonged or incomplete relaxation. LV distensibility is not only influenced by fixed anatomic abnormalities (such as fibrosis or hypertrophy) that determine the passive elastic properties of the left ventricle, but also is modulated by the dynamics of myocardial relaxation: prolonged or incomplete LV relaxation may restrict the rate and extent of LV filling and result in altered pressure-volume relations throughout diastole. Several studies indicate that impaired LV relaxation and filling in HC may be modified favorably by verapamil or nifedipine administered on a short-term basis in the catheterization laboratory, associated with improved diastolic pressure-volume relations. Verapamil also improves LV filling during oral therapy. Improved indexes of LV filling correlate with symptomatic improvement, both short-term and long-term: Approximately 80% of patients having a persistent increase in peak LV filling rate have persistent improvement in objective exercise tolerance compared with preverapamil values. Altered LV relaxation and filling are also often observed in patients with coronary artery disease (CAD) after myocardial infarction or during acute ischemia. Moreover, impaired filling occurs under resting conditions in many patients who have normal systolic function and no evidence of previous infarction. Nifedipine improves indexes of LV relaxation and distensibility during pacing-induced ischemia and verapamil improves indexes of LV filling at rest and during exercise-induced ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)


Molecular systematics of the new world screech-owls (Megascops: Aves, Strigidae): biogeographic and taxonomic implications.
Megascops screech-owls are endemic to the New World and range from southern Canada to the southern cone of South America. The 22 currently recognized Megascops species occupy a wide range of habitats and elevations, from desert to humid montane forest, and from sea level to the Andean tree line. Species and subspecies diagnoses of Megascops are notoriously difficult due to subtle plumage differences among taxa with frequent plumage polymorphism. Using three mitochondrial and three nuclear genes we estimated a phylogeny for all but one Megascops species. Phylogenies were estimated with Maximum Likelihood and Bayesian Inference, and a Bayesian chronogram was reconstructed to assess the spatio-temporal context of Megascops diversification. Megascops was paraphyletic in the recovered tree topologies if the Puerto Rican endemic M. nudipes is included in the genus. However, the remaining taxa are monophyletic and form three major clades: (1) M. choliba, M. koepckeae, M. albogularis, M. clarkii, and M. trichopsis; (2) M. petersoni, M. marshalli, M. hoyi, M. ingens, and M. colombianus; and (3) M. asio, M. kennicottii, M. cooperi, M. barbarus, M. sanctaecatarinae, M. roboratus, M. watsonii, M. atricapilla, M. guatemalae, and M. vermiculatus. Megascops watsonii is paraphyletic with some individuals more closely related to M. atricapilla than to other members in that polytypic species. Also, allopatric populations of some other Megascops species were highly divergent, with levels of genetic differentiation greater than between some recognized species-pairs. Diversification within the genus is hypothesized to have taken place during the last 8 million years, with a likely origin in Central America. The genus later expanded over much of the Americas and then diversified via multiple dispersal events from the Andes into the Neotropical lowlands.


Relationship between comfort and back posture and mobility in sitting-posture.
The objective of this work is to analyze the causes of lumbar discomfort while sitting on a chair, by analyzing the relationship of lumbar curvature, pelvic inclination and their mobilities with discomfort. An experiment has been performed with healthy subjects, in which comfort, postural and mobility parameters have been measured. Their relationship has been analyzed with multivariate analysis. Factorial analysis has been used to represent all the correlated variables measured. Logistic regression and discriminant analyses have been used to classify discomfort/absence of discomfort. The results show that great changes of posture are a good indicator of discomfort, and that lordotic postures with forward leaned pelvis and low mobility are the principal causes of the increase of discomfort.


[Percutaneous treatment of the pulmonary valve].
Right ventricular outflow tract diseases are historically outcomes of surgical reconstruction for heart defects in neonates or children (Tetralogy of Fallot, Ross surgery). This kind of surgery performed during childhood lead often to dysfunctional right ventricular outflow tract (stenosis, leak) in older infants or young adults. In this case, reintervention on the right ventricular outflow tract would be associated with a high surgical risk. Development of the first percutaneous valves in the year 2000 paved the way for the pulmonary revalvulation. This percutaneous procedure has emerged as a credible alternative to the surgery for multioperated high risk patients with congenital cardiopathies. Two valves are currently available on the French market (Melody®, Sapien®); they cover all therapy indications, except the example of very wide outflow tracts which remain a surgical issue. Medical teams in charge of these young patients have to be enough trained in order to limit risks during the procedure. To this end, several teams promote the percutaneous pulmonary revalvulation over surgical revalvulation, this latter becoming limited only to cases in which percutaneous treatment is not feasible.


Health care workers and key policy informant's knowledge of the use of calcium and low dose aspirin for prevention of preeclampsia in Malawian women.
This study investigated health care workers and key policy informant's knowledge, and barriers to the use of calcium and aspirin for preventing preeclampsia in Blantyre and Lilongwe, Malawi. A descriptive cross-sectional formative study using semi-structured In-Depth Interview (IDIs) was conducted at Queen Elizabeth Central Hospital (QECH), Reproductive Health Directorate, and the United Nations Population Development Fund (UNFPA) Office in 2021. Data was analyzed using NVIVO™ software. Thematic content analysis was used to analyze and interpret the findings. Emerging themes were then developed inductively and deductively. Doctors had greater knowledge of the use of calcium and aspirin for prevention of preeclampsia compared to nurses and key policy informants. Lack of knowledge, patient's late presentation, scarcity of calcium tablets and delays in implementing new guidelines were the barriers to use identified. This study shows that there are health care worker and policy level barriers that affect the implementation of calcium and aspirin use for the prevention of preeclampsia in Malawian women.


Do Parents' ADHD Symptoms Affect Treatment for their Children? The Impact of Parental ADHD on Adherence to Behavioral Parent Training for Childhood ADHD.
Nearly half of all youth with Attention-Deficit Hyperactivity Disorder (ADHD) have at least one parent who also meets criteria for the disorder, and intergenerational ADHD is a significant risk factor for poor outcomes following evidence-based behavioral parent training (BPT) programs. Given that BPT is predicated on consistent parental involvement, symptoms of ADHD in parents may be a significant barrier to effective engagement with BPT treatment. In the present investigation, we examine the effect of parental ADHD symptoms on BPT treatment engagement for children with ADHD-predominantly inattentive presentation (N = 148, ages 7-11). We examine the following parent- and clinician-rated treatment engagement domains: between-session skill adherence, in-session participation, perceived skill understanding, treatment-engagement attitudes, and session attendance. Parent- and clinician-rated between-session adherence was the only treatment engagement domain related significantly to parental ADHD symptoms. This finding was robust and remained even after accounting for symptoms of parental anxiety and depression, child ADHD symptom severity, and various sociodemographic factors (parental education level, household income, employment status, and being a single parent). These findings suggest that targeting parental ADHD symptoms in the context of parenting interventions may be a promising approach for improving adherence and treatment outcomes for BPT interventions.


Screening high-grade vesicoureteral reflux in young infants with a febrile urinary tract infection.
The lack of good evidence for improved outcomes in children and young infants with febrile urinary tract infection (UTI) after aggressive treatment for vesicoureteral reflux (VUR) has raised doubts regarding the need for routine voiding cystourethrography (VCUG), and the appropriate imaging evaluation in these children remains controversial. This prospective study aimed to determine whether abnormalities found on acute dimercaptosuccinic acid (DMSA) scan and ultrasound (US) can help indicate the necessity of voiding cystourethrography (VCUG) in young infants. For 3.5 years, all infants younger than 3 months presenting with first febrile UTI were prospectively studied. All infants were hospitalized and investigated using US (<3 days after admission), DMSA scan (<5 days after admission), and VCUG (7-10 days after antibiotic treatment) after diagnosis. The association among findings of US, DMSA scan, and VCUG were evaluated. From 220 infants, there were abnormal results in 136 (61.8%) US and in 111 (50.5%) DMSA scans. By US, ten infants (4.5%) with abscess or structural abnormalities other than VUR were diagnosed. High-grade (III-V) VUR was present in 39 patients (17.7%). The sensitivities for high-grade VUR of renal US alone (76.9%) or DMSA scan alone (82.1%) were not as good as that of the "OR rule" strategy, which had 92.3% sensitivity and 94.3% negative predictive value. To screen high-grade VUR in young infants with febrile UTI, US and acute DMSA scan could be performed first. VCUG is only indicated when abnormalities are apparent on either US or DMSA scan or both.


The economic impact of addressing the organ shortage with clinically high-risk allografts.
Expanding gaps between the number of patients awaiting transplantation and the number who receive organs in the United States has been associated with heightened disease severity among transplant candidates and more common use of organs from non-standard donors. We summarize data on the economic consequences of liver and renal allograft quality in contemporary practice. Policy makers and providers must work together to ensure that financial disincentives do not lead to wastage of lifesaving organs.


Low T3-syndrome and nutritional status as prognostic factors in patients undergoing bone marrow transplantation.
Bone marrow transplantation is known to be associated with considerable morbidity and mortality. The aim of this study was to determine the influence of nutritional status and development of sick euthyroid syndrome as prognostic factors for outcome after BMT. In 100 patients who underwent transplantation the following parameters were assessed before and at day 14 and 28 after transplantation: anthropometric data (body weight, body mass index, body composition, grip strength), rapid turnover proteins transferrin and prealbumin, T4, T3, free T4, reverse T3, thyroid-stimulating hormone and thyroglobulin. Following bone marrow transplantation, 22 patients died in the short-term follow-up (group A) before day 140 after BMT, 21 patients died during further follow-up between days 140 and 365 (group B) and 57 patients survived longer than 365 days (group C). All patients experienced a significant decrease of transferrin and T3, accompanied by an increase of rT3 and rT3/T3 ratio at day 14 after BMT. At day 28 after BMT, patients in group C showed recovery from these changes with an increase of transferrin and a fall in rT3 and the rT3/T3-ratio, which was not seen in patients who died during further follow-up (groups A and B). The observed changes were independent of other prognostically relevant factors (type of disease, HLA-match, immunosuppression). Impaired nutritional status and development of a sick euthyroid syndrome, without tendency to recovery, are associated with a higher probability of fatal outcome after bone marrow transplantation and have prognostic relevance in this group of patients.


Conditional cross-interval correlation analyses with applications to simultaneously recorded cerebellar Purkinje neurons.
Two conditional cross-correlation techniques are described for the analysis of two simultaneously recorded neuronal spike trains. The conditional interspike interval histogram describes the distribution of interspike intervals of a neuron conditioned by a preceding spike in another neuron. The conditional cross-interval histogram describes the distribution of cross-intervals of two neurons conditioned by a preceding spike in one of the neurons. These techniques could be used to reveal the temporal coupling in the discharge of two neurons recorded simultaneously. The techniques augment the description of the correlation obtained with conventional cross-correlation measures. When applied to the simple spike discharge of simultaneously recorded cerebellar Purkinje neurons, the methods reveal temporal interactions between neurons that are not readily apparent from conventional cross-correlograms. The patterns observed suggest a tightly coupled, temporal surround-inhibition among nearby Purkinje neurons.


Recent advances in the management of oral and maxillofacial trauma.
This review summarises recently published papers on maxillofacial trauma in 2 widely read journals: the British Journal of Oral and Maxillofacial Surgery (BJOMS) and the International Journal of Oral and Maxillofacial Surgery (IJOMS). Since a large proportion of the injuries seen in oral and maxillofacial surgery (OMFS) departments are fractures of the facial skeleton, we primarily focus on their assessment and treatment, but also cover problems that affect the temporomandibular joint (TMJ) (including ankylosis), military injuries, polytrauma, and the use of perioperative drugs. Between 2012 and 2013, 121 articles were published in the 2 journals. Most of the research concerned mandibular fractures, particularly those involving the condyle, but epidemiological studies and midfacial fractures were also well represented. Even though the incidence of facial injury is high, it is difficult to collect data particularly when long-term evaluation is required, as rates of compliance and attendance at follow up tend to be low. The number of large-scale studies was therefore small. A concerted effort to collaborate nationally and across specialties to undertake larger studies will help to improve outcomes.


Reducing the Risk of Stroke in Patients with Impaired Renal Function: Nutritional Issues.
Patients with renal failure have extremely high cardiovascular risk; in dialysis patients the risk of stroke is increased approximately 10-fold over that in the general population. Reasons include not only a high prevalence of traditional risk factors such as diabetes, hypertension and dyslipidemia, but also the accumulation of toxic substances that are eliminated by the kidneys, so have very high levels in patients with renal failure. These include plasma total homocysteine, asymmetric dimethylarginine, thiocyanate, and toxic products of the intestinal microbiome (Gut-Derived Uremic Toxins; GDUT), which include trimethylamine N- oxide (TMAO), produced from phosphatidylcholine (largely from egg yolk) and carnitine (largely from red meat). Other GDUT are produced from amino acids, largely from meat consumption. Deficiency of vitamin B12 is very common, raises plasma tHcy, and is easily treated. However, cyanocobalamin is toxic in patients with renal failure. To reduce the risk of stroke in renal failure it is important to limit the intake of meat, avoid egg yolk, and use methylcobalamin instead of cyanocobalamin, in addition to folic acid.