Quantitative analysis of signaling networks across differentially embedded tumors highlights interpatient heterogeneity in human glioblastoma.
Glioblastoma multiforme (GBM) is the most aggressive malignant primary brain tumor, with a dismal mean survival even with the current standard of care. Although in vitro cell systems can provide mechanistic insight into the regulatory networks governing GBM cell proliferation and migration, clinical samples provide a more physiologically relevant view of oncogenic signaling networks. However, clinical samples are not widely available and may be embedded for histopathologic analysis. With the goal of accurately identifying activated signaling networks in GBM tumor samples, we investigated the impact of embedding in optimal cutting temperature (OCT) compound followed by flash freezing in LN2 vs immediate flash freezing (iFF) in LN2 on protein expression and phosphorylation-mediated signaling networks. Quantitative proteomic and phosphoproteomic analysis of 8 pairs of tumor specimens revealed minimal impact of the different sample processing strategies and highlighted the large interpatient heterogeneity present in these tumors. Correlation analyses of the differentially processed tumor sections identified activated signaling networks present in selected tumors and revealed the differential expression of transcription, translation, and degradation associated proteins. This study demonstrates the capability of quantitative mass spectrometry for identification of in vivo oncogenic signaling networks from human tumor specimens that were either OCT-embedded or immediately flash-frozen.


Personal light-at-night exposures and components of variability in two common shift work industries: uses and implications for future research.
Objectives Shift workers' increased risk of various adverse health outcomes has been linked to light-at-night (LAN) exposure, but few studies have measured LAN exposure in workplaces. To inform future research methods, this study aimed to (i) measure shift workers' exposures to LAN across industries, occupations, and work environments and (ii) assess components of variance across different exposure groupings and metrics. Methods Between October 2015 and March 2016, 152 personal full-shift measurements were collected from 102 night shift workers in emergency health services (paramedics, dispatchers) and healthcare industries (nurses, care aides, security guards, unit clerks, and laboratory, pharmacy, and respiratory therapy staff) in the province of British Columbia, Canada. Descriptive and variance component analyses were conducted for the 23:00-05:00 period to characterize exposures using multiple metrics of potential biological relevance (median lux, 90 thpercentile lux, sum of minutes ≥30 lux, and sum of minutes ≥100 lux). Results Average exposure levels were highest in the healthcare industry. By occupation, laboratory workers and care aides displayed the highest and emergency dispatch officers displayed the lowest levels for all LAN exposure metrics. Between-group variance was large relative to within-group variance for all exposure groupings and metrics, and increased as grouping specificity increased (moving from industry to occupation). Conclusions Results from this study suggest that high-level grouping schemes may provide a simple yet effective way of characterizing individual LAN exposures in epidemiological studies of shift work. Ongoing measurement of LAN exposures and assessment of exposure variability is needed in future studies of shift workers as a means to increase sampling efficiency, reduce measurement error, and maximize researchers' ability to detect relationships where they exist.


Social anxiety disorder in the Canadian population: exploring gender differences in sociodemographic profile.
The present study examined the prevalence and sociodemographic profile of Canadians with social anxiety disorder using data from the Canadian Community Health Survey Cycle 1.2 (N = 36,984). Social anxiety disorder was assessed using the World Mental Health Composite International Diagnostic Interview and sociodemographic variables were explored by gender. Results suggested significant gender differences for prevalence, comorbid depression, marital status, living arrangements, employment status in the past 12 months, and self-reported mental health status. These observations suggest that individuals with social anxiety disorder experience life disruption, and that of all socially anxious respondents, females may be experiencing more distress than males.


May the best friend be an enemy if not recognized early: hypernatremic dehydration due to breastfeeding.
Hypernatremic dehydration is a serious condition in the newborn period. We present 5 infants with hypernatremic dehydration due to breastfeeding; one of them died because of brain edema during treatment.Hypernatremic dehydration in breast-fed newborns is secondary to insufficient lactation and all mothers should be encouraged about breastfeeding, taught the signs of successful breastfeeding, and the warning signs of dehydration. Here, we discuss hypernatremic dehydration in breastfeeding neonates, its causes and treatment.


Blood flow MRI of the human retina/choroid during rest and isometric exercise.
To investigate blood flow (BF) in the human retina/choroid during rest and handgrip isometric exercise using magnetic resonance imaging (MRI). Four healthy volunteers (25-36 years old) in multiple sessions (1-3) on different days. MRI studies were performed on a 3-Tesla scanner using a custom-made surface coil (7×5cm in diameter) at the spatial resolution of 0.5×0.8×6.0 mm. BF was measured using the pseudo-continuous arterial-spin-labeling technique with background suppression and turbo-spin-echo acquisition. During MRI, subjects rested for 1 minute followed by 1 minute of handgrip, repeating three times, while maintaining stable eye fixation on a target with cued eye blinks at the end of each data acquisition (every 4.6 seconds). Robust BF of the unanesthetized human retina/choroid was detected. Basal BF in the posterior retina/choroid was 149±48 mL/100 mL/min with a mean heart rate of 60±5 beats per minute, mean arterial pressure of 78±5 mm Hg, ocular perfusion pressure of 67±4 mm Hg at rest (mean±SD, n=4 subjects). Handgrip significantly increased retina/choroid BF by 25%±7%, heart rate by 19%±8%, mean arterial pressure by 22%±5% (measured at the middle of the handgrip task), and ocular perfusion pressure by 25%±6% (averaged across the entire handgrip task) (P<0.01), but did not change intraocular pressure, arterial oxygen saturation, end-tidal CO2, and respiration rate (P>0.05). This study demonstrates a novel MRI application to image quantitative BF of the human retina/choroid during rest and isometric exercise. Retina/choroid BF increases during brief handgrip exercise, paralleling increases in mean arterial pressure. Handgrip exercise changes ocular perfusion pressure free of potential drug side effect and can be done in the MRI scanner. MRI offers quantitative BF with large field of view without depth limitation, potentially providing insights into retinal pathophysiology.


Phagocytosis of Cryptococcus neoformans by alveolar macrophages.
Guinea pig pulmonary macrophages phagocytized but did not kill nonencapsulated cells of Cryptococcus neoformans. The phagocytic process was inhibited by cryptococcal capsular polysaccharide. Pulmonary macrophages, activated by preinjecting heat-killed bacteria into intact animals, did not kill the engulfed yeast cells. Labeled cells of C. neoformans were neither killed nor cleared from guinea pig lungs 6 h postexposure. The results of our experiments indicate that during the first few hours after the lung is exposed to the infectious particle of C. neoformans the pulmonary macrophage does not function primarily to kill engulfed yeast cells. We believe that a rapid yet transient acute inflammatory response probably plays a major role in this process during the first few hours after C. neoformans enters the lung.


Deep vein thrombosis during prolonged mechanical ventilation despite prophylaxis.
To determine the prevalence of deep vein thrombosis (DVT) among patients requiring prolonged mechanical ventilation in the intensive care unit. Prospective cohort study. Medical intensive care unit of a university-affiliated urban teaching hospital. Patients requiring mechanical ventilation for >7 days. All patients admitted to the medical intensive care unit requiring prolonged mechanical ventilation underwent duplex ultrasonography of their lower extremities and upper extremities every 7 days. The main outcome identified was the presence of DVT. Secondary outcomes included hospital mortality, hospital and intensive care unit lengths of stay, and the occurrence of pulmonary embolism. A total of 110 patients requiring mechanical ventilation for >7 days were enrolled. Prophylaxis against DVT was employed in 110 of the patients (100%). A total of 26 patients (23.6%) developed DVT. Patients with DVT were statistically more likely to have underlying malignancy (30.8% vs. 8.3%; p =.004) and longer durations of central venous catheterization (26.9 +/- 22.2 days vs. 14.5 +/- 12.1 days; p =.024) compared with patients without DVT. There were no statistically significant differences in hospital mortality or lengths of stay in the hospital and intensive care unit for patients with and without DVT. Patients documented to have DVT by using duplex ultrasonography had a statistically greater frequency of subsequent pulmonary embolism during their hospitalization (11.5% vs. 0.0%; p =.012). The occurrence of DVT is common among patients requiring prolonged mechanical ventilation in the intensive care unit setting despite the use of prophylaxis measures. These data suggest that alternative strategies for the prevention of DVT should be evaluated. Additionally, early detection methods should be considered to reduce the potential morbidity associated with untreated DVT in this high-risk population.


Biological and molecular biological characterization of the virus progeny from transformed clones MuSV-124 and MuSV-349: evidence for MuLV-specific nucleotide sequences in the MoMuSV size class of RNA from MoMuSV-124.
The genetic information of MoMuSV-349 and MoMuSV-124, two clones of productively transformed TB cells, was distributed between two size classes of RNA (mol. wt. 2.9 x 10(6)) in the proportions of 5:1. Some preparations of MoMuSV-124 lacked the large RNA. The virions produced by both clones also contained all the nucleotide sequences of Moloney leukaemia virus and the ratio of MuSV:MuLV produced by the two clones differed markedly. The distribution of the sequences specific for Moloney murine leukaemia virus (MoMuLV) between the two size classes of RNA was studied using molecular hybridization to DNA probes complementary to and representative of: (i) the Moloney murine sarcoma virus (MoMuSV) RNA genome (mol. wt. 1.9 x 10(6)); (ii) those nucleotide sequences shared by MoMuSV and MoMuLV; (iii) nucleotide sequences specific for MoMuSV; (iv) nucleotide sequences specific for MoMuLV. The only detectable Moloney leukaemia virus-specific nucleotide sequences present in MoMuSV-124 virions were in the RNA of mol. wt. 1.9 x 10(6), whereas these sequences were detected in the RNA of mol. wt. 2.9 x 10(6) isolated from MoMuSV-349 virions. The biological properties of the replicating information in MoMuSV-124 suggest that, consistent with the small size of RNA, it is defective. whereas MoMuSV-349 produces virions containing an intact MoMuLV genome, competent for replication.


Novel association between single-nucleotide polymorphisms of IKKβ at rs17875746 and rs12676482 and periodontitis.
Single-nucleotide polymorphisms (SNPs) in the IKKβ gene have been associated with susceptibility to various inflammatory illnesses, including periodontitis. The aim of the present study was to investigate the association between IKKβ SNPs (at rs17875746 and rs12676482) and periodontitis in an Iraqi Arab population. In this case-control study, 94 Iraqi volunteers were split into 2 groups, with the case group including 62 periodontitis patients (37 men and 25 women) and the control group including 32 racially matched healthy people (19 men and 13 women). Periodontal parameters were recorded for each individual. Then, 2 mL of venous blood was taken from each participant to isolate their genomic DNA. In particular, the genotyping of rs17875746 and rs12676482 in IKKβ was performed with the use of the polymerase chain reaction (PCR) sequencing methods. The effect of the distribution of IKKβ SNPs on periodontitis was assessed by counting the odds ratio (OR), which was 5.264 for rs17875746 and 0.900 for rs12676482. Surprisingly, allele T revealed a significantly higher association with periodontitis for rs17875746 (OR = 6.750) than allele G (p = 0.038). Overall, the GT genotype in rs17875746 had a higher chance of developing the disease (OR = 3.321) as compared to other genotypes. Meanwhile, the GA genotype in rs12676482 had a higher chance of developing the disease (OR = 1.242) as compared to other genotypes. In addition, rs17875746 showed a significant positive association with tooth mobility, a family history, clinical attachment loss (CAL), and gingival recession (GR) in the study groups. The IKKβ polymorphisms may increase genetic susceptibility to periodontitis in Iraqi Arab patients.


Dapagliflozin Ameliorates STZ-Induced Cardiac Hypertrophy in Type 2 Diabetic Rats by Inhibiting the Calpain-1 Expression and Nuclear Transfer of NF-κB.
To investigate the effect of dapagliflozin (DAPA) on cardiac hypertrophy induced by type 2 diabetes mellitus (T2DM) and its mechanism. SD rats with T2DM were divided into a T2DM group (n = 6) and DAPA group (n = 6). They were, respectively, fed with the same amount of normal saline and 1 mg/kg DAPA. The control group (n = 6) was also fed with normal saline. The hearts were tested by the application of echocardiography and hemodynamics. Subsequently, fasting blood glucose (FBG), serum total cholesterol (TC), and triglyceride (TG) as well as interleukin- (IL-) 10, IL-6, and tumor necrosis factor (TNF)-α in serum were tested. H&E and Masson staining was performed to observe the degree of cardiac tissue lesions, and expression of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), calpain-1, p-IκBα, and p65 in myocardial tissue was tested by qRT-PCR and Western blot. Compared with the control group, rats in the T2DM group exhibited significant diabetic symptoms: FBG was significantly elevated, and the levels of TC, TG, IL-6, and TNF-α were significantly increased, while the levels of IL-10 and the calpain activity were evidently decreased. However, DAPA treatment could improve the above changes. At the same time, the damage and fibrosis of the heart tissue in the DAPA group were markedly improved. Additionally, the mRNA expression of ANP and BNP in myocardial tissue of the DAPA group was markedly increased. And DAPA could inhibit the expression of p-IκBα/IκBα in the cytoplasm and p65 in the nucleus as well as the expression of calpain-1 in myocardial tissue. DAPA treatment ameliorates the cardiac hypertrophy caused by T2DM by decreasing body blood glucose, while reducing the expression of calpain-1 in cardiomyocytes and inhibiting the nuclear translocation of NF-κB.


Comparison and correlates of three preference-based health-related quality-of-life measures among overweight and obese women with urinary incontinence.
To compare three preference-based health-related quality-of-life (HRQL) measures and examine independent correlates of HRQL among overweight and obese women with urinary incontinence (UI) enrolled in a weight loss intervention trial. Participants completed baseline questionnaires, which included the Health Utilities Index 3 (HUI3) and Medical Outcomes Study Short Form-36 (SF-36). The SF-36 was used to derive SF-6D and estimated Quality of Well-Being (eQWB) scores. Height, weight, medical history, incontinence measures, and level of physical activity also were assessed. The intraclass correlation coefficient (ICC) was computed, and differences in mean scores across HRQL measures were examined. Potential correlates of HUI3, SF-6D, and eQWB scores were evaluated using multivariable generalized linear models. Mean ± SD scores for the HUI3, SF-6D, and eQWB were 0.81 ± 0.18, 0.75 ± 0.10, and 0.71 ± 0.06, respectively. Significant differences were observed across measures (P < 0.0001), and the overall ICC was 0.36. In multivariable analyses, BMI was negatively associated with HUI3 (P = 0.003) and eQWB (P < 0.001), and UI episode frequency was negatively associated with eQWB (P = 0.015) and SF-6D (P < 0.001). Significant differences in mean utilities across the HUI3, SF-6D, and eQWB indicate that these measures do not assess identical dimensions of HRQL. Both BMI and UI episode frequency were related to HRQL in this cohort; however, the magnitude of the relationship depended on the preference-based measure used. These findings highlight the need to consider the method used to generate HRQL values for calculating quality-adjusted life-years in cost-utility analyses, since choice of method may have a substantial impact on the outcome of the analysis.


Volumetric analysis of cleft lip deformity using 3D stereophotogrammetry.
To quantify and compare pre-operative and post-operative volumetric adjustments of the upper lip tissues in patients with cleft lip. The authors performed an anthropometric study and a quantitative analysis of the differences based on three-dimensional morphology of the nasolabial area. Twenty facial images using the three-dimensional stereophotogrammetry were taken from ten selected subjects on two separate occasions, sitting in natural head position. Facial landmarks were marked and measurements recorded, in order to calculate the volumetric adjustments in the soft tissues of the upper lip, comparing the preoperative and postoperative results. Student test and p-Value were performed for statistical analysis. The analysis of the 3D images showed variability with the pre- and postoperative volumes of the nasolabial area with: an increase of upper lip volume all patients; a complete view of the severity in the preoperative; and an improvement of the appearance in the postoperative. The amount of increase of the upper lip volume was established about 29,7%. For all measurements, the variability between pre- and post-operative was significant (p < 0.01). The 3D stereophotogrammetry technique allows a detailed preoperative evaluation and an accurate assessment of the surgical outcomes. The study provides a value of volumetric variation of the upper lip in individuals with cleft lip. Cleft lip, Nasolabial area, 3D Morphological Analysis, 3D Stereophotogrammetry, Upper lip volume.


What twin studies tell us about the heritability of brain development, morphology, and function: a review.
The development of brain structure and function shows large inter-individual variation. The extent to which this variation is due to genetic or environmental influences has been investigated in twin studies using structural and functional Magnetic Resonance Imaging (MRI). The current review presents an overview of twin studies using MRI in children, adults and elderly, and focuses on cross-sectional and longitudinal designs. The majority of the investigated brain measures are heritable to a large extent (60-80%), although spatial differences in heritability are observed as well. Cross-sectional studies suggest that heritability estimates slightly increase from childhood to adulthood. Long-term longitudinal studies are better suited to study developmental changes in heritability, but these studies are limited. Results so far suggest that the heritability of change over time is relatively low or absent, but more studies are needed to confirm these findings. Compared to brain structure, twin studies of brain function are scarce, and show much lower heritability estimates (~40%). The insights from heritability studies aid our understanding of individual differences in brain structure and function. With the recent start of large genetic MRI consortia, the chance of finding genes that explain the heritability of brain morphology increases. Gene identification may provide insight in biological mechanisms involved in brain processes, which in turn will learn us more about healthy and disturbed brain functioning.


Comparative metabolism of 7,12-dimethylbenz[a]anthracene by the perfused liver and liver microsomal preparations from Sprague-Dawley rats.
The metabolism of DMBA by microsomes and various cell cultures has been widely studied. However, the biotransformation of this compound by intact organs has not been well characterized. In order to compare the metabolism of DMBA in the whole liver with that in subcellular preparations, we used an in situ single-pass rat liver perfusion system and rat liver microsomes. [14C]DMBA was infused into the livers of Sprague-Dawley rats during the first 60 min of a 120 min perfusion. HPLC analysis of extracts of perfusate samples indicated that DMBA was rapidly oxidized in this system to a series of metabolites. The major products were polar metabolites including the trans-5,6- and the trans-10,11-dihydrodiols (46%), the trans-3,4-dihydrodiol (5%) and the 7-OHM-12-MBA and the 12-OHM-7-MBA metabolites (12%) of DMBA. Microsomes prepared from livers of corn oil treated rats were incubated with [14C]DMBA for 60 min, then extracted. In the microsomal system the major DMBA metabolites were the trans-8,9-dihydrodiol (6%), the 7- and 12-hydroxymethyl (20%), and the 3- and 4-hydroxy (11%) of DMBA with the more polar metabolites and the trans-3,4-dihydrodiol present at lower levels (12 and 3% respectively). This is the first report of DMBA metabolism in a whole liver preparation and the results are clearly different from those obtained in subcellular preparations in our laboratory and in cell culture systems elsewhere. These results have important implications for understanding DMBA biotransformation in vivo.


Sub-micron periodic structuring of sapphire by laser induced backside wet etching technique.
The periodic structuring of sapphire, by using laser induced backside wet etching technique (LIBWE) and 266 nm, 150 ps Nd:YAG laser radiation, is demonstrated here for first time. Sub-micron period Bragg reflectors are successfully patterned in sapphire wafers using modest energy densities and number of pulses. The gratings are characterized using diffraction efficiency measurements, AFM, and SEM. Issues related to the ablation process and to the phase mask holography are presented and discussed. The experimental results presented depict that the applied method is capable to produce relief structures of depth as deep as 100 nm, while maintaining high resolutions, close to the thermal diffusion length of the material corresponding to the ultrashort pulse duration.


Inter-organizational collaboration between healthcare providers.
Across OECD countries, healthcare organizations increasingly rely on inter-organizational collaboration (IOC). Yet, systematic insight into the relations across different healthcare sectors is lacking. The aim of this explorative study is twofold. First, to understand how IOC differs across healthcare sectors with regards to characteristics, motives and the role of health policy. Second, to understand which potential effects healthcare executives consider prior to the establishment of the collaborations. For this purpose, a survey was conducted among a representative panel of Dutch healthcare executives from medium-sized or large healthcare organizations. Almost half (n = 344, 48%) of the invited executives participated. Our results suggest that differences in policy changes and institutional developments across healthcare sectors affect the scope and type of IOC: hospitals generally operate in small horizontal collaborations, while larger and more complex mixed and non-horizontal collaborations are more present among nursing homes, disability care and mental care organizations. We find that before establishing IOCs, most healthcare executives conduct a self-assessment including the potential effects of the collaboration. The extensive overview of policy developments, collaboration types and intended outcomes presented in our study offers a useful starting point for a more in-depth assessment of the effectiveness of collaborations among healthcare organizations.


Lung Structure and Risk of Sleep Apnea in SPIROMICS.
SPIROMICS is a prospective cohort study that enrolled 2,981 participants with the goal of identifying new COPD subgroups and intermediate markers of disease progression. Individuals with COPD and sleep apnea (OSA) experience impaired quality of life and more frequent exacerbations. COPD severity also associates with CT-scan based emphysema and alterations in airway dimensions. To determine whether the combination of lung function and structure influences the risk of OSA among current and former smokers. Using two OSA risk scores, the Berlin Sleep Questionnaire (BSQ), and the DOISNORE50 (DIS), 1,767 current and former smokers were evaluated for association of lung structure and function with OSA risk. Study cohort mean age was 63 years, BMI 28 kg/m2, and FEV1 of 74.8% predicted. The majority were male (55%), white (77%), former smokers (59%), and had COPD (63%). A high-risk OSA score was reported in 36% and 61% using DIS and BSQ respectively. There was 9% increased odds of a high-risk DIS score (OR=1.09, 95%CI:1.03-1.14) and nominally increased odds of high-risk BSQ score for every 10% decrease in FEV1% predicted (OR=1.04, 95%CI:0.998-1.09). Lung function-OSA risk associations persisted after additionally adjusting for lung structure measurements (%emphysema, %air-trapping, PRM-fSAD, mean segmental wall area, tracheal %wall area, dysanapsis) for DIS (OR=1.12, 95%CI:1.03-1.22) and BSQ (OR=1.09, 95%CI:1.01-1.18). Lower lung function independently associates with having high-risk for OSA in current and former smokers. Lung structural elements, especially dysanapsis, functional small airways disease, and tracheal %wall area strengthened the effects on OSA risk.


Combinatorial cytotoxicity of gemcitabine and cytokine-activated killer cells in hepatocellular carcinoma via the NKG2D-MICA/B system.
Natural-killer group 2, member D (NKG2D) is an activating receptor on natural killer cells and activated T-cells, designated cytokine-activated killer (CAK) cells here. The MHC class I chain-related A and B (MICA and MICB, respectively) are ligands of NKG2D and are expressed on various human tumor cells, including hepatocellular carcinoma (HCC) cells. Here, we investigate whether gemcitabine, a chemotherapeutic agent, affects MICA/B expression in HCC. We used ELISA, RT-PCR and adherent target detachment assays to determine expression of MICA/B in HepG2 HCC cells and the level of cellular cytotoxicity generated by treatment with gemcitabine and/or CAK cells. Surface expression of MICA/B was evident after gemcitabine treatment, and MICB-specific mRNA was up-regulated. Pre-treatment with gemcitabine and subsequent exposure to CAK cells induced greater cytotoxicity than either treatment alone. Inclusion of soluble MICB significantly reduced cytotoxicity. Gemcitabine induced MICA/B expression in HepG2 cells, resulting in synergistic enhancement of the cytotoxic effects of NKG2D-high CAK cells. The combination of gemcitabine and CAK cells may have clinical therapeutic significance for HCC.


Differentiation of members of the human herpesviridae family by radioimmunoassay.
Many individuals who are seronegative for one member of the human Herpesviridae family are strongly seropositive for other members. Using sera from such individuals, the radioimmunoassay technique demonstrated absence of antigen-antibody cross-reactions between varicella-zoster virus (VZV) and herpes simplex virus (HSV) at levels of less than one part in 1,000. Sera containing antibody to both HSV and VZV were absorbed with antigens of one agent without significantly altering the amount of remaining antibody to the other antigen. This further suggests that HSV and VZV do not share a common antigen. The same radioimmunoassay technique and serum absorption method that revealed no serological cross-reactions between HSV and VZV revealed the expected cross-reaction between HSV type 1 (HSV-1) and HSV-2. Reciprocally absorbed anti-HSV-1 and anti-HSV 2 sera were able to differentiate the two HSV types reliably. No cross-reactions were seen between cytomegalovirus, VZV, and HSV or between Epstein-Barr virus, VZV, and HSV. We postulate that heterotypic antibody responses sometimes observed for VZV after primary infections by HSV may not be due to shared antigens, but to activation of latent VZV infections, release of new VZV antigens, and consequent stimulation of new antibody production to VZV.


Medial rectus muscle incarceration in pediatric medial orbital wall trapdoor fractures.
We describe two cases of orbital trapdoor fractures with medial rectus muscle incarceration. Small interventional case series. This is a retrospective university based report of two healthy males (11 and 14 years old) who developed diplopia following blunt orbital trauma. Both patients had decreased horizontal ocular motility of the involved eye with minimal additional evidence of trauma. Computed tomography (CT) demonstrated no significant bony displacement; however, the left medial rectus muscle was located within the ethmoid sinus in the first and had an abnormal size and shape in the second case. In both cases, during urgent surgical repair, the incarcerated medial rectus muscle was gently released from linear non-displaced medial wall fractures and ocular motility normalized postoperatively. In pediatric patients sustaining blunt orbital trauma, medial rectus incarceration should be considered and managed accordingly.


Nitric oxide contributes both to papilla-based resistance and the hypersensitive response in barley attacked by Blumeria graminis f. sp. hordei.
SUMMARY Nonspecific penetration resistance due to papilla formation and race-specific hypersensitive response (HR) can both contribute to Blumeria graminis resistance in barley. Some effective papillae form even in the susceptible cv. Pallas and the isoline P01 carries the additional Mla1 allele conditioning HR. The NO-specific stain DAF-2DA (4,5-diaminofluorescein-2-diacetate) revealed a transient NO generation burst commencing 10 h after inoculation (h.a.i.) in close association with sites of papilla formation in both barley lines. In P01 a burst of NO production throughout some attacked cells was initiated around 10-12 h.a.i. and this preceded whole-cell autofluorescence indicative of HR. The specificity of DAF-2DA staining was demonstrated by the suppression of staining following application of the NO scavenger C-PTIO (1H-imidazol-1-yloxy-2-(4-carboxyphenyl)-4,5-dihydro-4,4,5,5-tetramethyl-3-oxide). In addition, C-PTIO application increased penetration frequencies in both barley lines, indicating a role for NO in papilla-based resistance. Furthermore, C-PTIO application slightly delayed HR in P01 whereas, conversely, application of an NO donor, sodium nitroprusside, slightly accelerated HR in P01 and increased cell death frequency in Pallas. Thus, NO generation is one of the earliest responses of barley epidermal cell defence against B. graminis attack and may be important in both the initiation and the development of effective papillae and cell death due to HR.


Complementation of an hMSH2 defect in human colorectal carcinoma cells by human chromosome 2 transfer.
The human colorectal tumor cell line LoVo has a homozygous deletion in the hMSH2 gene from exon 3 to exon 8, is deficient in mismatch repair (MMR) activity, and exhibits microsatellite instability. To determine whether the introduction of a wild type hMSH2 into LoVo restores MMR activity and stabilizes microsatellite loci, we transferred a chromosome 2 fragment containing hMSH2 into a homologous recombination-proficient chicken DT40/human hybrid (DT40 2C) and a human chromosome 2 in a mouse A9 hybrid to LoVo. Transfers of these chromosomes into LoVo resulted in LoVo both with and without a wild-type hMSH2. Complete correlation was found between the presence of the wild-type hMSH2 and hMSH2 expression, an increased stability in microsatellite loci, and competency in MMR. The hMSH2-positive LoVo hybrids also showed an increased sensitivity to N-methyl-N'-nitro-N-nitrosoguanidine. This enhanced toxicity is associated with G(2) cell-cycle arrest followed by premature mitosis and cell death. These results suggest that hMSH2 may be responsible for complementing mutator and drug-resistant phenotypes in chromosome 2-transferred LoVo cells. To test whether the hMSH2 in DT40 2C cells can be modified by homologous recombination, we transfected DT40 2C with a targeting vector containing an hMSH2 exon 4 disrupted by the zeocin-resistant gene. The results showed that the hMSH2 locus in DT40 2C was efficiently targeted by an exogeneously transfected homologous sequence, suggesting that transfer of a modified hMSH2 from DT40 2C to LoVo via chromosome transfer could be used to determine the function of hMSH2.


Digital and analog readout systems for fiber-optic strain sensors as applied to the monitoring of roller element bearing systems.
A rotating machinery test rig was instrumented with fiber Fabry-Perot interferometer strain sensors for condition monitoring of rolling element bearings. Strain variations produced by ball passes were observed and analyzed in the time and frequency domain. Wavelength division multiplexing was utilized to simultaneously monitor the sensors with analog and digital readout systems--analog for high bandwidth and digital for high dynamic range and the monitoring of multiple sensors. The effects of imbalance on the shaft, changes in rotational speed, effects on the rotor system, and detection of bearing defects were investigated. Frequency peaks observed in the bearing sensor spectra closely matched predicted values. Imbalance and rotational speed tests showed good agreement with expected trends, and bearing defects were successfully detected.


Inbred mouse strains and genetic stability: a review.
Inbred mice were essential animal models for scientific research during the 20th century and will contribute decisive results in the current and next centuries. Far from becoming an obsolete research tool, the generation of new inbred strains is continuing and such strains are being used in many research fields. However, their genetic properties have been overlooked for decades, although recent research has revealed new insights into their genetic fragility and relative instability. Contrary to what we usually assume, inbred mice are far from being completely isogenic and both single-gene major mutations and polygenic mutational variability are continuously uploading into inbred populations as new sources of genetic polymorphisms. Note that several inbred strains from new major mutations are released every year, whereas small mutations can accumulate up to accounting for a significant percentage of the phenotypic variance (e.g. 4.5% in a recent study on C57BL/6J mice). Moreover, this genetic heterogeneity can be maintained for several generations by heterozygote selection and, if fixed instead of dropping off, genetic drift must be anticipated. The contribution of accidental genetic contamination in inbred strains must also be considered, although its incidence in current breeding stocks should be minimal, or even negligible. This review revisits several relevant topics for current inbred strains, discussing the latest cutting-edge results within the context of the genetic homogeneity and stability of laboratory mice. Inbred mice can no longer be considered as completely isogenic, but provide a remarkably homogeneous animal model with an inevitable moderate-to-low degree of genetic variability. Despite a certain degree of genetic heterogeneity becoming inescapable, inbred mice still provide very useful animal models with evident advantages when compared with outbred, that is, highly variable, populations.


Oxidation of aliphatic olefins by toluene dioxygenase: enzyme rates and product identification.
Toluene dioxygenase from Pseudomonas putida F1 has been studied extensively with aromatic substrates. The present work examined the toluene dioxygenase-catalyzed oxidation of various halogenated ethenes, propenes, butenes and nonhalogenated cis-2-pentene, an isomeric mix of 2-hexenes, cis-2-heptene, and cis-2-octene as substrates for toluene dioxygenase. Enzyme specific activities were determined for the more water-soluble C2 to C5 compounds and ranged from <4 to 52 nmol per min per mg of protein. Trichloroethene was oxidized at a rate of 33 nmol per min per mg of protein. Products from enzyme reactions were identified by gas chromatography-mass spectrometry. Proton and carbon nuclear magnetic resonance spectroscopy of compounds from whole-cell incubation confirmed the identity of products. Substrates lacking a halogen substituent on sp2 carbon atoms were dioxygenated, while those with halogen and one or more unsubstituted allylic methyl groups were monooxygenated to yield allylic alcohols. 2,3-Dichloro-1-propene, containing both a halogenated double bond and a halogenated allylic methyl group, underwent monooxygenation with allylic rearrangement to yield an isomeric mixture of cis- and trans-2,3-dichloro-2-propene-1-ol.


13C-breath tests in the study of microsomal liver function.
Conventional liver tests can be used to estimate a mixture of injury and function but none of these may be regarded as a reliable marker either to quantify functional hepatic reserve or to reflect life-threatening complications of acute and chronic liver diseases. To overcome this limit, many dynamic tests have been developed in order to evaluate the "hepatic functional mass". Among these tests we can include breath tests with 13C-labeled substrates undergoing different metabolic pathways. As concerning the evaluation of microsomal function, two main categories of breath tests have been developed based on the limiting step in the different substrates metabolism. The first group include aminopyrine, caffeine and diazepam, all substrates with a metabolism independent from hepatic blood flow and dependent almost exclusively from the enzymatic activity of different cytochromes P450. The other group is composed of substrates with flow dependent metabolism like methacetin, phenacetin, erythromycin. The aim of this review is to describe the clinical applications of microsomal liver breath tests in different hepatic diseases.


Flame retardants in indoor dust and air of a hotel in Japan.
Occurrence of flame retardants (FRs) in the indoor environment of highly flame-retarded public facilities is an important concern from the viewpoint of exposure because it is likely that FRs are used to a greater degree in these facilities than in homes. For this study, brominated flame-retardants (BFRs) and organophosphate flame-retardants and plasticizers (OPs), and brominated dibenzo-p-dioxins/furans (PBDD/DFs) were measured in eight floor dust samples taken from a Japanese commercial hotel that was assumed to have many flame-retardant materials. Concentrations of polybrominated diphenylethers (PBDEs) and hexabromocyclododecanes (HBCDs) varied by about two orders of magnitude, from 9.8-1700 ng/g (median of 1200 ng/g) and from 72-1300 ng/g (median of 740 ng/g), respectively. Concentrations of the two types of BFRs described above were most dominant among the investigated BFRs in the dust samples. It is inferred that BFR and PBDD/DF concentrations are on the same level as those in house and office dust samples reported based on past studies. Regarding concentrations of 11 OPs, 7 OPs were detected on the order of micrograms per gram, which are equivalent to or exceed the BFR concentrations such as PBDEs and HBCDs. Concentrations of the investigated compounds were not uniform among dust samples collected throughout the hotel: concentrations differed among floors, suggesting that localization of source products is associated with FR concentrations in dust. Passive air sampling was also conducted to monitor BFRs in the indoor air of hotel rooms: the performance of an air cleaner placed in the room was evaluated in terms of reducing airborne BFR concentrations. Monitoring results suggest that operation of an appropriate air cleaner can reduce both gaseous and particulate BFRs in indoor air.


[Actinomycetes--the test-organisms of genetic engineering].
The paper contains a short review of the data on using the methods of genetic engineering in studies of genetics and molecular biology in Streptomyces. The techniques of DNA introduction into actinomycetes and wide-spread vectors are briefly described. The origin of the actinomycete plasmids as chromosomal segments capable of autonomous replication is discussed. In this view, it is suggested that genetic instability in actinomycetes is connected with excision of specific DNA sequences from the chromosome at frequencies characteristic of recombination events. Also, amplification of short DNA segments within the chromosome resulting in tandem repeats is a consequence of unequal crossing over between direct repeats flanking the amplifying DNA and, possibly, of induction of replication of this DNA. The data on molecular cloning of actinomycete genes for primary metabolism and those for resistance to and biosynthesis of antibiotics, on using actinomycetes as the hosts for foreign genes to be expressed, as well as on analysis of nucleotide sequences of actinomycete DNA, are presented.


Fine-scale genetic structure reflects sex-specific dispersal strategies in a population of sociable weavers (Philetairus socius).
Dispersal is a critical driver of gene flow, with important consequences for population genetic structure, social interactions and other biological processes. Limited dispersal may result in kin-structured populations in which kin selection may operate, but it may also increase the risk of kin competition and inbreeding. Here, we use a combination of long-term field data and molecular genetics to examine dispersal patterns and their consequences for the population genetics of a highly social bird, the sociable weaver (Philetairus socius), which exhibits cooperation at various levels of sociality from nuclear family groups to its unique communal nests. Using 20 years of data, involving capture of 6508 birds and 3151 recaptures at 48 colonies, we found that both sexes exhibit philopatry and that any dispersal occurs over relatively short distances. Dispersal is female-biased, with females dispersing earlier, further, and to less closely related destination colonies than males. Genotyping data from 30 colonies showed that this pattern of dispersal is reflected by fine-scale genetic structure for both sexes, revealed by isolation by distance in terms of genetic relatedness and significant genetic variance among colonies. Both relationships were stronger among males than females. Crucially, significant relatedness extended beyond the level of the colony for both sexes. Such fine-scale population genetic structure may have played an important role in the evolution of cooperative behaviour in this species, but it may also result in a significant inbreeding risk, against which female-biased dispersal alone is unlikely to be an effective strategy.


Explorations of new phases in the Ga(III)/In(III)-Cu(II)-Se(IV)-O system.
Four new gallium(III)/indium(III), copper(II), selenium(IV) oxides, namely, Ga(2)Cu(SeO(3))(4) (1), Ga(2)CuO(SeO(3))(3) (2), and M(2)Cu(3)(SeO(3))(6) (M = Ga 3, In 4), have been synthesized by hydrothermal or high-temperature solid-state reactions. The structure of Ga(2)Cu(SeO(3))(4) (1) features a 2D layer of corner-sharing GaO(6) and CuO(6) octahedra with the SeO(3) groups hanging on both sides of the 2D layer. Ga(2)CuO(SeO(3))(3) (2) features a pillared layered structure in which the 1D Cu(SeO(3))(3)(4-) chains act as the pillars between 2D layers formed by corner- and edge-sharing GaO(n) (n = 4, 5) polyhedra. Although the chemical compositions of M(2)Cu(3)(SeO(3))(6) (M = Ga 3, In 4) are comparable, they belong to two different structural types. Ga(2)Cu(3)(SeO(3))(6) (3) exhibits a pillared layered structure built by [Ga(2)Cu(3)(SeO(3))(4)](4+) thick layers with Se(3)O(3)(2-) groups as pillars. The structure of In(2)Cu(3)(SeO(3))(6) (4) features a 3D network composed of [In(2)(SeO(3))(2)](2+) layers and [Cu(3)(SeO(3))(4)](2-) layers interconnected through Se-O-Cu and In-O-Cu bridges, exhibiting 8-MR helical tunnels along the a-axis. Results of magnetic property measurements indicate that there are considerable antiferromagnetic interactions between copper(II) centers in Ga(2)CuO(SeO(3))(3) (2) and M(2)Cu(3)(SeO(3))(6) (M = Ga 3, In 4). Interestingly, Ga(2)Cu(3)(SeO(3))(6) (3) behaves as a weak ferromagnet below the critical temperature of T(c) = 15 K. Further magnetic studies indicate that the compound is a canted antiferromagnet with a large canting angle of about 7.1 degrees.


Stereochemistry modulates the stability of reduced interstrand cross-links arising from R- and S-alpha-CH3-gamma-OH-1,N2-propano-2'-deoxyguanosine in the 5'-CpG-3' DNA sequence.
The solution structures of 5'-Cp-N2-dG-3'-R-(alpha)-CH3-propyl-5'-Cp-N2-dG-3' and 5'-Cp-N2-dG-3'-S-(alpha)-CH3-propyl-5'-Cp-N2-dG-3' interstrand DNA cross-links in the 5'-CpG-3' sequence were determined by NMR spectroscopy. These were utilized as chemically stable surrogates for the corresponding carbinolamine interstrand cross-links arising from the crotonaldehyde- and acetaldehyde-derived R- and S-alpha-CH3-gamma-OH-1,N2-propanodeoxyguanosine adducts. The results provide an explanation for the observation that interstrand cross-link formation in the 5'-CpG-3' sequence by the R- and S-alpha-CH3-gamma-OH-1,N2-propanodeoxyguanosine adducts is dependent upon stereochemistry, favoring the R-alpha-CH3-gamma-OH-1,N2-propanodeoxyguanosine adduct [Kozekov, I. D., Nechev, L. V., Moseley, M. S., Harris, C. M., Rizzo, C. J., Stone, M. P., and Harris, T. M. (2003) J. Am. Chem. Soc. 125, 50-61]. Molecular dynamics calculations, restrained by NOE-based distances and empirical restraints, revealed that both the 5'-Cp-N2-dG-3'-R-(alpha)-CH3-propyl-5'-Cp-N2-dG-3' and 5'-Cp-N2-dG-3'-S-(alpha)-CH3-propyl-5'-Cp-N2-dG-3' cross-links were located in the minor groove and retained Watson-Crick hydrogen bonds at the tandem cross-linked C.G base pairs. However, for the 5'-Cp-N2-dG-3'-R-(alpha)-CH3-propyl-5'-Cp-N2-dG-3' cross-link, the (alpha)-CH3 group was positioned in the center of the minor groove, whereas for the 5'-Cp-N2-dG-3'-S-(alpha)-CH3-propyl-5'-Cp-N2-dG-3' cross-link, the (alpha)-CH3 group was positioned in the 3' direction, showing steric interference with the DNA helix. The 5'-Cp-N2-dG-3'-S-(alpha)-CH3-propyl-5'-Cp-N2-dG-3' cross-link exhibited a lower thermal stability as evidenced by NMR spectroscopy as a function of temperature. The two cross-links also exhibited apparent differences in the conformation of the interstrand three-carbon cross-link, which may also contribute to the lower apparent thermodynamic stability of the 5'-Cp-N2-dG-3'-S-(alpha)-CH3-propyl-5'-Cp-N2-dG-3' cross-link.


Uveitis in mouse and man.
Uveitis is underappreciated as a sight-threatening cause of blindness. There are two broad causative classes of uveitis: infectious and non-infectious. Non-infectious uveitis is considered a prototypical autoimmune disorder based mainly on data from experimental models in the mouse. Several different experimental models exist that reflect the different types of uveitis in man (anterior, intermediate, and posterior uveitis). These models have demonstrated that uveitis is predominantly a Th1/Th17 mediated disease, although innate immune cells play a significant role both in induction of disease and in tissue damage. Most experimental models of uveitis rely on activation of the innate immune system by use of adjuvants that activate a range of pathogen recognition receptors (PRRs). This begs the question of the underlying role of initial and/or persistent infection, including latent infection, in immune-mediated uveitis in which active infection cannot be demonstrated. This further raises the possibility of pathogenic mechanisms such as antigenic cross-reactivity and molecular mimicry. Alternatively, residual/latent antigen from infectious agents may act as "endogenous" adjuvants for induction of immune reactions to damaged/altered self antigen, suggesting a commonality in pathogenesis for both infectious and non-infectious uveitis in man.


Synthesis of metallasiloxanes of group 13-15 and their application in catalysis.
Herein we report on the synthesis, characterization and catalytic application of metallasiloxanes of group 13-15. Reactions of R(Me)Si(OH)2 (R = N(SiMe3)-2,6-iPr2C6H3) (A) with Bi(NEt2)3, Sb(NEt2)3, Ge[N(SiMe3)2]2 and AlMe3 afforded [R(Me)SiO2BiNEt2]2 (1), [R(Me)SiO2SbOSi(OH)(Me)R]2 (2), [R(Me)SiO2]3(GeH)2 (3), and [R(Me)SiO2AlMe(THF)]2 (4), respectively. Reactions of RSi(OH)3 (B) with Bi(NEt2)3 and AlMe3 produced complexes (RSiO3Bi)4 (5) and (RSiO3)2[AlMe(THF)]3 (6). Compounds 1-6 have been characterized by IR and NMR spectroscopy, single crystal X-ray structure and elemental analysis. Each of the compounds 1, 2 and 4 features an eight-membered ring of composition Si2O4Bi2, Si2O4Sb2 and Si2O4Al2, while 3 and 6 exhibit a bicyclic structure with the respective skeletons of Si3O6Ge2 and Si2O6Al3. Compound 5 has a cubic core of Si4O12Bi4. Compounds 1-6 exhibit very good catalytic activity in the addition reaction of trimethylsilyl cyanide (TMSCN) with benzaldehyde. Compound 5 was found to be the best catalyst and its activity was probed in the reactions of TMSCN with a number of aldehydes and ketones.


More fertile florets and grains per spike can be achieved at higher temperature in wheat lines with high spike biomass and sugar content at booting.
An understanding of processes regulating wheat floret and grain number at higher temperatures is required to better exploit genetic variation. In this study we tested the hypothesis that at higher temperatures, a reduction in floret fertility is associated with a decrease in soluble sugars and this response is exacerbated in genotypes low in water soluble carbohydrates (WSC). Four recombinant inbred lines contrasting for stem WSC were grown at 20/10°C and 11h photoperiod until terminal spikelet, and then continued in a factorial combination of 20/10°C or 28/14°C with 11h or 16h photoperiod until anthesis. Across environments, High WSC lines had more grains per spike associated with more florets per spike. The number of fertile florets was associated with spike biomass at booting and, by extension, with glucose amount, both higher in High WSC lines. At booting, High WSC lines had higher fixed 13C and higher levels of expression of genes involved in photosynthesis and sucrose transport and lower in sucrose degradation compared with Low WSC lines. At higher temperature, the intrinsic rate of floret development rate before booting was slower in High WSC lines. Grain set declined with the intrinsic rate of floret development before booting, with an advantage for High WSC lines at 28/14°C and 16h. Genotypic and environmental action on floret fertility and grain set was summarised in a model.


Introduction of enterostatin (VPDPR) and a related sequence into soybean proglycinin A1aB1b subunit by site-directed mutagenesis.
Enterostatin (VPDPR), having anoretic and hypocholesterolemic activities, and its homologue LPYPR, a hypocholesterolemic peptide found in the glycinin A5A4B3 subunit, were introduced into the corresponding site (TNGPQ) of the proglycinin A1aB1b subunit by site-directed mutagenesis. Modified proglycinins were expressed in E. coli and recovered from the insoluble fraction. VPDPR and LPYPR were released by the action of chymotrypsin and trypsin as expected. The overall yields of purified VPDPR and LPYPR were 40% and 62%, respectively.


Proliferatory defect of invariant population and accumulation of non-invariant CD1d-restricted natural killer T cells in the joints of RA patients.
While numerical and functional defects of invariant NKT cells have been demonstrated in rheumatoid arthritis (RA), the detailed characterization of proliferative and secretory responses following CD1d-mediated presentation is lacking; the presence of non-invariant populations has never been assessed in human autoimmunity. We have evaluated both invariant and non-invariant populations in the blood and synovial fluid from patients to assess feasibility of NKT cell-directed manipulations in RA. NKT cell populations were quantified by anti-CD4/anti-Vα24 staining and/or CD1d tetramers. Proliferation was measured in cultures of mononuclear cells following stimulations with αGalCer and cytokine secretion determined by multi-bead assay. We have confirmed a proliferative defect of iNKT cells in both peripheral blood and synovial fluid from RA patients, but no changes in baseline frequencies. Moreover, we have detected an enlargement of non-invariant cell pool in synovial fluid samples. In addition, we noted an evident Th2 shift following exposure to αGalCer and pronounced IL-6 secretion. While RA patients suffer from defective proliferative responses of invariant NKT cells, non-invariant cells accumulate at the site of inflammation. While stimulation with αGalCer results in reduced TNF-α and increased suppressive IL-10, abundantly produced IL-6 could potentially contribute to the induction of Th17 cells in the joints.


Polytomous Rasch analysis as a tool for revision of the severity of disability code of the ICIDH.
To develop a preliminary proposal for the revision of the severity code of the ICIDH-D 1980. Quantitative analysis (polytomous Rasch analysis) of linked existing data sources including items about walking and dressing disability. The Rasch analysis provided estimates of threshold parameters for walking and dressing item categories. Factor analysis showed that more than one dimension was present, but that the first factor could definitely be interpreted as 'disability'. The reliability of the solutions was satisfactory (0.88 for walking and 0.91 for dressing). Based on the results, tentatively a new severity code is proposed with more distinct categories of 'difficulty' than the existing code, and the use of technical aids and personal assistance in the higher ranks. The Rasch method could be a useful tool for calibrating and measuring disability, as well as for converting existing disability data into a new uniform severity of disability code.


[Double action potentials in the command neurons of Helix pomatia in response to the action of cobalt ions].
Cobalt chloride (20 mmol/l) in physiological solution results in generation of doublets of spikes in Helix pomatia command neurons in response to intracellularly injected depolarizing current. The extraspikes arise in arborizations of neuron and are determined by influx sodium ions. It is supposed that facilitation of extraspikes in apparently due to long-lasting blockade of calcium-dependent potassium current by Co2+ ions.


Ultrasound Detection of Arteria Comitans: A Novel Technique to Locate the Sciatic Nerve.
In the gluteal and thigh region, the arteria comitans accompanies the sciatic nerve for a short distance, then penetrates the nerve and runs to the lower part of the thigh. There is no study that recognizes this artery as a guide to the location of the sciatic nerve. In this report, we describe a series of 6 knee arthroplasty patients in whom ultrasound-guided sciatic nerve block was successfully performed using color Doppler and pulsed wave Doppler to visualize the arteria comitans as a guide to the location of the sciatic nerve. We have found that detecting the arteria comitans as a landmark is novel and may offer an additional tool with the existing methods for sciatic nerve block.


HIV-1 RNA dimerization: It takes two to tango.
Each viral particle of HIV-1, the infectious agent of AIDS, contains two copies of the full-length viral genomic RNA. Encapsidating two copies of genomic RNA is one of the characteristics of the retrovirus family. The two RNA molecules are both positive-sense and often identical; furthermore, each RNA encodes the full complement of genetic information required for viral replication. The two strands of RNA are intricately entwined within the core of the mature infectious virus as a ribonuclear complex with the viral proteins, including nucleocapsid. Multiple steps in the biogenesis of the genomic full-length RNA are involved in achieving this location and dimeric state. The viral sequences and proteins involved in the process of RNA dimerization, both for the initial interstrand contact and subsequent steps that result in the condensed, stable conformation of the genomic RNA, are outlined in this review. In addition, the impact of the dimeric state of HIV-1 viral RNA is discussed with respect to its importance in efficient viral replication and, consequently, the potential development of antiviral strategies designed to disrupt the formation of dimeric RNA.


The structure-function relationship of activated protein C. Lessons from natural and engineered mutations.
Protein C is the central enzyme of the natural anticoagulant pathway and its activated form APC (activated protein C) is able to proteolyse non-active as well as active coagulation factors V and VIII. Proteolysis renders these cofactors inactive, resulting in an attenuation of thrombin formation and overall down-regulation of coagulation. Presences of the APC cofactor, protein S, thrombomodulin, endothelial protein C receptor and a phospholipid surface are important for the expression of anticoagulant APC activity. Notably, APC also has direct cytoprotective effects on cells: APC is able to protect the endothelial barrier function and expresses anti-inflammatory and anti-apoptotic activities. Exact molecular mechanisms have thus far not been completely described but it has been shown that both the protease activated receptor 1 and EPCR are essential for the cytoprotective activity of APC. Recently it was shown that also other receptors like sphingosine 1 phosphate receptor 1, Cd11b/CD18 and tyrosine kinase with immunoglobulin-like and EGF-like domains 2 are likewise important for APC signalling. Mutagenesis studies are being performed to map the various APC functions and interactions onto its 3D structure and to dissect anticoagulant and cytoprotective properties. The results of these studies have provided a wealth of structure-function information. With this review we describe the state-of-the-art of the intricate structure-function relationships of APC, a protein that harbours several important functions for the maintenance of both humoral and tissue homeostasis.


Cultural and Religious Educational Needs of Overseas Nurses Working in the Kingdom of Saudi Arabia and the United Arab Emirates.
A competent transcultural health care service has been identified as essential for the delivery of safe health care in the United Arab Emirates (UAE) and the Kingdom of Saudi Arabia (KSA) and indeed internationally. Delivery of contextually informed educational programs to new employees forms an important component of achieving this requirement. Nurse educators have an essential role in identifying the cultural and religious knowledge needed by new employees and in designing programs to address these needs. The objective of this article was to explore the cultural and religious educational needs of overseas nurses working with Muslim patients in the KSA and the UAE as derived from the experience of nurses themselves. Written narratives from nurses employed to work primarily with Muslim nurses were analyzed using a qualitative descriptive methodology. In the UAE and the KSA context, and perhaps for nurses working with Muslim-Arabic patients worldwide, the culturally and religiously specific topics that need to be a component of preemployment education include the basic Islamic principles (5 daily prayers, Ramadan fasting, Zamzam water, and time management skills to accommodate religious practices within care); Kinship and Social Factors (family structure, gender-related issues, and social support system); and Basic Arabic language skills.


Molecular aspects of bacterial colonization.
Bacteria have developed a wide variety of molecular mechanisms that permit firm adherence to a biologic surface. This review summarizes basic principles involved in this process, as exemplified by adherence of the group A streptococcus to oral epithelium, staphylococci to indwelling prostheses, and Escherichia coli to uroepithelium and enterocytes.


Diagnostic accuracy of NMP 22 and urine cytology for detection of transitional cell carcinoma urinary bladder taking cystoscopy as gold standard.
To determine diagnostic accuracy of NMP 22 and urine cytology in the detection of transitional cell carcinoma (TCC) urinary bladder taking cystoscopy as a gold standard in patients having provisional diagnosis of bladder cancer (BC). This cross sectional validational study enrolled 380 patients fulfilling selection criteria and was conducted at Armed Forces Institute of Urology (AFIU) Rawalpindi, Pakistan form July 2018 to July 2019. The urine sample collected underwent NMP22 and cytological analysis followed by rigid cystoscopy. Reports of all three tests divided patients into positive or negative for malignancy as per defined criteria. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and diagnostic accuracy of NMP 22, urine cytology and their combination was determined. Receiver operating characteristic (ROC) curve analysis performed and area under the curve (AUC) compared among these tests. The average age of patients was 53.08 ± 12.41 years having male to female ratio 3.75:1(300 males and 80 females). NMP 22 had better sensitivity and comparable specificity to cytology (81.9 & 81.2% vs 54 & 93.9%). Combination of NMP 22 / cytology outperformed both in terms of sensitivity (91.63 vs 81.83 vs 53.96), NPV (87.59 vs 77.46 vs 61.02) and diagnostic accuracy (85.26 vs 81.58 vs 71.32) but at the cost of specificity (76.97 vs 81.21 vs 93.94) and PPV (83.83 vs 85.02 vs 92.06). ROC curve revealed statistically significant higher AUC (0.843 vs .815 vs .73) for combination as compared to NMP 22 and Cytology (p < 0.001). NMP22 is a quick, point of care test having higher sensitivity, NPV and accuracy but similar specificity and PPV to urine cytology for detection of TCC urinary bladder. Combination outperformed both in terms of sensitivity while having modest specificity.


eDRAM: Effective early disease risk assessment with matrix factorization on a large-scale medical database: A case study on rheumatoid arthritis.
Recently, a number of analytical approaches for probing medical databases have been developed to assist in disease risk assessment and to determine the association of a clinical condition with others, so that better and intelligent healthcare can be provided. The early assessment of disease risk is an emerging topic in medical informatics. If diseases are detected at an early stage, prognosis can be improved and medical resources can be used more efficiently. For example, if rheumatoid arthritis (RA) is detected at an early stage, appropriate medications can be used to prevent bone deterioration. In early disease risk assessment, finding important risk factors from large-scale medical databases and performing individual disease risk assessment have been challenging tasks. A number of recent studies have considered risk factor analysis approaches, such as association rule mining, sequential rule mining, regression, and expert advice. In this study, to improve disease risk assessment, machine learning and matrix factorization techniques were integrated to discover important and implicit risk factors. A novel framework is proposed that can effectively assess early disease risks, and RA is used as a case study. This framework comprises three main stages: data preprocessing, risk factor optimization, and early disease risk assessment. This is the first study integrating matrix factorization and machine learning for disease risk assessment that is applied to a nation-wide and longitudinal medical diagnostic database. In the experimental evaluations, a cohort established from a large-scale medical database was used that included 1007 RA-diagnosed patients and 921,192 control patients examined over a nine-year follow-up period (2000-2008). The evaluation results demonstrate that the proposed approach is more efficient and stable for disease risk assessment than state-of-the-art methods.


CD38 molecule: structural and biochemical analysis on human T lymphocytes, thymocytes, and plasma cells.
The structure of the CD38 molecule has been evaluated by one- and two-dimensional gel analysis and by enzymatic digestions. The source of the Ag was mainly membrane preparations obtained from MLC cells, from normal thymocytes, and from the plasmocytoma line LP-1. Membranes were solubilized in NP-40 and the extracts fractionated by immunoaffinity chromatography [using a specific anti-CD38 antibody (A10 mAb) covalently linked to Sepharose protein A]. The purified Ag migrated as a single chain of Mr = 45,000 not associated with beta 2-microglobulin. Two-dimensional IEF gel electrophoresis revealed five spots (isoelectric point (pI) range: 6.5 to 6.9). After neuraminidase treatment, the mobility of the five polypeptides shifted to a more basic pI. Endoglycosidase-H treatment reduced the Mr of CD38 by 20%, revealing a broader band centered at Mr = 36,000. Treatment of CD38 molecule with V8 Staphylococcus aureus protease yielded a single dominant band at Mr = 38,000 which was still reactive with A10 mAb. The CD38 molecular was trypsin-resistant in both denatured or native conditions. These results clearly show the glycoprotein nature of CD38 molecule, which includes 2 to 4 N-linked oligosaccharide chains containing sialic acid residues. Furthermore, the present data indicate that the CD38 molecule does not display an apparent biochemical polymorphism among the different CD38+ cells or lines.


Trinuclear-based copper(I) pyrazolate polymers: effect of trimer π-acid···halide/pseudohalide interactions on the supramolecular structure and phosphorescence.
Under different situations, solvothermal reactions of 3,5-diethyl-4-(4-pyridyl)-pyrazole (HL) with CuX or CuX(2) (X = Cl, Br, I, and SCN) afforded five copper(I) coordination polymers, {CuX[CuL](3)·solvent}(n) (X = Cl, 1; Br, 2; I, 3; X = SCN and solvent = MeCN, 4) and {Cu(2)I(2)[CuL](3)}(n) (5). X-ray diffraction analyses show that all the complexes have trinuclear [CuL](3) (referred as Cu(3)) secondary building units featuring planar nine-membered Cu(3)N(6) metallocycles with three peripheral pyridyl groups as connectors, which are further linked by CuX or Cu(2)X(2) motifs to generate single- or double-strand chains. Interestingly, the Cu(I) atoms within the Cu(3) units in 1-5 behave as coordinatively unsaturated π-acid centers to contact soft halide/pseudohalide X atoms of CuX and Cu(2)X(2) motifs, which lead to novel sandwich substructures of [(Cu(3))(Cu(2)X(2))(Cu(3))] (X = Br, I, and SCN) in 2-4. In addition, both the π-acid [Cu(3)]···X contacts and intertrimer Cu···Cu interactions contribute to the one-dimensional (1D) double-strand and 2D/3D supramolecular structures of 1-5. All of these complexes exhibit high thermostability and bright solid-state phosphorescence upon exposure to UV radiation at room temperature. The emissions arise from the mixtures of metal-centered charge transfer, metal to ligand charge transfer, and halide-to-ligand charge transfer excited states, and can be tuned by intermolecular π-acid [Cu(3)]···halide/pseudohalide contacts.


Development of the Commercial Manufacturing Process for Ipatasertib.
Ipatasertib is a potent small molecule Akt kinase inhibitor currently being tested in Phase III clinical trials for the treatment of metastatic castration-resistant prostate cancer and triple negative metastatic breast cancer. In this paper an overview of the development achievements towards the commercial manufacturing process is given. The convergent synthesis consists of ten steps with eight isolated intermediates and utilizes a wide range of chemical techniques and technologies to build-up this complex drug. All three stereocenters are introduced using enzyme or metal catalysis.


Comparison of direct analysis in real-time mass spectrometry, atmospheric solids analysis probe-mass spectrometry, and ion mobility spectrometry for ensuring food safety by rapid screening of poppy seeds.
The opium poppy (Papaver somniferum) is a global commercial crop that has been historically valued for both medicinal and culinary purposes. Naturally occurring opium alkaloids including morphine, codeine, thebaine, noscapine, and papaverine are found primarily in the latex produced by the plant. If the plant is allowed to fully mature, poppy seeds that do not contain the opium alkaloids will form within the pods and may be used in the food industry. It is possible for the seeds to become contaminated with alkaloids by the latex during harvesting, posing a potential health risk for consumers. In the USA, there have been more than 600 reported adverse events including 19 fatalities that may be linked to the consumption of a contaminated poppy-containing product such as home-brewed poppy seed tea. Unwashed poppy seeds and pods may be purchased over the Internet and shipped worldwide. The Forensic Chemistry Center, US Food and Drug Administration (FDA) has evaluated several mass spectrometers (MS) capable of rapid screening to be used for high-throughput analysis of samples such as poppy seeds. These include a direct analysis in real-time (DART) ambient ionization source coupled to a single-quadrupole MS, an atmospheric solids analysis probe (ASAP) ionization source coupled to the same MS, and ion mobility spectrometers (IMS). These instruments have been used to analyze 17 poppy seed samples for the presence of alkaloids, and the results were compared to data obtained using liquid chromatography with mass spectral detection (LC-MS/MS). Results from the 17 poppy seed samples indicate that the DART-MS, ASAP-MS, and IMS devices detect many of the same alkaloids confirmed during the LC-MS/MS analyses, although both the false-positive and false-negative rates are higher, possibly due to the non-homogeneity of the samples and the lack of chromatographic separation.


Economics and financing of vaccines for diarrheal diseases.
The considerable burden of infectious disease-caused diarrhea around the world has motivated the continuing development of a number of vaccine candidates over the past several decades with some reaching the market. As with all major public health interventions, understanding the economics and financing of vaccines against diarrheal diseases is essential to their development and implementation. This review focuses on each of the major infectious pathogens that commonly cause diarrhea, the current understanding of their economic burden, the status of vaccine development, and existing economic evaluations of the vaccines. While the literature on the economics and financing of vaccines against diarrhea diseases is growing, there is considerable room for more inquiry. Substantial gaps exist for many pathogens, circumstances, and effects. Economics and financing studies are integral to vaccine development and implementation.


High-affinity L-arabinose transport operon. Nucleotide sequence and analysis of gene products.
The nucleotide sequence of the "high-affinity" L-arabinose transport operon has been determined 3' from the regulatory region and found to contain three open reading frames designated araF, araG and araH. The first gene 3' to the regulatory region, araF, encodes the 23-residue signal peptide and the 306-residue mature form of the L-arabinose binding protein (33,200 Mr). The binding protein, which has been described elsewhere, is hydrophilic, soluble and found in the periplasm of Escherichia coli. This gene is followed by an intragenic space of 72 nucleotides, which contains a region of dyad symmetry 23 nucleotides long capable of forming an 11-member stem-loop. The second gene, designated araG, contains an open reading frame capable of encoding an equally hydrophilic protein containing 504 residues (55,000 Mr). Following a 14-nucleotide spacer, which does not appear to have any secondary structure, the third open reading frame, herein designated araH, is capable of encoding a hydrophobic protein containing 329 residues (34,000 Mr) that can only be envisioned as having an integral membrane location. 3' to araH there is a T-rich region containing a 24-nucleotide area of dyad symmetry centered 55 nucleotides from the termination codon. Analysis of the derived primary sequences of the araG and araH products indicates the nature and potential features of these components. The araG protein was found to possess internal homology between its amino and carboxyl-terminal halves, suggesting a common origin. The araG gene product has been shown to be homologous to the rbsA gene product, the hisP product, the ptsB product and the malK product, all of which presumably play similar roles in their respective transport systems. Putative ATP binding sites are observed within the regions of homology. The araH gene product has been shown to be homologous to the rbsC gene product, which is the first observed homology between two purported membrane proteins.


Microhydration of substituted diamondoid radical cations of biological relevance: infrared spectra of amantadine+-(H2O)n = 1-3 clusters.
Hydration of biomolecules and pharmaceutical compounds has a strong impact on their structure, reactivity, and function. Herein, we explore the microhydration structure around the radical cation of the widespread pharmaceutical drug amantadine (C16H15NH2, Ama) by infrared photodissociation (IRPD) spectroscopy of mass-selected Ama+Wn = 1-3 clusters (W = H2O) recorded in the NH, CH, and OH stretch range of the cation ground electronic state. Analysis of the size-dependent frequency shifts by dispersion-corrected density functional theory calculations (B3LYP-D3/cc-pVTZ) provides detailed information about the acidity of the protons of the NH2 group of Ama+ and the structure and strength of the NHO and OHO hydrogen bonds (H-bonds) of the hydration network. The preferred sequential cluster growth begins with hydration of the two acidic NH protons of the NH2 group (n = 1-2) and continues with an extension of the H-bonded hydration network by forming an OHO H-bond of the third W to one ligand in the first hydration subshell (n = 3), like in the W2 dimer. For n = 2, a minor population corresponds to Ama+W2 structures with a W2 unit attached to Ama+via a NHW2 H-bond. Although the N-H proton donor bonds are progressively destabilized by gradual microhydration, no proton transfer to the Wn solvent cluster is observed in the investigated size range (n ≤ 3). Besides the microhydration structure, we also obtain a first impression of the structure and IR spectrum of bare Ama+, as well as the effects of both ionization and hydration on the structure of the adamantyl cage. Comparison of Ama+ with aliphatic and aromatic primary amine radical cations reveals differences in the acidity of the NH2 group and the resulting interaction with W caused by substitution of the cycloalkyl cage.


[Animal experiment testing of polyurethane soft foam (SYSpur) as an episcleral filling material].
Soft polyurethane foam was sutured to the sclerae of 28 rabbit eyes in a manner similar to scleral buckling in retinal detachment surgery. During the follow-up period no tissue incompatibility was observed and wound healing appeared to be without complications. Microscopic examination revealed fibrocytes growing through the sponge and after 24 weeks the polyurethane meshwork was completely filled with granulation tissue.


Adult Hepatic Progenitor Cell Niche: How it affects the Progenitor Cell Fate.
The hepatic progenitor cell (HPC) niche is a special microenvironment composed of different cell types, extracellular matrix (ECM) components, growth factors and cytokines released by the niche cells that help to maintain the characteristics of HPCs and the balance between their activation, proliferation and differentiation. Composition of this special microenvironment, created in response to specific liver damage, together with critical interactions between different partners of the HPC niche can determine the fate decision and differentiation pathways of HPCs. A number of recent studies have shed light on factors and signals from the HPC niche that determines the choice of HPCs differentiation towards a specific cell type depending on the nature of the liver injury and resultant microenvironment created by this injury. This paper seeks to provide an in-depth review, through a literature review and the authors' experiences, of the most recent findings on the role of the HPC niche in fate choice option of HPCs toward either hepatocytes or bile duct epithelial cells and its clinical relevance.


Case Report: HAVCR2 mutation-associated Hemophagocytic lymphohistiocytosis.
Germline HAVCR2 mutation has been reported to be associated with subcutaneous panniculitis-like T-cell lymphoma (SPTCL) leading to Hemophagocytic lymphohistiocytosis (HLH). Several studies have indicated that HAVCR2 mutation can cause HLH even in the absence of lymphoma, though the exact mechanism remains unclear. In this article, we reported five cases of HAVCR2 mutation-associated HLH. Our analysis revealed an elevated level of IL-1RA in the serum of these patients. Furthermore, we investigated the potential mechanisms underlying HLH associated with HAVCR2 mutation based on changes in cytokine levels. Our findings suggest that HAVCR2 mutation may represent a distinct genetic defect underlying HLH, differing from traditional primary HLH.


[Sensitivity to doxycycline (vibramycin) of the microflora isolated from the patients in a therapeutic clinic].
Sensitivity of microflora to tetracycline, oxytetracycline, chlortetracycline and doxycicline was studied. A total of 237 pure cultures of Strep. viridans (54), beta-hemolytic streptococci (27), pathogenic staphylococci (52), non-pathogenic staphylococci (53) and Coli bacteria (51) were tested with the agar-diffusion method using standard discs. Doxycicline was most active and chortetracycline was least active. The maximum sensitivity to doxycicline was found in beta-hemolytic streptococci (85.4%) and the minimum sensitivity to that antibiotic was found in Coli bacteria (39.2%) and Strep. viridans (35.6%), which was superior to that with respect to the other tetracyclines. Coincidence of the clinical effect with the microflora sensitivity and high percentage of sensitivity to doxycicline among Staph. aureus, which is important in treatment of severe infections caused by the organism were observed.


Testicular vasomotion in different mammals.
Vasomotion is a rhythmical variation in arterial blood flow present in many different organs among them the rat testis. Vasomotion is suggested to play an important role for the transvascular fluid exchange and the exchange of nutrients over the capillary wall as well as the formation of interstitial fluid. The present study was undertaken to elucidate whether vasomotion is present in the testes of different species independent of their anatomical vascular topography. Blood flow in the testes of mouse, brush-tailed possum, tammar wallaby, ram and human was investigated by using a laser Doppler flowmeter. Vasomotion was found in all the species investigated.


Endorectal coil MR imaging findings in hemospermia.
The purpose of this study was to illustrate the spectrum of abnormalities found at endorectal coil magnetic resonance (MR) imaging in patients with hemospermia. Ninety patients aged between 23 and 71 years (mean age 41 years) presenting with hemospermia underwent evaluation with endorectal coil MR imaging at 1.5 T. Duration of hemospermia ranged between 5 days and 4 years (mean 15 months). MR examination protocol included T1-weighted spin-echo (SE) and T2-weighted fast SE MR images obtained in the sagittal, coronal, and axial planes. Abnormalities were observed on endorectal-coil MR images in 49 of 90 patients (54%). Blood within the seminal vesicle or the ejaculatory duct was recognized in 23 of 90 patients (25%). Dilatation of the seminal vesicles or the ejaculatory duct was observed in 31 of 90 patients (34%). Cystic lesions were identified in 14 cases, eight of which involved the utriculus and six the ejaculatory duct. Calculi within the seminal vesicles were depicted in seven patients. No malignant disease was demonstrated. In conclusion, despite the evidence that hemospermia is most often a benign and self-limiting condition, we found that endorectal coil MR imaging can detect abnormal findings in more than half of the patients, and may be helpful in assessing the level at which hemorrhage occurred and in defining the cause of the disease.


SALSA: A Regulator of the Early Steps of Complement Activation on Mucosal Surfaces.
Complement is present mainly in blood. However, following mechanical damage or inflammation, serous exudates enter the mucosal surfaces. Here, the complement proteins interact with other endogenous molecules to keep microbes from entering the parenteral tissues. One of the mucosal proteins known to interact with the early complement components of both the classical and the lectin pathway is the salivary scavenger and agglutinin (SALSA). SALSA is also known as deleted in malignant brain tumors 1 and gp340. It is found both attached to the epithelium and secreted into the surrounding fluids of most mucosal surfaces. SALSA has been shown to bind directly to C1q, mannose-binding lectin, and the ficolins. Through these interactions SALSA regulates activation of the complement system. In addition, SALSA interacts with surfactant proteins A and D, secretory IgA, and lactoferrin. Ulcerative colitis and Crohn's disease are examples of diseases, where complement activation in mucosal tissues may occur. This review describes the latest advances in our understanding of how the early complement components interact with the SALSA molecule. Furthermore, we discuss how these interactions may affect disease propagation on mucosal surfaces in immunological and inflammatory diseases.


External qigong for chronic pain.
External qigong as a pharmacotherapy adjunct was investigated in 50 subjects with chronic pain (pain lasting > 3 months with pain score of > or = 3 on 0-10 numeric analog scale) who presented to a qigong healing center. Participants were randomized to receive either external qigong treatment (EQT) or equivalent attention time (EAT) in weekly 30-min sessions for four consecutive weeks. Outcomes were assessed before and after sessions. The primary outcome measure was intensity of pain by a 10-cm visual analog scale used to rate all pain severity measurements. At 8-week follow-up, participants were contacted by telephone and mailed a questionnaire. Most had experienced pain for > 5 years (66%); the rest, for > 3 to 5 years (8%), 1 to 3 years (10%), or < 1 year but > 3 months (10%). The most frequent concomitant diagnoses were multifactorial (26%), osteoarthritis (18%), and low back pain (12%). Most patients were also receiving other treatments (74%); none previously had EQT. Participants were randomly assigned to EQT (n = 26) or EAT (n = 24). These groups had no significant differences at baseline except for prior awareness of qigong (EQT 31% vs. EAT 63%; p = 0.025). Compared to the EAT group, EQT participants had a significant decrease in pain intensity in the 2nd (p = 0.003), 3rd (p < 0.001), and 4th weeks of treatment (p = 0.003). At week 8, these differences in overall decreased pain intensity persisted but were not statistically significant.


Sonification of Golf Putting Gesture Reduces Swing Movement Variability in Novices.
Purpose: To study whether novices can use sonification to enhance golf putting performance and swing movements. Method: Forty participants first performed a series of 2 m and 4 m putts, where swing velocities associated with successful trials were used to calculate their mean velocity profile (MVP). Participants were then divided into four groups with different auditory conditions: static pink noise unrelated to movement, auditory guidance based on personalized MVP, and two sonification strategies that mapped the real-time error between observed and MVP swings to modulate either the stereo display or roughness of the auditory guidance signal. Participants then performed a series of 2 m and 4 m putts with the auditory condition designated to their group. Results: In general our results showed significant correlations between swing movement variability and putting performance for all sonification groups. More specifically, in comparison to the group exposed to static pink noise, participants who were presented auditory guidance significantly reduced the deviation from their average swing movement. In addition, participants exposed to error-based sonification with stereo display modulation significantly lowered their variability in timing swing movements. These results provide further evidence of the benefits of sonification for novices performing complex motor skill tasks. Conclusions: More importantly, our findings suggest participants were able to better use online error-based sonification rather than auditory guidance to reduce variability in the execution and timing of their movements.


Risk factors of delayed extubation, prolonged length of stay in the intensive care unit, and mortality in patients undergoing coronary artery bypass graft with fast-track cardiac anesthesia: a new cardiac risk score.
Risk factors of delayed extubation, prolonged intensive care unit (ICU) length of stay (LOS), and mortality have not been studied for patients administered fast-track cardiac anesthesia (FTCA). The authors' goals were to determine risk factors of outcomes and cardiac risk scores (CRS) for CABG patients undergoing FTCA. Consecutive CABG patients undergoing FTCA were prospectively studied. Outcome variables were delayed extubation > 10 h, prolonged ICU LOS > 48 h, and mortality. Univariate analyses were performed followed by multiple logistic regression to derive risk factors of the three outcomes. Simplified integer-based CRS were derived from logistic models. Bootstrap validation was performed to assess and compare the predictive abilities of CRS and logistic models for the three outcomes. The authors studied 885 patients. Twenty-five percent had delayed extubation, 17% had prolonged ICU LOS, and 2.6% died. Risk factors of delayed extubation were increased age, female gender, postoperative use of intraaortic balloon pump, inotropes, bleeding, and atrial arrhythmia. Risk factors of prolonged ICU LOS were those of delayed extubation plus preoperative myocardial infarction and postoperative renal insufficiency. Risk factors of mortality were female gender, emergency surgery, and poor left ventricular function. CRSs were modeled for the three outcomes. The area under the receiver operating characteristic curve for the CRS-logistic models was not significantly different: 0.707/0.702 for delayed extubation, 0.851/0.855 for prolonged ICU LOS, and 0.657/0.699 for mortality. In CABG patients undergoing FTCA, the authors derived and validated risk factors of delayed extubation, prolonged ICU LOS, and mortality. Furthermore, they developed a simplified CRS system with similar predictive abilities as the logistic models.


[Treatment of giant vulvar condylomata acuminata combining CO2 laser and electrosurgery].
Since no antiviral treatment exists for human papilloma viruses (HPV), the clinician's role is to treat all detectable lesions in order to help the patient's immune system fight the virus and to prevent transmission by contact with lesions. HPV-associated lesions have been treated by a wide range of modalities, which may be divided into chemical, surgical and immunity-stimulating methods. We treated patients with large vulva lesions with Electrosurgery in combination with laser CO2 vaporization. HPV-associated lesions have been treated by a wide range of modalities, which may be divided into chemical, surgical and immunity-stimulating methods.


A Phase II Study of Allogeneic GM-CSF-Transfected Pancreatic Tumor Vaccine (GVAX) with Ipilimumab as Maintenance Treatment for Metastatic Pancreatic Cancer.
This phase II study tested granulocyte-macrophage colony-stimulating factor (GM-CSF)-allogeneic pancreatic tumor cells (GVAX) and ipilimumab in metastatic pancreatic ductal adenocarcinoma (PDA) in the maintenance setting. Patients with PDA who were treated with front-line chemotherapy consisting of 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) in the metastatic setting and had ongoing response or stable disease after 8-12 doses were eligible. Patients were randomized 1:1 to treatment with GVAX and ipilimumab given every 3 weeks for four doses then every 8 weeks (Arm A) or to FOLFIRINOX continuation (Arm B). The primary objective was to compare overall survival (OS) between the two arms. Eighty-two patients were included in the final analysis (Arm A: 40; Arm B: 42). The study was stopped for futility after interim analysis. Median OS was 9.38 months [95% confidence interval (CI), 5.0-12.2] for Arm A and 14.7 months (95% CI, 11.6-20.0) for Arm B (HR, 1.75; P = 0.019). Using immune-related response criteria, two partial responses (5.7%) were observed in Arm A and four (13.8%) in Arm B. GVAX + ipilimumab promoted T-cell differentiation into effector memory phenotypes both in the periphery and in the tumor microenvironment and increased M1 macrophages in the tumor. GVAX and ipilimumab maintenance therapy did not improve OS over continuation of chemotherapy and resulted in a numerically inferior survival in metastatic PDA. However, clinical responses and biological effects on immune cells were observed. Further study of novel combinations in the maintenance treatment of metastatic PDA is feasible.


Two-sided residual refocusing for an acoustic lens-based photoacoustic imaging system.
In photoacoustic (PA) cameras, an acoustic lens-based system can form a focused image of an object plane. A real-time C-scan PA image can be formed by simply time gating the transducer response. While most of the focusing action is performed by the lens, residual refocusing is needed to image multiple depths with high resolution simultaneously. However, a refocusing algorithm for a PA camera has not been studied so far in the literature. In this work, we reformulate this residual refocusing problem for a PA camera into a two-sided wave propagation from a planar sensor array. One part of the problem deals with forward wave propagation while the other deals with time reversal. We have chosen a fast Fourier transform (FFT) based wave propagation model for the refocusing to maintain the real-time nature of the system. We have conducted point spread function (PSF) measurement experiments at multiple depths and refocused the signal using the proposed method. The full width at half maximum (FWHM), peak value and signal to noise ratio (SNR) of the refocused PSF is analyzed to quantify the effect of refocusing. We believe that using a two-dimensional transducer array combined with the proposed refocusing can lead to real-time volumetric imaging using a PA camera.


Efficacy of an experimental dentifrice formulation on primary school children in Ga-Rankuwa, Pretoria.
The purpose of this study was to assess the efficacy of a dentifrice containing 1 per cent chlorhexidine gluconate at reducing plaque formation and gingival inflammation over a 12 week period. The effects of the test toothpaste were compared with control and conventional dentifrices in a randomised double-blind clinical trial of parallel design. Following baseline examination at which gingival and plaque indices (GI and PI) were measured, 156 primary school children were assigned to one of three groups that were matched for age, gender, GI and PI. After plaque control instruction the pupils were requested to use the dentifrice twice daily. After 6 and 12 week intervals the PI and GI were reassessed. There was no significant difference in GI between groups. The PI was significantly lower (p < 0.002) after use of the chlorhexidine containing dentifrice compared with the other two products.


Multicenter analysis of CIREN occupant lumbar bone mineral density and correlation with age and fracture incidence.
This study aimed to quantify lumbar volumetric bone mineral density (vBMD) for 873 seriously injured Crash Injury Research and Engineering Network (CIREN) motor vehicle crash occupants (372 male, 501 female) from 8 centers using phantomless computed tomography scans and to associate vBMD with age, fracture incidence, and osteopenia/osteoporosis diagnoses. The novelty of this work is that it associates vBMD with region of injury by applying an established method for vBMD measurement using phantomless computed tomography (CT). A validated phantomless CT calibration method that uses patient-specific fat and muscle measurements to calibrate vBMD measured from the L1-L5 trabeculae was applied on 873 occupants from various CIREN centers. CT-measured lumbar vBMD < 145 mg/cc is indicative of osteopenia using a published threshold. CIREN occupant lumbar vBMD in milligrams per cubic centimeter was regressed against age, osteopenia/osteoporosis comorbidities, height, weight, body mass index (BMI), and the incidence of fracture in vertebral (cervical, thoracic, lumbar) and rib/sternum regions. Among the 873 occupants analyzed, 11% (92 occupants) were diagnosed as osteopenic in CIREN. Of these 92 occupants, 42% (39 occupants) had normal vBMD measures (≥145 mg/cc), suggesting possible misclassification in CIREN. Of the 134 occupants classified as osteopenic in vBMD analysis, 60% were not classified as osteopenic in CIREN, suggesting undiagnosed osteopenia, and 40% were correctly classified in CIREN. Age was negatively correlated with vBMD (P <.0001) and occupants with <145 mg/cc vBMD sustained a median number of 2 rib/sternum fractures compared to a median value of 0 rib/sternum fractures for the ≥145 mg/cc vBMD group (P <.0001). Vertebral fracture analysis revealed that the thoracolumbar region was the most common region of injury in the spine. Though the incidence of fracture was not significantly different in the thoracic (10% versus 6%, P =.122) and lumbar (16% versus 13%, P =.227) regions between the 2 bone quality groups, the proportion of thoracolumbar fractures was significantly higher in occupants with <145 mg/cc vBMD versus occupants with ≥145 mg/cc vBMD (24% versus 17%, P =.043). Low lumbar vertebral bone quality is associated with an increased number of rib/sternum fractures and a greater incidence of thoracolumbar vertebral body fractures within the CIREN population analyzed.


Bimetal composites for photocatalytic reduction of CO2 to CO in the near-infrared region by the SPR effect.
A major challenge in the field of photocatalytic carbon dioxide (CO2) reduction is to design catalyst systems featuring high selectivity for CO production, long-term stability and a composition of Earth-abundant elements. Here, we present a metal-organic framework (MOF) based catalyst to mitigate the technical problems associated with the above-mentioned features. We report a carbon-coated CuNi alloy nanocatalyst obtained by high temperature vacuum treatment of a MOF material (CuNiBTC). The resulting carbon encapsulated CuNi (denoted as CuNi/C) nanoparticles possess a well-designed core-shell composite structure with graphene shells. Meanwhile, we investigated the reaction mechanism of CO2 on the surface of the CuNi/C photocatalyst in an aqueous solution containing triethanolamine. The experimental results show that the activity and catalytic yield of CuNi/C are much higher than those of Cu/C and Ni/C alone. At the same time, the catalytic activity of CuNi/C is also affected by changing the reaction temperature in the preparation process. As a result, the CuNi/C samples can achieve nearly 90% selectivity for NIR-light-driven CO2 reduction to CO. Our approach demonstrates the potential of non-semiconductor materials as catalysts for efficient and selective reduction of CO2 to CO.


Knowledge and awareness regarding menstruation and HIV/AIDS among schoolgoing adolescent girls.
Menstruation in our country is associated with various myths and restrictions leading to lack of awareness among adolescent girls. Insufficient menstrual hygiene practices are the cause of stress associated with menstruation and reproductive tract infections. Sexually transmitted infections and HIV/AIDS are not openly discussed in our society making adolescents vulnerable to them. To assess the knowledge of school going adolescent girls regarding menstrual hygiene and HIV/AIDS. Girls studying in class 8th-12th standard and who have attained menarche were included in the study. A predesigned questionnaire, which consisted of questions related to menstrual awareness and knowledge about HIV/AIDS was used for data collection. Data was analysed using SPSS software and results were interpreted into percentages. 282 girls took part in the study. Mean age of girls was 14.70 ± 1.5 years. Median age of girls was 15 years. Knowledge regarding menstrual hygiene and HIV/AIDS was found to be only satisfactory leaving a scope of improvement. Mother was the main source of information regarding both menstruation and HIV/AIDS. A comprehensive health education programme involving mothers is required to remove various misconceptions and taboos associated with menstruation and make it a pleasant experience for adolescent girls. Information, education and awareness programmes need to be strengthened to spread awareness regarding HIV/AIDS.