An Evaluation of Kiosks for Direct-to-Consumer Telemedicine Using the National Quality Forum Assessment Framework.
Background: Evaluation of direct-to-consumer (DTC) telemedicine programs has focused on care delivery via personal electronic devices. Telemedicine kiosks for the delivery of virtual urgent care services have not been systematically described. Introduction: Our institution has placed kiosks for DTC urgent care in pharmacies. These kiosks can be used without a personal electronic device. Materials and Methods: Retrospective review of adult patients using pharmacy-based kiosks (kiosk) or personal electronic devices (app) for DTC evaluation. Data for patient characteristics, wait time, technical quality, visit duration diagnosis codes, follow-up recommendations, and whether the patient was traveling were compared. Results were interpreted using the National Quality Forum framework for telemedicine service evaluation, focused on access, experience, and effectiveness. Comparisons were made using chi-square test, Student's t-test, and Wilcoxon rank-sum tests. Results: Over 1 year there were 1,996 DTC visits; 238 (12%) initiated from kiosks. Kiosk patients were slightly older (mean age 38 ± 13 vs. 35 ± 11; p < 0.001), more likely to be male (52% vs. 39%; p < 0.001), more likely to be remote from home (25% vs. 3%; p < 0.001), and had less technical difficulty (10% vs. 19%; p = 0.003). Referral for urgent in-person evaluation was low in both groups (10% kiosk vs. 16%; app p = 0.017). Discussion: Kiosks may increase access to care and improve technical experience. Low urgent referral rates suggest effective care for both types of visit. Conclusions: Despite their potential advantages, kiosk visits accounted for a minority of overall visits for our DTC telemedicine service line, and daily use of each kiosk location was low.


Meningiomas induced by high dose cranial irradiation.
The authors present four patients with a history of high dose cranial irradiation, who were diagnosed years later to have symptomatic meningiomas requiring surgical management. Relevant literature pertaining to these rare tumours is reviewed and their unusual characteristics highlighted. Their aetio-pathogenesis and management strategies are discussed.


Resemblance in appearance and the equal environments assumption in twin studies of personality traits.
The equal environments hypothesis of twin methodology was examined for the variable of similarity of appearance as it affects the personality ratings of young twins. There were two separate samples, the first with 95 pairs of same-sex twins and the second with 111 pairs. The average age of the twins in both samples was 3-1/2 years. Mothers rated their twins on four personality traits and on confusability of appearance. Not surprisingly, identical twins were markedly more similar in appearance than fraternal twins. The effect of this inequality on the personality ratings of the two types of twins was examined by correlating ratings of similarity of appearance with the absolute difference on the four personality traits for each pair of twins. None of the correlations was significant for the identical twins, suggesting that greater resemblance in appearance in identical twins does not make them more similar in personality. Indeed, the data suggested a contrast effect in which identical twins who were easily mistaken in appearance tended to be rated as less similar in personality. Thus, although similarity of appearance may create unequal environments for the two types of twins, it does not appear to bias twin studies in the direction of inflated heritabilities, at least for rating studies of the personality of young twins.


Raising gestational choline intake alters gene expression in DMBA-evoked mammary tumors and prolongs survival.
Choline is an essential nutrient that serves as a donor of metabolic methyl groups used during gestation to establish the epigenetic DNA methylation patterns that modulate tissue-specific gene expression. Because the mammary gland begins its development prenatally, we hypothesized that choline availability in utero may affect the gland's susceptibility to cancer. During gestational days 11-17, pregnant rats were fed a control, choline-supplemented, or choline-deficient diet (8, 36, and 0 mmol/kg of choline, respectively). On postnatal day 65, the female offspring received 25 mg/kg of a carcinogen 7,12-dimethylbenz[alpha]anthracene. Approximately 70% of the rats developed mammary adenocarcinomas; prenatal diet did not affect tumor latency, incidence, size, and multiplicity. Tumor growth rate was inversely related to choline content in the prenatal diet, resulting in 50% longer survival until euthanasia, determined by tumor size, of the prenatally choline-supplemented rats compared with the prenatally choline-deficient rats. This was accompanied by distinct expression patterns of approximately 70 genes in tumors derived from the three dietary groups. Tumors from the prenatally choline-supplemented rats overexpressed genes that confer favorable prognosis in human cancers (Klf6, Klf9, Nid2, Ntn4, Per1, and Txnip) and underexpressed those associated with aggressive disease (Bcar3, Cldn12, Csf1, Jag1, Lgals3, Lypd3, Nme1, Ptges2, Ptgs1, and Smarcb1). DNA methylation within the tumor suppressor gene, stratifin (Sfn, 14-3-3sigma), was proportional to the prenatal choline supply and correlated inversely with the expression of its mRNA and protein in tumors, suggesting that an epigenetic mechanism may underlie the altered molecular phenotype and tumor growth. Our results suggest a role for adequate maternal choline nutrition during pregnancy in prevention/alleviation of breast cancer in daughters.


[Dental and mandibular studies on mummies. Contribution of a stomatologist].
This is the sequence to an investigation on a mummy, 1965. Two further mummies could be examined: the first, a woman about 34 years old, from the 1st to 3rd century, shows similar advanced destruction of the teeth as the mummy investigated in 1965, caused by sand in the hand milled bread flour. This caused an early loss of molars by exaggerated abrasion, exposure of the pulps and periodontal bone loss. There was no evidence of occlusal caries. The second mummy was a 18-year-old young woman, 800-700 b. C. From the inscriptions on the sarcophagus name, family and living circumstances could be found. The same damages were found here, there was only a gradual difference owing to age difference. An interesting special finding was the absence of lip closure and the postmortal damage to the front teeth which may have been caused by the ritual of mouth opening.


Novel multi-energy X-ray imaging methods: Experimental results of new image processing techniques to improve material separation in computed tomography and direct radiography.
We present novel multi-energy X-ray imaging methods for direct radiography and computed tomography. The goal is to determine the contribution of thickness, mass density and atomic composition to the measured X-ray absorption in the sample. Algorithms have been developed by our own to calculate new X-ray images using data from an unlimited amount of scans/images of different tube voltages by pixelwise fitting of the detected gray levels. The resulting images then show a contrast that is influenced either by the atomic number of the elements in the sample (photoelectric interactions) or by the mass density (Compton scattering). For better visualization, those images can be combined to a color image where different materials can easily be distinguished. In the case of computed tomography no established true multi-energy methodology that does not require an energy sensitive detector is known to the authors. The existing dual-energy methods often yield noisy results that need spatial averaging for clear interpretation. The goal of the method presented here is to qualitatively calculate atomic number and mass density images without loosing resolution while reducing the noise by the use of more than two X-ray energies. The resulting images are generated without the need of calibration stan-dards in an automatic and fast data processing routine. They provide additional information that might be of special interest in cases like archaeology where the destruction of a sample to determine its composition is no option, but a increase in measurement time is of little concern.


Restriction Spectrum Imaging Improves Risk Stratification in Patients with Glioblastoma.
ADC as a marker of tumor cellularity has been promising for evaluating the response to therapy in patients with glioblastoma but does not successfully stratify patients according to outcomes, especially in the upfront setting. Here we investigate whether restriction spectrum imaging, an advanced diffusion imaging model, performed after an operation but before radiation therapy, could improve risk stratification in patients with newly diagnosed glioblastoma relative to ADC. Pre-radiation therapy diffusion-weighted and structural imaging of 40 patients with glioblastoma were examined retrospectively. Restriction spectrum imaging and ADC-based hypercellularity volume fraction (restriction spectrum imaging-FLAIR volume fraction, restriction spectrum imaging-contrast-enhanced volume fraction, ADC-FLAIR volume fraction, ADC-contrast-enhanced volume fraction) and intensities (restriction spectrum imaging-FLAIR 90th percentile, restriction spectrum imaging-contrast-enhanced 90th percentile, ADC-FLAIR 10th percentile, ADC-contrast-enhanced 10th percentile) within the contrast-enhanced and FLAIR hyperintensity VOIs were calculated. The association of diffusion imaging metrics, contrast-enhanced volume, and FLAIR hyperintensity volume with progression-free survival and overall survival was evaluated by using Cox proportional hazards models. Among the diffusion metrics, restriction spectrum imaging-FLAIR volume fraction was the strongest prognostic metric of progression-free survival (P = .036) and overall survival (P = .007) in a multivariate Cox proportional hazards analysis, with higher values indicating earlier progression and shorter survival. Restriction spectrum imaging-FLAIR 90th percentile was also associated with overall survival (P = .043), with higher intensities, indicating shorter survival. None of the ADC metrics were associated with progression-free survival/overall survival. Contrast-enhanced volume exhibited a trend toward significance for overall survival (P = .063). Restriction spectrum imaging-derived cellularity in FLAIR hyperintensity regions may be a more robust prognostic marker than ADC and conventional imaging for early progression and poorer survival in patients with glioblastoma. However, future studies with larger samples are needed to explore its predictive ability.


Time-dependent effects of antidepressant drugs on the low dose of apomorphine-induced locomotor hypoactivity in rats.
In the present study the hypothesis of antidepressant-induced subsensitivity of presynaptic dopamine receptors was readdressed. We used the behavioral model of low dose of apomorphine-induced locomotor hypoactivity in rats. Indeed, repeated administration of imipramine and citalopram attenuated the effect of low dose of apomorphine. However, the most interesting finding of the present study was the observation that similar and even stronger attenuation of low dose of apomorphine-induced hypoactivity was obtained by the acute treatment with imipramine, citalopram and amitriptyline, followed by 14 drug free days. That means that the acute antidepressant drug treatment seems to be sufficient to trigger the changes at the level of dopamine D2 presynaptic receptors and/or signal transduction mechanisms as a function of time, regardless of whether the drug is again administered. On the other hand, such the effect of time was not observed in the experiments using D-amphetamine as a motor stimulant. Only the repeated administration of antidepressant drugs enhanced the locomotor hyperactivity induced by D-amphetamine. Acute treatment, neither 2 h nor 14 days after the last dose, changed the D-amphetamine-induced hyperactivity. Such a difference in the time-dependent effects of antidepressant drugs on the locomotor activity induced by either the low dose of apomorphine or D-amphetamine may possibly result from the different mechanisms involved in the regulation of the biosynthesis of dopamine presynaptic and postsynaptic receptors in the rat brain.


Design of small molecules targeting I-BAR proteins.
Missing in metastasis (MIM, also MTSS1) is a member of the inverse Bin-Amphiphysin-Rvs (I-BAR) family that senses and stabilizes negative membrane protrusions. Abnormal expression of MIM has been frequently associated with a subset of human cancers and may play different roles in different stages of tumor progression. Overexpression of MIM-I-BAR in 293A cells potentiated the cell growth and increased the toxic response to paclitaxel. To modulate the function of MIM within cells, we designed several short peptide derivatives to target I-BAR dimerization. One of these derivatives had a cyclic configuration with a potency to disrupt the dimerization of MIM or ABBA proteins in vitro, and to be readily internalized into cells. Exposure of cells expressing MIM-I-BAR to this compound abolished increased susceptibility to paclitaxel and partially inhibited the IBAR- mediated endocytosis. Our data suggests that this cyclic peptide can be used as a tool to study the function of intracellular MIM and as a lead to develop a therapy targeting human diseases involving abnormal MIM expressions.


QUANTITATIVE GENETICS OF SEXUAL SELECTION IN THE FIELD CRICKET, GRYLLUS INTEGER.
Major theories of sexual selection predict heritable variation in female preferences and male traits and a positive genetic correlation between preference and trait. Here we show that female Texas field crickets, Gryllus integer, have heritable genetic variation for the male calling song stimulus level that produces the greatest phonotactic response. Approximately 34% of the variation in female preferences was due to additive genetic effects. Female choosiness, that is, the strength of the female response to her most preferred stimulus relative to her average response to all stimuli, did not show significant genetic effects. The male calling song character was not related to male size or age but did show significant genetic effects. Approximately 39% of the variation in the number of pulses per trill was due to additive genetic variation. The genetic correlation estimated for the field population was 0.51 ± 0.17. The number of pulses per trill produced by males is under stabilizing sexual selection.


Nuclearia pattersoni sp. n. (Filosea), a new species of amphizoic amoeba isolated from gills of roach (Rutilus rutilus), and its rickettsial endosymbiont.
A new species of amphizoic amoeba, Nuclearia pattersoni sp. n., isolated from gills of Rutilus rutilus L. is described. It is characterised by elongate flattened trophozoites of irregular shape. The longer dimension of their bodies is 13.2 (11.0-15.7) microm. Filopodia radiating mostly from the poles are 2 to 2.5 times longer than the body. The diameter of less frequently observed spherical trophozoites is 8.2-10.8 microm; their filopodia radiate to all directions. Cyst-like stages have shorter pseudopodia that arise from one pole only. The surface of locomotive forms from agar plate cultures has a thin amorphous glycocalyx, while most cells are covered by two layers of extracellular matrix. Mitochondria have flattened cristae, dictyosomes are located in the perinuclear zone. A conspicuous ultrastructural feature of the morphologically similar N. simplex, perinuclear striated band, is not present. Light microscopic and ultrastructural data are completed with the sequence of SSU rRNA gene and phylogenetic analysis including sequences of related taxa. The bacterial endosymbiont found in N. pattersoni type strain RR2G2 is assigned to the genus Rickettsia.


Drug-associated blood cell dyscrasias.
Many therapeutic drugs have been associated with hematologic adverse drug events (ADEs) in animals. Some drugs, notably chemotherapeutic agents and oxidant compounds, cause dose-dependent bone marrow suppression, while others induce idiosyncratic ADEs. Major mechanisms associated with ADEs include immune- or oxidant-mediated destruction of blood cells and toxic bone marrow injury. General classes of drugs that can cause idiosyncratic ADEs include estrogenic compounds, NSAIDs, antibiotics, antifungals, antithyroid drugs, anticonvulsants, antiparasitics, and cardiac drugs. ADEs associated with chemotherapeutic agents, phenylbutazone, phenobarbital, propylthiouracil (in cats), methimazole (in cats), and azathioprine occur frequently enough to warrant performing periodic complete blood counts during the course of treatment.


Leukemia inhibitory factor functions in parallel with interleukin-6 to promote ovarian cancer growth.
Ovarian carcinoma-associated mesenchymal stem cells (CA-MSC) produce not only high levels of interleukin-6 (IL6) but also the related cytokine leukemia inhibitory factor (LIF). IL6-mediated activation of STAT3 is implicated as a critical therapeutic target for cancer therapy. Less is known about the role of LIF, which can similarly activate STAT3, in ovarian cancer. We therefore sought to evaluate the tumorigenic effects of CA-MSC paracrine LIF signaling and the redundancy of IL6 and LIF in activating ovarian cancer STAT3 mediated cancer growth. As expected, we found that both IL6 and LIF induce STAT3 phosphorylation in tumor cells. In addition, both IL6 and LIF increased the percentage of ALDH+ ovarian cancer stem-like cells (CSC). Supporting redundancy of function by the two cytokines, CA-MSC induced STAT3 phosphorylation and increased cancer cell "stemness". This effect was not inhibited by LIF or IL6 blocking antibodies alone, but was prevented by dual IL6/LIF blockade or JAK2 inhibition. Similarly, small hairpin RNA (shRNA)-mediated reduction of IL6 or LIF in CA-MSC partially decreased but could not completely abrograte the ability of CA-MSC to induce STAT3 phosphorylation and stemness. Importantly, the in vivo pro-tumorigenic effect of CA-MSC is abrogated by dual blockade with the JAK2 inhibitor ruxolitinib to a much greater extent than treatment with anti-IL6 or anti-LIF antibody alone. Ruxolitinib treatment also improves survival in the immunocompetent ovarian cancer mouse model system with ID8 tumor cells plus MSC. Ruxolitinib-treated tumors in both the immunocompromised and immunocompetent animal models demonstrate decreased phospho-STAT3, indicating on-target activity. In conclusion, CA-MSC activate ovarian cancer cell STAT3 signaling via IL6 and LIF and increase tumor cell stemness. This functional redundancy suggests that therapeutic targeting of a single cytokine may be less effective than strategies such as dual inhibitor therapy or targeting shared downstream factors of the JAK/STAT pathway.


Perinatal reactions of the rabbit lung to maternal endotoxemia.
The reactions of the fetal and newborn lung to in utero injury were investigated in rabbits using as a model maternal administration of Escherichia coli endotoxin, 2 to 4 mug per kg. of body weight, injected intravenously at the 29th gestational day. At 6 hours after endotoxin injection, the lung revealed diffuse alveolar damage-sparing type II cells which appeared resistant to injury but more mature than type II cells from control lungs. These changes were followed by a reparative phase which over a 2-day period resulted in increased interstitial cellularity, replacement of the damaged type I cells by proliferated type II cells, and marked intraalveolar accumulation of myelin figures. The above reactions were associated with an average increase of 100 per cent in the phospholipid content of the surfactant fraction isolated from lung washing. Postnatally, the lungs showed structural changes resembling those seen in hyaline membrane disease of the newborn. The findings suggest that the response of the alveolar epithelim to injury inudced late in gestation follows a pattern similar to that described previously in adult lung, and is assoicated with in utero increased release of surfactant. It is proposed that alveolar injury and repair, including reduction of the intracellular surfactant reservoir occurring prior to breathing, may interfere postnatally with formation and maintenance of a normal surfactant layer, thereby predisposing to respiratory distress.


Expression of a human surfactant protein C mutation associated with interstitial lung disease disrupts lung development in transgenic mice.
Surfactant Protein C (SP-C) is a secreted transmembrane protein that is exclusively expressed by alveolar type II epithelial cells of the lung. SP-C associates with surfactant lipids to reduce surface tension within the alveolus, maintaining lung volume at end expiration. Mutations in the gene encoding SP-C (SFTPC) have recently been linked to chronic lung disease in children and adults. The goal of this study was to determine whether a disease-linked mutation in SFTPC causes lung disease in transgenic mice. The SFTPC mutation, designated g.1728 G --> A, results in the deletion of exon4, generating a truncated form of SP-C (SP-C(Deltaexon4)). cDNA encoding SP-C(Deltaexon4) was constitutively expressed in type II epithelial cells of transgenic mice. Viable F0 transgene-positive mice were not generated after two separate rounds of pronuclear injections. Histological analysis of lung tissue harvested from embryonic day 17.5 F0 transgene-positive fetuses revealed that SP-C(Deltaexon4) caused a dose-dependent disruption in branching morphogenesis of the lung associated with epithelial cell cytotoxicity. Transient expression of SP-C(Deltaexon4) in isolated type II epithelial cells or HEK293 cells resulted in incomplete processing of the mutant proprotein, a dose-dependent increase in BiP transcription, trapping of the proprotein in the endoplasmic reticulum, and rapid degradation via a proteasome-dependent pathway. Taken together, these data suggest that the g.1728 G --> A mutation causes misfolding of the SP-C proprotein with subsequent induction of the unfolded protein response and endoplasmic reticulum-associated degradation pathways ultimately resulting in disrupted lung morphogenesis.


Breast Cancer Survivors' Attitudes toward eMental Health: A Cross-Sectional Study.
Breast cancer survivors' (BCS) attitudes toward eMental Health (eMH) are largely unknown, and adoption predictors and their interrelationships remain unclear. This study aimed to explore BCS' attitudes toward eMH and investigate associated variables. A cross-sectional study involving 336 Portuguese BCS was conducted. Attitudes toward eMH, depression and anxiety symptoms, health-related quality of life, and sociodemographic, clinical, and internet-related variables were assessed using validated questionnaires. Spearman-ranked correlations, χ2, and multiple regression analyses were computed to explore associations between attitudes and collected variables. BCS held a neutral stance toward eMH. In models adjusted for age and education, positive attitudes were statistically significantly associated with increased depressive symptoms and worse emotional, cognitive, and body image functioning. Social network use, online health information and mental healthcare seeking, higher self-reported knowledge of eMH, and previous use of remote healthcare were positively associated with better attitudes toward eMH. eMH programs targeting BCS seem to be a promising strategy for providing supportive psychosocial care to BCS. However, increasing awareness about eMH efficacy and security may be necessary to improve its acceptance and use among BCS. Additional research is necessary to understand how BCS' unmet care needs, and specifically their psychological distress severity, may impact BCS' acceptance and use of eMH.


Remarkable metal counterion effect on the internucleotide J-couplings and chemical shifts of the N-H...N hydrogen bonds in the W-C base pairs.
The effects of metal ion binding on the (2h) J(NN)-coupling and delta( (1)H)/Deltadelta( (15)N) chemical shifts of N-H...N H-bond units in internucleotide base pairs were explored by a combination of density functional theory calculations and molecular dynamics (MD) simulations. Results indicate that the NMR parameters vary considerably upon cation binding to the natural GC or AT base pairs, and thus can be used to identify the status of the base pairs, if cation-perturbed. The basic trend is that cation perturbation causes (2h) J(NN) to increase, Deltadelta( (15)N) to decrease, and delta( (1)H) to shift upfield for GC, and in the opposite directions for AT. The magnitudes of variation are closely related to the Lewis acidity of the metal ions. For both base pair series (M(z+)GC and M(z+)AT), these NMR parameters are linearly correlated among themselves. Their values depend strongly on the energy gaps (Delta(ELP-->sigma*)) and the second-order interaction energies ( E(2)) between the donor N lone pair (LP(N)) and the acceptor sigma* N-H localized NBO orbitals. In addition, the (2h) J NN changes are also sensitive to the amount of sigma charge transfer from LP(N) to sigma*(N-H) NBOs or from the purine to the pyrimidine moieties. The different trends are a consequence of the different H-bond patterns combined with the polarization effect of the metal ions in the cationized M(z+)AT series, M(z+) <-- A --> T, and the cationized GC series, M(z+) <-- G <-- C. The predicted cation-induced systematic trends of (2h) J(NN) and delta( (15)N, (1)H) in N-H...N H-bond units may provide a new approach to the determination of H-bond structure and strength in Watson-Crick base pairs, and provide an alternative probe of the heterogeneity of DNA sequences.


Implications of NQO1 in cancer therapy.
quinone oxidoreductase (NQO1), an obligatory two-electron reductase, is a ubiquitous cytosolic enzyme that catalyzes the reduction of quinone substrates. The NQO1- mediated two-electron reduction of quinones can be either chemoprotection/detoxification or a chemotherapeutic response, depending on the target quinones. When toxic quinones are reduced by NQO1, they are conjugated with glutathione or glucuronic acid and excreted from the cells. Based on this protective effect of NQO1, the use of dietary compounds to induce the expression of NQO1 has emerged as a promising strategy for cancer prevention. On the other hand, NQO1-mediated two-electron reduction converts certain quinone compounds (such as mitomycin C, E09, RH1 and -lapachone) to cytotoxic agents, leading to cell death. It has been known that NQO1 is expressed at high levels in numerous human cancers, including breast, colon, cervix, lung, and pancreas, as compared with normal tissues. This implies that tumors can be preferentially damaged relative to normal tissue by cytotoxic quinone drugs. Importantly, NQO1 has been shown to stabilize many proteins, including p53 and p33ING1b, by inhibiting their proteasomal degradation. This review will summarize the biological roles of NQO1 in cancer, with emphasis on recent findings and the potential of NQO1 as a therapeutic target for the cancer therapy.


Certified Reference Material for Use in 1H, 31P, and 19F Quantitative NMR, Ensuring Traceability to the International System of Units.
In recent years, quantitative NMR (qNMR) spectroscopy has become one of the most important tools for content determination of organic substances and quantitative evaluation of impurities. Using Certified Reference Materials (CRMs) as internal or external standards, the extensively used qNMR method can be applied for purity determination, including unbroken traceability to the International System of Units (SI). The implementation of qNMR toward new application fields, e.g., metabolomics, environmental analysis, and physiological pathway studies, brings along more complex molecules and systems, thus making use of 1H qNMR challenging. A smart workaround is possible by the use of other NMR active nuclei, namely 31P and 19F. This article presents the development of three classes of qNMR CRMs based on different NMR active nuclei (1H, 31P, and 19F), and the corresponding approaches to establish traceability to the SI through primary CRMs from the National Institute of Standards and Technology and the National Metrology Institute of Japan. These TraceCERT® qNMR CRMs are produced under ISO/IEC 17025 and ISO Guide 34 using high-performance qNMR.


Lipopolysaccharide deacylation by an endogenous lipase controls innate antibody responses to Gram-negative bacteria.
T cell-independent type 1 agonists such as Gram-negative bacterial lipopolysaccharides can stimulate B lymphocytes to proliferate and produce antibodies by signaling through Toll-like receptors. This phenomenon is well established in vitro, yet polyclonal B cell responses after bacterial infection in vivo are often weak and short-lived. We show here that B cell proliferation and polyclonal antibody production in response to Gram-negative bacterial infection are modulated by acyloxyacyl hydrolase, a host enzyme that deacylates bacterial lipopolysaccharides. Deacylation of lipopolysaccharide occurred over several days, allowing lipopolysaccharide to act as an innate immune stimulant yet limiting the eventual amount of B cell proliferation and polyclonal antibody production. Control of lipopolysaccharide activation by acyloxyacyl hydrolase indicates that mammals can regulate immune responses to bacterial infection by chemical modification of a Toll-like receptor agonist.


The Influence of Bariatric Surgery on Pregnancy and Perinatal Outcomes-A Case-Control Study.
Obesity in pregnant women increases the incidence of pregnancy-induced comorbidities and the rate of operative deliveries. As bariatric surgery is the reference method of treatment of obesity, we wanted to evaluate its influence on the course of pregnancy and perinatal outcomes. Data was collected from 627 female patients after bariatric surgery, of whom 107 had a history of pregnancy after the surgery, and 345 non-bariatric patients who had a delivery at a tertiary perinatal center. Sixty-one cases were matched (1:1) with controls for age, pre-pregnancy BMI and presence of pre-pregnancy comorbidities. The main endpoints were gestational diabetes mellitus (GDM), pregnancy-induced hypertension (PIH), small (SGA) and large for gestational age infants (LGA) and cesarean sections (CS). Patients after bariatric procedures were significantly less likely to have GDM (19.67%/37.7%; p = 0.0433), PIH (11.47%/16.39%; p = 0.6072) and preterm delivery (13.11%/37.7%; p = 0.0026). The CS rate was higher (57.38%/40.98%; p = 0.0987). There was an increased risk of SGA (18.03%/13.11%; p = 0.6072) and a decreased risk of LGA (6.56%/16.39%; p = 0.146). Patients after bariatric surgery have a decreased risk of pregnancy-induced comorbidities, preterm deliveries and LGA infants, with an increase in rate of CS and SGA infants compared to general population matched for pre-pregnancy BMI, age and presence of pre-pregnancy comorbidities.


Interaction between tumour necrosis factor alpha ribozyme and cellular proteins. Involvement in ribozyme stability and activity.
Ribozymes are RNA molecules that cleave other RNA molecules. Thus, ribozymes offer a new way of inhibiting expression of specific genes whose nucleotide sequences are known. Intracellular stability of ribozymes is an important factor for their efficacy. We previously showed that hammerhead ribozyme directed against mRNA of tumour necrosis factor alpha (TNF alpha) slowly acquires resistance to degradation in cultured human cells. In order to explain this resistance, we now report on endogenous cellular protein(s) that bind to TNF alpha-ribozyme (TNF alpha-Rz) in solution to form stable complexes during native gel electrophoresis. Suppression of the effects of ribonucleases in the cytoplasmic extracts allowed approximately 80% of the input ribozyme RNA to be recovered in the form of complexes, indicating that complex formation protected the ribozyme from degradation. Treatment of the ribozyme-protein complexes with proteinase K prior to electrophoresis led to the recovery of full-length ribozyme. Interestingly, ribozyme-protein complexes retained cleavage activity, suggesting that the binding is in reversible equilibrium. Analysis of protein cytoplasmic extracts for binding to sub-fragments of TNF alpha-Rz demonstrated that protein binds to a conformational epitope formed by an interaction between the 5' end of TNF alpha-Rz and its catalytic domain. Competition of the ribozyme-protein binding with a ribozyme construct containing DNA instead of RNA at the 5' end, indicated that the ribose phosphate backbone of the 5' end is required for strong binding. The protein responsible for the formation of the complex with low electrophoretic mobility was found to be specific for the TNF alpha-Rz, since ribozyme for HIV-1 integrase gene (Int-Rz), or for human interleukin-2 (IL2-Rz) did not compete significantly with the TNF alpha-Rz binding. Covalent linkage of the IL2-Rz to the 3' end of TNF alpha-Rz, or to the proposed RNA protein binding site conferred protein binding and enhanced the stability and activity of the chimeric molecules. The RNA epitope identified in this study, through its endogenous protein binding, may serve as an oligonucleotide cassette for enhancing the in vivo stability and activity of other RNA molecules in general. This RNA epitope will also be useful in the study of RNA-protein interactions.


[Immunologically defined tumor-associated antigens: the possibilities and limitations of their use in gastroenterology].
The array of tumor-associated antigens has been extended recently by introducing novel mucin-like antigens, i.e. CA19-9, CA50, DU-PAN-2, TAG72/CA72-4 to gastroenterological oncology. Particularly in pancreatic cancer preoperative staging, postoperative prognosis, and follow-up have been improved considerably by determinations of these new tumormarkers. Yet, despite their irrelevance to screening procedures they may contribute to the differential diagnosis between benign and neoplastic pancreatic diseases ruling out false positive results by serial determinations. In contrast in colorectal cancer CEA is still superior to the tumor markers mentioned. Whether all of these tumormarkers indeed represent a diagnostic progress especially for tumors with no marker available like gastric cancer still has to be determined.


UCP2 deficiency helps to restrict the pathogenesis of experimental cutaneous and visceral leishmaniosis in mice.
Uncoupling protein 2 (UCP2) is a mitochondrial transporter that has been shown to lower the production of reactive oxygen species (ROS). Intracellular pathogens such as Leishmania upregulate UCP2 and thereby suppress ROS production in infected host tissues, allowing the multiplication of parasites within murine phagocytes. This makes host UCP2 and ROS production potential targets in the development of antileishmanial therapies. Here we explore how UCP2 affects the outcome of cutaneous leishmaniosis (CL) and visceral leishmaniosis (VL) in wild-type (WT) C57BL/6 mice and in C57BL/6 mice lacking the UCP2 gene (UCP2KO). To investigate the effects of host UCP2 deficiency on Leishmania infection, we evaluated parasite loads and cytokine production in target organs. Parasite loads were significantly lower in infected UCP2KO mice than in infected WT mice. We also found that UCP2KO mice produced significantly more interferon-γ (IFN-γ), IL-17 and IL-13 than WT mice (P<0.05), suggesting that UCP2KO mice are resistant to Leishmania infection. In this way, UCP2KO mice were better able than their WT counterparts to overcome L. major and L. infantum infections. These findings suggest that upregulating host ROS levels, perhaps by inhibiting UPC2, may be an effective approach to preventing leishmaniosis.


Narratives of change and reform processes: global and local transactions in French psychiatric hospital reform after the Second World War.
As with the rest of biomedicine, psychiatry has, since the Second World War, developed under the strong influence of the transnational accumulation of a whole series of practices and knowledge. Anthropology has taught us to pay attention to the transactions between local-level actors and those operating at the global level in the construction of this new world of medicine. This article examines the role played by the recommendations of the WHO Expert Committee of Mental Health in the reform of the French mental health system during the 1950s. Rooted in the experience of practitioners and administrators participating in the process of reforming local psychiatric systems, the recommendations of the WHO Expert Committee developed a new vision of regulating psychiatry, based on professionalism and an idea of a normativity of the doctor-patient relation. This article shows how, by mobilizing the WHO reports' recommendations, French administrators and doctors succeeded in creating a typically French object: "the psychiatric sector", founded on elaborating a new mandate for the psychiatric profession. The article thus questions the deinstitutionalization model as an explanation of transformations of the structure of the French psychiatry system in the post-war period.


Colorimetric Detection of Mercury(II) Ion in Aqueous Solution Using Silver Nanoparticles.
Novel green-chemistry synthesis of silver nanoparticles (AgNPs) is introduced as a low-cost, rapid and easy-to-use analytical method for mercury ion detection. Aqueous fruit extract of water apple (Syzygium aqueum) was used for the first time as bioreductant to synthesize stable AgNPs. The prepared AgNPs have a yellowish-brown color with a surface plasmon resonance peak at 420 nm. The addition of Hg(II) ions then changes the AgNPs color to colorless. The color change was in proportion to the concentration of Hg(II) ions. The presence of other metal ions in the system was also evaluated. The proposed method shows good selectivity and sensitivity towards Hg(II) ions. Using UV-visible spectrophotometry, the detection limit of the developed method was 8.5 × 10-7 M. The proposed method has been successfully applied for determination of Hg(II) ions in tap and lake water samples with precision better than 5%.


Screening immediate family members for carrier identification and counseling: a cost-effective and practical approach.
To screen immediate family members of thalassaemia patients for carrier identification and counselling. The cross-sectional study was conducted at an urban thalassaemia treatment and prevention centre in Karachi, Pakistan, from January to December 2008, and involved 188 siblings of 100 thalassaemia patients. Complete blood count, including haemogram, was performed in the siblings. Samples with MCV < 75fl and MCH < 25% were subjected to haemoglobin-electrophoresis. Haemoglobin A2 of 3.5% to 7.0% was labelled as beta-thalassaemia minor. Those with haemoglobin A2 of 3.0-3.4% but red blood cell count of > 4.5 x 1012/L were reported as equivocal and were screened for iron deficiency anaemia and a repeat haemoglobin A2 estimation was done on high performance liquid chromatography. Equivocal results of the chromoatography were screened for thalassaemia mutation. Mean values along with standard deviation were worked out for relevant variables. Of the 188 subjects, there were 124 (66%) males and 64 (34%) females. The mean age was 16.5 +/- 6.3 years (range: 3 months to 30 years) and the mean family size was 1.88 +/- 3.8 (range: 1-12) children per family. There were 51 (51%) first-cousin marriages in this group. Of the siblings, 65 (34.5%) were identified as normal, while 117 (62.2%) were reported as beta-thalassaemia carriers. Six asymptomatic siblings were reported as consistent with beta-thalassaemia major. There were 62.2% siblings identified as beta thalassaemia carriers in the study as opposed to 5-8% carriers in the general population. We also identified six asymptomatic and unidentified cases of beta-thalassaemia intermedia in these families. Therefore, in our context where both resources and budgets are limited, it is practical to focus on siblings of identified thalasaemia patients.


Construction and validation of a prognostic model based on ten signature cell cycle-related genes for early-stage lung squamous cell carcinoma.
We performed a bioinformatics analysis to screen for cell cycle-related differentially expressed genes (DEGs) and constructed a model for the prognostic prediction of patients with early-stage lung squamous cell carcinoma (LSCC). From a gene expression omnibus (GEO) database, the GSE157011 dataset was randomly divided into an internal training group and an internal testing group at a 1:1 ratio, and the GSE30219, GSE37745, GSE42127, and GSE73403 datasets were merged as the external validation group. We performed single-sample gene set enrichment analysis (ssGSEA), univariate Cox analysis, and difference analysis, and identified 372 cell cycle-related genes. Additionally, we combined LASSO/Cox regression analysis to construct a prognostic model. Then, patients were divided into high-risk and low-risk groups according to risk scores. The internal testing group, discovery set, and external verification set were used to assess model reliability. We used a nomogram to predict patient prognoses based on clinical features and risk values. Clinical relevance analysis and the Human Protein Atlas (HPA) database were used to verify signature gene expression. Ten cell cycle-related DEGs (EIF2B1, FSD1L, FSTL3, ORC3, HMMR, SETD6, PRELP, PIGW, HSD17B6, and GNG7) were identified and a model based on the internal training group constructed. From this, patients in the low-risk group had a higher survival rate when compared with the high-risk group. Time-dependent receiver operating characteristic (tROC) and Cox regression analyses showed the model was efficient and accurate. Clinical relevance analysis and the HPA database showed that DEGs were significantly dysregulated in LSCC tissue. Our model predicted the prognosis of early-stage LSCC patients and demonstrated potential applications for clinical decision-making and individualized therapy.


Development of the Abbreviated Masculine Gender Role Stress Scale.
Data gathered from 6 independent samples (n = 1,729) that assessed men's masculine gender role stress in college and community males were aggregated used to determine the reliability and validity of an abbreviated version of the Masculine Gender Role Stress (MGRS) Scale. The 15 items with the highest item-to-total scale correlations were used to create an abbreviated MGRS Scale. Psychometric properties of each of the 15 items were examined with item response theory (IRT) analysis, using the discrimination and threshold parameters. IRT results showed that the abbreviated scale may hold promise at capturing the same amount of information as the full 40-item scale. Relative to the 40-item scale, the total score of the abbreviated MGRS Scale demonstrated comparable convergent validity using the measurement domains of masculine identity, hypermasculinity, trait anger, anger expression, and alcohol involvement. An abbreviated MGRS Scale may be recommended for use in clinical practice and research settings to reduce cost, time, and patient/participant burden. Additionally, IRT analyses identified items with higher discrimination and threshold parameters that may be used to screen for problematic gender role stress in men who may be seen in routine clinical or medical practice.


Complete remission of refractory gestational trophoblastic disease with brain metastases treated with multicycle ifosfamide, carboplatin, and etoposide (ICE) and stem cell rescue.
Patients with chemotherapy-refractory gestational trophoblastic disease and brain metastasis are considered to have a very poor prognosis. We present the case of a patient who had failed several chemotherapeutic regimens. Despite transient responses to chemotherapy, she had not achieved a complete remission in 3 years, and had developed systemic disease and recurrent brain metastasis. She was treated with four cycles of high-dose ifosfamide, carboplatin, and etoposide with blood progenitor cell support. She tolerated this regimen well and has obtained a complete remission that is ongoing for 12 months.


Pituitary apoplexy after anticoagulation for unstable angina.
To describe a patient with an undiagnosed pituitary macroadenoma, in whom pituitary apoplexy developed after heparin anticoagulation for treatment of unstable angina. We chronicle the clinical course, treatment, and outcome in a 53-year-old woman with pituitary apoplexy. Potential risk factors are also discussed. In a patient with coronary artery disease and unstable angina, heparin anticoagulation therapy was initiated. Shortly thereafter, severe frontal headaches, nausea and vomiting, high fever, diplopia, and visual field deficits developed. A workup for infectious causes and analysis of cerebrospinal fluid were negative. Contrast-enhanced computed tomography of the head revealed a pituitary macroadenoma with a central area of hemorrhage, and pituitary apoplexy was diagnosed. Hydrocortisone sodium succinate was administered intravenously, and ultimately, transsphenoidal resection was performed. Postoperatively, diabetes insipidus developed and persisted. Neurologically, she had near-total blindness of the right eye and temporal hemianopia of the left eye. Although pituitary apoplexy is rare, its occurrence can be associated with certain risk factors, including anticoagulation. Clinicians should be aware of this serious condition so that timely diagnosis and treatment can provide the best chance of recovery.


Temperature Determination by EPR at 275 GHz and the Detection of Temperature Jumps in Aqueous Samples.
Second-moment analysis along two dimensions of continuous-wave EPR spectra of nitroxides enables EPR thermometry in a broad temperature range. Simulations show that the temperature can be derived in both the slow-motion and the fast-motion regime, which is experimentally verified at 275 GHz for H2O/glycerol (50/50% by volume) and pure water. We demonstrate that this tool allows the calibration of temperature jumps induced by infrared laser irradiation of a submicroliter sample in the single-mode cavity of a 275 GHz spectrometer, which prepares for kinetic studies of processes involving paramagnetic species.


Role of parent support and peer support in adolescent substance use: a test of mediated effects.
This research tested comparative effects of parent and peer support on adolescent substance use (tobacco, alcohol, and marijuana) with data from 2 assessments of a multiethnic sample of 1,826 adolescents, mean age 12.3 years. Multiple regression analyses indicated that parental support was inversely related to substance use and that peer support was positively related to substance use, as a suppression effect. Structural modeling analyses indicated that effects of support were mediated through pathways involving good self-control, poor self-control, and risk-taking tendency; parent and peer support had different patterns of relations to these mediators. The mediators had pathways to substance use through positive and negative recent events and through peer affiliations. Effects for gender and ethnicity were also noted. Mechanisms of operation for parent and peer support are discussed.


[Processes connected with hatching of larvae from eggs of parasitic nematodes].
Influence of such factors as temperature, pH, CO2 level and oxidation- reduction potential value in the alimentary tract of host on the stimulation of invasive eggs was studied. Changes of these factors lead to change in permeability of inner layer of egg-shell. Then the hatching fluid is released and its enzymes digest the egg-shell. In the nematodes, which have the free-living larvae, the initiation process can depend on parasite or environmental agents.


Effects of long-term oral beta-carotene supplementation on lipid peroxidation in patients with cystic fibrosis.
The aim of this study was to determine the efficacy of oral beta-carotene supplementation for the correction of an oxidant-antioxidant imbalance in cystic fibrosis (CF). We studied 24-patients with cystic fibrosis and 14 healthy controls. 13 CF-patients were allocated to a CF-supplementation group, which received 1 mg beta-carotene/kg BW/d up to a body weight (BW) of 50 kg, patients with a BW greater 50 kg received 50 mg beta-carotene/d for 12 weeks. For the following 12 weeks all patients of the CF-supplementation group were treated with 10 mg beta-carotene/d. Placebos with starch were applied to 11 CF-patients. Baseline plasma beta-carotene concentrations of CF patients (mean +/- SD, 0.08 +/- 0.04 mumol/l) were significantly lower than those of age-matched controls (o.3 +/- 0.1 mumol/l) (p < 0.001). beta-carotene concentrations of the CF-supplementation group increased rapidly and reached a value of 0.6 mumol/l after 12 weeks of supplementation. Normal values were measured for plasma ascorbate and alpha-tocopherol. Plasma retinol concentrations were in the lower normal range and did not increase during supplementation. Total antioxidative capacity in plasma of the CF-supplementation group increased after 12 weeks of supplementation at an extent of 12%. Positive influence was indicated by a decrease of plasma malondialdehyde. Thus oral beta-carotene supplementation is effective in normalizing status of beta-carotene and malondialdehyde in CF patients.


[Q fever in acute exacerbation of chronic lower respiratory tract infection].
We studied the effect of Q fever in acute exacerbation of chronic lower respiratory tract infection. The subjects consisted of 80 cases with acute exacerbation of chronic lower respiratory tract infection treated during the period from March 2002 till October 2004. Q fever was diagnosed using a PanBio Coxiella burnetii ELISA test kit. Two cases (2.5%) were positive for IgM in the acute stage, and were diagnosed as having acute infection by C. burnetii. They were elderly women with bronchiectasis, aged 76 and 82. They had no history of keeping cats or dogs, but the onset of acute exacerbation of chronic lower respiratory tract infection was June and March which is the breeding seasons for cats and dogs. Acute exacerbation of chronic lower respiratory tract infection were considerd to be a mixed infection with Pseudomonas aeruginosa (the 76-year-case) and Haemophilus influenzae (the 82-year-case). It is concluded that C. burnetii can induce exacerbation of chronic lower respiratory tract infection, their cases were considerd to be mixed infection with C. burnetii and other bacteria.


Targeting the Hippo Pathway and Cancer through the TEAD Family of Transcription Factors.
The Hippo pathway is a critical transcriptional signaling pathway that regulates cell growth, proliferation and organ development. The transcriptional enhanced associate domain (TEAD) protein family consists of four paralogous transcription factors that function to modulate gene expression in response to the Hippo signaling pathway. Transcriptional activation of these proteins occurs upon binding to the co-activator YAP/TAZ whose entry into the nucleus is regulated by Lats1/2 kinase. In recent years, it has become apparent that the dysregulation and/or overexpression of Hippo pathway effectors is implicated in a wide range of cancers, including prostate, gastric and liver cancer. A large body of work has been dedicated to understanding the therapeutic potential of modulating the phosphorylation and localization of YAP/TAZ. However, YAP/TAZ are considered to be natively unfolded and may be intractable as drug targets. Therefore, TEAD proteins present themselves as an excellent therapeutic target for intervention of the Hippo pathway. This review summarizes the functional role of TEAD proteins in cancer and assesses the therapeutic potential of antagonizing TEAD function in vivo.


Amyloid fibril protein related to prealbumin in familial amyloidotic polyneuropathy.
Amyloid fibrils were concentrated from the kidney, thyroid, and peripheral nerve of six patients with familial amyloidotic polyneuropathy (FAP). The fibril concentrates were solubilized in 6 M guanidine.HCl and fractionated on Sephadex G-100 columns. The elution profile of all FAP amyloid fibril concentrates revealed a protein of apparent Mr of 14,000, designated the FAP protein, that was absent from normal human tissues treated by the same procedure and from fibrils of a primary amyloidosis liver. Antisera against whole denatured fibril concentrates prepared in rabbits reacted with the FAP protein and a component in normal human serum corresponding to prealbumin. It was further established that the FAP protein shared common antigenic determinants with human prealbumin by its reaction of identity with normal prealbumin using commercial antisera against human prealbumin. Amyloid AL or AA proteins could not be identified in FAP fibrils by sensitive immunochemical assay methods. These results suggest that the FAP protein is a unique and significant component of the FAP amyloid fibrils and that it is closely related to the 13,745 Mr prealbumin subunit.


Detoxification of lithocholic acid, a toxic bile acid: relevance to drug hepatotoxicity.
Lithocholic acid, a monohydroxy, secondary bile acid, is formed by bacterial 7-dehydroxylation of the primary bile acid chenodeoxycholic acid (CDCA) and of the secondary bile acid ursodeoxycholic acid (UDCA). Lithocholic acid and its precursor CDCA are toxic when fed to the rabbit, rhesus monkey, and baboon, but not when CDCA, as well as UDCA, is used for therapeutic purposes in man. Older studies showed that the species specific toxicity of lithocholic acid could be explained by efficient sulfation of lithocholic acid in man and in chimpanzee, but not in the rabbit, rhesus monkey, or baboon. Rodents detoxify lithocholic acid by hydroxylation, but this does not occur in species in which it is toxic. Recent studies suggest that lithocholic acid induces its own detoxification by activating nuclear receptors to promote transcription of genes encoding sulfotransferase. In addition, work with CaCo2 cells suggest that lithocholic acid may undergo sulfation in the enterocyte and be effluxed back into the intestinal lumen. The evolution of trihydroxy bile acids in vertebrates may have occurred to decrease the formation of lithocholic acid. Lithocholic acid is a rare example of a toxic endobiotic; a variety of mechanisms have evolved to solve the problem of efficient detoxification.


P046 Tofacitinib Induced Resolution of Severe Colitis and Reactive Atypia in an Adolescent Patient With IBD.
Tofacitinib is an anti-JAK/STAT small molecule approved for treatment of adults (but not children and adolescents) with moderate to severe ulcerative colitis. Data is limited in children and teens although two major centers have shown efficacy as both mono- and dual - combination therapy using tofacitinib in pediatric patients refractory to anti-TNF agents. We present a 16-year-old female diagnosed with inflammatory ileocolonic Crohn's disease without upper gastrointestinal involvement after presenting with several months of abdominal pain, diarrhea, and unintentional weight loss. Laboratory evaluation was notable for normal inflammatory markers, albumin and complete blood count and an elevated stool lactoferrin. Initial endoscopic evaluation revealed moderate to severe pancolitis and patchy ileitis; biopsies noted mild chronic active ileitis and moderate to severe chronic active pancolitis without dysplastic or atypical changes. She was started on infliximab for induction and maintenance therapy and dosage was increased due to suboptimal levels and marginal symptomatic improvement. However, despite increased dosing plus a course of budesonide (Uceris), she had minimal improvement in her symptoms and ongoing elevation of her lactoferrin. Given an equivocal result on a Clostridium difficile testing (GDH antigen positive only), she was started on oral vancomycin which resulted in mild improvement, but not resolution, of diarrhea and abdominal pain. This was continued after completion of a 14-day course (and subsequent negative testing) due to increased stool frequency with discontinuation of the medication and improvement with reinitiating it. She had severe pancolitis (Mayo 2 - 3) but normal TI on repeat colonoscopy 5 months after diagnosis. Biopsies (reviewed by a panel of adult GI pathologists) were notable for reactive atypia with features concerning for early dysplasia in the ascending and descending colon. Due to disease severity and rapid progression plus histologic changes concerning for possible dysplasia despite optimized therapy with infliximab and repeat negative C. difficile testing, she was started on tofacitinib 10 mg twice daily along with oral vancomycin. She had complete resolution of diarrhea, abdominal pain, and early satiety within a week; repeat fecal lactoferrin was negative (<30). She underwent repeat colonoscopy with chromoendoscopy 5 months after initiation of tofacitinib which revealed mild acute ileitis but no active colonic inflammation, atypia or dysplasia. This is the first report to our knowledge that an adolescent patient with colonic predominant Crohn's disease has complete resolution of atypia and possible early dysplasia with tofacitinib therapy.


Highly sensitive and selective analysis of widely targeted metabolomics using gas chromatography/triple-quadrupole mass spectrometry.
In metabolomics studies, gas chromatography coupled with time-of-flight or quadrupole mass spectrometry has frequently been used for the non-targeted analysis of hydrophilic metabolites. However, because the analytical platform employs the deconvolution method to extract single-metabolite information from co-eluted peaks and background noise, the extracted peak is artificial product depending on the mathematical parameters and is not completely compatible with the pure component obtained by analyzing a standard compound. Moreover, it has insufficient ability for quantitative metabolomics. Therefore, highly sensitive and selective methods capable of pure peak extraction without any complicated mathematical techniques are needed. For this purpose, we have developed a novel analytical method using gas chromatography coupled with triple-quadrupole mass spectrometry (GC-QqQ/MS). We developed a selected reaction monitoring (SRM) method to analyze the trimethylsilyl derivatives of 110 metabolites, using electron ionization. This methodology enables us to utilize two complementary techniques-non-targeted and widely targeted metabolomics in the same sample preparation protocol, which would facilitate the formulation or verification of novel hypotheses in biological sciences. The GC-QqQ/MS analysis can accurately identify a metabolite using multichannel SRM transitions and intensity ratios in the analysis of living organisms. In addition, our methodology offers a wide dynamic range, high sensitivity, and highly reproducible metabolite profiles, which will contribute to the biomarker discoveries and quality evaluations in biology, medicine, and food sciences.


SMC3 may play an important role in atopic asthma development.
As a common disease with a complex risk, including genetic and environmental factors, atopic asthma is prevalent but treatable. The aim of the study was to predict the underlying mechanism of asthma and identify target genes for the disease. The affymetrix chip data, GSE18965, were available from Gene Expression Omnibus and the differentially expressed genes (DEGs) between nine atopic asthmatic specimens and seven healthy nonatopic samples were identified by R. Then Gene Ontology and pathway enrichment analyses were performed to these DEGs. Further, search tool for the retrieval of interacting genes/proteins (STRING) was used to select protein-protein interaction (PPI) for DEGs, and then the network was visualized by Cytoscape. Finally, transcription factor binding site analysis was conducted to the hot gene. Total 565 DEGs were identified, including 535 upregulated and 30 downregulated genes. The upregulated genes, such as structural maintenance of chromosome (SMC)3, significantly affected cellular component of extracellular matrix (P = 1.56E-04). Otherwise, DEGs were remarkably enriched in three pathways, including transforming growth factor-beta signaling pathway (P = 0.005252649). Further, SMC3 was detected as hot gene in PPI network, and NET (Elk3) was predicted as the significant transcription factor for this gene. SMC3 may play an important role in atopic asthma development; therefore, it has the potential to be the target for the disease. Moreover, our findings provide more knowledge about the mechanism of atopic asthma and help the researchers to explore it in future.


[Ultrastructure of macrophages detected after implantation of the Alloplant allogenic biomaterial].
The ultrastructure of macrophages detected in rats after subcutaneous implantation of the dispersed allogenic Alloplant biomaterial was studied. It was found that with the Alloplant biomaterial implantation the conditions were created promoting the concentration and complete maturation of different macrophage subpopulations. Their functional activity and interaction with other cellular populations result in complete regeneration of the connective tissue. The data obtained confirm the concept of main regulatory role of macrophages in the intercellular interactions during tissue repair and support the hypothesis of bicomponent mechanism of collagen fiber formation in the place of the Alloplant biomaterial implantation.


Growth hormone response to clonidine in the nervous pointer dog model of anxiety.
Blunted growth hormone responses to clonidine have been reported in most studies of humans with panic disorder but have been an inconsistent finding in the study of other anxiety syndromes. The growth hormone response to oral clonidine (100 micrograms/kg) was investigated in the adult nervous pointer dog, a genetic animal model of anxiety. Compared with placebo, clonidine produced significant increases in plasma levels of growth hormone; however, there were no differences in the growth hormone (GH) responses to clonidine in the nervous compared with the normal pointer dogs. Findings in this animal model are discussed within the context of noradrenergic-hypothalamic-GH dysfunction reported in some but not all types of anxiety disorders in humans.


Amino acids induce high seed-specific expression driven by a soybean (Glycine max) glycinin seed storage protein promoter.
We characterize GFP expression driven by a soybean glycinin promoter in transgenic soybean. We demonstrate specific amino acid-mediated induction of this promoter in developing soybean seeds in vitro. In plants, gene expression is primarily regulated by promoter regions which are located upstream of gene coding sequences. Promoters allow transcription in certain tissues and respond to environmental stimuli as well as other inductive phenomena. In soybean, seed storage proteins (SSPs) accumulate during seed development and account for most of the monetary and nutritional value of this crop. To better study the regulatory functions of a SSP promoter, we developed a cotyledon culture system where media and media addenda were evaluated for their effects on cotyledon development and promoter activity. Stably transformed soybean events containing a glycinin SSP promoter regulating the green fluorescent protein (GFP) were generated. Promoter activity, as visualized by GFP expression, was only observed in developing in planta seeds and in vitro-cultured isolated embryos and cotyledons from developing seeds when specific media addenda were included. Asparagine, proline, and especially glutamine induced glycinin promoter activity in cultured cotyledons from developing seeds. Other amino acids did not induce the glycinin promoter. Here, we report, for the first time, induction of a reintroduced glycinin SSP promoter by specific amino acids in cotyledon tissues during seed development.


Outcome of Neoadjuvant Intra-Arterial Chemotherapy and Radical Hysterectomy for Treatment of Bulky Stage IB to Stage IIB Uterine Cervical Cancer: Can Postoperative Irradiation Be Avoided?
We evaluated whether our neoadjuvant intra-arterial chemotherapy (NAIC) effectively precludes the need for postoperative radiation therapy in patients treated by radical hysterectomy for IB2 to IIB cervical cancer. Study subjects were 52 patients with a bulky cervical tumor diagnosed and treated at Juntendo University Hospital or Juntendo Nerima Hospital. The NAIC combined cisplatin, epirubicin, mitomycin-C, and 5-fluorouracil; and radical hysterectomy was to be performed after 2 cycles. The main variables analyzed were clinical and histologic response to NAIC, NAIC-related adverse events, adjuvant chemotherapies, relapse-free and overall survival, recurrence, and prognostic factors. Patients were judged eligible for radical hysterectomy, and 51 underwent the surgery. The overall positive response (complete response [CR] + partial response [PR]) to NAIC was 88.5%. Median follow-up time was 84 months (5-136 months). Three-year relapse-free survival and overall survival were 80.5% and 77.8%, respectively. The recurrence rate was 19.2% (10/52 patients). Seven (13.5%) of the 52 patients died from the disease during follow-up. Lymph node status (positive vs negative) and the histologic effect of NAIC (grades 0-1 vs grades 2-3) were shown to be prognostic factors (P = 0.024 and P = 0.021, respectively). Our NAIC strategy seems to be well tolerated and beneficial for patients with bulky IB2 to IIB cervical cancer. With this strategy, radiation therapy remains an option in cases of recurrence. For cases in which lymph node metastasis is found or the histologic effect of NAIC is low, our adjuvant chemotherapy regimen may need adjustment to improve prognosis.


Myxidium biliare sp. n. (Myxozoa) from gall bladder of Galaxias maculatus (Osmeriformes: Galaxiidae) in Patagonia (Argentina).
Myxidium biliare sp. n., a new myxosporean species parasitizing the gall bladder of Galaxias maculatus (Jenyns), in Patagonia, is described. Its coelozoic plasmodia were floating free in the bile. Spores are fusiform 13.7 +/- 0.9 microm long and 6.9 +/- 0.6 microm wide, with rounded ends in frontal view and slightly pointed ends in sutural view; shell with ridges and sinuous sutural line. Both maximum prevalence and maximum percentage of immature plasmodia occurred in summer. In winter the prevalence and the percentage of immature plasmodia fell to their lowest values. Prevalence was independent of host sex but increased with host length. Prevalence in 15 Patagonian Andean lakes (situated from 39 degrees 25'S to 41 degrees 30'S) ranged between 4.2% and 70%.


Preliminary investigation of the advertising and availability of PREPs, the new "safe" tobacco products.
The tobacco industry recently introduced a new set of "safe" cigarettes and nicotine delivery devices that purportedly entail reduced tobacco-related disease risk due to their lower level of some carcinogens and toxins. Little is know about the biological impact of these potential reduced exposure products (PREPs) and nothing is known about their advertising and availability. Hence, two pilot studies were conducted to examine the latter issues for the first time. In Study 1, we examined tobacco ads in 10 popular magazines 1998--2002 and found that only 1% of ads were for PREPs. In Study 2, we attempted to purchase PREPs in a random sample of 113 small stores and found that only 4.4% sold any PREP. These preliminary findings tentatively suggest that the industry might not yet be heavily invested in products that have the potential to increase tobacco use by decreasing its perceived harm. Studies with larger samples are recommended.


Identification of lipophylic constituents of the nest of Frieseomelitta silvestrii (FRIESE, 1902).
Bees are becoming more and more valued for the extremely important role they play in ecological communities, especially for their pollinating action. The state of Roraima, Brazil has areas of native vegetation and variety of stingless bees, and this potential is still untapped. The objective of this study was to determine the chemical composition of materials collected from the nests of Frieseomelitta silvestrii (FRIESE, 1902), identified in São Luiz, in Roraima state, Brazil. The chemical composition of the collected material was determined by gas chromatography coupled to mass spectrometry (GC-MS). The dichloromethane extracts of propolis, cerumen threads and resin present in the stingless bee nest presented differentiated profiles with the occurrence of low polarity compounds.


Changes in serum prealbumin as a marker for nitrogen balance in surgical oncology patients.
Serum prealbumin has long been used as a marker of nutritional status. However, prealbumin is a negative acute phase reactant influenced by several non-nutritional-related factors including surgery, infection, and cancer. An increasing prealbumin has been correlated with a positive nitrogen balance in general surgery patients receiving parenteral nutrition (PN) with 88% specificity and 70% sensitivity. To date, no trial has evaluated the effect of concurrent cancer and surgery on the value of prealbumin in predicting nitrogen balance. This study is a concurrent retrospective design of post-operative patients (≥ 19 years of age) identified by the nutrition support service who received PN for ≥ 5 days, had a baseline and follow-up serum prealbumin and C-reactive Protein (CRP) measured, as well as a 24-h urinary urea nitrogen (UUN) performed between days 5-10 of PN. Exclusion criteria include anuric renal failure, Child-Pugh Class C liver failure, pregnancy, and corticosteroid use. Prealbumin was correlated to nitrogen balance, measuring sensitivity, specificity, and negative and positive predictive values. Information was collected regarding patient demographics and presence or absence of metastatic cancer. Thirty patients were identified and evaluated for this study from December 1st, 2010 to July 15th, 2011. Patients included in the study had a mean age of 57 years old (range 20-82), 53% male, with a mean weight of 84 kg (range 42-140) and body mass index (BMI) of 29 kg/m2 (range 14.9-56.8). The mean daily caloric dose of PN per actual body weight was 21 kcal/kg (range 10-34) and the mean daily protein dose was 1.4 g/kg (range 1-2). Forty seven percent of patients were obese (BMI > 30 kg/m2) and were prescribed high-protein hypocaloric PN. The most common indication for PN was post-operative ileus (23/30 patients). 24-h urine collection for UUN was performed on average of day 8 after PN initiation (range 5-10 days). Nitrogen balance as calculated from 24-h UUN was positive in 17/30 patients. A positive prealbumin change of greater than 2.8 mg/dL was found to have a statistically significant association with positive nitrogen balance (p = 0.02). At the cut off level of positive 2.8 mg/dL, the likelihood of a positive nitrogen balance had a sensitivity of 82% (95% confidence interval (CI) 64-100%); specificity of 62% (95% CI 35-88%); positive predictive value of 74% (95% CI 54-93%); negative predictive value of 73% (95% CI 46-99%). No absolute value for prealbumin level (e.g., > 20 mg/dL) was found to be a significant predictor of positive nitrogen balance. CRP levels at initiation of PN were significantly elevated with a mean level of 147 mg/dL. These results indicate a positive change in serum prealbumin (> 2.8 mg/dL) has sufficient sensitivity (82%) to predict positive changes in nitrogen balance in the surgical oncology population. However, the low specificity (62%) makes it less useful in predicting a negative nitrogen balance. Absolute prealbumin levels were greatly affected by inflammation, as evidenced by CRP levels, and single values were not useful in predicting positive nitrogen balance. Positive changes in serum prealbumin levels have previously been associated with a positive nitrogen balance (NB) in surgical patients receiving parenteral nutrition (PN); however, it is unclear if this is true in oncologic surgery patients. This study highlights how changing levels of serum prealbumin and C-reactive protein correlates to NB for cancer patients in the post-operative period requiring PN. Changes in prealbumin levels from baseline showed sufficient sensitivity, but not specificity to utilize routinely for predicting NB in this population.


Diverting the 5-exo-Trig Oxypalladation to Formally 6-endo-Trig Fluorocycloetherification Product through 1,2-O/Pd(IV) Dyotropic Rearrangement.
Pd-catalyzed cyclizative functionalization of γ-hydroxyalkenes affords tetrahydrofuran derivatives via a key 5-exo-trig oxypalladation step. Herein, we report a palladium(II)-catalyzed, Selectfluor-mediated formal 6-endo-trig fluorocycloetherification of γ-hydroxyalkenes for the synthesis of functionalized tetrahydropyrans. Mechanistically, an σ-alkyl-Pd(II) intermediate resulting from the 5-exo-trig oxypalladation process is isolated and characterized by X-ray crystallographic analysis. Its oxidation with Selectfluor to Pd(IV) triggers the chemoselective 1,2-O/Pd(IV) dyotropic rearrangement affording, after C-F bond-forming reductive elimination, the tetrahydropyrans with concurrent generation of a tertiary carbon-fluorine bond. The occurrence of this 1,2-positional interchange is further evidenced by trapping the rearranged quaternary C(sp3)-Pd bond by an internal nucleophile that is materialized by the development of a Pd(II)-catalyzed oxidative bis-heterocyclization of alkenes.


Circadian and circannual variations in plasma immunoreactive insulin (IRI) and C-peptide concentrations in elderly subjects.
Groups of 49-51 elderly men and women 77 +/- 8 years of age, institutionalized at the Berceni Clinical Hospital, Bucharest, Romania, were studied over a 24 hour span in spring, summer, fall and winter. All subjects followed a diurnal activity pattern with rest at night and ate three meals per day with breakfast at about 08:30, lunch at about 13:00, dinner at 18:30. The meals were similar, although not identical for all subjects during all seasons. On each day of sampling, blood was collected at four hourly intervals over a 24 hrs span. Immunoreactive insulin (IRI) and C-peptide were determined in plasma and glucose (during fall and winter only) in serum. Circadian variations of all three parameters were found and the rhythm parameters were determined statistically by cosinor analysis. The acrophases of the circadian rhythm of IRI and C-peptide were the same during all four seasons. The circadian acrophase of plasma IRI and C-peptide precedes that of serum glucose. The circadian mean concentrations of IRI and C-peptide show a circannual variation with higher values in winter and fall than in spring and summer for plasma insulin and with higher values for summer and fall than in spring for C-peptide. Sex differences in IRI and C-peptide concentrations with higher values in men are manifested during certain circadian and circannual stages but not during others.


The impact of housing environment color on zebrafish anxiety-like behavioral and physiological (cortisol) responses.
Color of the environment is an important factor modulating human and animal behavior and physiology. Animal models are a valuable tool to understand how colors affect social, cognitive and affective responses. The zebrafish (Danio rerio) is rapidly emerging as an important organism in neuroscience and physiology. Here, we examine whether the color of housing environment influences zebrafish anxiety-like behavior and whole-body cortisol levels. Overall, housing for 15 days in transparent and white holding tanks increases, and in black or blue tanks decreases, baseline anxiety-like behavior in adult zebrafish. Housing in blue tanks (vs. white) also reduced their whole-body cortisol levels. Taken together, our data suggest that color of the housing environment affects neurobehavioral and endocrine responses in zebrafish, with multiple implications for behavioral phenomics and animal welfare. Our study also reinforces zebrafish as a promising model organism to study neurobiology of compex brain-environment interactions.


Associations Between Family Risk Factors and Child Neglect Types in U.S. Army Communities.
Recent theory and empirical research suggest that child neglect is a heterogeneous phenomenon characterized by various types. This study examined family risk factors associated with five neglect types including failure to provide physical needs, lack of supervision, emotional neglect, moral-legal neglect, and educational neglect in 390 substantiated cases of neglect in four U.S. Army communities. Family factors associated with elevated risk of each neglect type relative to other types were identified using multivariate regression. Relatively distinct sets of family risk factors were differentially associated with the neglect types. Family mental health problems and larger family size were associated with risk of failure to provide physical needs, childcare problems and larger family size were associated with risk of supervisory neglect, and family disagreements were associated with risk of emotional neglect. None of the family factors were associated with elevated risk of moral-legal or educational neglect. Results can inform the development of indicated and relapse prevention strategies for families affected by different neglect types.


Testing the equivalence of the aversive core of personality and a blend of agreeableness(-related) items.
There is an ongoing debate in personality research whether the common core of aversive ("dark") traits can be approximated by or even considered equivalent to one of the constructs that have been labeled "Agreeableness". In particular, it has been suggested that the low pole of (what we term) AG+, a broad blend of Big Five Agreeableness and the HEXACO factors Honesty-Humility, Agreeableness, and Altruism, is essentially equivalent to the Dark Factor of Personality (D). Based on theoretical differences, we herein test empirically whether D and AG+ are isomorphic. Self-report data on D, AG+, and eight criterion measures reflecting justifying beliefs, inflicting disutility on others, and affiliative tendencies were collected in a pre-registered study (N = 1156) and analyzed via confirmatory factor modeling. Results speak against unity of D and AG+ (35% shared variance) and support the notion that D subsumes a broader range of aversive content (i.e., justifying beliefs and inflicting disutility on others) than AG+, which, in turn, subsumes a slightly broader range of non-aversive, affiliative tendencies. We conclude that AG+ is non-equivalent to the common core of aversive traits, D.


Cerebro-oculo-nasal syndrome: another case and review of the literature.
Cerebro-Oculo-Nasal syndrome; a new multiple congenital anomaly/mental retardation syndrome was first reported by Richieri-Costa and Guion-Almeida in 1993 (Am J Med Genet 47:702-706) in two patients. To the best of our knowledge four additional cases have been reported. The main features of the syndrome are anophthalmia/microphthalmia, abnormal nares, and central nervous system anomalies. In this report, an additional sporadic case of this syndrome is presented. A 6-year-old girl from a non-consanguineous couple with normal prenatal growth parameters and retarded postnatal growth had anophthalmia, uplifted right nares with skin tag, and slight clefting at the tip of the nose, upper lip and gingiva. She also had a high-arched narrow palate, slightly low set ears, hypertelorism, a CNS defect and mental retardation. Additional findings were hypoplastic teeth with dental malocclusion, muscular hypotonia and midline hyperpigmentation over the anterior neck and the abdomen.


Critical considerations in the development of an assay for sulfidopeptide leukotrienes in plasma.
A sensitive and specific assay has been developed for measurement of total sulfidopeptide leukotrienes (LT) in plasma. LTC4 and LTD4 in plasma are converted to LTE4 which is then extracted by C18 Sep-Pak binding and elution. Total LTE4 is resolved by reverse phase high performance liquid chromatography (RP-HPLC) and quantitated by radioimmunoassay (RIA). A [3H]LTE4 internal standard is added to the starting plasma sample to allow overall recovery to be calculated and to define the fractions from RP-HPLC to be assayed for LTE4-like immunoreactivity. The correlation between the measured increase in LTE4 concentration after addition of incremental amounts of LTC4 and LTE4 to plasma was 0.989 and 0.978, respectively, with slopes of 1.05 and 1.11. Addition of 51 pg/ml LTE4 to 5 ml plasma was detectable; the measured increase was 48 +/- 12 pg/ml (mean +/- SE, n = 7). The intra-assay coefficient of variation for 341 pg/ml of added LTC4 was 3.2% (n = 6). Sulfidopeptide leukotrienes could not be detected in blood samples taken from 12 normal volunteers in whom the theoretical detection limit, calculated from the sensitivity of the RIA, the overall recovery of LTE4, and the volume of plasma extracted, was 83 +/- 4 pg LTE4/ml plasma (0.19 +/- 0.01 pmol sulfidopeptide leukotriene/ml plasma; mean +/- SE).


Regulation of orotic acid biosynthesis and excretion induced by oral glutamine administration in mice.
Glutamine, the most abundant amino acid in blood and tissues, is degraded by the renal and splanchnic tissues, especially the small intestinal mucosa. Due to the activity of glutaminase, it may be broken down in these tissues and contribute to ammoniagenicity. Glutamine, either directly or through ammonia production, may act as a nitrogenous source for pyrimidine biosynthesis. We have evaluated the effect of glutamine on orotate metabolism in mice, by gavaging (ig) L-glutamine, 1.0 to 4.0 mmol/100 g of body wt/day, during 6 weeks of experimentation. Glutamine at doses of 2.5 to 4.0 mmol/100 g of body wt caused a significant increase in plasma ammonia and urinary orotate. The regulation of the orotic acid biosynthesis and excretion was studied by testing the effects of various inhibitors in mice force-fed with glutamine (4 mmol/100 g of body wt, ig). The orotic aciduria was insensitive to acivicin (1 and 5 mg/100 g of body wt, ip), a specific inhibitor of the cytoplasmic carbamyl phosphate synthetase-II, thus pointing toward the mitochondrion as the principal source of carbamyl phosphate. Cycloheximide (15 and 100 mg/kg of body wt, ip) caused a significant decrease in urinary orotate indicating that the induction of orotate synthesis by glutamine may be associated with the translation of a specific protein. However, orotate excretion was significantly decreased by N-(phosphonoacetyl)-L-aspartate (PALA) (5 mg/100 g of body wt, ip) due to its inhibitory effect on the aspartate transcarbamylase activity. There was a significant increase of urinary orotate following ingestion of adenine supplemented diets (0.1% and 0.2%), suggesting the blockage of the utilization of orotate for nucleotide biosynthesis by glutamine. Since orotate synthesis may also be influenced by ornithine metabolism, we evaluated the effect of glutamine administration on various ornithine-metabolizing enzymes. There was a decrease in hepatic ornithine decarboxylase activity with no change in hepatic ornithine aminotransferase activity following the administration of glutamine. This observation indicates that an increased metabolic utilization of ornithine is not responsible for the increase in orotate excretion, which may be caused principally through an effect of glutamine on mitochondrial carbamyl phosphate synthesis.


Integrative expression network analysis of microRNA and gene isoforms in sacred lotus.
Gene expression is complex and regulated by multiple molecular mechanisms, such as miRNA-mediated gene inhibition and alternative-splicing of pre-mRNAs. However, the coordination of interaction between miRNAs with different splicing isoforms, and the change of splicing isoform in response to different cellular environments are largely unexplored in plants. In this study, we analyzed the miRNA and mRNA transcriptome from lotus (Nelumbo nucifera), an economically important flowering plant. Through RNA-seq analyses on miRNAs and their target genes (isoforms) among six lotus tissues, expression of most miRNAs seem to be negatively correlated with their targets and tend to be tissue-specific. Further, our results showed that preferential interactions between miRNAs and hub gene isoforms in one coexpression module which is highly correlated with leaf. Intriguingly, for many genes, their corresponding isoforms were assigned to different co-expressed modules, and they exhibited more divergent mRNA structures including presence and absence of miRNA binding sites, suggesting functional divergence for many isoforms is escalated by both structural and expression divergence. Further detailed functional enrichment analysis of miRNA targets revealed that miRNAs are involved in the regulation of lotus growth and development by regulating plant hormone-related pathway genes. Taken together, our comprehensive analyses of miRNA and mRNA transcriptome elucidate the coordination of interaction between miRNAs and different splicing isoforms, and highlight the functional divergence of many transcript isoforms from the same locus in lotus.


Integrated process development-a robust, rapid method for inclusion body harvesting and processing at the microscale level.
Escherichia coli stores large amounts of highly pure product within inclusion bodies (IBs). To take advantage of this beneficial feature, after cell disintegration, the first step to optimal product recovery is efficient IB preparation. This step is also important in evaluating upstream optimization and process development, due to the potential impact of bioprocessing conditions on product quality and on the nanoscale properties of IBs. Proper IB preparation is often neglected, due to laboratory-scale methods requiring large amounts of materials and labor. Miniaturization and parallelization can accelerate analyses of individual processing steps and provide a deeper understanding of up- and downstream processing interdependencies. Consequently, reproducible, predictive microscale methods are in demand. In the present study, we complemented a recently established high-throughput cell disruption method with a microscale method for preparing purified IBs. This preparation provided results comparable to laboratory-scale IB processing, regarding impurity depletion, and product loss. Furthermore, with this method, we performed a "design of experiments" study to demonstrate the influence of fermentation conditions on the performance of subsequent downstream steps and product quality. We showed that this approach provided a 300-fold reduction in material consumption for each fermentation condition and a 24-fold reduction in processing time for 24 samples.


Age structure of Anopheles subpictus (Diptera:Culicidae) collected by a light trap in Halmahela, Indonesia.
Age structure of Anopheles subpictus Grassi was studied at a Halmahela village, Indonesia. Ovary development of females reared with 2% sugar solution after emergence ceased at Stage I and their ovary size remained small (mean length x width = 0.68 x 0.18 mm). Females with such small ovaries occupied 21.2% of unfed Stage I females in cattle-bait samples. The remaining unfed Stage I or II females had cleary larger ovaries (mean 1.17 x 0.39 mm). Unfed Stage I or II females collected by the outdoor light trap all had large ovaries (mean 1.42 x 0.34 mm) irrespective of stages and parity. The parous rate of unfed stage I or II females collected by the light trap (86.6%) was significantly higher than that of cattle-bait samples (69.6%). Feasibility of using outdoor light trapping in malaria entomology was discussed.


[Effects of petroleum ether extract of Peucedanum praeruptorum Dunn on rabbit trachea smooth muscles].
The contractions of isolated rabbit trachea smooth muscles by acetylcholine and potassium chloride were attenuated by petroleum ether extract of Peucedanum praeruptorum pretreatment. The dose-effect curve of acetylcholine was shifted to the right, and the maximal response was diminished. The effect was non-competitive and dose-dependent.


Water equivalent thickness values of materials used in beams of protons, helium, carbon and iron ions.
Heavy charged particle beam radiotherapy for cancer is of increasing interest because it delivers a highly conformal radiation dose to the target volume. Accurate knowledge of the range of a heavy charged particle beam after it penetrates a patient's body or other materials in the beam line is very important and is usually stated in terms of the water equivalent thickness (WET). However, methods of calculating WET for heavy charged particle beams are lacking. Our objective was to test several simple analytical formulas previously developed for proton beams for their ability to calculate WET values for materials exposed to beams of protons, helium, carbon and iron ions. Experimentally measured heavy charged particle beam ranges and WET values from an iterative numerical method were compared with the WET values calculated by the analytical formulas. In most cases, the deviations were within 1 mm. We conclude that the analytical formulas originally developed for proton beams can also be used to calculate WET values for helium, carbon and iron ion beams with good accuracy.


Heterologous diploid nuclei in the violet root rot fungus, Helicobasidium mompa.
Allelic genes hga1-1 and hga1-2, which encode G protein alpha subunit in the violet root rot fungus, Helicobasidium mompa, were sequenced and characterized. Restriction fragment polymorphism (RFLP) analysis determined that the gene is present as a single locus in the single basidiospore isolates, while strain V169 possessed both alleles of this gene. Therefore, although basidiospore isolates are dikaryon, they are homokaryotic. Field-isolated strain V169, the putative parent strain, is a dikaryotic heterokaryon. Allelic genes hga1-1 and hga1-2 segregated in almost a 1:3 ratio among single basidiospore isolates from the same fruiting body. Moreover, the copy number of hga1-1 was found to be less than that of hga1-2 in the V169 strain. These results suggest that one of the nuclei in the V169 parent strain is homozygous diploid and the other heterozygous diploid. This parent strain produced four homokaryotic and dikaryon basidiospores on each basidium.


Implementation of rotavirus immunization in Philadelphia, Pennsylvania: high levels of vaccine ineligibility and off-label use.
Our goal was to predict, using delayed diphtheria-tetanus-acellular pertussis vaccination as an indicator, whether the current narrowly defined age limits for pentavalent rotavirus vaccine exclude a substantial proportion of children from complete immunization against rotavirus and to assess adherence of providers to recommended age limits by examining the first 6 months of use of pentavalent rotavirus vaccine in Philadelphia, Pennsylvania. Data from a computerized children's immunization registry in Philadelphia were analyzed. Demographics and age at immunization with first 3 diphtheria-tetanus-acellular pertussis doses were examined from 2001 to 2005. Similar characteristics were evaluated for children who received pentavalent rotavirus vaccine doses during the first 6 months of its availability (August 2006 through January 2007). During the 5-year period, 24 403 of 103 967 recipients of first diphtheria-tetanus-acellular pertussis vaccine were >12 weeks of age; only 56 411 of 79 564 first diphtheria-tetanus-acellular pertussis recipients <or=12 weeks of age received the first 3 doses at ages that they could have completed the pentavalent rotavirus vaccine series if vaccines were given at the same visit. Children using public providers were more likely to have delayed immunization. During the first 6 months of pentavalent rotavirus vaccine implementation, 5566 pentavalent rotavirus vaccine doses were recorded in the Kids Immunization Database/Tracking System: 3912 first doses, 1419 second doses, and 235 third doses. Of 3912 first-dose pentavalent rotavirus vaccine recipients, 770 were >12 weeks of age. Hospital-based providers were less likely to administer pentavalent rotavirus vaccine off-label. With the current level of vaccine implementation and current pentavalent rotavirus vaccine recommendations for series initiation, a substantial proportion of children are expected to be excluded from receiving any pentavalent rotavirus vaccine or completing the series. In the first 6 months of availability, pentavalent rotavirus vaccine frequently was used off-label for age, underscoring the importance of education of immunization providers. Current outreach programs for finding 10-month-old toddlers delinquent for immunizations will not improve the possibility of protection against rotavirus.


Cerebellar role in fear-conditioning consolidation.
Some cerebellar structures are known to be involved in the memorization of several conditioned responses. The role of the interpositus nucleus (IN) and the vermis (VE) in fear-conditioning consolidation was investigated by means of a combined behavioral and neurophysiological technique. The IN and VE were subjected to fully reversible tetrodotoxin (TTX) inactivation during consolidation in adult male Wistar rats that underwent acoustic conditioned stimulus (CS) and context fear training. TTX was injected in different groups of rats at increasing intervals after the acquisition session. Memory was assessed as conditioned freezing duration measured during retention testing, always performed 72 and 96 h after the stereotaxic TTX administration. This schedule ensures that there is no interference with normal cerebellar function during either the acquisition or the retrieval phase so that any amnesic effect may be due only to consolidation disruption. Our results show that IN functional integrity is necessary for acoustic CS fear response memory formation up to the 96-h after-acquisition delay. VE functional integrity was shown to be necessary for memory formation of both context (up to the 96-h after-acquisition delay) and acoustic CS (up to the 192-h after-acquisition delay) fear responses. The present findings help to elucidate the role of the cerebellum in memory consolidation and better define the neural circuits involved in fear memories.


US Religious Congregations' Programming to Support Veterans: A Mixed Methods Study.
Religious congregations may be well equipped to address veterans' reintegration needs, but little is known about the prevalence and nature of such support. We conducted a mixed methods study using nationally representative congregational survey data and in-depth interviews with congregational leaders. Overall, 28% of congregations nationally reported having programming to support veterans and positive, independent predictors included: community context (county veteran presence, high-poverty census tract, rural compared to urban location); congregational resources (more adult attendees, having a paid employee that spent time on service programs); and external engagement (assessing community needs, collaboration, and social service participation). Qualitative interviews revealed a range of activities, including attending to spiritual issues, supporting mental, physical and social well-being, and addressing vocational, legal, financial, and material needs.


The restoration of endodontically treated, single-rooted teeth with cast or direct posts and cores: a systematic review.
Direct post-and-core restorations with prefabricated posts are becoming increasingly popular. A literature review was conducted to compare the clinical and in vitro performance of cast posts and cores to that of direct cores with prefabricated posts in single-rooted teeth. Research on the restoration of endodontically treated teeth was identified through a search of electronic databases. The search yielded a total of 1773 references. After these references were subjected to strict inclusion criteria, 10 in vitro and 6 in vivo studies remained and critically reviewed. A comparison of fracture loads in the in vitro studies revealed no significant difference between cast and direct posts and cores. Meta-analysis of the data suggested that there is no difference in fracture behavior associated with the 2 treatment modalities. An overall survival analysis was not possible for the in vivo studies. The survival for cast posts and cores in 2 studies ranged from 87.2% to 88.1% and in a third study reached 86.4% for direct cores after 72 months. Randomized clinical trials on this topic were not available but should be conducted to verify published findings.


Human coagulation factor IX: a systematic review of its characteristics.
Human coagulation factor IX (FIX) is a vitamin K dependent glycoprotein. It is used in therapy of factor IX deficiency, known as haemophilia B. This article explained the coagulation process involved in FIX and the principle of haemophilia B caused by its absence. We searched and aligned the sequence information of IX in the NCBI's EST database to predict its structure and understand the molecular biological basis of its function. Further, by sorting out the development history of FIX, we summarized the general process of its isolation and purification. Finally, the clinical indications and complications of FIX were overviewed. Through a comprehensive description of the characteristics of FIX, we hope to give readers a clear understanding and put forward our views on the future development of the product.


Rare presentation of AICA syndrome.
We report a rare presentation of an anterior inferior cerebellar artery (AICA) infarct in a 74-year-old woman with acute-onset nausea, vomiting, vertigo and gait instability long before the full onset of symptoms and a negative MRI on admission. Over the next several days the patient developed left facial weakness, numbness, hypoacusis, and limb and gait ataxia, and was found to have acute infarcts of the left pons and cerebellar peduncle consistent with an AICA syndrome. We discuss this rare stepwise presentation in AICA syndrome and possible underlying pathophysiology. Such patients at risk for cerebrovascular disease should undergo a careful history, exam and follow-up, even with negative MRI findings, as their symptoms may precede a serious vascular event.