Gender-Affirming Hormone Treatment Induces Facial Feminization in Transwomen and Masculinization in Transmen: Quantification by 3D Scanning and Patient-Reported Outcome Measures.
Hormone treatment induces feminization of the body in transwomen and masculinization in transmen. However, the effect of hormone treatment on facial characteristics is still unknown. We aimed to study whether hormone treatment induces facial feminization and masculinization and how this potential change affects satisfaction and self-esteem. In this single-center cohort study, we included 27 transwomen and 15 transmen who received standardized hormone treatment in the Center of Expertise on Gender Dysphoria, VU University Medical Center Amsterdam. Facial 3-dimensional images were obtained at baseline and at 3 and 12 months. At each image, 22 facial landmarks were placed. Furthermore, the FACE-Q Satisfaction with Facial Appearance Overall and the Rosenberg self-esteem scale were obtained at the same measurement points. The main outcome measures included the relative local shift of skin in millimeters in the 22 landmarks in the transverse (x-axis), coronal (y-axis), and sagittal (z-axis) anatomic axes, the color maps, and the outcomes of the questionnaires. After 12 months, cheek tissue in transwomen increased, with 0.50 mm (95% CI 0.04-0.96) in the x-axis and 1.08 mm (95% CI 0.31-1.85) in the z-axis. Tissue in the jaws decreased with -0.60 mm (95% CI -1.28-0.08) in the x-axis and -0.18 mm (95% CI -0.03-0.33) in the y-axis. Cheek tissue in transmen decreased with -0.45 mm (95% CI -1.00-0.11) in the x-axis and -0.84 mm (95% CI -1.92-0.25) in the z-axis. These changes already started after 3 months. An increase in satisfaction with the facial appearance was found in both transwomen and transmen. There were no changes in reported self-esteem. These results could lead to more realistic expectations of facial changes. Furthermore, our results suggest that the face continues to change for at least a year, which could suggest that performing facial feminization surgery after 1 year of hormone treatment might be too early. This study is the first that provides insight into the facial changes in transgender individuals receiving hormone treatment, and it introduces an objective method to examine (small) facial changes. Our study is limited by the poor reliability of the landmarks, the difficulty of facial fixation, and the lack of gender-specific questions in the questionnaires. Hormone treatment in transwomen induces an increase in cheek tissue and a decrease in jaw tissue. In transmen a tendency of decrease in cheek tissue and an increase in jaw tissue was found. These changes are in the direction of the desired gender. Tebbens M, Nota NM, Liberton NPTJ, et al. Gender-Affirming Hormone Treatment Induces Facial Feminization in Transwomen and Masculinization in Transmen: Quantification by 3D Scanning and Patient-Reported Outcome Measures. J Sex Med 2019;16:746-754.


The value of eliminating foods according to food-specific immunoglobulin G antibodies in irritable bowel syndrome with diarrhoea.
This study investigated the role of food intolerance in irritable bowel syndrome with diarrhoea (D-IBS). Specific immunoglobulin G (IgG) antibodies against 14 common food antigens in the serum were measured in 77 patients with D-IBS and 26 healthy controls. Food-specific IgG antibodies were identified in 39 (50.65%) patients with D-IBS patients compared with four (15.38%) controls. For 12 weeks following the serological testing, 35 patients with D-IBS and food intolerance consumed diets that excluded the identified food. Changes in the main symptoms of D-IBS were evaluated before treatment and regularly during treatment in these patients. After 4 weeks' dietary therapy, most symptoms of D-IBS had improved. By 12 weeks, all symptom scores had decreased significantly compared with the baseline scores. The 12-week specific-food exclusion diets resulted in significant improvements in abdominal pain (bloating level and frequency), diarrhoea frequency, abdominal distension, stool shape, general feelings of distress and total symptom score compared with baseline in patients with D-IBS.


Modeling perimenopause in Sprague-Dawley rats by chemical manipulation of the transition to ovarian failure.
Various age-related diseases increase in incidence during perimenopause. However, our understanding of the effects of aging compared with hormonal changes of perimenopause in mediating these disease risks is incomplete, in part due to the lack of an experimental perimenopause model. We therefore aimed to determine whether manipulation of the transition to ovarian failure in rats via the use of 4-vinylcyclohexene diepoxide (VCD) could be used to model and accelerate hormonal changes characteristic of perimenopause. We examined long-term (11 to 20 mo), dose-dependent effects of VCD on reproductive function in 1- and 3-mo-old female Sprague-Dawley rats. Twenty-five daily doses of VCD (80 or 160 mg/kg daily compared with vehicle alone) depleted ovarian follicles in a dose-dependent fashion in rats of both ages, accelerated the onset of acyclicity, and caused dose-dependent increases in follicle-stimulating hormone that exceeded those naturally occurring with age in control rats but left serum levels of 17β-estradiol unchanged, with continued ovarian production of androstenedione. High-dose VCD caused considerable nonovarian toxicities in 3-mo-old Sprague-Dawley rats, making this an unsuitable model. In contrast, 1-mo-old rats had more robust dose-dependent increases in follicle-stimulating hormone without evidence of systemic toxicity in response to either VCD dose. Because perimenopause is characterized by an increase in follicle-stimulating hormone with continued secretion of ovarian steroids, VCD acceleration of an analogous hormonal milieu in 1-mo-old Sprague-Dawley rats may be useful for probing the hormonal effects of perimenopause on age-related disease risk.


Tet-assisted bisulfite sequencing of 5-hydroxymethylcytosine.
A complete understanding of the potential function of 5-hydroxymethylcytosine (5-hmC), a DNA cytosine modification in mammalian cells, requires an accurate single-base resolution sequencing method. Here we describe a modified bisulfite-sequencing method, Tet-assisted bisulfite sequencing (TAB-seq), which can identify 5-hmC at single-base resolution, as well as determine its abundance at each modification site. This protocol involves β-glucosyltransferase (β-GT)-mediated protection of 5-hmC (glucosylation) and recombinant mouse Tet1(mTet1)-mediated oxidation of 5-methylcytosine (5-mC) to 5-carboxylcytosine (5-caC). After the subsequent bisulfite treatment and PCR amplification, both cytosine and 5-caC (derived from 5-mC) are converted to thymine (T), whereas 5-hmC reads as C. The treated genomic DNA is suitable for both whole-genome and locus-specific sequencing. The entire procedure (which does not include data analysis) can be completed in 14 d for whole-genome sequencing or 7 d for locus-specific sequencing.


Evaluating Patients' Expectations From a Novel Patient-Centered Perspective Predicts Knee Arthroplasty Outcome.
One-in-five patients are dissatisfied following knee arthroplasty and <50% have fulfilled expectations. The relationship between knee-arthroplasty expectations and surgical outcome remains unclear. Are expectations regarding the impact of pain on postoperative life predictive of one-year outcome? Does the impact of pain on preoperative quality of life (QOL) influence this relationship? Longitudinal cohort of 1044 uni-compartmental (43%) or total knee-arthroplasty (57%) (UKA or TKA) patients, aged mean 69 ± 9 years. Preoperatively, patients reported the impact of pain on QOL and expected impact of pain on life one-year post-arthroplasty. One-year postoperative outcomes: non-return to desired activity, surgical dissatisfaction, not achieving Oxford Knee Score minimal important change (OKS <MIC). Logistic regression including covariates was performed for all patients and subgroups (better vs worse pre-operative pain-related QOL; UKA vs TKA). Expecting moderate-to-extreme pain (vs no pain) predicted non-return to activity (odds ratio [95% confidence interval], 2.3 [1.3, 4.1]), dissatisfaction (4.0 [1.7, 9.3]), OKS <MIC (3.1 [1.5, 6.3]). Expecting mild pain (vs no pain) predicted worse outcomes for patients with better preoperative pain-related QOL (non-return to activity: 2.7 [1.5, 4.8], OKS <MIC: 2.5 [1.1, 5.5]). Expecting moderate-to-extreme pain (vs. no pain) predicted worse outcomes for patients with worse preoperative pain-related QOL (non-return to activity: 2.4 [1.1, 5.5], dissatisfaction: 5.0 [1.7, 14.8], OKS <MIC: 3.4 [1.4, 8.6]). The odds of a poor outcome in people with worse expectations was higher for UKA patients. Expecting a worse outcome predicted surgical dissatisfaction, less clinical improvement and non-return to desired activity. Patients expecting a more optimistic outcome relative to preoperative status achieved better surgical outcomes.


A transcriptional timetable of autumn senescence.
We have developed genomic tools to allow the genus Populus (aspens and cottonwoods) to be exploited as a full-featured model for investigating fundamental aspects of tree biology. We have undertaken large-scale expressed sequence tag (EST) sequencing programs and created Populus microarrays with significant gene coverage. One of the important aspects of plant biology that cannot be studied in annual plants is the gene activity involved in the induction of autumn leaf senescence. On the basis of 36,354 Populus ESTs, obtained from seven cDNA libraries, we have created a DNA microarray consisting of 13,490 clones, spotted in duplicate. Of these clones, 12,376 (92%) were confirmed by resequencing and all sequences were annotated and functionally classified. Here we have used the microarray to study transcript abundance in leaves of a free-growing aspen tree (Populus tremula) in northern Sweden during natural autumn senescence. Of the 13,490 spotted clones, 3,792 represented genes with significant expression in all leaf samples from the seven studied dates. We observed a major shift in gene expression, coinciding with massive chlorophyll degradation, that reflected a shift from photosynthetic competence to energy generation by mitochondrial respiration, oxidation of fatty acids and nutrient mobilization. Autumn senescence had much in common with senescence in annual plants; for example many proteases were induced. We also found evidence for increased transcriptional activity before the appearance of visible signs of senescence, presumably preparing the leaf for degradation of its components.


Firearms, hanging, and drowning suicides in the Republic of ireland.
The firearms climate in Ireland is rapidly changing, and there is currently no research on the risk profiles of those dying through firearms suicides. To compare the sociodemographic profile of firearms suicide deaths with hanging and drowning suicides. Analyses are based on data for 9,674 suicides that occurred between 1980 and 2005 and provided by the Central Statistics Office of Ireland (CSO). Risk factors included were gender, place of residence, employment status (agri-employed/not agri-employed), marital status, and age. Those dying by shooting were twice as likely to be male than those dying by hanging (95% CI = 1.5 to 2.6) and 6.7 times more likely than those dying by drowning (95% CI = 4.9 to 9.1). They were also more likely to have resided in a rural location (hanging OR = 3.8, 95% CI = 2.8 to 5.0; drowning OR = 4.2, 95% CI = 3.1 to 5.6) and to have been agri-employed (hanging OR = 1.3, 95% CI = 1.1 to 1.6; drowning OR = 1.4, 95% CI = 1.1 to 1.7). Firearms suicides were significantly younger (H = 458.9, p < .0005). Model fit statistics from logistic regressions are presented. Factors included in the study were limited to those recorded by the CSO. The findings have implications for awareness training for suicide prevention workers and for those concerned with Ireland's increasingly liberal firearms climate.


Monitoring dietary intake and physical activity electronically: feasibility, usability, and ecological validity of a mobile-based Ecological Momentary Assessment tool.
Despite the growing body of research on complex lifestyle behaviors (eg, Dietary Intake [DI] and Physical Activity [PA]), monitoring of these behaviors has been hampered by a lack of suitable methods. A possible solution to this deficiency is mobile-based Ecological Momentary Assessment (mEMA), which enables researchers to collect data on participants' states in real-time by means of a smartphone application. However, feasibility, usability, and ecological validity need to be anticipated and managed in order to enhance the validity of mEMA. To examine the feasibility, usability, and ecological validity of a mEMA application (app) with regard to DI and PA among Dutch vocational education students. The students (n=30) participated in the mEMA study for seven consecutive days. They downloaded the mEMA app on their smartphone. Feasibility and usability of the mEMA app were evaluated by completing an online evaluation after seven days of participation. Ecological validity was measured by assessing the degree to which the content of the mEMA app approximated the real-world setting that was being examined, through several multiple-choice questions. Compliance rates, as registered by the mEMA app, declined 46% over a seven-day period, while self-reported compliance, as measured with an online evaluation questionnaire afterwards, indicated a smaller decrease in compliance (29%). The students evaluated the mEMA app as feasible and usable. Ecological validity analyses showed that all DI and almost all PA multiple-choice options were covered with the compound response categories. The mEMA app offers the opportunity to assess complex health behaviors (eg, DI and PA) in real-time settings, in which specifically routinized behaviors are involved. However, the mEMA app faced several challenges that needed to be overcome in order to improve its validity. Overall, the present study showed that the mEMA app is a usable and ecologically valid tool to measure DI and PA behaviors among vocational education students, but compliance is still limited.


Isolation and identification of pectenotoxins-13 and -14 from Dinophysis acuta in New Zealand.
Two novel pectenotoxins (PTXs), PTX-13 and -14, were isolated from extracts of Dinophysis acuta collected from the west coast of South Island, New Zealand. The compounds were identified as oxidized analogues of PTX-2 by NMR spectroscopic and LC-MS studies. PTX-13 (32R-hydroxyPTX-2) corresponds to the unidentified analogue PTX-11x reported by [Suzuki et al., 2003. Liquid chromatography-mass spectrometry of spiroketal stereoisomers of pectenotoxins and the analysis of novel pectenotoxin isomers in the toxic dinoflagellate Dinophysis acuta from New Zealand. J. Chromatogr. A 992, 141-150]. PTX-13 underwent slow deuteration at the 13beta-position during NMR analysis. PTX-14 corresponds to the 32,36-dehydration product of PTX-13, and may be an artifact.


Noncommuting conserved charges in quantum many-body thermalization.
In statistical mechanics, a small system exchanges conserved quantities-heat, particles, electric charge, etc.-with a bath. The small system thermalizes to the canonical ensemble or the grand canonical ensemble, etc., depending on the quantities. The conserved quantities are represented by operators usually assumed to commute with each other. This assumption was removed within quantum-information-theoretic (QI-theoretic) thermodynamics recently. The small system's long-time state was dubbed "the non-Abelian thermal state (NATS)." We propose an experimental protocol for observing a system thermalize to the NATS. We illustrate with a chain of spins, a subset of which forms the system of interest. The conserved quantities manifest as spin components. Heisenberg interactions push the conserved quantities between the system and the effective bath, the rest of the chain. We predict long-time expectation values, extending the NATS theory from abstract idealization to finite systems that thermalize with finite couplings for finite times. Numerical simulations support the analytics: The system thermalizes to near the NATS, rather than to the canonical prediction. Our proposal can be implemented with ultracold atoms, nitrogen-vacancy centers, trapped ions, quantum dots, and perhaps nuclear magnetic resonance. This work introduces noncommuting conserved quantities from QI-theoretic thermodynamics into quantum many-body physics: atomic, molecular, and optical physics and condensed matter.


Vascular complications of pancreas transplantation.
The purpose of our study was to focus on the early diagnosis and treatment of vascular complications after simultaneous pancreas-kidney (SPK) transplantation. Description of the technique for salvage of the graft after venous thrombosis (VT) is also provided. From July 1994 to December 2002, 14 patients of 206 SPK transplant recipients had partial VT. Partial splenic VT (PSVT) was documented in 10 patients (4.8%), two had complete thrombosis of the splenic vein, one partial superior mesenteric thrombosis, and one developed partial thrombosis of the splenic and superior mesenteric vein. Four patients developed complete VT of the pancreas allograft and one superior mesenteric artery thrombosis. Our experience with four arteriovenous fistulae is also reported. The immunosuppression included tacrolimus, steroids, and monoclonal antibody to the IL-2 receptor. Thymoglobulin was introduced in June 2000 in our protocol combined with rapamycin or mycophenolate mofetil. These cases were identified following the intravenous (iv) use of tacrolimus with or without anti-IL-2R therapy. One case of complete VT is also reported one month following transplantation in a recipient with high rapamycin levels. Diagnosis was established during routine color Doppler ultrasonography. Partial VT was effectively treated with anticoagulation. Complete VT required surgical thrombectomy. In our series, the pancreas was salvaged successfully in all patients with the technique described here. Early diagnosis of vascular complications after pancreas transplantation is of paramount importance for the appropriate treatment with organ salvage. Based on our experience, we suggest that VT can be effectively treated with anticoagulation. Aspirin is sufficient for PSVT.


Effect of point of care testing for C reactive protein and training in communication skills on antibiotic use in lower respiratory tract infections: cluster randomised trial.
To assess the effect of general practitioner testing for C reactive protein (disease approach) and receiving training in enhanced communication skills (illness approach) on antibiotic prescribing for lower respiratory tract infection. Pragmatic, 2x2 factorial, cluster randomised controlled trial. 20 general practices in the Netherlands. 40 general practitioners from 20 practices recruited 431 patients with lower respiratory tract infection. The primary outcome was antibiotic prescribing at the index consultation. Secondary outcomes were antibiotic prescribing during 28 days' follow-up, reconsultation, clinical recovery, and patients' satisfaction and enablement. General practitioners' use of C reactive protein point of care testing and training in enhanced communication skills separately and combined, and usual care. General practitioners in the C reactive protein test group prescribed antibiotics to 31% of patients compared with 53% in the no test group (P=0.02). General practitioners trained in enhanced communication skills prescribed antibiotics to 27% of patients compared with 54% in the no training group (P<0.01). Both interventions showed a statistically significant effect on antibiotic prescribing at any point during the 28 days' follow-up. Clinicians in the combined intervention group prescribed antibiotics to 23% of patients (interaction term was non-significant). Patients' recovery and satisfaction were similar in all study groups. Both general practitioners' use of point of care testing for C reactive protein and training in enhanced communication skills significantly reduced antibiotic prescribing for lower respiratory tract infection without compromising patients' recovery and satisfaction with care. A combination of the illness and disease focused approaches may be necessary to achieve the greatest reduction in antibiotic prescribing for this common condition in primary care. Current Controlled Trials ISRCTN85154857.


Hearing health and care: the need for improved hearing loss prevention and hearing conservation practices.
Hearing loss affects 31 million Americans, particularly veterans who were exposed to harmful levels of noise during military functions. Many veterans also receive treatment with ototoxic medications, which may exacerbate preexisting hearing loss. Thus, hearing loss is the most common and tinnitus the third most common service-connected disability among veterans. Poor implementation of hearing protection programs and a lack of audiometric testing during medical treatment leave veterans vulnerable to unrecognized and untreated hearing loss until speech communication is impaired. Individualized audiometric testing techniques, including assessment of high frequencies, can be used in clinical and occupational settings to detect early hearing loss. Antioxidants also may alleviate cochlear damage caused by noise and ototoxicity. Ultimately, hearing loss prevention requires education on reducing occupational and recreational noise exposure and counseling on the risks and options available to patients. Technological advances will improve monitoring, allow better noise engineering controls, and lead to more effective hearing protection.


Dissociation of estrogen receptor expression and in vivo stem cell activity in the mammary gland.
The role of estrogen in promoting mammary stem cell proliferation remains controversial. It is unclear if estrogen receptor (ER)-expressing cells have stem/progenitor activity themselves or if they act in a paracrine fashion to stimulate stem cell proliferation. We have used flow cytometry to prospectively isolate mouse mammary ER-expressing epithelial cells and shown, using analysis of gene expression patterns and cell type-specific markers, that they form a distinct luminal epithelial cell subpopulation that expresses not only the ER but also the progesterone and prolactin receptors. Furthermore, we have used an in vivo functional transplantation assay to directly demonstrate that the ER-expressing luminal epithelial subpopulation contains little in vivo stem cell activity. Rather, the mammary stem cell activity is found within the basal mammary epithelial cell population. Therefore, ER-expressing cells of the mammary epithelium are distinct from the mammary stem cell population, and the effects of estrogen on mammary stem cells are likely to be mediated indirectly. These results are important for our understanding of cellular responses to hormonal stimulation in the normal breast and in breast cancer.


Predictors of depressed left ventricular function in patients presenting with ST-elevation myocardial infarction.
Early in the course of ST-segment elevation myocardial infarction (STEMI), therapies that may harm patients who develop left ventricular (LV) dysfunction, such as β-blockers, are often administered. The investigators analyzed the ACTIVATE-SF database, a registry of consecutive STEMI activations presenting to 2 medical centers at the University of California, San Francisco. LV dysfunction was defined as an ejection fraction ≤40% on echocardiography. Of 211 patients included in the analysis, 66 (31%) had LV ejection fractions ≤40%. Patients with LV dysfunction were older (63 ± 15 vs 56 ± 13 years, p = 0.002). In multivariate regression models, decreased renal function (reference group, creatinine <1.0 mg/dl; adjusted odds ratio [AOR] creatinine >1.5 mg/dl 6.35, 95% confidence interval [CI] 1.66 to 24.31, p = 0.007), a history of coronary artery disease (AOR 3.12, 95% CI 1.26 to 7.71, p = 0.014), ST-segment elevation >2 mm on 12-lead electrocardiography (AOR 2.78, 95% CI 1.31 to 5.87, p = 0.008), and need for mechanical ventilation (AOR 3.98, 95% CI 1.41 to 11.19, p = 0.009) increased the odds of LV dysfunction. Inferior ST-segment elevations were associated with 88% decreased odds of LV dysfunction (AOR 0.12, 95% CI 0.06 to 0.35, p <0.001). A prediction score using these characteristics stratified patients into low-, intermediate-, and high-risk groups for LV dysfunction; positive likelihood ratios for LV dysfunction in these groups were 0.07, 1.14, and 4.93, respectively. In conclusion, 5 key predictors of in-hospital LV dysfunction after STEMI were identified; a risk score based on these predictors helps to quickly identify patients presenting with STEMI who are at the highest risk for developing significant LV dysfunction and could guide optimal therapeutic choices.


Chemical composition, energy and amino acid digestibility in double-low rapeseed meal fed to growing pigs.
The nutritional value of rapeseed meal may be variable due to the variation of its chemical composition. And a precise understanding of the nutritional value of an ingredient is beneficial for the accurate diet formulation and reduction of feed costs. This study was conducted to determine the chemical composition, digestible energy (DE) and metabolizable energy (ME) content, and apparent ileal digestibility (AID) and standardized ileal digestibility (SID) of amino acids (AA) for growing pigs. Thirteen solvent-extracted double-low rapeseed meal (DLRSM) samples were obtained from the main double-low rapeseed producing areas in China. The DE and ME contents of the 13 DLRSM samples were measured in growing pigs (six pigs per DLRSM sample, average initial body weight (BW) = 48.3 kg). The AID and SID of AA of 10 DLRSM samples were determined in 12 crossbred barrows (average initial BW = 35.3 kg) by using two 6 × 6 Latin square designs. Each Latin square comprised one N-free diet and 5 DLRSM test diets. The chemical composition of DLRSM varied among samples, and the coefficient of variation was greater than 10 % for ether extract (EE), neutral detergent fiber (NDF), acid detergent fiber (ADF), calcium (Ca), and total glucosinolates. The AA content of DLRSM varied among samples especially for lysine (Lys) and methionine (Met). On a dry matter (DM) basis, the apparent total tract digestibility (ATTD) of gross energy (GE), the DE and ME and the ME:DE ratio of DLRSM averaged 62.39 %, 2862 kcal/kg and 2723 kcal/kg, and 94.95 %, respectively. The mean value of SID of Lys was 70.52 % which varied from 66.54-76.54 %. The SID of crude protein (CP), Met, and threonine (Thr) averaged 72.81 %, 82.41 %, and 69.76 %, respectively. There was great variability in chemical composition especially in the concentration of EE, NDF and ADF, but no significant differences in energy content of the DLRSM samples were observed. In addition, the AID and SID of all AA were relatively similar among DLRSM samples except for that of Lys.


Electrochemical detection of sugar-related compounds using boron-doped diamond electrodes.
Electrochemical detection of sugar-related compounds was conducted using a boron-doped diamond (BDD) electrode as a detector for flow-injection analysis (FIA). Sugar-related compounds oxidize at high applied potentials, for which the BDD electrode is suitable for electrochemical measurements. Conditions for an FIA system with a BDD detector were optimized, and the following detection limits were achieved for sugar-related compounds: monosaccharides, 25-100 pmol; sugar alcohols, 10 pmol; and oligosaccharides, 10 pmol. The detection limit for monosaccharide D-glucose (Glu) was 105 pmol (S/N = 3). A linear range was acquired from the detection limit to 50 nmol, and the relative standard deviation was 0.65% (20 nmol, n = 6). A high-performance liquid chromatography (HPLC) column was added to the system between the sample injector and the detector and detection limits to the picomole level were achieved, which is the same for the HPLC system and the FIA system. The electrochemical oxidation reaction of Glu was examined using cyclic voltammetry with the BDD detector. The reaction proved to be irreversible, and proceeded according to the following two-step mechanism: (1) application of a high potential (2.00 V vs. Ag/AgCl) to the electrode causes water to electrolyze on the electrode surface with the simultaneous generation of a hydroxyl radical on the surface, and (2) the hydroxyl radical indirectly oxidizes Glu. Thus, Glu can be detected by an increase in the oxidation current caused by reactions with hydroxy radicals.


Chronic rhinosinusitis with nasal polyps: a proteomic analysis.
Chronic rhinosinusitis with nasal polyps (CRSwNP) is a severe subtype of chronic rhinosinusitis that can affect patients despite medical and surgical interventions. The purpose of this study was to utilize the techniques of proteomics to investigate differences in protein abundance within the sinonasal mucosa of patients with CRSwNP compared to healthy controls. In a case-control study at a tertiary-care academic medical center, sinonasal mucosa was harvested from 3 patients with CRSwNP and 3 control patients undergoing transsphenoidal excision of pituitary tumors. Two-dimensional gel electrophoresis was used to identify proteins with elevated or reduced abundance in CRSwNP patients compared to controls. The proteins showing the greatest abundance differences were characterized by mass spectrometry. More than 300 differentially abundant proteins (p < or = 0.05) were identified. Many of these protein species were involved in the host inflammatory response. Proteins up-regulated in CRSwNP patients included eosinophil lysophospholipase by a ratio (R) of 18.13, RHO-GDP dissociation inhibitor 2 (R = 2.80), and apolipoprotein A-1 (R = 1.73). Down-regulated proteins in CRSwNP patients included catalase (R = -5.87), annexin A1 (R = -6.27), and keratin II-8 (R = -6.73). A detailed analysis of additional protein species is outlined. The proteomic approach allows detection of significant differences in protein abundance in CRSwNP and provides unique insight into the pathophysiology of this common disease.


The Melancholia Scale and the Newcastle Scales. Item-combinations and inter-observer reliability.
The reliability of the total scores on three rating scales (Melancholia Scale and the two Newcastle Scales) and the algorithms leading to the Feighner, Research Diagnostic Criteria, and the DSM-III subtypes of depression have been compared. The degree of inter-observer agreements for the various item-combinations was significantly higher than would be expected by chance. The average agreement for each assessment system ranged from 80 to 93 per cent. This 7 to 20 per cent lack of total agreement probably reflects the limitation of clinical assessments including the influence of halo effects.


Disparate effects of similar phenolic phytochemicals as inhibitors of oxidative damage to cellular DNA.
Phenolic phytochemicals are natural plant substances whose cellular effects have not been completely determined. Nordihydroguaiaretic acid (NDGA) and curcumin are two phenolic phytochemicals with similar molecular structures, suggesting that they possess comparable chemical properties particularly in terms of antioxidant activity. To examine this possibility in a cellular system, this study evaluated the capacities of NDGA and curcumin to function as antioxidants in inhibiting oxidative damage to DNA. Jurkat T-lymphocytes were pre-incubated for 30 min with 0-25 microM of either NDGA or curcumin to allow for uptake. The phenolic phytochemical-treated cells were then oxidatively challenged with 25 microM hydrogen peroxide (H2O2). Afterwards, cells were subjected to alkaline micro-gel electrophoresis (i.e. comet assay) to assess the extent of single-strand breaks in DNA. In a concentration-dependent manner, NDGA inhibited H2O2-induced DNA damage, whereas curcumin did not. In fact, incubating Jurkat T-lymphocytes with curcumin alone actually induced DNA damage. This effect of curcumin on DNA did not appear to reflect the DNA fragmentation associated with apoptosis because there was no proteolytic cleavage of poly-(ADP-ribose)-polymerase, which is considered an early marker of apoptosis. Curcumin-induced damage to DNA was prevented by pre-treatment of the cells with the lipophilic antioxidant, alpha-tocopherol, suggesting that curcumin damaged DNA through oxygen radicals. Therefore, it is concluded that NDGA has antioxidant activity but curcumin has prooxidant activity in cultured cells based on their opposite effects on DNA.


Mechanistic insight provided by glutaredoxin within a fusion to redox-sensitive yellow fluorescent protein.
Redox-sensitive yellow fluorescent protein (rxYFP) contains a dithiol disulfide pair that is thermodynamically suitable for monitoring intracellular glutathione redox potential. Glutaredoxin 1 (Grx1p) from yeast is known to catalyze the redox equilibrium between rxYFP and glutathione, and here, we have generated a fusion of the two proteins, rxYFP-Grx1p. In comparison to isolated subunits, intramolecular transfer of reducing equivalents made the fusion protein kinetically superior in reactions with glutathione. The rate of GSSG oxidation was thus improved by a factor of 3300. The reaction with GSSG most likely takes place entirely through a glutathionylated intermediate and not through transfer of an intramolecular disulfide bond. However, during oxidation by H(2)O(2), hydroxyethyl disulfide, or cystine, the glutaredoxin domain reacted first, followed by a rate-limiting (0.13 min(-)(1)) transfer of a disulfide bond to the other domain. Thus, reactivity toward other oxidants remains low, giving almost absolute glutathione specificity. We have further studied CPYC --> CPYS variants in the active site of Grx1p and found that the single Cys variant had elevated oxidoreductase activity separately and in the fusion. This could not be ascribed to the lack of an unproductive side reaction to glutaredoxin disulfide. Instead, slower alkylation kinetics with iodoacetamide indicates a better leaving-group capability of the remaining cysteine residue, which can explain the increased activity.


Determination of lymphatic vascular identity and developmental timecourse in zebrafish (Danio rerio).
Zebrafish lymphatics have been shown to share a number of characteristics with their human counterparts, making the fish a potentially useful model for studying lymphatic development and disease. The utility of the zebrafish lymphatic model would be substantially enhanced by an improved understanding of the spatiotemporal development of the primary lymphatic vasculature. The goal of this project is to identify and map the major zebrafish lymphatic structures throughout embryonic to early juvenile stages of development. Two transgenic lines, kdr-1:RASmCherryxfli1:GFP and stabilin1:YFP, were recently derived to assist in the study of developing lymphatic vasculature, but their specificity has not been rigorously tested. In the course of the present study, we experimentally validate the utility of these two marker lines as potential tools for establishing lymphatic vascular identity and visualizing developmental lymphangiogenesis. We introduced twenty nanometer red florescent microspheres into the blood vasculature of flil:GFP zebrafish and collected tiled optical z-sections at time intervals spanning early development. Three-dimensional reconstructions of the vasculature were used to differentiate between blood and lymphatic vessels. Age-matched injected embryos were compared to the two transgenic lines to further assess their specificity. We created a spatiotemporal map of the major lymphatic vessels in the developing zebrafish including a previously unidentified lymphatic vessel in the gastrointestinal tract. We conclude that the kdr-1:RASmCherryxfli1:GFP line accurately identifies developing lymphatic vessels with the exception of those associated with the gastrointestinal tract. The stabilin1:YFP line, however, is less reliable, as it marks both venous vessels and lymphatic vessels.


Technical Note: Dosimetric characterization of the dynamic beam flattening MLC sequence on a ring shaped, Jawless Linear Accelerator with double stacked MLC.
To characterize the dosimetric features and limitations of the dynamic beam flattening (DBF) on the Halcyon 2.0 linear accelerator (Varian Medical Systems). A predefined multi-leaf collimator (MLC) sequence was introduced and used to flatten the 6 MV flattening filter free (FFF) beam on the Halcyon 2.0. Dosimetric characterizations of the flattened beams, including beam flatness, symmetry, percent depth dose (PDD), output factor and MU linearity, were investigated. Flatness and symmetry were obtained from profile measurements with both radiographic films (EDR2) and a two dimensional ion-chamber array (IC Profiler, Sun Nuclear Corporation). MU linearity, output factors, and PDDs were measured in a water tank with a CC13 ion chamber (Scanditronix Wellhöfer, Nuremburg, Germany). In addition, the effect of the DBF sequence on 3D plan quality was evaluated by creating DBF plans for a 4-field box rectum and an AP/PA spine plan. Patient specific QA was performed on these plans. At 100 cm SSD and 10 cm depth, a flatness of <3% was observed on both transversal and radial profiles for all square field sizes ≥10 cm with DBF. For both larger and smaller field sizes the flatness showed a tendency to increase as the fields got bigger or smaller, respectively. Similar trends in flatness were observed at all depths measured. All measured output factors for square field sizes ≥5 cm were within 1% of the TPS prediction. Linearity was ≤2.02% for all measurements. For both treatment sites, the MD judged the plans created for the Halcyon without the use of DBF not to be clinically acceptable, however considered both the TrueBeam plan and the Halcyon plan with the DBF sequence to be clinically acceptable. The DBF sequence on the Halcyon and its characteristics were investigated. The analysis indicates that the DBF sequence can be used on the Halcyon to generate clinically acceptable 3D treatment plans.


Sequence-dependent mechanical properties of double-stranded RNA.
The mechanical properties of double-stranded RNA (dsRNA) are involved in many of its biological functions and are relevant for future nanotechnology applications. DsRNA must tightly bend to fit inside viral capsids or deform upon the interaction with proteins that regulate gene silencing or the immune response against viral attacks. However, the question of how the nucleotide sequence affects the global mechanical properties of dsRNA has so far remained largely unexplored. Here, we have employed state-of-the-art atomistic molecular dynamics simulations to unveil the mechanical response of different RNA duplexes to an external force. Our results reveal that, similarly to dsDNA, the mechanical properties of dsRNA are highly sequence-dependent. However, we find that the nucleotide sequence affects in a strikingly different manner the stretching and twisting response of RNA and DNA duplexes under force. We find that the elastic response of dsRNA is dominated by the local high flexibility of pyrimidine-purine steps. Moreover, the flexibility of pyrimidine-purine steps is independent of the sequence context, and the global flexibility of the duplex reasonably scales with the number of this kind of base-pair dinucleotides. We conclude that disparities of the mechanical response of dinucleotides are responsible for the differences observed in the mechanical properties of RNA and DNA duplexes.


Duffy antigen receptor for chemokines gene polymorphisms and malaria in Mangaluru, India.
Duffy blood group antigens serve as receptors for Plasmodium vivax invasion into erythrocytes, and they are determined by polymorphisms of the Duffy antigen receptor for chemokines (DARC), also known as Fy glycoprotein (FY). Duffy negativity, i.e., absence of the antigens, protects against P. vivax infection and is rare among non-African populations. However, data on DARC polymorphisms and their impact on Plasmodium infection in India are scarce. In a case-control study among 909 malaria patients and 909 healthy community controls in Mangaluru, southwestern India, DARC polymorphisms T-33C (rs2814778), G125A (rs12075), C265T (rs34599082), and G298A (rs13962) were genotyped. Associations of the polymorphisms with the odds of malaria, parasite species and manifestation were assessed. Among patients, vivax malaria (70%) predominated over falciparum malaria (9%) and mixed species infections (21%). DARC T-33C was absent and C265T was rare (1%). FYB carriage (deduced from DARC G125A) was not associated with the risk of malaria per se but it protected against severe falciparum malaria (P = 0.03), and hospitalization (P = 0.006) due to falciparum malaria. Vice versa, carriage of DARC 298A was associated with increased odds of malaria (aOR, 1.46 (1.07-1.99), P = 0.015) and vivax malaria (aOR, 1.60 (1.14-2.22), P = 0.006) and with several reported symptoms and findings of the patients. This report from southern India is the first to show an independent effect of the DARC 298A polymorphism on the risk of malaria. Functional studies are required to understand the underlying mechanism. Moreover, FYB carriage appears to protect against severe falciparum malaria in southern India.


Troponin elevation after percutaneous coronary intervention directly represents the extent of irreversible myocardial injury: insights from cardiovascular magnetic resonance imaging.
Although troponin elevation after percutaneous coronary intervention (PCI) is common, uncertainties remain about the mechanisms of its release and its relationship to the volume of myocardial tissue loss. Delayed-enhancement MRI of the heart has been shown to reliably quantify areas of irreversible myocardial injury. To investigate the quantitative relationship between irreversible injury and cardiac troponin release, we studied the incidence and extent of new irreversible injury in patients undergoing PCI and correlated it to postprocedural changes in cardiac troponin I. Fifty patients undergoing PCI were studied with preprocedural and postprocedural (24 hours) delayed-enhancement MRI for assessment of new irreversible myocardial injury. Cardiac troponin I measurements were obtained before PCI and 24 hours after PCI. Of these 50 patients, 24 underwent a further third MRI scan at a median of 8 months after the procedure. Mean patient age was 64+/-12 years. After the procedure, 14 patients (28%) had evidence of new myocardial hyperenhancement, with a mean mass of 6.0+/-5.8 g, or 5.0+/-4.8% of total left ventricular mass. All of these patients had raised troponin I levels (range 1.0 to 9.4 mug/L). Thirty-four patients (68%) had no elevated troponin I and no evidence of new myocardial necrosis on MRI. There was a strong correlation between the rise in troponin I measurements at 24 hours and mean mass of new myocardial hyperenhancement, both early (r=0.84; P<0.001) and late (r=0.71; P<0.001) after PCI, although there was a trend for a reduction in the size of PCI-induced myocardial injury in the late follow-up scan (P=0.07). In the setting of PCI, patients demonstrating postprocedural elevation in troponin I have evidence of new irreversible myocardial injury on delayed-enhancement MRI. The magnitude of this injury correlates directly with the extent of troponin elevation.


Pathophysiology, diagnosis and treatment of non-erosive reflux disease (NERD).
Up to 70% of patients with typical symptoms of gastroesophageal reflux disease (GERD) have neither definite endoscopic oesophageal breaks nor Barrett's oesophagus at upper endoscopy. These patients suffer from non-erosive reflux disease (NERD), also termed endoscopy-negative reflux disease or symptomatic GERD. NERD patients appear as a heterogeneous population with multiple and substantially different mechanisms implicated in the genesis of symptoms. In fact, patients with NERD may be divided into 3 groups on the basis of 24-hour pH monitoring: 1) patients with an abnormal acid exposure time (AET); 2) patients who demonstrate a normal AET, but in whom symptoms and reflux events are significantly correlated (hypersensitive oesophagus) and 3) patients with typical reflux symptoms but in whom all parameters of the pH study are normal. There is no gold standard for the diagnosis of NERD but a well-taken history can be, usually, sufficient to confirm the diagnosis and begin therapy. Thus, the more sensitive tool for the diagnosis of NERD is proton pump-inhibitor (PPI) test. The aims of NERD treatment are: symptoms relieve, restore quality of life and maintain clinical remission. Proton pump-inhibitors (PPIs) in full doses represent the treatment of choice of NERD patients, even if overall, clinical trials showed a lower efficacy in symptoms control when compared to patients with erosive oesophagitis. Patients with NERD often need long-term therapy for symptoms control. ''On demand'' PPI therapy has been considered as the most cost-effective strategy for the long-term treatment of NERD. In conclusion, many data indicate that NERD is a disorder in its own right that shares symptoms with other GERD groups. However further studies are needed to better define the natural history and improve the treatment of this disorder.


Minimal dose of aerosolized interferon-alpha in human subjects: biological consequences and side-effects.
Interferon-alpha (IFN-alpha) is a leucocyte-derived cytokine with pleiotropic effects on the cells of the immune system, including the ability to promote viral and microbial killing. This study was designed to evaluate the biologically active dosage of aerosolized lymphoblastoid IFN-alpha, in normal subjects and patients with chronic bronchitis, using serum 2'-5' oligoadenylate synthetase (OAS) as a marker of IFN-alpha activity. Three groups of subjects were included: two healthy groups and one of patients with chronic bronchitis. Group A (controls, n = 5) was studied in order to determine the minimal IFN-alpha dose able to induce biological effects without side-effects. IFN-alpha was given in a dose escalation trial including 0, 0.3 x 10(6), 1.0 x 10(6) and 3.0 x 10(6) IU.day-1 (5 day administration). Only the administration of 3.0 x 10(6) IU.day-1 of IFN-alpha induced a significant biological activity, increasing serum levels of OAS. Group B (controls, n = 5) and C (chronic bronchitis, n = 5) were given 3.0 x 10(6) IU.day-1 (10 day administration) in order to study serum, bronchoalveolar lavage fluid (BALF) and BALF cell modifications, after treatment. OAS serum levels and nitroblue tetrazolium (NBT) reduction tests, the latter used as a measure of phagocyte cell activity, increased both in normal subjects and in patients with chronic bronchitis. No significant change of serum IFN-alpha levels was found. It is concluded that aerosolized IFN-alpha administration to the lung is well-tolerated at biologically active doses. The activity can be monitored by quantifying OAS serum levels through a simple blood test.


Collective dynamics underpins Rayleigh behavior in disordered polycrystalline ferroelectrics.
Nanoscale and mesoscopic disorder and associated local hysteretic responses underpin the unique properties of spin and cluster glasses, phase-separated oxides, polycrystalline ferroelectrics, and ferromagnets alike. Despite the rich history of the field, the relationship between the statistical descriptors of hysteresis behavior such as Preisach density, and micro and nanostructure has remained elusive. By using polycrystalline ferroelectric capacitors as a model system, we now report quantitative nonlinearity measurements in 0.025-1 microm(3) volumes, approximately 10(6) times smaller than previously possible. We discover that the onset of nonlinear behavior with thickness proceeds through formation and increase of areal density of micron-scale regions with large nonlinear response embedded in a more weakly nonlinear matrix. This observation indicates that large-scale collective domain wall dynamics, as opposed to motion of noninteracting walls, underpins Rayleigh behavior in disordered ferroelectrics. The measurements provide evidence for the existence and extent of the domain avalanches in ferroelectric materials, forcing us to rethink 100-year old paradigms.


The application of polyphenols in food preservation.
Polyphenols are a kind of complex secondary metabolites in nature, widely exist in the flowers, bark, roots, stems, leaves, and fruits of plants. Numerous studies have shown that plant-derived polyphenols have a variety of bioactivities due to their unique chemical structure, such as antioxidant, antimicrobial, and prevention of chronic diseases, cardiovascular disease, cancer, osteoporosis, and neurodegeneration. With the gradual rise of natural product development, plant polyphenols have gradually become one of the research hotspots in the field of food science due to their wide distribution in the plants, and the diversity of physiological functions. Owing to the extraordinary antioxidant and antibacterial activity of polyphenols, plant-derived polyphenols offer an alternative to chemical additives used in the food industry, such as oil, seafood, meat, beverages, and food package materials. Based on this, this chapter provides an overview of the potential antioxidant and antibacterial mechanisms of plant polyphenols and their application in food preservation, it would be providing a reference for the future development of polyphenols in the food industry.


A new method for the analysis of tetramethyllead in blood.
In this paper a method for the determination of alkyllead compounds in blood is described. The method is based on extraction of the aklyllead compounds into an organic solvent, followed by separation by high-resolution gas chromatography. A graphite-furnace atomic absorption spectrophotometer is used as the detector. A detection limit of 0.01 micrograms/ml for tetramethyllead was obtained in blood samples. The method was used for the investigation of occupational exposure to tetramethyllead in gasoline. Blood samples from tank cleaners and gasoline pump servicemen showed detectable amounts of tetramethyllead. The reference group did not show any detectable levels of tetramethyllead.


MRI of soft tissue tumors.
Magnetic resonance imaging (MRI) is the only noninvasive method of defining a soft tissue tumor. The extent of the tumor and the question of involvement or noninvolvement of various adjacent tissues and structures can be determined. This information, determination of lymphatic and distant metastatic spread, is invaluable for staging and management of the disease. Whether or not the tumor type can be reliably determined, or even whether the malignant or benign nature of the tumor can be ascertained on MRI examination, is open to question. Review of the literature indicates proponents on both sides of the issue. This review illustrates the imaging features that are relevant to suggesting a histologic diagnosis, and the pitfalls that are encountered in trying to determine the malignancy or benignity of a lesion. The clinical significance of these determinations is also discussed.


[The effect of bromocryptin on rotational activity in rats].
The experiments were made in rats with unilateral lesion to the nigrostriatal tract, which was induced by the highly active dopaminergic neurotoxin 1-methyl-4-phenyl-pyridinium. The rotational activity of rats was evaluated after intragastric and subcutaneous bromocryptine given in a single dose of 10 mg/kg and 25 mg/kg one, two, three and four times. The highest effect of the drug was seen when it was used in the maximum dose of 25 mg/kg, but when the agent is repeatedly given in the above dose, it failed to enhance the rotational activity of rats. The findings may provide evidence for possibilities of increasing the doses of bromocryptine in practical medicine, and for designing the injectable dosage form of the drug.


How reliable and safe is full-body low-dose radiography (LODOX Statscan) in detecting foreign bodies ingested by adults?
Foreign body ingestion is common and potentially lethal. This study evaluates the use of low-dose Statscans (LODOX) in emergency departments. This comparative cross-sectional study retrospectively assessed 28289 digital chest x-rays and 2301 LODOX scans performed between 2006 and 2010 at a tertiary emergency centre. The radiographic appearance, image quality and location of ingested foreign bodies were evaluated in standard digital chest and LODOX radiography. The mean irradiation (μSv) and cumulative mean radiation dose per patient with the ingested foreign body were calculated according to literature-based data, together with the sensitivity and specificity for each modality. A total of 62 foreign bodies were detected in 39 patients, of whom 19 were investigated with LODOX and 20 with conventional digital chest radiography. Thirty-three foreign bodies were located in the two upper abdominal quadrants, 21 in the lower quadrants-which are not visible on conventional digital chest radiography-seven in the oesophagus and one in the bronchial system. The sensitivity and specificity of digital chest radiography were 44.4% and 94.1%, respectively, and for the LODOX Statscan 90% and 100%, respectively. The calculated mean radiation dose for LODOX investigations was 184 μS, compared with 524 μS for digital chest radiography. LODOX Statscan is superior to digital chest radiography in the diagnostic work-up of ingested foreign bodies because it makes it possible to enlarge the field of view to the entire body, has higher sensitivity and specificity, and reduces the radiation dose by 65%.


Harnessing the PI3K/Akt/mTOR pathway in T-cell acute lymphoblastic leukemia: eliminating activity by targeting at different levels.
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignant hematological disorder arising in the thymus from T-cell progenitors. T-ALL mainly affects children and young adults, and remains fatal in 20% of adolescents and 50% of adults, despite progress in polychemotherapy protocols. Therefore, innovative targeted therapies are desperately needed for patients with a dismal prognosis. Aberrant activation of PI3K/Akt/mTOR signaling is a common event in T-ALL patients and portends a poor prognosis. Preclinical studies have highlighted that modulators of PI3K/Akt/mTOR signaling could have a therapeutic relevance in T-ALL. However, the best strategy for inhibiting this highly complex signal transduction pathway is still unclear, as the pharmaceutical companies have disclosed an impressive array of small molecules targeting this signaling network at different levels. Here, we demonstrate that a dual PI3K/PDK1 inhibitor, NVP-BAG956, displayed the most powerful cytotoxic affects against T-ALL cell lines and primary patients samples, when compared with a pan class I PI3K inhibitor (GDC-0941), an allosteric Akt inhibitor (MK-2206), an mTORC1 allosteric inhibitor (RAD-001), or an ATP-competitive mTORC1/mTORC2 inhibitor (KU63794). Moreover, we also document that combinations of some of the aforementioned drugs strongly synergized against T-ALL cells at concentrations well below their respective IC50. This observation indicates that vertical inhibition at different levels of the PI3K/Akt/mTOR network could be considered as a future innovative strategy for treating T-ALL patients.


Temperament as a predictor of symptomatology in children: addressing contamination of measures.
Temperament has been conceptualized as an important predictor of children's psychological adjustment. However, even with reliable and valid measures, there is the additional problem of overlapping item content across measures of temperament and symptoms that threatens the interpretability of such associations. This study assessed this possible confounding using both confirmatory factor analysis (CFA) and expert ratings. A number of items from temperament measures of negative and positive emotionality, impulsivity, and attention focusing were shown to overlap with items measuring depressive and conduct problem symptoms. CFAs demonstrated that temperament could be reliably measured after eliminating overlapping items. Negative emotionality and impulsivity showed a positive relation to symptom measures, whereas positive emotionality and attention showed a negative relation to symptom measures. The pattern of associations indicated consistent relations between negative emotionality and depression and between impulsivity and conduct problems. The results show that even after removal of the threat to validity presented by overlap in measures, there continue to be significant, interpretable relations between temperament and symptoms.


AGR2, a mucinous ovarian cancer marker, promotes cell proliferation and migration.
Ovarian cancer is a leading cause of death in women. Early detection of ovarian cancer is essential to decrease mortality. However, the early diagnosis of ovarian cancer is difficult due to a lack of clinical symptoms and suitable molecular diagnostic markers. Thus, identification of meaningful tumor biomarkers with potential clinical application is clearly needed. To search for a biomarker for the early detection of ovarian cancer, we identified human anterior gradient 2 (AGR2) from our systematic analysis of paired normal and ovarian tumor tissue cDNA microarray. We noted a marked overexpression of AGR2 mRNA and protein in early stage mucinous ovarian tumors compared to normal ovarian tissues and serous type ovarian tumors by Western blot analysis and immunohistochemistry. To further elucidate the role of AGR2 in ovarian tumorigenesis, stable 2774 human ovarian cancer cell lines overexpressing AGR2 were established. Forced expression of AGR2 in 2774 cells enhanced the growth and migration of ovarian cancer cells. AGR2 protein was detected in the serum of mucinous ovarian cancer patients by Western blot and ELISA analysis. Thus, AGR2 is a potential biomarker for the diagnosis of mucinous ovarian cancer and an ELISA assay may facilitate the early detection of mucinous ovarian cancer using patient serum.


Early onset severe pre-eclampsia: expectant management at a secondary hospital in close association with a tertiary institution.
Early onset severe pre-eclampsia is ideally managed in a tertiary setting. We investigated the possibility of safe management at secondary level, in close co-operation with the tertiary centre. Prospective case series over 39 months. Secondary referral centre. All women (n= 131) between 24 and 34 weeks of gestation with severe pre-eclampsia, where both mother and fetus were otherwise stable. After admission, frequent intensive but non-invasive monitoring of mother and fetus was performed. Women were delivered on achieving 34 weeks, or if fetal distress or major maternal complications developed. Transfer to the tertiary centre was individualised. Prolongation of gestation, maternal complications, perinatal outcome and number of tertiary referrals. Most women [n= 116 (88.5%)] were managed entirely at the secondary hospital. Major maternal complications occurred in 44 (33.6%) cases with placental abruption (22.9%) the most common. One maternal death occurred and two women required intensive care admission. A mean of 11.6 days was gained before delivery with the mean delivery gestation being 31.8 weeks. The most frequent reason for delivery was fetal distress (55.2%). There were four intrauterine deaths. The perinatal mortality rate (> or =1000 g) was 44.4/1000, and the early neonatal mortality rate (> or =500 g) was 30.5/1000. The maternal and perinatal outcomes are comparable to those achieved by other tertiary units. This model of expectant management of early onset, severe pre-eclampsia is encouraging but requires close co-operation between secondary and tertiary institutions. Referrals to the tertiary centre were optimised, reducing their workload and costs, and patients were managed closer to their communities.


Advances in the Treatment of Cholinergic Anti-Inflammatory Pathways in Gastrointestinal Diseases by Electrical Stimulation of Vagus Nerve.
The cholinergic anti-inflammatory pathway (CAIP) has been proposed as a key mechanism by which the brain, through the vagus nerve (VN), modulates the immune system in the body. Recent studies of VN stimulation (VNS) in vivo systems have shown that it plays an anti-inflammatory role through CAIP. Inflammatory diseases in the gastrointestinal tract are frequent and difficult to treat. The mechanism of the anti-inflammatory effect of VNS through CAIP is not fully known. The current review covers anatomy, molecular mechanisms, and the application in gastrointestinal diseases of the vagal CAIP. Key Messages: CAIP bridges immune and nervous systems and plays pleiotropic roles in modulating inflammation in animal models by targeting different immune, proinflammatory, epithelial and endothelial cells, and signaling pathways. Numerous animal studies have shown beneficial effects of stimulation of this pathway in models of inflammatory diseases, either through (electrical) stimulation of the VN or pharmacological approaches. In this review, we focus on the anti-inflammatory benefits of VNS as a means of providing new insights into treating inflammation-related gastrointestinal diseases, as exemplified by those described herein.


Unwanted and wanted exposure to online pornography in a national sample of youth Internet users.
The goal was to assess the extent of unwanted and wanted exposure to online pornography among youth Internet users and associated risk factors. A telephone survey of a nationally representative sample of 1500 youth Internet users aged 10 to 17 years was conducted between March and June 2005. Forty-two percent of youth Internet users had been exposed to online pornography in the past year. Of those, 66% reported only unwanted exposure. Multinomial logistic regression analysis was used to compare youth with unwanted exposure only or any wanted exposure with those with no exposure. Unwanted exposure was related to only 1 Internet activity, namely, using file-sharing programs to download images. Filtering and blocking software reduced the risk of unwanted exposure, as did attending an Internet safety presentation by law enforcement personnel. Unwanted exposure rates were higher for teens, youth who reported being harassed or sexually solicited online or interpersonally victimized offline, and youth who scored in the borderline or clinically significant range on the Child Behavior Checklist subscale for depression. Wanted exposure rates were higher for teens, boys, and youth who used file-sharing programs to download images, talked online to unknown persons about sex, used the Internet at friends' homes, or scored in the borderline or clinically significant range on the Child Behavior Checklist subscale for rule-breaking. Depression also could be a risk factor for some youth. Youth who used filtering and blocking software had lower odds of wanted exposure. More research concerning the potential impact of Internet pornography on youth is warranted, given the high rate of exposure, the fact that much exposure is unwanted, and the fact that youth with certain vulnerabilities, such as depression, interpersonal victimization, and delinquent tendencies, have more exposure.


Stress biomarkers' associations to pain in the neck, shoulder and back in healthy media workers: 12-month prospective follow-up.
Physiological and psychological mechanisms have been proposed to link stress and musculoskeletal pain (MSP), and a number of stress biomarkers in patients with chronic pain have shown to be associated with stress-related disorders as well as health and recovery. The aim was to study if similar results might be found in a working population, in stress and computer intensive occupations with mild/moderate pain in neck, shoulder and back. The questions were if there are: (1) associations between self rated neck, shoulder and back pain (VAS) on one hand and stress-related (catabolic), recovery related (anabolic) variables, cardiovascular/lifestyle factors and immune markers on the other hand. (2) associations between long term changes in pain and stress marker values (6 month period). (3) predictive values in stress biomarkers for pain (12 month period) A study group with 121 media workers, 67 males (average 45 years) and 53 females (average 43 years), at three news departments of a media company was recruited. Pain occurrence and pain level in neck, shoulder, upper and low back were self-rated at three times with a 6-month interval towards the last month. Stress biomarker sampling was performed, at the same intervals. An additional similar questionnaire with momentary ratings focusing on "at present" i.e. within the same hour as stress biomarker sampling was performed. There were no changes in medicine intake or computer working hours during the 12 month study period. The total pain level and prevalence of pain decreased between baseline and 12 months follow-up. The rate of participation was 95%. Cross-sectional analyses on differences in stress biomarkers in groups of "no pain" and "pain" showed less beneficial stress biomarker levels (P < 0.05) in the "pain" group after age and gender adjustments in: S-DHEA-S and P-endothelin, S-insulin and P-fibrinogen. Analyses of each gender separately, adjusted for age, revealed in males differences in S-insulin, saliva cortisol 3, and P-endothelin. Furthermore, tendencies were seen in BMI, P-fibrinogen, and S-testosterone. In the female "pain" group a less beneficial P-BNP level was found. Longitudinal analysis of changes in pain levels and stress biomarkers within an interval of 6 months showed beneficial changes in the following stress markers: P-NPY, S-albumin, S-growth hormone and S-HDL when pain decreased, and vice versa when pain increased. Linear regression analyses showed statistically significant predicting values at the initial test instance for pain 12 months later in lower S-DHEA-S and S-albumin and higher B-HbA1c and P-fibrinogen. In stepwise regression and after age and gender adjustments, the associations with S-DHEA-S remained statistically significant. The present study shows that individuals in working life with a high level of regenerative/anabolic activity have less pain than other subjects, and that decreased regenerative/anabolic activity is associated with increasing pain. The levels of NPY, albumin, GH and HDL increased when pain decreased and vice versa. Low DHEA-S predicted pain 12 months later. These findings might contribute to increased knowledge about strategies to prevent further progression of neck/shoulder/back pain in persons who are "not yet in chronic pain".


[Comparison of recovery time of bolus and continuous infusion mivacurium.].
Mivacurium is a short-acting neuromuscular blocker (NMB), with total duration not exceeding 24 minutes. Early publications have reported no significant differences in recovery time, regardless of the route administration. However, clinical experience points out to longer recovery times when the drug is administered in continuous infusion. This study aimed at comparing recovery time of bolus administration and continuous infusion of mivacurium in a group of young adult patients. Forty young patients with no neuromuscular disease were enrolled in the study. Patients were premedicated with midazolam and monitored in the OR with ECG in D II and non-invasive automatic blood pressure. All patients received propofol and fentanyl and anesthesia was maintained with isoflurane, nitrous oxide and oxygen. Accelerometric neuromuscular transmission monitor was installed after induction and capnograph and gases analyzer were installed after intubation. Patients were divided in 2 equal groups according to mivacurium administration regimen: group 1 received initial bolus dose alone, and group 2, after the initial bolus dose and having recovered 10% of T1, received continuous infusion to maintain T1 within this value. For both groups, T1 and T4/T1 values were recorded during recovery, as from T1 in 10% of initial response, every minute up to 30 minutes. Demographics were homogeneous between groups. Group 2 had slower recovery as compared to group 1. There have been major variations in infusion doses among patients and for the same patient during infusion. In young adult patients without evidences of disease, mivacurium recovery is longer after continuous infusion as compared to bolus infusion. As a consequence of infusion dose variation among patients and for each patient, we recommend the use of neuromuscular transmission monitor to maintain constant and stable relaxation.


GOLPH3 promotes glioblastoma cell migration and invasion via the mTOR-YB1 pathway in vitro.
The identification of genes involved in carcinogenesis and tumor progression is of great interest, since these genes might be possible as candidates for new tumor targeted therapy strategies. Our previous study shows that Golgi phosphoprotein 3 (GOLPH3) is involved in glioma cell migration and invasion, the critical characteristics of malignant gliomas. In this study, we explored the mechanism of GOLPH3 affecting cell migration and invasion and found that GOLPH3 promotes glioblastoma (GBM) cell migration and invasion via the mammalian target of rapamycin(mTOR)-Y-box binding protein-1 (YB1) pathway in vitro. Both the protein levels of GOLPH3 and YB1 were up-regulated in human glioma tissues and they exhibited direct correlation with each other. In addition, down-regulation of GOLPH3 inhibited glioma cell migration and invasion, while over-expression of GOLPH3 enhanced them. Meanwhile, GOLPH3 down-regulation led to a significant decrease of YB1 level as well as mTOR activity, both required for glioma cell migration and invasion. On the contrary, YB1 level and mTOR activity increased after GOLPH3 over-expression. YB1 down-regulation or mTOR ATP site inhibitor INK128 treatment inhibited cell migration and invasion, similar to the effect of GOLPH3 down-regulation. Furthermore, over-expression of GOLPH3 induced glioma cell migration and invasion was blocked by INK128 and YB1 down-regulation. Taken together, these results show that GOLPH3 promotes glioblastoma cell migration and invasion via the mTOR-YB1pathway, indicating that GOLPH3-mTOR-YB1 pathway might be a new therapeutic target for glioma treatment.


Molecular contacts for chlorosome envelope proteins revealed by cross-linking studies with chlorosomes from Chlorobium tepidum.
Chlorosomes are unique light-harvesting antennae found in two phyla of green bacteria: Chlorobi and Chloroflexi. In the green sulfur bacterium Chlorobium tepidum, 10 proteins (CsmA, CsmB, CsmC, CsmD, CsmE, CsmF, CsmH, CsmI, CsmJ, and CsmX) exist in the chlorosome envelope. Chlorosomes from the wild type and mutants lacking a single chlorosome protein were cross-linked with the zero-length cross-linker 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide (EDC) and analyzed by gel electrophoresis. Similar cross-linking products were observed when the time and temperature were varied or when EDC was replaced with glutaraldehyde. Specific interactions between chlorosome proteins in cross-linked products were identified by immunoblotting with polyclonal antibodies raised against recombinant chlorosome proteins. We confirmed these interactions by demonstrating that these products were missing in appropriate mutants. Confirming the location of CsmA in the paracrystalline baseplate, cross-linking showed that CsmA forms dimers, trimers, and homomultimers as large as dodecamers and that CsmA directly interacts with the Fenna-Matthews-Olson protein. Cross-linking further suggests that the precursor form of CsmA is inserted near the edges of the baseplate, where CsmA and pre-CsmA interact with CsmB and CsmF. Several chlorosome proteins, including CsmA, CsmC, CsmD, CsmH, CsmI, CsmJ, and CsmX, were shown to exist as homomultimers in the chlorosome envelope. On the basis of the structural information obtained from these cross-linking experiments, a model for the locations and interactions of the proteins of the chlorosome envelope is proposed.


Differential requirements for hematopoietic commitment between human and rhesus embryonic stem cells.
Progress toward clinical application of ESC-derived hematopoietic cellular transplantation will require rigorous evaluation in a large animal allogeneic model. However, in contrast to human ESCs (hESCs), efforts to induce conclusive hematopoietic differentiation from rhesus macaque ESCs (rESCs) have been unsuccessful. Characterizing these poorly understood functional differences will facilitate progress in this area and likely clarify the critical steps involved in the hematopoietic differentiation of ESCs. To accomplish this goal, we compared the hematopoietic differentiation of hESCs with that of rESCs in both EB culture and stroma coculture. Initially, undifferentiated rESCs and hESCs were adapted to growth on Matrigel without a change in their phenotype or karyotype. Subsequent differentiation of rESCs in OP9 stroma led to the development of CD34(+)CD45(-) cells that gave rise to endothelial cell networks in methylcellulose culture. In the same conditions, hESCs exhibited convincing hematopoietic differentiation. In cytokine-supplemented EB culture, rESCs demonstrated improved hematopoietic differentiation with higher levels of CD34(+) and detectable levels of CD45(+) cells. However, these levels remained dramatically lower than those for hESCs in identical culture conditions. Subsequent plating of cytokine-supplemented rhesus EBs in methylcellulose culture led to the formation of mixed colonies of erythroid, myeloid, and endothelial cells, confirming the existence of bipotential hematoendothelial progenitors in the cytokine-supplemented EB cultures. Evaluation of four different rESC lines confirmed the validity of these disparities. Although rESCs have the potential for hematopoietic differentiation, they exhibit a pause at the hemangioblast stage of hematopoietic development in culture conditions developed for hESCs.


Synapses form in skeletal muscles lacking neuregulin receptors.
The formation of the neuromuscular junction (NMJ) is directed by reciprocal interactions between motor neurons and muscle fibers. Neuregulin (NRG) and Agrin from motor nerve terminals are both implicated. Here, we demonstrate that NMJs can form in the absence of the NRG receptors ErbB2 and ErbB4 in mouse muscle. Postsynaptic differentiation is, however, induced by Agrin. We therefore conclude that NRG signaling to muscle is not required for NMJ formation. The effects of NRG signaling to muscle may be mediated indirectly through Schwann cells.


Up-regulation of the Kv3.4 potassium channel subunit in early stages of Alzheimer's disease.
Gene expression throughout the different stages of Alzheimer's disease was analysed in samples from cerebral cortex. The gene encoding the voltage-gated potassium channel Kv3.4 was already overexpressed in early stages of the disease, and in advanced stages Kv3.4 was present at high levels in neurodegenerative structures. This subunit regulates delayed-rectifier currents, which are primary determinants of spike repolarization in neurones. In unique samples from a patient with Alzheimer's disease whose amount of amyloid plaques was decreased by beta amyloid immunization, Kv3.4 was overexpressed. The channel subunit was expressed in the neuropil, in the remaining conventional plaques in the frontal cortex and in collapsed plaques in the orbitary cortex. Therefore, amyloid deposition in plaques does not seem to be responsible for the increase in Kv3.4 levels. Nevertheless, Kv3.4 up-regulation is related to amyloid pathology, given that transgenic mice with the Swedish mutation of amyloid precursor protein showed increased expression of Kv3.4. Up-regulation of voltage-gated potassium channel subunits alters potassium currents in neurones and leads to altered synaptic activity that may underlie the neurodegeneration observed in Alzheimer's disease. Thus, Kv3.4 likely represents a novel therapeutic target for the disease.


Lack of association of MYO9B genetic variants with coeliac disease in a British cohort.
Development of coeliac disease involves an interaction between environmental factors (especially dietary wheat, rye, and barley antigens) and genetic factors (there is strong inherited disease susceptibility). The known human leucocyte antigen (HLA)-DQ2 and -DQ8 association explains only a minority of disease heritability. A recent study in the Dutch population suggested that genetic variation in the 3' region of myosin IXB (MYO9B) predisposes to coeliac disease. MYO9B is a Rho family GTPase activating protein involved in epithelial cell cytoskeletal organisation. MYO9B is hypothesised to influence intestinal permeability and hence intestinal antigen presentation. Four single nucleotide polymorphisms were chosen to tag all common haplotypes of the MYO9B 3' haplotype block (exons 15-27). We genotyped 375 coeliac disease cases and 1366 controls (371 healthy and 995 population based). All individuals were of White UK Caucasian ethnicity. UK healthy control and population control allele frequencies were similar for all MYO9B variants. Case control analysis showed no significant association of any variant or haplotype with coeliac disease. Genetic variation in MYO9B does not have a major effect on coeliac disease susceptibility in the UK population. Differences between populations, a weaker effect size than originally described, or possibly a type I error in the Dutch study might explain these findings.


Submicroscopic deletions in 5q- associated malignancies.
The deletion of the long arm of chromosome 5 is common in myelodysplastic syndromes (MDS) but is not limited to the 5q- syndrome as it is also seen in acute myeloid leukemia (AML), where it is often associated with other karyotypic aberrations. The aim of this study was to investigate whether deletions of known suppressor sequences occur in myeloid malignancies associated with 5q-. Thirty patients with MDS or AML were selected for the presence of a 5q karyotypic deletion, either isolated (19 cases) or associated with other chromosome changes (11 cases). Multiple fluorescent in situ hybridization (FISH) in interphase nuclei was applied in all cases using a panel of eleven probes for known suppressor genes or loci deleted in MDS/AML. Metaphase FISH was also performed to clarify discrepancies between conventional and molecular cytogenetics. No additional deletions were found in nineteen cases with an isolated 5q-. Mono-allelic deletions where found in 9/11 cases, 3 of which were related to monosomies by conventional cytogenetics. Interphase-FISH showed p53, AML1, D13S25, NF1, or Ikaros in six out of nine (66%) patients with 5q- and additional karyotypic changes. Metaphase FISH was helpful in assigning some of these cryptic events to non-proliferating cells. Our study emphasizes that isolated 5q- is the marker of a highly stable clone in both MDS and AML. AML with isolated 5q- are molecularly closer to 5q- syndrome than to AML with complex changes. Interphase-FISH data strongly support a mutator phenotype underlying complex karyotypes with a 5q deletion.


NIR lanthanide luminescence by energy transfer from appended terpyridine-boradiazaindacene dyes.
Mononuclear trivalent lanthanide complexes with formula [Ln(L)(NO(3))(3)] [in which L=4,4-difluoro-8-(2':2'';6'':2'''-terpyridin-4''-yl)-1,3,5,7-tetramethyl-2,6-diethyl-4-bora-3a,4a-diaza-s-indacene (Boditerpy)] are reported for Ln=Yb, Nd, Er, La and Gd. According to the crystal structure of the Yb complex, the lanthanide ion is bound to the terdentate terpyridine and the inner coordination sphere of the nine-coordinate lanthanide ion is completed by three bidentate nitrate anions. The coordination polyhedron can be described as a distorted tricapped antiprism. The terpyridine chelate is almost planar and tilted by nearly 60 degrees from the indacene subunit. FT-IR spectra confirm the bidentate binding mode of the nitrate anions for the other complexes. NMR and ES-MS spectra (through characteristic isotopic patterns) confirm the chemical formulation. The complexes have high molar absorption coefficients in the visible spectral region (65,000 M(-1) cm(-1) at 529 nm) and display sizeable NIR luminescence (900 to 1600 nm, for Ln=Yb, Nd and Er), upon irradiation through the electronic state of the indacene moiety at 514 nm. Crystal-field splitting was analysed at low temperature. The quantum yield of the Yb solution (10(-4) M) in dichloromethane amounts to 0.31 %, corresponding to a sensitisation efficacy of the ligand of ca. 63 %.


Cryofocus fast gas chromatography combustion isotope ratio mass spectrometry for rapid detection of synthetic steroid use in sport doping.
Sports doping requires high precision carbon isotope ratio (CIR) analysis of endogenous steroids using gas chromatography-combustion isotope ratio mass spectrometry (GCC-IRMS), however methods are relatively slow and cumbersome. A cryofocusing fast GCC-IRMS (Cryofocus Fast GCC-IRMS) was developed and optimized with minimal peak broadening using a programmable temperature vaporization (PTV) inlet and a low dead volume narrow-bore continuous capillary combustion interface to an IRMS. PTV injection, followed with cryofocusing before steroid analytes were volatilized by a hot jet, was used to initiate chromatography. Compared to ramping temperature using a conventional GC oven, cryofocusing with hot jet volatilization reduced analysis time by a factor of 3 to 4 and reduced peak widths to ∼800 ms. Well separated peak isotope ratios were measured with SD(δ13C) < 0.5‰ over a range of 10-50 ng of each steroid on column and were accurate from 2 ng to 100 ng. Characterization of the current experimental system with well characterized pure steroid isotopic standards demonstrates how the technique can be applied to steroid mixtures derived from real urine samples. Cryofocus Fast GCC-IRMS advances toward the goal of routine CIR testing of steroids in all urine samples for doping control.


Functional impacts of NRXN1 knockdown on neurodevelopment in stem cell models.
Exonic deletions in NRXN1 have been associated with several neurodevelopmental disorders, including autism, schizophrenia and developmental delay. However, the molecular mechanism by which NRXN1 deletions impact neurodevelopment remains unclear. Here we used human induced pluripotent stem cells (hiPSCs) and human embryonic stem cells (hESCs) as models to investigate the functional impacts of NRXN1 knockdown. We first generated hiPSCs from skin fibroblasts and differentiated them into neural stem cells (NSCs). We reduced NRXN1 expression in NSCs via a controlled shRNAmir-based knockdown system during differentiation, and monitored the transcriptome alteration by RNA-Seq and quantitative PCR at several time points. Interestingly, half reduction of NRXN1 expression resulted in changes of expression levels for the cell adhesion pathway (20 genes, P = 2.8×10(-6)) and neuron differentiation pathway (13 genes, P = 2.1×10(-4)), implicating that single-gene perturbation can impact biological networks important for neurodevelopment. Furthermore, astrocyte marker GFAP was significantly reduced in a time dependent manner that correlated with NRXN1 reduction. This observation was reproduced in both hiPSCs and hESCs. In summary, based on in vitro models, NRXN1 deletions impact several biological processes during neurodevelopment, including synaptic adhesion and neuron differentiation. Our study highlights the utility of stem cell models in understanding the functional roles of copy number variations (CNVs) in conferring susceptibility to neurodevelopmental diseases.


Climate variability and change and their potential health effects in small island states: information for adaptation planning in the health sector.
Small island states are likely the countries most vulnerable to climate variability and longterm climate change. Climate models suggest that small island states will experience warmer temperatures and changes in rainfall, soil moisture budgets, prevailing winds (speed and direction), and patterns of wave action. El Niño events likely will strengthen shortterm and interannual climate variations. In addition, global mean sea level is projected to increase by 0.09-0.88 m by 2100, with variable effects on regional and local sea level. To better understand the potential human health consequences of these projected changes, a series of workshops and a conference organized by the World Health Organization, in partnership with the World Meteorological Organization and the United Nations Environment Programme, addressed the following issues: the current distribution and burden of climate-sensitive diseases in small island states, the potential future health impacts of climate variability and change, the interventions currently used to reduce the burden of climate-sensitive diseases, additional interventions that are needed to adapt to current and future health impacts, and the health implications of climate variability and change in other sectors. Information on these issues is synthesized and key recommendations are identified for improving the capacity of the health sector to anticipate and prepare for climate variability and change in small island states.


Effect of electro-acupuncture stimulation of different frequencies and intensities on ovarian blood flow in anaesthetized rats with steroid-induced polycystic ovaries.
Maintenance of ovarian blood flow (OBF) is suggested to be important for regular ovulation in women with polycystic ovaries (PCO). The purpose of the present study was to investigate whether electro-acupuncture (EA) of different frequencies and intensities can improve the OBF of anaesthetized rat in the animal model of PCO. PCO was experimentally induced by a single intramuscular (i.m.) injection of estradiol valerate (EV) in rats. Control rats were given i.m. injection of oil. The involvement of the two ovarian sympathetic nerves; superior ovarian nerve (SON) and plexus ovarian nerve (OPN), in OBF responses was elucidated by severance of SON and OPN in both control and PCO rats. How systemic circulatory changes affect OBF was evaluated by continuous recording of the blood pressure. OBF was measured on the surface of the ovary-using laser Doppler flowmetry. Acupuncture needles were inserted bilaterally into the abdominal and hind limb muscles and connected to an electrical stimulator. Two frequencies--2 Hz (low) and 80 Hz (high)--with three different intensities--1.5, 3, and 6 mA--were applied for 35 s. Low-frequency EA at intensities of 3 and 6 mA elicited significant increases in OBF in the Control group compared to baseline. In the PCO group the increases in OBF were significant only when stimulating with low-frequency EA at 6 mA. After severance of the ovarian sympathetic nerves, the increased response of OBF that had been induced by low-frequency EA in both the Control and PCO group was abolished, indicating that the OBF response is mediated via the ovarian sympathetic nerves. High-frequency EA at 6 mA significantly decreased OBF and mean arterial blood pressure (MAP) in the Control group compared to baseline. In the PCO group, the same stimulation produced similar decreases in MAP, but not in OBF. Low-frequency EA stimulation with a strong intensity (6 mA) increases OBF in rats with steroid-induced PCO whereas less strong intensity (3 mA) induces similar changes in control rats. Severance of the ovarian sympathetic nerves, abolish this OBF increase in both study groups, which suggests that the responses of OBF to EA are mediated via the ovarian sympathetic nerves.


Quantification of supercolonial traits in the yellow crazy ant, Anoplolepis gracilipes.
Supercoloniality is a social structure displayed by many invasive ant species, but there has been surprisingly little research quantifying the extent to which individual species display traits underlying such social organisation. This study quantifies three traits for the yellow crazy ant, Anoplolepis gracilipes Smith (Hymenoptera: Formicidae): little or no aggression between workers from different nests; the exchange of workers among nests; and resource exchange among nests, as well as supercolony structure arising from patterns of distribution and density of detections. Supercolonies displayed a structural continuum from being small ( < 10 ha) and "aggregated" with great continuity among detections through to being large (>10,000 ha) and "diffuse" with little continuity among detections. Smaller supercolonies had greater ant densities than larger supercolonies. In laboratory trials, no aggression was observed between workers from different nests sourced from different supercolonies, and paired nests merged within 24 hours. Workers lacked nest fidelity by rapidly populating artificial nests containing alien queens. The daily worker turnover rate per nest was estimated to be below 20%. Resources were readily moved among nests, with a resource being detected up to 13 m away from a source within 24 hours, and as far as 32 m after four days. The rate and distance of resource movement increased with increasing worker and nest density. This research has demonstrated that A. gracilipes displays supercoloniality equivalent to that of the well-studied Argentine ant Linepithema humile. Quantification of these traits is required for other supercolonial species to improve our understanding of this social strategy, especially for invasive ants to aid in understanding factors that promote invasion success and to improve management.


Antidepressants and the serotonin syndrome in general practice.
As a consequence of the greater use of agents affecting the serotonergic system, a syndrome of serotonin hyperstimulation has been recognized more frequently. The serotonin syndrome is characterized by a constellation of symptoms that include mental status changes, agitation, myoclonus, hyperreflexia, sweating, shivering, tremor, diarrhoea, lack of coordination, and fever. Deaths have been reported. To identify cases of the serotonin syndrome among patients prescribed a new antidepressant in general practice, and to determine doctors' awareness of the syndrome. Patients who were dispensed nefazodone in England between 1996 and 1997 were identified using dispensed prescription data. Prescribing doctors were sent questionnaires as part of a post-marketing surveillance study. Patients reported to have experienced two or more features of the serotonin syndrome were identified, and specific questionnaires were sent to their general practitioners. There was a 96.2% return rate of serotonin syndrome questionnaires. Nineteen cases met criteria for the syndrome (incidence = 0.4 cases per 1000 patient-months of treatment with nefazodone). Eight patients developed symptoms while taking nefazodone alone. Serotonergic symptoms were reported to a similar degree with five other antidepressants studied by the same method. In total, 85.4% of responding general practitioners were unaware of the serotonin syndrome. Improved awareness of the syndrome is needed within general practice. There is a need to distinguish the relatively minor serotonergic symptoms from those of a severe, life-threatening serotonin syndrome.


[Care of elderly subject with iron deficiency anaemia: evaluation of geriatric practice].
The anemia with iron deficiency is frequent in the elder subjects. Few studies have reported the practice of the geriatric medicine about anemia. A national survey asked geriatric medical practitioners of hospital geriatric ward from June till September, 2013. Questionnaires were sent, filled over the phone. On 568 sent questionnaires, 312 (55%) were filled. The frequency of the anemia is considered of 46 ± 21%. The definition of the anemia in an elderly person is on average 10.7 ± 0.8 g/dL, taking into account the situation of the patient. The wanted biological examinations are the haemoglobin and the ferritinaemia, but many people suggest measuring also folates and vitamin B12 given strong prevalence of comorbidity. Prevalence of iron deficiency anemia estimated between 20 and 80% because of high prevalence of mixed cause which modified the answer. The major causes were reported as of digestive, gynecological and post-operative origins. The treatment is proposed from 9 g/dL. The oral iron and the transfusions are the most quoted. The possibility of injectable iron is reported only by 17%, of the geriatricians. The answers of the geriatricians show strong coherences in the management of the iron deficiency anemia. Guidelines should be adapted for elderly people for exercice capacity, mainly on high frequency of mixed cases.


Role of temperature in the recombination reaction on dye-sensitized solar cells.
The performance of photovoltaic (PV) devices as a function of temperature is crucial for technical development and for accurate commercial information. Along with solar irradiance, temperature is the most important operating factor of the PV device performance. Normally, it is widely accepted that dye sensitized solar cells (DSC) show minimal energy efficiency dependence with temperature (20-60 °C). The energy efficiency in DSCs depends on the light absorption, charge transport (ohmic resistances) and recombination rates. In this study, the recombination reaction kinetics was studied within a wide temperature range. A unique laser assisted sealing technique that allows studying the temperature effect between -5 °C and 105 °C without electrolyte leakage or external contamination was used. To the best of our knowledge, this is the highest operating temperature ever considered in kinetic studies of liquid state DSCs. The electrochemical reaction between electrons and triiodide/iodide ions was shown to be the most important factor for determining the energy efficiency of DSCs as a function of temperature. It was concluded that the activation energy of the recombination reactions depends on the interface where it happens - TiO2/electrolyte and SnO2-F/electrolyte - and on the temperature. It was found that in addition to temperature having a deep influence on the recombination reaction rate, the energy of the injecting electron is also critical. These conclusions should provide solid ground for further developments in the DSCs and perovskite solar cells, and allow a better comparison of the energy efficiency of different PV technologies over a range of operating temperatures.


B lymphocytes may escape tolerance by revising their antigen receptors.
To explore mechanisms that prevent autoreactivity in nonautoimmune mice, endogenous immunoglobulin (Ig) light (L) chains that associate with a transgenic anti-DNA heavy chain were analyzed. The antibodies from splenic B cell hybridomas of such mice did not bind double-stranded DNA (dsDNA) and their L chain sequences showed a biased use of V kappa and J kappa gene segments. The 44 L chains in this survey were coded for by just 18 germline genes. Six of the genes, each belonging to a different V kappa group, were used more than once and accounted for three fourths of all sequences. Based on the distribution of V kappa genes, the L chain repertoire in this line of transgenic mice was estimated at 37 V kappa genes. The most frequently observed gene, a member of the V kappa 12/13 group, was identified in 16 hybrids. In addition, the majority of V kappa genes used J kappa 5. We interpret the skewed representation of V kappa and J kappa gene segments to result from negative selection. Based on the data, we suggest that V kappa rearrangements giving rise to anti-dsDNA reactivity are removed from the repertoire by a corrective mechanism capable of editing self-reactive Ig.


Toxocara cati larva migrans in domestic pigs--detected at slaughterhouse control in Norway.
Routine Trichinella meat inspection at the slaughterhouse detected one larva in a pooled batch of 100 pig samples. The larva was sent to the Norwegian Veterinary Institute (NVI) for species identification.Morphological examination revealed that the larva was not Trichinella spp. Molecular analysis was performed. PCR and sequencing of 5S/ITS identified the larva as Toxocara cati. A second round of digests was carried out at the meat inspection laboratory, in smaller batches to try to identify the infected animal. No further larvae were detected and it was not possible to identify which of the 100 animals the larva had come from. This is the first time that Toxocara cati has been reported in slaughterhouse pigs in Norway.Although the infected individual could not be identified, the meat originated from one of six potential farms. A small survey regarding rodent control and cats was sent to each of these farms. Cats had restricted access to food storage areas (two farms reported that cats had access) whilst none of the farms allowed cats into the production housing. Cats were, however, present on all the farms (mostly stray cats of unknown health status). Half of the farms also reported seeing rodents in the pig housing during the previous six months and half reported finding rodents in the feed and straw storage areas. We were unable to narrow down the source of infection - however contamination of food or bedding material, with cat faeces or infected rodents, in addition to the presence of infected rodents in pig housing remain potential routes of infection.


Interpersonal Relationships and Suicidal Ideation in Youth with Bipolar Disorder.
This study examines how relationship quality in family and peer domains are associated with suicidal ideation (SI) in youth with bipolar disorder (BP). We assessed 404 Course and Outcome of Bipolar Youth study participants for psychiatric disorders and SI at intake and for family/peer relationships the month after intake. Multivariate logistic regression examined associations between relationships and SI, controlling for significant covariates. There were 144 youth (36%) who reported SI at intake; bivariate analyses indicated they had significantly worse family/peer relationships. Multivariate analyses showed that family/peer relationships were associated with current SI, controlling for significant covariates. Results support associations between poor relationships and SI in BP youth, regardless of current mood symptom severity. Clinicians should assess relationships when completing risk assessments with BP youth.