Leptospirosis in American Samoa--estimating and mapping risk using environmental data.
The recent emergence of leptospirosis has been linked to many environmental drivers of disease transmission. Accurate epidemiological data are lacking because of under-diagnosis, poor laboratory capacity, and inadequate surveillance. Predictive risk maps have been produced for many diseases to identify high-risk areas for infection and guide allocation of public health resources, and are particularly useful where disease surveillance is poor. To date, no predictive risk maps have been produced for leptospirosis. The objectives of this study were to estimate leptospirosis seroprevalence at geographic locations based on environmental factors, produce a predictive disease risk map for American Samoa, and assess the accuracy of the maps in predicting infection risk. Data on seroprevalence and risk factors were obtained from a recent study of leptospirosis in American Samoa. Data on environmental variables were obtained from local sources, and included rainfall, altitude, vegetation, soil type, and location of backyard piggeries. Multivariable logistic regression was performed to investigate associations between seropositivity and risk factors. Using the multivariable models, seroprevalence at geographic locations was predicted based on environmental variables. Goodness of fit of models was measured using area under the curve of the receiver operating characteristic, and the percentage of cases correctly classified as seropositive. Environmental predictors of seroprevalence included living below median altitude of a village, in agricultural areas, on clay soil, and higher density of piggeries above the house. Models had acceptable goodness of fit, and correctly classified ∼84% of cases. Environmental variables could be used to identify high-risk areas for leptospirosis. Environmental monitoring could potentially be a valuable strategy for leptospirosis control, and allow us to move from disease surveillance to environmental health hazard surveillance as a more cost-effective tool for directing public health interventions.


Passive detection and localization of fatigue cracking in aluminum plates using Green's function reconstruction from ambient noise.
Recent theoretical and experimental studies have demonstrated that a local Green's function can be retrieved from the cross-correlation of ambient noise field. This technique can be used to detect fatigue cracking in metallic structures, owing to the fact that the presence of crack can lead to a change in Green's function. This paper presents a method of structural fatigue cracking characterization method by measuring Green's function reconstruction from noise excitation and verifies the feasibility of crack detection in poor noise source distribution. Fatigue cracks usually generate nonlinear effects, in which different wave amplitudes and frequency compositions can cause different nonlinear responses. This study also undertakes analysis of the capacity of the proposed approach to identify fatigue cracking under different noise amplitudes and frequency ranges. Experimental investigations of an aluminum plate are conducted to assess the cross-correlations of received noise between sensor pairs and finally to detect the introduced fatigue crack. A damage index is proposed according to the variation between cross-correlations obtained from the pristine crack closed state and the crack opening-closure state when sufficient noise amplitude is used to generate nonlinearity. A probability distribution map of damage is calculated based on damage indices. The fatigue crack introduced in the aluminum plate is successfully identified and oriented, verifying that a fatigue crack can be detected by reconstructing Green's functions from an imperfect diffuse field in which ambient noise sources exist locally.


Repeated positive acceleration exposure exacerbates endothelial dysfunction in high-fat-diet-induced hyperlipidemic rats.
It remains unclear whether exposure to repeated positive acceleration (+Gz) can exacerbate endothelial dysfunction on the basis of hyperlipidemia. The aim of this study was to investigate the effect of repeated +Gz exposure on endothelial function in high-fat-diet-induced hyperlipidemic rats. Male Sprague-Dawley rats were randomly divided into control, repeat +Gz exposure, high-fat diet (HFD), and +Gz + HFD groups. The rats in the +Gz group were exposed to +Gz and the rats in the HFD group were fed a diet with 2% cholesterol. The rats in the +Gz + HFD group received both the +Gz exposure and HFD. Eight weeks later, the endothelium-dependent relaxation of the aorta was tested and the ultrastructure of the endothelial cells was observed using transmission electron microscopy. Quantitative real-time polymerase chain reaction and Western blot were used to detect the mRNA and protein expression of endothelial function-associated proteins. Repeated +Gz exposure elevated the serum level of LDL-C in HFD rats. In the +Gz + HFD rats, the ACh-induced relaxation in the aorta rings was significantly attenuated and the endothelial cells of the aorta were dramatically damaged compared with HFD rats. Nitric oxide content and eNOS expression in the aortic tissue were markedly decreased and the oxidative stress was more serious in the +Gz + HFD rats compared with HFD rats. In addition, repeated +Gz exposure significantly increased serum ox-LDL level and LOX-1 expression in the aorta of HFD rats, thereby activating NF-κB p65 and upregulating the expression of interleukin 6, ICAM-1 and VAP-1. Repeated +Gz exposure promotes endothelial dysfunction in HFD-induced hyperlipidemic rats.


Serum bile acid level and fatty acid composition in Chinese children with non-alcoholic fatty liver disease.
To determine serum bile acid (BA) and fatty acid (FA) profiles in Chinese children with non-alcoholic fatty liver disease (NAFLD). A total 76 children aged 4-17 years were categorized into three groups according to the presence and absence of as well as the severity of NAFLD, that is, non-NAFLD (control), mild and moderate to severe NAFLD groups, respectively, based on their liver ultrasonography findings. Serum BA and FA profiles were quantified separately by mass spectrometry and gas chromatography. General linear models were performed to assess the differences among the groups. After adjusted for potential confounders, children with NAFLD had higher levels of chenodeoxycholic acid (CDCA), unconjugated primary BAs (CDCA + cholic acid) but lower levels of deoxycholic acid (DCA), taurodeoxycholic acid (TDCA), glycodeoxycholic acid (GDCA), total DCA (DCA + TDCA + GDCA), glycolithocholic acid (GLCA) and total lithocholic acid (GLCA + taurolithocholic acid) than children without NAFLD. As for FAs, children with mild and moderate to severe NAFLD had higher levels of n-7 monounsaturated FA. Circulating BA and FA profiles may change in children with NAFLD. Further studies are needed to determine their associations and to understand the underlying mechanism of action.


Advances in clotting factor treatment for congenital hemorrhagic disorders.
During the last 50 years, clotting factor replacement has evolved from the use of frozen plasma in the 1950s, through the serendipitous discovery of cryoprecipitate in the 1960s and the development of purified clotting factors in the 1970s and 1980s, to the era of recombinant clotting factors beginning in the 1990s. The dawn of the new millennium has seen the refinement of recombinant factor (rF) VIII with enhanced safety via the elimination of plasma-derived culture media or product stabilizers. During the last decade of the 20th century, a cure for hemophilia through gene therapy became a possibility. This was, in part, facilitated by availability of large (dogs) and small (mice) animal models for hemophilia A and B. Although this review will focus primarily on clotting factor replacement, the reader may refer to recent discourse on gene therapy for hemophilia.


Myotonic dystrophy associated with 47 XYY syndrome.
A case of myotonic dystrophy with 47 XYY presented with tall stature and mental retardation. The patient was a 37-year-old male. In addition to grip myotonia and percussion myotonia, severe weakness and atrophy were noted in the face and the neck muscles and in the distal muscles of the four limbs. He also had diabetes mellitus, cataracts and sexual behavior abnormalities. He was found to be 47 XYY from chromosomal examinations. The combination of 47 XYY syndrome and myotonic dystrophy has not been reported previously.


Cardiovascular risk factors in children and early prevention of heart disease.
Clinical and anatomical observations from the Bogalusa Heart Study over a 15-year span provide data on cardiovascular risk factors and the early natural history of arteriosclerosis. These studies established that: cardiovascular risk can be predicted in early life; interrelationships of risk factors in children are similar to those observed in adults; and concentrations of serum lipoproteins change during sexual maturation. Strategies involving the general population and high-risk groups should be considered to help reduce atherosclerosis and coronary artery disease. Active modification of risk factors in the general populace would include using such methods as screening, education, and mass-media campaigns. Educational promotion ("Heart Smart") has already been implemented in the New Orleans area, focusing on using the total school environment to teach cardiovascular health and to encourage children to adopt desirable lifestyles. Inclusion of cardiovascular health education into general educational studies of children should be a major objective of the future.


Millisecond kinetics of nanocrystal cation exchange using microfluidic X-ray absorption spectroscopy.
We describe the use of a flow-focusing microfluidic reactor to measure the kinetics of the CdSe-to-Ag2Se nanocrystal cation exchange reaction using micro-X-ray absorption spectroscopy (microXAS). The small microreactor dimensions facilitate the millisecond mixing of CdSe nanocrystals and Ag+ reactant solutions, and the transposition of the reaction time onto spatial coordinates enables the in situ observation of the millisecond reaction using microXAS. Selenium K-edge absorption spectra show the progression of CdSe nanocrystals to Ag2Se over the course of 100 ms without the presence of long-lived intermediates. These results, along with supporting stopped-flow absorption experiments, suggest that this nanocrystal cation exchange reaction is highly efficient and provide insight into how the reaction progresses in individual particles. This experiment illustrates the value and potential of in situ microfluidic X-ray synchrotron techniques for detailed studies of the millisecond structural transformations of nanoparticles and other solution-phase reactions in which diffusive mixing initiates changes in local bond structures or oxidation states.


Maximum-distention retrograde urethrocystography in healthy male dogs: occurrence of vesicoureteral reflux.
Twenty-four healthy, mature male Beagles were examined radiographically for vesicoureteral reflux (VUR) by maximum-distention retrograde urethrocystography. Bilateral VUR was observed in 9 dogs and unilateral VUR was observed in 3 dogs. The VUR occurred when the bladder was full or nearly full when maximum bladder filling was defined by trigonal-prostatic urethral dilation. The refluxed contrast medium reached the renal pelves in all but 3 of the 21 affected ureters.


The Pennsylvania Trauma Outcomes Study Risk-Adjusted Mortality Model: Results of a Statewide Benchmarking Program.
Trauma centers need objective feedback on performance to inform quality improvement efforts. The Trauma Quality Improvement Program recently published recommended methodology for case mix adjustment and benchmarking performance. We tested the feasibility of applying this methodology to develop risk-adjusted mortality models for a statewide trauma system. We performed a retrospective cohort study of patients ≥16 years old at Pennsylvania trauma centers from 2011 to 2013 (n = 100,278). Our main outcome measure was observed-to-expected mortality ratios (overall and within blunt, penetrating, multisystem, isolated head, and geriatric subgroups). Patient demographic variables, physiology, mechanism of injury, transfer status, injury severity, and pre-existing conditions were included as predictor variables. The statistical model had excellent discrimination (area under the curve = 0.94). Funnel plots of observed-to-expected identified five centers with lower than expected mortality and two centers with higher than expected mortality. No centers were outliers for management of penetrating trauma, but five centers had lower and three had higher than expected mortality for blunt trauma. It is feasible to use Trauma Quality Improvement Program methodology to develop risk-adjusted models for statewide trauma systems. Even with smaller numbers of trauma centers that are available in national datasets, it is possible to identify high and low outliers in performance.


Racial-ethnic identity in mid-adolescence: content and change as predictors of academic achievement.
Three aspects of racial-ethnic identity (REI)-feeling connected to one's racial-ethnic group (Connectedness), being aware that others may not value the in-group (Awareness of Racism), and feeling that one's in-group is characterized by academic attainment (Embedded Achievement)-were hypothesized to promote academic achievement. Youth randomly selected from 3 low-income, urban schools (n=98 African American, n=41 Latino) reported on their REI 4 times over 2 school years. Hierarchical linear modeling shows a small increase in REI and the predicted REI-grades relationship. Youth high in both REI Connectedness and Embedded Achievement attained better grade point average (GPA) at each point in time; youth high in REI Connectedness and Awareness of Racism at the beginning of 8th grade attained better GPA through 9th grade. Effects are not moderated by race-ethnicity.


Increased rate of cholic acid formation from 3 alpha,7 alpha-dihydroxy-5 beta-cholestane in perfused livers from diabetic rats.
The formation of bile acids from 3 alpha,7 alpha-dihydroxy-5 beta-cholestane was comparatively investigated in the perfused livers from normal, streptozotocin-diabetic, and insulin-treated diabetic rats. During the infusion of the sterol substrate, cholic acid accounted for only 11% of the total biliary bile acids in the normal rats, while it increased drastically to 57% in the diabetic rats. This increased proportion of cholic acid tended to be normalized by treatment of the diabetic animals with insulin. These results suggest the possible acceleration of cholic acid formation, involving 12 alpha-hydroxylation of 3 alpha,7 alpha-dihydroxy-5 beta-cholestane or one of its metabolites in an insulin-deficient state in rats.


Severe Bone Marrow Edema Among Patients Who Underwent Prior Marrow Stimulation Technique Is a Significant Predictor of Graft Failure After Autologous Chondrocyte Implantation.
Autologous chondrocyte implantation (ACI) is a well-established cartilage repair procedure; however, numerous studies have shown higher ACI graft failure rates after prior marrow stimulation techniques (MSTs). To identify which factors may predict decreased graft survival after ACI among patients who underwent a prior MST. A secondary aim was to investigate the specificity of these predictors. Case-control study; Level of evidence, 3. In this review of prospectively collected data, the authors analyzed 38 patients who had failed prior MST surgery and subsequently underwent collagen-covered ACI (case group). The case group was divided into graft failure ACI (n = 8, 21%) and successful ACI (n = 30, 79%). Fourteen clinical variables were categorized and analyzed to determine predictors for failure of the ACI graft: age, body mass index, sex, defect characteristics (number, size, location, etiology, type), presence of kissing lesion, intraoperative presence of intralesional osteophyte, time between an MST and ACI, previous surgery, duration of the symptoms, and concomitant surgical procedure. Preoperative magnetic resonance imaging (MRI) was used to evaluate the severity of subchondral bone marrow edema (BME), graded I (absent) to IV (severe), and the presence of subchondral cyst, hypertrophic sclerosis, and intralesional osteophyte. The effects of these MRI findings on the graft survivor were also investigated. Concurrently, a control group without a prior MST was matched to investigate the specificity of the previously determined predictors. These patients were matched individually according to age, sex, body mass index, and outcome of the procedure (failure [n = 8] or successful [n = 30] per the case group). In the case group, the presence of preoperative severe BME was significantly higher among patients with failed ACI as compared with patients with successful ACI (P < .001). In the control group, the presence of severe BME was not significantly different between the failure and successful groups (P = .747). The ACI graft failure rate among patients with a prior MST and preoperative grade IV BME was 83.7% at 5 years postoperatively, resulting in a significantly lower survival rate as compared with patients with a prior MST and without severe BME (5-year graft failure rate, 6.5%; P < .001). All the other parameters did not differ significantly. After a prior MST, the presence of grade IV BME by MRI was a predictive factor for graft failure among patients who then underwent second-generation ACI.


Botulinum toxin A in the treatment of Raynaud's phenomenon: a systematic review.
The management of Raynaud's phenomenon in its most severe form is challenging, and current medical and surgical treatment methods frequently do not lead to optimal symptom control and prevention of ischemic complications. The aim of the study was to critically evaluate all existing evidence on the use of botulinum toxin A in the management of Raynaud's phenomenon. We adopted the PRISMA methodology and searched Cochrane Library, MEDLINE, SCOPUS, EULAR and ACR congresses abstract archives for Raynaud* AND botulinum toxin OR onabotulinum. All studies that contained reports of botulinum toxin A use and its outcome in Raynaud's phenomenon were included in the review. Eleven studies met our inclusion criteria and involved a total of 125 patients. Two reviewers extracted data from the studies under review and achieved a consensus in their selection. The main outcomes measured were pain reduction and healing of digital ulcers. The level of evidence across studies was very low to moderate. There is insufficient evidence to assess the efficacy of botulinum toxin A in Raynaud's phenomenon. Despite many promising reports, further research in the form of randomized controlled trials is warranted in order to investigate this new treatment method for Raynaud's phenomenon.


Therapeutic hypothermia for stroke: Unique challenges at the bedside.
Therapeutic hypothermia has shown promise as a means to improving neurological outcomes at several neurological conditions. At the clinical level, it has been shown to improve outcomes in comatose survivors of cardiac arrest and in neonatal hypoxic ischemic encephalopathy, but has yet to be convincingly demonstrated in stroke. While numerous preclinical studies have shown benefit in stroke models, translating this to the clinical level has proven challenging. Major obstacles include cooling patients with typical stroke who are awake and breathing spontaneously but often have significant comorbidities. Solutions around these problems include selective brain cooling and cooling to lesser depths or avoiding hyperthermia. This review will cover the mechanisms of protection by therapeutic hypothermia, as well as recent progress made in selective brain cooling and the neuroprotective effects of only slightly lowering brain temperature. Therapeutic hypothermia for stroke has been shown to be feasible, but has yet to be definitively proven effective. There is clearly much work to be undertaken in this area.


Two large-exposure-ratio image fusion by improved morphological segmentation.
The fusion of two large-exposure-ratio images, especially in the rocket launch field, is a challenging task because of fast-moving objects and differential features from daily scenes. Based on the large-exposure-ratio images, we propose a principle of halo formation at the boundaries of over-exposed areas. To avoid the halos in the fusion images, an improved morphological segmentation (IMS) method is developed to segment the over-exposed regions and boundaries. The IMS method is inspired by the mountain topography and builds a bridge between the 3D patches and quadratic polynomial coefficients. An improved multiscale method with segmentation in high-exposed images is proposed. In the rocket launch observation experiment, we constructed a two-camera simultaneous imaging system to avoid the dynamic scenes. The result of our proposed fusion method could best preserve the details and colors of the flames in low-exposed images and has the best subjective observation. The objective matrices also demonstrate superior edge and contrast performances over mainstream methods.


Increased Cardiovascular Risk in Patients with Adrenal Insufficiency: A Short Review.
Cardiovascular disease (CVD) is the most common cause of death in the world. Recent studies have shown an association between adrenal insufficiency (AI) and increased cardiovascular risk (CVR). Patients with AI receive glucocorticoid (GC) replacement therapy which can lead to varying levels of blood cortisol. It was shown that these imbalances in blood cortisol may lead to a higher prevalence of coronary heart disease, major adverse coronary events, and increased mortality. GC substitution is essential in the treatment of AI without which the disease has been shown to be fatal. The most frequently used GC formula for replacement therapy is hydrocortisone (HC). There is no uniform opinion on hydrocortisone replacement therapy. Alternative GC such as prednisolone is also in use. Overreplacement of GC may lead to adverse effects including obesity, high blood pressure, and hyperglycaemia. Outcome may vary between primary and secondary AI mainly due to differences in the renin-angiotensin-aldosterone system (RAAS). Furthermore, decreased blood levels of cortisol may lead to a compensatory secretion of inflammatory mediators such as Interleukin-1 (IL-1), Interleukin-6 (IL-6), and/or tumor-necrosis factor (TNF). Physicians and patients should be properly educated about the increased risk of CVD in patients with AI.


Effect of Aromatase Inhibitor Therapy on Sleep and Activity Patterns in Early-stage Breast Cancer.
Adherence to aromatase inhibitor (AI) therapy is poor, often because of treatment-emergent side effects, including musculoskeletal symptoms, fatigue, and insomnia. In the present analysis, we examined the sleep patterns and daytime function both objectively using actigraphy and subjectively using validated questionnaires in women initiating AI therapy. Postmenopausal women with stage 0-III hormone receptor-positive breast cancer who were initiating AI therapy were eligible. The patients wore actigraphy devices for 10 consecutive days and completed questionnaires at baseline before the initiation of AI and after 3 months of AI therapy. Associations between the baseline demographics and symptoms, changes in patient-reported outcomes and actigraphy measures from baseline to 3 months of AI therapy and discontinuation of AI therapy were examined using sign tests, logistic regression models, Spearman's correlation, and linear mixed models. Forty-two patients (86%) completed the baseline assessments and 23 patients (47%) completed both the baseline and the 3-month assessments. Objectively measured daytime function as measured by total daytime activity decreased during the 3 months after starting AI (232,566 activity count vs. 204,205 activity count; P = .023), and the decrease was more evident in women with higher baseline physical function. Reduced daytime activity correlated with increased fatigue (ρ = -0.49; P = .017). Daytime function decreased after initiation of AI therapy and correlated moderately with increased fatigue, although no association was identified with changes in pain or sleep quality. Additional studies are required to understand why function is reduced, which could have implications for interventions to improve patient tolerance of, and persistence with, AI therapy.


Blockade of interleukin-6 signaling enhances hepatic steatosis but improves liver injury in methionine choline-deficient diet-fed mice.
Inflammatory processes have an important role in the development of hepatic steatosis and progression to nonalcoholic steatohepatitis (NASH). Interleukin-6 (IL-6) is known to be a proinflammatory cytokine, but also promotes liver regeneration and protects the liver against various forms of damage. The role of IL-6/Glycoprotein 130 (GP130) in NASH remains unclear. In this study, we determined whether blocking IL-6/GP130 signaling prevents progression of steatohepatitis in a mouse NASH model. Six-week-old male C57/BL6 mice were fed either chow control or a methionine choline-deficient (MCD) diet for 8 weeks. Half of the MCD diet-fed mice were treated with 15 mg/kg rat anti-mouse IL-6 receptor antibody (MR16-1), intraperitoneally twice weekly, the remainder and chow-fed mice were injected with 15 mg/kg rat IgG as a control. Hepatic steatosis, injury, fibrosis, apoptosis, markers of lipid peroxidation/oxidant stress and IL-6-related gene expressions were evaluated. MR16-1 treatment decreased signal transducer and activator of transcription 3 activities and expression of suppressor of cytokine signaling 3 in MCD diet-treated mouse livers. Although this treatment enhanced intrahepatic lipid accumulation accompanied by increased sterol regulatory element-binding protein 1 and decreased peroxisome proliferator-activated receptor-alpha expression, elevated plasma alanine aminotransferase levels were improved with decreased plasma free fatty acid levels, lipid peroxidation/oxidant stress and hepatic apoptosis. Blocking IL-6/GP130 signaling by MR16-1 enhanced MCD diet-induced hepatic steatosis, but ameliorated liver injury. These findings suggest that hepatic IL-6 signaling has a protective role against the progression of hepatic steatosis but may enhance liver inflammation.


The Glycoside Oleandrin Reduces Glioma Growth with Direct and Indirect Effects on Tumor Cells.
Oleandrin is a glycoside that inhibits the ubiquitous enzyme Na+/K+-ATPase. In addition to its known effects on cardiac muscle, recent in vitro and in vivo evidence highlighted its potential for anticancer properties. Here, we evaluated for the first time the effect of oleandrin on brain tumors. To this aim, mice were transplanted with human or murine glioma and analyzed for tumor progression upon oleandrin treatment. In both systems, oleandrin impaired glioma development, reduced tumor size, and inhibited cell proliferation. We demonstrated that oleandrin does the following: (1) enhances the brain-derived neurotrophic factor (BDNF) level in the brain; (2) reduces both microglia/macrophage infiltration and CD68 immunoreactivity in the tumor mass; (3) decreases astrogliosis in peritumoral area; and (4) reduces glioma cell infiltration in healthy parenchyma. In BDNF-deficient mice (bdnftm1Jae/J) and in glioma cells silenced for TrkB receptor expression, oleandrin was not effective, indicating a crucial role for BDNF in oleandrin's protective and antitumor functions. In addition, we found that oleandrin increases survival of temozolomide-treated mice. These results encourage the development of oleandrin as possible coadjuvant agent in clinical trials of glioma treatment.SIGNIFICANCE STATEMENT In this work, we paved the road for a new therapeutic approach for the treatment of brain tumors, demonstrating the potential of using the cardioactive glycoside oleandrin as a coadjuvant drug to standard chemotherapeutics such as temozolomide. In murine models of glioma, we demonstrated that oleandrin significantly increased mouse survival and reduced tumor growth both directly on tumor cells and indirectly by promoting an antitumor brain microenvironment with a key protective role played by the neurotrophin brain-derived neurotrophic factor.


The effect of the radiosensitizer misonidazole on motor nerve conduction velocity in the mouse.
The clinical use of misonidazole as a hypoxic cell radiosensitizer is at present limited by its neurotoxicity at high doses (Urtasun et al., 1977; Dische et al., 1977). An in vivo neurological end point, viz. measurement of nerve conduction velocity, has been developed to examine sensitizer action. Conduction velocity in mice was measured as a function of time after a single dose of misonidazole and as a function of drug dose. Doses greater than 0.33 mg/g produced significant transient reductions in velocity. The time course of the reduction in velocity closely followed the uptake/excretion profile of misonidazole from blood serum.


The dual-pathway model of binge eating: Is there a need for modification?
The dual-pathway model proposes that body dissatisfaction might lead to binge eating (BE) through restraint eating and negative affect. Both pathways have been confirmed longitudinally, but there is evidence that the affect-pathway might rather be found in the short-term, whereas other variables might be involved over longer periods. Research suggests that self-esteem represents a key-factor in the etiology of BE in adolescent girls and might serve as a mediator between body dissatisfaction and eating pathology. Based on these findings, the aim of this study was to investigate the original dual-pathway model across 20 months and to evaluate a modified version of the model with self-esteem instead of negative affect as a mediator in the affect-pathway. We assessed eating pathology, negative affect and self-esteem by self-report in a sample of 523 adolescent girls at two time points separated by 20 months. Data were analyzed using a cross-lagged panel design. Both, the original and the modified model provided good fit to the data, but results yielded limited support for the assumptions of the original model. Neither restraint eating nor negative affect mediated the link between body dissatisfaction and BE. The modified model fit the data slightly better and results indicated that low self-esteem mediated the relationship between body dissatisfaction and BE. Notably, our results indicated that restraint eating might even reduce the risk for BE through the enhancement of self-esteem. Results suggest that the dual-pathway model could benefit from the inclusion of a more trait-like variable such as self-esteem when evaluated across the long-term. Furthermore, our findings indicate that healthy restraint eating might have positive effects on self-esteem, thereby reducing risk for BE in adolescent girls, who are dissatisfied with their bodies.


Alginate encapsulation of Begonia microshoots for short-term storage and distribution.
Synthetic seeds were formed from shoot tips of two in vitro grown Begonia cultivars using 3% sodium alginate in Murashige and Skoog medium (MS) salt solution as the gel matrix and 100 mM calcium chloride for complexation. Synthetic seed formation was achieved by releasing the sodium alginate/explant combination into 100 mM calcium chloride (CaCl₂ ·H₂O) solution for 30 or 45 min. Both control and encapsulated shoots were transferred into sterile Petri dishes and stored at 4°C or 22°C for 0, 2, 4, 6, or 8 weeks. Conversion of synthetic seeds into plantlets for both storage environments was assessed in MS medium or peat-based substrate. No significant difference was found between the 30 and 45 min CaCl₂ ·H₂O treatments or the two cultivars. Encapsulation of explants improved survival rate over time irrespective of the medium type or storage environment. Survival rates of 88, 53, 28, and 11% for encapsulated microshoots versus 73, 13, 0, and 0% for control explants were achieved in microshoots stored for 2, 4, 6, and 8 weeks, respectively. The best results were obtained when synthetic seeds were stored at 4°C and germinated on MS medium. Regenerated plantlets were successfully established in potting soil.


Vermicomposting of Organic Waste with Eisenia fetida Increases the Content of Exchangeable Nutrients in Soil.
Vermicomposting is a green technique used to produce organic compost from organic waste with the aid of specific earthworm species. The resulting compost is rich in nutrients that can improve plant health and fertility. This study was conducted to produce organic compost using a developed vermicomposting technique. And that is to enhance and increase the exchangeable nutritional content in the soil for utilization in sustainable agriculture. The experiment was carried out with Eisenia fetida worms in a treatment technique using sugarcane straw, remnants of garden tree leaves, kitchen wastes and cow manure. The physiochemical parameters, namely temperature, moisture, acidity, electrical conductivity and 10 different nutrients, were assessed in vermicompost samples and garden soil sample (without earthworms). The results revealed higher N, C and P content in the vermicompost than in the garden soil sample. This study confirms that vermicompost has a high nutrient value and can be considered a promising method for safely disposing organic waste, improving crop production and achieving long-term food security.


Tenosynovial giant cell tumor.
Tenosynovial Giant Cell Tumor (TGCT) is a group of typically benign lesions arising from the synovium of joints, bursae and tendon sheaths. Depending on their growth pattern and clinical course, they are divided into localized and diffuse types. It is predominantly caused by a mutation in the stromal cells of the synovial membrane leading to overexpression of the colony stimulating factor 1 that recruits CSF1R-expressing cells of the mononuclear phagocyte lineage into the tumor mass. The lesions contain mainly histiocyte-like and synovial cells accompanied by varying numbers of multinucleated giant cells, mononuclear cells, foam cells, inflammatory cells and hemosiderin deposits. The gold standard for detect- ing and monitoring the disease is MRI, where the characteristic hemosiderin accumulation can be best appreciated, but it is a histological examination that is most conclusive. The main treatment is surgical resection of all pathological tissue, but radio- and chemotherapy are also viable options for certain groups of patients.


Au-PbS core-shell nanocrystals: plasmonic absorption enhancement and electrical doping via intra-particle charge transfer.
We present a comparative study of optical and electronic properties for PbS nanocrystals and Au-PbS core-shell nanostructures. In Au-PbS nanostructures, we observed two nontrivial synergistic effects: (i) extinction enhancement due to coupling of surface plasmon resonance in the Au core to the excitonic states in the semiconducting PbS shell, and (ii) strong p-type electronic doping of Au-PbS nanocrystal solids that we explained by the intraparticle charge transfer between the PbS shell and the Au core.


Comparison of two polymeric transition metal complexes with 1,4-benzenedicarboxylate ions as bridging ligands, [Co(C8H4O4)(C12H8N2)(H2O)] and [Cu(C8H4O4)(C10H9N3)].H2O.
The title complexes, catena-poly[[aqua(1,10-phenanthroline-kappa(2)N,N')cobalt(II)]-micro-benzene-1,4-dicarboxylato-kappa(2)O(1):O(4)], [Co(C(8)H(4)O(4))(C(12)H(8)N(2))(H(2)O)], (I), and catena-poly[[[(di-2-pyridyl-kappaN-amine)copper(II)]-micro-benzene-1,4-dicarboxylato-kappa(4)O(1),O(1'):O(4),O(4')] hydrate], [Cu(C(8)H(4)O(4))(C(10)H(9)N(3))].H(2)O, (II), take the form of zigzag chains, with the 1,4-benzenedicarboxylate ion acting as an amphimonodentate ligand in (I) and a bis-bidentate ligand in (II). The Co(II) ion in (I) is five-coordinate and has a distorted trigonal-bipyramidal geometry. The Cu(II) ion in (II) is in a very distorted octahedral 4+2 environment, with the octahedron elongated along the trans O-Cu-O bonds and with a trans O-Cu-O angle of only 137.22 (8) degrees.


Solvent Quality and Aggregation State of Asphaltenes on Interfacial Mechanics and Jamming Behavior at the Oil/Water Interface.
The formation of highly stable water-in-oil emulsions results in complications in both upstream and downstream processing. Emulsion stability in these systems has been connected to the adsorption of surface-active asphaltenes that are assumed to form a rigidified film at the oil/water (o/w) interface. Full characterization of this behavior is needed to allow for engineered solutions for enhanced oil recovery. Interfacial properties, such as surface pressure and interfacial elasticity, are implicated in the stabilizing mechanism for these observed films. Asphaltenes are known to be interfacially active in both good solvents (aromatics) and poor solvents (high ratio of aliphatic to aromatic). However, due to inherent complexities present in asphaltene studies, the details of the mechanical properties of the interface remain poorly understood. Despite the widely accepted perception that asphaltenes form persistent rigid films at fluid-fluid interfaces, the connection between bulk solution properties and interfacial mechanics has not been resolved. Here, the effects of solvent quality on the interfacial properties of asphaltene dispersions are determined by using a well-defined asphaltene/solvent system. Interfacial rigidity is observed only under poor solvent conditions, while the good solvent system remains fluid-like. The interfacial rheology under good and poor solvent conditions is measured simultaneously with surface pressure measurements to track interfacial development. It is shown that surface pressure and dilatational modulus measurements are not indicators of whether an interface demonstrates rigid behavior under large compressions. Finally, conditions required for asphaltene-coated interfaces to exhibit the mechanical behavior associated with a rigidified interface are defined. This work provides a framework for quantifying the impact of the aggregation state of asphaltenes on the stability and mechanics at the o/w interface.


Ideal Cardiovascular Health and Risk of Cardiovascular Events or Mortality: A Systematic Review and Meta-Analysis of Prospective Studies.
Cardiovascular diseases (CVD) remain the leading cause of morbidity and mortality worldwide, hence significant efforts have been made to establish behavior and risk factors associated with CVD. The American Heart Association proposed a 7-metric tool to promote ideal cardiovascular health (CVH). Recent data demonstrated that a higher number of ideal CVH metrics was associated with a lower risk of CVD, stroke, and mortality. Our study aimed to perform a systematic review and meta-analysis of prospective studies investigating the association of ideal CVH metrics and CVD, stroke, and cardiovascular mortality (CVM) in the general population. Medline and Scopus databases were searched from January 2010 to June 2022 for prospective studies reporting CVH metrics and outcomes on composite-CVD, coronary heart disease, myocardial infarction, stroke, and CVM. Each CVH metrics group was compared to another. Twenty-two studies totaling 3,240,660 adults (57.8% men) were analyzed. The follow-up duration was 12.0 ± 7.2 years. Our analysis confirmed that a higher number of ideal CVH metrics led to lower risk for CVD and CVM (statistically significant for composite-CVD, stroke, and CVM; p < 0.05). Conclusion: Even modest improvements in CVH are associated with CV-morbidity and mortality benefits, providing a strong public health message about the importance of a healthier lifestyle.


2018 Academic Emergency Medicine Consensus Conference: Advancing Pediatric Emergency Medicine Education Through Research and Scholarship.
To achieve high-quality emergency care for pediatric patients nationwide, it is necessary to define the key elements for pediatric emergency medicine (PEM) education and scholarship that would: 1) close the gaps in fundamental PEM education and 2) promote systems and standards that assure an ongoing communication of best practices between tertiary pediatric institutions, general (nonchildren's) hospital emergency departments, and urgent care centers. A working group of medical educators was formed to review the literature, develop a framework for consensus discussion at the breakout session, and then translate their findings into recommendations for future research and scholarship. The breakout session consensus discussion yielded many recommendations. The group concluded that future progress depends on multicenter collaborations as a PEM education research network and a unified vision for PEM education that bridges organizations, providers, and institutions to assure the best possible outcomes for acutely ill or injured children.


Survival in early onset dementia: effects of urbanization and socio-economic deprivation.
We estimated survival of patients with early onset Alzheimer's disease (AD) or vascular dementia (VaD) presenting to psychiatric hospitals in Scotland (1974-1988) and related this to age, gender and socio-economic variables. Hospital records of 1794 early onset dementia patients were reviewed. We identified 451 patients with early onset AD and 384 with VaD. Survival to death was calculated from symptom onset and presentation. Small geographical areas (postcode sectors) were classified by urban/rural category and deprivation score. Five-year survival from presentation of early onset AD was 32% for men and 43% for women compared to 22% for men and 36% for women with VaD. We conclude that increased age at presentation was associated with shorter survival in early onset AD and VaD. Socio-economic deprivation was associated with longer survival in VaD. The effects of urban/rural score were accounted for by the major effects of socio-economic deprivation.


Divide and conquer: processive transport enables multidrug transporters to tackle challenging drugs.
Multidrug transporters are membrane proteins that catalyze efflux of antibiotics and other toxic compounds from cells, thereby conferring drug resistance on various organisms. Unlike most solute transporters that transport a single type of compound or similar analogues, multidrug transporters are extremely promiscuous. They transport a broad spectrum of dissimilar drugs and represent a serious obstacle to antimicrobial or anticancer chemotherapy. Many challenging aspects of multidrug transporters, which are unique, have been studied in detail, including their ability to interact with chemically unrelated drugs, and how they utilize energy to drive efflux of compounds that are not only structurally but electrically different. A new and surprising dimension of the promiscuous nature of multidrug transporters has been described recently: they can move long molecules through the membrane in a processive manner.


Trace and transference: therapy in a post-structuralist era.
As leader of the deconstruction movement, Jacques Derrida has had a profound effect on modern thinking. In this article, the author applies Derridean concepts to psychotherapy. Using the concepts of trace and differance, identity and therapeutic relationships are described. Transference and countertransference are regarded as traces, resulting in a breakdown of the therapist/patient dichotomy. Using the Derridean notion of "play" and "dissemination" opens psychotherapeutic options that allow the patient to explore how meaning is derived in his/her life. Questions of how feelings and behaviors are constructed are also examined. In summary, a deconstructive therapeutic approach results in an array of freedom and possibilities.


A rare case of Lemierre`s syndrome caused by Porphyromonas asaccharolytica.
Lemierre's syndrome is only very rarely caused by Porphyromonas asaccharolytica. Here, we report the case of a 35-year-old man who developed a left peritonsillar abscess, thrombophlebitis of the left internal jugular vein, and septic embolization of both lungs. Anaerobic P. asaccharolytica was isolated in the blood cultures, and we subsequently confirmed the diagnosis as Lemierre's syndrome. Our case indicates that although P. asaccharolytica is not commonly found in oral cavities, this organism may still cause Lemierre's syndrome. Consequently, when it is detected in blood cultures, the treating physician should perform the medical examination while keeping in mind the possibility that the patient could have Lemierre's syndrome.


Immunomodulation by tachykinin neuropeptides.
Substance P (SP) is an 11-amino-acid neuropeptide found in sensory neurons in the peripheral nervous system. In addition to having well-characterized functions as a peptide neurotransmitter, it also plays a major role in modulating inflammatory and immune responses. SP can alter the proliferative and physiological responses of both lymphocytes and macrophages. These effects are mediated by specific high-affinity SP receptors which have been characterized both kinetically and biochemically. The principle SP binding protein present on human lymphocyte cell membranes is a 58,000-MW hydrophobic glycoprotein. Cellular responses subsequent to the binding of substance P to its receptor that have been identified in various cell populations include phosphatidyl inositol turnover, arachidonic acid metabolism, immunoglobulin synthesis, and enzyme production and secretion. Evidence also suggests that SP modulation of inflammation is a factor in the pathophysiology of certain diseases such as rheumatoid arthritis.


A blind structure prediction of ice XIV.
Evidence points to several hydrogen ordered ice phases of ice XII that exhibit topologically distinct hydrogen networks from one another and which are formed under kinetically controlled conditions.


Ferulic acid modulates nitric oxide synthase expression in focal cerebral ischemia.
Nitric oxide (NO) is generated by three different NO synthase (NOS) isoforms, endothelial NOS (eNOS), inducible NOS (iNOS), and neuronal NOS (nNOS). It is known that eNOS produces NO, which exerts a protective effect, while iNOS produces NO with neurotoxic effects. Ferulic acid preserves neuronal cells against from cerebral ischemia and glutamate-induced excitotoxicity. This study confirmed the neuroprotective effect of ferulic acid and investigated the levels of three NOS isoforms in focal cerebral ischemia with or without ferulic acid. Rats were immediately treated with ferulic acid (100 mg/kg, i.v.) after middle cerebral artery occlusion (MCAO). Brains tissues were collected at 24 h after the onset of occlusion. The expressions of these three isoforms in cerebral ischemia with ferulic acid were analyzed using Western blot technique. Ferulic acid treatment significantly decreases the number of TUNEL-positive cells in the cerebral cortex against MCAO injury. The levels of eNOS decreased in MCAO-operated animals, while ferulic acid treatment attenuated the MCAO-induced decrease of eNOS. However, iNOS and nNOS expression levels increased during MCAO, and ferulic acid prevented injury-induced increase of these isoforms. Thus, these findings suggest that the up- and down modulation of three isoforms by ferulic acid is associated with a neuroprotective mechanism.


Advances in the management of malignant hemopathies: the role of statins.
Today, hematology is dependent on molecular biology for diagnosis, establishing the prognosis and treatment guidance in more and more diseases. One useful technique in this respect is the gene expression profiling, whose use is not yet a matter of routine. The discovery that the expression of LDL-receptor and cholesterol synthesis is increased in the cells of some leukemias and lymphomas and that some statins induced DNA damages and increased the level of reactive oxygen species, opens the possibility of using statins in the treatment of certain malignant hemopathies. Patents regarding their association with dipyridamole, retinoids, tipifarnib, cytostatics or chemotherapy programs contribute to increasing their effectiveness. Statins can increase the apoptosis of malignant cells and restore the chemosensitivity in patients with different malignant hemopathies. Techniques of molecular biology are useful for identifying patients who have indication for statins. The main adverse effects of statins are increased transaminase levels and myopathy. The last may be anticipated and treated today.


The role of PTRF/Cavin1 as a biomarker in both glioma and serum exosomes.
Exosomes play critical roles in intercellular communication in both nearby and distant cells in individuals and organs. Polymerase I and transcript release factor (PTRF), also known as Cavin1, has previously been described as a critical factor in caveola formation, and aberrant PTRF expression has been reported in various malignancies. However, the function of PTRF in tumor progression remains controversial, and its role in glioma is poorly understood. In this study, we report that PTRF is associated with malignancy grade and poor prognosis in glioma patients. Our previous study using two proteomics methods, tandem mass tag (TMT) and data-independent acquisition (DIA), showed that EGFRvIII overexpression increased PTRF expression at the protein level. In contrast, blocking PI3K and AKT using LY294002 and MK-2206, respectively, decreased PTRF expression, showing that PTRF is regulated in the EGFR/PI3K/AKT pathway. ChIP-PCR analysis showed that PTRF is transcriptionally regulated by the H3K4me3 and H3K27me3 modifications. Furthermore, PTRF overexpression increased exosome secretion and induced cell growth in vitro. More importantly, overexpressing PTRF induced the malignancy of nearby cells in vivo, suggesting that PTRF alters the microenvironment through intercellular communication via exosomes. Furthermore, analysis of clinical samples showed a positive correlation between tumor grade and PTRF expression in both tumor tissues and exosomes isolated from blood harvested from glioma patients, and PTRF expression in exosomes isolated from the sera of GBM patients was decreased after surgery. In conclusion, PTRF serves as a promising biomarker in both tumor samples and serum exosomes, thus facilitating the detection of glioma and potentially serving as a therapeutic target for glioblastoma multiforme.


Cricothyroid muscle activity during sleep in normal adult humans.
Previous investigators reported that cricothyroid (CT) muscle usually exhibits phasic inspiratory activity in normal adult humans during wakefulness. The purpose of this study was to determine respiratory-related CT activity in normal adult humans during sleep. Nighttime polysomnograms were performed in 16 subjects. Hooked-wire electrodes were percutaneously implanted in CT with 21-gauge needle-catheter unit that allowed artifact-free monopolar recordings during electrode placement. During wakefulness, CT was usually phasically active on inspiration, with tonic activity throughout the respiratory cycle. Phasic inspiratory activity was present throughout sleep in all subjects, even those without respiratory-related CT activity during wakefulness. Compared with non-rapid-eye-movement (NREM) sleep, phasic CT activity uniformly increased in rapid-eye-movement (REM) sleep. No differences were apparent in height of phasic CT activity between phasic and tonic REM sleep. Application of nasal continuous positive pressure in stage 3/4 NREM sleep was associated with a decrease in phasic CT activity. Passively induced hypocapnia with positive-pressure ventilation via a nose mask in stage 3/4 NREM sleep was associated with a disappearance of phasic CT activity. Cessation of positive-pressure ventilation under hypocapnic conditions frequently resulted in apnea. Phasic CT activity remained absent during apnea but reappeared coincident with or soon after resumption of spontaneous respiration. In summary, CT's phasic inspiratory activity and respiratory-related response to various stimuli during sleep were very similar to those of posterior cricoarytenoid muscle, the principal vocal cord abductor.


[Factors affecting the response of thalidomide therapy for patients with multiple myeloma].
Factors that affect the response of multiple myeloma patients to thalidomide were evaluated in 40 patients who were not eligible for chemotherapy (untreated: 14, relapse/refractory: 26). The complete response (CR) rate was 2.5%; partial response (PR) 50.0%; minimal response (MR) 25.0%; no change (NC) 12.5%; and progressive disease 10.0%. The response to thalidomide could be evaluated after four weeks of treatment. Significantly higher responses were associated with untreated patients, patients with combined use of thalidomide plus dexamethasone, and patients with kappa light chain. Patients who responded well to thalidomide showed a significantly higher progression-free survival (PFS) rate. In patients with kappa light chain, PFS and overall survival rates were significantly higher than those with lambda light chain. Frequent adverse reactions were numbness (47.5%), constipation (32.5%), and eruption (30.0%). In patients previously treated with vincristine, numbness occurred in a significantly higher percentage of patients.


[Flow rate of minor salivary glands in elderly patients wearing complete dentures].
Minor salivary glands show diverse levels of secretion in different regions of the oral cavity. The smallest production can be measured at the palatal glands, the highest in the buccal and the lingual glands. The labial glands show an intermediate value between the palatal and the buccal flow rate. According to the literature, secretion of the minor salivary glands decreases with age, yet only few data are available regarding the influence of removable dentures on the flow rate. The aim of this study was to assess the influence of complete dentures on the palatal, the labial and the whole saliva flow rate on elderly patients. A further aim was to compare the results obtained by the two measuring methods (weighing method and the PERIOTRON method), used to determine the flow rates of the minor salivary glands. According to the results of this study neither whole resting saliva flow rate nor the flow rate of the minor salivary glands (palatal, buccal) was influenced by long term removable denture wearing (denture wearers and controls -- weighing method: palatal: right side 2.4 +/- 3.3 microl/min/cm2, left side 1 +/- 3.8 microl/min/cm2 and labial: 1.4 +/- 2.6 microl/min/cm2; controls: right side 3.7 +/- 5.2 microl/min/cm2, left side 1.4 +/- 2.5 microl/min/cm2 and labial 1.8 +/- 3.9 microl/min/cm whole resting saliva flow: 0.32 +/- 0.26 ml/min and 0.29 +/- 0.24 ml/min respectively) (The data of denture wearers and controls -- PERIOTRON method: palatal right side 4 +/- 4.6 microl/min/cm2, palatal left side 3.5 +/- 3.6 microl/min/cm2 and labial 0.9 +/- 0.6 microl/min/cm2; controls: palatal right side 2.2 +/- 3.1 microl/min/cm2, palatal left side 1.8 +/- 1.8 microl/min/cm2 and labial 1.9 +/- 3 microl/min/cm2). Authors could not show difference between the weighing method and the PERIOTRON method applied in the measurement of the saliva flow rate of the minor glands.


Klinefelter's syndrome and extragonadal germ cell tumors.
A 25-year-old man presented with diffuse metastatic pure choriocarcinoma, thyrotoxicosis, and cardiac tamponade. No discernable testicular primary tumor was found. The patient's peripheral blood karyotype was 47, XXY and phenotypic features of Klinefelter's syndrome were present. The patient was treated with aggressive combination chemotherapy followed by salvage surgery and remains in complete remission 3 years after diagnosis. Pure choriocarcinoma, although rare as a primary testicular neoplasm, accounts for 15% of extragonadal germ cell tumors in general and 30% of germ cell tumors in patients with Klinefelter's syndrome. Historically, the diagnosis of pure choriocarcinoma has been thought to convey a very poor prognosis. The occurrence of hyperthyroidism is unique to tumors containing choriocarcinomatous elements and the management of this disorder is discussed. Treatment of extragonadal germ cell tumors is also discussed with special reference to the roles of combination chemotherapy and salvage surgery.


Essential Role of Triplet Diradical Character for Large Magnetoresistance in Quinoidal Organic Semiconductor with High Electron Mobility.
A diradicaloid molecule with high semiconducting performance is synthesized based on the quinoidal benzo[1,2-b:4,5-b']dithiophene structure. The diradical character is investigated by quantum chemical calculations and variable temperature electron spin resonance. The diode devices based on this molecule show a large change in electric current in magnetic fields below 100 mT with a strong dependence on the measurement temperatures; as the population of the triplet diradicals increases at high temperatures, the magnetoconductance (MC) values increase. As a result, a MC of -19.4% is achieved at 120 °C, which is the largest negative MC observed for organic molecules to date. In contrast, a smaller diradicaloid molecule based on quinoidal thieno[3,2-b]thiophene without thermally accessible triplet state shows no MC, indicating the essential role of the triplet diradicals. The strong correlation between the MC and the triplet diradical concentrations suggests that the charge conduction in the diradicaloid is suppressed through a spin-blocking mechanism, which can be controlled through the magnetic modulation of the hyperfine fields. The compound forms high-crystallinity thin films and has high monopolar electron transport in organic field-effect transistors, with an average mobility of 1.01 cm2 V-1 s-1 for edge-cast films.


Palladium-catalyzed coupling of hydroxylamines with aryl bromides, chlorides, and iodides.
The bis-pyrazole phosphine ligand BippyPhos is effective for the palladium-catalyzed cross-coupling of hydroxylamines with aryl bromides, chlorides, and iodides. Reactions proceed smoothly at 80 degrees C in toluene in the presence of Cs(2)CO(3) to give synthetically versatile N-arylhydroxylamine products in good to excellent yield.


Analysis of new N-category on prognosis of oesophageal cancer with positive lymph nodes in a Chinese population.
The 7(th) edition of the new TNM classification system for oesophageal cancer (EC) has been published. N-category is now divided into N0, N1, N2 and N3. In this study, we aimed to validate the prognostic ability of the new N classification system in EC with positive lymph nodes in a Chinese population, and evaluate whether the new N classification system can help the decision-making for postoperative adjuvant therapy. From 2002 to 2008, thoracic EC who underwent oesophagectomy were retrospectively analysed. Patients pathological stage 6(th) edition of the American Joint Committee on Cancer / Union International Against Cancer (AJCC/UICC) TNM classification were switched to pathological stage 7(th) edition for this analysis. Patients with pathological stage T1-4N1-3M0 EC were selected. Kaplan-Meier method and Cox regression analysis were employed to compare overall survival (OS). A total of 545 patients met the inclusion criteria: 346 (63.5%) received oesophagectomy alone, 199 (36.5%) received oesophagectomy and adjuvant radiotherapy, and 36.1% (197/545) received oesophagectomy and adjuvant chemotherapy. Univariate analysis and multivariate analysis revealed significant difference in OS among patients at different postoperative pN-category (p<0.001). This was also present in patients receiving postoperative radiotherapy (p<0.001) and those undergoing postoperative chemotherapy (p<0.001). There was no marked difference in OS between patients receiving postoperative adjuvant therapy and surgery alone at the same postoperative pN-category, except that postoperative radiotherapy marginally improved OS in patients with pN2 and pN3 disease. Our results validated the prognostic ability of new N classification system. The N-category is an independent prognostic factor in patients with resectable thoracic EC who were positive for lymph nodes in a Chinese population. Further studies are required to clarify the role of new N classification system in the decision-making for postoperative adjuvant therapy.


Longitudinal relations between marital aggression and children's sleep: the role of emotional insecurity.
To gain a better understanding of relations between marital aggression and children's sleep problems, we examined children's emotional insecurity as a process variable and a moderator of effects using 3 waves of data spanning 5 years. Participants were 176 children at Time 1 (T1; M age = 8.68 years), 141 children at Time 2 (T2; M age = 10.70 years), and 113 children at Time 3 (T3; M age = 13.60 years) and their parents. Parents reported on marital aggression, children reported on their emotional insecurity about the parental marital relationship, and children's sleep was measured via self-reports and actigraphy. After controlling for autoregressive effects, marital aggression predicted increases in emotional insecurity 2 years later (T2), which in turn predicted an increase in sleep problems 3 years later (T3). Moderation analyses indicated that a higher level of emotional insecurity was a vulnerability factor for sleep problems in the context of greater marital aggression. Findings add to this emerging literature and illustrate the importance of considering sleep in the family context.


Effect of orexin B on CYP17A1 and CYP19A3 expression and oestradiol, oestrone and testosterone secretion in the porcine uterus during early pregnancy and the oestrous cycle.
Orexin A (OXA) and B (OXB) are hypothalamic neuropeptides identified as regulators of food intake, energy homoeostasis, sleep-wake cycle and arousal. They also create an integrative link between energy homoeostasis and reproduction. Although their functions in the ovaries and testes have been partially explored, to date, less attention has been focused on the role of the peptides in the uterus. The aim of this study was to investigate the effect of one of orexins - orexin B on oestradiol (E2), oestrone (E1) and testosterone (T) secretion by porcine endometrial and myometrial slices as well as the gene expression of key steroidogenic enzymes responsible for steroid production (CYP17A1, CYP19A3) during the luteal phase of the oestrous cycle (days 10 to 11) and early pregnancy (days 10 to 11, 12 to 13, 15 to 16, 27 to 28). Orexin B suppressed E2 secretion by endometrial slices on days 10 to 11 and 15 to 16 of pregnancy, and days 10 to 11 of the cycle. In the myometrium, OXB inhibited E2 production on days 10 to 11 of pregnancy, whereas on days 12 to 13 it enhanced steroid output. Endometrial E1 release was potentiated by the peptide during all studied periods of the cycle and pregnancy, with the exception of days 12 to 13, when an inhibitory effect was observed. Myometrial secretion of E1 was increased, except on days 27 to 28. Testosterone secretion by endometrial slices was increased on days 12 to 13 and 27 to 28 of pregnancy. On days 10 to 11 of the cycle, T release was stimulated in response to the lowest and decreased under the influence of the highest dose of OXB. In the myometrium, T production was inhibited by OXB on days 10 to 11 of pregnancy and during the corresponding period of the cycle. On days 27 to 28 of pregnancy, T release was potentiated by the lowest dose of OXB. Expression of both genes was modified by OXB depending on the period of pregnancy and the type of examined uterine tissues. Our findings suggest that OXB, through modulation of uterine steroidogenesis, may have a regulatory role in the uterus.


Individual-level and neighborhood-level income measures: agreement and association with outcomes in a cardiac disease cohort.
Census-based measures of income often are used as proxies for individual-level income. Yet, the validity of such area-based measures relative to 'true' individual-level income has not been fully characterized. The objectives of this study were (1) to determine whether area-based measures of household income are a suitable proxy for self-reported household income and (2) to assess whether these measures are associated with outcomes in a cardiac disease cohort. We used a prospective cohort from the Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease (APPROACH) cardiac catheterization registry. A total of 4372 patients having undergone cardiac catheterization and who also completed a 1-year follow-up questionnaire on self-reported income level were studied. Our measurements were survival to 2.5 years after catheterization and health-related quality of life (EuroQoL). Agreement between the 2 income measures generally was poor (unweighted Kappa = 0.07), particularly for the low-income patients. Despite this poor agreement, both income measures were positively associated with survival and EuroQoL scores. An outcome analysis that simultaneously considered individual level income and area-based income revealed that low-income individuals have poorer survival and lower quality of life scores if they live in low income neighborhoods, but not if they live in high income neighborhoods. The area-based estimates of household income in these data demonstrate poor agreement with self-reported household income at the level of individual patients, particularly for low-income patients. Despite this, both income measures appear to be prognostically relevant, perhaps because individual and neighborhood income measure different constructs.


[Quantitative salivary gland scintigraphy--a recommended examination prior to and after radioiodine therapy].
The aim of this study was to evaluate possible deterioration of salivary gland function due to radioiodine therapy with low activities using standardized quantitative salivary gland scintigraphy (qSZ). In addition, the prevalence of sialopathies was estimated in patients with thyroid dysfunction. Prior to routine thyroid scintigraphy qSZ was performed after i.v. injection of 36-126 MBq 99mTc-pertechnetate, and both uptake and excretion fraction were calculated as a measure of parenchymal function and saliva excretion, respectively 312 healthy patients served as reference for a normal data base. 144 patients underwent qSZ prior to and 3 months after radioiodine therapy. Results of qSZ in another 674 thyroid patients were evaluated for determining the prevalence of salivary gland dysfunction. Normal uptake was 0.45 +/- 0.14% and 0.39 +/- 0.12%, and normal excretion fraction amounted to 49.5 +/- 10.6% and 39.1 +/- 9.2% in parotid and submandibular glands, respectively. Despite salivary gland stimulation with ascorbic acid during radioiodine therapy a significant activity-related functional impairment of 14-90% could be measured after application of 0.4-24 GBq of 131I. Prevalence of pretreatment sialopathies was 77/674 = 11.4% in single glands, and there was a global salivary gland functional impairment in 52/674 = 7.7%. Together with thyroid scintigraphy qSZ is an easy to perform examination without additional radiation burden. It can be recommended in all patients prior to and after radioiodine therapy both in order to quantify and to document possible parenchymal impairment induced even by low activities of 131I.


Sub-Picosecond Nanodiodes for Low-Power Ultrafast Electronics.
The tradeoff between ultrahigh speed and low power is a dominant challenge in continuously improving modern electronics. Fundamental electronic devices with ultrafast response are highly desired in low-power electronics. However, conventional semiconductor electronic devices now near the speed limit from the physical roadblocks including short-channel effect, restricted carrier velocity, and heat death. Currently emerging electronic devices also face formidable difficulties to achieve high-speed performance at low operating voltage without heat disturbance. Here, a novel fabricated coplanar tip-to-edge semiconductor-free nanostructure with asymmetric sub-10 nm air channel is reported, stimulating electric-field accelerated scattering-free transport of electrons and resulting in ultrafast response of record sub-picoseconds at a low turn-on voltage around 0.7 V. Simulation results show a typical electrical response down to 64 fs, which is ≈103 times faster than that of conventional semiconductor electronic devices. The coplanar asymmetric nanostructure allows a high rectifying ratio up to 106 which is superior to that of the most promising 2D semiconducting nanodiodes. In addition, heat death is overcome due to the inherent advantages from the novel nanostructure and underlying working mechanism. The intriguing nanodiodes will attract broadly interests in electronics due to their potential as rudimentary building blocks in ultrafast electronic integrated circuits.


The surmountable effect of FSCPX, an irreversible A(1) adenosine receptor antagonist, on the negative inotropic action of A(1) adenosine receptor full agonists in isolated guinea pig left atria.
A1 adenosine receptors (A1 receptors) are widely expressed in mammalian tissues; therefore attaining proper tissue selectivity is a cornerstone of drug development. The fact that partial agonists chiefly act on tissues with great receptor reserve can be exploited to achieve an appropriate degree of tissue selectivity. To the best of our knowledge, the A1 receptor reserve has not been yet quantified for the atrial contractility. A1 receptor reserve was determined for the direct negative inotropic effect of three A1 receptor full agonists (NECA, CPA and CHA) in isolated, paced guinea pig left atria, with the use of FSCPX, an irreversible A1 receptor antagonist. FSCPX caused an apparently pure dextral displacement of the concentration-response curves of A1 receptor agonists. Accordingly, the atrial A1 receptor function converging to inotropy showed a considerably great, approximately 80-92 % of receptor reserve for a near maximal (about 91-96 %) effect, which is greater than historical atrial A1 receptor reserve data for any effects other than inotropy. Consequently, the guinea pig atrial contractility is very sensitive to A1 receptor stimulation. Thus, it is worthwhile considering that even partial A1 receptor agonists, given in any indication, might decrease the atrial contractile force, as an undesirable side effect, in humans.


Understanding the possibilities and limitations of assistive technology in health and welfare services for people with intellectual disabilities, staff perspectives.
Little is known regarding what assistive technology (AT) exists and how it is used in welfare services for people with intellectual disabilities (ID). This study aimed to explore healthcare staff's perspectives and insights regarding AT in daily support and welfare services for people with ID. We also sought to explore the associations between the use of AT and workplace-related factors and background characteristics (e.g., gender, age, and experience). Three focus group discussions were conducted with 11 informants (8 women, 3 men) working in home-based and day services. Also, 176 healthcare staff (43 men, 133 women) who worked in municipal home-based services and day services completed a questionnaire comprised of background questions and 14 items with a five-point answer scale. Number of years using AT was positively associated with a positive attitude and use of AT among the staff. Staff were mainly positive towards AT and believed that it could represent various possibilities in the everyday lives of people with ID and their own service delivery. However, the staff expressed uncertainties and ethical concerns regarding AT, and they experienced a lack of knowledge, focus, and awareness about technology in services for this group. The quantitative results mainly showed positive associations between believing in AT's usefulness and using it in services for people with ID. The findings indicate that providing equipment and resources, personal interests, and staff attitudes are essential factors in successfully implementing AT for people with ID.Implications for rehabilitationHealthcare staff have a positive attitude towards using AT for people with intellectual disabilities, but they also perceive uncertainty and ethical concerns.The staff believe that there is a broad range of AT devices and systems available that can support the independence and participation of people with intellectual disabilities.The staff need to receive more training and technical supports from their workplace and AT-related experience is associated positively with the use of assistive technology by the staff.


Alpha- and beta-blocking agents: pharmacology and properties.
Adrenergic receptors have been separated into alpha and beta groups, which have then been further subdivided. Agents have been developed that block each type of receptor with varying degrees of specificity between the sub-types, leading to differences in pharmacodynamic profile. A more recent innovation has been the development of multiple action beta-blocking drugs, ie, those not only blocking the beta receptors but also possessing a peripheral vasodilator effect that may be due to alpha blockade, beta-2 stimulation, or a vasodilator action independent of either alpha or beta receptors.


The novel GLP-1/GIP dual agonist DA3-CH improves rat type 2 diabetes through activating AMPK/ACC signaling pathway.
Type 2 diabetes mellitus (T2DM) accounts for more than 95% of all diabetes. DA3-CH is a novel dual receptor agonist of glucagon like peptide-1 (GLP-1) and glucose dependent insulin stimulating polypeptide (GIP). The regulatory role of DA3-CH in T2DM has not been reported. T2DM rat model was established successfully with high sugar and fat feed and streptomycin (STZ) induction. The mRNA and protein expression were measured with RT-PCR and western blotting. The apoptosis level in the pancreatic tissue was evaluated with Tunel staining. Blood glucose, fat, and oxidative stress indicators were measured. DA3-CH greatly improved T2DM symptoms by reducing blood glucose, blood fat, pancreatic tissue injury, apoptosis, and oxidative stress condition. The inactivation of Adenylate activated protein kinase (AMPK)/acetyl CoA carboxylase (ACC) signaling pathway in T2DM rats was promoted by DA3-CH. The influence of DA3-CH was significantly reversed by Com-C, the inhibitor of AMPK/ACC signaling pathway. DA3-CH might improve T2DM through targeting AMPK/ACC signaling pathway. This study might provide a novel therapeutic strategy for the prevention and treatment of T2DM through targeting DA3-CH and AMPK/ACC signaling pathway.


Infection in surgical patients: effects on mortality, hospitalization, and postdischarge care.
In-hospital mortality, length of stay (LOS), and level of postdischarge care in infected and noninfected surgical patients were studied. An analysis was conducted of a database that included diagnostic, procedure, and drug data collected when surgical patients were discharged from the hospital. Hospitals consisted of 90 nongovernment, nonspecialty, teaching, and nonteaching acute care hospitals of more than 100 beds. Patients in the database included 288,906 patients of all ages hospitalized between July and September 1994. Patients selected of those who had undergone procedures likely to pose a moderate to high risk of infection. Of the 288,906 patients, 12,384 had undergone a moderate- to high-risk procedure; of these, 1,479 (11.9%) had had an infection during their hospitalization. Infection rates ranged from 1.9% to 25.4%, depending on the procedure. The in-hospital mortality rate in infected patients was 14.5%, versus 1.8% for noninfected patients. Similarly, LOS in infected patients (median, 14 days) was substantially greater than in noninfected patients (4 days). About 24% of infected patients required additional professional care after discharge, compared with 7% of noninfected patients. Infection occurs in a substantial portion of surgical patients and is associated with a higher death rate, longer hospitalization, and more intense postdischarge care.


Integrative transcriptomic, proteomic and metabolomic analysis reveals the dynamic regulation of secondary metabolism upon development of Prunella vulgaris L.
Prunella vulgaris L. (P. vulgaris, Labiatae) is a perennial medicinal and edible plant widely used in China, Korea, Japan and Europe. The reddish brown spica of P. vulgaris (Prunellae Spica), which is collected in summer, has been commonly used in traditional medicine and food industry, while it is also used with whole grass in Europe and Taiwan. To clarify the regulatory pathways and mechanism of quality formation in P. vulgaris, targeted metabolomic, transcriptomic, and proteomic analyses of Prunellae Spica samples from five consecutive developmental stages were carried out. The results showed that terpenoids were mainly synthesized in the maturity stage of Prunellae Spica, with the key enzymes and coding genes in downstream pathways being mainly expressed during ripening, while related enzymes in the upstream pathway showed the opposite pattern. Flavonoids mainly accumulated before ripening, with highly expressed pathway enzymes and coding genes. The accumulation of phenylpropanoids was relatively active throughout the development process. Rosmarinic acid (RA) and its synthetic intermediate products mainly accumulated via more active pathway enzymes and coding genes before ripening. The regulatory factors and metabolites related to RA synthesis were mainly enriched in phenylpropanoid biosynthesis, plant hormone signal transduction, plant pathogen interaction, oxidative phosphorylation, and endoplasmic reticulum protein processing pathways.


Does the wide use of quaternary ammonium compounds enhance the selection and spread of antimicrobial resistance and thus threaten our health?
Quaternary ammonium compounds (QACs) are widely used biocides that possess antimicrobial effect against a broad range of microorganisms. These compounds are used for numerous industrial purposes, water treatment, antifungal treatment in horticulture, as well as in pharmaceutical and everyday consumer products as preserving agents, foam boosters, and detergents. Resistance toward QACs is widespread among a diverse range of microorganisms and is facilitated by several mechanisms such as modifications in the membrane composition, expression of stress response and repair systems, or expression of efflux pump genes. Development of resistance in both pathogenic and nonpathogenic bacteria has been related to application in human medicine and the food industry. QACs in cosmetic products will inevitably come into intimate contact with the skin or mucosal linings in the mouth and thus are likely to add to the selection pressure toward more QAC-resistant microorganisms among the skin or mouth flora. There is increasing evidence of coresistance and cross-resistance between QACs and a range of other clinically important antibiotics and disinfectants. Use of QACs may have driven the fixation and spread of certain resistance cassette collectors (class 1 integrons), currently responsible for a major part of antimicrobial resistance in gram-negative bacteria. More indiscriminate use of QACs such as in cosmetic products may drive the selection of further new genetic elements that will aid in the persistence and spread of antimicrobial resistance and thus in limiting our treatment options for microbial infections.


Safety of a Bioactive Polyphenol Dietary Supplement in Pediatric Subjects with Acute Diarrhoea.
The hematological and clinical chemistry profile for children aged 6 months to 5 years with acute diarrhoea was measured in a double blind clinical trial. Subjects were randomized to the study group (N = 44) given a bioactive polyphenol dietary supplement in oral rehydration solution (ORS) or to the control group (N = 41) given distilled water as a placebo in ORS twice daily for up to 4 days. All subjects received 10 mg zinc daily for the 4 days in the study. Venous blood was collected for complete blood count, electrolytes, liver function, and creatinine upon enrollment (baseline) and at the end of 4 days (end of study); mean values were compared by 95% confidence intervals. Overall, blood factors measured either remained the same over the 4 days or increased or decreased at the same levels between the two groups during the study period. All values were within accepted ranges for paediatric subjects except serum AST (SGOT), where the mean value of the study group approached the upper bound of the range on day 4 but was comparable to the value of the control group. Consumption of this supplement twice daily for 4 days is safe for children and infants.


Prospective Assessment of Acute Blood Markers of Brain Injury in Sport-Related Concussion.
There is a pressing need to identify objective biomarkers for the assessment of sport-related concussion (SRC) to reduce the reliance on clinical judgment for the management of these injuries. The goal of the current study was to prospectively establish the acute effects of SRC on serum levels of S100 calcium-binding protein beta (S100B), glial fibrillary acidic protein (GFAP), and ubiquitin C-terminal hydrolase-L1 (UCH-L1). Collegiate and high school football players were enrolled and provided blood at pre-season. Injured athletes participated in follow-up visits at ∼6 and 24-48 h following documented SRC (n = 32). Uninjured football players participated in similar follow-up visits and served as controls (n = 29). The median time between injury and blood collection was 2 h (6 h visit) and 22.5 h (24-48 h visit) in concussed athletes. Concussed athletes had significantly elevated UCH-L1 levels at the 6 h visit relative to pre-season levels (Z = 2.22, p = 0.03) and levels in control athletes (Z = 3.02, p = 0.003). Concussed athletes also had elevated S100B at 6 h relative to pre-season (Z = 2.07, p = 0.04) and controls (Z = 2.75, p = 0.006). Both markers showed fair discrimination between concussed and control athletes (UCH-L1 area under receiver operating characteristic curve [AUC] [95% CI] = 0.74 [0.61-0.88], S100B AUC = 0.72 [0.58-0.87]). Percent-change of UCH-L1 and S100B at 6 h relative to pre-season also showed fair discrimination (AUC = 0.79 [0.66-0.92] and AUC = 0.77 [0.64-0.90]). GFAP levels did not differ between groups or in concussed athletes relative to pre-season. This study provides prospective evidence of significant increases in serum levels of UCH-L1 and S100B during the early acute period following SRC, and lays the foundation for future studies examining the clinical potential for blood-based biomarkers in the early detection of concussion.


[GABA, a key transmitter for fetal brain maturation].
GABA, the principal inhibitory transmitter excites immature neurons in all animal species studied. This is due to the higher intracellular concentration of chloride at early developmental stages. Excitatory actions of GABA play an important action in brain maturation. Recent observations also suggest an abrupt shift during delivery that exerts a neuro-protective action contributing to reduce the sequels of trauma and anoxic episodes. These observations have important clinical implications in relation to delivery associated insults but also preterm delivery and more generally consumption of agents during gestation.


Brain structure and spatial sensitivity profile assessing by near-infrared spectroscopy modeling based on 3D MRI data.
The goal of this study is to prove that the light propagation in the head by used the 3-D optical model from in vivo MRI data set can also provide significant characteristics on the spatial sensitivity of cerebral cortex folding geometry based on Monte Carlo simulation. Thus, we proposed a MRI based approach for 3-D brain modeling of near-infrared spectroscopy (NIRS). In the results, the spatial sensitivity profile of the cerebral cortex folding geometry and the arrangement of source-detector separation have being necessarily considered for applications of functional NIRS. The optimal choice of source-detector separation is suggested within 3-3.5 cm by the received intensity with different source-detector separations and the ratio of received light from the gray and white matter layer is greater than 50%. Additionally, this study has demonstrated the capability of NIRS in not only assessing the functional but also detecting the structural change of the brain by taking advantage of the low scattering and absorption coefficients observed in CSF of sagittal view.


Activation of cytosolic phospholipase A2 by transforming growth factor-alpha in HEL-30 keratinocytes.
In the mouse keratinocyte line HEL-30 the epidermal mitogen transforming growth factor-alpha (TGF-alpha) stimulated the rapid release of arachidonic acid in a dose- and time-dependent manner. The liberation of arachidonic acid was due to the activation of a Ca(2+)-dependent cytosolic phospholipase A2 (cPLA2). The activation mechanism critically depended on a functionally active epidermal growth factor receptor tyrosine kinase and occurred independently of phospholipase C-mediated increases in cellular diacylglycerol and inositol 1,4,5-trisphosphate concentrations and protein kinase C activation. The activation included an increase in cytosolic PLA2 (cPLA2) activity and an association of the enzyme with the membrane fraction. Both activation steps apparently occurred in the presence of basal cytoplasmic Ca2+ concentrations. Moreover, cPLA2 or a closely associated protein was found to be phosphorylated on tyrosine upon TGF-alpha challenge of the cells. The data suggest that tyrosine phosphorylation is involved in the TGF-alpha-induced activation of cPLA2.


Effects of tamoxifen dose and nutrition scheme during growth on stimulation of the reproductive system in cornish breed cocks.
The effects of tamoxifen (TAM) antiestrogen dose as well as protein and energy content in feed on stimulation of the reproductive system development in meat type cocks were studied. The experiment was conducted on males of the Dominant White Cornish chicken breed. The optimum TAM dose for stimulation of reproductive system development was at the level of 5 mg per kg body weight. The effects of TAM administration on the following traits were investigated: body weight, breast muscle thickness, age at sexual maturity, egg fertilization and hatchability. No effect of TAM on breast muscle thickness was found. It was also noted that semen obtained from 11 to 12 week old males of the Dominant White Cornish breed could be used successfully in the insemination of females.


The economic impact of uterine fibroids in the United States: a summary of published estimates.
To present a summary of published estimates of the economic burden of uterine fibroids in the United States and identify areas for additional research. A search of three electronic databases, MEDLINE, EMBASE, and Current Contents, was conducted, along with a review of information on the Internet and abstraction of economic data. Only 10 papers and 1 Internet document met our inclusion criteria and were used to abstract data. Cost estimates for surgically invasive treatments of uterine fibroids included hysterectomy (USD 5,012-7,934), myomectomy (USD 5,425-11,839), and uterine artery embolization (UAE) (USD 5,425-7,645) (2004 USD). One cost-effectiveness study estimated lower costs and higher quality-adjusted life years with UAE compared with hysterectomy. A second study estimated potential savings of USD 4.2 million in hospital charges in the United States if higher rates of vaginal (vs. abdominal) hysterectomy would be achieved after pretreatment with gonadotropin hormone-releasing hormone (GnRH) agonists compared to without pretreatment with GnRH agonists (80% vs. 13%). There were no estimates of the total direct and indirect economic burden of uterine fibroids. Neither estimates of the costs for the ambulatory care of fibroids nor studies estimating the indirect costs associated with the management of fibroids and their symptoms were found. This summary of published U.S. economic estimates shows that despite the high prevalence of fibroids and their impact on clinical practice and women's lives, there is very little published information on their economic impact apart from data showing standard treatments for uterine fibroids are invasive and expensive. Reduction in the need for and cost of invasive procedures by the increased usage of noninvasive treatments could potentially achieve significant national cost savings, but further clinical and economic studies are needed.


The role of striatum and prefrontal cortex in the prevention of amphetamine-induced schizophrenia-like effects mediated by nitric oxide compounds.
Pharmacological manipulation of nitric oxide (NO) has been suggested as a promising treatment for schizophrenia symptoms. A single infusion of sodium nitroprusside, a NO donor with short half-life, was found to improve schizophrenia symptoms. However, an increasing number of preclinical studies have demonstrated the potential beneficial effects of both NO donors and inhibitors. We investigated the potential synergistic effect of sub-effective doses of the NO donor sodium nitroprusside or the NO inhibitor 7-Nitroindazole (7NI) combined with clozapine, a standard atypical antipsychotic, on counteracting amphetamine or MK-801-induced psychosis-like behaviors. The impact of sodium nitroprusside and 7NI on cAMP regulation in the prefrontal cortex and striatum was also evaluated. Confirming previous results, we found that both NO donors and inhibitors prevented amphetamine-induced effects (prepulse inhibition [PPI] disruption and hyperlocomotion). In addition, we observed a synergistic effect of sodium nitroprusside and clozapine on antagonizing the disruptive effects of amphetamine, but not MK-801, in the PPI test. The sub-effective dose of 7NI tested did not prevent amphetamine or MK-induced PPI effects when combined with clozapine. Interestingly, cAMP levels were significantly decreased in the prefrontal cortex after treatment with sodium nitroprusside. In the striatum, both sodium nitroprusside and 7NI blocked the amphetamine-induced increase of cAMP. Our data corroborate previous findings on the dopaminergic mechanisms involved in the action of sodium nitroprusside. It is likely that the differential effects of sodium nitroprusside are related to its ability to modify cAMP levels in the prefrontal cortex.


Physiological and genetic mapping study of tolerance to root-knot nematode in rice.
The root-knot nematode Meloidogyne graminicola is an obligate biotrophic parasite and a major pest of rice (Oryza sativa) for which resistant varieties are not currently available. Quantitative trait loci (QTLs) for partial resistance to M. graminicola were identified using a mapping population based on two rice varieties, Bala x Azucena. Experiments were carried out to investigate the interactions between M. graminicola and these two varieties in terms of nematode establishment, reproduction and effect on rice yield. Nematode establishment was also assessed in the mapping population. Meloidogyne graminicola consistently caused more galling and had higher reproductive success in Azucena than in Bala. M. graminicola did not significantly reduce yield in Bala, but caused a yield reduction of almost half in Azucena, suggesting that the partial resistance to nematode establishment was related to nematode tolerance. A total of six significant or putative QTLs for nematode tolerance were detected. For two of the QTLs detected, Azucena was the donor of the tolerance alleles, suggesting it may be possible to breed plants with greater tolerance than Bala.


[Use of mannitol and propranolol in the treatment of experimental acute renal failure (histomorphological study)].
Experimental research was carried out in order to ascertain whether administration of drugs capable of acting on the renal circulation, such as mannitol and propanol, in addition to improving the renal function, also have a protective effect on the histomorphological alterations induced by the acute renal ischemia. On the basis of the results of the research the Authors conclude by asserting that the combined use of mannitol and propanol has a real protective effect in preventing or attenuating lesions of the kidney caused by serious acute renal failure.


Reelin induces a radial glial phenotype in human neural progenitor cells by activation of Notch-1.
Reelin and Notch-1 signaling pathways have been recently found to be necessary to induce the expression of brain lipid binding protein (BLBP) and to promote the process extension and the maturation of the neuronal progenitors, the radial glial cells. In this study, we report the cross talk between these two pathways. Both in vitro Reelin treatment and overexpression of Notch-1 intracellular domain (NICD) induced BLBP expression and a radial glial phenotype in an immortalized human neural progenitor (HNP) cell line, isolated from the cortex of 14 weeks old fetus. Reelin treatment increased the level of NICD, indicating that Reelin signaling directly activates Notch-1. In addition, reducing NICD release, by inhibiting gamma-secretase activity, inhibited the Reelin-induced radial glial phenotype in human neural progenitor cells. Furthermore, we found that Dab-1, an adaptor protein downstream of Reelin, was co-immunoprecipitated with Notch-1 and NICD. These data indicate that Reelin signaling induces BLBP expression and a radial glial phenotype in human neural progenitor cells via the activation of Notch-1. This study suggest that Reelin signaling may act to fine tune Notch-1 activation to favor the induction of a radial glial phenotype prenataly and would thus offer an insight into how Notch-1 signaling leads to different cellular fates at different developmental stages.


Alteplase for Acute Ischemic Stroke after Heparin Reversal with Protamine: A Case Report and Review.
Few patients presenting with acute ischemic stroke (AIS) are eligible for alteplase, especially those receiving ongoing anticoagulation. We describe the first reported case of a patient receiving full-dose intravenous (IV) alteplase for AIS after heparin reversal with protamine. A 73-year-old man presented with AIS. He was treated with IV heparin, tirofiban, loading-dose prasugrel, and aspirin before percutaneous coronary intervention (PCI) for placement of a right coronary artery stent. One hour following PCI, he abruptly developed left hemiparesis and dysphagia. The National Institutes of Health Stroke Scale was 12, and activated partial thromboplastin time (aPTT) was longer than 150 seconds. Head computed tomography (CT) showed no acute pathology, and CT angiogram showed no large-vessel occlusion amenable to mechanical thrombectomy. Repeat aPTT, obtained 45 minutes later, was 110 seconds, at which time protamine 40 mg IV was administered. At 144 minutes from last known well time, full-dose IV alteplase (0.9 mg/kg) was administered. Follow-up head imaging at 25 hours showed right pontine and cerebellar AIS with no evidence of hemorrhage. The patient was discharged to inpatient rehabilitation 2 days later. Modified Rankin Scale at 3 months was 3, improved from 5 at discharge. Given the lack of adverse events associated with IV alteplase in our patient, we advocate cautious evaluation for potential reversal of acutely administered anticoagulation to facilitate alteplase administration in severely disabled patients who are not eligible for mechanical intervention and would have been excluded from definitive AIS treatment.


α-Toxin Regulates Local Granulocyte Expansion from Hematopoietic Stem and Progenitor Cells in Staphylococcus aureus-Infected Wounds.
The immune response to Staphylococcus aureus infection in skin involves the recruitment of polymorphonuclear neutrophils (PMNs) from the bone marrow via the circulation and local granulopoiesis from hematopoietic stem and progenitor cells (HSPCs) that also traffic to infected skin wounds. We focus on regulation of PMN number and function and the role of pore-forming α-toxin (AT), a virulence factor that causes host cell lysis and elicits inflammasome-mediated IL-1β secretion in wounds. Infection with wild-type S. aureus enriched in AT reduced PMN recruitment and resulted in sustained bacterial burden and delayed wound healing. In contrast, PMN recruitment to wounds infected with an isogenic AT-deficient S. aureus strain was unimpeded, exhibiting efficient bacterial clearance and hastened wound resolution. HSPCs recruited to infected wounds were unaffected by AT production and were activated to expand PMN numbers in proportion to S. aureus abundance in a manner regulated by TLR2 and IL-1R signaling. Immunodeficient MyD88-knockout mice infected with S. aureus experienced lethal sepsis that was reversed by PMN expansion mediated by injection of wild-type HSPCs directly into wounds. We conclude that AT-induced IL-1β promotes local granulopoiesis and effective resolution of S. aureus-infected wounds, revealing a potential antibiotic-free strategy for tuning the innate immune response to treat methicillin-resistant S. aureus infection in immunodeficient patients.


Growth of Nanosized Single Crystals for Efficient Perovskite Light-Emitting Diodes.
Organic-inorganic hybrid perovskites are emerging as promising emitting materials due to their narrow full-width at half-maximum emissions, color tunability, and high photoluminescence quantum yields (PLQYs). However, the thermal generation of free charges at room temperature results in a low radiative recombination rate and an excitation-intensity-dependent PLQY, which is associated with the trap density. Here, we report perovskite films composed of uniform nanosized single crystals (average diameter = 31.7 nm) produced by introducing bulky amine ligands and performing the growth at a lower temperature. By effectively controlling the crystal growth, we maximized the radiative bimolecular recombination yield by reducing the trap density and spatially confining the charges. Finally, highly bright and efficient green emissive perovskite light-emitting diodes that do not suffer from electroluminescence blinking were achieved with a luminance of up to 55 400 cd m-2, current efficiency of 55.2 cd A-1, and external quantum efficiency of 12.1%.