Association between the Use of Complete Dentures and Frailty in Edentulous Mexican Elders.
Edentulism and use of complete dentures (CD), which are common among elderly people, increase the risk for malnutrition and weight loss, components of frailty syndrome. To identify if CD use is associated with the presence of frailty in a group of edentulous people aged ≥70 years, residing in Mexico City. This was a cross-sectional analysis of baseline data of a cohort study. The study population consisted of 33,347 people living independently in one district of Mexico City, 149 edentulous subjects were interviewed and examined for this analysis. Frail people experienced 3 or more of the following 5 components: unintentional weight loss, poor endurance and energy, low physical activity, slowness, and weakness. Dental variables were CD use, CD functionality, self-perception of oral health, use of dental services the previous year, xerostomia, and chewing problems. Age, sex, education level, cognitive impairment, urinary incontinence, number of falls, hospitalization, and number of drugs consumed were considered. Univariate analysis and a logistic regression model were used. The prevalence of frailty was 23.5%. The probability of being frail increased among participants with osteoporosis (OR = 3.2), urinary incontinence (OR = 3.8), cognitive impairment (OR = 4.1), and non-use of CD (OR = 5.2); for each additional drug taken per day, the risk of frailty increased by 28.9%. The non-use of CD in edentulous older persons can be a risk marker for frailty, health evaluation of the elderly should include a dental assessment.


Male obesity and subfertility, is it really about increased adiposity?
The prevalence of overweight and obesity in reproductive-aged men is increasing worldwide, with >70% of men >18 years classified as overweight or obese in some western nations. Male obesity is associated with male subfertility, impairing sex hormones, reducing sperm counts, increasing oxidative sperm DNA damage and changing the epigenetic status of sperm. These changes to sperm function as a result of obesity, are further associated with impaired embryo development, reduced live birth rates and increased miscarriage rates in humans. Animal models have suggested that these adverse reproductive effects can be transmitted to the offspring; suggesting that men's health at conception may affect the health of their children. In addition to higher adiposity, male obesity is associated with comorbidities, including metabolic syndrome, hypercholesterolemia, hyperleptinemia and a pro-inflammatory state, all which have independently been linked with male subfertility. Taken together, these findings suggest that the effects of male obesity on fertility are likely multifactorial, with associated comorbidities also influencing sperm, pregnancy and subsequent child health.


Rac1 regulation of surface expression of protease-activated receptor-1 and responsiveness to thrombin in vascular smooth muscle cells.
Protease-activated receptor-1 (PAR1) mediates the thrombin-induced proliferation and hypertrophy of vascular smooth muscle cells. A role of Rac1 in the regulation of PAR1 expression was investigated. Treatment with simvastatin, a hydroxy-3-methyl-glutaryl coenzyme A reductase inhibitor, for 24 hours attenuated the transient [Ca2+]i elevation induced by thrombin. Immunofluorescence staining revealed that simvastatin decreased the surface expression of PAR1 in a manner dependent on protein geranylgeranylation. Introduction of a Rac1/Cdc42 inhibitory fragment but not a RhoA inhibitory fragment using a cell-penetrating peptide also attenuated the response to thrombin and decreased the surface expression of PAR1. Finally, downregulation of Rac1, but not RhoA, using an RNA interference technique attenuated the thrombin-induced [Ca2+]i elevation. However, the level of PAR1 mRNA and the total amount of PAR1 protein remained unchanged. Here, we provide for the first time 3 lines of evidence that Rac1 plays a critical role in maintaining the surface expression of PAR1 and the responsiveness to thrombin in vascular smooth muscle cells. Rac1 is suggested to regulate the constitutive trafficking of PAR1 and thereby regulate the surface expression of PAR1.


[Simultaneous determination of 83 glucocorticoids in cosmetics by ultra performance liquid chromatography-tandem mass spectrometry].
Glucocorticoids, which are a class of steroidal hormones secreted by the adrenal cortex, have significant anti-inflammatory, immunosuppressive, and anti-allergic effects. Thus, these compounds are widely used in clinical practice. However, the long-term use of cosmetics containing glucocorticoids can lead to serious consequences, such as hormone-dependent dermatitis, hypertension, and other serious injuries. The Safety and Technical Specification for Cosmetics (2015 edition) and Regulation (EC) No. 1223/2009 of the European Parliament and Council on cosmetic products list glucocorticoids as prohibited raw materials. According to the National Medical Products Administration, reports on the illegal addition of glucocorticoids to cosmetics by manufacturers have increased in recent years. Therefore, establishing high-throughput screening methods to ensure the quality and safety of cosmetics is imperative. In this study, a comprehensive analytical method based on ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was developed for the rapid screening of 83 glucocorticoids in cosmetics. A series of conditions were optimized using three matrices that are commonly used in cosmetics: water, lotion, and cream (o/w-type). Four mobile-phase systems and three chromatographic columns were then optimized to achieve the best separation effects. Various MS parameters, such as the capillary voltages, cone voltages, desolvation gas flow rates, and collision energies of the ion pairs of the target compounds, were also optimized. Furthermore, pretreatment was essential for glucocorticoid determination owing to the complex matrix effects of cosmetics. The analytes were divided into two groups, with lg Kow=4 as the limit, to compare the effects of the extraction solvent on recoveries. The extraction recoveries of target analytes with six extraction methods, namely, extraction with acetonitrile, extraction with acetone, extraction with ethyl acetate, dispersion in saturated sodium chloride solution followed by extraction with acetonitrile, dispersion in saturated sodium chloride solution followed by extraction with acetone, and dispersion in saturated sodium chloride solution followed by extraction with ethyl acetate, were compared. The recoveries from QuEChERS and solid-phase extraction (SPE) purification were also compared. Based on the experimental results, the final sample pretreatment method included acetonitrile vortex dispersion, ultrasonic extraction, and sample loading after filtration. The 83 target compounds were separated on a Thermo Accucore PFP column (100 mm×2.1 mm, 2.6 μm) with 0.1% (v/v) acetic acid in acetonitrile and 0.1% (v/v) acetic acid in water as the mobile phases. The analytes were determined by dynamic multiple-reaction monitoring (MRM) in electrospray positive ionization mode (ESI+) and quantified using the external standard method. Matrix standard curves were used to reduce matrix effects. The calibration curves of the 83 target compounds were linear in the mass concentration range of 2-200 μg/L (r>0.995). At three levels of addition, the recoveries were 74.5%-112.4%, and the relative standard deviations (RSDs, n=6) were 0.8%-9.9%. The limits of detection (LODs, S/N≥3) were 0.001-0.023 μg/g, and the limits of quantification (LOQs, S/N≥10) were 0.002-0.076 μg/g. The developed method was used to detect glucocorticoids in 41 cosmetic samples. Fluocinolone acetonide, beclomethasone dipropionate, desonide 21-acetate, and desonide were detected in four samples. The content range of glucocorticoids in the positive samples was 0.53-634.27 μg/g. Notably, desonide 21-acetate, which is not included in the scope of the statutory detection method, was detected in two batches of samples. In conclusion, the proposed method is simple, sensitive, reliable, and suitable for the high-throughput analysis of the 83 glucocorticoids in cosmetics with different matrices. This method could provide reliable technical support for the daily supervision of cosmetics and serve as a supplement to current glucocorticoid standards.


New learning based super-resolution: use of DWT and IGMRF prior.
In this paper, we propose a new learning-based approach for super-resolving an image captured at low spatial resolution. Given the low spatial resolution test image and a database consisting of low and high spatial resolution images, we obtain super-resolution for the test image. We first obtain an initial high-resolution (HR) estimate by learning the high-frequency details from the available database. A new discrete wavelet transform (DWT) based approach is proposed for learning that uses a set of low-resolution (LR) images and their corresponding HR versions. Since the super-resolution is an ill-posed problem, we obtain the final solution using a regularization framework. The LR image is modeled as the aliased and noisy version of the corresponding HR image, and the aliasing matrix entries are estimated using the test image and the initial HR estimate. The prior model for the super-resolved image is chosen as an Inhomogeneous Gaussian Markov random field (IGMRF) and the model parameters are estimated using the same initial HR estimate. A maximum a posteriori (MAP) estimation is used to arrive at the cost function which is minimized using a simple gradient descent approach. We demonstrate the effectiveness of the proposed approach by conducting the experiments on gray scale as well as on color images. The method is compared with the standard interpolation technique and also with existing learning-based approaches. The proposed approach can be used in applications such as wildlife sensor networks, remote surveillance where the memory, the transmission bandwidth, and the camera cost are the main constraints.


5-hydroxytryptamine-moduline, a new endogenous cerebral peptide, controls the serotonergic activity via its specific interaction with 5-hydroxytryptamine1B/1D receptors.
The serotonergic system controls the activity of neurotransmissions involved in numerous physiological functions. It is also thought to be crucially implicated in various pathologies, including psychiatric disorders such as depression, anxiety, and aggressiveness. The properties of 5-hydroxytryptamine (5-HT)-moduline, a novel endogenous peptide, have been tested in vitro and in vivo. Binding studies have shown that the peptide specifically interacts with 5-HT1B/1D receptors via a noncompetitive mechanism corresponding to a high apparent affinity (EC50 = 10(10) M). The interaction was shown in rat and guinea pig brain tissues and in cells transfected with either 5-HT1B or 5-HT1D beta receptor gene. [3H]5-HT-moduline binds to a single population of sites in mammalian brain (Kd = 0.4 nM in rat, Kd = 0.8 nM in guinea pig) as well as in transfected cells expressing the 5-HT1B or the 5-HT1D beta receptors (Kd = 0.2 and 0.6 nM, respectively). Furthermore, the binding is clearly specific of the LSAL sequence. Autoradiographic studies showed an heterogeneous brain distribution of this site. The interaction of 5-HT-moduline with the 5-HT1B/1D receptor corresponds to a decrease in the functional activity of the receptor (i.e., a decrease in the inhibitory effect of a 5-HT1B agonist on the evoked release of [3H]5-HT from synaptosomal preparation). It was also shown that 5-HT-moduline possess an in vivo effect in the social interaction test in mouse. Finally, it was demonstrated that 5-HT-moduline was released from brain synaptosomal preparation by a K+/Ca(2+)-dependent mechanism. In conclusion, 5-HT-moduline is a novel endogenous peptide regulating the serotonergic activity via a direct action at presynaptic 5-HT receptor. It may play an important role in the physiological mechanisms involving the serotonergic system, particularly in mechanisms corresponding to the elaboration of an appropriate response of the central nervous system to a given stimulus.


The relationship between occupational metal exposure and arterial compliance.
The objective of this study was to evaluate the relationship between cumulative occupational exposure to various metals and arterial compliance in welders. The observational follow-up study consisted of 25 subjects. Levels of nickel (Ni), lead, cadmium, manganese, and arsenic from toenails were assessed using mass spectrometry. Arterial compliance as reflected by augmentation index (AIx) was measured using SphygmoCor Px Pulse Wave Analysis System. Linear regression models were used to assess the associations. For every 1 unit increase in log-transformed toenail Ni, there was a statistically significant 5.68 (95% confidence interval, 1.38 to 9.98; P = 0.01) unit increase in AIx. No significant associations were found between AIx and lead, cadmium, manganese, and arsenic. Cumulative Ni exposure is associated with increased arterial stiffness in welders and may increase risk of adverse cardiovascular outcomes.


Change in antihypertensive drug prescribing after guideline implementation: a controlled before and after study.
Antihypertensive drug choices and treatment levels are not in accordance with the existing guidelines. We aimed to assess the impact of a guideline implementation intervention on antihypertensive drug prescribing. In this controlled before and after study, the effects of a multifaceted (education, audit and feedback, local care pathway) quality programme was evaluated. The intervention was carried out in a health centre between 2002 and 2003. From each health care unit (n = 31), a doctor-nurse pair was trained to act as peer facilitators in the intervention.All antihypertensive drugs prescribed by 25 facilitator general practitioners (intervention GPs) and 53 control GPs were retrieved from the nationwide Prescription Register for three-month periods in 2001 and 2003. The proportions of patients receiving specific antihypertensive drugs and multiple antihypertensive drugs were measured before and after the intervention for three subgroups of hypertension patients: hypertension only, with coronary heart disease, and with diabetes. In all subgroups, the use of multiple concurrent medications increased. For intervention patients with hypertension only, the odds ratio (OR) was 1.12 (95% CI 0.99, 1.25; p = 0.06) and for controls 1.13 (1.05, 1.21; p = 0.002). We observed no statistically significant differences in the change in the prescribing of specific antihypertensive agents between the intervention and control groups. The use of agents acting on the renin-angiotensin-aldosterone system increased in all subgroups (hypertension only intervention patients OR 1.19 (1.06, 1.34; p = 0.004) and controls OR 1.24 (1.15, 1.34; p < 0.0001). A multifaceted guideline implementation intervention does not necessarily lead to significant changes in prescribing performance. Rigorous planning of the interventions and quality projects and their evaluation are essential.


[The prognostic value of cytomegalovirus antigenemia and viremia for the development of cytomegalovirus disease and the survival of AIDS patients].
To analyse risk factors for morbidity and survival associated with blood cytomegalovirus (CMV) detection with the antigenemia method among AIDS patients. CMV antigenemia and CMV blood cultures in 277 AIDS patients IgG-CMV sero-positive with a CD4 level lower than 200 x 10(6)/l under antiretroviral monotherapy were analysed. We consider cases the 116 patients with one or more positive blood samples tested for pp65 antigenemia or CMV culture. They were matched with 161 control patients with negative antigenemia or viremia. Multivariate analysis pointed out a significant positive association for blood CMV reactivation with the following variables: CMV disease development and CMV urine detection, sex-acquired HIV infection, CD4+ < 50 x 10(6)/l and matched time from AIDS diagnosis to CMV blood culture correlated with positive antigenemias. Quantitative antigenemia title showed predictive value for risk of CMV disease although 23% of retinitis patients had persistent undetectable antigenemia. CMV invasive disease developed in 48% of cases and 11% of controls (relative risk [RR]: 7.9; 95% confidence interval [CI]: 4.2-14.7). Mortality after 12 months of follow-up was 73% vs 52% respectively (p < 0.001). Time survival curves after CD4+ count adjusting remained significantly lower for case patients (median, 127 days vs 355 days; p < 0.01 by log-rank test). Increased death rate was found in patients with CMV disease (74%), followed by patients with CMV antigenemia but no disease (70%) and patients without antigenemia or CMV disease (mortality 49%). CMV blood detection in AIDS patients may be considered as a bad prognosis marker for CMV morbidity and survival. This risk increases with higher CMV antigenemias. Therefore, pre-emptive anti-CMV therapy should be considered in this restricted population.


Circulation of a Simbu Serogroup Virus, Causing Schmallenberg Virus-Like Clinical Signs in Northern Jordan.
Schmallenberg virus (SBV)-like clinical cases of abortions in northern Jordan in early 2013, together with the emergence of SBV in Europe in 2011, its rapid spread within the following years and the detection of this virus in Turkey, raised questions about the distribution of SBV or related orthobunyaviruses. To evaluate the occurrence of SBV or related members of the Simbu serogroup of orthobunyaviruses in Jordan, bulk milk (cattle) and serum samples (cattle, sheep and goat) collected in northern Jordan in 2013 were first tested by commercially available SBV antibody ELISAs. Indeed, 3 of 47 bulk milk samples and 57 of 115 serum samples provided positive results, but SBV specificity of the ELISA results could not be confirmed by virus neutralization assays. Instead, subsequent cross-neutralization tests were able to further investigate the specificity of these antibodies. Here, a significant inhibition of Aino virus was observed. Thus, the causative agent was most likely a Simbu serogroup virus closely related to Aino virus. Consequently, these results confirm that members of this group of virus are not only present in Europe, Africa or Australia, but also in the Middle East.


Corynebacterium lipophiloflavum sp. nov. isolated from a patient with bacterial vaginosis.
A unique coryneform bacterium was isolated from a patient with bacterial vaginosis. Chemotaxonomical investigations demonstrated that the unknown bacterium belonged to the genus Corynebacterium. The yellow-pigmented, slightly lipophilic, oxidative, urea-hydrolyzing bacterium could be phenotypically readily differentiated from the other members of the genus Corynebacterium. Comparative 16S rRNA gene analysis revealed that the bacterium represented a new subline within the genus Corynebacterium for which the name Corynebacterium lipophiloflavum sp. nov. is proposed. The type strain is CCUG 37336 (DSM 44291).


Psychometric evaluation of critical incident video instruments for nursing education.
The Critical Incident Video (CIV) Project is a mixed method longitudinal study that uses CIVs to prepare nursing faculty members to address common teaching challenges. CIVs are short videos that present unresolved teaching challenges. Given the lack of specific instruments for evaluating the usefulness of CIVs, the aim of this phase of the project was to develop and test two instruments measuring the pedagogical effects of CIVs. The CIV Preparation and Confidence Scale (CIVPCS©) and the CIV Simulation Experience Scale (CIVSES©) were assessed for validity and reliability. Using a Delphi method, a convenience sample of 23 nurse educators provided feedback enhancing the validity and clarity of the CIVPCS©. Reliability of the CIVPCS© was determined using Cronbach's alpha and test-retest method. No changes were recommended for the CIVSES©. Findings from the assessment of these newly developed CIV instruments are reported and implications for faculty development are discussed.


Wnt-PLC-IP3-Connexin-Ca2+ axis maintains ependymal motile cilia in zebrafish spinal cord.
Ependymal cells (ECs) are multiciliated neuroepithelial cells that line the ventricles of the brain and the central canal of the spinal cord (SC). How ependymal motile cilia are maintained remains largely unexplored. Here we show that zebrafish embryos deficient in Wnt signaling have defective motile cilia, yet harbor intact basal bodies. With respect to maintenance of ependymal motile cilia, plcδ3a is a target gene of Wnt signaling. Lack of Connexin43 (Cx43), especially its channel function, decreases motile cilia and intercellular Ca2+ wave (ICW) propagation. Genetic ablation of cx43 in zebrafish and mice diminished motile cilia. Finally, Cx43 is also expressed in ECs of the human SC. Taken together, our findings indicate that gap junction mediated ICWs play an important role in the maintenance of ependymal motile cilia, and suggest that the enhancement of functional gap junctions by pharmacological or genetic manipulations may be adopted to ameliorate motile ciliopathy.


Cocaine-induced release of CXCL10 from pericytes regulates monocyte transmigration into the CNS.
Cocaine is known to facilitate the transmigration of inflammatory leukocytes into the brain, an important mechanism underlying neuroinflammation. Pericytes are well-recognized as important constituents of the blood-brain barrier (BBB), playing a key role in maintaining barrier integrity. In the present study, we demonstrate for the first time that exposure of human brain vascular pericytes to cocaine results in enhanced secretion of CXCL10, leading, in turn, to increased monocyte transmigration across the BBB both in vitro and in vivo. This process involved translocation of σ-1 receptor (σ-1R) and interaction of σ-1R with c-Src kinase, leading to activation of the Src-PDGFR-β-NF-κB pathway. These findings imply a novel role for pericytes as a source of CXCL10 in the pericyte-monocyte cross talk in cocaine-mediated neuroinflammation, underpinning their role as active components of the innate immune responses.


Prevalence of food allergens sensitization and food allergies in a group of allergic Honduran children.
Food allergy is a public health problem that has increased in the last decade. Despite the increasing rates in children, quality data on the burden of these diseases is lacking particularly in developing countries. Honduras has no studies in pediatric patients. The objective of this research was to identify the most common sensitization patterns to food through epicutaneous skin testing and food allergy rates in children and their correlation with common allergic diseases in a group of patients from Hospital of Pediatrics Maria. Cross-sectional retrospective, descriptive study in which records and database of all allergic patients in the immunology outpatient clinic from Hospital of Pediatrics Maria were reviewed between the periods of January 2015 through June 2016. A total of 365 children were analyzed, the age of participants were in the range from 1 to 18 years, with an average of 9.8 years. Sensitization to food allergens were found in 23, and 58.3% were poly-sensitized. The most common food allergens that patients were sensitized to: milk 9.0%, eggs 6.9%, peanut 4.9% and pork meat 4.4%. Food allergy was confirmed via oral food challenged in 9.3% of the patients. The most frequent food allergies found were: cow's milk allergy 6%, hen's egg allergy 5.2% and wheat allergy 1.9%. Milk and egg were the most common a food allergens found in the population studied. Most of the patients were found to be poly-sensitized. The frequent food allergies confirmed via oral food challenge were cow's milk allergy, hen's egg allergy and wheat allergy.


Corticosteroid therapy augments gastroduodenal permeability to sucrose.
The aim of the present study was to investigate whether corticosteroid therapy alters gastroduodenal mucosal permeability and whether permeability alteration is associated with macroscopic mucosal damage. Eight patients taking oral corticosteroid therapy (total prednisone-equivalent dose, 1.5+/-0.1 g; duration, approximately 30 days), nine patients with multiple sclerosis taking high-dose intravenous methyl-prednisolone therapy (total dose, 11.7+/-0.5 g; duration, approximately 9 days), and 20 age- and gender-matched controls were studied. Gastroduodenal permeability was determined using sucrose as a site-specific permeability probe. Five-hour urine was collected after ingesting 100 g of sucrose and its urinary excretion rate was measured using high-pressure liquid chromatography. Gastroduodenal endoscopy was performed before steroid therapy to exclude subjects with evidence of macroscopic mucosal lesions. The sucrose test and endoscopy were repeated after completion of corticosteroid therapy. The urinary sucrose excretion rates were similar in the control group and in patient groups before corticosteroid therapy. The median excretion rate of sucrose increased four (one to 28)- and eight (two to 35)-fold, respectively, as compared with pretreatment values in patients taking oral steroid and high-dose intravenous methyl-prednisolone therapy (p < 0.01). Considering all patients together, subjects who received a mean prednisone-equivalent dose of 8.4+/-1.5 g exhibited mucosal lesions, whereas patients who received 3.3+/-1.8 g did not (p = 0.06). The post-therapy increments in sucrose excretion rates were associated with neither the presence of macroscopic lesions nor with the total steroid dose received. Corticosteroid therapy augments gastroduodenal permeability and high doses are associated with macroscopic mucosal lesions. Steroid-induced permeability increase does not appear to be associated with the presence of macroscopic mucosal lesions.


A modular transcriptome map of mature B cell lymphomas.
Germinal center-derived B cell lymphomas are tumors of the lymphoid tissues representing one of the most heterogeneous malignancies. Here we characterize the variety of transcriptomic phenotypes of this disease based on 873 biopsy specimens collected in the German Cancer Aid MMML (Molecular Mechanisms in Malignant Lymphoma) consortium. They include diffuse large B cell lymphoma (DLBCL), follicular lymphoma (FL), Burkitt's lymphoma, mixed FL/DLBCL lymphomas, primary mediastinal large B cell lymphoma, multiple myeloma, IRF4-rearranged large cell lymphoma, MYC-negative Burkitt-like lymphoma with chr. 11q aberration and mantle cell lymphoma. We apply self-organizing map (SOM) machine learning to microarray-derived expression data to generate a holistic view on the transcriptome landscape of lymphomas, to describe the multidimensional nature of gene regulation and to pursue a modular view on co-expression. Expression data were complemented by pathological, genetic and clinical characteristics. We present a transcriptome map of B cell lymphomas that allows visual comparison between the SOM portraits of different lymphoma strata and individual cases. It decomposes into one dozen modules of co-expressed genes related to different functional categories, to genetic defects and to the pathogenesis of lymphomas. On a molecular level, this disease rather forms a continuum of expression states than clearly separated phenotypes. We introduced the concept of combinatorial pattern types (PATs) that stratifies the lymphomas into nine PAT groups and, on a coarser level, into five prominent cancer hallmark types with proliferation, inflammation and stroma signatures. Inflammation signatures in combination with healthy B cell and tonsil characteristics associate with better overall survival rates, while proliferation in combination with inflammation and plasma cell characteristics worsens it. A phenotypic similarity tree is presented that reveals possible progression paths along the transcriptional dimensions. Our analysis provided a novel look on the transition range between FL and DLBCL, on DLBCL with poor prognosis showing expression patterns resembling that of Burkitt's lymphoma and particularly on 'double-hit' MYC and BCL2 transformed lymphomas. The transcriptome map provides a tool that aggregates, refines and visualizes the data collected in the MMML study and interprets them in the light of previous knowledge to provide orientation and support in current and future studies on lymphomas and on other cancer entities.


Evaluation of the birthweight values of newborns presenting at the Mother-Child Health and Family Planning Center in Yenibosna, Istanbul, Turkey.
This study was conducted to examine the effect of a number of variables related to the mother (age, educational level, employment status, cigarette smoking during pregnancy) and to the baby (sex and birth order) on newborns' birthweight. The research was carried out in the province of Istanbul, one of Turkey's large metropolises, at the Mother-Child Health and Family Planning Center in the district of Yenibosna, where 0-1 month old infants had been brought in for phenylketonuria screening and vaccinations. The mean age of the mothers was 26.1 +/- 4.8 years and the mean birthweight of the newborns was 3236.7 +/- 542.2 g. Of the infants, 6.3% were classified as having a low birthweight and 8.3% were large infants. The mean birthweight showed a statistical significance depending upon the infants' sex and birth order. The mean birthweight of the infants of the working mothers, as opposed to the unemployed mothers and the mothers in nuclear families, as opposed to the mothers in extended families, was higher.


Chromatographic detection of low-molecular-mass metal complexes in the cytosol of Saccharomyces cerevisiae.
Fluorescence-based chelators are commonly used to probe labile low-molecular-mass (LMM) metal pools in the cytosol of eukaryotic cells, but such chelators destroy the complexes of interest during detection. The objective of this study was to use chromatography to directly detect such complexes. Towards this end, 47 batches of cytosol were isolated from fermenting S. cerevisiae yeast cells and passed through a 10 kDa cut-off membrane. The metal contents of the cytosol and resulting flow-through solution (FTS) were determined. FTSs were applied to a size-exclusion LC column located in an anaerobic refrigerated glove box. The LC system was coupled to an online inductively-coupled-plasma mass spectrometer (ICP-MS) for detection of individual metals. Iron-detected chromatograms of cytosolic FTSs from WT cells exhibited 2-4 major species with apparent masses between 500-1300 Da. Increasing the iron concentration in the growth medium 40-fold increased the overall intensity of these peaks. Approximately 3 LMM cytosolic copper complexes with apparent masses between 300-1300 Da were also detected; their LC intensities were weak, but these increased with increasing concentrations of copper in the growth medium. Observed higher-mass copper-detected peaks were tentatively assigned to copper-bound metallothioneins Cup1 and Crs5. FTSs from strains in which Cup1 or the Cox17 copper chaperone were deleted altered the distribution of LMM copper complexes. LMM zinc- and manganese-detected species were also present in cytosol, albeit at low concentrations. Supplementing the growth medium with zinc increased the intensity of the zinc peak assigned to Crs5 but the intensities of LMM zinc complexes were unaffected. Phosphorus-detected chromatograms were dominated by peaks at apparent masses 400-800 Da, with minor peaks at 1000-1500 Da in some batches. Sulfur chromatograms contained a low-intensity peak that comigrated with a glutathione standard; quantification suggested a GSH concentration in the cytosol of ca. 13 mM. A second LMM sulfur peak that migrated at an apparent mass of 100 Da was also evident.


A transcriptome signature distinguished sporadic from postradiotherapy radiation-induced sarcomas.
Exposure to ionizing radiation is a known risk factor for cancer. However, up to now, rigorously defined scientific criteria that could establish case-by-case the radiation-induced (RI) origin of a tumour have been lacking. To identify genes that could constitute a RI signature, we compared the transcriptome of 12 sarcomas arising in the irradiation field of a primary tumour following radiotherapy with the transcriptome of 12 sporadic sarcomas. This learning/training set contained four leiomyosarcomas, four osteosarcomas and four angiosarcomas in each subgroup. We identified a signature of 135 genes discriminating RI from sporadic sarcomas. The robustness of this signature was tested by the blind case-by-case classification of an independent set of 36 sarcomas of various histologies. Thirty-one sarcomas were classified as RI or sporadic; it was not possible to propose an aetiology for the five others. After the code break, it was found that one sporadic sarcoma was misclassified as RI. Thus, the signature is robust with a sensitivity of 96%, a positive and a negative predictive value of 96 and 100%, respectively and a specificity of 62%. The functions of the genes of the signature suggest that RI sarcomas were subject to chronic oxidative stress probably due to mitochondrial dysfunction.


Strongly correlated plexcitonics: evolution of the Fano resonance in the presence of Kondo correlations.
We study the optical absorption of a system consisting of a diatomic molecule that exhibits strong electron correlations coupled to metal nanoparticles possessing plasmon resonances by invoking the time-dependent non-crossing approximation. We investigate the evolution of the Fano resonance arising from the plasmon-exciton coupling when both atoms are Coulomb blockaded. We found that the Fano resonance rapidly dwindles as the ambient temperature exceeds the Kondo temperature of the singly occupied discrete state with higher energy and vanishes entirely at elevated temperatures. Our results show that even boosting the plasmon-exciton coupling above this temperature scale fails to revive the Fano resonance. We propose a microscopic model that accounts for these results. We suggest that a possible remedy for observation of the Fano resonance at high ambient temperatures is to position the singly occupied discrete state with the higher energy as close as possible to the Fermi level of the contacts while keeping the emitter resonance constant to prevent the merger of the Fano and plasmon resonances.


Accelerated phase contrast flow imaging with direct complex difference reconstruction.
To propose and evaluate a new model-based reconstruction method for highly accelerated phase-contrast magnetic resonance imaging (PC-MRI) with sparse sampling. This work presents a new constrained reconstruction method based on low-rank and sparsity constraints to accelerate PC-MRI. More specifically, we formulate the image reconstruction problem into separate reconstructions of flow-reference image sequence and complex differences. We then utilize the joint partial separability and sparsity constraints to enable high quality reconstruction from highly undersampled (k,t)-space data. We further integrate the proposed method with ESPIRiT based parallel imaging model to effectively handle multichannel acquisition. The proposed method was evaluated with in vivo data acquired from both 2D and 3D PC flow imaging experiments, and compared with several state-of-the-art methods. Experimental results demonstrate that the proposed method leads to more accurate velocity reconstruction from highly undersampled (k,t)-space data, and particularly superior capability of capturing the peak velocity of blood flow. In terms of flow visualization, blood flow patterns obtained from the proposed reconstruction also exhibit better agreement with those obtained from the fully sampled reference. The proposed method achieves improved accuracy over several state-of-the-art methods for velocity reconstruction with highly accelerated (k,t)-space data. Magn Reson Med 77:1036-1048, 2017. © 2016 International Society for Magnetic Resonance in Medicine.


Nitrogen and photosynthetic function of hermatypic corals. Oxygen exchange of Stylophora pistillata coral under artificial feeding.
The change of Stylophora pistillata coral photosynthetic function (oxygen exchange and biomass of symbionts) under starvation and food enrichment was studied to understand the role of heterotrophy in nitrogen supplements of zooxanthellae. The starvation caused the decrease of frequency of zooxanthellae cells division in 7-10 times. The number of degraded algae cells increased in same proportion and, as a result, the density of zooxanthellae in corals decreased about two times during one-two weeks. Under starvation corals kept their photosynthetic capacity at the level of corals in situ by means of enhancing the zooxanthellae gross photosynthesis. The respiration rate of coral had tendency to increase and the dry mass of polyp tissue to decrease. Under artificial feeding which was following starvation the zooxanthellae density increased in 1.5-2 times, and particular food caused more intensive accumulation of zooxanthellae comparing to dissolved inorganic ammonium. The feeding regime did not affect dry mass of polyp tissue and chlorophyll content as well as respiration and gross productivity of the corals. The conclusion about high effectiveness of particular feeding for supplying symbiotic algae with nitrogen was made and trophic status of zooxanthellae in hospite was determined as unlimited by nitrogen.


[Study on Clinical Application and Supervision of LC-MS in in Vitro Diagnosis Test].
From the perspective of technical evaluation, this study reviewed the current situation of application and clinical application of medical device products were detected by liquid chromatography-tandem mass spectrometry in the market in recent years. The regulatory requirements of these products in China, USA, EU and Japan were compared and analyzed, and the monitoring situation of adverse events after listing, the standards for reference and the domestic and foreign regulatory documents were combined, the clinical application and regulatory risks of the product were analyzed. The problems such as pre-treatment, system matching, adequacy of performance index requirements, inter-room consistency, reference interval and registration unit were discussed and suggestions for supervision were given, with a view to the field of product R&D and production, review and approval of supervision to provide technical reference.


Intravascular ultrasound for iliac artery imaging. Clinical review.
IVUS is able to produce trans-sectional images of the iliac arteries at a high resolution. The three layered appearance of the arterial wall can be visualized. In the atherosclerotic diseased artery calcified plaques can be discerned from non-calcified plaques, and the distribution of the plaque-eccentric or concentric-can be determined. IVUS seems to be superior to arteriography in quantifying the degree of stenosis, being able to relate the luminal area to the mediabounded area at the same site of the artery. The discrepancy between IVUS and arteriography is even greater when evaluating residualstenosis after PTA. Structures such as rupture, intimal flaps and dissection are better visualized with IVUS. In stenotic iliac arteries IVUS has been able to evaluate the effect of PTA and stenting and relating the effect to the morphology of the plaque. IVUS measurements seem to be important predictors of the patency of iliac PTA. The ability of IVUS to evaluate the adaptation of stents to the arterial wall makes it particularly suited as a control procedure for the deployment of endovascular stented grafts. Finally IVUS has the ability to disclose insufficiency of endarterecomy, by visualizing remaining intraluminal material.


Production and processing of soybeans and nutrition and safety of isoflavone and other soy products for human health.
Functional foods are intended to help consumers reduce or manage the risks for certain diseases while maintaining body function and structure. Functional foods are regulated differently depending upon the country. For example, the United States has not defined the term functional food in regulation. Thus, functional foods are treated just like conventional foods for obtaining regulatory safety approval. However, the sales of soy products, soy-enriched foods, and dietary supplements have grown tremendously during the past 3 years because of the increasing consumer awareness of soy as a healthy food ingredient. Isoflavones in soy are believed to have preventive effects for several hormone-dependent diseases, mainly due to their weak estrogenic activity. This mini-review discusses some of the important issues to be considered in using soy and isoflavone products as health foods, including production, composition, products, and processing of soy products, and the fate of isoflavones during processing, their bioavailability, and safety. Some of these issues may affect the choice of raw or basic material sources, processing conditions, quality control procedures/measures, and marketing strategies for both soy-based foods and isoflavones.


Conservation and divergence among Salmonella enterica subspecies.
Genome sequencing efforts of taxonomically proximate organisms successfully divulged proteomic diversity embedded within closely related organisms. The Salmonella enterica subspecies represents a group of enterobacteric pathogens known to share similar genomic content yet possess diverse host specificity and distinct disease symptoms. Study of Salmonella enterica subspecies proteomes reports an overestimation of the proximity among the subspecies. Interestingly, orthology comparison among Salmonella typhi and Salmonella typhimurium across the proteome suggested the metabolic proteins possessed the highest propensity of the divergence, while proteins involved in environment information processing and genetic information processing are least susceptible to evolution. Consistent with earlier reports, transporter proteins and transcription factors are the most populated protein families in the Salmonellae. Several of the unique domains present in Salmonella typhi and Salmonella typhimurium genomes were introduced into the genome through phage invasion and eventually selected. Redundancy and divergence is observed among the metabolic pathway proteins. Though complying with essentiality of their function, the metabolic proteins possess the highest propensity of sampling sequence space for imbibing new function. The detailed cross-genome analysis of the subspecies provides an understanding of diversity and unique attributes defined in the individual Salmonella enterica genomes.


FcRL4 Expression Identifies a Pro-inflammatory B Cell Subset in Viremic HIV-Infected Subjects.
In autoimmune diseases, toll-like receptor (TLR)-stimulated pro-inflammatory IL-6-secreting B cells exert pathogenic roles. Similarly, B cell Fc receptor-like 4 (FcRL4) expression amplifies TLR stimulation, and in rheumatoid arthritis patients, FcRL4 expression identifies a pro-inflammatory B cell subset. B cells from HIV-infected subjects also express heightened levels of FcRL4 and secrete high levels of IL-6: a critical mediator of HIV disease progression. In this study, we sought to determine if FcRL4 identifies a pro-inflammatory B cell subset in HIV-infected subjects and further elucidate the mechanisms underlying FcRL4 amplification of TLR stimulation. We determine that tissue-like memory B cells express the highest endogenous levels of FcRL4 positively correlating with IL-6 expression (p = 0.0022, r = 0.8667), but activated memory B cells exhibit the highest frequency of FcRL4hiIL-6hi cells. FcRL4hi B cells exhibit an activated TLR-signaling pathway identified by elevated phosphorylation levels of: pERK (p = 0.0373), p38 (p = 0.0337), p65 (p = 0.1097), and cJUN (p = 0.0239), concomitant with significantly elevated expression of the TLR-signaling modulator hematopoietic cell kinase (HcK, p = 0.0414). Compared to FcRL4neg B cells from healthy controls, TLR9-stimulated FcRL4pos B cells express significantly higher levels of lL-6 (p = 0.0179). Further, TLR9-stimulated B cells also upregulate the expression of FcRL4 (p = 0.0415) and HcK (p = 0.0386). In B-cell lines, siRNA-mediated HcK knockdown downmodulates TLR9-induced FcRL4-mediated activation quantified by CD23 upregulation (p = 0.0553). We present data suggesting that, in viremic HIV-infected individuals, FcRL4 expression identifies unique IL-6 producing pro-inflammatory B-cell subsets. Further, TLR stimulation likely modulates FcRL4 expression and FcRL4 expression is associated with Hck, potentially enhancing the activation of TLR-signaling associated transcription factors. Pathogenic B-cells have been identified in other disease settings, and this study represents a novel report describing a pro-inflammatory B cell subset in HIV-infected patients.


Inter-relatedness of some isoenzymes of cytochrome P-450 from rat, rabbit and human, determined with monoclonal antibodies.
Monoclonal antibodies have been raised to rat liver cytochromes P-450 b and c, and rabbit liver cytochrome P-450 form 4. A total of six antibodies have been studied. Each antibody reacted strongly both with its homologous antigen and with microsomal fractions selectively enriched with that antigen by treatment of animals with inducing compounds. However, several of the antibodies showed cross-reactivity, either within or between species. A combination of enzyme-linked immunosorbent assay, immunoadsorption, Western blotting and competitive radioimmunoassay revealed that each of the antibodies reacted with a different epitope. Proteolytic digestion of antigen followed by Western blotting of the peptide fragments enabled antibodies, otherwise identical in their reactivity, to be distinguished. It is concluded that complex structural relationships exist amongst the different isoenzymes of cytochrome P-450 and that epitope mapping will help in characterizing both animal and human cytochromes P-450.


Peptide uptake in Candida albicans.
Transport of radioactively labelled peptides has been used to characterize a common transport system for di- and tripeptides in Candida albicans. This permease is energy-dependent and has a requirement for L-amino acid residues, an alpha-linkage between residues and a free amino terminus. Transport was followed by the accumulation inside the cell of intact peptides and component amino acids. After transport of glycyl-[U-14C]phenylalanine the radioactive material was accumulated inside the cell and subsequently leaked into the medium under certain conditions.


Explaining the adjustment of adolescents with type 1 diabetes: role of diabetes-specific and psychosocial factors.
The aim of this study was to explain adjustment (diabetes-related quality of life, general well-being, and psychopathology) in adolescents with type 1 diabetes by testing the direct, mediating, and moderating effects of diabetes-specific and psychosocial factors, using an adapted version of the Disability-Stress-Coping model of Wallander and Varni. A total of 437 adolescents (54.5% girls; age range 11-19 years) with type 1 diabetes (mean +/- SD diabetes duration 6.13 +/- 3.78 years) were recruited from 25 hospitals in the Netherlands. Questionnaires were completed by the adolescents and their family members. Metabolic control was assessed by measuring A1C in all participants in one laboratory. Diabetes stress mediated between A1C and adjustment, after controlling for protective factors, and explained an additional 16% variance in quality of life and a 15% variance in general well-being, whereas a 19% additional variance in psychopathology was explained by both diabetes-related and general stress. No moderating effects were identified after controlling for the main effects of all risk and protective factors in the model. Both diabetes-related and general stress are critical predictors of the adjustment of adolescents with type 1 diabetes. Protective factors such as self-worth and social support may mediate the effects of generic stress and thus should be encouraged. Diabetes-related stress has the potential to displace the effects of protective factors and thus may play a critical role in the development of maladjustment in adolescents with type 1 diabetes.


Interaction of atriopeptin III with lipids and detergents.
Atriopeptin III, a potent natural hypotensive agent, contains little alpha-helical structure but substantial amounts of beta-structure. The peptide can self-associate at millimolar concentrations or can associate with the anionic phospholipid, dimyristoylphosphatidylglycerol. Both of these processes are accompanied by a conformational change suggesting the formation of an increased amount of beta-structure. The peptide can broaden the transition and lower the transition enthalpy of dimyristoylphosphatidylglycerol. The results demonstrate that a peptide hormone can associate with lipid largely in the form of a beta-structure.


ANRIL regulates multiple molecules of pathogenetic significance in diabetic nephropathy.
Hyperglycemia-induced transcriptional alterations lead to aberrant synthesis of a large number of pathogenetic molecules leading to functional and structural damage to multiple end organs including the kidneys. Diabetic nephropathy (DN) remains a major cause of end stage renal disease. Multiple epigenetic mechanisms, including alteration of long non-coding RNAs (lncRNAs) may play a significant role mediating the cellular transcriptional activities. We have previously shown that lncRNA ANRIL may mediate diabetes associated molecular, functional and structural abnormalities in DN. Here we explored downstream mechanisms of ANRIL alteration in DN. We used renal cortical tissues from ANRIL knockout (KO) mice and wild type (WT) mice, with or without streptozotocin (STZ) induced diabetes for RNA sequencing. The differentially expressed genes were identified using edgeR and DESeq2 computational methods. KEGG and Reactome pathway analyses and network analyses using STRING and IPA were subsequently performed. Diabetic animals showed hyperglycemia, reduced body weight gain, polyuria and increased urinary albumin. Both albuminuria and polyuria were corrected in the KO diabetic mice. RNA analyses showed Diabetes induced alterations of a large number of transcripts in the wild type (WT) animals. ANRIL knockout (KO) prevented a large number of such alterations. The altered transcripts include metabolic pathways, apoptosis, extracellular matrix protein synthesis and degradation, NFKB related pathways, AGE-RAGE interaction pathways etc. ANRIL KO prevented majority of these pathways. These findings suggest that as ANRIL regulates a large number of molecules of pathogenetic significance, it may potentially be a drug target for DN and other chronic diabetic complications.


[Spatial and temporal variation of the fish community inhabiting the Laguna Grande de Obispo, Gulf of Cariaco, Sucre State, Venezuela].
The monthly species composition and the spatial and temporal variation of fish community of Laguna Grande de Obispo, Gulf of Canaco, Sucre State, Venezuela were analyzed. The samples were collected using two beach seines of different size from December 1995 to November 1996. A cluster analysis for stations inside the lagoon and time of capture showed 4 major groups, defined principally with ecological parameters of each area. Fishing with large seine in and outside the lagoon showed two large groups which were divided into 10 subgroups in function of station and time, while an inverse analysis of the same sample differentiated into 8 groups of species. based on distribution, dominance, and occurrence. Xenomeianiris brasiliensis, Mugil curema and Eucinostomus argenteus were the most abundant species in both time and space. An analysis of conglomerate on the whole fish community of the sampling period indicated the existence of two groups: i) the first half of the year including December 1995 and October 1996 and ii) the second half of the year. The distribution of fishes in relation to ecological factors is discussed.


Pharmacokinetics of ceftriaxone in patients with renal failure and in those undergoing hemodialysis.
The pharmacokinetic parameters of ceftriaxone in eight patients with end-stage renal disease were determined during dialysis and during the interdialysis period. The mean half-life, clearance, and apparent volume of distribution during dialysis were 16 h, 722 ml/h, and 16.7 liters, respectively. During the interdialysis period, the half-life was 14 h, clearance was 739 ml/h, and volume of distributions was 14 liters. Individual variability in plasma concentrations occurred even in patients with apparently normal hepatic function. Based on these parameters, a dose of 1 g every 24 h would yield concentrations in excess of the concentrations needed to inhibit most gram-positive and gram-negative aerobic species.


Skin disorders, including pyoderma, scabies, and tinea infections.
Pyoderma, scabies, and tinea are common childhood skin disorders too often considered to be merely of nuisance value. More than 111 million children are believed to have pyoderma, with many also co-infected with scabies, tinea, or both. These skin disorders cannot be differentiated by ethnicity or socioeconomic status but, in high-prevalence areas, poverty and overcrowded living conditions are important underlying social determinants. Each is transmitted primarily through direct skin-to-skin contact. For many Indigenous children, these skin conditions are part of everyday life. Although rarely directly resulting in hospitalization or death, there is a high and largely unmet demand for effective management at the primary health-care level, particularly for pyoderma and scabies. Despite particularly high prevalence in some settings, treatment is not sought for many children, and when sought, the clinical benefit from such consultations is variable. The lack of standard, evidence-based recommendations is of much concern. The current evidence base for clinical diagnosis and treatment of these common childhood skin disorders is highlighted.


The molecular adjuvant mC3d enhances the immunogenicity of FimA from type I fimbriae of Salmonella enterica serovar Enteritidis.
The fimbriae of Salmonella enterica serovar Enteritidis are used for colonization and invasion into host cells, and have drawn considerable interest because fimbriae can serve as potential immunogens against many pathogenic bacteria that colonize on epithelial surfaces. The purpose of the study is to use a molecular adjuvant, C3d, to enhance the immunogenicity of FimA proteins against Salmonella enterica serovar Enteritidis. FimA of type I fimbriae from Salmonella enteritidis and FimA with one copy of mC3d, two copies of mC3d2 and three copies of mC3d3 were cloned into the expression vector pCold-TF. Soluble fusion proteins of FimA with different copy of mC3d were induced by IPTG and expressed into Escherichia coli BL21 (DE3). Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) showed that the recombinant proteins from pCold-TF-fimA, TF-fimA-mC3d, TF-fimA-mC3d2, TF-fimA-mC3d3 were 70 kDa, 100 kDa, 130 kDa and 160 kDa, respectively. The fusion protein was recognized by rabbit anti-fimbriae polyclonal antibodies, and then visualized by goat anti-rabbit polyclonal antibodies with a chrome appearance by enzyme-subtract interaction. The recombinant proteins were purified by Ni-TED (tris-carboxymethyl ethylene diamine), immobilized metal ion affinity chromatography (IMAC). Balb/c mice were subcutaneously immunized with the purified proteins and the immune response was monitored by an enzyme-linked immunosorbent assay (ELISA) for FimA-specific antibody. The immunized mice were challenged with a 10-fold LD50 dose (i.e., 100 CFU) of Salmonella enterica serovar Enteritidis standard strain (SD-2) 1 week after the second immunization. The immunized mice with the fusion proteins FimA-mC3d2 and FimA-mC3d3 had increased levels of ELISA titer of antibody that were 2 and 4 logs, respectively, more immunogenic than the TF-FimA protein alone. The challenge results showed that immune protection rate in the mice immunized with 10 μg of FimA, FimA-mC3d2, and FimA-mC3d3 were 50%, 75% and 100%, respectively. We conclude that mC3d can be expressed in a prokaryotic vector and enhance the immune response of the recombinant protein. FimA-mC3d3 is potentially a subunit vaccine against S. enterica serovar Enteritidis infection.


Rapid prediction of MRI-induced RF heating of active implantable medical devices using machine learning.
The interaction between an active implantable medical device and magnetic resonance imaging (MRI) radiofrequency (RF) fields can cause excessive tissue heating. Existing methods for predicting RF heating in the presence of an implant rely on either extensive phantom experiments or electromagnetic (EM) simulations with varying degrees of approximation of the MR environment, the patient, or the implant. On the contrary, fast MR thermometry techniques can provide a reliable real-time map of temperature rise in the tissue in the vicinity of conductive implants. In this proof-of-concept study, we examined whether a machine learning (ML) based model could predict the temperature increase in the tissue near the tip of an implanted lead after several minutes of RF exposure based on only a few seconds of experimentally measured temperature values. We performed phantom experiments with a commercial deep brain stimulation (DBS) system to train a fully connected feedforward neural network (NN) to predict temperature rise after ~3 minutes of scanning at a 3 T scanner using only data from the first 5 seconds. The NN effectively predicted ΔTmax-R2 = 0.99 for predictions in the test dataset. Our model also showed potential in predicting RF heating for other various scenarios, including a DBS system at a different field strength (1.5 T MRI, R2 = 0.87), different field polarization (1.2 T vertical MRI, R2 = 0.79), and an unseen implant (cardiac leads at 1.5 T MRI, R2 = 0.91). Our results indicate great potential for the application of ML in combination with fast MR thermometry techniques for rapid prediction of RF heating for implants in various MR environments.Clinical Relevance- Machine learning-based algorithms can potentially enable rapid prediction of MRI-induced RF heating in the presence of unknown AIMDs in various MR environments.


Unfolding, aggregation, and seeded amyloid formation of lysine-58-cleaved beta 2-microglobulin.
Beta(2)-microglobulin (beta(2)m) is the amyloidogenic protein in dialysis-related amyloidosis, but the mechanisms underlying beta(2)m fibrillogenesis in vivo are largely unknown. We study a structural variant of beta(2)m that has been linked to cancer and inflammation and may be present in the circulation of dialysis patients. This beta(2)m variant, DeltaK58-beta(2)m, is a disulfide-linked two-chain molecule consisting of amino acid residues 1-57 and 59-99 of intact beta(2)m, and we here demonstrate and characterize its decreased conformational stability as compared to wild-type (wt) beta(2)m. Using amide hydrogen/deuterium exchange monitored by mass spectrometry, we show that DeltaK58-beta(2)m has increased unfolding rates compared to wt-beta(2)m and that unfolding is highly temperature dependent. The unfolding rate is 1 order of magnitude faster in DeltaK58-beta(2)m than in wt-beta(2)m, and at 37 degrees C the half-time for unfolding is more than 170-fold faster than at 15 degrees C. Conformational changes are also reflected by a very prominent Congo red binding of DeltaK58-beta(2)m at 37 degrees C, by the evolution of thioflavin T fluorescence, and by changes in intrinsic fluorescence. After a few days at 37 degrees C, in contrast to wt-beta(2)m, DeltaK58-beta(2)m forms well-defined high molecular weight aggregates that are detected by size-exclusion chromatography. Atomic force microscopy after seeding with amyloid-beta(2)m fibrils under conditions that induce minimal fibrillation in wt-beta(2)m shows extensive amyloid fibrillation in DeltaK58-beta(2)m samples. The results highlight the instability and amyloidogenicity under near physiological conditions of a slightly modified beta(2)m variant generated by limited proteolysis and illustrate stages of amyloid formation from early conformational variants to overt fibrillation.


Perspectives on follow-up care and research for childhood cancer survivors: results from an international SIOP meet-the-expert questionnaire in Kyoto, 2018.
Survival of childhood cancer has increased over the past decades. This has led to the development of strategies aiming to enhance follow-up care and research, for which priorities may vary globally. We explored perspectives of an international healthcare workers panel. Attendants of a meet-the-expert session on childhood cancer survivorship at the 2018 SIOP conference completed a survey about their view on important follow-up care and research aspects for survivors below and over 18 years. We analysed overarching categories and subtopics, and compared Asian versus European and North American healthcare workers. A total of 58 participants from different medical specialties (67.2% paediatric oncologists) and continents (48.3% Asia, 39.7% Europe/North America) responded. Follow-up care priorities for survivors below and over 18 years included physical care (39.3% ≤18 years, 35.9% >18 years) and healthcare structure (29.4%, 26.0%). Physical care was also the most important research aspect for both age groups (52.5%, 50.7%). Psychological support was the most frequently reported subtopic. Asian clinicians (n = 22) primarily prioritized physical care aspects of follow-up care, whereas European/North American (n = 19) clinicians underscored the importance of healthcare structure. Physical care is the most important aspect of survivorship care and research according to clinicians from several continents. Asian and European/North American respondents shared most priorities, however, healthcare structure was a more important category for European/North American clinicians. The most common subtopic was psychological support, underlining also the need to involve psychologists in follow-up.


Classification of grasps by robot hands.
Grasping robotic hands is classified into three categories based on the object connectivity. We decompose the space of contact forces into four subspaces and develop a method to determine the dimensions of the subspaces with respect to the connectivity of the grasped object. The relationships we obtain reveal the kinematic and static characteristics of three categories of grasps. It indicates how contact forces can be decomposed corresponding to each type of grasp. The technique also provides a guideline for determining the distribution of contact forces on grasped objects. We analyze how power grasps are identified from the object connectivity and used to synthesize hand configurations for grasping and manipulation tasks. A physical interpretation of the subspaces and the determination of their dimensions are illustrated by examples.


Hypertensive disorders of pregnancy and menopausal symptoms: a cross-sectional study from the data registry on experiences of aging, menopause, and sexuality.
Hypertensive disorders of pregnancy and menopausal symptoms, specifically vasomotor symptoms, have both been associated with cardiovascular disease risk in women. However, data are sparse on the association between these two female-specific cardiovascular risk factors. This study was conducted to investigate the association between a history of a hypertensive disorder of pregnancy and menopausal symptoms. This was a cross-sectional study of women aged 40 to 65 years seen for specialty consultation in women's health clinics at Mayo Clinic Rochester, MN and Scottsdale, AZ, between May, 2015 and September, 2019. A self-reported history of hypertensive disorders of pregnancy served as the independent variable, and menopause symptoms as assessed by the Menopause Rating Scale were the primary outcome measure. Of 2,684 women included in the analysis, 180 had a self-reported history of a hypertensive disorder of pregnancy. The total menopausal symptom scores as well as somatic and psychological domain scores were higher in women with a history of a hypertensive disorder of pregnancy compared to women without a history of a hypertensive disorder of pregnancy or to women without a pregnancy. On multivariable analysis, women with a hypertensive disorder of pregnancy using hormone therapy had significantly higher total menopause symptom scores than women with no such history. In this large cross-sectional study, a history of hypertensive disorders of pregnancy was associated with more bothersome menopausal symptoms. Additional study is needed to determine the strength of this association, underlying mechanisms of the association, and clinical implications for cardiovascular risk prediction in women.


Australian trial of topical minoxidil and placebo in early male pattern baldness.
One hundred and sixty nine men with early male pattern baldness (androgenic alopecia) were treated in a random, double-blind fashion with either 2% minoxidil solution or placebo vehicle for 24 weeks, one ml applied twice daily. After 24 weeks all patients received the active solution until week 48. After 24 weeks the minoxidil treated patients had increased their non-vellus hair counts significantly more than the placebo treated group; means were 37.6 and 8.8 hairs per reference area, 95% C.I. for difference = 10.85 to 60.75. The rate of non-vellus hair regrowth was also greater among minoxidil treated patients than placebo treated patients. Nine (12.5%) evaluable minoxidil treated patients compared with 2 (2.7%) evaluable placebo treated patients reported moderate or dense hair regrowth at week 24. Minimal regrowth was reported by 18 (25%) active group and 15 (20%) placebo group patients. The investigators considered that 3 (2%) of the minoxidil group and none of the placebo group had moderate hair regrowth and that none had dense regrowth. After 48 weeks treatment 28 (23%) patients considered that they had moderate hair regrowth and the investigators considered that 14 (12%) patients had moderate regrowth. None had dense growth. No serious adverse reactions or deaths were reported. Minoxidil solution appeared to be an efficacious and safe treatment for early androgenic alopecia.


Coarse-grained simulations of poly(propylene imine) dendrimers in solution.
The behavior of poly(propylene imine) (PPI) dendrimers in concentrated solutions has been investigated using molecular dynamics simulations containing up to a thousand PPI dendrimers of generation 4 or 5 in explicit water. To deal with large system sizes and time scales required to study the solutions over a wide range of dendrimer concentrations, a previously published coarse-grained model was applied. Simulation results on the radius of gyration, structure factor, intermolecular spacing, dendrimer interpenetration, and water penetration are compared with available experimental data, providing a clear concentration dependent molecular picture of PPI dendrimers. It is shown that with increasing concentration the dendrimer volume diminishes accompanied by a reduction of internalized water, ultimately resulting in solvent filled cavities between stacked dendrimers. Concurrently dendrimer interpenetration increases only slightly, leaving each dendrimer a separate entity also at high concentrations. Moreover, we compare apparent structure factors, as calculated in experimental studies relying on the decoupling approximation and the constant atomic form factor assumption, with directly computed structure factors. We demonstrate that these already diverge at rather low concentrations, not because of small changes in form factor, but rather because the decoupling approximation fails as monomer positions of separate dendrimers become correlated at concentrations well below the overlap concentration.


Paranormal belief, experience, and the Keirsey Temperament Sorter.
121 college students completed the Anomalous Experience Inventory and the Keirsey Temperament Sorter. Multiple regression analyses provided significant models predicting both Paranormal Experience and Belief; the main predictors were the other subscales of the Anomalous Experience Inventory with the Keirsey variables playing only a minor role.


Prevalence of renal disease in asymptomatic heroin addicts.
Renal function was studied in 145 asymptomatic male heroin addicts admitted to a methadone detoxification program. The mean duration of addiction was ten years. Three patients had protein excretion greater than 150 mg/24 hr; in one of these, membranous glomerulonephritis was found. All except one had normal creatinine clearance. Hypertension was present in 2.7%. This study does not support the concept that heroin addiction is associated with a high prevalence of renal disease.


Sleep-disordered breathing and obesity: pathophysiology, complications, and treatment.
Sleep-disordered breathing (SDB) is a medical condition that has increasingly recognized adverse health effects. Obesity is the primary risk factor for the development of SDB and contributes to cardiovascular and metabolic abnormalities in this population. However, accumulating evidence suggests that SDB may be related to the development of these abnormalities independent of obesity. Periodic apneas and hypopneas during sleep result in intermittent hypoxemia, arousals, and sleep disturbances. These pathophysiologic characteristics of SDB are likely mechanisms underlying cardiovascular and metabolic abnormalities including hypertension and other cardiovascular diseases, altered adipokines, inflammatory cytokines, insulin resistance, and glucose intolerance. Treatment of SDB with continuous positive airway pressure reverses some but not all of these abnormalities; however, studies to date have demonstrated inconsistent findings. Weight loss strategies, including diet, exercise, medications, and bariatric surgery, have been evaluated as a treatment strategy for SDB. In preliminary studies, dietary intervention and exercise reduced severity of SDB. One study demonstrated improvements in SDB severity using the weight-reducing medication sibutramine. In morbidly obese subjects, bariatric surgery effectively induces weight loss and improvement in SDB severity and symptoms, but long-term benefits remain uncertain. Large randomized trials are required to determine the utility of these strategies as long-term approaches to improving SDB and reducing associated complications.


Massage therapy of moderate and light pressure and vibrator effects on EEG and heart rate.
Three types of commonly used massage therapy techniques were assessed in a sample of 36 healthy adults, randomly assigned to: (1) moderate massage, (2) light massage, or (3) vibratory stimulation group (n = 12 per group). Changes in anxiety and stress were assessed, and EEG and EKG were recorded. Anxiety scores decreased for all groups, but the moderate pressure massage group reported the greatest decrease in stress. The moderate massage group also experienced a decrease in heart rate and EEG changes including an increase in delta and a decrease in alpha and beta activity, suggesting a relaxation response. Finally, this group showed increased positive affect, as indicated by a shift toward left frontal EEG activation. The light massage group showed increased arousal, as indicated by decreased delta and increased deta activity and increased heart rate. The vibratory stimulation group also showed increased arousal, as indicated by increased heart rate and increased theta, alpha, and beta activity.


Use of drainability and filterability simulations for evaluation of oxidative treatment and polymer conditioning of sludge.
In the traditional view of sludge structure, a two-phase system is visualized. The solid phase is often illustrated as consisting of uniform, spherical, negatively charged particles. This simplistic picture limits the understanding of both conditioning and dewatering. Specifically, it limits us to only two strategies for destabiiization: charge neutralization (using cationic coagulant species with either uniform or patch effects), and bridging (using polymeric flocculants). In fact, the situation is more complex in many respects. In this paper, we compared chemical conditioning of anaerobically digested biosolids using (1) conventional polymeric flocculation, and (2) treatment by chemical oxidants. Since these strategies may alter dewatering behavior by very different mechanisms, we report comparisons using a lab-scale simulator of belt press dewatering, including separate steps for the drainage and filtration processes. This allows greater insight into the effects of these conditioning methods and how they might be properly employed.


Analysis of renal diseases detected in renal biopsies of adult patients: A single-center experience.
Renal biopsy is crucial while evaluating for the diagnosis of glomerular, vascular, tubulointerstitial, and genetic diseases. It gives vital information which helps in estimating the disease prognosis, progression, and management. This is the retrospective analysis of all adult patients aged above 18 years, who underwent percutaneous renal biopsy at The Kidney Center Post Graduate Training Institute, Karachi, over a duration of 18 years, i.e., January 1, 1996, to December 2013. Renal graft biopsies and those which were inadequate were excluded from analysis. Of the1962 biopsies performed, we included 1521 biopsies in our assessment. The mean age of the population was 38 ± 15.26 years (range 18-88 years). There were 920 (60.5%) males and 601 (39.5%) females. The most common clinical indication of kidney biopsy was nephrotic syndrome, i.e., 741 (45.7%), followed by chronic kidney disease, 253 (16.6%); acute renal failure, 184; (12.1%) and rapidly progressive glomerulonephritis (GN), 124 (8.2%). Primary GN was found in the majority of the patients, 984 (64.7%), followed by secondary GN in 249 (16.4%), tubulointerstitial disease in 224 (14.7%), and vascular disease in 64 (4.2%). In primary GN, focal segmental glomerulosclerosis was the most common histopathological diagnosis in 297 (19.5%) patients, followed by MGN in 224 (14.7%), chronic GN in 98 (6.4%), crescentic GN in 93 (6.1%), minimal change disease in 87 (5.7%), membranoproliferative glomerulonephritis in 58 (3.8%), and postinfection glomerulonephritis in 53 (3.5%) patients. This study shows that focal segmental glomerulosclerosis is the most common lesion in renal biopsy in the young age group followed by membranous nephropathy. Diabetic nephropathy and chronic interstitial nephritis were dominant secondary pathological lesions in older age group, whereas lupus nephritis was the most common secondary disease in young age females.


High dose intravenous streptokinase for acute myocardial infarction: preliminary results of a multicenter trial.
To assess the efficacy of intravenous streptokinase in patients with acute myocardial infarction, 40 patients (30 men and 10 women, mean age 54 years) with acute myocardial infarction were given 1.5 million U of streptokinase intravenously in 1 hour, and coronary arteriography was performed repeatedly to assess reperfusion. Streptokinase treatment was begun 270 +/- 86 (mean +/- SD) minutes after the onset of chest pain. Of the 40 patients, 34 had total or near total coronary occlusion before streptokinase administration. In 14 (41%) of these 34 patients, some reperfusion occurred during the 90 minutes after the administration of streptokinase, but in only 11 of the 14 was reperfusion present at 90 minutes. After streptokinase administration, all patients received heparin for 8 to 10 days; they were subsequently administered aspirin and dipyridamole. Clinical evidence of reocclusion during the first 24 hours of heparin therapy occurred in one patient. Thus, when given to patients with acute myocardial infarction and total coronary occlusion an average of 4 1/2 hours after the onset of chest pain, high dose intravenous streptokinase achieves reperfusion in only about 40% and results in sustained reperfusion in only about 30%.


Fast electron transport dynamics and energy deposition in magnetized, imploded cylindrical plasma.
Inertial confinement fusion approaches involve the creation of high-energy-density states through compression. High gain scenarios may be enabled by the beneficial heating from fast electrons produced with an intense laser and by energy containment with a high-strength magnetic field. Here, we report experimental measurements from a configuration integrating a magnetized, imploded cylindrical plasma and intense laser-driven electrons as well as multi-stage simulations that show fast electrons transport pathways at different times during the implosion and quantify their energy deposition contribution. The experiment consisted of a CH foam cylinder, inside an external coaxial magnetic field of 5 T, that was imploded using 36 OMEGA laser beams. Two-dimensional (2D) hydrodynamic modelling predicts the CH density reaches [Formula: see text], the temperature reaches 920 eV and the external B-field is amplified at maximum compression to 580 T. At pre-determined times during the compression, the intense OMEGA EP laser irradiated one end of the cylinder to accelerate relativistic electrons into the dense imploded plasma providing additional heating. The relativistic electron beam generation was simulated using a 2D particle-in-cell (PIC) code. Finally, three-dimensional hybrid-PIC simulations calculated the electron propagation and energy deposition inside the target and revealed the roles the compressed and self-generated B-fields play in transport. During a time window before the maximum compression time, the self-generated B-field on the compression front confines the injected electrons inside the target, increasing the temperature through Joule heating. For a stronger B-field seed of 20 T, the electrons are predicted to be guided into the compressed target and provide additional collisional heating. This article is part of a discussion meeting issue 'Prospects for high gain inertial fusion energy (part 2)'.


Effect of Sodium Fluoride on the Proliferation and Gene Differential Expression in Human RPMI8226 Cells.
Although fluoride is known to reduce the incidence of caries, chronic excessive fluoride exposure can impair human health, even resulting in fluorosis. Now the underlying mechanisms of fluoride-induced toxicity are not fully understood. So, we conducted this study with the purpose of investigating the effect of sodium fluoride (NaF) in human RPMI8226 cells. In this experiment, human RPMI8226 cells were cultured with varied doses of fluoride (10, 20, 40, 80, 160, 320 μM). After 48 h exposure, the change of cell viability was examined by CCK-8 assay, and also the messenger RNA (mRNA) expression of relevant genes was assessed by QRT-PCR. Compared to the control group, fluoride exposure increased the human RPMI8226 cells viability at relatively lower levels (10-160 μM); however, when the concentration reached to 320 μM, the cell proliferation was significantly inhibited (p < 0.05). In addition, the genes mRNA expression, including ANKRD1, CRSP6, KLF2, SBNO2, ZNF649, FANCM, PDGFA, RNF152, CDK10, and CETN2 changed in a concentration-dependent manner and increased with fluoride exposure concentration. The results suggest that overexposure to fluoride (160-320 μM) can induce cytotoxicity and regulate relevant genes expression. Our findings provide novel insights into the mechanisms of action of fluoride-induced toxicity.


Cytoarchitecture of the Hippocampal Formation in the African Giant Rat (Cricetomys gambianus, Waterhouse).
The African Giant Rat, AGR is an indigenous nocturnal rodent noted for its unique olfactory and cognitive abilities. They have been deployed more recently in the detection of landmines and diagnosis of tuberculosis - two scourges that have had a tremendous negative impact on the African landscape. This olfactory-aided cognition has been linked to the hippocampus. While the anatomical infrastructure of the olfactory bulb of the AGR has been elucidated, little is known about the adaptive cytoarchitecture of the AGR hippocampal formation. This study describes the histological features, including subfields and stratifications of the AGR hippocampus using Nissl and Golgi stains. The basic cytoarchitecture of the AGR hippocampus observed in this study, with respect to stratification, subfields and cell types, is similar to those reported in the laboratory rats. Cell types identified in the AGR hippocampus include pyramidal cells, granule cells and mossy cells with mossy fibers and Schaffer collaterals also delineated. Hippocampal proper subfields CA1 to CA4 were identified. CA3 pyramidal neurons formed a well-defined cell layer starting in between the upper and lower ends of the dentate gyrus and had larger, more distinct pyramidal cells and higher cell layer thickness (240.0±6.0 µm) relative to subfields CA1 (87.0±2.0 µm) and CA2 (109.0±4.20 µm) with significant statistical differences at p<0.001. The detailed, delicate arrangement of various cell types and subfields, intricate wiring with synapses and laminar organization of the hippocampal formation noticed in the AGR strongly supports the canonical trisynaptic circuitry of the hippocampus. It will however be necessary to carry out densitometric studies and detailed neurochemical profiling of the AGR hippocampus to fully elucidate the functional leverage of this unique rodent. We, therefore, suggest the suitability of this rodent as a model for olfaction-linked memory studies.


EMPA-REG OUTCOME: The Endocrinologist's Point of View.
For many years, it was widely accepted that control of plasma lipids and blood pressure could lower macrovascular risk in patients with type 2 diabetes mellitus (T2DM), whereas the benefits of lowering plasma glucose were largely limited to improvements in microvascular complications. The Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients-Removing Excess Glucose (EMPA-REG OUTCOME) study demonstrated for the first time that a glucose-lowering agent, the sodium glucose cotransporter 2 (SGLT2) inhibitor empagliflozin, could reduce major adverse cardiovascular events, cardiovascular mortality, hospitalization for heart failure, and overall mortality when given in addition to standard care in patients with T2DM at high cardiovascular risk. These results were entirely unexpected and have led to much speculation regarding the potential mechanisms underlying cardiovascular benefits. In this review, the results of EMPA-REG OUTCOME are summarized and put into perspective for the endocrinologist who is treating patients with T2DM and cardiovascular disease.


Co-production of surfactin and a novel bacteriocin by Bacillus subtilis subsp. subtilis H4 isolated from Bikalga, an African alkaline Hibiscus sabdariffa seed fermented condiment.
Bikalga is a Hibiscus sabdariffa seed fermented condiment widely consumed in Burkina Faso and neighboring countries. The fermentation is dominated by Bacillus subtilis group species. Ten B. subtilis subsp. subtilis (six isolates) and Bacillus licheniformis (four isolates) isolated from traditional Bikalga were examined for their antimicrobial activity against a panel of 36 indicator organisms including Gram-positive and Gram-negative bacteria and yeasts. The Bacillus spp. isolates showed variable inhibitory abilities depending on the method used. Both Gram-positive and Gram-negative bacteria were inhibited in the agar spot assay while only Gram-positive pathogens were inhibited in the agar well diffusion assay. Cell free supernatants (CFS) of pure cultures of 3 B. subtilis subsp. subtilis (G2, H4 and F1) strains inhibited growth of Listeria monocytogenes, Micrococcus luteus, Staphylococcus aureus and Bacillus cereus, while CFS of 2 B. licheniformis (E3 and F9) strains only inhibited M. luteus. The antimicrobial substance(s) produced by B. subtilis subsp. subtilis H4 was further characterized. The antimicrobial substance(s) produced by H4 was detected from mid-exponential growth phase. The activity was sensitive to protease and trypsin, but resistant to the proteolytic action of proteinase K and papain. Treatment with α-amylase and lipase II resulted in a complete loss of antimicrobial effect, indicating that a sugar moiety and lipid moiety are necessary for the activity. Treatment with mercapto-ethanol resulted in a significant loss, indicative of the presence of disulfide bridges. The antimicrobial activity of H4 was heat resistant and active at pH3-10. PCR detection of yiwB, sboA, spoX, albA and spaS, etnS genes and genes coding for surfactins and plipastatins (fengycins) indicated a potential for subtilosin, subtilin and lipopeptide production, respectively. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) was carried out and a single band of approximately 4kDa had antimicrobial activity. Ultra high performance liquid chromatography-time of flight mass spectrometry (UHPLC-TOFMS) analysis of the 4kDa band allowed identification of surfactin and a protein with a monoisotopic mass of 3346.59Da, which is dissimilar in size to subtilosin and subtilin. Surfactin is a cyclic lipoheptapeptide, which contains a β-hydroxy fatty acid, but no di-sulfide bridges or sugar residues. The complete loss of activity upon amylase treatment indicates that surfactin was not responsible for the observed antimicrobial effect. However, it cannot completely be ruled out that surfactin acts synergistically with the detected protein, though further investigations are needed to confirm this.


A study of mutations in the c-kit gene of 32 dogs with mastocytoma.
Mutations in the intracellular juxtamembrane domain of the c-kit gene in 32 dogs with different grades of histologically confirmed mastocytoma were studied. Transcript RNAs extracted from neoplastic tissue surgically collected from dogs of different breeds and from a negative control were reverse transcribed into complementary DNA and amplified by polymerase chain reaction. The region corresponding to the c-kit juxtamembrane domain was sequenced and compared with GenBank sequences. Two different types of mutations were identified within exon 11: a previously underscribed single-nucleotide substitution and a 6-bp deletion. The c-kit juxtamembrane domain sequences of all dogs were grouped in 3 clusters. No mutations were detected in tissues constitutively expressing c-kit (cerebellum and spleen), obtained from dogs not affected by mastocytoma (controls). All the substitutions were found in dogs bearing grade I or II mast cell tumors; the deletion was detected in 1 dog with grade II mastocytoma.


Polychlorinated biphenyls, dioxins, furans, and organochlorine pesticides in belted kingfisher eggs from the upper Hudson River basin, New York, USA.
Nesting belted kingfishers (hereafter kingfishers, Ceryle alcyon) were studied on the Hudson River near Fort Edward south to New Baltimore (NY, USA) and three nearby river drainages in 2004. Concentrations of 28 organochlorine pesticides, 160 polychlorinated biphenyl (PCB) congeners, and 17 dioxin and furan (PCDD-F) congeners were quantified in kingfisher eggs. The pattern of organochlorine pesticides and PCDD-F congeners did not differ significantly between 14 eggs collected from individual nests on the Hudson River and five eggs similarly collected on three other nearby rivers. In contrast, the pattern of PCB congeners in eggs collected on the Hudson River differed significantly from the other rivers. The differences in patterns of PCB congeners were associated with a higher representation of lower-numbered congeners on the Hudson River than the other rivers. The higher prevalence of the lower-numbered congeners and lower prevalence of the higher-numbered congeners is consistent with Aroclor 1016 and 1242 being the source of the PCBs on the Hudson River. Concentrations in a sample egg collected at each nest were compared to nest survival and egg success (the proportion of eggs hatching in a clutch if at least one egg hatched) of the remaining eggs in the clutch. Models that predicted nest survival and egg success as functions of contaminant levels were poorly distinguished from models that presumed no such associations. Small sample sizes could have contributed to the inability to distinguish among contaminant and no toxicant models. However, we cannot rule out the possibility that contaminant concentrations on the Hudson River were not sufficiently high to demonstrate a relationship between contaminant concentrations and reproductive success in kingfishers.


Implications of pharmaceutical industry funding on clinical research.
This commentary explores the influence of industry funding and offers suggestions for overcoming some of the problems. First, it is difficult to obtain funding from some sources for research with limited commercial value. Second, lack of communication among researchers can impede scientific progress. Stopping research before meaningful results are available is another area of concern. Next, suppressed or delayed publication of data may bias the results of meta-analyses, resulting in incorrect risk-benefit profiles for drugs. Finally, commercially funded clinical research is more likely to yield positive results than when funding comes from other sources. Possible solutions are explored.


Foods for infants allergic to cow's milk.
This article provides a reference guide to commercially available baby foods in South Africa and indicates which of these foods contain cow's milk. This information is of importance in the nutritional management of babies.


A low-power configurable neural recording system for epileptic seizure detection.
This paper describes a low-power configurable neural recording system capable of capturing and digitizing both neural action-potential (AP) and fast-ripple (FR) signals. It demonstrates the functionality of epileptic seizure detection through FR recording. This system features a fixed-gain, variable-bandwidth (BW) front-end circuit and a sigma-delta ADC with scalable bandwidth and power consumption. The ADC employs a 2nd-order single-bit sigma-delta modulator (SDM) followed by a low-power decimation filter. Direct impulse-response implementation of a sinc(3) filter and 8-cycle data pipelining in an IIR filter are proposed for the decimation filter design to improve the power and area efficiency. In measurements, the front end exhibits 39.6-dB DC gain, 0.8 Hz to 5.2 kHz of BW, 5.86- μVrms input-referred noise, and 2.4- μW power consumption in AP mode, while showing 38.5-dB DC gain, 250 to 486 Hz of BW, 2.48- μVrms noise, and 4.5- μW power consumption in FR mode. The noise efficiency factor (NEF) is 2.93 and 7.6 for the AP and FR modes, respectively. At 77-dB dynamic range (DR), the ADC has a peak SNR and SNDR of 75.9 dB and 67 dB, respectively, while consuming 2.75-mW power in AP mode. It achieves 78-dB DR, 76.2-dB peak SNR, 73.2-dB peak SNDR, and 588- μW power consumption in FR mode. Both analog and digital power supply voltages are 2.8 V. The chip is fabricated in a standard 0.6- μm CMOS process. The die size is 11.25 mm(2).


Validation and reproducibility of ultrasonography in the detection of synovitis in the knee: a comparison with arthroscopy and clinical examination.
Accurate detection of synovitis is important in both the diagnosis and outcome assessment of arthritis. This study was undertaken to assess the validity and reproducibility of ultrasonography (US) as a means of detecting synovitis in the knee, by comparing US findings with findings of arthroscopy and clinical examination. Sixty consecutive patients with knee pain due to various arthritides had a clinical examination and US of their knee performed immediately prior to arthroscopy. All 3 assessments were performed by different clinicians who were blinded to the results obtained with the other modalities. US and clinical examination were compared with arthroscopically detected synovitis as the gold standard. Data from a subset of patients were used for calculating the inter- and intrareader reproducibility of US results, using a standard dichotomous (absence/presence of synovitis) as well as a graded (absence/grade of synovitis) scoring system. With the use of arthroscopy as the gold standard, US had a higher sensitivity (98% versus 85%), specificity (88% versus 25%), accuracy (97% versus 77%), positive predictive value (98% versus 88%), and negative predictive value (88% versus 20%) compared with clinical examination. The Cohen kappa values for inter- and intrareader reproducibility of US for distinguishing between presence and absence of synovitis were 0.71 and 0.85, respectively (P < 0.05 for both). The weighted kappa values for distinguishing grade of synovitis were 0.65 for inter- and 0.74 for intrareader reproducibility. The kappa value for intrareader reproducibility of arthroscopy results was 0.88. Ultrasonography is a valid and reproducible technique for detecting synovitis in the knee, and is more accurate than clinical examination. It may be valuable as a tool in studies investigating pain, diagnosis, and treatment response in knee arthritis.


On the operating mode of bimetallic systems for environmental remediation.
This letter challenges the concept that Fe(0)/Me(0) bimetallic systems enhance contaminant reduction on Me(0) surfaces. It is shown on a pure thermodynamic perspective that any enhancement of contaminant reduction by Fe(0) in the presence of a second more electropositive elemental metal (Me(0)) is the result of an indirect process resulting from iron corrosion. This demonstration validates the concept that aqueous contaminant removal in the presence of Fe(0) mostly occurs within an in situ generated oxide film on Fe(0).


Differential effects of the anticonvulsants phenobarbital, ethosuximide and carbamazepine on neuromuscular transmission.
The actions of the anticonvulsants phenobarbital, ethosuximide and carbamazepine were examined electrophysiologically at the frog neuromuscular junction. Phenobarbital reduced miniature end-plate potential (MEPP) amplitude, did not significantly affect end-plate potential amplitude and increased quantal content. Ethosuximide decreased MEPP and end-plate potential amplitudes proportionally; quantal content was unchanged. Carbamazepine decreased end-plate potential amplitude more than MEPP amplitude; quantal content was decreased. In a solution containing elevated (7.5 mM) K+, phenobarbital and carbamazepine increased MEPP frequency, whereas ethosuximide had no effect. Carbamazepine had to be dissolved in a solvent, propylene glycol, which was shown to produce small, but sometimes statistically significant, alterations in the measured parameters of neuromuscular transmission. The results show that all three of these anticonvulsants depress postjunctional sensitivity to released acetylcholine producing parallel dose-response curves for MEPP amplitude inhibition. These experiments also show that these drugs exhibit different mechanisms of action with respect to nerve-stimulated neurotransmitter release from nerve terminals at the neuromuscular junction: phenobarbital enhances acetylcholine release, ethosuximide has no effect and carbamazepine decreases transmitter release.


The anaplerotic phosphoenolpyruvate carboxylase of the tricarboxylic acid cycle deficient Acholeplasma laidlawii B-PG9.
Phosphoenolpyruvate carboxylase (EC 18.104.22.168) (PEP-C) was purified approximately 770-fold from the mollicute Acholeplasma laidlawii B-PG9. The partially purified PEP-C required phosphoenolpyruvate (PEP) and MnCl2 at pH 7.4 or MgCl2 at pH 8.6 for optimal activity. The product is oxaloacetate as detected by a malate dehydrogenase indicator system. The KmA (PEP variable) was 0.66 mM and the KmB (bicarbonate variable) was 1.02 mM. At low bicarbonate concentrations (0.5 mM), PEP-C activity was stimulated approximately 240% by fructose 1,6-bisphosphate. Aspartate was a non-competitive inhibitor of PEP-C activity. The KiA (PEP variable) for aspartate was 0.69 mM and the KiB (bicarbonate variable) was 0.99 mM. Malate, citrate, isocitrate, 2-oxoglutarate, acetyl-CoA, CMP, CDP, GDP, GTP, ADP and ATP had no effect on the PEP-C reaction. The Hill interaction coefficient was 0.98-1.11. The molecular mass by sucrose density gradient analysis was 353 kDa; by gel filtration chromatography it was 384 kDa. The Stokes radius was about 7.4 nm. PEP-C activity and its inhibition by aspartate in Acholeplasma laidlawii B-PG-9 extracts may reflect an involvement of this enzyme in the interdependent regulation of protein, lipid and nucleic acid precursor metabolism of this TCA-cycle-deficient and cytochrome-less mollicute.


Long-Term Ranibizumab Treatment in Neovascular Age-Related Macular Degeneration: A Belgian Subanalysis from the Global Real-World LUMINOUSTM Study.
To evaluate long-term, real-world treatment patterns and outcomes of ranibizumab 0.5 mg for neovascular age-related macular degeneration (nAMD) in a Belgian cohort. This Belgian (BE) cohort of the 5-year global observational LUMINOUS study included 229 patients with nAMD. Outcomes included visual acuity (VA), central retinal thickness (CRT) and safety. The mean age was 79.5±7.7 years. The majority of patients (67.7%) were female and all patients were Caucasian. Most patients previously received ranibizumab with only 17.5% of patients being treatment-naïve. The injection frequency declined over time irrespective of prior treatment status (p<0.0001), with treatment-naïve eyes receiving a mean of 4.2±2.9 yearly injections and prior-ranibizumab eyes 3.6±2.7. Regression analysis confirmed first-year VA increases for treatment-naïve eyes (p=0.002) followed by a slight decrease of -1.8 letters per year. For prior-ranibizumab eyes, the visual changes over 1 year were statistically non-significant (p=0.90) but declined slightly after year one (p<0.0001). Anatomically, the CRT of treatment-naïve eyes decreased over time from baseline (p<0.0001), whereas the CRT of prior-ranibizumab eyes remained stable (p=0.43). No new safety findings were identified. LUMINOUS-BE reconfirms the well-characterized benefit-risk profile of ranibizumab for nAMD treatment. The observed low injection frequency reflects a need for more rigorous treatment in real-world settings. NCT01318941.