Validation of the Iranian/Persian Version of the Perceived Therapeutic Efficacy Scale for Type 2 Diabetes.
The theory if self-efficacy is the central concept of social cognitive theory with emphasis on the constructs of efficacy expectation, outcome expectation. Efficacy expectation is defined as the person's confidence to carry out a specific behavior. Outcome expectation is beliefs that carrying out a specific behavior will lead to a specific outcome. While the benefit of measuring outcome expectations has been established, there has been no large scale within the Iranian context. The purpose of this study is to examine the reliability-validity of the Persian version of the Perceived Therapeutic Efficacy Scale (PTES). This study was conducted among 160 patients with type 2 diabetes mellitus (T2DM) using a self-administered instrument measuring outcome expectation. We used a methodological study design to assess the validity and reliability of the translated Persian version of the instrument. The findings of the present study support the uni-dimensionality of the Persian version of the instrument. The 10 items of the scale account for 73.54% of the total variance and the un-rotated factor loadings ranged from 0.66 to 0.93. Moreover, this study offers support for convergent validity and internal consistency of the scale. Our study demonstrated good convergent validity, factor structure and internal consistency in a sample of 160 Iranian adults with T2DM. Therefore, the Persian version of the scale is a valid and reliable instrument and can be used in research and clinical settings.


Substrate specificity of formylglycinamidine synthetase.
Formylglycinamidine ribonucleotide (FGAM) synthetase, which catalyzes the conversion of formylglycinamide ribonucleotide (FGAR), glutamine, and ATP to FGAM, ADP, glutamate, and Pi, has been purified to homogeneity (sp act. 0.20 mumol min-1 mg-1) from chicken liver by an alternative procedure to that of Buchanan et al. [Buchanan, J. M., Ohnoki, S., & Hong, B. S. (1978) Methods Enzymol. 51, 193-201] (sp act. 0.12 mumol min-1 mg-1). A variety of new analogues of formylglycinamide ribonucleotide have been prepared in which the formylglycinamide arm (R = CH2NHCHO) has been replaced by R = CH3, CH2OH, CH2Cl, CH2NH3, CH2NHCOCH3, CH2NHCOCH2Cl, CH2NHCO2CH2Ph, and L-CHC-H3NHCHO. These compounds have been characterized by 1H and 13C NMR spectroscopy. With compounds R = CH3, CH2OH, and CH2NHCOCH3 and ATP, in the presence or absence of glutamine, FGAM synthetase catalyzes the production of Pi at 4.5, 48, and 20%, respectively, the rate of production of Pi from formylglycinamide ribonucleotide. Only R = CH2NHCOCH3 causes glutaminase activity as well as ATPase activity and has been shown to be converted to the amidine analogue. Both FGAR (R = CH2NHCHO) and the FGAR analogue (R = CH2NHCHOCH3) in the presence of ATP and FGAM synthetase and in the absence of glutamine form a complex isolable by Sephadex G-50 chromatography. FGAM synthetase is thus highly specific for its formylglycine side chain. [18O]-beta-FGAR was prepared biosynthetically, and FGAM synthetase was shown by 31P NMR spectroscopy to catalyze the transfer of amide 18O to inorganic phosphate.


A Rare Presentation of Lupus Nephritis Flare up with Posterior Reversible Leucoencephalopathy.
Systemic lupus erythematosus (SLE) is associated with various neurologic or psychiatric abnormalities and Posterior Reversible Leuco Encephalopathy Syndrome (PRES) is very rare neurological manifestation in SLE. PRES is associated with various clinical manifestations, like, seizures, visual loss, headaches, vomiting altered mental status and rarely focal neurological deficits. Other predisposing condition associated with PRES is eclampsia, accelerated hypertension, uraemia, transplantation, autoimmune diseases and/or use of immunosuppressive drugs. It is important to recognise PRES since it is a potentially reversible. We describe an unusual case of PRES caused by uraemia during lupus flare up in a patient with biopsy proven class IV lupus nephritis who presented with features of asymmetrical quadriparesis which completely reversed after haemodialysis sessions and treating lupus flare up. In our case she presented with quadriparesis which is a rare presentation and hypertensive encephalopathy was not present.


The m3 muscarinic acetylcholine receptor is coupled to mitogen-activated protein kinase via protein kinase C and epidermal growth factor receptor kinase.
The acetylcholine analogue carbachol rapidly activated mitogen-activated protein kinase (MAPK), and caused tyrosine phosphorylation of the adapter protein p52 Shc and the epidermalgrowth factor (EGF) receptor, in human embryonic kidney cells stably expressing m3 muscarinic receptors. The protein kinase C (PKC) inhibitor GF109203X caused a significant partial inhibition of m3 receptor-mediated activation of MAPK. The PKC-independent MAPK activity elicited by carbachol in the presence of GF109203X was reproducibly abolished by AG1478, an inhibitor of EGF-receptor tyrosine kinase activity, and by the Src tyrosine kinase inhibitor PP1. In a subset of these experiments, GF109203X concomitantly increased carbachol-induced tyrosine phosphorylation of p52 Shc and the EGF receptor. In co-stimulation experiments, carbachol and EGF activated MAPK in a non-additive fashion; moreover, EGF-induced association of Shc with the phosphorylated EGF receptor was inhibited by carbachol. This effect of carbachol was blocked by GF109203X. The results indicate that MAPK activation by m3 receptor stimulation is regulated by two pathways; one dependent on PKC, and the other mediated via the EGF receptor and Src. Moreover, the EGF-receptor-dependent pathway may be subject to negative-feedback regulation via m3 receptor-coupled activation of PKC.


Estimation of benzathine penicillin G demand for congenital syphilis elimination with adoption of dual HIV/syphilis rapid diagnostic tests in eleven high burden countries.
WHO recommends use of rapid dual HIV/syphilis tests for screening pregnant women (PW) during antenatal care to prevent mother-to-child transmission. Scale-up of testing implies a need to accurately forecast and procure benzathine penicillin (BPG) to treat the additionally identified PW with syphilis. Country-reported ANC coverage, PW syphilis screening and treatment coverage values in 2019 were scaled linearly to EMTCT targets by 2030 (constant increasing slope from 2019 figures to 95% in 2030) for 11 focus countries. Antenatal syphilis screening coverage was substituted with HIV screening coverage to estimate potential contribution of rapid dual HIV/syphilis tests in identifying additional PW with syphilis. BPG demand was calculated for 2019-2030 accordingly. The estimated demand for BPG (in 2.4 million unit vials) using current maternal syphilis prevalence and treatment coverage will increase from a baseline of 414,459 doses in 2019 to 683,067 doses (+65%) in 2021 assuming immediate replacement of single HIV test kits with rapid dual HIV/syphilis tests for these 11 countries. Continued scale up of syphilis screening and treatment coverage to reach elimination coverage of 95% will result in an estimated demand increase of 160%, (663,969 doses) from 2019 baseline for a total demand of 1,078,428 BPG doses by 2030. Demand for BPG will increase following adoption of rapid dual HIV/syphilis test kits due to increases in maternal diagnoses of syphilis. To eliminate congenital syphilis, MNCH clinical programs will need to synergize with disease surveillance programs to accurately forecast BPG demand with scale up of antenatal syphilis screening to ensure adequate treatment is available for pregnant women diagnosed with syphilis.


Nutrition during Pregnancy: Findings from the National Institute of Child Health and Human Development (NICHD) Fetal Growth Studies-Singleton Cohort.
Accumulating evidence indicates that maternal diets are important for optimizing maternal and offspring health. Existing research lacks comprehensive profiles of maternal diets throughout pregnancy, especially in a racially/ethnically diverse obstetrical population. The aim was to characterize diets in a longitudinal US pregnancy cohort by trimester, race/ethnicity, and prepregnancy BMI. Data were obtained from pregnant women in the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Fetal Growth Studies-Singleton cohort (2009-2013). A food-frequency questionnaire (FFQ) at 8-13 wk of gestation assessed periconception and first-trimester diet (n = 1615). Automated, self-administered, 24-h dietary recalls targeted at 16-22, 24-29, 30-33, and 34-37 wk of gestation assessed second- and third-trimester diets (n = 1817 women/6791 recalls). The Healthy Eating Index-2010 (HEI-2010) assessed diet quality (i.e., adherence to US Dietary Guidelines). Variations in weighted energy-adjusted means for foods and nutrients were examined by trimester, self-identified race/ethnicity, and self-reported prepregnancy BMI. Mean (95% CI) HEI-2010 was 65.9 (64.9, 67.0) during periconception to the first trimester assessed with an FFQ and 51.6 (50.8, 52.4) and 51.5 (50.7, 52.3) during the second trimester and third trimester, respectively, assessed using 24-h recalls. No significant differences were observed between the second and third trimester in macronutrients, micronutrients, foods, or HEI-2010 components (P ≥ 0.05). Periconception to first-trimester HEI-2010 was highest among Asian/Pacific Islander [67.2 (65.9, 68.6)] and lowest among non-Hispanic Black [58.7 (57.5, 60.0)] women and highest among women with normal weight [67.2 (66.1, 68.4)] and lowest among women with obesity [63.5 (62.1, 64.9)]. Similar rankings were observed in the second/third trimesters. Most pregnant women in this cohort reported dietary intakes that, on average, did not meet US Dietary Guidelines for nonpregnant individuals. Also, diet differed across race/ethnic groups and by prepregnancy BMI, with the lowest overall dietary quality in all trimesters among non-Hispanic Black women and women with obesity. No meaningful changes in dietary intake were observed between the second and third trimesters.


Stable carbon isotopic composition of the wine and CO2 bubbles of sparkling wines: detecting C4 sugar additions.
Sparkling wines have become a popular beverage in recent years, and the production of these wines is subject to adulteration during fermentation. This study investigated the stable carbon isotopic composition (expressed as delta(13)C) of the wine and of the CO(2) bubbles produced during the second fermentation for a number of sparkling wines produced in different countries around the world. Carbon isotope ratio analyses were used to estimate the addition of sugar obtained from C(4) plants (sugar cane or corn). The average delta(13)C values of the Brazilian brut, demi-sec, and doux sparkling wines were -20.5 +/- 1.2 per thousand (n = 18), -18.1 +/- 1.3 per thousand (n = 9), and -15.8 per thousand (n = 1), respectively. These values were statistically heavier (more positive carbon isotope ratio values) than the average delta(13)C of sparkling wines produced in other parts of South America (Argentina and Chile, -26.1 +/- 1.6 per thousand, n = 5) and Europe (France, Germany, Italy, Portugal, and Spain, -25.5 +/- 1.2 per thousand, n = 12), but not statistically different from sparkling wines produced in the United States or Australia. The most likely explanation for differences in the carbon isotope ratios of wines from these different regions is the addition of C(4) sugar during the production of some sparkling wines from Australia, Brazil, and the United States. The isotopic composition of the CO(2) bubbles (delta(13)C-CO(2)) followed similar trends. The average delta(13)C-CO(2) of most of the Brazilian and Argentine sparkling wines was -10.8 +/- 1.2 per thousand (n = 23), indicating that the likely source of carbon for the second fermentation was sugar cane. Conversely, the average delta(13)C-CO(2) of most of the sparkling wines produced in Chile and Europe was -22.0 +/- 1.2 per thousand (n = 13), suggesting that a different sugar (most likely sugar beet) was most used in the second fermentation. It was concluded that in many cases, the carbon isotope ratios of sparkling wine and CO(2) bubbles can provide valuable information about the sugar sources.


Charcot-Marie-Tooth disease: genetic and clinical spectrum in a Spanish clinical series.
To determine the genetic distribution and the phenotypic correlation of an extensive series of patients with Charcot-Marie-Tooth disease in a geographically well-defined Mediterranean area. A thorough genetic screening, including most of the known genes involved in this disease, was performed and analyzed in this longitudinal descriptive study. Clinical data were analyzed and compared among the genetic subgroups. Molecular diagnosis was accomplished in 365 of 438 patients (83.3%), with a higher success rate in demyelinating forms of the disease. The CMT1A duplication (PMP22 gene) was the most frequent genetic diagnosis (50.4%), followed by mutations in the GJB1 gene (15.3%), and in the GDAP1 gene (11.5%). Mutations in 13 other genes were identified, but were much less frequent. Sixteen novel mutations were detected and characterized phenotypically. The relatively high frequency of GDAP1 mutations, coupled with the scarceness of MFN2 mutations (1.1%) and the high proportion of recessive inheritance (11.6%) in this series exemplify the particularity of the genetic distribution of Charcot-Marie-Tooth disease in this region.


Pathological fractures; a consideration with metachondromatosis and differential diagnoses. Osteochondromatosis and Gauchers disease.
Metachondromatosis is a condition that causes gross conical metaphyseal expansion (sometimes irregular), cortical thinning, exostoses. Metachondromatous lesions occur mainly in the extremities and are roughly symmetrical. The lesions can involve the bones of the hand and all long bones in the arms and legs. The distribution in this case additionally involved the acromion process and ischia. The bone changes, although dramatic, can be confused with other types of metaphyseal dysplasia such as Gaucher disease and multiple exostoses. This paper will review the literature with regard to Metachondromatosis, Gaucher disease and Osteochondromatosis due to their similarities. The case study serves as an example of these findings and documents a history of fractures secondary to the obvious bone changes. Clinical manifestations of these conditions and how they may present to the manual therapist are discussed. With respect to Metachondromatosis, the manual therapist needs to be mindful of pathological fractures that can occur with little trauma. Manual therapists are cautioned against using long bones as levers for spinal manipulation in these patients.


Ethnocultural identity and induced abortion in Kazakstan.
This study analyzes ethnic differences in induced abortion among ever-married women in Kazakstan, drawing on data from the 1995 Kazakstan Demographic and Health Survey. Instead of conventional ethnic markers, such as "Kazak" or "Russian," it focuses on more complex ethnocultural identities that combine ascribed ethnicity with language use. Because of the history of russification in Kazakstan, three ethnocultural groups are defined and compared--Kazak women who chose to be interviewed in Kazak, Kazak women who chose to be interviewed in Russian, and women of European background interviewed in Russian. Whereas women of European origin were the most likely to undergo induced abortion, the Russian-interviewed Kazaks had higher abortion ratios and were more likely to terminate their pregnancies than were the Kazak-interviewed Kazaks, net of other characteristics. The implications of the results for induced abortion trends and family planning policy in Kazakstan are discussed in addition to other findings.


G-protein alpha subunit Gi(alpha)2 mediates erythropoietin signal transduction in human erythroid precursors.
Erythropoietin induces a dose-dependent increase in cytosolic calcium in human erythroblasts that is mediated by a voltage-independent Ca2+ channel. Inhibition of this response to erythropoietin by pertussis toxin suggests involvement of guanine nucleotide-binding regulatory proteins (G-proteins). The role of G-proteins in regulation of the erythropoietin-modulated Ca2+ channel was delineated here by microinjection of G-protein modulators or subunits into human erythroid precursors. This is the first report on the use of microinjection to study erythropoietin signal transduction in normal precursor cells. Fura-2 loaded day-10 burst-forming units-erythroid-derived erythroblasts were used for microinjection and free intracellular calcium concentration ([Ca(i)]) was measured with digital video imaging. BCECF (1,2',7'-bis(2-carboxyethyl)-5-(and -6-)-carboxyfluorescein) was included in microinjectate, and an increase in BCECF fluorescence was evidence of successful microinjection. Cells were microinjected with nonhydrolyzable analogues of GTP, GTPgammaS or GDPbetaS, which maintain the alpha subunit in an activated or inactivated state, respectively. [Ca(i)] increased significantly in a dose-dependent manner after microinjection of GTPgammaS. However, injection of GDPbetaS blocked the erythropoietin-induced calcium increase, providing direct evidence that activation of a G-protein is required. To delineate which G-protein subunits are involved, alpha or betagamma transducin subunits were purified and microinjected as a sink for betagamma or alpha subunits in the erythroblast, respectively. Transducin betagamma, but not alpha, subunits eliminated the calcium response to erythropoietin, demonstrating the primary role of the alpha subunit. Microinjected antibodies to Gi(alpha)2, but not Gi(alpha)1 or Gi(alpha)3, blocked the erythropoietin-stimulated [Ca(i)] rise, identifying Gi(alpha)2 as the subunit involved. This was confirmed by the ability of microinjected recombinant myristoylated Gi(alpha)2, but not Gi(alpha)1 or Gi(alpha)3 subunits, to reconstitute the response of pertussis toxin-treated erythroblasts to erythropoietin. These data directly demonstrate a physiologic function of G-proteins in hematopoietic cells and show that Gi(alpha)2 is required in erythropoietin modulation of [Ca(i)] via influx through calcium channels.


Expression of neuropsin in the keratinizing epithelial tissue-immunohistochemical analysis of wild-type and nude mice.
Neuropsin is a trypsin-type serine protease that was first cloned from the mouse brain as a factor related to neural plasticity. Subsequent in situ hybridization histochemical analysis indicated a broad localization of its mRNA throughout the whole body, although the details remain obscure. In this study, we showed that neuropsin immunoreactivity is localized in the keratinized stratified epithelia of the mouse epidermis, hair, tongue, palate, nasal cavity, pharynges, esophagus, and forestomach. In the skin and mucous membranes, neuropsin immunoreactivity was found in the stratum spinosum and the stratum granulosum. The immunoreactivity in the former sublayer was mainly present in the cytoplasm, but that in the latter sublayer was exclusively present in the intercellular space or on the outer surface of the cell membrane and thus exhibited a lamellar-like peripheral distribution. During development, the appearance of neuropsin immunoreactivity in the various epithelia was found at embryonic days 14.5-15.5, prior to formation of the stratum corneum. More extensive expression of neuropsin immunoreactivity was found in the nude mouse skin and mucous membranes than in wild-type mice. Because the nude mouse is characterized by genetic impairment of keratinization, such abnormal neuropsin expression might be caused or affected by this impairment. Therefore, neuropsin, an extracellular serine protease, is suggested to be involved in keratinization in the stratified epithelia.


Operative Volume of Newborn Surgery in German University Hospitals: High Volume Versus Low Volume Centers.
Adequate patient volume is essential for the maintenance of quality, meaningful research, and training of the next generation of pediatric surgeons. The role of university hospitals is to fulfill these tasks at the highest possible level. Due to decentralization of pediatric surgical care during the last decades, there is a trend toward reduction of operative caseloads. The aim of this study was to assess the operative volume of the most relevant congenital malformations at German academic pediatric surgical institutions over the past years. Nineteen chairpersons representing university-chairs in pediatric surgery in Germany submitted data on 10 index procedures regarding congenital malformations or neonatal abdominal emergencies over a 3-year period (2015 through 2017). All institutions were categorized according to the total number of respective cases into "high," "medium," and "low" volume centers by terciles. Some operative numbers were verified using data from health insurance companies, when available. Finally, the ratio of cumulative case load versus prevalence of the particular malformation was calculated for the study period. From 2015 through 2017, a total 2,162 newborns underwent surgery for congenital malformations and neonatal abdominal emergencies at German academic medical centers, representing 51% of all expected newborn cases nationwide. The median of cases per center within the study period was 101 (range 18-258). Four institutions (21%) were classified as "high volume" centers, four (21%) as "medium volume" centers, and 11 (58%) as "low volume" centers. The proportion of patients operated on in high-volume centers varied per disease category: esophageal atresia/tracheoesophageal fistula: 40%, duodenal atresia: 40%, small and large bowel atresia: 39%, anorectal malformations: 40%, congenital diaphragmatic hernia: 56%, gastroschisis: 39%, omphalocele: 41%, Hirschsprung disease: 45%, posterior urethral valves: 39%, and necrotizing enterocolitis (NEC)/focal intestinal perforation (FIP)/gastric perforation (GP): 45%. This study provides a national benchmark for neonatal surgery performed in German university hospitals. The rarity of these cases highlights the difficulties for individual pediatric surgeons to gain adequate clinical and surgical experience and research capabilities. Therefore, a discussion on the centralization of care for these rare entities is necessary.


Diabetic endovascular disease: role of coronary artery revascularization.
This century brings a pandemic of diabetes mellitus, with marked increases in early-accelerated atherosclerosis. When asymptomatic patients with diabetes present for evaluation, they have more extensive coronary atherosclerosis, lower ejection fractions, higher rates of previous cardiac events, and more silent ischemia than the normal population. The challenge faced by clinicians is to accurately identify asymptomatic patients with diabetes who have significant coronary ischemia that would benefit from revascularization. Diabetic endovascular disease has all the high-risk features to promote atherosclerosis and coronary occlusion: hyperglycemia-induced endothelial dysfunction, impaired fibrinolysis, increased platelet aggregation, plaque instability, dysfunctional arterial remodeling, and fibrotic and calcified coronary arteries. The optimal revascularization strategy for patients with diabetes is an ongoing debate. The advent of drug-eluting stents has changed the landscape, and some have suggested that the current role of coronary artery bypass grafting may be reduced by as much as 46%. Unfortunately, there is limited evidence from randomized, controlled trials that reflects current practice and could guide clinicians in making the best choices for patients with diabetes and coronary disease. It is hoped that ongoing trials--including Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D), Future Revascularization Evaluation in Patients with Diabetes Mellitus: Optimal Management of Multivessel Disease (FREEDOM), and Coronary Artery Revascularisation in Diabetes (CARDia)--will answer many of the remaining questions. Still, the best treatment includes lifestyle modification and early prevention strategies with global risk reduction.


Salivary alpha-amylase in biobehavioral research: recent developments and applications.
In the history of science, technical advances often precede periods of rapid accumulation of knowledge. Within the past three decades, discoveries that enabled the noninvasive measurement of the psychobiology of stress (in saliva) have added new dimensions to the study of health and human development. This widespread enthusiasm has led to somewhat of a renaissance in behavioral science. At the cutting edge, the focus is on testing innovative theoretical models of individual differences in behavior as a function of multilevel biosocial processes in the context of everyday life. Several new studies have generated renewed interest in salivary alpha-amylase (sAA) as a surrogate marker of the autonomic/sympathetic nervous system component of the psychobiology of stress. This article reviews sAA's properties and functions; presents illustrative findings relating sAA to stress and the physiology of stress, behavior, cognitive function, and health; and provides practical information regarding specimen collection and assay. The overarching intent is to accelerate the learning curve such that investigators avoid potential pitfalls associated with integrating this unique salivary analyte into the next generation of biobehavioral research.


[Non-conventional pharmacological agents for the treatment of bipolar disorder: Α systematic review of the evidence].
Bipolar disorder (BD) has a complex and variable clinical picture which is characterized by many different phacets and phases and as a result its therapeutical options are also complex and often unsatisfactory. Typically the so-called "mood stabilizers" are used in the treatment of BD and in this class lithium and specific antiepileptics are included. The present study aimed to systematically review the literature concerning the presence of randomized double blind clinical trials of 'non conventional' pharmaceutical treatment options. The present systematic review utilized the PRISMA method and searched the MEDLINE through January 1st 2015 with the use of appropriate key words. In order to identify randomized controlled trials- RCTs a combination of the words "bipolar", "manic", "mania", "manic depression" and "manic depressive" with "randomized" was used. Webpages with lists of trials were also searched including http://clinicaltrials.gov and http://www.clinicalstudyresults.org as well as the official webpages of all pharma companies with products marketed in the treatment of BD. The reference lists of various review papers were also searched. The MEDLINE was searched with the combination of the words "guidelines" or "algorithms" with "mania", "manic", "bipolar", "manicdepressive" or "manic depression" in order to identify articles with treatment guidelines. The reference list of these articles were also scanned. From 3,284 papers which were initially traced, only 47 papers were included in the present study. From those agents studied in acute mania, tamoxifen is efficacious as monotherapy and as combination therapy with lithium and other mood stabilizers, however its safety profile is relatively poor. Allopurinol manifests efficacy in combination with lithium but not with other agents and its safety profile is satisfactory. Methoxyprogesterone is efficacious in combination with mood stabilizers and its safety profile is very good. In acute bipolar depression the combinations of FEWP with carbamazepine and ketamine, modafinil, pramipexole, pregnenolone and maybe armodafinil with mood stabilizers are efficacious. The safety profile of these combinations is medium. The use of celecoxib, lisdexamfetamine and memantine have negative data. Concerning the maintenance treatment, the data are negative for memantine and for Nacetylcysteine. Although most of the data concerning the usefulness of "non-conventional" pharmacotherapeutic agents in the treatment of bipolar disorder are negative, it is encouraging that those agents who have been proven efficacious probably exert their therapeutic effect through pathways which differ from usual and probably different from those classically considered in most biological models of bipolar illness. In this way there constitute new paradigms and open new horizons in the understanding of the disease.


Validation of immunodetection (ELISA) of ricin using a biological activity assay.
The suitability of enzyme-linked immunosorbent assay (ELISA) for residual ricin toxicity determination was investigated in this study. Ricin was thermally treated at 80 to 90 °C for up to 9 min, and its residual concentration was determined by means of a commercial ELISA kit, and its bioactivity (amount of adenine released from DNA) was determined by means of a biological activity assay (BAA). Results showed that inactivation of ricin followed 1st-order kinetics. The half-life values for loss of bioactivity at 80, 85, and 90 °C were 1.93, 0.65, and 0.41 min, respectively. Similarly, the half-life values for reduction in ricin concentration determined by ELISA were 3.06, 0.79, and 0.43 min, respectively. The half-lives determined by both assays were only significantly different at 80 °C. The Z, Q(10), and Arrhenius activation energy values determined by both assays were dissimilar: 11.74 ˚C, 7.12 and 50.1 kcal/mol, respectively, by ELISA; and 14.87 °C, 4.71 and 39.5 kcal/mol, respectively, by BAA. Nevertheless, our findings indicate that the 2 assays were highly correlated (R(2) = 1), and it can be concluded that ELISA would be a reliable method for detecting residual toxicity of heat-treated ricin based on fraction lost. Practical Application: The results of this study indicate that immunodetection, even though not a direct measurement of the biological activity of ricin, is suitable for determining the residual bioactivity of ricin since immunodetection and the biological activity assay used in this investigation were highly correlated. Therefore, ELISA can be used for routine assessment of residual activity or toxicity of ricin in thermally treated foods.


Antiangiogenic activity of chemopreventive drugs.
Tumors growing within the host form dynamic aberrant tissue that consists of host components, including the stroma, an expanding vasculature and often chronic inflammation, in addition to the tumor cells themselves. These host components can contribute to, rather than limit, tumor expansion, whereas deprivation of vessel formation has the potential to confine tumors in small, clinically silent foci. Therapeutic inhibition of vessel formation could be best suited to preventive strategies aimed at the suppression of angiogenesis in primary tumors in subjects at risk, or of micrometastases after surgical removal of a primary tumor. Our analysis of potential cancer chemopreventive molecules including N-acetylcysteine, green tea flavonoids and 4-hydroxyphenyl-retinamide has identified antiangiogenic activities that could account--at least in part--for the tumor prevention effects observed with these compounds. These drugs appear to target common mechanisms of tumor angiogenesis that may permit identification of critical targets for antiangiogenic therapy and antiangiogenic chemoprevention.


Dynamics of facial actions for assessing smile genuineness.
Applying computer vision techniques to distinguish between spontaneous and posed smiles is an active research topic of affective computing. Although there have been many works published addressing this problem and a couple of excellent benchmark databases created, the existing state-of-the-art approaches do not exploit the action units defined within the Facial Action Coding System that has become a standard in facial expression analysis. In this work, we explore the possibilities of extracting discriminative features directly from the dynamics of facial action units to differentiate between genuine and posed smiles. We report the results of our experimental study which shows that the proposed features offer competitive performance to those based on facial landmark analysis and on textural descriptors extracted from spatial-temporal blocks. We make these features publicly available for the UvA-NEMO and BBC databases, which will allow other researchers to further improve the classification scores, while preserving the interpretation capabilities attributed to the use of facial action units. Moreover, we have developed a new technique for identifying the smile phases, which is robust against the noise and allows for continuous analysis of facial videos.


Von Willebrand factor as a biological sensor of blood flow to monitor percutaneous aortic valve interventions.
Percutaneous aortic valve procedures are a major breakthrough in the management of patients with aortic stenosis. Residual gradient and residual aortic regurgitation are major predictors of midterm and long-term outcome after percutaneous aortic valve procedures. We hypothesized that (1) induction/recovery of high molecular weight (HMW) multimers of von Willebrand factor defect could be instantaneous after acute changes in blood flow, (2) a bedside point-of-care assay (platelet function analyzer-closure time adenine DI-phosphate [PFA-CADP]), reflecting HMW multimers changes, could be used to monitor in real-time percutaneous aortic valve procedures. To investigate the time course of HMW multimers changes in models and patients with instantaneous induction/reversal of pathological high shear and its related bedside assessment. We investigated the time course of the induction/recovery of HMW multimers defects under instantaneous changes in shear stress in an aortic stenosis rabbit model and in patients undergoing implantation of a continuous flow left ventricular assist device. We further investigated the recovery of HMW multimers and monitored these changes with PFA-CADP in aortic stenosis patients undergoing transcatheter aortic valve implantation or balloon valvuloplasty. Experiments in the aortic stenosis rabbit model and in left ventricular assist device patients demonstrated that induction/recovery of HMW multimers occurs within 5 minutes. Transcatheter aortic valve implantation patients experienced an acute decrease in shear stress and a recovery of HMW multimers within minutes of implantation which was sustained overtime. In patients with residual high shear or with residual aortic regurgitation, no recovery of HMW multimers was observed. PFA-CADP profiles mimicked HMW multimers recovery both in transcatheter aortic valve implantation patients without aortic regurgitation (correction) and transcatheter aortic valve implantation patients with aortic regurgitation or balloon valvuloplasty patients (no correction). These results demonstrate that variations in von Willebrand factor multimeric pattern are highly dynamic, occurring within minutes after changes in blood flow. It also demonstrates that PFA-CADP can evaluate in real time the results of transcatheter aortic valve procedures.


[The advisability of modifying the current outline of blood coagulation].
The necessity of modifying the scheme of blood coagulation employed in the practice of clinicians is determined by the fact that the schemes offered before were short of the following important moments: 1) the whole totality of the mechanisms of factor VII activation (by factors III, XIIa, IXa, Xa, IIa, phospholipids and lipoproteins) and importance of its activation and increase of the level to reveal the risk of the development of the DIC syndrome, thromboses, sudden cardiac death; 2) formation during transformation of fibrinogen to fibrin of high molecular weight complexes of fibrin monomers (stabilized and not stabilized by factor XIIIa), whose presence in the blood plasma and serum provides important evidence for intravascular coagulation; 3) peptide splitting from prothrombin (fragments 1, 2) and fibrinogen (peptides A and B, 1-42, 15-42) the determination of which is also used for revealing activation of the blood and fibrinolytic system. Those and a number of other characteristic features are taken into account in the scheme of blood coagulation offered by the authors. A scheme of the functioning of the main anticoagulant mechanisms (antithrombin III and heparinoids; thrombomodulin, the system of proteins C and S) is also provided.


No Detectable Effect on Visual Responses Using Functional MRI in a Rodent Model of α-Synuclein Expression.
Parkinson's disease (PD) is a progressive neurodegenerative disease that is typically diagnosed late in its progression. There is a need for biomarkers suitable for monitoring the disease progression at earlier stages to guide the development of novel neuroprotective therapies. One potential biomarker, α-synuclein, has been found in both the familial cases of PD, as well as the sporadic cases and is considered a key feature of PD. α-synuclein is naturally present in the retina, and it has been suggested that early symptoms of the visual system may be used as a biomarker for PD. Here, we use a viral vector to induce a unilateral expression of human wild-type α-synuclein in rats as a mechanistic model of protein aggregation in PD. We employed functional magnetic resonance imaging (fMRI) to investigate whether adeno-associated virus (AAV) mediated expression of human wild-type α-synuclein alter functional activity in the visual system. A total of 16 rats were injected with either AAV-α-synuclein (n = 7) or AAV-null (n = 9) in the substantia nigra pars compacta (SNc) of the left hemisphere. The expression of α-synuclein was validated by a motor assay and postmortem immunohistochemistry. Five months after the introduction of the AAV-vector, fMRI showed robust blood oxygen level-dependent (BOLD) responses to light stimulation in the visual systems of both control and AAV-α-synuclein animals. However, our results demonstrate that the expression of AAV-α-synuclein does not affect functional activation of the visual system. This negative finding suggests that fMRI-based read-outs of visual responses may not be a sensitive biomarker for PD.


Atopic status in patients with brittle and non-brittle asthma: a case-control study.
Sensitization to inhaled and ingested allergens is an important process in determining the subsequent clinical expression of asthma. Allergen exposure has also been reported to be associated with admission to hospital with acute severe asthma. Patients with brittle asthma, characterized by widely variable peak expiratory flow are at increased risk of life-threatening episodes but the role of atopy in these patients is unknown. To determine the atopic status of patients with brittle asthma using a case-control design. We have assessed the atopic status by skin-prick tests to 19 common allergens, and total and specific immunoglobulin E (IgE) in 29 patients with well characterized brittle asthma and an age, sex and treatment-matched control group without brittle asthma. Mean weal diameters were higher in brittle compared to non-brittle asthma for grass pollen (4.64 vs 2.17; P = 0.01), horse hair (6.28 vs 2.64; P = 0.02), feathers (2.96 vs 1.52; P = 0.01), wheat (1.48 vs 0.66; P = 0.001) and chocolate (1.09 vs 0.41; P = 0.05). Mean radioallergosorbent (RAST) scores to house dust mite were also greater in brittle asthma patients (19.3 vs 7.65; P = 0.05). Patients with brittle asthma also exhibited a significantly greater degree of atopy when weal diameters to all 19 allergens were summated to produce an atopy score (brittle 44.35 vs non-brittle 23.72; P = 0.04). There were no significant differences between the two groups in either the number of positive skin tests (using a 4 mm definition of skin-test positivity), total IgE or RASTs (using a weak +ve score to define positivity). However, the use of differing definitions of atopy (1, 2, 3, 4 and 5 mm skin test weal diameters) resulted in marked intra-group variation in atopic status in both brittle and non-brittle asthma patients. The greater degree of atopy seen may be an important factor in patients with brittle asthma. The varying interpretations of the classification of what constitutes the presence or absence of atopy, based on mean weal diameters of skin-prick tests, or from IgE or RAST positivity shows that there is considerable potential variation in the degree of difference between the two groups depending on what criteria are used. Although internationally agreed definitions of atopic status have been devised a more rigorous application, or review of these guidelines needs to accompany future epidemiological studies of allergic sensitization.


CNS-Draining Meningeal Lymphatic Vasculature: Roles, Conundrums and Future Challenges.
A genuine and functional lymphatic vascular system is found in the meninges that sheath the central nervous system (CNS). This unexpected (re)discovery led to a reevaluation of CNS fluid and solute drainage mechanisms, neuroimmune interactions and the involvement of meningeal lymphatics in the initiation and progression of neurological disorders. In this manuscript, we provide an overview of the development, morphology and unique functional features of meningeal lymphatics. An outline of the different factors that affect meningeal lymphatic function, such as growth factor signaling and aging, and their impact on the continuous drainage of brain-derived molecules and meningeal immune cells into the cervical lymph nodes is also provided. We also highlight the most recent discoveries about the roles of the CNS-draining lymphatic vasculature in different pathologies that have a strong neuroinflammatory component, including brain trauma, tumors, and aging-associated neurodegenerative diseases like Alzheimer's and Parkinson's. Lastly, we provide a critical appraisal of the conundrums, challenges and exciting questions involving the meningeal lymphatic system that ought to be investigated in years to come.


Th1/Th2 balance in mouse delayed-type hypersensitivity model with mercuric chloride via skin and oral mucosa.
In order to compare delayed-type hypersensitivity (DTH) among different exposure sites, we evaluated the sensitization potency of mercuric chloride (HgCl(2)) via exposure to the skin, or oral or esophageal mucosa using the mouse ear swelling test. Furthermore, we investigated in vitro splenocyte proliferation reaction and cytokine profile in HgCl(2)-exposed and control mice. Sensitization with HgCl(2) was established via the skin and oral mucosa but not via the esophageal mucosa. The splenocyte proliferation reaction was significantly enhanced to a similar degree in skin and oral mucosa-sensitized mice compared with in the control mice. IL-10 levels from cultured splenocytes were significantly increased in skin and oral mucosa-sensitized mice compared with those in control mice, whilst IFN-γ significantly increased only in splenocytes from skin-sensitized mice. These results suggest that exposure of the skin or oral mucosa to HgCl(2) can induce DTH, but that Th1/Th2 balance differs according to the site of antigen exposure.


[The thyroid hormone system in mucoviscidosis].
Endocrine disorders do not represent primary manifestations in children with cystic fibrosis. Abnormal thyroid gland function is commonly observed in patients with chronic nonthyroidal illnesses. Serum concentrations of TSH, T4 and T3 were measured and a TRH-stimulation test (200 micrograms Relefact per kg body weight) was performed in 24 patients with CF 6 to 16 1/2 years of age. As compared to the controls, CF patients had increased basal TSH and lower T4 and T3 concentrations. Finally they exhibited higher TRH-stimulated TSH and decreased peripheral T4 and T3. There was no correlation to the nutritional status or the Shwachman scores. In all patients with CF albumin, TBG and TBPA were also normal. Our results indicate a subclinical hypothyroidism in CF. Routine therapy with thyroid hormones is neither necessary nor recommended.


Effect of dexamethasone on nitric oxide synthase and Caspase-3 gene expressions in endotoxemia in neonate rat brain.
To investigate the gene and protein expressions of three isoforms of nitric oxide synthase (NOS) and gene expression of Caspase-3, and effect of dexamethasone on them in neonatal rats with lipopolysaccharide (LPS)-induced endotoxemic brain damage. Expressions of the three isoforms of NOS and caspase-3 mRNA in the brain were investigated by RT-PCR in postnatal 7-day Wistar rats with acute endotoxemia by intraperitoneal administration of LPS. Regional distributions of NOSs were examined by immunohistochemical technique. nNOS and Caspase-3 mRNA were obviously detected. eNOS mRNA was faintly expressed, but iNOS mRNA was undetectable in the control rat brain. The expressions of NOS mRNA of three isoforms were weak 2 h after LPS (5 mg/mg) delivery, peaked at 6 h, and thereafter, reduced gradually up to 24 h. The expression intensity was in the order of nNOS> iNOS> eNOS. Widespread nNOS, scattered eNOS distribution and negative iNOS were identified in the control rat brain and all isoforms of NOS could be induced by LPS which reached the apex at 24 h in the order of nNOS> iNOS> eNOS as detected by immunostaining. Although Caspase-3 mRNA could be found in all groups, DNA fragmentation was only seen at 6 h and 24 h. The expressions of NOS and Caspase-3 mRNA were inhibited in the rat brain when dexamethasone was administrated. LPS-induced NO production induces apoptosis of neurons through mechanism involving the Caspase-3 activation, which may play an important role in the pathogenesis of brain damage during endotoxemia, and neuro-protective effects of dexamethasone may be partially realized by inhibiting the expression of NOS mRNA.


Survey of U.S. Critical Care Practitioners on Net Ultrafiltration Prescription and Practice among Critically Ill Patients Receiving Kidney Replacement Therapy.
The current prescription and practice of net ultrafiltration among critically ill patients receiving kidney replacement therapy in the U.S. are unclear. To assess the attitudes of U.S. critical care practitioners on net ultrafiltration (UFNET) prescription and practice among critically ill patients with acute kidney injury treated with kidney replacement therapy. A secondary analysis was conducted of a multinational survey of intensivists, nephrologists, advanced practice providers, and ICU and dialysis nurses practising in the U.S. Of 1,569 respondents, 465 (29.6%) practitioners were from the U.S. Mainly were nurses and advanced practice providers (58%) and intensivists (38.2%). The median duration of practice was 8.7 (IQR, 4.2-19.4) years. Practitioners reported using continuous kidney replacement therapy (as the first modality in 60% (IQR 20%-90%) for UFNET. It was found that there was a significant variation in assessment of prescribed-to-delivered dose of UFNET, use of continuous kidney replacement therapy for UFNET, methods used to achieve UFNET, and assessment of net fluid balance during continuous kidney replacement therapy. There was also variation in interventions performed for managing hemodynamic instability, perceived barriers to UFNET, belief that early and protocol-based fluid removal is beneficial, and willingness to enroll patients in a clinical trial. There was considerable practice variation in UFNET among critical care practitioners in the U.S., reflecting the need to generate evidence-based practice guidelines for UFNET.


Enhanced Survival of High-Risk Medulloblastoma-Bearing Mice after Multimodal Treatment with Radiotherapy, Decitabine, and Abacavir.
Children with high-risk SHH/TP53-mut and Group 3 medulloblastoma (MB) have a 5-year overall survival of only 40%. Innovative approaches to enhance survival while preventing adverse effects are urgently needed. We investigated an innovative therapy approach combining irradiation (RT), decitabine (DEC), and abacavir (ABC) in a patient-derived orthotopic SHH/TP53-mut and Group 3 MB mouse model. MB-bearing mice were treated with DEC, ABC and RT. Mouse survival, tumor growth (BLI, MRT) tumor histology (H/E), proliferation (Ki-67), and endothelial (CD31) staining were analyzed. Gene expression was examined by microarray and RT-PCR (Ki-67, VEGF, CD31, CD15, CD133, nestin, CD68, IBA). The RT/DEC/ABC therapy inhibited tumor growth and enhanced mouse survival. Ki-67 decreased in SHH/TP53-mut MBs after RT, DEC, RT/ABC, and RT/DEC/ABC therapy. CD31 was higher in SHH/TP53-mut compared to Group 3 MBs and decreased after RT/DEC/ABC. Microarray analyses showed a therapy-induced downregulation of cell cycle genes. By RT-PCR, no therapy-induced effect on stem cell fraction or immune cell invasion/activation could be shown. We showed for the first time that RT/DEC/ABC therapy improves survival of orthotopic SHH/TP53-mut and Group 3 MB-bearing mice without inducing adverse effects suggesting the potential for an adjuvant application of this multimodal therapy approach in the human clinic.


[The not choreic neurological complications of rheumatic disease (author's transl)].
The authors discuss the importance of neurological complications of rheumatic disease, which differ from those of Sydenham's chorea: encephalitis; acute cerebral circulatory insufficiency of cardiovascular basis; thrombosis and cerebral haemorrhage; cerebral emboli; and vasculitis. The case of a 13 year old boy who presented with an acute cerebral episode during an active phase of rheumatic fever is described. The E.E.G. showed a right hemisphere disturbance with a slight involvement of the controlateral hemisphere. The cardiac evidence was indicative of a rheumatic carditis. The clinical progress and EEG were rapidly favourable. The possible pathogenetic hypotheses of this case are taken into consideration, and the authors suggest that one must suspect a rheumatic etiology when an acute cerebral syndrome is established in a child or a young adult with current or previous rheumatic fever.


The effect of early human diet on caudate volumes and IQ.
Early nutrition in animals affects both behavior and brain structure. In humans, randomized trials show that early nutrition affects later cognition, notably in males. We hypothesized that early nutrition also influences brain structure, measurable using magnetic resonance imaging. Prior research suggested that the caudate nucleus may be especially vulnerable to early environment and that its size relates to IQ. To test the hypothesis that the caudate nucleus could be a neural substrate for cognitive effects of early nutrition, we compared two groups of adolescents, assigned a Standard- or High-nutrient diet in the postnatal weeks after preterm birth. Groups had similar birth status and neonatal course. Scans and IQ data were obtained from 76 adolescents and volumes of several subcortical structures were calculated. The High-nutrient group had significantly larger caudate volumes and higher Verbal IQ (VIQ). Caudate volumes correlated significantly with VIQ in the Standard-nutrient group only. Caudate volume was influenced by early nutrition and related selectively to VIQ in males, but not in females. Our findings may partly explain the effects of early diet on cognition and the predominant effects in males. They are among the first to show that human brain structure can be influenced by early nutrition.


Mode of onset of psychosis and family involvement in help-seeking as determinants of duration of untreated psychosis.
The duration of untreated psychosis (DUP) is a potentially modifiable determinant of the early course of nonaffective psychotic disorders, though a paucity of research has addressed determinants of DUP. Recent data from London and Nottingham, UK indicated that a shorter DUP was predicted by: (1) an acute mode of onset, (2) employment, and (3) active involvement of at least one family member in seeking evaluation (Morgan et al. Br J Psychiatry 189:446-452, 2006). The present analysis was conducted in an effort to replicate those findings in a predominantly low-income, urban, African American sample. DUP and the three key predictors of interest were assessed using standardized procedures. All analytic plans replicated those of Morgan and colleagues (Morgan et al. Br J Psychiatry 189:446-452, 2006) to the largest extent possible. Sufficient information was available to rate DUP for 73 patients. The median DUP was 23.4 weeks. Bivariate tests, survival analysis, and Cox regression revealed that an insidious mode of onset was associated with a substantially longer DUP compared with an acute onset, and that family involvement in help-seeking was independently associated with a longer duration. While mode of onset is a reliable illness-related determinant of DUP, further research is needed on the complex ways in which family-related variables influence DUP.


[Lennox-Gastaut syndrome].
The Lennox-Gestaut syndrome is classified as an epileptic syndrome shown by the presence of various types of generalized seizures (tonic, atonic and atypical absences) which appear at a certain age (1-8 years), with an interictal EEG showing an abnormally slow basic rhythm interrupted by slow spike-and-wave complexes (< 3 Hz) and progressive mental deterioration. From the aetiological point of view there are cryptogenic (25%) and symptomatic (75%) forms. There is a previous history of West syndrome in 9.4-30% of the symptomatic cases. The commonest types of seizures are tonic (17-95%), atypical absences (17-60%) and atonic (25-56%). The mixed form of an epileptic state with typical absences and tonic seizures is the most frequent (27%). Follow-up studies show that in 90% and 100% of cryptogenic and symptomatic patients, respectively, mental retardation develops and the initial seizures persist in 67% and 45% of the patients with cryptogenic and symptomatic forms respectively, when they become adults. There is still no successful treatment for these seizures and progressive mental deterioration occurs even when using the newer anti-epileptic drugs. Electrical stimulation of the vagus nerve seems a promising possibility but further experience is necessary.


Bleeding and New Cancer Diagnosis in Patients With Atherosclerosis.
Patients treated with antithrombotic drugs are at risk of bleeding. Bleeding may be the first manifestation of underlying cancer. We examined new cancers diagnosed in relation to gastrointestinal or genitourinary bleeding among patients enrolled in the COMPASS trial (Cardiovascular Outcomes for People Using Anticoagulation Strategies) and determined the hazard of new cancer diagnosis after bleeding at these sites. Of 27 395 patients enrolled (mean age, 68 years; women, 21%), 2678 (9.8%) experienced any (major or minor) bleeding, 713 (2.6%) experienced major bleeding, and 1084 (4.0%) were diagnosed with cancer during a mean follow-up of 23 months. Among 2678 who experienced bleeding, 257 (9.9%) were subsequently diagnosed with cancer. Gastrointestinal bleeding was associated with a 20-fold higher hazard of new gastrointestinal cancer diagnosis (7.4% versus 0.5%; hazard ratio [HR], 20.6 [95% CI, 15.2-27.8]) and 1.7-fold higher hazard of new nongastrointestinal cancer diagnosis (3.8% versus 3.1%; HR, 1.70 [95% CI, 1.20-2.40]). Genitourinary bleeding was associated with a 32-fold higher hazard of new genitourinary cancer diagnosis (15.8% versus 0.8%; HR, 32.5 [95% CI, 24.7-42.9]), and urinary bleeding was associated with a 98-fold higher hazard of new urinary cancer diagnosis (14.2% versus 0.2%; HR, 98.5; 95% CI, 68.0-142.7). Nongastrointestinal, nongenitourinary bleeding was associated with a 3-fold higher hazard of nongastrointestinal, nongenitourinary cancers (4.4% versus 1.9%; HR, 3.02 [95% CI, 2.32-3.91]). In patients with atherosclerosis treated with antithrombotic drugs, any gastrointestinal or genitourinary bleeding was associated with higher rates of new cancer diagnosis. Any gastrointestinal or genitourinary bleeding should prompt investigation for cancers at these sites. URL: https://www.clinicaltrials.gov. Unique identifier: NCT01776424.


Malignant B cells skew the balance of regulatory T cells and TH17 cells in B-cell non-Hodgkin's lymphoma.
Using biopsy specimens from patients with B-cell non-Hodgkin's lymphoma, we observed a significantly low frequency of T(H)17 cells, including several samples with no detectable amount of interleukin (IL)-17-producing cells present in the tumor microenvironment. We found that, in the absence of lymphoma B cells, treatment with IL-1beta/IL-6 or lipopolysaccharide (LPS) enhanced IL-17 expression in CD4(+) T cells and this enhancement was attenuated when CD4(+) T cells were cocultured with lymphoma B cells. Blockade of CD27-CD70 or CD28-CD80/86 interactions by anti-CD70 or anti-CD80/86 antibodies restored LPS-mediated induction of IL-17 expression in CD4(+) T cells cocultured with lymphoma B cells. Because a subset of lymphoma B cells express IL-2 and given that IL-2 signaling is critically important in the development of regulatory T (T(reg)) cells, we tested the role of IL-2 signaling in T(H)17 cell development. We found that treatment with anti-IL-2 antibody to interrupt IL-2 signaling significantly inhibited Foxp3 expression in CD4(+) T cells. In contrast, interruption of IL-2 signaling up-regulated IL-17 expression in CD4(+) T cells and restored lymphoma-mediated down-regulation of IL-17-producing cells. Furthermore, the reversal of T(reg) cell activity by LPS or CpG-A resulted in an enhancement of IL-17-producing cells. Taken together, our study indicated that lymphoma B cells play an important role in skewing the balance between T(reg) and T(H)17 cells resulting in the establishment of a profoundly inhibitory tumor microenvironment.


Annular converging wave cavity.
A new type of resonator that generates an annular geometric mode by use of spherical mirrors has been developed. The four-element cavity consists of an external confocal unstable resonator with a double-sided 45 degrees coupling mirror and a flat feedback mirror. The flat feedback mirror is placed on the plane wave side of the confocal cavity to form an annular mode between the feedback mirror and the coupling mirror. A plane annular wave (matched to an annular gain medium) is fed back into the unstable resonator that alternately converges and diverges to produce a diverging annular output beam. Experiments were performed on a cw HF laser. Observations of mode patterns on the flat feedback mirror and the convex mirror and of far-field beam quality were made. Far-field measurements indicated near-diffraction-limited beam quality for a peak on-axis intensity mode on the convex mirror. A nearly uniform annular mode was observed on the flat feedback mirror.


Predicting tumor cell repopulation after response: mathematical modeling of cancer cell growth.
The kinetics of regrowth of tumor cells after treatment may offer a new end-point for clinical trials. Based on our testing, it is best described in this manner: y(t) = a*exp(-b*t) + c*exp(d*t). Human malignant glioma cells U87 MG were treated with etoposide and allowed to regrow after treatment. The cell number versus time data were fitted mathematically to the two-term exponential model. Parameters b and d were independent of the drug concentration, while a increased c decreased as the drug dose increased. The concentration independence of b and d indicated that both cell proliferation and cell death kinetics were independent of the drug treatment, which suggests constant times for cell cycle and apoptosis. The concentration dependence of c suggests that the time until the cells started regrowing depended on the treatment, repair mechanisms taking longer after heavy damage. The two-term exponential model predicted tumor repopulation in this in vitro system. These results indicated that the velocities of the logarithm of cell growth and cell death were independent of drug treatment, while the recovery time of the tumor repopulation was dependent on the drug dose. The two-term exponential model can be used to predict tumor repopulation in an in vitro system and this model will be further tested using clinical data.


beta-Amyloid is associated with reduced cognitive function in healthy older adults.
Though elevated beta-amyloid deposition is associated with Alzheimer's disease, recent evidence suggests beta-amyloid is elevated in healthy older adults prior to the onset of Alzheimer's disease. No study has yet investigated whether reduced cognitive function is related to beta-amyloid elevation in healthy older adults. Thirty-five healthy older adults underwent neuropsychological testing and fasting blood draw with subsequent serum beta-amyloid 1-40 level quantification. beta-amyloid was negatively correlated with several aspects of cognition. Findings indicate that beta-amyloid level is associated with cognitive function in healthy older adults in a pattern similar to early Alzheimer's disease. Further work investigating possible mechanisms is needed.


CAMTA-Mediated Regulation of Salicylic Acid Immunity Pathway Genes in Arabidopsis Exposed to Low Temperature and Pathogen Infection.
Arabidopsis thaliana calmodulin binding transcription activator (CAMTA) factors repress the expression of genes involved in salicylic acid (SA) biosynthesis and SA-mediated immunity in healthy plants grown at warm temperature (22°C). This repression is overcome in plants exposed to low temperature (4°C) for more than a week and in plants infected by biotrophic and hemibiotrophic pathogens. Here, we present evidence that CAMTA3-mediated repression of SA pathway genes in nonstressed plants involves the action of an N-terminal repression module (NRM) that acts independently of calmodulin (CaM) binding to the IQ and CaM binding (CaMB) domains, a finding that is contrary to current thinking that CAMTA3 repression activity requires binding of CaM to the CaMB domain. Induction of SA pathway genes in response to low temperature did not occur in plants expressing only the CAMTA3-NRM region of the protein. Mutational analysis provided evidence that the repression activity of the NRM was suppressed by action of the IQ and CaMB domains responding to signals generated in response to low temperature. Plants expressing the CAMTA3-NRM region were also impaired in defense against the bacterial hemibiotrophic pathogen Pseudomonas syringae pv tomato DC3000. Our results indicate that the regulation of CAMTA3 repression activity by low temperature and pathogen infection involves related mechanisms, but with distinct differences.


Antioxidant properties of topical Caulerpa sp. extract on UVB-induced photoaging in mice.
Caulerpa sp., a genus of seaweed native to the Indo-Pacific region, has been known for its antioxidant properties and health benefits when consumed as food. Previous studies have reported Caulerpa sp.'s potential as a strong antioxidant, but its effects on the skin in a topical preparation, especially its role in ultraviolet (UV) protection, have not been studied extensively. Our study investigated the protective effects of 0.2% and 0.4% Caulerpa sp. extract gels on photoaging in the UVB-irradiated skin of Wistar mice. The subjects were divided into naive control, vehicle control, and 3 treatment groups (0.2% Caulerpa sp. extract gel, 0.4% Caulerpa sp. extract gel, and 0.02% astaxanthin gel as a standard antioxidant). The groups, except the naive control group, received a total of 840 mJ/cm2 of UVB irradiation in four weeks. Protective effects of the extract were measured through the evaluation of collagen expression, matrix metalloproteinase (MMP)-1 expression and levels, and 8-OhDG expression. Mice who received topical application of Caulerpa sp. extract gel had higher collagen expression, better-preserved collagen structure, lower levels of MMP-1, and less MMP-1 and 8-OHdG expressions compared to the vehicle control group. There was no difference between different concentrations of the extract. Our findings demonstrated that topical application of Caulerpa sp. extract gel significantly protected UVB-irradiated mice skin from photoaging.


Hepatic arterial infusion of mitoxantrone in the treatment of primary hepatocellular carcinoma.
Twenty-three patients (16 male, seven female) with hepatocellular carcinoma (HCC) were treated by hepatic arterial infusion (HAI) of mitoxantrone every 4 weeks. At each treatment, a catheter was inserted percutaneously into the main hepatic artery via the femoral artery under image intensification. Treatment consisted of a 24-hour continuous HAI of mitoxantrone, 6 mg/m2/d X 3 (eight patients) or 10 mg/m2/d X 3 (14 patients) without heparin. Eight patients had only one infusion, nine patients four infusions, five patients three infusions, two patients two infusions, and one patient five infusions. A partial response was seen in six patients, with a median duration of 20 weeks (range, 18 to 38 weeks). Five patients achieved stable disease, with a median duration of 20 weeks (range, 11 to 42 weeks). The median survival of the overall group was 22 weeks. Survivals of responding, stable, and nonresponding patients were 32 weeks, 24 weeks, and 9 weeks, respectively. Complications of catheter placement included asymptomatic dissection of the hepatic artery (one patient), and asymptomatic thrombosis of the hepatic artery (five patients). Three patients experienced mild nausea and vomiting, and six patients had mild to moderate alopecia. Granulocytopenia was frequent at both dose schedules. The granulocyte nadir was greater than 1,000/microL in 34% of evaluable courses, 500 to 1,000/microL in 32%, and less than 500/microL in 34% of courses. Two patients developed neutropenia-associated fever. A platelet nadir below 100,000/microL was seen after only 10% of courses, and only two patients had platelets below 50,000/microL. Seven patients received doxorubicin after progression on mitoxantrone. Four received systemic doxorubicin, 50 mg/m2, and three HAI of doxorubicin, 25 mg/m2, for three days. Two patients achieved partial response (18 weeks and 32 weeks) to HAI doxorubicin. Mitoxantrone has activity in HCC and is well tolerated when administered by HAI. It is not entirely cross-resistant with doxorubicin.


miR-132-3p, miR-106b-5p, and miR-19b-3p Are Associated with Brain-Derived Neurotrophic Factor Production and Clinical Activity in Multiple Sclerosis: A Pilot Study.
Introduction: Brain-derived neurotrophic factor (BDNF) levels are reduced in advanced stages of multiple sclerosis (MS) and may be associated with reduced regenerative capability in progressive MS. This has brought increased attention to factors regulating BDNF production in MS. Our aim was to investigate the link between neurotrophin-regulating microRNAs (miRNA) and disease progression in MS. Materials and Methods: Serum levels of BDNF and peripheral blood mononuclear cell (PBMC) expression levels of miR-132-3p, miR-106b-5p and miR-19b-3p were respectively measured by ELISA and real time PCR in twelve relapsing remitting MS (RRMS) patients, seven secondary progressive MS (SPMS) patients and fourteen healthy controls. Results: Serum BDNF levels were significantly reduced in SPMS patients, while selected miRNAs were significantly upregulated in PBMC of RRMS and SPMS patients. miR-106b-5p and miR-19b-3p respectively showed the highest sensitivity and specificity for MS diagnosis by receiver operating characteristic curve analysis. There was a negative correlation between levels of BDNF and the miRNAs in RRMS. Likewise, levels of BDNF and the investigated miRNAs showed positive and negative correlations respectively with the expanded disability status scale in RRMS and SPMS patients. miR-132-3p and miR-106b-5p levels showed positive correlations with the progression index in SPMS patients. Conclusion: Our results suggest that increased disability is associated with downregulation of miR-132-3p, miR-106b-5p and miR-19b-3p in RRMS patients and putatively promotes increased production of neuroprotective BDNF as a compensatory mechanism. This link between the investigated miRNAs and BDNF in RRMS does not appears to hold for SPMS. This might be one of the factors contributing to reduced regenerative ability in the progressive stage of MS.


Predictors of death from chronic graft-versus-host disease after bone marrow transplantation.
Chronic graft-v-host disease (chronic GVHD) is a frequent cause of late morbidity and death after bone marrow transplantation (BMT). The actuarial survival after onset of chronic GVHD in 85 patients was 42% (95%Cl = 29%, 54%) at 10 years. Baseline characteristics present at the onset of chronic GVHD (before therapy) in 85 patients were reviewed to determine which were risk factors for death. In a multivariate proportional hazards analysis, three baseline factors emerged as independent predictors of death: progressive presentation (chronic GVHD following acute GVHD without resolution of acute GVHD; hazard ratio of 4.1, 95% Cl = 2.1 to 7.8), lichenoid changes on skin histology (hazard ratio of 2.2, 95% Cl = 1.1 to 4.3), and elevation of serum bilirubin greater than 1.2 mg/dL (hazard ratio = 2.1, 95% Cl = 1.1 to 4.1). Actuarial survival of 23 chronic GVHD patients with none of these risk factors was 70% at 6 years (95% Cl = 38%, 88%). Thirty-eight patients with one of these risk factors had a projected 6-year survival of 43% (95% Cl = 21%, 63%). The 29 patients with any combination of two or more of these factors had a projected 6-year survival of only 20% (95% Cl = 8%, 37%). Identification of baseline risk factors should facilitate design of trials of chronic GVHD therapies and assignment of high-risk patients to more aggressive innovative therapeutic regimens.


A novel tumor-related protein, C7orf24, identified by proteome differential display of bladder urothelial carcinoma.
Proteome analysis of bladder cancer with narrow-range pH 2-DE has identified a novel protein on chromosome 7 encoded by ORF 24 (C7orf24) as one of the highly expressed proteins in cancer cells. C7orf24 is currently registered in the protein database as a hypothetical protein with unknown function. The homologs of C7orf24 in other animals have also been registered as putative protein genes. Western blot analysis using a mAb against C7orf24 confirmed its higher expression in bladder cancer compared with normal tissue. Several other cancer cell lines were also found to express C7orf24. However, the introduction of C7orf24 into Rat-1 or NIH3T3 cells did not cause malignant transformation. A stable transfectant of NIH3T3 cells with recombinant retrovirus vector was produced for a growth rate assay, and a higher growth rate was observed in C7orf24-expressing cells compared with the controls. Six kinds of small interfering RNAs (siRNAs) were then produced, and C7orf24-siRNA#5 showed a strong knockdown effect on protein expression and significant antiproliferative effects on cancer cell lines were demonstrated by the MTT assay. Therefore, C7orf24 may have an important role in cancer cell proliferation, and may be an appropriate therapeutic target molecule against cancer.


Juvenile idiopathic arthritis subtype- and sex-specific associations with genetic variants in the PSMA6/PSMC6/PSMA3 gene cluster.
The ubiquitin proteasome system plays an exceptional biological role in the antigen processing and immune response and it could potentially be involved in pathogenesis of many immunity-related diseases, including juvenile idiopathic arthritis (JIA). The PSMB5 (rs11543947), PSMA6 (rs2277460, rs1048990), PSMC6 (rs2295826, rs2295827), and PSMA3 (rs2348071) proteasomal genes were genotyped on JIA subtype- and sex-specific association; plasma proteasome levels was measured in patients having risk and protective four-locus genotypes and eventual functional significance of allele substitutions was evaluated in silico. Loci rs11543947 and rs1048990 were identified as disease neutral and other loci as disease susceptible (p < 0.05). The rs2277460, rs2295826, and rs2295827 loci had the strongest association with oligoarthritis [odds ratio (OR) = 2.024, 95% confidence interval (CI) 1.101-3.722; OR = 2.371, 95% CI 1.390-4.044; OR = 2.183, 95% CI 1.272-2.737, respectively), but the rs2348071 locus was associated with polyarthritis in females (OR = 3.438, 95% CI 1.626-7.265). A strong (p < 0.001) association was detected between the rs2277460/rs2295826/rs2295827/rs2348071 four-locus genotypes and the healthy phenotype when all loci were homozygous on common alleles (OR 0.439, 95% CI 0.283-0.681) and with the disease phenotype when the rs2348071 and the rs2295826 and/or rs2295827 loci were represented by risk genotypes simultaneously (OR 4.674, 95% CI 2.096-10.425). Rarely observed in controls, the double rs2277460/rs2348071 heterozygotes were rather frequent in affected males and more strongly associated with polyarthritis (p < 0.05). Haplotypes carrying the rare rs2295826/rs2295827 and rs2277460 alleles showed a strong (p < 0.001) association with oligo- and polyarthritis, respectively. The plasma proteasome level was found to be significantly higher in females having four-locus risk genotypes compared with protective genotypes (p < 0.001). Sequence affinity to transcription factors and similarity to splicing signals, microRNAs and/or hairpin precursors potentially depend on allele substitutions in disease susceptible loci. We demonstrate for the first time evidence of a sex-specific association of PSMA6/PSMC6/PSMA3 genetic variants with subtypes of JIA and plasma proteasome concentrations. Theoretical models of the functional significance of allele substitutions are discussed.


Supplementation with Angelica keiskei inhibits expression of inflammatory mediators in the gastric mucosa of Helicobacter pylori-infected mice.
Oxidative stress is involved in the pathogenesis of Helicobacter pylori-associated gastric ulceration and carcinogenesis. The oxidant-sensitive transcription factor, nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB), regulates expression of inflammatory mediators such as interferon γ (IFN-γ), cyclooxygenase 2 (COX-2), and inducible nitric oxide synthase (iNOS). These inflammatory mediators increased in gastric mucosal tissues from patients infected with H pylori. Angelica keiskei (AK), a green leafy vegetable, is rich in carotenoids and flavonoids and shows antioxidant and anti-inflammatory activities. Therefore, we hypothesized that AK may protect the gastric mucosa of H pylori-infected mice against inflammation. We determined lipid peroxide abundance, myeloperoxidase activity, expression levels of inflammatory mediators (IFN-γ, COX-2, and iNOS), NF-κB-DNA binding activity, and histologic changes in gastric mucosal tissues. The antioxidant N-acetylcysteine served as the positive control treatment. Supplementation with AK suppressed increases in lipid peroxide abundance, myeloperoxidase activity, induction of inflammatory mediators (IFN-γ, COX-2, and iNOS), activation of NF-κB, and degradation of nuclear factor of κ light polypeptide gene enhancer in B-cells inhibitor α in gastric mucosal tissue from H pylori-infected mice. Inhibition of H pylori-induced alterations by AK was similar to that by N-acetylcysteine. Taken together, these results suggest that supplementation with AK may prevent H pylori-induced gastric inflammation by inhibiting NF-κB-mediated induction of inflammatory mediators in the gastric mucosa of patients infected with H pylori.


Fall-grown oat to extend the fall grazing season for replacement dairy heifers.
Our objective was to assess the pasture productivity and forage characteristics of 2 fall-grown oat (Avena sativa L.) cultivars, specifically for extending the grazing season and reducing reliance on harvested forages by replacement dairy heifers. A total of 160 gravid Holstein heifers (80 heifers/yr) were stratified by weight, and assigned to 1 of 10 identical research pens (8 heifers/pen). Initial body weights were 480 ± 43.5 kg in 2011 and 509 ± 39.4 kg in 2012. During both years of the trial, four 1.0-ha pasture replicates were seeded in August with Ogle oat (Schumitsch Seed Inc., Antigo, WI), and 4 separate, but similarly configured, pasture replicates were seeded with Forage Plus oat (Kratz Farms, Slinger, WI). Heifer groups were maintained as units, assigned to specific pastures, and then allowed to graze fall-oat pastures for 6h daily before returning to the barn, where they were offered a forage-based basal total mixed ration. Two heifer groups were retained in confinement (without grazing) as controls and offered the identical total mixed ration as pasture groups. During 2011, available forage mass increased with strong linear and quadratic effects for both cultivars, peaking at almost 9 Mg/ha on October 31. In contrast, forage mass was not affected by evaluation date in 2012, remaining ≤ 2,639 kg/ha across all dates because of droughty climatic conditions. During 2012, Ogle exhibited greater forage mass than Forage Plus across all sampling dates (2,678 vs. 1,856 kg/ha), largely because of its more rapid maturation rate and greater canopy height. Estimates of energy density for oat forage ranged from 59.6 to 69.1% during 2011, and ranged narrowly from 68.4 to 70.4% during 2012. For 2011, responses for both cultivars had strong quadratic character, in which the most energy-dense forages occurred in mid November, largely due to accumulation of water-soluble carbohydrates that reached maximum concentrations of 18.2 and 15.1% for Forage Plus and Ogle, respectively. Across the 2-yr trial, average daily gain for grazing heifer groups tended to be greater than heifers remaining in confinement (0.85 vs. 0.74 kg/d), but both management strategies produced weight gains within reasonable proximity to normal targets for heifers in this weight range. Fall-grown oat should be managed as stockpiled forage for deferred grazing, and good utilization of fall-oat forage can be accomplished by a one-time removal of standing forage, facilitated by a single lead wire advanced daily to prevent waste.


Lifetime estimation of wireless body area sensor network for patient health monitoring.
Wireless Body Area Sensor Networks (WBASN) is an emerging technology which utilizes wireless sensor nodes to implement real-time wearable health monitoring of patients to enhance independent living. These sensor nodes can be worn externally to monitor multiple bio-parameters (such as blood oxygen saturation (SpO(2)), blood pressure and heart activity) of multiple patients at a central location in the hospital. It is important to have an estimate of the time the first node will fail in order to replace or recharge the battery because the loss of critical data is not acceptable. Simulation is used to determine the lifetime of WBASN. The lifetime of the WBASN is defined as the duration of time until the first node fails due to battery depletion. In this paper, a parametric model of a health monitoring network (HMN) is created with sets of random input distributions. Probabilistic analysis is used to determine the timing and distribution of node failure in the HMN.


Investigation of Rare Protein Conformational Transitions via Dissipation-Corrected Targeted Molecular Dynamics.
To sample rare events, dissipation-corrected targeted molecular dynamics (dcTMD) applies a constant velocity constraint along a one-dimensional reaction coordinate s, which drives an atomistic system from an initial state into a target state. Employing a cumulant approximation of Jarzynski's identity, the free energy ΔG(s) is calculated from the mean external work and dissipated work of the process. By calculating the friction coefficient Γ(s) from the dissipated work, in a second step, the equilibrium dynamics of the process can be studied by propagating a Langevin equation. While so far dcTMD has been mostly applied to study the unbinding of protein-ligand complexes, here its applicability to rare conformational transitions within a protein and the prediction of their kinetics are investigated. As this typically requires the introduction of multiple collective variables {xj} = x, a theoretical framework is outlined to calculate the associated free energy ΔG(x) and friction Γ(x) from dcTMD simulations along coordinate s. Adopting the α-β transition of alanine dipeptide as well as the open-closed transition of T4 lysozyme as representative examples, the virtues and shortcomings of dcTMD to predict protein conformational transitions and the related kinetics are studied.


Empirical models to identify mechanisms driving reductions in tissue mercury concentration during culture of farmed southern bluefin tuna Thunnus maccoyii.
Two empirical models are presented to elucidate the mechanisms driving reductions in the mercury concentration of southern bluefin tuna (SBT) during culture. Model 1 predicts temporal fluctuations in mercury concentration in response to growth dilution. Model 2 predicts the combined effects of growth dilution and linear mercury accumulation. Model 2 was found to be the more accurate model. Over a typical farming period of 136 days, growth dilution resulted in a reduction in mean mercury concentration of SBT edible tissues from 0.51 mg/kg down to 0.33 mg/kg. Extended culture beyond 136 days resulted in an increase in mercury concentration due to the combined effects of mercury accumulation and seasonal lipid depletion. Results indicate that under current industry practice, cultured SBT can be consumed twice as frequently as that of wild caught SBT while maintaining total dietary mercury intake below national recommendations.


The primary care-specialty income gap: why it matters.
A large, widening gap exists between the incomes of primary care physicians and those of many specialists. This disparity is important because noncompetitive primary care incomes discourage medical school graduates from choosing primary care careers. The Resource-Based Relative Value Scale, designed to reduce the inequality between fees for office visits and payment for procedures, failed to prevent the widening primary care-specialty income gap for 4 reasons: 1) The volume of diagnostic and imaging procedures has increased far more rapidly than the volume of office visits, which benefits specialists who perform those procedures; 2) the process of updating fees every 5 years is heavily influenced by the Relative Value Scale Update Committee, which is composed mainly of specialists; 3) Medicare's formula for controlling physician payments penalizes primary care physicians; and 4) private insurers tend to pay for procedures, but not for office visits, at higher levels than those paid by Medicare. Payment reform is essential to guarantee a healthy primary care base to the U.S. health care system.


Draft Genome Sequence of Erwinia dacicola, a Dominant Endosymbiont of Olive Flies.
Erwinia dacicola is a dominant endosymbiont of the pestiferous olive fly. Its genome is similar in size and GC content to those of free-living Erwinia species, including the plant pathogen Erwinia amylovora. The E. dacicola genome encodes the metabolic capability to supplement and detoxify the olive fly's diet in larval and adult stages.


Cardiometabolic risk factors in Turkish children with hepatosteatosis.
Aslan A, Erdemli S, Durukan Günaydın G, Aslan M, Yazar RÖ, Kabaalioğlu A, Ağırbaşlı MA. Cardiometabolic risk factors in Turkish children with hepatosteatosis. Turk J Pediatr 2019; 61: 714-722. We aimed to investigate the prevalence of cardiometabolic (CM) risk factors (impaired fasting glucose ( > 100 mg/dL), high blood pressure, overweight or obesity, high serum triglycerides (TG) and low serum high-density lipoprotein cholesterol levels) in children with hepatosteatosis detected by abdominal ultrasound. Children whom ultrasound examination revealed hepatic steatosis were included in the study. Medical records, anthropometric and biochemical parameters were reviewed for the presence of the CM risk factors. Presence of ≥3 risk factors was defined as metabolic syndrome (MS). One hundred and forty-eight children and adolescents (67 boys, 81girls, and mean age 12.1±2.7 years) with hepatosteatosis were included. Sonographic hepatosteatosis grades of 1, 2 and 3 were observed in 111 (75%), 33 (22.3%), and 4 (2.7%) subjects, respectively. MS was observed in 36 patients (24.3%). The number of CM risk factors and degree of hepatic steatosis were correlated (r=0.183, p=0.026). Serum TG levels in girls and age in boys were significantly associated with the presence of medium to severe hepatosteatosis (grades 2 or 3) (R2=.342, =.040 and R2=.538, p=.001, respectively). CM risk factors and MS are common in children with hepatosteatosis. The presence and grade of hepatosteatosis on ultrasound can be used as surrogate markers of MS and CM risk in children.


Can 24-hour urine stone risk profiles predict urinary stone composition?
Distinguishing calcium oxalate from uric acid stones is critical to identify those patients who may benefit from dissolution therapy and can also help direct preventive measures for stone growth. We aim to study whether 24-hour urine analysis may predict the urinary stone composition. We retrospectively identified patients with calcium oxalate and uric acid stone compositions who also had a 24-hour urine collection within 3 months of stone analysis. Patients with calcium phosphate, cystine, and other stone compositions were excluded. Subjects were divided based on their stone type (calcium oxalate vs uric acid stones) and were compared according to demographic data and 24-hour urine analysis. Logistic regression analysis was performed to assess the association between stone composition and covariates. A nomogram was then constructed to predict uric acid stones over calcium oxalate stones. Of the 1163 patients identified, 1054 (90.6%) had calcium oxalate stones and 109 (9.4%) had uric acid stones. On logistic regression, body mass index (BMI) (odds ratio [OR] 1.351, 95% confidence interval [CI] 1.133-1.609; P<0.001), urinary sodium (OR 1.021, 95% CI 1.004-1.037; P=0.013), calcium (OR 0.987, 95% CI 0.979-0.996; P=0.003), oxalate (OR 0.890, 95% CI 0.804-0.985; P=0.024), and uric acid (OR 0.989, 95% CI 0.982-0.997; P=0.005) were significant predictors for urinary stone composition. The nomogram with the highest concordance index (c-index=0.855) was obtained using age, BMI, urinary sodium, calcium, oxalate, and uric acid as variables. Distinguishing uric acid from calcium oxalate stones can be performed with relative accuracy using parameters from the 24-hour urine stone risk profile and the patient's BMI and age.


Active microrheology and simultaneous visualization of sheared phospholipid monolayers.
Two-dimensional films of surface-active agents-from phospholipids and proteins to nanoparticles and colloids-stabilize fluid interfaces, which are essential to the science, technology and engineering of everyday life. The 2D nature of interfaces present unique challenges and opportunities: coupling between the 2D films and the bulk fluids complicates the measurement of surface dynamic properties, but allows the interfacial microstructure to be directly visualized during deformation. Here we present a novel technique that combines active microrheology with fluorescence microscopy to visualize fluid interfaces as they deform under applied stress, allowing structure and rheology to be correlated on the micron-scale in monolayer films. We show that even simple, single-component lipid monolayers can exhibit viscoelasticity, history dependence, a yield stress and hours-long time scales for elastic recoil and aging. Simultaneous visualization of the monolayer under stress shows that the rich dynamical response results from the cooperative dynamics and deformation of liquid-crystalline domains and their boundaries.


Inhibition of the emergence of multi drug resistant Staphylococcus aureus by Withania somnifera root extracts.
To search systematically for an alternative therapy with compounds particularly from plant origin. Efficacy test of different root extracts of Withania somnifera (W. somnifera) (L) Dunal against multi drug resistant (MDR) Staphylococcus aureus (S. aureus) variants was performed following the agar well diffusion method. Evaluation of susceptibility pattern of the isolates was carried out by employing disk diffusion method using standard antibiotic disks. In vitro study with W. somnifera root extracts was found to be effective against all the MDR S. aureus strains isolated from local and patient sources. Different root extracts of WS showed different degree of effectiveness against the isolates. The major active principles responsible for the antibacterial efficacy were mainly present in methanol (MeOH)extract and ethanol (EtOH) extracts as well as in butanol (BuOH) extract fraction. Amongst all the extracts the BuOH fraction was found to be most active against all the isolates but aqueous extract was the least active one. Finally it may be concluded that the antimicrobials from W. somnifera may raise an alternative therapy for MDR staphylococcal infections in near future.


Noradrenaline and cyclic AMP--independent growth stimulation in newt limb blastemata.
Adult newts regenerate functional limbs after amputation. This process normally depends on the trophic influence of nerves on the regenerating limbs, particularly in the early stages before differentiation of the regeneration blastema, when it stimulates growth by maintaining high rates of macromolecular synthesis. The sequence of biochemical events involved is unknown, but it has been suggested that intracellular cyclic AMP may be a second messenger within the blastema. Many studies have indicated that the neural agent(s) involved might be protein. The recent finding that blastemata contain high levels of catecholamines, however, has implicated noradrenaline (NA) as the neurotrophic agent, and suggested that it works via stimulation of beta-adrenergic receptors on the blastemal cells, thereby raising the intracellular concentrations of cyclic AMP. To test this hypothesis we studied the ability of NA alone and in combination with alpha-and beta-adrenergic antagonists to increase cyclic AMP levels and to mimic the effects of nerves by maintaining high rates of protein synthesis and high mitotic indices (MI) in denervated blastemata in organ culture. We find that although NA raises cyclic AMP levels through a beta-adrenergic effect, it does not maintain high rates of protein synthesis or high MI in cultured blastemata. It is unlikely therefore, that this hypothesis applies.


Mindfulness interventions improve momentary and trait measures of attentional control: Evidence from a randomized controlled trial.
Mindfulness interventions have been shown to improve several subcomponents of attention; however, the psychological mechanisms driving these improvements are unknown. Mindfulness interventions train individuals to monitor present moment experiences while adopting an attitude of acceptance toward these experiences. We conducted a theoretically driven randomized controlled trial to test the putative mechanisms of mindfulness training that drive improvements in attentional control. Participants were randomly assigned to 1 of 3 conditions: (a) monitor and accept (MA) training, a standard 8-week mindfulness-based stress reduction (MBSR) intervention that included cultivation of both monitoring and acceptance skills; (b) monitor only (MO) training, a well-matched modified 8-week MBSR-adapted intervention that focused on monitoring skills only; or (c) no treatment (NT) control. Momentary attentional control was measured via ecological momentary assessment for 3 days at baseline and postintervention. Trait attentional control was assessed at baseline and postintervention using traditional self-report. Participants also completed a dichotic listening task to assess sustained attention at baseline and postintervention. We found that MA and MO participants improved in momentary and trait attentional control (but not attention task performance) relative to NT participants. Analyses of indirect effects were consistent with the possibility that increased momentary attentional control partially accounts for MA/MO intervention-related increases in trait attentional control. This randomized controlled trial provides one of the first experimental tests of the mechanisms of mindfulness interventions that drive improvements in attention outcomes. These findings support the notion that present-focused monitoring skills training drives mindfulness intervention-related improvements in momentary attentional control, which in turn fosters greater trait attentional control. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Pancreatic cancer in Israel: the epidemiology, possibilities of prevention, early detection and screening.
Pancreatic cancer is not a common malignancy in Israel, but it is the third most common cause of cancer mortality, attributable to a lack of screening tests, inaccessibility of the pancreas, and late cancer stage at diagnosis. We reviewed the epidemiology, known risk factors and screening methods available in Israel and describe the Israeli national consortium that was established to identify persons at risk and decide on screening methods to detect and treat their early-stage pancreatic cancer. In collaboration with the Israel National Cancer Registry, we evaluated the incidence and trends of the disease in the Jewish and non-Jewish populations. The consortium reviewed known lifestyle risk habits, genetic causes, and screening methodologies used and available in Israel. Overall, there are about 600 new patients per year, with the highest incidence occurring in Jewish men of European birth (age-standardized rate 8.11/10(5) for 2003-06). The 5 year survival is about 5%. The consortium concluded that screening will be based on endoscopic ultrasonography. Pancreatic cancer patients and families at risk will be enrolled, demographic and lifestyle data collected and a cancer pedigree generated. Risk factors will be identified and genetic tests performed as required. This concerted national program to identify persons at risk, recommend which environmental risk factors to avoid and treat, and perform endoscopic ultrasound and genetic screening where appropriate, might reduce the incidence of invasive pancreatic cancer and/or improve its prognosis.


Peripheral blood CD14(+) cells from healthy subjects carry a circular conformation of latent cytomegalovirus genome.
The majority of the human population harbors latent cytomegalovirus. Although CD14(+) peripheral blood mononuclear cells have been implicated as sites of latency, the conformation of the latent viral genome in these cells is unknown. In this study, the conformation of viral genomic DNA was assessed in CD14(+) cells from healthy virus seropositive carriers using an electrophoretic separation on native agarose gels in combination with polymerase chain reaction detection. Here we show that the viral genome migrates as a circular plasmid with a mobility equivalent to a circular 230-kb Shigella flexneri megaplasmid marker. Neither linear nor complex or integrated forms of the viral genome were detected. This report provides further evidence that the CD14(+) cell population is an important site of viral latency in the naturally infected human host. Detection of the viral genome as a circular plasmid during latency suggests that this virus maintains its genome in a manner analogous to other herpesviruses where latent viral genome conformation has been studied.


Widespread decline of Congo rainforest greenness in the past decade.
Tropical forests are global epicentres of biodiversity and important modulators of climate change, and are mainly constrained by rainfall patterns. The severe short-term droughts that occurred recently in Amazonia have drawn attention to the vulnerability of tropical forests to climatic disturbances. The central African rainforests, the second-largest on Earth, have experienced a long-term drying trend whose impacts on vegetation dynamics remain mostly unknown because in situ observations are very limited. The Congolese forest, with its drier conditions and higher percentage of semi-evergreen trees, may be more tolerant to short-term rainfall reduction than are wetter tropical forests, but for a long-term drought there may be critical thresholds of water availability below which higher-biomass, closed-canopy forests transition to more open, lower-biomass forests. Here we present observational evidence for a widespread decline in forest greenness over the past decade based on analyses of satellite data (optical, thermal, microwave and gravity) from several independent sensors over the Congo basin. This decline in vegetation greenness, particularly in the northern Congolese forest, is generally consistent with decreases in rainfall, terrestrial water storage, water content in aboveground woody and leaf biomass, and the canopy backscatter anomaly caused by changes in structure and moisture in upper forest layers. It is also consistent with increases in photosynthetically active radiation and land surface temperature. These multiple lines of evidence indicate that this large-scale vegetation browning, or loss of photosynthetic capacity, may be partially attributable to the long-term drying trend. Our results suggest that a continued gradual decline of photosynthetic capacity and moisture content driven by the persistent drying trend could alter the composition and structure of the Congolese forest to favour the spread of drought-tolerant species.