Urinary beta2-microglobulin is associated with acute renal allograft rejection.
Identifying urinary biomarkers associated with acute rejection (AR) of kidney allografts could improve recipient care by allowing AR to be diagnosed noninvasively and treated earlier. We attempted to identify novel biomarkers associated with AR by analyzing urinary proteins by using matrix-associated laser desorption ionization time-of-flight mass spectroscopy (MALDI-TOF MS). Using MALDI-TOF MS, we analyzed urine samples from 30 renal allograft recipients with biopsy-proven AR, 15 allograft recipients without AR, preoperative samples from 29 kidney donors, and 10 subjects with proteinuric native kidney disease. In samples obtained at the time of AR, we identified a protein peak at 11.7 kd that correlated strongly with AR. In regard to its predictive power for AR, this protein peak showed sensitivity of 83.3%, specificity of 80%, positive predictive value of 89%, and negative predictive value of 70.6%, suggesting that this protein is highly associated with AR. We identified this peak as being beta2-microglobulin. This was validated by using enzyme-linked immunosorbent assay, which documented the presence of high urinary beta2-microglobulin levels in subjects with AR. Beta2-microglobulin could be a strong biomarker for AR if used in conjunction with other biomarkers, producing an AR-specific urinary protein signature. This possibility must be confirmed in a larger cohort of kidney transplant recipients.


Two-photon absorption in tetraphenylporphycenes: are porphycenes better candidates than porphyrins for providing optimal optical properties for two-photon photodynamic therapy?
Porphycenes are structural isomers of porphyrins that have many unique properties and features. In the present work, the resonant two-photon absorption of 2,7,12,17-tetraphenylporphycene (TPPo) and its palladium(II) complex (PdTPPo) has been investigated. The data obtained are compared to those from the isomeric compound, meso-tetraphenylporphyrin (TPP). Detection of phosphorescence from singlet molecular oxygen, O2(a(1)Delta(g)), produced upon irradiation of these compounds, was used to obtain two-photon excitation spectra and to quantify two-photon absorption cross sections, delta. In the spectral region of 750-850 nm, the two-photon absorption cross sections at the band maxima for both TPPo and PdTPPo, delta = 2280 and 1750 GM, respectively, are significantly larger than that for TPP. This difference is attributed to the phenomenon of so-called resonance enhancement; for the porphycenes, the two-photon transition is nearly resonant with a comparatively intense one-photon Q-band transition. The results of quantum mechanical calculations using density functional quadratic response theory are in excellent agreement with the experimental data and, as such, demonstrate that comparatively high-level quantum chemical methods can be used to interpret and predict nonlinear optical properties from such large molecular systems. One important point realized through these experiments and calculations is that one must exercise caution when using qualitative molecular-symmetry-derived arguments to predict the expected spectral relationship between allowed one- and two-photon transitions. From a practical perspective, this study establishes that, in comparison to porphyrins and other tetrapyrrolic macrocyclic systems, porphycenes exhibit many desirable attributes for use as sensitizers in two-photon initiated photodynamic therapy.


Running with the Red Queen: the role of biotic conflicts in evolution.
What are the causes of natural selection? Over 40 years ago, Van Valen proposed the Red Queen hypothesis, which emphasized the primacy of biotic conflict over abiotic forces in driving selection. Species must continually evolve to survive in the face of their evolving enemies, yet on average their fitness remains unchanged. We define three modes of Red Queen coevolution to unify both fluctuating and directional selection within the Red Queen framework. Empirical evidence from natural interspecific antagonisms provides support for each of these modes of coevolution and suggests that they often operate simultaneously. We argue that understanding the evolutionary forces associated with interspecific interactions requires incorporation of a community framework, in which new interactions occur frequently. During their early phases, these newly established interactions are likely to drive fast evolution of both parties. We further argue that a more complete synthesis of Red Queen forces requires incorporation of the evolutionary conflicts within species that arise from sexual reproduction. Reciprocally, taking the Red Queen's perspective advances our understanding of the evolution of these intraspecific conflicts.


Changes in right ventricular relaxation during acute anterior myocardial infarction in pigs.
To determine the effect of an anteroseptal myocardial infarction on right ventricular systolic and diastolic function, we studied 12 pigs before and 1 h after left anterior descending coronary artery occlusion. Total arterial occlusion was achieved by the percutaneous, transcatheter placement of a 1 mm Teflon plug into the mid portion of the artery. The resulting infarction involved 28 (SEM 3)% of the left ventricular wall, in the anterior and septal regions. A small rim of the right ventricular free wall adjacent to the septum and the right ventricular apex were also affected. End diastolic pressures in both ventricles rose significantly: left ventricular from 12(1) to 20(2) mm Hg and right ventricular from 8(1) to 10(1) mm Hg. Right ventricular peak systolic pressure increased from 29(2) to 35(2) mm Hg while left ventricular peak systolic pressure did not change. One hour after infarction the half time of isovolumic relaxation of the right ventricle was prolonged from 6.9(0.5) to 8.7(0.4) ms. Ejection fraction in both ventricles was depressed: from 46(1) to 34(2)% in the right ventricle and from 69(3) to 49(3) in the left ventricle. There was no change in either right or left ventricular dP/dt. These data suggest that right ventricular systolic and diastolic dysfunction occurs as the result of an anteroseptal myocardial infarction in pigs.


Feasibility of distributing rapid diagnostic tests for malaria in the retail sector: evidence from an implementation study in Uganda.
Despite the benefits of malaria diagnosis, most presumed malaria episodes are never tested. A primary reason is the absence of diagnostic tests in retail establishments, where many patients seek care. Malaria rapid diagnostic tests (RDTs) in drug shops hold promise for guiding appropriate treatment. However, retail providers generally lack awareness of RDTs and training to administer them. Further, unsubsidized RDTs may be unaffordable to patients and unattractive to retailers. This paper reports results from an intervention study testing the feasibility of RDT distribution in Ugandan drug shops. 92 drug shops in 58 villages were offered subsidized RDTs for sale after completing training. Data on RDT purchases, storage, administration and disposal were collected, and samples were sent for quality testing. Household surveys were conducted to capture treatment outcomes. Estimated daily RDT sales varied substantially across shops, from zero to 8.46 RDTs per days. Overall compliance with storage, treatment and disposal guidelines was excellent. All RDTs (100%) collected from shops passed quality testing. The median price charged for RDTs was 1000USH ($0.40), corresponding to a 100% markup, and the same price as blood slides in local health clinics. RDTs affected treatment decisions. RDT-positive patients were 23 percentage points more likely to buy Artemisinin Combination Therapies (ACTs) (p = .005) and 33.1 percentage points more likely to buy other antimalarials (p<.001) than RDT-negative patients, and were 5.6 percentage points more likely to buy ACTs (p = .05) and 31.4 percentage points more likely to buy other antimalarials (p<.001) than those not tested at all. Despite some heterogeneity, shops demonstrated a desire to stock RDTs and use them to guide treatment recommendations. Most shops stored, administered and disposed of RDTs properly and charged mark-ups similar to those charged on common medicines. Results from this study suggest that distributing RDTs through the retail sector is feasible and can reduce inappropriate treatment for suspected malaria.


Photoswitchable fluorescent proteins enable monochromatic multilabel imaging and dual color fluorescence nanoscopy.
Fluorescent proteins that can be reversibly photoswitched between a fluorescent and a nonfluorescent state are important for innovative microscopy schemes, such as protein tracking, fluorescence resonance energy transfer imaging, sub-diffraction resolution microscopy and others. However, all available monomeric reversibly switchable fluorescent proteins (RSFPs) have similar properties and switching characteristics, thereby limiting their use. Here, we introduce two bright green fluorescent RSFPs, bsDronpa and Padron, generated by extensive mutagenesis of the RSFP Dronpa, with unique absorption and switching characteristics. Whereas bsDronpa features a broad absorption spectrum extending into the UV, Padron displays a switching behavior that is reversed to that of all green fluorescent RSFPs known to date. These two RSFPs enable live-cell fluorescence microscopy with multiple labels using a single detection color, because they can be distinguished by photoswitching. Furthermore, we demonstrate dual-color fluorescence microscopy with sub-diffraction resolution using bsDronpa and Dronpa whose emission maxima are separated by <20 nm.


Effects of placebos without deception compared with no treatment: protocol for a systematic review and meta-analysis.
Placebos have long provided a robust control for evaluating active pharmacological preparations, but frequently demonstrate a variable therapeutic effect when delivered in double-blinded placebo-controlled trials. Delivery of placebos as treatment alone has been considered unethical, as it has been thought that deception is essential for their effect. However, recent evidence suggests that clinical benefit can be derived from placebos delivered without deception (unblinded/open-label) manner. Here, we present a protocol for the first systematic review and meta-analysis of studies of the effects of non-deceptive placebos compared with no treatment. This protocol will compare the effect of placebos delivered non-deceptively to no treatment. It will also assess the methods of delivery used for non-deceptive placebos. Studies will be sought through relevant database searches and will include those within disease settings and those among healthy controls. To be included, trials must include both non-deceptive (open-label) placebo and no treatment groups. All data extraction and analysis will be conducted by two independent reviewers. The analysis will evaluate any differences in outcome measures between the non-deceptive placebo and no treatment groups. Outcome measures will be the clinically-relevant outcomes detailed in the primary papers. The delivery methods, such as verbal instructions, which may provide positive expectations and outcomes, of non-deceptive placebos will also be assessed. Each study will be comprehensively assessed for bias. Subgroup analyses will identify any discrepancies among heterogeneous data. This review does not require ethical approval. The completed review will be widely disseminated by publication and social media where appropriate. This protocol has been registered on PROSPERO (2015:CRD42015023347).


Autoantibodies against Cytochrome P450 Side-Chain Cleavage Enzyme in Dogs (Canis lupus familiaris) Affected with Hypoadrenocorticism (Addison's Disease).
Canine hypoadrenocorticism likely arises from immune-mediated destruction of adrenocortical tissue, leading to glucocorticoid and mineralocorticoid deficiency. In humans with autoimmune Addison's disease (AAD) or autoimmune polyendocrine syndrome (APS), circulating autoantibodies have been demonstrated against enzymes associated with adrenal steroid synthesis. The current study investigates autoantibodies against steroid synthesis enzymes in dogs with spontaneous hypoadrenocorticism. Coding regions of canine CYP21A2 (21-hydroxylase; 21-OH), CYP17A1 (17-hydroxylase; 17-OH), CYP11A1 (P450 side-chain cleavage enzyme; P450scc) and HSD3B2 (3β hydroxysteroid dehydrogenase; 3βHSD) were amplified, cloned and expressed as 35S-methionine radiolabelled recombinant protein. In a pilot study, serum samples from 20 dogs with hypoadrenocorticism and four unaffected control dogs were screened by radio-immunoprecipitation assay. There was no evidence of reactivity against 21-OH, 17-OH or 3βHSD, but five dogs with hypoadrenocorticism showed immunoreactivity to P450scc compared with controls. Serum samples were subsequently obtained from 213 dogs diagnosed with hypoadrenocorticism and 110 dogs from a hospital control population. Thirty control dogs were randomly selected to establish a threshold for antibody positivity (mean + 3 × standard deviation). Dogs with hypoadrenocorticism were more likely to be P450scc autoantibody positive than hospital controls (24% vs. 1.2%, respectively; p = 0.0016). Sex was significantly associated with the presence of P450scc autoantibodies in the case population, with 30% of females testing positive compared with 17% of males (p = 0.037). Significant associations with breed (p = 0.015) and DLA-type (DQA1*006:01 allele; p = 0.017) were also found. This cross-sectional study indicates that P450scc autoantibodies are present in a proportion of dogs affected with hypoadrenocorticism.


Serum 25-hydroxyvitamin D is not associated with insulin resistance or beta cell function in Canadian Cree.
Epidemiological studies report inverse associations between blood vitamin D, as measured by 25-hydroxyvitamin D [25(OH)D] concentrations, and insulin resistance (IR) among predominantly overweight individuals. In a cross-sectional survey of 5 Cree communities in Quebec, Canada, we determined if 25(OH)D is associated with IR and β-cell function in a largely obese, ethnic minority at high risk of developing type 2 diabetes. A total of 510 participants (≥18 y) without type 1 or type 2 diabetes, assessed for serum 25(OH)D, fasting plasma glucose and insulin, and anthropometric and lifestyle variables, were included in the analyses. Multivariable linear regressions adjusted for covariates were performed for homeostasis model assessment of IR (HOMA-IR) and β-cell function (HOMA-B) in relation to serum 25(OH)D. Serum 25(OH)D (per 10 nmol/L increment) was inversely associated with HOMA-IR (β = -0.005; SE = 0.002; P = 0.004) and HOMA-B (β = -0.004; SE = 0.002; P = 0.006) in models adjusted for age, sex, physical activity, education, alcohol consumption, and smoking. When further adjusted for BMI, associations were no longer significant for either HOMA-IR (β = 0.001, SE = 0.002, P = 0.572) or HOMA-B (β = 0.001, SE = 0.001, P = 0.498). The modest inverse associations between 25(OH)D and IR reported previously were not observed in this population after adjusting for adiposity. Future longitudinal studies investigating the interrelationship among 25(OH)D, adiposity, and the risk of developing metabolic syndrome and type 2 diabetes are warranted.


Molecular and histological endpoints for developmental reproductive toxicity in Xenopus tropicalis: Levonorgestrel perturbs anti-Müllerian hormone and progesterone receptor expression.
There is an increasing concern regarding the risks associated with developmental exposure to endocrine disrupting chemicals and the consequences for reproductive capability. The present study aimed to refine the Xenopus (Silurana) tropicalis test system for developmental reproductive toxicity by characterising molecular and histological features of sexual development, and to explore effects of exposure to the progestagen levonorgestrel (LNG). Larvae were exposed to LNG (0, 3, 30, 300 ng/L) over the first three weeks of development, encompassing the beginning of gonadal differentiation. mRNA levels of amh (anti-Müllerian hormone), amhr2 (amh receptor 2), ipgr (intracellular progesterone receptor), mpgr beta (membrane progesterone receptor beta), and cyp19a1 (cytochrome p450 19a1) were quantified in larvae and juveniles (4 weeks post-metamorphosis). Relative cyp19a1 and amh expression was used as a molecular marker for phenotypic sex of larvae. Gonadal and Müllerian duct development were characterised histologically in juveniles. Compared to controls, LNG exposure increased the expression of amh and ipgr in male larvae. In juveniles, mpgr beta expression was increased in both sexes and amhr2 expression was decreased in males, implying persistent effects of developmental progestagen exposure on amh and pgr expression signalling. No effects of LNG on the gonadal or Müllerian duct development were found, implying that the exposure window was not critical with regard to these endpoints. In juveniles, folliculogenesis had initiated and the Müllerian ducts were larger in females than in males. This new knowledge on sexual development in X. tropicalis is useful in the development of early life-stage endpoints for developmental reproductive toxicity.


The use of exhaled nitric oxide in the management of asthma.
It has recently become clear that airways disease associated with eosinophilic airway inflammation, but not other patterns of inflammation, is closely associated with favourable short-and long-term responses to corticosteroid therapy, irrespective of the clinical context in which it occurs. Moreover, a raised exhaled nitric oxide (FE(NO)) is a reasonable marker of eosinophilic airway inflammation, which has a number of advantages as a diagnostic and monitoring tool. In this review we outline essential background information on the use of FE(NO) in clinical practice and discuss some recent work evaluating the clinical value of this technique.


Three pathways to mature macrophages in the early mouse yolk sac.
The existence of macrophages (Mphi) of yolk-sac (YS) origin has been reported in all vertebrate models. However, the nature of their precursors and pathways of differentiation have not been elucidated. Phenotypic and differentiation potential analyses of YS at 7.5 to 10 postcoital days (dpc), performed in CX3CR1(GFP) embryos, allowed us to discern 3 independent Mphi populations. A first transient wave consisted of mature, maternal-derived Mphipresent as early as 7.5 to 8 dpc. A second wave of committed Mphi precursors arose at 8 dpc (2-4 somite stage) and was followed by a third wave of erythromyeloid precursors (4-6 somite stage). Both types of precursors displayed similar phenotypes and gave rise to CX3CR1/green fluorescent protein (GFP)-positive Mphi, but differed by their differentiation potential, at the clonal level. The combined data of phenotypic, gene-expression, and in situ analyses allowed us to conclude that the previously named "primitive Mphi" corresponded to a mixture of the first transient wave and committed Mphi precursors. Both YS-derived precursors followed a developmental pathway common to adult Mphi and could be qualified as definitive.


Impact of the clinical Pilates exercises and verbal education on exercise beliefs and psychosocial factors in healthy women.
[Purpose] Exercise is one of the most important components of a healthy life. The purpose of this study was to analyze exercise beliefs and psychosocial factors in sedentary and active healthy women and observe the changes in these parameters resulting from clinical Pilates exercises and verbal education in healthy women. [Subjects and Methods] Sixty-six healthy women were included in the study. Participants were divided into clinical Pilates (n=21), verbal education (n=25), and control groups (n=20). Prior to and at the end of the study, demographic information, body mass index, waist-hip circumference, exercise beliefs, physical activity index, and psychosocial factors (Rosenberg self-esteem scale, Body Cathexis Index, SF-36 quality of life, Beck Depression Scale, visual analog scale for tiredness) of the subjects were recorded. [Results] Meaningful changes for all the parameters took place in the clinical Pilates and verbal education groups. Our analyses indicated that the changes in the clinical Pilates group were more meaningful than those in the verbal education group. When the data of the study groups were compared with those of the control group, the clinical Pilates group showed meaningful differences. [Conclusion] The result of this study indicate that both clinical Pilates and verbal education are effective in changing exercise beliefs and physical and psychosocial parameters.


How irritating: the role of TRPA1 in sensing cigarette smoke and aerogenic oxidants in the airways.
Airway irritants cause a variety of lung pathologies. Two separate studies, the first recently reported in the JCI by Bessac et al. and the second reported by Andrè et al. in the current issue of the JCI (see the related article beginning on page 2574), have identified irritants that activate transient receptor potential cation channel, subfamily A, member 1 (TRPA1) receptors in airway sensory neurons, resulting in neurogenic inflammation and respiratory hypersensitivity. The identification of TRPA1 activation by toxicants from cigarette smoke and polluted air, such as crotonaldehyde, acrolein, and oxidizing agents such as hydrogen peroxide, is an important finding. These two studies enhance our understanding of how pollution and cigarette smoke can damage airway function and will hopefully pave the way for the development of rational alternative therapeutics for such airway injury.


Modulation of Locomotion and Reproduction by FLP Neuropeptides in the Nematode Caenorhabditis elegans.
Neuropeptides function in animals to modulate most, if not all, complex behaviors. In invertebrates, neuropeptides can function as the primary neurotransmitter of a neuron, but more generally they co-localize with a small molecule neurotransmitter, as is commonly seen in vertebrates. Because a single neuron can express multiple neuropeptides and because neuropeptides can bind to multiple G protein-coupled receptors, neuropeptide actions increase the complexity by which the neural connectome can be activated or inhibited. Humans are estimated to have 90 plus neuropeptide genes; by contrast, nematodes, a relatively simple organism, have a slightly larger complement of neuropeptide genes. For instance, the nematode Caenorhabditis elegans has over 100 neuropeptide-encoding genes, of which at least 31 genes encode peptides of the FMRFamide family. To understand the function of this large FMRFamide peptide family, we isolated knockouts of different FMRFamide-encoding genes and generated transgenic animals in which the peptides are overexpressed. We assayed these animals on two basic behaviors: locomotion and reproduction. Modulating levels of different neuropeptides have strong as well as subtle effects on these behaviors. These data suggest that neuropeptides play critical roles in C. elegans to fine tune neural circuits controlling locomotion and reproduction.


15-Hydroxyprostaglandin dehydrogenase inactivation as a mechanism of resistance to celecoxib chemoprevention of colon tumors.
Pharmacologic inhibitors of the prostaglandin-synthesizing COX-2 oncogene prevent the development of premalignant human colon adenomas. However, resistance to treatment is common. In this study, we show that the adenoma prevention activity of the COX-2 inhibitor celecoxib requires the concomitant presence of the 15-hydroxyprostaglandin dehydrogenase (15-PGDH) tumor suppressor gene, and that loss of 15-PGDH expression imparts resistance to celecoxib's anti-tumor effects. We first demonstrate that the adenoma-preventive activity of celecoxib is abrogated in mice genetically lacking 15-PGDH. In FVB mice, celecoxib prevents 85% of azoxymethane-induced tumors >1 mm in size, but is essentially inactive in preventing tumor induction in 15-PGDH-null animals. Indeed, celecoxib treated 15-PGDH null animals develop more tumors than do celecoxib naive WT mice. In parallel with the loss of tumor prevention activity, celecoxib-mediated suppression of colonic PGE(2) levels is also markedly attenuated in 15-PGDH-null versus WT mice. Finally, as predicted by the murine models, humans with low colonic 15-PGDH levels also exhibit celecoxib resistance. Specifically, in a colon adenoma prevention trial, in all cases tested, individuals who developed new adenomas while receiving celecoxib treatment were also found as having low colonic 15-PGDH levels.


Heregulin targets gamma-catenin to the nucleolus by a mechanism dependent on the DF3/MUC1 oncoprotein.
The DF3/MUC1 transmembrane oncoprotein is aberrantly overexpressed in most human breast carcinomas and interacts with the Wnt effector gamma-catenin. Here, we demonstrate that MUC1 associates constitutively with ErbB2 in human breast cancer cells and that treatment with heregulin/neuregulin-1 (HRG) increases the formation of MUC1-ErbB2 complexes. The importance of the MUC1-ErbB2 interaction is supported by the demonstration that HRG induces binding of MUC1 and gamma-catenin and targeting of the MUC1-gamma-catenin complex to the nucleolus. Significantly, nucleolar localization of gamma-catenin in response to HRG is dependent on MUC1 expression. Moreover, mutation of a RRK motif in the MUC1 cytoplasmic domain abrogates HRG-induced nucleolar localization of MUC1 and gamma-catenin. In concert with these results, we show nucleolar localization of MUC1 and gamma-catenin in human breast carcinomas but not in normal mammary ductal epithelium. These findings demonstrate that MUC1 functions in cross talk between ErbB2 and Wnt pathways by acting as a shuttle for HRG-induced nucleolar targeting of gamma-catenin.


Impact of health claims: what has been achieved and what is the future?
Using health claims on foods in the European Union and the United States for more than two decades did not have a noticeable positive impact on public health and neither on the innovation or sales of such food products. The objective was to assess the reasons for this limited impact using a narrative review approach. Consumers assess the value of health claims on foods case-by-case in a way that can be explored with the opportunity, ability, and motivation framework. Perceived relevance of a health claim seems to be an important motivational factor in consumer responses. Thus, targeted marketing of foods with health claims should be applied specifically to those consumers for which the claimed benefit is relevant. Language for the health claim should be used that is reflective for the scientific substantiation as well as credible and clearly understood by the target consumer. The food should be a credible carrier for the claimed benefit, and not be compromised on taste and other sensory properties. Finally, consumers should be made more aware of what health claims are, and what they are not, in relation to healthy eating. With these adaptations the use and impact of health claims may become more effective.


Sensory thalamus and periaqueductal grey area local field potential signals during bladder filling.
The periaqueductal grey area and sensory thalamus are thought to be important nuclei involved in the supraspinal bladder control network. Deep brain stimulation of the periqueductal grey area has been shown to increase bladder capacity in the human. In a single patient, we have recorded local field potential signals from implanted deep brain stimulation electrodes within the sensory thalamus during filling cystometry with periaqueductal grey area deep brain stimulation in the ON and OFF states. In the OFF stimulation state, we demonstrate correlations between bladder volume and oscillations in the high gamma frequency band in the sensory thalamus. Stimulation of the periaqueductal grey area abolishes this correlated activity in the gamma frequency band and also suppresses oscillations within the sensory thalamus in the alpha frequency band. These findings support the involvement of the sensory thalamus in the afferent limb of bladder-related brain networks. They also suggest that periaqueductal grey area deep brain stimulation may disrupt the normal processing of afferent signals within the sensory thalamus which may be related to the effect of stimulation on bladder capacity.


Migration protocol to estimate metal exposure from mouthing copper and tin alloy objects.
Low blood lead levels previously thought to pose no health risks may have an adverse impact on the cognitive development of children. This concern has given rise to new regulatory restrictions upon lead metal containing products intended for child use. However few reliable experimental testing methods to estimate exposure levels from these materials are available. The present work describes a migration test using a mimetic saliva fluid to estimate the chronic exposure of children to metals such as lead while mouthing metallic objects. The surrogate saliva medium was composed of: 150 mM NaCl, 0.16% porcine Mucin and 5 mM buffer MOPS, adjusted to pH 7.2. Alloys samples, in the form of polished metallic disc of known surface area, were subjected to an eight hours test. Two whitemetal alloys Sn/Pb/Sb/Cu and three brass alloys Cu/Zn/Pb were tested using the saliva migration protocol. In the case of the whitemetal alloys, first order release kinetics resulting in the release of 0.03 and 0.51 μg lead/cm2 after 8 hours of tests were observed, for lead contents of 0.05-0.07% and 5.5%, respectively. Brasses exhibited linear incremental release rates of 0.043, 0.175 and 0.243 μg lead/cm2h for lead contents of 0.1-0.2%, 1.7-2.2% and 3.1-3.5%, respectively. The linear regression analysis of lead release rates relative to Pb content in brasses yielded a slope of 0.08 μg lead/cm2h%Pb (r2 = 0.92). Lead release rates were used to estimate the mean daily mouthing exposure of a child to lead, according to age-specific estimates of mouthing time behavior. Calculated daily intakes were used as oral inputs for the IEUBK toxicokinetic model, predicting only marginal changes in blood lead levels (0.2 μg lead/dL or less) for children aged 0.5 to 1 years old exposed to either class of alloy. The results of this study as a whole support the use of migration data of metal ions, rather than total metal content, to estimate health risk from exposure to metals and metal alloys substances in children.


Molecular cloning, expression and mutagenesis of an anti-insulin single chain Fv (scFv).
The immunoglobulin variable region genes of a murine anti-insulin IgG-producing hybridoma were rescued and cloned into a bacterial expression vector. The variable regions of the gamma heavy chain and the kappa light chain were expressed independently and together as a single chain antibody (scFv). The variable heavy chain alone demonstrated the ability to bind to insulin. The kappa light chain did not show any binding activity towards insulin. The scFv was constructed by PCR assembly using a (Gly4Ser)3 linker between the carboxyl end of the variable heavy chain and the amino terminus of the kappa light chain. The scFv bound insulin at an IC50 of 3.5 x 10(-8) M whereas the parent antibody bound insulin at 1.0 x 10(-8) M. Mutagenesis of the variable heavy chain complementarity determining regions (CDR) indicated that CDR1 and CDR3 were important for binding to insulin. Position 99 in CDR3 of the heavy chain was found to be a critical position for the ability of the scFv to bind to insulin.


Computational generation of the Purkinje network driven by clinical measurements: the case of pathological propagations.
To properly describe the electrical activity of the left ventricle, it is necessary to model the Purkinje fibers, responsible for the fast and coordinate ventricular activation, and their interaction with the muscular propagation. The aim of this work is to propose a methodology for the generation of a patient-specific Purkinje network driven by clinical measurements of the activation times related to pathological propagations. In this case, one needs to consider a strongly coupled problem between the network and the muscle, where the feedback from the latter to the former cannot be neglected as in a normal propagation. We apply the proposed strategy to data acquired on three subjects, one of them suffering from muscular conduction problems owing to a scar and the other two with a muscular pre-excitation syndrome (Wolff-Parkinson-White). To assess the accuracy of the proposed method, we compare the results obtained by using the patient-specific Purkinje network generated by our strategy with the ones obtained by using a non-patient-specific network. The results show that the mean absolute errors in the activation time is reduced for all the cases, highlighting the importance of including a patient-specific Purkinje network in computational models.


Significantly Reduced Genoprevalence of Vaccine-Type HPV-16/18 Infections among Vaccinated Compared to Non-Vaccinated Young Women 5.5 Years after a Bivalent HPV-16/18 Vaccine (Cervarix®) Pilot Project in Uganda.
The objective of this study was to determine the prevalence and some predictors for vaccine and non-vaccine types of HPV infections among bivalent HPV vaccinated and non-vaccinated young women in Uganda. This was a comparative cross sectional study 5.5 years after a bivalent HPV 16/18 vaccination (Cervarix®, GlaxoSmithKline, Belgium) pilot project in western Uganda. Cervical swabs were collected between July 2014-August 2014 and analyzed with a HPV genotyping test, CLART® HPV2 assay (Genomica, Madrid Spain) which is based on PCR followed by microarray for determination of genotype. Blood samples were also tested for HIV and syphilis infections as well as CD4 and CD8 lymphocyte levels. The age range of the participants was 15-24 years and mean age was 18.6(SD 1.4). Vaccine-type HPV-16/18 strains were significantly less prevalent among vaccinated women compared to non-vaccinated women (0.5% vs 5.6%, p 0.006, OR 95% CI 0.08(0.01-0.64). At type-specific level, significant difference was observed for HPV16 only. Other STIs (HIV/syphilis) were important risk factors for HPV infections including both vaccine types and non-vaccine types. In addition, for non-vaccine HPV types, living in an urban area, having a low BMI, low CD4 count and having had a high number of life time sexual partners were also significant risk factors. Our data concurs with the existing literature from other parts of the world regarding the effectiveness of bivalent HPV-16/18 vaccine in reducing the prevalence of HPV infections particularly vaccine HPV- 16/18 strains among vaccinated women. This study reinforces the recommendation to vaccinate young girls before sexual debut and integrate other STI particularly HIV and syphilis interventions into HPV vaccination packages.


No HIV stage is dominant in driving the HIV epidemic in sub-Saharan Africa.
To estimate the role of each of the HIV progression stages in fueling HIV transmission in sub-Saharan Africa by using the recent measurements of HIV transmission probability per coital per HIV stage in the Rakai study. A mathematical model, parameterized by empirical data from the Rakai, Masaka, and Four-City studies, was used to estimate the proportion of infections due to each of the HIV stages in two representative epidemics in sub-Saharan Africa. The first setting represents a hyperendemic HIV epidemic (Kisumu, Kenya) whereas the second setting represents a generalized but not hyperendemic HIV epidemic (Yaoundé, Cameroon). We estimate that 17, 51, and 32% of HIV transmissions in Kisumu were due to index cases in their acute, latent, and late stages, respectively. In Yaoundé, the fractions were 25, 44, and 31%. We found that the relative contribution of each stage varied with the epidemic evolution with the acute stage prevailing early on when the infection is concentrated in the high-risk groups with the late stage playing a major role as the epidemic matured and stabilized. The latent stage contribution remained largely stable throughout the epidemic and contributed about half of all transmissions. No HIV stage dominated the epidemical though the latent stage provided the largest contribution. The role of each stage depends on the phase of the epidemic and on the prevailing levels of sexual risk behavior in the populations in which HIV is spreading. These findings may influence the design and implementation of different HIV interventions.


Frequency of acute coronary syndrome in patients presenting to the emergency department with chest pain after methamphetamine use.
We reviewed the frequency of acute coronary syndrome (ACS) in patients presenting to our emergency department (ED) with chest pain after methamphetamine (MAP) use during a 2-year interval. Thirty-three patients (25 males, 8 females; average age 40.4 +/- 8.0 years) with a total of 36 visits met study inclusion criteria: 1) non-traumatic chest pain, 2) positive MAP urine toxicology screen, 3) admission to "rule-out" myocardial infarction, 4) chest radiograph demonstrating no infiltrates. An ACS was diagnosed in 9 patients (25%). Three patients (8%) (2 ACS and 1 non-ACS) suffered cardiac complications (ventricular fibrillation, ventricular tachycardia, supraventricular tachycardia, respectively). Age, gender, cardiac risk factors, prior coronary artery disease, initial systolic blood pressure and heart rate did not differ significantly in the ACS and non-ACS groups. The initial and subsequent electrocardiograms (EKG) were normal in 1/9 (11%) patients with ACS and 16/27 (59%) without ACS (p < 0.05). Our findings suggest that: 1) ACS is common in patients hospitalized for chest pain after MAP use, and 2) the frequency of other potentially life-threatening cardiac complications is not negligible. A normal EKG lowers the likelihood of ACS, but an abnormal EKG is not helpful in distinguishing patients with or without ACS.


Toll-like receptors activate innate and adaptive immunity by using dendritic cell-intrinsic and -extrinsic mechanisms.
Toll-like receptors (TLRs) play prominent roles in initiating immune responses to infection, but their roles in particular cell types in vivo are not established. Here we report the generation of mice selectively lacking the crucial TLR-signaling adaptor MyD88 in dendritic cells (DCs). In these mice, the early production of inflammatory cytokines, especially IL-12, was substantially reduced after TLR stimulation. Whereas the innate interferon-gamma response of natural killer cells and of natural killer T cells and the Th1 polarization of antigen-specific CD4(+) T cells were severely compromised after treatment with a soluble TLR9 ligand, they were largely intact after administration of an aggregated TLR9 ligand. These results demonstrate that the physical form of a TLR ligand affects which cells can respond to it and that DCs and other innate immune cells can respond via TLRs and collaborate in promoting Th1 adaptive immune responses to an aggregated stimulus.


Cell death in normal and rough eye mutants of Drosophila.
The regular, reiterated cellular pattern of the Drosophila compound eye makes it a sensitive amplifier of defects in cell death. Quantitative and histological methods reveal a phase of cell death between 35 and 50 h of development which removes between 2 and 3 surplus cells per ommatidium. The timing of this epoch is consistent with cell death as the last fate to be specified in the progressive sequence of cell fates that build the ommatidium. An ultrastructural survey of cell death suggests dying cells in the fly eye have similarities as well as differences with standard descriptions of programmed cell death. A failure of cell death to remove surplus cells disorganizes the retinal lattice. A screen of rough eye mutants identifies two genes, roughest and echinus, required for the normal elimination of cells from the retinal epithelium. The use of an enhancer trap as a cell lineage marker shows that the cone cells, like other retinal cells, are not clonally related to each other or to their neighbors.


Sport specific fitness testing of elite badminton players.
There is a scarcity of descriptive data on the performance capacity of elite badminton players, whose fitness requirements are quite specific. The purpose of this paper is to investigate the physiological response of elite badminton players in a sport-specific fitness test. Twelve Hong Kong national badminton team players performed a field test on a badminton court. Six light bulbs were connected to a programming device causing individual bulbs to light up in a given sequence. The players were instructed to react to the flashes by running towards them, and striking shuttles mounted in the vicinity of the bulbs. Exercise intensity was controlled by altering the interval between successive lightings. A low correlation (r = 0.65) was found between the results of the field test and the rank-order list of subjects, based on an objective on-field physiological assessment and subjective ranking. This may be explained by the requirements of other factors besides physical fitness which contribute to success in elite level badminton competition. These factors may include, for example, technical skill, mental power, and aesthetic judgements on the court. Maximum mean (s.d.) heart rate data (187(8) beats.min-1) and blood lactate values (10.4(2.9) mmol.l-1) in this study showed that players were under maximal load during the field test. From the testing data, it seems reasonable to speculate that the intensity of level 3 (20 light pulses.min-1; 3.0 s.pulse-1) and level 4 (22 light pulses.min-1; 2.7 s.pulse-1) simulates the requirement of actual games energy expenditure of the Hong Kong badminton players exercising at close to their anaerobic threshold. The results also show that an estimate of fitness can be derived from measurements involving exercise closely resembling that which is specific for the sports activity in question. Improved training advice and guidance may result from such studies.


Physicochemical Trapping of Neurotransmitters in Polymer-Mediated Gold Nanoparticle Aggregates for Surface-Enhanced Raman Spectroscopy.
Because of the sharp distance dependence of surface-enhanced Raman spectroscopy (SERS), analyte molecules that do not exhibit strong affinity for Au/Ag often elude detection. New methods of integrating such analytes with SERS substrates are required to circumvent this limitation and expand the sensitivity of SERS to new molecules and applications. We communicate here a solution-phase, capture agent-free method of aggregating Au nanospheres in the presence of five neurotransmitters (dopamine, epinephrine, norepinephrine, serotonin, and histamine) and preventing sedimentation by encapsulating the aggregated nanospheres with polyvinylpyrrolidone, thereby trapping the neurotransmitters in close proximity to the Au nanospheres and enabling SER detection. The primary advantages of this physicochemical trapping method, which is generalizable to analytes beyond the scope of this work, are the high signal-to-noise ratio and spectral consistency down to nM levels. Normal Raman spectra and density functional theory calculations corroborate the accuracy of the spectra. Spectra collected over a wide range of concentrations were used to construct adsorption isotherms for all five neurotransmitters, from which adsorption dissociation constants were calculated, spanning from 5.7 × 10-4 M to 1.7 × 10-10 M. We expect this method to produce high quality SER spectra of any molecule with an Au affinity known or expected (based on functional groups) to be within that range. Our results have implications for plasmonic detection of these neurotransmitters, particularly for mixtures of those that exhibited disparate Au affinity in our study. We also present evidence that this method produces spectra of sufficient resolution to explore hypotheses related to surface adsorption behavior.


[Comparison of noninvasive techniques in evaluation of the Björk-Shiley and the St. Jude Medical valve prostheses in mitral position].
Pressure gradients and left ventricular function were assessed by Doppler echocardiography in 50 patients with Björk-Shiley mitral valve and 50 patients with St. Jude Medical valve prosthesis. There was correlation between pressure gradient and valve size, and between effective valve orifice area and valve size for St. Jude Medical valve. These correlations were not found in Björk-Shiley valve. Clinical improvement and cardiac function were quite satisfactory in 20 patients with Björk-Shiley valve and in 32 patients with St. Jude Medical valve whose pressure gradients were less than 10 mmHg. Twenty eight of 50 patients with Björk-Shiley valve and 42 of 50 patients with St. Jude Medical valve showed good response to the exercise test. Eight patients underwent reoperation because of unacceptably high gradient caused by thrombus and pannus formation. The patients who show high pressure gradient across the valve prosthesis should be followed up cautiously.


Correlation between DNA methyltransferases expression and Epstein-Barr virus, JC polyomavirus and Helicobacter pylori infections in gastric carcinomas.
It' is accepted that aberrant expression of DNA methyltransferases (DNMTs) is responsible for hypermethylation in genes. However, there are limited data related to factors inducing aberrant expression of DNMTs. A total of 43 surgically resected gastrc carcinomas (GC) samples were analysed. Using immunohistochemistry assay we have determined expression level of DNMT1 and 3b. The presence of H.pylori was evaluated by histology, whereas JC polyomavirus (JCV) and Epstein-Barr virus (EBV) detection were carried out by PCR and in situ hybridization techniques, respectively. High expression of DNMT1 and 3b were detected in 46.5% and 53.5% of GC cases, respectively. Co-expression of DNMT1 and 3b were found in 37.2% of cases. Using different techniques, H. pylori, JCV and EBV were detected in 55.8%, 32.6% and 9%, respectively. Moreover, in 37% of cases, we noted the presence of JCV and/or EBV infections. H.pylori co-infection was found in 64.3% (9/14) of JCV positive cases and in 50% of EBV positive GC, without a reliable significant relationship. Correlation analyses have showed a marked increase in DNMT1 expression in EBV associated GC (P= 0.02). Also, co-expression of DNMT1 and 3b was significantly associated with EBV infection in GC (P=0.05). Similarly, JCV associated GC mostly displayed DNMT1 positive status, but the difference did not reach the significant threshold. Nevertheless, infection with JCV and/or EBV was significantly correlated with increased expression of DNMT1 in GC (P= 0.05). Our study suggests that EBV and JCV infections in GC correlated with deregulation of DNA methyltransferases.


LevelMerge: Collaborative Game Level Editing by Merging Labeled Graphs.
Game development is commonly seen as a collaborative effort, with teams cooperating on the same project. Nowadays, a variety of cloud-based services have shown the benefits of performing tasks in real-time collaboration with others. In this article, we present a system for collaborative game level editing. We model this problem as a special instance of merging labeled directed acyclic graphs. We propose an algorithm that guarantees that the shared game level is always coherent between edits, both hierarchically and semantically. We establish real-time collaboration by initiating merges automatically and by augmenting the game editor interface to allow users to monitor all others edits in real time. We validate our algorithm by merging complex edits and large game levels. We further validate the collaborative workflow by running a user study with expert game developers, showing that our system works well and collaborative workflows are beneficial to game development.


[Hematuria of papillary or medullar origin: a difficult diagnosis entity].
Renal haemangiomas of renal papillary or medullar origin are a difficult diagnosis entity, being one of the most frequent processes of chronic episodes of hematuria, secondary to benign disease, mainly in young patients. The objective of this paper is to show the difficulty of this diagnosis and the need to suspect it in cases with clinical history similar to the ones described in these cases. We report 4 cases of spontaneous hematuria of renal origin, with clinical presentation as renal colic, from the historical case series of the Fundacion Jimenez Díaz-Capio, the last two from the years 2005-6. We present the diagnostic and therapeutic methodology employed, including angio-CT and flexible ureterorenoscopy (URS) as well as various treatment options. Hematuria was identified as "essential" when any relation with tumor or lithiasic pathologies was ruled out, and of renal origin when the source was clearly pointed. We interpreted it was related to angiomas or microangiomas of papillary or medullar origin. In one case, the vascular malformation was interpreted as an arterial venous fistula (AVF) at that level. Hematuria stopped spontaneously in two cases after exploratory URS. The eldest historical case required surgical expiration of the caliceal structures. Years ago, following the professional development of Urology as speciality, conventional surgery was carried out in all these cases, of very difficult diagnosis, with a very small number of cases undergoing a conservative approach based on the examination of renal cavities trying to observe and find the bleeding point. Most cases underwent complete or partial nephrectomy. Currently, the possibility of exploration of all renal cavities with the flexible ureterorenoscope enables a better diagnosis of the lesions and a more conservative treatment. The ultimate diagnosis of renal papillary angioma is the pathologic diagnosis, without pathognomonic data in the imaging tests. This pathology is thought of at the end of the diagnostic workup, and when the papillary area is identified as the source of bleeding. The historical case series, with the pathologic findings from nephrectomy specimens, permits us to point out this entity as papillary angioma, in patients with similar clinical presentation.


Rheological properties of phospholipid-stabilized parenteral oil-in-water emulsions--effects of electrolyte concentration and presence of heparin.
The rheological properties of the parenteral oil-in-water emulsion Intralipid were investigated. The viscosity data at different phase volumes correlated well with that obtained via a theoretical model developed by Yaron and Gal-Or. The model also describes the temperature dependence well. The effects of electrolyte addition were also investigated. Monovalent sodium chloride had practically no influence on viscosity. Calcium chloride, on the other hand, had a large impact on viscosity even at low concentrations. It was shown that the obtained maximum in viscosity coincided with the zeta-potential being close to zero. The resulting increase in viscosity is due to flocculation that leads to an increase in apparent phase volume. A similar behaviour was obtained with magnesium chloride with the difference that the maximum in viscosity was shifted to higher electrolyte concentrations. This is interpreted as that because magnesium binds strongly to the hydration water than does calcium. The addition of the negatively charged anti-coagulant heparin causes flocculation in the presence of small amounts of calcium. The amounts of calcium needed for such bridging flocculation is lower than what is needed in order to create a positive potential at the surfaces of the droplets. A fraction of the flocs is not broken down even by extensive shear.


A sliding selectivity scale for lipid binding to membrane proteins.
Biological membranes form barriers that are essential for cellular integrity and compartmentalisation. Proteins in the membrane have co-evolved with their hydrophobic lipid environment, which serves as a solvent for proteins with very diverse requirements. As a result, their interactions range from non-selective to highly discriminating. Mass spectrometry enables us to monitor how lipids interact with membrane proteins and assess their effects on structure and dynamics. Recent studies illustrate the ability to differentiate specific lipid binding, preferential interactions with lipid subsets, and nonselective annular contacts. Here, we consider the biological implications of different lipid-binding scenarios and propose that binding occurs on a sliding selectivity scale, in line with the view of biological membranes as facilitators of dynamic protein and lipid organization.


Convergent evolution of a mobile bony tongue in flighted dinosaurs and pterosaurs.
The tongue, with fleshy, muscular, and bony components, is an innovation of the earliest land-dwelling vertebrates with key functions in both feeding and respiration. Here, we bring together evidence from preserved hyoid elements from dinosaurs and outgroup archosaurs, including pterosaurs, with enhanced contrast x-ray computed tomography data from extant taxa. Midline ossification is a key component of the origin of an avian hyoid. The elaboration of the avian tongue includes the evolution of multiple novel midline hyoid bones and a larynx suspended caudal to these midline elements. While variable in dentition and skull shape, most bird-line archosaurs show a simple hyoid structure. Bony, or well-mineralized, hyoid structures in dinosaurs show limited modification in response to dietary shifts and across significant changes in body-size. In Dinosauria, at least one such narrow, midline element is variably mineralized in some basal paravian theropods. Only in derived ornithischians, pterosaurs and birds is further significant hyoid elaboration recorded. Furthermore, only in the latter two taxa does the bony tongue structure include elongation of paired hyobranchial elements that have been associated in functional studies with hyolingual mobility. Pterosaurs and enantiornithine birds achieve similar elongation and inferred mobility via elongation of ceratobranchial elements while within ornithurine birds, including living Aves, ossified and separate paired epibranchial elements (caudal to the ceratobranchials) confer an increase in hyobranchial length. The mobile tongues seen in living birds may be present in other flighted archosaurs showing a similar elongation. Shifts from hypercarnivory to more diverse feeding ecologies and diets, with the evolution of novel locomotor strategies like flight, may explain the evolution of more complex tongue function.


The effect of two different high-flux dialysis membranes on insulin resistance in non-diabetic end-stage renal disease patients.
The aim of this study was to investigate the effect of two different types of high-flux dialysis membranes on insulin resistance among patients who are receiving hemodialysis (HD) due to end-stage renal failure (ESRF). Forty-six (21 female, 25 male) patients were included in the study, who were on HD treatment due to stage-5 chronic renal failure. Prior to the study, fasting insulin resistance via Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) and fractioned urea clearance (Kt/V) values were calculated using the urokinetic model. The polysulfone (PS) dialysis membrane of all patients included in the study was replaced with "polyarylethersulfone, polyvinylpyrrolidone, polyamide (PPP)" high-flux membrane that has the same surface area over 12 weeks. At the end of the 12-week period, HOMA and Kt/V values were recalculated. At the end of the 12-week period, Kt/V values rose statistically significant from 1.575 to 1.752 (p = 0.002). HOMA-IR values declined, though not statistically significant, from 3.268 to 2.926 (p = 0.085). PPP high-flux membrane increased the Kt/V values significantly compared to the PS membrane, while it decreased the insulin resistance and increased insulin sensitivity. The two different types of high-flux dialysis membranes used for HD have different effects on insulin sensitivity. Compared to the PS membrane, PPP high-flux membrane decreased insulin resistance by increasing insulin sensitivity among non-diabetic ESRF patients.


Mortality of 403 patients with mood disorders 48 to 52 years after their psychiatric hospitalisation.
The purpose is to analyse differences in mortality among patients with major depressive disorders (MDD), bipolar-II (BP-II), bipolar-I (BP-I) disorders and mania with or without minor depressive disorders and to identify risk factors of mortality. The sample represents all admissions for depression or mania over 5 years (1959-1963) to the Psychiatric Hospital of Zurich University, serving a large area. 403 patients were included and followed up every 5 years until 1985; thereafter, mortality data were collected repeatedly until 2009 when 352 (87 %) patients had died. Standardised mortality ratios (SMRs) were computed and survival analyses applied. With the exception of BP-II disorder, the three other diagnostic groups showed elevated SMRs. The group with mania had the highest SMR for cardiovascular deaths and the group with MDD the highest for deaths by suicide. Mortality was also high among patients with late-onset MDD. Across the diagnostic spectrum, we found differences in risk factors for mortality, such as a family history of suicides and personality type: more anxious patients with MDD lived longer, and among patients with BP disorders, more tense (aggressive) types had shorter lives. Long-term medication had a protective effect against mortality in patients with MDD during years 1-9 and in patients with BP disorders during years 1-19 after admission. We found marked differences in causes of death and risk factors between subgroups of mood disorders. For the purpose of further research, it would be recommendable to distinguish pure mania from bipolar disorders.


Evaluation of Acute Oral Toxicity of Ethanol Leaves Extract of Catharanthus roseus in Wistar Albino Rats.
Herbal drugs have gained importance globally in the treatment of various diseases. Catharanthus roseus is traditionally used as an anti diabetic and anti cancer drug. To the best of our knowledge limited data are available on acute and sub acute toxicity of C. roseus extract despite its wide spread use in traditional medicine. The present study was under taken to evaluate the acute oral toxicity of the ethanol leaves extract of C. roseus. To investigate the acute oral toxic effects of ethanol leaves extract of C. roseus. The objective of the study was to evaluate organ toxicity related to heart, liver and kidney in wistar albino rats. The experiment was done based on the Organization for Economic Co-operation and Development (OECD) guideline 420. The study included twenty five non pregnant female wistar rats (n=25). Sighting study was done using the fixed dose method. The study was conducted by giving a single dose of test drug varying from 5, 50, 300 and 2000 mg and animals were observed for fourteen days. Blood samples were collected and biochemical findings SGPT, SGOT, urea, creatinine, creatinine phosphokinase and Lactate Dehydrogenase (LDH) were analyzed. Food consumption, water intake and histopathology changes were evaluated. Catharanthus roseus Extract (CRE) at a dose of 2000 mg did not produce mortality. SGOT, SGPT, Creatinine phosphokinase, LDH, urea and creatinine were elevated in 300 mg and 2000 mg doses. Though there was no mortality, the extract of C. roseus higher than 300 mg can produce signs of biochemical and histopathological toxicity in liver, kidney and heart. It is recommended that lower doses than the studied ones should be used for treatment.


Structure, sex, and strength and knee and hip kinematics during landing.
Researchers have observed that medial knee collapse is a mechanism of knee injury. Lower extremity alignment, sex, and strength have been cited as contributing to landing mechanics. To determine the relationship among measurements of asymmetry of unilateral hip rotation (AUHR); mobility of the foot, which we described as relative arch deformity (RAD); hip abduction-external rotation strength; sex; and medial collapse of the knee during a single-leg jump landing. We hypothesized that AUHR and RAD would be positively correlated with movements often associated with medial collapse of the knee, including hip adduction and internal rotation excursions and knee abduction and rotation excursions. Descriptive laboratory study. Research laboratory. Thirty women and 15 men (age = 21 ± 2 years, height = 171.7 ± 9.5 cm, mass = 68.4 ± 9.5 kg) who had no history of surgery or recent injury and who participated in regular physical activity volunteered. Participants performed 3 double-leg forward jumps with a single-leg landing. Three-dimensional kinematic data were sampled at 100 Hz using an electromagnetic tracking system. We evaluated AUHR and RAD on the preferred leg and evaluated isometric peak hip abductor-external rotation torque. We assessed AUHR by calculating the difference between internal and external hip rotation in the prone position (AUHR = internal rotation - external rotation). We evaluated RAD using the Arch Height Index Measurement System. Correlations and linear regression analyses were used to assess relationships among AUHR, RAD, sex, peak hip abduction-external rotation torque, and kinematic variables for 3-dimensional motion of the hip and knee. The dependent variables were joint angles at contact and joint excursions between contact and peak knee flexion. We found that AUHR was correlated with hip adduction excursion (R = 0.36, P = .02). Asymmetry of unilateral hip rotation, sex, and peak hip abduction-external rotation torque were predictive of knee abduction excursion (adjusted R(2) = 0.47, P < .001). Asymmetry of unilateral hip rotation and sex were predictive of knee external rotation excursion (adjusted R(2) = 0.23, P = .001). The RAD was correlated with hip adduction at contact (R(2) = 0.10, R = 0.32, P = .04) and knee flexion excursion (R(2) = 0.11, R = -0.34, P = .03). Asymmetry of unilateral hip rotation, sex, and hip strength were associated with kinematic components of medial knee collapse.


Bread enriched with green coffee extract has chemoprotective and antigenotoxic activities in human cells.
Recent studies have shown that bread supplemented with functional ingredients was more chemoprotective than nonsupplemented bread. Here we investigated components of a German wheat bread supplemented with green coffee antioxidants (GC) to assess basic biological activities in human cells in culture. We analyzed chlorogenic acid (ChA) in the bread and determined antioxidative activities. Human colon (HT29) and liver (HepG2) cells were incubated with GC and with aqueous extracts of freeze-dried breads, after which cell survival (4' ,6-diamino-2- phenylindole dihydrochloride assay) and H(2)O(2)-induced DNA damage (comet assay) were determined. GC and supplemented bread contained 7- and 880-fold more ChA than normal bread and were significantly more antioxidative (ferric reducing ability of plasma assay, 2.9- and 265-fold; Trolox equivalent antioxidant capacity assay, 1.3- and 24-fold, respectively). Treatment of cells for 24 to 72 h with the samples resulted in a significant inhibition of cell survival in a dose-dependent manner. HepG2 liver cells were more susceptible than HT29 colon cells. No genotoxicity or cytotoxicity was observed after treatment of cells with GC, ChA, or the bread samples. H(2)O(2)-induced DNA damage was reduced significantly after treatment with GC, ChA, and supplemented bread. In conclusion, the supplementation of bread with GC improves the chemoprotective property of normal bread under these in vitro cell culture conditions. Supplementation also increases ChA content and antioxidative capacity. The treatment of the cells with supplemented bread increases resistance of colon and liver cells against H(2)O(2), a source of oxidative stress.


Plant Virus Nanoparticles for Vaccine Applications.
In the rapidly evolving field of nanotechnology, plant virus nanoparticles (pVNPs) are emerging as powerful tools in diverse applications ranging from biomedicine to materials science. The proteinaceous structure of plant viruses allows the capsid structure to be modified by genetic engineering and/or chemical conjugation with nanoscale precision. This means that pVNPs can be engineered to display peptides and proteins on their external surface, including immunodominant peptides derived from pathogens allowing pVNPs to be used for active immunization. In this context, pVNPs are safer than VNPs derived from mammalian viruses because there is no risk of infection or reversion to pathogenicity. Furthermore, pVNPs can be produced rapidly and inexpensively in natural host plants or heterologous production platforms. In this review, we discuss the use of pVNPs for the delivery of peptide antigens to the host immune in pre-clinical studies with the final aim of promoting systemic immunity against the corresponding pathogens. Furthermore, we described the versatility of plant viruses, with innate immunostimulatory properties, in providing a huge natural resource of carriers that can be used to develop the next generation of sustainable vaccines.


Total nutritional capacity and inflammation inhibition effect of Acalypha alnifolia Klein ex wild-An unexplored wild leafy vegetable.
Investigation of the nutritional as well as trace elements of a wild leafy vegetable, Acalypha alnifolia, and evaluation of the analgesic, anti-inflammatory, and antipyretic properties of acetone and methanol leaf extracts are the main objectives of the present study. The powdered A. alnifolia leaf sample was subjected to nutritional and mineral analysis. Plant leaves were extracted (using the Soxhlet apparatus) as successive solvent extractions. The extract doses of 200 and 400 mg/kg of acetone and methanol extracts were used for pharmacology study. The analgesic, anti-inflammatory, and antipyretic experiments were carried out by using animal models. The obtained result proves that the plant possesses essential nutritive values and useful biological properties. The higher dose of acetone extract has significant potency when compared with methanol extract at p < 0.005. On the whole, the plant is rich in minerals and has good biological properties; hence, this plant is suggested for cultivation and regular use for nutritional supplement.


Modelling the propagation of effects of chronic exposure to ionising radiation from individuals to populations.
This study evaluated the potential effect of ionising radiation on population growth using simple population models and parameter values derived from chronic exposure experiments in two invertebrate species with contrasting life-history strategies. In the earthworm Eisenia fetida, models predicted increasing delay in population growth with increasing gamma dose rate (up to 0.6 generation times at 11 mGy h(-1)). Population extinction was predicted at 43 mGy h(-1). In the microcrustacean Daphnia magna, models predicted increasing delay in population growth with increasing alpha dose rate (up to 0.8 generation times at 15.0 mGy h(-1)), only after two successive generations were exposed. The study examined population effects of changes in different individual endpoints (including survival, number of offspring produced and time to first reproduction). Models showed that the two species did not respond equally to equivalent levels of change, the fast growing daphnids being more susceptible to reduction in fecundity or delay in reproduction than the slow growing earthworms. This suggested that susceptibility of a population to ionising radiation cannot be considered independent of the species' life history.


[Echinococcosis/hydatidosis in the VII Region of Chile: diagnosis and educational intervention].
This study was designed to embrace three areas: a) serologic and radiologic diagnosis and surgical treatment of hydatidosis in an asymptomatic human population, b) animal diagnosis and the treatment of dogs, and c) evaluation of extent of knowledge and performance of educational interventions among rural families and health, livestock, and education professionals and technicians, in order to help control the disease transmission cycle. Indirect hemagglutination and ELISA tests were performed on 5,556 apparently healthy people. Of these, 42 (0.8%) had positive results on both tests, for a seroprevalence of 754.6 per 100,000. These 42 subjects were scheduled for liver ultrasonography and a chest x-ray; of the 26 who complied, 16 showed images compatible with a hydatid cyst. Those 16 cases were sent to the hospital for surgery. In 9 of the cases the diagnosis was confirmed surgically, for a prevalence of 161.7 per 100,000. Arecoline hydrobromide was administered as a laxative to 2,358 dogs to detect the strobilar form of Echinococcus granulosus, and positive results were found in 11% of the dogs. Official data for slaughterhouses indicated the presence of hydatid cysts in 13% of the cattle, 4.4% of the sleep, and 4.2% of the pigs slaughtered in the region. The educational program included an evaluation of the extent of knowledge by surveying heads of household; an educational intervention among families through an informal active participatory process using educational games, in which 1,082 families participated; and an educational intervention with professionals and technicians using distance and in-person approaches. To evaluate the program, the results of knowledge tests before and after educational interventions with 200 families (cases) were compared with those from 95 families who did not participate (controls). Of the 1,423 heads of household initially surveyed about their knowledge of echinococcosis/hydatidosis, 783 of them (55%) said they knew nothing about the infection. It was found that the participatory educational games were well adapted to the lifestyle of people from rural areas and made change possible. Training was provided to 276 health professionals, 201 technical assistants, and 453 rural teachers. The program reached 100% of the staff members of the area's rural primary health care services.


Comparative antinociceptive and sedative effects of epidural romifidine and detomidine in buffalo (Bubalus bubalis).
In this study, comparative antinociceptive and sedative effects of epidural administration of romifidine and detomidine in buffalo were evaluated. Eighteen healthy adult buffalo, allocated randomly in three groups (two experimental and one control; n=6) received either 50 μg/kg of romifidine or detomidine diluted in sterile saline (0.9 per cent) to a final volume of 20 ml, or an equivalent volume of sterile saline epidurally. Antinociception, sedation and ataxia parameters were recorded immediately after drug administration. Epidural romifidine and detomidine produced mild to deep sedation and complete antinociception of the perineum, inguinal area and flank, and extended distally to the coronary band of the hindlimbs and cranially to the chest area. Times to onset of antinociception and sedation were significantly shorter with romifidine than with detomidine. The antinociceptive and sedative effects were significantly longer with romifidine than with detomidine. Romifidine or detomidine could be used to provide a reliable, long-lasting and cost-effective method for achieving epidural anaesthesia for standing surgical procedures in buffalo. Romifidine induces a longer antinociceptive effect and a more rapid onset than detomidine. Consequently, epidural romifidine may offer better therapeutic benefits in the management of acute postoperative pain.


Effects of Different Body Postures on the Intraocular Pressure in Patients with Primary Angle-Closure Disease.
Eyes with primary angle-closure disease showed higher intraocular pressure (IOP) in the recumbent postures including supine and lateral decubitus (LD) positions compared with the sitting position. The purpose of this study was to investigate the effects of different body postures on the IOP in eyes with primary angle-closure suspect (PACS), primary angle closure (PAC), or primary angle-closure glaucoma (PACG). This is a comparative case series of 31 patients with bilateral PAC disease, such as PACS, PAC, and PACG. The IOP was measured using Tonopen AVIA in sitting, supine, and right or left LD positions. Patients were instructed to rest their heads on the pillows in supine and LD positions. The eye on the lower side in the LD position was called dependent eye. The main outcome was the difference in IOP among different body postures. Among the 62 eyes (31 patients), PACG, PAC, and PACS were noted in 44, 12, and 6 eyes, respectively. The IOP was not significantly different between the two eyes in sitting and supine positions, whereas the IOP was significantly higher in the dependent eye than in the nondependent eye in LD positions. Compared with that measured in the supine position, IOP differences of the dependent eye were higher than those of the nondependent eye when measured in LD position (right LD vs. supine, P = .02; left LD vs. supine, P = .01). In addition, when the study patients were divided into three groups according to their diagnosis, no significant differences were observed in the IOPs and IOP differences among the three groups. Posture-induced IOP changes were comparable among eyes with PACS, PAC, and PACG.


Enhanced NF-κB activity impairs vascular function through PARP-1-, SP-1-, and COX-2-dependent mechanisms in type 2 diabetes.
Type 2 diabetes (T2D) is associated with vascular dysfunction. We hypothesized that increased nuclear factor-κB (NF-κB) signaling contributes to vascular dysfunction in T2D. We treated type 2 diabetic (db(-)/db(-)) and control (db(-)/db(+)) mice with two NF-κB inhibitors (6 mg/kg dehydroxymethylepoxyquinomicin twice a week and 500 μg/kg/day IKK-NBD peptide) for 4 weeks. Pressure-induced myogenic tone was significantly potentiated, while endothelium-dependent relaxation (EDR) was impaired in small coronary arterioles and mesenteric resistance artery from diabetic mice compared with controls. Interestingly, diabetic mice treated with NF-κB inhibitors had significantly reduced myogenic tone potentiation and improved EDR. Importantly, vascular function was also rescued in db(-)/db(-p50NF-κB-/-) and db(-)/db(-PARP-1-/-) double knockout mice compared with db(-)/db(-) mice. Additionally, the acute in vitro downregulation of NF-κB-p65 using p65NF-κB short hairpin RNA lentivirus in arteries from db(-)/db(-) mice also improved vascular function. The NF-κB inhibition did not affect blood glucose level or body weight. The RNA levels for Sp-1 and eNOS phosphorylation were decreased, while p65NF-κB phosphorylation, cleaved poly(ADP-ribose) polymerase (PARP)-1, and cyclooxygenase (COX)-2 expression were increased in arteries from diabetic mice, which were restored after NF-κB inhibition and in db(-)/db(-p50NF-κB-/-) and db(-)/db(-PARP-1-/-) mice. In the current study, we provided evidence that enhanced NF-κB activity impairs vascular function by PARP-1-, Sp-1-, and COX-2-dependent mechanisms in male type 2 diabetic mice. Therefore, NF-κB could be a potential target to overcome diabetes-induced vascular dysfunction.


Point-of-sale marketing of heated tobacco products in Israel: cause for concern.
Understanding how PMI markets IQOS at the point-of-sale in Israel is critical to determining whether marketing practices adhere to regulations and appeal to groups most at risk at initiating new tobacco products, such as adolescents. An article by Bar-Zev, Levine, Rubinstein, Khateb, and Berg (2019) examined the marketing of IQOS in retail stores in Israel. They found that while no free samples or promotions were provided at the point-of-sale, IQOS and their related HEETS (HeatSticks) were placed near youth-oriented merchandise and in prominent locations easily seen by youth. Further, package colors were used to indicate tobacco flavorings and strength, and retailers described the IQOS products as being less harmful, a cessation device, and not producing smoke. These findings are concerning given numerous studies linking marketing of novel tobacco products, product misperceptions, and subsequent tobacco use. Studies are needed to ensure that the marketing of IQOS, including the use of package colors, product placement at point-of-sales, and other product characteristics are significantly reducing harm and risk of tobacco-related disease to IQOS users, and that the health of the population as a whole, including those not using IQOS or other tobacco products, will not be harmed. Until such evidence is available, caution is warranted and regulations needed in the marketing of these novel products.


Copper excess, zinc deficiency, and cognition loss in Alzheimer's disease.
In this special issue about biofactors causing cognitive impairment, we present evidence for and discuss two such biofactors. One is excess copper, causing neuronal toxicity. The other is zinc deficiency, causing neuronal damage. We present evidence that Alzheimer's disease (AD) has become an epidemic in developed, but not undeveloped, countries and that the epidemic is a new disease phenomenon, beginning in the early 1900s and exploding in the last 50 years. This leads to the conclusion that something in the developed environment is a major risk factor for AD. We hypothesize that the factor is inorganic copper, leached from the copper plumbing, the use of which coincides with the AD epidemic. We present a web of evidence supporting this hypothesis. Regarding zinc, we have shown that patients with AD are zinc deficient when compared with age-matched controls. Zinc has critical functions in the brain, and lack of zinc can cause neuronal death. A nonblinded study about 20 years ago showed considerable improvement in AD with zinc therapy, and a mouse AD model study also showed significant cognitive benefit from zinc supplementation. In a small blinded study we carried out, post hoc analysis revealed that 6 months of zinc therapy resulted in significant benefit relative to placebo controls in two cognitive measuring systems. These two factors may be linked in that zinc therapy significantly reduced free copper levels. Thus, zinc may act by lowering copper toxicity or by direct benefit on neuronal health, or both.


Scalable Bayesian nonparametric measures for exploring pairwise dependence via Dirichlet Process Mixtures.
In this article we propose novel Bayesian nonparametric methods using Dirichlet Process Mixture (DPM) models for detecting pairwise dependence between random variables while accounting for uncertainty in the form of the underlying distributions. A key criteria is that the procedures should scale to large data sets. In this regard we find that the formal calculation of the Bayes factor for a dependent-vs.-independent DPM joint probability measure is not feasible computationally. To address this we present Bayesian diagnostic measures for characterising evidence against a "null model" of pairwise independence. In simulation studies, as well as for a real data analysis, we show that our approach provides a useful tool for the exploratory nonparametric Bayesian analysis of large multivariate data sets.


Improving quantitative dosimetry in (177)Lu-DOTATATE SPECT by energy window-based scatter corrections.
Patient-specific dosimetry of lutetium-177 ((177)Lu)-DOTATATE treatment in neuroendocrine tumours is important, because uptake differs across patients. Single photon emission computer tomography (SPECT)-based dosimetry requires a conversion factor between the obtained counts and the activity, which depends on the collimator type, the utilized energy windows and the applied scatter correction techniques. In this study, energy window subtraction-based scatter correction methods are compared experimentally and quantitatively. (177)Lu SPECT images of a phantom with known activity concentration ratio between the uniform background and filled hollow spheres were acquired for three different collimators: low-energy high resolution (LEHR), low-energy general purpose (LEGP) and medium-energy general purpose (MEGP). Counts were collected in several energy windows, and scatter correction was performed by applying different methods such as effective scatter source estimation (ESSE), triple-energy and dual-energy window, double-photopeak window and downscatter correction. The intensity ratio between the spheres and the background was measured and corrected for the partial volume effect and used to compare the performance of the methods. Low-energy collimators combined with 208 keV energy windows give rise to artefacts. For the 113 keV energy window, large differences were observed in the ratios for the spheres. For MEGP collimators with the ESSE correction technique, the measured ratio was close to the real ratio, and the differences between spheres were small. For quantitative (177)Lu imaging MEGP collimators are advised. Both energy peaks can be utilized when the ESSE correction technique is applied. The difference between the calculated and the real ratio is less than 10% for both energy windows.


Stress profiling of longevity mutants identifies Afg3 as a mitochondrial determinant of cytoplasmic mRNA translation and aging.
Although environmental stress likely plays a significant role in promoting aging, the relationship remains poorly understood. To characterize this interaction in a more comprehensive manner, we examined the stress response profiles for 46 long-lived yeast mutant strains across four different stress conditions (oxidative, ER, DNA damage, and thermal), grouping genes based on their associated stress response profiles. Unexpectedly, cells lacking the mitochondrial AAA protease gene AFG3 clustered strongly with long-lived strains lacking cytosolic ribosomal proteins of the large subunit. Similar to these ribosomal protein mutants, afg3Δ cells show reduced cytoplasmic mRNA translation, enhanced resistance to tunicamycin that is independent of the ER unfolded protein response, and Sir2-independent but Gcn4-dependent lifespan extension. These data demonstrate an unexpected link between a mitochondrial protease, cytoplasmic mRNA translation, and aging.


Intestinal cell targeting of a stable recombinant Cu-Zn SOD from Cucumis melo fused to a gliadin peptide.
The mRNA encoding full length chloroplastic Cu-Zn SOD (superoxide dismutase) of Cucumis melo (Cantaloupe melon) was cloned. This sequence was then used to generate a mature recombinant SOD by deleting the first 64 codons expected to encode a chloroplastic peptide signal. A second hybrid SOD was created by inserting ten codons to encode a gliadin peptide at the N-terminal end of the mature SOD. Taking account of codon bias, both recombinant proteins were successfully expressed and produced in Escherichia coli. Both recombinant SODs display an enzymatic activity of ~5000U mg(-1) and were shown to be stable for at least 4h at 37°C in biological fluids mimicking the conditions of intestinal transit. These recombinant proteins were capable in vitro, albeit at different levels, of reducing ROS-induced-apoptosis of human epithelial cells. They also stimulated production and release in a time-dependent manner of an autologous SOD activity from cells located into jejunum biopsies. Nevertheless, the fused gliadin peptide enable the recombinant Cu-Zn SOD to maintain a sufficiently sustained interaction with the intestinal cells membrane in vivo rather than being eliminated with the flow. According to these observations, the new hybrid Cu-Zn SOD should show promise in applications for managing inflammatory bowel diseases.


Source-water odor during winter in the Yellow River area of China: Occurrence and diagnosis.
Yellow River source water has long suffered from odor problems in winter. In this study, odor characteristics, potential odorants, and algae in the source water of six cities (Lanzhou, Yinchuan, Hohhot, Zhengzhou, Jinan and Dongying) along the Yellow River were determined in winter (February to March 2014). According to flavor profile analysis (FPA), moderate to strong fishy odors occurred in all cities, except for Lanzhou. At the same time, mild earthy/musty odors and septic/swampy odors were also detected. The strong fishy odor (FPA intensity, 8.5) in Yinchuan was attributed to the abnormal growth of Dinobryon (cell density, 5.7 × 104 cells/mL), while the fishy odors in Hohhot, Zhengzhou, Jinan, and Dongying might be caused by Melosira and Cyclotella, Cryptomonas, Dinobryon, and Synedra, respectively. Unsaturated aldehydes, which have been reported to cause fishy odors, were not detected in all samples. However, some saturated aldehydes, including hexanal, heptanal, nonanal, decanal, and benzaldehyde, were detected with a total concentration range of 690 ng/L to 2166 ng/L, and might have partly contributed to the fishy odors. In addition, 2-MIB (5.77-21.12 ng/L) and geosmin (2.26-9.73 ng/L) were responsible for the earthy/musty odors in the Yellow River source waters, and dimethyl disulfide (648.2 ng/L) was responsible for the rancid/swampy odor (FPA intensity, 8.0) episode in Yinchuan. This is a comprehensive study reporting on the occurrence and possible reasons for the odor issues in the Yellow River source water during winter.


Spatiotemporal properties of vestibular responses in area MSTd.
Recent studies have shown that many neurons in the primate dorsal medial superior temporal area (MSTd) show spatial tuning during inertial motion and that these responses are vestibular in origin. Given their well-studied role in processing visual self-motion cues (i.e., optic flow), these neurons may be involved in the integration of visual and vestibular signals to facilitate robust perception of self-motion. However, the temporal structure of vestibular responses in MSTd has not been characterized in detail. Specifically, it is not known whether MSTd neurons encode velocity, acceleration, or some combination of motion parameters not explicitly encoded by vestibular afferents. In this study, we have applied a frequency-domain analysis to single-unit responses during translation in three dimensions (3D). The analysis quantifies the stimulus-driven temporal modulation of each response as well as the degree to which this modulation reflects the velocity and/or acceleration profile of the stimulus. We show that MSTd neurons signal a combination of velocity and acceleration components with the velocity component being stronger for most neurons. These two components can exist both within and across motion directions, although their spatial tuning did not show a systematic relationship across the population. From these results, vestibular responses in MSTd appear to show characteristic features of spatiotemporal convergence, similar to previous findings in the brain stem and thalamus. The predominance of velocity encoding in this region may reflect the suitability of these signals to be integrated with visual signals regarding self-motion perception.


Activity limitations and factors influencing functional outcome of patients with stroke following rehabilitation at a specialised facility in the Western Cape.
Determining the functional abilities and factors influencing outcome of patients with stroke following rehabilitation are essential for the planning of future interventions and services in order to optimise recovery. To determine the activity limitations and factors influencing functional outcome of patients with stroke managed at a specialised rehabilitation centre. A longitudinal study design was used to determine the functional outcomes of patients admitted to the centre on admission and discharge. A data gathering sheet was developed to collect information pertaining to the demographicand medical profile and process of rehabilitation, whereas the Barthel Index was used to collect data relating to functional abilities. For analysis, descriptive statistics as well as inferential statistics (Student t test) were utilised to determine the paired differences. Six prognostic factors influencing functional outcome were selected and tested using linear (bivariate) regression. The mean Barthel Index scores on admission and at discharge were 58.85 and 81.59 respectively. A significant improvement was noted in the execution of functional task of patients with stroke (p< 0.01) between the data collection points. Despite the significant overall improvement, results show a high prevalence of dependence with walking and stair climbing at discharge. Only functional ability on admission (r=0.49) predicted a favourable functional outcome at discharge. This study highlights the limitations of younger stroke survivors and the need for continued rehabilitation following in-patient care. It further underscores the administration of a functional rating scale on admission in order to aggressively manage activity limitations.


Waste design and source control lead to flexibility in wastewater management.
The concepts of waste design and source control are introduced as contracts between wastewater handling agencies and consumers and consumers and industry respectively. Waste design serves to produce waste streams that are optimized in composition and time sequence for easy transport and treatment. Source control makes services and installations available, which allow the consumer to adhere to the specification of waste design. Increased delegation of responsibility to the consumer is expected to result in more flexible wastewater handling systems.


Impulse control disorders and related behaviours (ICD-RBs) in Parkinson's disease patients: Assessment using "Questionnaire for impulsive-compulsive disorders in Parkinson's disease" (QUIP).
There is limited data on the prevalence of impulse control disorder and related behaviors (ICD-RBs) in Indian patients with Parkinson's Disease (PD). In the context of potential genetic and environmental factors affecting the expression of ICD-RBs, studying other multiethnic populations may bring in-sights into the mechanisms of these disorders. To ascertain point prevalence estimate of ICD-RBs in Indian PD patients, using the validated "Questionnaire for Impulsive-Compulsive Disorders in Parkinson's disease (QUIP)" and to examine their association with Dopamine replacement therapy (DRT). This was a hospital based observational cross-sectional study. After taking informed consent, patients and their informants (spouse, or primary caregiver) were made to complete the QUIP, and were instructed to answer questions based on behaviors that occurred anytime during PD that lasted at least four consecutive weeks. Total of 299 patients participated in the study. At least one ICD-RB was present in 128 (42.8%), at least one Impulse control disorder (ICD) was present in 74 (24.75%) and at least one Impulse control related compulsive behaviour (ICRB) was present in 93 (31.1%) patients. Punding was the most frequent (12.4%) followed by hyper sexuality (11.04%), compulsive hobbyism (9.4%), compulsive shopping (8.4%), compulsive medication use (7.7%), compulsive eating (5.35%), walkabout (4%) and pathological gambling (3.3%). ≥ 2 ICD-RBs were observed in 15.7% of patients. After multivariate analysis, younger age of onset, being unmarried were specifically associated with presence of ICD. Longer disease duration was specifically associated with presence of ICRB. Whereas smoking and higher dopamine levodopa equivalent daily doses (DA LEDD) were associated with both presence of ICD and ICRB. Higher LD LEDD was specifically associated with presence of ICD-RB. Our study revealed a relatively higher frequency of ICD-RBs, probably because of the use of screening instrument and because we combined both ICDs and ICRBs. Also high proportion of DA use (81.6%) among our patients might be responsible. The role of genetic factors that might increase the risk of developing ICD-RBs in this population needs further exploration.


Active photonic crystal terahertz laser.
We present the design and the realization of active photonic crystal (PhC) semiconductor lasers. The PhC consists of semiconductor nanostructure pillars which provide gain at a quantized transition energy. The vertical layer sequence is that of a terahertz quantum cascade laser. Thereby, the artificial crystal itself provides the optical gain and the lateral confinement. The cavities do not rely on a central defect, the lasing is observed in flat-band regions at high symmetry points. The experimental results are in excellent agreement with the finite-difference time-domain simulations. For the vertical confinement a double-metal waveguide is used. The lasers are showing a stable single-mode emission under all driving conditions. Varying the period of the PhC allows to tune the frequency by 400 GHz.


Anti-malarial drug effects on parasite dynamics in vivax malaria.
Relapses of Plasmodium vivax malaria are prevented by 8-aminoquinolines. If hypnozoites survive, then the subsequent blood stage infections in early relapses (< 2 months) are suppressed by the slowly eliminated anti-malarial drugs used to treat the blood stage infection (chloroquine, artemisinin combination treatments), but they are not usually eliminated. The 8-aminoquinolines have significant blood stage activity which contributes to therapeutic responses. The latent interval from primary infection to early relapse depends on the number of activatable hypnozoites, the dose of anti-malarial, its pharmacokinetic properties, the level of resistance (minimum inhibitory concentration) and immunity. The dose-response relationship for radical curative efficacy of primaquine and tafenoquine is steep over the total dose range from 1.5 to 5 mg base/kg which may explain the poor efficacy of tafenoquine at the currently recommended dose.


Effect of mattress and pillow encasings on children with asthma and house dust mite allergy.
House dust mite (HDM) allergy is a frequent cause of allergic asthma in children. Reduction of exposure seems to be the most logical way to treat these patients. Our aim was to investigate whether mattress and pillow encasings resulted in an effective long-term control of HDM allergen levels, thereby reducing the need for asthma medication in children with asthma and HDM allergy. In a prospective, double-blind, placebo-controlled study 60 children (age range, 6-15 years) with asthma and HDM allergy were randomized to active (allergy control) or placebo mattress and pillow encasings. After a 2-week baseline period, follow-up was performed every 3 months for 1 year. During the entire study period, the dose of inhaled steroids was tapered off to the lowest effective dose according to well-defined criteria. Fifty-two patients completed the trial, and 5 were excluded, leaving data from 47 children (26 in the active treatment group and 21 in the placebo group) for analysis. A significant perennial reduction in HDM allergen concentrations was seen only for the active treatment group. Also, a significant decrease in the dose of inhaled steroids (mean, 408 to 227 microg/d; P <.001) was found for the active treatment group only, with significant differences between groups after 9 and 12 months. After 1 year, the dose of inhaled steroids was reduced by at least 50% in significantly more children in the active treatment group than in the placebo group (73% vs 24%, P <.01). Encasing of mattresses and pillows resulted in a significant long-term reduction in HDM allergen concentrations in mattresses and in the need for inhaled steroids in children with asthma and HDM allergy.


[Emergency care for victims of accidents and violence in Brazil].
To analyze positive results, challenges, limitations, and potential benefits associated with the Brazilian Policy for the Reduction of Morbidity and Mortality due to Accidents and Violence (PNRMAV) with regard to hospital emergency and urgent care services. From 2004-2007, a study was carried out in four Brazilian state capitals and the Federal District. The following areas were evaluated: the availability of standard practices for managing victims of accident or violence; availability and quality of adult and pediatric intensive care beds; patient management training for health care professionals; communication among the health care areas to provide better care to victims; and structure and organization of hospital services. The study included an exploratory stage, fieldwork, analysis, and dissemination of data. Both quantitative (absolute and relative frequencies) and qualitative methods (analysis of interactions between explicit and inferred information from statements and field records) were employed in the analysis. The study revealed positive results from the implementation of PNRMAV. The following focal areas were identified: (1) the need to invest in the response capacity of primary care services, (2) the importance of strengthening and promoting the emergency and urgent care network, (3) the importance of investing in appropriate equipment and of planning maintenance so that availability is not impacted, and (4) the need to invest in continuing education for health care professionals. The partial success obtained with PNRMAV shows that it is possible to include the topic of violence and accidents in the public health agenda and to implement life-promoting strategies at different levels.