Comparative leaf growth strategies in response to low-water and low-light availability: variation in leaf physiology underlies variation in leaf mass per area in Populus tremuloides.
Developmental phenotypic plasticity can allow plants to buffer the effects of abiotic and biotic environmental stressors. Therefore, it is vital to improve our understanding of how phenotypic plasticity in ecological functional traits is coordinated with variation in physiological performance in plants. To identify coordinated leaf responses to low-water (LW) versus low-light (LL) availability, we measured leaf mass per area (LMA), leaf anatomical characteristics and leaf gas exchange of juvenile Populus tremuloides Michx. trees. Spongy mesophyll tissue surface area (Asmes/A) was correlated with intrinsic water-use efficiency (WUEi: photosynthesis, (Aarea)/stomatal conductance (gs)). Under LW availability, these changes occurred at the cost of greater leaf tissue density and reduced expansive growth, as leaves were denser but were only 20% the final area of control leaves, resulting in elevated LMA and elevated WUEi. Low light resulted in reduced palisade mesophyll surface area (Apmes/A) while spongy mesophyll surface area was maintained (Asmes/A), with no changes to WUEi. These leaf morphological changes may be a plastic strategy to increase laminar light capture while maintaining WUEi. With reduced density and thickness, however, leaves were 50% the area of control leaves, ultimately resulting in reduced LMA. Our results illustrate that P. tremuloides saplings partially maintain physiological function in response to water and light limitation by inducing developmental plasticity in LMA with underlying anatomical changes. We discuss additional implications of these results in the context of developmental plasticity, growth trade-offs and the ecological impacts of climate change.


The functional organization of the internal components of Rice dwarf virus.
The capsid structures of particles of Rice dwarf virus that consisted of different components, namely, intact particles, empty particles lacking the 12 segments of double-stranded RNA (dsRNA), and virus-like particles composed of only the P3 core and P8 outer capsid proteins, generated with a baculovirus gene-expression system, were determined by cryo-electron microscopy. Combining the results with those of biochemical analysis, we assigned proteins of the transcriptional machinery and dsRNA to density clusters around the 5-fold axes and along the radial concentric layers, respectively. P7 protein, a component of the transcriptional machinery, was assigned to the outermost region of the density clusters. The density connecting the transcription complex to the outermost RNA densities implied interactions between the dsRNA and the P7 protein. Our structural analysis and the non-specific nucleic acid-binding activity of P7 explain the spiral organization of dsRNA around the 5-fold axis.


Elevated plasma adiponectin and decreased plasma homocysteine and asymmetric dimethylarginine in children with type 1 diabetes.
Type 1 diabetes has a bad prognosis concerning the pathogenesis of cardiovascular diseases (CVD). The purpose of this study was to evaluate different possible new risk indices for CVD in children with type 1 diabetes. The present study included 30 children with diabetes (mean HbA1C 9.8%), aged between 4.7 and 18.6 years and with no clinical evidence of vascular complications, and 30 healthy subjects matched by sex, age and body mass index. Blood pressure was measured and blood samples were obtained for lipid profile, creatinine, glucose, high sensitive C-reactive protein (hsCRP), intercellular adhesion molecule-1 (ICAM-1), asymmetric dimethylarginine (ADMA), adiponectin and homocysteine. Children with diabetes had significantly higher blood pressure, plasma hsCRP, ICAM-1, adiponectin levels and lower homocysteine, ADMA concentrations than their control subjects. In multivariate regression analysis, the best predictors for systolic blood pressure were diabetes group, plasma homocysteine concentration and BMI (Adj R(2) = 0.38, p<0.0001), and for diastolic blood pressure diabetes group and triglycerides level (Adj R(2) = 0.27, p<0.0001). Children with diabetes, in view of their higher future risk of CVD, are characterized by a higher concentration of protective adiponectin and paradoxically lower blood concentrations of some other possible risk markers of atherosclerosis, i.e. ADMA and homocysteine compared to healthy children.


Insecticidal Constituents of Essential Oil Derived from Zanthoxylum armatum against Two Stored-Product Insects.
In the course of our search for natural bioactive chemicals and investigations on their insecticidal activities from some medicinal plants growing in China, the essential oil derived from the twigs of Zanthoxylum armatum (Rutaceae) was found to possess strong insecticidal activities against two stored-product insects, Lasioderma serricorne and Tribolium castaneum. A total of 32 constituents of the essential oil were identified by GC and GC-MS analysis, and it revealed (E)-anethole (20.5%), 1,8-cineole (14.0%), 2-tridecanone (12.5%), limonene (9.0%) and piperitone (8.0%) as major components, followed by β-phellandrene (6.3%), β-pinene (5.1%) and 4-terpineol (4.4%). From the essential oil, five compounds were isolated and identified as (E)-anethole, 1,8-cineole, 2-tridecanone, limonene and piperitone. The results of insecticidal bioassays showed that the essential oil of Z. armatum exhibited strong fumigant toxicity towards L. serricorne and T. castaneum with LC50 values of 13.83 and 4.28 mg/L air, respectively, and also possessed contact toxicity against two insect species with LD50 values of 18.74 and 32.16 μg/adult, respectively. Among the active compounds, piperitone performed the strongest fumigant toxicity against L. serricorne (LC50 = 1.21 mg/L air) and contact toxicity against T. castaneum (LD50 = 3.16 μg/adult). 1,8-Cineole, limonene and piperitone showed similar fumigant toxicity against T. castaneum with LC50 values of 5.47, 6.21 and 7.12 mg/L air, respectively. Meanwhile, L. serricorne was the most sensitive to 2-tridecanone (LD50 = 5.74 μg/adult) in the progress of contact toxicity assay.


Help bring back the celebration of life: a community-based participatory study of rural Aboriginal women's maternity experiences and outcomes.
Despite clear evidence regarding how social determinants of health and structural inequities shape health, Aboriginal women's birth outcomes are not adequately understood as arising from the historical, economic and social circumstances of their lives. The purpose of this study was to understand rural Aboriginal women's experiences of maternity care and factors shaping those experiences. Aboriginal women from the Nuxalk, Haida and 'Namgis First Nations and academics from the University of British Columbia in nursing, medicine and counselling psychology used ethnographic methods within a participatory action research framework. We interviewed over 100 women, and involved additional community members through interviews and community meetings. Data were analyzed within each community and across communities. Most participants described distressing experiences during pregnancy and birthing as they grappled with diminishing local maternity care choices, racism and challenging economic circumstances. Rural Aboriginal women's birthing experiences are shaped by the intersections among rural circumstances, the effects of historical and ongoing colonization, and concurrent efforts toward self-determination and more vibrant cultures and communities. Women's experiences and birth outcomes could be significantly improved if health care providers learned about and accounted for Aboriginal people's varied encounters with historical and ongoing colonization that unequivocally shapes health and health care. Practitioners who better understand Aboriginal women's birth outcomes in context can better care in every interaction, particularly by enhancing women's power, choice, and control over their experiences. Efforts to improve maternity care that account for the social and historical production of health inequities are crucial.


BCR/ABL expression of myeloid progenitors increases beta1-integrin mediated adhesion to stromal cells.
The expression of the fusion protein BCR/ABL is a hallmark of chronic myeloid leukemia. BCR/ABL is a constitutively active tyrosine kinase influencing cell proliferation, apoptosis, and differentiation. To what extent and by which mechanism BCR/ABL affects the adhesion of leukemic cells to bone marrow stromal cells (BMSC) is controversial. To characterize adhesion of BCR/ABL-transformed 32D cells (32D-BCR/ABL) to the BMSC line M2-10B4, we used washing assays and single-cell force spectroscopy (SCFS). Compared to control 32D cells (32D-V), 32D-BCR/ABL developed threefold higher adhesion forces. This enhanced cell adhesion could be reduced to control levels after specifically inhibiting the activity of the tyrosine kinase BCR/ABL using imatinib mesylate (IM). SCFS showed that the adhesion forces of 32D-BCR/ABL were strongest to fibronectin and collagen type I, suggesting that beta1-integrin has a major role in mediating the adhesion of leukemic cells to BMSC. Indeed, the beta1-integrin blocking antibody Ha2/5 abrogated the attachment of 32D-V and 32D-BCR/ABL cells to BMSC. Although 32D-BCR/ABL cells show significantly increased beta1-integrin expression, no significant difference of beta1-integrin mRNA levels could be detected, indicating a post-transcriptional regulation of beta1-comprising integrin heterodimers by BCR/ABL. The data presented here argue that the interaction of beta1-integrin and extracellular matrix components is functionally important in leukemic cells expressing high-levels of BCR/ABL, and could provide a rationale for the development of optimized targeted therapies.


Dose of selective serotonin uptake inhibitors across pregnancy: clinical implications.
The use of antidepressants during pregnancy has undergone considerable scrutiny with respect to safety issues, though limited data with respect to dose management and symptom resolution is available. Previous reports on tricyclic antidepressants (TCAs) have demonstrated the need to adjust maternal dose later in pregnancy to maintain therapeutic serum concentrations. However, there is no data on the dosage of selective serotonin uptake inhibitors (SSRIs) required to maintain symptom resolution in women treated for major depression during pregnancy. The purpose of this study, then, was to assess the medication dosage requirements of SSRIs during this time. In this naturalistic study, pregnant women with a primary diagnosis of major depression were followed prospectively through pregnancy at monthly intervals with symptom assessment. Subjects were included in data analysis if they presented prior to 28 weeks gestation, were treated with SSRI monotherapy, received all psychiatric treatment during the pregnancy at the Emory Pregnancy and Postpartum Mood Disorders Program, and achieved euthymia after initial treatment intervention (CGI = 1 and Beck Depression Inventory (BDI) < 9) during pregnancy or failed to respond after eight weeks of treatment. Medication selection was based on personal treatment history or family treatment history (if any), and the published data on SSRIs in pregnancy. All medication dose adjustments were based on depressive symptoms as measured by the BDI and a psychiatric interview (ZNS). Thirty-four pregnant women were included in final analysis. Two thirds of the subjects (n = 22) required an increase in their daily dose of medication to maintain euthymia. The dose increases occurred at 27.1 +/- 7.1 weeks gestation, with mean BDI scores of 16.4 +/- 9.6, compared to a mean treatment response BDI of 6.9 +/- 5.4. Subject's age, education, past personal and familial psychiatric history were not significantly associated with dose adjustment. These novel data on SSRI daily dose in pregnancy parallels the extant literature with tricyclic antidepressants (TCA). Further work to determine the predictors of dose adjustments will provide guidelines for minimizing fetal exposure to both medication and maternal mental illness.


Do current methods for endotracheal tube cuff inflation create pressures above the recommended range? A review of the evidence.
Inflation and measurement of endotracheal (ET) tube cuff pressure is often not seen as a critical aspect of care in surgical patients. The morbidity associated by an overinflated cuff has been regularly highlighted in literature, for example mucosal ulceration (Combes et al 2001) and vocal cord paralysis (Holley & Gildea 1971). This article will outline techniques for the methods of inflation based on the latest scientific evidence. The author will seek to examine if intraoperative cuff assessment and monitoring should become routine for the anaesthetic practitioner and if current practice for inflating cuffs creates pressures outside the safe range.


Attentional patterns involved in coping strategies in a sport context.
We investigated the relationship between coping strategies and attentional bias after a sport competition. We administered the Ways of Coping Checklist (Paulhan, Nuissier, Quintard, Cousson, & Bourgeois, 1994) to 145 athletes immediately after they had participated in a sport competition. We also assessed attentional bias using a dot probe detection task. Results revealed that emotion-focused coping strategies led athletes to orient their attention away from threat, whereas athletes who adopted problem-focused coping strategies focused their attention toward threat. More precisely, problem-focused coping strategies are related to a facilitated detection of threat, not to disengagement difficulties. The vigilance attentional bias seems to be a compensatory strategy to cope with a stressful situation, such as sport competition.


Specific patterns of canine scavenging in indoor settings.
Postmortem animal mutilations due to domestic dogs in isolated domestic deaths are taphonomic modifications regularly observed by forensic pathologists. They are rarely described in the literature; however, even though they present specific patterns. Through 41 cases, 10 at the forensic institute in Lille (France) and 31 at the New York City Office of Chief Medical Examiner (USA), plus 22 cases from the literature, specific locations and patterns of postmortem scavenging lesions are proposed. These lesions are mainly distributed in three locations: the face, especially the nose and the mouth (73.1%), the neck (43.1%), and the arm (shoulder/upper limb [29.2%], hand [26.8%]). We discuss the time span between death and scavenging, the consequences on identification, and comparison with outdoor settings. Outdoor scavenging lesions are mainly located on the trunk and limbs usually sparing the head, which strongly differs from indoor distribution and imply different animal motivations.


Symptomatic treatment of brain tumor patients with sodium selenite, oxygen, and other supportive measures.
Patients (16 women and 16 men) with brain tumors previously treated conservatively by surgery, radiation, and/or chemotherapy with typical symptoms of increased intracranial pressure were consecutively enrolled to test the effects of pharmacological dosages of sodium selenite (selenase) in conjunction with other supportive therapies (biological response modifiers, detoxification, chemotherapy, immunotherapy, oxygen therapy). The rationale for the use of sodium selenite was that the whole-blood selenium levels were subnormal in 70% of the patients on admission. Patients also frequently presented abnormal levels of other minerals, especially lowered sodium and elevated potassium levels, which appears to be characteristic of brain tumor patients. Sodium selenite was administered by infusion at dosages of 1000 microg Se in physiological saline/d for 4-8 wk. In 76% of the patients, a definite, and in 24% a slight improvement of the general condition and a decrease in symptoms, such as nausea, emesis, headache, vertigo, unsteady gait, speech disorders, and Jacksonian seizures, were observed. In all treated patients, improvements of erythrocyte, hemoglobin, and thrombocyte counts were observed. Additional beneficial effects were noted in the patients receiving the oxygen therapy. It is concluded that the sodium selenite can be employed with oxygen therapy and other supportive measures in the management of brain tumor patients.


Sequencing Analysis of Genetic Loci for Resistance for Late Leaf Spot and Rust in Peanut (Arachis hypogaea L.).
The aim of this study was to identify candidate resistance genes for late leaf spot (LLS) and rust diseases in peanut (Arachis hypogaea L.). We used a double-digest restriction-site associated DNA sequencing (ddRAD-Seq) technique based on next-generation sequencing (NGS) for genotyping analysis across the recombinant inbred lines (RILs) derived from a cross between a susceptible line, TAG 24, and a resistant line, GPBD 4. A total of 171 SNPs from the ddRAD-Seq together with 282 markers published in the previous studies were mapped on a genetic map covering 1510.1 cM. Subsequent quantitative trait locus (QTL) analysis revealed major genetic loci for LLS and rust resistance on chromosomes A02 and A03, respectively. Heterogeneous inbred family-derived near isogenic lines and the pedigree of the resistant gene donor, A. cardenasii Krapov. & W.C. Greg., including the resistant derivatives of ICGV 86855 and VG 9514 as well as GPBD 4, were employed for whole-genome resequencing analysis. The results indicated the QTL candidates for LLS and rust resistance were located in 1.4- and 2.7-Mb genome regions on A02 and A03, respectively. In these regions, four and six resistance-related genes with deleterious mutations were selected as candidates for LLS and rust resistance, respectively. These delimited genomic regions may be beneficial in breeding programs aimed at improving disease resistance and enhancing peanut productivity.


Hollow nickel nanocorn arrays as three-dimensional and conductive support for metal oxides to boost supercapacitive performance.
A novel three-dimensional (3D) metal/metal oxide core/branch array electrode has been fabricated as a supercapacitor electrode. Hollow Ni nanocorn arrays are constructed on Ni foams and act as a highly conductive and stable support to Co3O4 nanoflakes. Enhanced pseudocapacitive performance compared to bare Co3O4 nanosheets is demonstrated with high rate capability and excellent cycling stability.


Identification of a conserved receptor-binding site on the fiber proteins of CAR-recognizing adenoviridae.
The human adenovirus serotype 5 (Ad5) is used widely for applications in human gene therapy. Cellular attachment of Ad5 is mediated by binding of the carboxyl-terminal knob of its fiber coat protein to the Coxsackie adenovirus receptor (CAR) protein. However, Ad5 binding to CAR hampers the development of adenovirus vectors capable of specifically targeting (diseased) tissues or organs. Through sequence analysis and mutagenesis, a conserved receptor-binding region was identified on the side of three divergent CAR-binding knobs. The feasibility of simultaneous CAR ablation and redirection of an adenovirus to a new receptor is demonstrated.


Identification of unknown microcontaminants in Dutch river water by liquid chromatography-high resolution mass spectrometry and nuclear magnetic resonance spectroscopy.
In the past decade during automated surface water monitoring in the river Meuse at border station Eijsden in The Netherlands, a set of unknown compounds were repeatedly detected by online liquid chromatography-diode-array detection in a relatively high signal intensity. Because of the unknown nature of the compounds, the consequently unknown fate of this mixture in water treatment processes, the location being close to the water inlet of a drinking water supply company and their possible adverse public health effects, it was deemed necessary to elucidate the identity of the compounds. No data are available for the occurrence of these unknowns at downstream locations. After concentration and fractionation of a sample by preparative Liquid Chromatography, identification experiments were performed using Liquid Chromatography-High Resolution Mass Spectrometry (LC-HR-MS) combined with High Resolution Nuclear Magnetic Resonance Spectroscopy (HR-NMR). Accurate mass determination of the unknown parent compound and its fragments obtained in MS/MS provided relevant information on the elemental composition of the unknown compounds. With the use of NMR techniques and the information about the elemental composition, the identity of the compounds in the different sample fractions was determined. Beside some regularly detected compounds in surface water, like caffeine and bisphenol-S, five dihydroxydiphenylmethane isomers were identified. The major unknown compound was identified as 4,4'-dihydroxy-3,5,3',5'-tetra(hydroxymethyl)diphenylmethane. This compound was confirmed by analysis of the pure reference compound. This is one of the first studies that employs the combination of high resolution MS with NMR for identification of truly unknown compounds in surface waters at the μg/L level. Five of the seven identified compounds are unexpected and not contained in the CAS database, while they can be presumed to be products generated during the production of resins.


Heterogeneous photocatalytic degradation of antiviral drug didanosine mediated by rose bengal and TiO2 nanoparticles.
There is a great concern among the researcher to remove the problem of the persistent organic pollutants in wastewater. Pharmaceutical agrochemical and personal care products are generally considered Persistent organic pollutants. Therefore, it is a matter of concern to develop new techniques how to remove these pollutants safely at low cost. This study mainly focuses on the commonly used antiviral drug didanosine and one most commonly used dye rose bengal. In this study, an organic dye rose bengal and TiO2 nanoparticles have been used in combination with UV light to achieve the photodegradation of selected pharmaceutical products and the dye was also degraded by using TiO2 Nanoparticles. The formation of three oxidation products was detected by using a very popular separation technique thin layer and column chromatography. The isolated photoproduct was characterized by using advanced characterization techniques like FTIR (Fourier transform infrared spectroscopy), UV Spectroscopy, and Proton and 13C NMR (Nuclear Magnetic Resonance spectroscopy). The role of singlet oxygen as an active species in this reaction was confirmed by using D2O as a reaction medium. The role of singlet oxygen in this photochemical reaction was also established by the addition of sodium azide. The TiO2 nanophotocatalyst efficiently degrade the didanosine and rose bengal in the presence of the UV light. In the TiO2-induced photocatalytic degradation of didanosine and dyes, the hydroxyl and superoxide radical anion play a prominent role. The finding of this manuscript is very useful to develop an efficient low-cost method for the treatment of wastewater contaminated by antiviral drugs, similar pharmaceutical products and dyes. This study was also very helpful to establish a plausible mechanism behind the phototoxicity of the didanosine.


Probing local and long-range structure simultaneously: an in situ study of the high-temperature phase transition of alpha-AlF3.
We show in this Communication that the combination of Rietveld and pair distribution function (PDF) analyses allows unique insight into the nature and driving force of the phase transition of alpha-AlF3, which was not available from conventional structural analysis methods alone. The use of image plate technology allows structural changes to be followed in "real time" and reduces the time required to collect high-resolution PDF data from hours (with a conventional solid state detector) to seconds. This methodology produces raw data that can simultaneously be analyzed by both Rietveld and PDF analysis.


When is altruistic punishment useful in social dilemmas?
It is not fully understood how cooperation emerges in a population of individuals with no connections or prior experience with each other. Strategy selection that is purely based on accumulated payoffs promotes free riders who put their self interests above that of any group. How could cooperation persist in these settings? Researchers have posited direct or indirect reciprocity as possible explanations but these theories fail if interactions are not repeated or reputations are ignored. Altruistic punishment may provide an answer. Punishers impose a penalty, such as a fine, on defectors. The idea is a sufficiently high enough penalty-or even the threat of a high penalty-will convince defectors that cooperation is more beneficial. The punishment is altruistic because punishers pay a cost to impose a penalty and expect nothing in return (including no future reciprocity). Empirical and human studies have shown when some individuals are punishers, and they are common, cooperation levels tend to increase. But it has never been specified exactly how large this majority of punishers must be to promote cooperation. Here we analyze cooperation, defection and punishment in a social dilemma, public goods game, and precisely identify the necessary conditions to make altruistic punishment an effective strategy for improving group cooperation levels.


Vascular endothelium is the organ chiefly responsible for the catabolism of plasma asymmetric dimethylarginine--an explanation for the elevation of plasma ADMA in disorders characterized by endothelial dysfunction.
Plasma levels of asymmetric dimethylarginine (ADMA), an endogenously produced competitive inhibitor of nitric oxide synthase (NOS), have been found to be elevated in a large number of disorders characterized by endothelial dysfunction; this remarkable phenomenon has yet to receive a plausible explanation. ADMA arises by proteolysis of methylated proteins throughout the body; the majority of this ADMA is catabolized by the enzyme dimethylarginine dimethylaminohydrolase (DDAH), found in many tissues, including those that express NOS. Since the production of ADMA can be considered constitutive, and little intact ADMA emerges in the urine, impaired catabolism is most likely responsible for elevations of plasma ADMA. The association of elevated ADMA with endotheliopathy is readily explained if we assume that vascular endothelium is the organ chiefly responsible for the catabolism of plasma ADMA--a view that is credible owing to the privileged access of endothelium to plasma, the capacity of endothelium for active transport of arginine (and methylated arginines), and the ample DDAH activity of healthy endothelial cells--and further assume that endothelial dysfunction is often attended by a loss of DDAH activity and/or an impairment of arginine transport, reducing the efficiency of ADMA catabolism. Indeed, there is recent evidence that DDAH is inhibited by endothelial oxidative stress, a typical feature of endotheliopathy; there is also some reason to suspect that arginine transport may be less efficient in dysfunctional endothelium. From this perspective, increased plasma ADMA is not the primary cause of the endothelial dysfunction in various disorders, but rather its effect--though the rise in ADMA can then exacerbate this dysfunction by inhibiting endothelial NOS. Supplemental arginine should be of some clinical benefit in disorders characterized by elevated ADMA, since it can offset that adverse impact of ADMA on NOS activity, and possibly exert other beneficial effects on endothelium--but it cannot be expected to reverse the primary cause of the endothelial dysfunction. Whether or not ADMA plays an important pathogenic role, it seems likely to emerge as a potent risk factor for adverse vascular events, since it may be viewed as a barometer of endothelial health.


[Studies on the adaptation of five legumes species to copper tailings].
Pot experiments with five legumes were conducted in five different amendment substrates for the reclamation of copper tailings in Tongling, Anhui province. The five tested legumes species are Glycine max, Phaseolus angularis, P. calcaratus, P. radiatus, P. mininus. The results showed that the main factors to restrict growing of the vegetation are poor nutrient and high concentration of Cu. The seeds of the legumes species could germinate, but they germinated later in the substrates with higher proportion of copper tailings than in the substrates with lower proportion of copper tailings. After clipping, G. max, P. angularis, P. calcaratus, P. radiatus were alive all the time, but some of the other two legumes species were dead because of the their non-adaptation to the copper tailings. At the same amendment group, the chlorophyll contents of G. max and P. calcaratus were higher than that of other three experimental species on the 50th day. The height and the biomass of G. max and P. calcaratus were higher than that of other three experimental species on the 70th day too. According to the biological characteristics of the five species during the growth periods about indexes of the seeding survival, chlorophyll content, height and biomass, G. max and P. calcaratus are more adaptive and tolerant than the other legumes and the TA75 amendment approach is the more reasonable for the reclamation of copper tailings.


Molecular recognition properties of FN3 monobodies that bind the Src SH3 domain.
We have constructed a phage-displayed library based on the human fibronectin tenth type III domain (FN3) scaffold by randomizing residues in its FG and BC loops. Screening against the SH3 domain of human c-Src yielded six different clones. Five of these contained proline-rich sequences in their FG loop that resembled class I (i.e., +xxPxxP) peptide ligands for the Src SH3 domain. The sixth clone lacked the proline-rich sequence and showed particularly high binding specificity to the Src SH3 domain among various SH3 domains tested. Competitive binding, loop replacement, and NMR perturbation experiments were conducted to analyze the recognition properties of selected binders. The strongest binder was able to pull down full-length c-Src from murine fibroblast cell extracts, further demonstrating the potential of this scaffold for use as an antibody mimetic.


A systematic review and meta-analysis on the cardio-protective activity of naringin based on pre-clinical evidences.
The cardioprotective role of naringin has been scientifically well demonstrated in various experimental models such as diabetic cardiomyopathy, ischemic heart diseases, diet-induced cardiac injury, antihypertensive and anti-platelet activities through various mechanisms. However, there is no meta-analysis performed on the cardioprotective activity of naringin. This systematic review and meta-analysis were focused to summarize and conclude the therapeutic benefits of naringin in various cardiovascular disorders using pre-clinical evidence. The online search was performed using electronic databases such as PubMed/Medline, Scopus, ScienceDirect, and Google scholar. The search was mainly focused on the role of naringin in various cardiovascular disorders in experimental animals. Based on the inclusion and exclusion criteria 34 studies were selected. The meta-analysis revealed that naringin could significantly alleviate various physical and chemical stimuli induced cardiovascular disorders such as diabetic cardiomyopathy, ischemic heart diseases, oxidative stress-induced cardiac injury, diet-induced cardiovascular dysfunctions in experimental models involving multiple mechanisms such as antioxidant (ROS/RNS pathways), anti-inflammatory (COX-2, IL-6, TNF-α, NF-κB pathways), enhancing angiogenic factors (VEGF, VCAM, HIF-1α, iNO), suppressing the apoptotic factors (BCL-2, BAX, caspases) and modulation of PCSK-9, PKCα/β, PPAR-α, JAK/STAT, MAPKs (p38α, ERK1/2, JNK), and PI3K/AKT/mTOR/p70S6K associated pathways. Further, these changes at the cellular and molecular levels were manifested as improvement in the structural, functional, and physiology of the heart upon the naringin treatment. In conclusion, this systematic review and meta-analysis support the available scientific evidence on the therapeutic benefits of naringin in the management of various cardiovascular conditions.


The Mystery of Chemotherapy Brain: Kynurenines, Tubulin and Biophoton Release.
The majority of patients receiving chemotherapy experience post-chemotherapy cognitive impairment, sometimes referred to as "chemo brain" or "chemo fog." The cognitive impairment associated with this syndrome can be severe, and can sometimes last for many years after therapy discontinuation. Despite extensive investigations, its etiology is unknown. We argue that chemo brain results from damage to tubulin within microtubules. This damage can occur directly from tubulin inhibitors such as taxanes, epothilones or vinca alkaloids. Other chemotherapies stimulate increased mitochondrial activity and biophoton release. This results in abnormal tryptophan metabolism and excess production of neurotoxic kynurenines, which, in turn, damage microtubules.


A nosocomial outbreak of diarrheal disease due to Yersinia enterocolitica serotype 0:5, biotype 1.
An outbreak of diarrheal disease due to Yersinia enterocolitica serotype 0:5 , biotype 1, involved nine hospitalized patients. The possible source of this infection was two patients who were both hospitalized with a history of several weeks of intermittent diarrhea. Person-to-person contact was the probable mode of transmission of the disease. The present report describes the second known nosocomial outbreak of infection due to Y. enterocolitica, Serotype 0:5 of Y. enterocolitica is not commonly encountered, and its involvement in an outbreak of gastroenteritis has not been previously reported. The importance of the enrichment technique in the isolation of Y. enterocolitica is demonstrated.


Genomic organization of a human cystine transporter gene (SLC3A1) and identification of novel mutations causing cystinuria.
Cystinuria is a common inherited aminoaciduria that leads to recurrent cystine nephrolithiasis. Mutations in a gene encoding a renal amino acid transporter (SLC3A1) have been identified in patients with cystinuria establishing one molecular cause for the disease. To facilitate systematic screening of this gene for mutations, we have delineated the complete genomic organization of the SLC3A1 coding region using polymerase chain reaction strategies. The complete coding region of the gene is contained within a single yeast artificial chromosome clone and consists of 10 exons and 9 introns. Oligonucleotide primers capable of amplifying selected exons have been made and used in mutational analysis of DNA from 24 cystinuria probands. We illustrate the usefulness of this approach by identifying two novel SLC3A1 mutations. One novel mutation causes replacement of a highly conserved arginine residue (arginine-452) with tryptophan in the cytoplasmic loop between the putative third and fourth membrane spanning segments. A second previously unreported mutation results in replacement of a highly conserved tyrosine (tyrosine-461) residue with histidine in the same region of the protein. In addition, we detected three previously reported SLC3A1 mutations, R270X, 1500 +1/G to T, and M467T, the latter being present in approximately 20% of cystinuria chromosomes examined. Our findings provide a foundation for the development of more accessible diagnostic screening assays for detecting SLC3A1 mutations using patient genomic DNA, and also contribute to the emerging spectrum of cystinuria genotypes.


Liposomal vector mediated delivery of the 3p FUS1 gene demonstrates potent antitumor activity against human lung cancer in vivo.
Lung cancer is one of the leading causes of death in the world. The underlying cause for lung cancer has been attributed to various factors that include alteration and mutation in the tumor suppressor genes. Restoration of normal function of the tumor suppressor gene is a potential therapeutic strategy. Recent studies have identified a group of candidate tumor suppressor genes on human chromosome 3p21.3 that are frequently deleted in human lung and breast cancers. Among the various genes identified in the 3p21.3 region, we tested the antitumor activity of the FUS1 gene in two human non-small-cell lung cancer (NSCLC) xenografts in vivo. Intratumoral administration of FUS1 gene complexed to DOTAP:cholesterol (DOTAP:Chol) liposome into subcutaneous H1299 and A549 lung tumor xenograft resulted in significant (P = .02) inhibition of tumor growth. Furthermore, intravenous injections of DOTAP:Chol-FUS1 complex into mice bearing experimental A549 lung metastasis demonstrated significant (P = .001) decrease in the number of metastatic tumor nodules. Finally, lung tumor-bearing animals when treated with DOTAP:Chol-FUS1 complex demonstrate prolonged survival (median survival time: 80 days, P = .01) compared to control animals. This result demonstrates the potent tumor suppressive activity of the FUS1 gene and is a promising therapeutic agent for treatment of primary and disseminated human lung cancer.


Chemotherapy for advanced gastric cancer.
Gastric cancer currently ranks second in global cancer mortality. Most patients are either diagnosed at an advanced stage, or develop a relapse after apparently curative operation. Apart from supportive measures, systemic chemotherapy is the only treatment option available in this situation. To assess the effect of chemotherapy versus best supportive care, combination versus single agent chemotherapy and different combination chemotherapy regimens in advanced gastric cancer. We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 1, 2004), MEDLINE and EMBASE up to February 2004 and reference lists of articles. We also contacted pharmaceutical companies as well as national and international experts. Randomised controlled trials on systemic intravenous chemotherapy versus best supportive care, combination versus single agent chemotherapy and different combination chemotherapies in advanced gastric cancer. Two authors independently extracted data. A third investigator was consulted in case of disagreements. We contacted study authors to obtain missing information. Chemotherapy versus best supportive care consistently demonstrated a significant benefit in terms of overall survival in favour of the group receiving chemotherapy (Hazard Ratios (HR) 0.39; 95% confidence intervals (CI) 0.28 to 0.52). Combination versus single-agent chemotherapy provides evidence for a survival benefit in favour of combination chemotherapy (HR 0.85; 95% CI 0.76 to 0.96). Numbers included in these comparisons were 184 and 1338 participants respectively. This benefit is achieved at the price of increased toxicity in the combination chemotherapy arms. When comparing 5-FU/cisplatin-containing combination therapy regimens with anthracyclines versus those without anthracyclines (HR 0.77; 95% CI 0.62 to 0.95 based on 501 participants) and 5-FU/anthracycline-containing combinations with cisplatin versus those without cisplatin (HR 0.83; 95% CI 0.76 to 0.91 based on 1147 participants), there was a significant survival benefit for regimens including 5-FU, anthracyclines and cisplatin. Chemotherapy significantly improves survival in comparison to best supportive care. In addition, combination chemotherapy improves survival compared to single-agent 5-FU, but the effect size is much smaller. Among the combination chemotherapy regimens studied, best survival results are achieved with regimens containing 5-FU, anthracyclines and cisplatin. In this category, ECF (epirubicin, cisplatin and continuous infusion 5-FU) is tolerated best.


Nine-year follow-up of a home-visitation program: a randomized trial.
To evaluate the extent to which a home-visitation program (Early Start) had benefits for child abuse, child behavior, and parental- and family-level benefits to the 9-year follow-up. A randomized controlled trial in which 220 families receiving Early Start were contrasted with a control series of 223 families not receiving the program. Families were enrolled in the program for up to 5 years. Outcomes were assessed at 6 months, annually from 1 year to 6 years, and at 9 years after trial entry. Comparisons between the Early Start and control series showed that families in the Early Start program showed significant (P < .05) benefits in reduced risk of hospital attendance for unintentional injury, lower risk of parent-reported harsh punishment, lower levels of physical punishment, higher parenting competence scores, and more positive child behavioral adjustment scores. Effect sizes (Cohen's "d") ranged from 0.13 to 0.29 (median = 0.25). There were no significant differences (all P values > .05) between the Early Start and control series on a range of measures of parental behavior and family outcomes, including maternal depression, parental substance use, intimate partner violence, adverse economic outcomes, and life stress. The Early Start program was associated with small to moderate benefits in a range of areas relating to child abuse, physical punishment, child behavior, and parenting competence. There was little evidence to suggest that the Early Start program had benefits that extended to the level of parents or family overall.


The serine proteinase chain of human complement component C1s. Cyanogen bromide cleavage and N-terminal sequences of the fragments.
Human complement component C1s was purified from fresh blood by conventional methods of precipitation and chromatography. The single-chain zymogen form was activated by treatment with C1r. Reduction and carboxymethylation then allowed the light chain and heavy chain to be separated on DEAE-Sepharose CL-6B in 8 M-urea. Liquid-phase sequencing of the light chain determined 50 residues from the N-terminus. CNBr-cleavage fragments of the light chain were separated by high-pressure liquid chromatography on gel-permeation and reverse-phase columns. N-Terminal sequencing of these fragments determined the order of a further 138 residues, giving a total of 188 residues or about 75% of the light chain. Seven of these eight sequences could be readily aligned with the amino acid sequences of other serine proteinases. The typical serine proteinase active-site residues are clearly conserved in C1s, and the specificity-related side chain of the substrate-binding pocket is aspartic acid, as in trypsin, consistent with the proteolytic action of C1s on C4 at an arginine residue. Somewhat surprisingly, when the C1s sequence is compared with that of complement subcomponent C1r, the percentage difference (59%) is approximately the same as that found between the other mammalian serine proteinases (56-71%).


National outbreak of Salmonella Give linked to a local food manufacturer in Malta, October 2016.
Salmonella Give is a rare serotype across Europe. In October 2016, a national outbreak of S. Give occurred in Malta. We describe the epidemiological, environmental, microbiological and veterinary investigations. Whole-genome sequencing (WGS) was performed on human, food, environmental and veterinary isolates. Thirty-six human cases were reported between October and November 2016, 10 (28%) of whom required hospitalisation. Twenty-six (72%) cases were linked to four restaurants. S. Give was isolated from ready-to-eat antipasti served by three restaurants which were all supplied by the same local food manufacturer. Food-trace-back investigations identified S. Give in packaged bean dips, ham, pork and an asymptomatic food handler at the manufacturer; inspections found inadequate separation between raw and ready-to-eat food during processing. WGS indicated two genetically distinguishable strains of S. Give with two distinct clusters identified; one cluster linked to the local food manufacturer and a second linked to veterinary samples. Epidemiological, environmental and WGS evidence pointed towards cross-contamination of raw and ready-to-eat foods at the local manufacturer as the likely source of one cluster. Severity of illness indicates a high virulence of this specific serotype. To prevent future cases and outbreaks, adherence to food safety practices at manufacturing level need to be reinforced.


Eating disorder psychopathology in adults and adolescents with anorexia nervosa: A network approach.
The aim of this study was to assess and compare eating disorder feature networks in adult and adolescent patients with anorexia nervosa. Patients seeking treatment for anorexia nervosa in inpatient and outpatient settings were consecutively recruited from January 2008 to September 2019. Body mass index was measured, and each patient completed the Eating Disorder Examination Questionnaire. The sample comprised 547 adolescent and 724 adult patients with anorexia nervosa. Network analysis showed that in both adults and adolescents, the most central and highly interconnected nodes in the network were related to shape overvaluation and desiring weight loss. The network comparison test identified similar global strength and network invariance, confirming the similarity of the two network structures. The network structures in adult and adolescent patients with anorexia nervosa are similar, and lend weight to the cognitive behavioral theory that overvaluation of shape and weight is the core feature of anorexia nervosa psychopathology.


Membrane lipids protected from oxidation by red wine tannins: a proton NMR study.
Dietary polyphenols widespread in vegetables and beverages like red wine and tea have been reported to possess antioxidant properties that could have positive effects on human health. In this study, we propose a new in situ and non-invasive method based on proton liquid-state nuclear magnetic resonance (NMR) to determine the antioxidant efficiency of red wine tannins on a twice-unsaturated phospholipid, 1,2-dilinoleoyl-sn-glycero-3-phosphocholine (DLiPC), embedded in a membrane model. Four tannins were studied: (+)-catechin (C), (-)-epicatechin (EC), (-)-epicatechin gallate (ECG), and (-)-epigallocatechin gallate (EGCG). The lipid degradation kinetics was determined by measuring the loss of the bis-allylic protons during oxidation induced by a radical initiator, 2,2'-Azobis(2-methylpropionamidine) dihydrochloride (AAPH). The antioxidant efficiency, i.e. the ability of tannins to slow down the lipid oxidation rate, was shown to be higher for galloylated tannins, ECG and EGCG. Furthermore, the mixture of four tannins was more efficient than the most effective tannin, EGCG, demonstrating a synergistic effect. To better understand the antioxidant action mechanism of polyphenols on lipid membranes, the tannin location was investigated by NMR and molecular dynamics. A correlation between antioxidant action of tannins and their location at the membrane interface (inserted at the glycerol backbone level) could thus be established.


Insulin therapy: problems in an African country.
Major problems of metabolic control are encountered in the 40% of Ethiopian diabetic patients who require insulin. Important contributory factors include the cost of insulin, its erratic supply, and difficulties with handling syringes and obtaining sterility. Economic and social factors also aggravate poor dietary control, a situation exacerbated by religious customs. Geographical and manpower problems contribute to the problem through unsatisfactory follow-up arrangements.


Trends in Diagnosis Related Groups for Inpatient Admissions and Associated Changes in Payment From 2012 to 2016.
Hospitals are reimbursed based on Diagnosis Related Groups (DRGs), which are defined, in part, by patients having 1 or more complications or comorbidities within a given DRG family. Hospitals have made substantial investment in efforts to document these complications and comorbidities. To examine temporal trends in DRGs with a major complication or comorbidity, compare these findings with 2 alternative measures of disease severity, and estimate associated changes in payment. This retrospective cohort study used data from the all-payer National Inpatient Sample for admissions assigned to 1 of the top 20 reimbursed DRG families at US acute care hospitals from January 1, 2012, to December 31, 2016. Data were analyzed from July 10, 2018, to May 29, 2019. Quarter year of hospitalization. The primary outcome was the proportion of DRGs with a major complication or comorbidity. Secondary outcomes were comorbidity scores, risk-adjusted mortality rates, and estimated payment. Changes in assigned DRGs, comorbidity scores, and risk-adjusted mortality rates were analyzed by linear regression. Payment changes were estimated for each DRG by calculating the Centers for Medicare & Medicaid Services weighted payment using 2012 and 2016 case mix and hospitalization counts. Between 2012 and 2016, there were 62 167 976 hospitalizations for the 20 highest-reimbursed DRG families; the sample was 32.9% male and 66.8% White, with a median age of 57 years (interquartile range, 31-73 years). Within 15 of these DRG families (75%), the proportion of DRGs with a major complication or comorbidity increased significantly over time. Over the same period, comorbidity scores were largely stable, with a decrease in 6 DRG families (30%), no change in 10 (50%), and an increase in 4 (20%). Among 19 DRG families with a calculable mortality rate, the risk-adjusted mortality rate significantly decreased in 8 (42%), did not change in 9 (47%), and increased in 2 (11%). The observed DRG shifts were associated with at least $1.2 billion in increased payment. In this cohort study, between 2012 and 2016, the proportion of admissions assigned to a DRG with major complication or comorbidity increased for 15 of the top 20 reimbursed DRG families. This change was not accompanied by commensurate increases in disease severity but was associated with increased payment.


Estimation of laminar BOLD activation profiles using deconvolution with a physiological point spread function.
The specificity of gradient echo (GE)-BOLD laminar fMRI activation profiles is degraded by intracortical veins that drain blood from lower to upper cortical layers, propagating activation signal in the same direction. This work describes an approach to obtain layer specific profiles by deconvolving the measured profiles with a physiological Point Spread Function (PSF). It is shown that the PSF can be characterised by a TE-dependent peak to tail (p2t) value that is independent of cortical depth and can be estimated by simulation. An experimental estimation of individual p2t values and the sensitivity of the deconvolved profiles to variations in p2t is obtained using laminar data measured with a multi-echo 3D-FLASH sequence. These profiles are echo time dependent, but the underlying neuronal response is the same, allowing a data-based estimation of the PSF. The deconvolved profiles are highly similar to the gold-standard obtained from extremely high resolution 3D-EPI data, for a range of p2t values of 5-9, which covers both the empirically determined value (6.8) and the value obtained by simulation (6.3). -Comparison with Existing Method(s) Corrected profiles show a flatter shape across the cortex and a high level of similarity with the gold-standard, defined as a subset of profiles that are unaffected by intracortical veins. We conclude that deconvolution is a robust approach for removing the effect of signal propagation through intracortical veins. This makes it possible to obtain profiles with high laminar specificity while benefitting from the higher efficiency of GE-BOLD sequences.


Cost-Effectiveness Analysis of Syndesmotic Screw Versus Suture Button Fixation in Tibiofibular Syndesmotic Injuries.
To evaluate the cost effectiveness of suture buttons compared with syndesmotic screws for repair of tibiofibular syndesmotic injuries. A decision tree model was constructed to describe outcomes after syndesmosis repair using suture buttons and syndesmotic screws from the perspective of a capitated health care system. Outcomes were uneventful healing, removal of symptomatic implants, deep infection, and persistent diastasis requiring revision. Weighted literature averages were used to estimate variables for a baseline model. Outcomes were measured in quality adjusted life years. Procedure and implant costs were derived from Medicare reimbursement rates and the University Health System Consortium. An incremental cost-effectiveness ratio threshold of $50,000 per quality-adjusted life years was used to evaluate cost effectiveness. The baseline model did not identify suture buttons to be cost effective. Sensitivity analysis demonstrates the model to be exquisitely sensitive to small changes in reoperation rates and implant price. At median University Health System Consortium implant prices, if the removal rate for symptomatic screws is below 13.7%, then screws are cost effective. If the screw removal rate is greater than 17.5%, then a suture button is cost effective. Within this interval, detailed analysis of the model suggests that screws may be the cost-effective strategy, but that determination should be taken with caution. Moving away from the practice of routinely removing all syndesmotic screws has changed the financial landscape of syndesmosis repair. At their median cost, suture buttons are likely to be cost effective over screws for symptomatic screw removal rates greater than 17.5%. Cost effectiveness is sensitive to changes in implant removal rates and the number of devices used per patient. Economic Level IV. See Instructions for Authors for a complete description of levels of evidence.


[Biochemical characteristics of various adaptation mechanisms in acute alcoholic intoxication].
Phase character of metabolic shifts (ethanol, acetaldehyde, catecholamines content, alcohol dehydrogenase and aldehyde dehydrogenase activity) has been revealed in the experiments on white non-inbred rats after a single administration of a sub-narcotic dose of ethanol. Some adaptation-adjustment mechanisms have been established which promote the decrease of the toxic effect of alcohol (induction of activity of alcohol-metabolising enzymes and condensation of acetaldehyde with catecholamines).


Dietary fibre, diabetes and obesity.
An increased intake of dietary fibre appears to be useful for the treatment of both obesity and diabetes mellitus. Fibre-rich food is usually satisfying without being calorically dense. Supplementing a normal diet with gel-forming fibres, such as guar gum, leads to an increased satiation probably due to a slower gastric emptying. Recent long-term studies have confirmed the usefulness of viscous fibres as an adjunct to regular dietary treatment of obesity. Apart from a beneficial effect during caloric restriction, dietary fibre may improve some of the metabolic aberrations seen in obesity. Gel-forming fibres are particularly effective in reducing elevated LDL-cholesterol without changing the HDL-fraction. Impaired glucose tolerance or manifest diabetes is also improved. These effects are probably in part associated with the gelling property of the fibre which leads to an increased viscosity of the unstirred layer thereby delaying the absorption process. Other sources of dietary fibre with a high content of viscous gums, such as oats, have been shown to reduce LDL-cholesterol. Increased intake of viscous fibre leads to a gradual reduction in fasting glucose levels in diabetics. The reason for this is unclear but it cannot readily be explained by a delayed absorption process. Since insulin levels are also reduced these findings suggest that insulin resistance is alleviated. Recent studies with the euglycemic clamp technique support this possibility. Glucose uptake by isolated fat cells and both insulin sensitivity and responsiveness are also increased.


Cytomegalovirus is not an occupational risk for nurses in renal transplant and neonatal units. Results of a prospective surveillance study.
The risk of inpatient-to-nurse transmission of cytomegalovirus (CMV) was assessed in a five-year prospective seroepidemiologic study. We enrolled 263 renal transplant/hemodialysis nurses, 204 neonatal intensive care nurses, 225 student nurses, and 251 blood donor controls. Prevalence of CMV antibody in these 943 subjects was 33.7% and did not differ significantly among the four study groups. Sixteen subjects experienced primary CMV infections. The yearly seroconversion rate, calculated from age-related seroprevalence data, was 1.9%. The rate of seroconversion during the study, established by observing 519 seronegative subjects for 10 420 person-months, was 1.84% per year and did not differ significantly among the study groups. The proportions of patients with CMV infection (1.1% to 11.9%) and disease (0.5% to 3.4%) on study wards were not related to seroconversion in the nurses. The slow rate of acquisition of CMV in susceptible adults suggests that transmission requires prolonged, intimate contact. Nurses and nursing students who practice good personal hygiene are no more likely to acquire CMV than their peers in the community.


A Systematic Review and Meta-analysis of the Diagnostic Accuracy of Prostate Health Index and 4-Kallikrein Panel Score in Predicting Overall and High-grade Prostate Cancer.
Markers for prostate cancer (PCa) have progressed over recent years. In particular, the prostate health index (PHI) and the 4-kallikrein (4K) panel have been demonstrated to improve the diagnosis of PCa. We aimed to review the diagnostic accuracy of PHI and the 4K panel for PCa detection. We performed a systematic literature search of PubMed, EMBASE, Cochrane, and Academic One File databases until July 2016. We included diagnostic accuracy studies that used PHI or 4K panel for the diagnosis of PCa or high-grade PCa. The methodological quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Twenty-eight studies including 16,762 patients have been included for the analysis. The pooled data showed a sensitivity of 0.89 and 0.74 for PHI and 4K panel, respectively, for PCa detection and a pooled specificity of 0.34 and 0.60 for PHI and 4K panel, respectively. The derived area under the curve (AUC) from the hierarchical summary receiver operating characteristic (HSROC) showed an accuracy of 0.76 and 0.72 for PHI and 4K panel respectively. For high-grade PCa detection, the pooled sensitivity was 0.93 and 0.87 for PHI and 4K panel, respectively, whereas the pooled specificity was 0.34 and 0.61 for PHI and 4K panel, respectively. The derived AUC from the HSROC showed an accuracy of 0.82 and 0.81 for PHI and 4K panel, respectively. Both PHI and the 4K panel provided good diagnostic accuracy in detecting overall and high-grade PCa.


Biomechanical Features of Graphene-Augmented Inorganic Nanofibrous Scaffolds and Their Physical Interaction with Viruses.
Nanofibrous substrates and scaffolds are widely being studied as matrices for 3D cell cultures, and disease models as well as for analytics and diagnostic purposes. These scaffolds usually comprise randomly oriented fibers. Much less common are nanofibrous scaffolds made of stiff inorganic materials such as alumina. Well-aligned matrices are a promising tool for evaluation of behavior of biological objects affected by micro/nano-topologies as well as anisotropy. In this work, for the first time, we report a joint analysis of biomechanical properties of new ultra-anisotropic, self-aligned ceramic nanofibers augmented with two modifications of graphene shells (GAIN scaffolds) and their interaction of three different viral types (influenza virus A, picornavirus (human parechovirus) and potato virus). It was discovered that nano-topology and structure of the graphene layers have a significant implication on mechanical properties of GAIN scaffolds resulting in non-linear behavior. It was demonstrated that the viral adhesion to GAIN scaffolds is likely to be guided by physical cues in dependence on mutual steric factors, as the scaffolds lack common cell membrane proteins and receptors which viruses usually deploy for transfection. The study may have implications for selective viral adsorption, infected cells analysis, and potentially opening new tools for anti-viral drugs development.


Differential incision of bulky carcinogen-DNA adducts by the UvrABC nuclease: comparison of incision rates and the interactions of Uvr subunits with lesions of different structures.
The UvrABC nuclease system from Escherichia coli removes DNA damages induced by a wide range of chemical carcinogens with variable efficiencies. The interactions with UvrABC proteins of the following three lesions site-specifically positioned in DNA, and of known conformations, were investigated: (i) adducts derived from the binding of the (-)-(7S,8R,9R,10S) enantiomer of 7,8-dihydroxy-9, 10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene [(-)-anti-BPDE] by cis-covalent addition to N(2)-2'-deoxyguanosine [(-)-cis-anti-BP-N(2)-dG], (ii) an adduct derived from the binding of the (+)-(1R,2S,3S,4R) enantiomer of 1,2-dihydroxy-3,4-epoxy-1,2,3, 4-tetrahydro-5-methylchrysene [(+)-anti-5-MeCDE] by trans addition to N(2)-2'-deoxyguanosine [(+)-trans-anti-MC-N(2)-dG], and (iii) a C8-2'-deoxyguanosine adduct (C8-AP-dG) formed by reductively activated 1-nitropyrene (1-NP). The influence of these three different adducts on UvrA binding affinities, formation of UvrB-DNA complexes by quantitative gel mobility shift analyses, and the rates of UvrABC incision were investigated. The binding affinities of UvrA varied among the three adducts. UvrA bound to the DNA adduct (+)-trans-anti-MC-N(2)-dG with the highest affinity (K(d) = 17 +/- 2 nM) and to the DNA containing C8-AP-dG with the least affinity (K(d) = 28 +/- 1 nM). The extent of complex formation with UvrB was also the lowest with the C8-AP-dG adduct. 5' Incisions occurred at the eighth phosphate from the modified guanine. The major 3' incision site corresponded to the fifth phosphodiester bond for all three adducts. However, additional 3' incisions were observed at the fourth and sixth phosphates in the case of the C8-AP-dG adduct, whereas in the case of the (-)-cis-anti-BP-N(2)-dG and (+)-trans-anti-MC-N(2)-dG lesions additional 3' cleavage occurred at the sixth and seventh phosphodiester bonds. Both the initial rate and the extent of 5' and 3' incisions revealed that C8-AP-dG was repaired less efficiently in comparison to the (-)-cis-anti-BP-N(2)-dG and (+)-trans-anti-MC-N(2)-dG containing DNA adducts. Our study showed that UvrA recognizes conformational changes induced by structurally different lesions and that in certain cases the binding affinities of UvrA and UvrB can be correlated with the incision rates. The size of the bubble formed around the damaged site with mismatched bases also appears to influence the incision rates. A particularly noteworthy finding in this study is that UvrABC repair of a substrate with no base opposite C8-AP-dG was quite inefficient as compared to the same adduct with a C opposite it. These findings are discussed in terms of the available NMR solution structures.


Environmental inequities and low birth weight.
The effects of environmental exposures to toxic agents, are related to different levels of exposure, genetic and biological susceptibility, risk perception and socioeconomic status (SES). In the present study we suggest that environmental influences on human reproduction should include investigations on SES, that can play an important role in embryo-foetal development. Low birth weight (LBW) is a risk factor for developing in adulthood coronary hearth disease, hypertension and type 2 diabetes. Maternal nutritional status and other hypothesis could explain LBW, however, environmental exposures are recognised as essential risk factors. Different studies evidenced an increased risk of LBW in relation to increased environmental air levels of particulate matter, carbon monoxide, and sulphur dioxide. Considering different risk possibilities and different risk perceptions, there is a need of a different scientific approach in which the scientific knowledge is connected with ethical and socioeconomic factors, for risk management, in order to overcome the environmental health inequities based on social contest.


Transcriptional regulation of Mycobacterium tuberculosis hupB gene expression.
The influence of iron levels on the transcription of the hupB gene in Mycobacterium tuberculosis is the focus of this study. Studies in our laboratory showed HupB to be co-expressed with the two siderophores in low-iron organisms. Mycobactin biosynthesis is repressed by the IdeR-Fe(2+) complex that binds the IdeR box in the mbtB promoter. Recently, we demonstrated the positive regulatory effect of HupB on mycobactin biosynthesis by demonstrating its binding to a 10 bp HupB box in the mbtB promoter. Earlier, we observed that HupB, expressed maximally in low-iron media (0.02 µg Fe ml(-1); 0.36 µM Fe) was still detectable at 8 µg Fe ml(-1) (144 µM Fe) when the siderophores were absent and complete repression was seen only at 12 µg Fe ml(-1) (216 µM Fe). In this study, we observed elevated levels of hupB transcripts in iron-limited organisms. IdeR, and not FurA, functioned as the iron regulator, by binding to two IdeR boxes in the hupB promoter. Interestingly, the 10 bp HupB box, first reported in the mbtB promoter, was identified in the hupB promoter. Using DNA footprinting and electrophoretic mobility shift assays, we demonstrated the functionality of the HupB box and the two IdeR boxes. The high hupB transcript levels expressed by the organism and the in vitro protein-DNA interaction studies led us to hypothesize the sequence of events occurring in response to changes in the intracellular iron concentration, emphasizing the roles played by IdeR and HupB in iron homeostasis.


Nonlinear pressure-flow relationship is able to detect asymmetry of brain blood circulation associated with midline shift.
Reliable and noninvasive assessment of cerebral blood flow regulation is a major challenge in acute care monitoring. This study assessed dynamics of flow regulation and its relationship to asymmetry of initial computed tomography (CT) scan using multimodal pressure flow (MMPF) analysis. Data of 27 patients (38 +/- 15 years old) with traumatic brain injury (TBI) were analyzed. Patients were selected from bigger cohort according to criteria of having midline shift on initial CT scan and intact skull (no craniotomy or bone flap). The MMPF analysis was used to extract the oscillations in cerebral perfusion pressure (CPP) and blood flow velocity (BFV) signals at frequency of artificial ventilation, and to calculate the instantaneous phase difference between CPP and BFV oscillations. Mean CPP-BFV phase difference was used to quantify pressure and flow relationship. The TBI subjects had smaller mean BP-BFV phase shifts (left, 8.7 +/- 9.6; right 10.2 +/- 8.3 MCAs, mean +/- SD) than values previously obtained in healthy subjects (left, 37.3 +/- 7.6 degrees; right, 38.0 +/- 8.9 degrees; p < 0.0001), suggesting impaired blood flow regulation after TBI. The difference in phase shift between CPP and BFV in the left and right side was strongly correlated to the midline shift (R = 0.78; p < 0.0001). These findings indicate that the MMPF method allows reliable assessment of alterations in pressure and flow relationship after TBI. Moreover, mean pressure-flow phase shift is sensitive to the displacement of midline of the brain, and may potentially serve as a marker of asymmetry of cerebral autoregulation.


A comparison of composite post buildups and cast gold post-and-core buildups for the restoration of nonvital teeth after 5 to 10 years.
The aim of this study was to compare the cumulative survival rates and the complication rates of established methods of indirect cast posts and cores and direct posts and composite cores over at least 5 years within a retrospective study of patients who received fixed restorations. The patients were questioned according to a protocol and were examined clinically and radiologically. Of the 101 patients who were recruited, 72 came for a follow-up examination. Forty-one cast posts and cores and 31 composite cores were examined clinically and radiologically after an average observation period of 8.56 (SD 1.45) years. Four teeth were extracted during the observation period, and 2 more were extracted at the time of the examination. This resulted in cumulative survival rates of 90.2% for cast posts and cores and 93.5% for composite cores. There were 28 complications altogether, consisting of 2 (7.1%) root fractures, 8 (28.6%) teeth with increased probing depths, 3 (10.7%) with increased degrees of mobility, 4 (14.3%) with caries, 9 (32.1%) with periapical radiolucency and/or retrograde filling, and 2 (7.1%) with loss of retention. No statistically significant differences between the 2 methods could be found regarding survival and complication rates. It can be concluded that over an average observation period of 8.56 years the indirect cast post-and-core buildup and the direct composite post buildup can be considered of similar value.


Abnormal topological organization in white matter structural networks revealed by diffusion tensor tractography in unmedicated patients with obsessive-compulsive disorder.
Obsessive-compulsive disorder (OCD) is a chronic psychiatric disorder defined by recurrent thoughts, intrusive and distressing impulses, or images and ritualistic behaviors. Although focal diverse regional abnormalities white matter integrity in specific brain regions have been widely studied in populations with OCD, alterations in the structural connectivities among them remain poorly understood. The aim was to investigate the abnormalities in the topological efficiency of the white matter networks and the correlation between the network metrics and Yale-Brown Obsessive-Compulsive Scale scores in unmedicated OCD patients, using diffusion tensor tractography and graph theoretical approaches. This study used diffusion tensor imaging and deterministic tractography to map the white matter structural networks in 26 OCD patients and 39 age- and gender-matched healthy controls; and then applied graph theoretical methods to investigate abnormalities in the global and regional properties of the white matter network in these patients. The patients and control participants both showed small-world organization of the white matter networks. However, the OCD patients exhibited significant abnormal global topology, including decreases in global efficiency (t = -2.32, p = 0.02) and increases in shortest path length, Lp (t = 2.30, p = 0.02), the normalized weighted shortest path length, λ (t = 2.08, p=0.04), and the normalized clustering coefficient, γ (t = 2.26, p = 0.03), of their white matter structural networks compared with healthy controls. Further, the OCD patients showed a reduction in nodal efficiency predominately in the frontal regions, the parietal regions and caudate nucleus. The normalized weighted shortest path length of the network metrics was significantly negatively correlated with obsessive subscale of the Yale-Brown Obsessive-Compulsive Scale (r = -0.57, p = 0.0058). These findings demonstrate the abnormal topological efficiency in the white matter networks in OCD patients.


Iron Magnetic Nanoparticle-Induced ROS Generation from Catechol-Containing Microgel for Environmental and Biomedical Applications.
Reactive oxygen species (ROS) can degrade organic compounds and function as a broad-spectrum disinfectant. Here, dopamine methacrylamide (DMA) was used to prepare catechol-containing microgels, which can release ROS via metal-catechol interaction. A combination of the microgel and iron magnetic nanoparticle (FeMNP) significantly reduced the concentration of four organic dyes (Alizarin Red S, Rhodamine B, Crystal Violet, and Malachite Green) and an antibiotic drug, ciprofloxacin, dissolved in solution. Degradation of dye occurred across a wide range of pH levels (pH 3-9). This simple combination was also antimicrobial against both Escherichia coli and Staphylococcus aureus. Electron paramagnetic resonance spectroscopy (EPR) results indicate that singlet oxygen was generated during the reaction between catechol and FeMNP at both pH 3 and 7.4, which was responsible for the degradation of organic compounds and bactericidal features of the microgel. Unlike autoxidation that only occurs at a neutral to basic pH, FeMNP-induced catechol oxidation generated singlet oxygen over a wide range of pH level. Additionally, catechol chelates heavy metal ions, resulting in their removal from solution and repurposed these metal ions for dye degradation. This multifunctional microgel can potentially be used for environmental applications for the removal of organic pollutants and heavy metal ions from wastewater, as well as reducing bacterial infection in biomedical applications.


There's more than one way to build a medical home.
The patient-centered medical home (PCMH) is a critical aspect of delivery system reform. The purpose of this study was to examine variations in achievement of PCMH requirements across different types of practices. We used data on the points awarded, by standard and element, to 2369 practices recognized by September 2013 under the National Committee for Quality Assurance PCMH program, 2011 version. We tested for differences across practice types in the percentage of practices achieving full credit for 27 element scores using likelihood ratio χ2 tests with an adjustment for multiple comparisons. Of the practices, 45% were affiliated with health systems, 22.6% were community health centers, and 5.3% were military treatment facilities. The remaining practices were physician-owned, 10% with at least 5 clinicians and 17.3% with less than 5. Even among Level 3 practices, there were significant differences across the practice types in the percentage of practices achieving full credit for 19 of 27 elements. Different types of practices demonstrated strengths in different medical home capabilities. Even among practices with the highest level of PCMH achievement, there are variations in key medical home capabilities. While research is needed to identify PCMH components having the greatest impact on outcomes, this research shows that the NCQA model is flexible enough to adapt to the strengths and needs of practices and the patients they serve. Efforts to support widespread dissemination of the PCMH model and practice transformation should recognize and build on these variations.


Suppression of LPS-induced inflammatory responses by the hydroxyl groups of dexamethasone.
The innate immune response is a central process that is activated during pathogenic infection in order to maintain physiological homeostasis. It is well known that dexamethasone (Dex), a synthetic glucocorticoid, is a potent immunosuppressant that inhibits the cytokine production induced by bacterial lipopolysaccharides (LPS). Nevertheless, the extent to which the functional groups of Dex control the excessive activation of inflammatory reactions remains unknown. Furthermore, importantly, the role of Dex in the innate immune response remains unclear. Here we explore the mechanism of LPS-induced TNF-α secretion and reveal p38 MAPK signaling as a target of Dex that is involved in control of tumor necrosis factor-α (TNF-α)-converting enzyme (TACE) activity; that later mediates the shedding of TNF-α that allows its secretion. We further demonstrate that the 11-hydroxyl and 21-hydroxyl groups of Dex are the main groups that are involved in reducing LPS-induced TNF-α secretion by activated macrophages. Blockage of the hydroxyl groups of Dex inhibits immunosuppressant effect of Dex during LPS-induced TNF-α secretion and mouse mortality. Our findings demonstrate Dex signaling is involved in the control of innate immunity.


Enhancement of cell viability after treatment with polyunsaturated fatty acids.
Attention-deficit/hyperactivity disorder (ADHD) is highly prevalent in children and adolescents and both environmental and genetic factors play major roles. Polyunsaturated fatty acids (PUFAs) are postulated to contribute to the development of the infant brain and an imbalance in these may increase the risk of ADHD. In recent clinical studies, supplementation with PUFAs improved symptoms of ADHD in some cases. Similarly, some beneficial effects were observed with PUFA treatment in neuronal cell cultures. Therefore, in this study, we hypothesized that a specific PUFA combination (available on the market as Equazen™ [Vifor Pharma, Switzerland]) along with iron, zinc, or vitamin B5 (vitB5) would produce an additive beneficial effect on the viability of rat pheochromocytoma-12 dopaminergic cells. The specific PUFA combination alone, as well as added to each of the three nutrients, was tested in a dose-response manner. The specific PUFAs significantly improved cell viability, starting at very low doses (100pM) from 60h up to 90h; while the combined treatment with vitB5 and minerals did not provide additional benefit. Our results confirmed the beneficial effect of the specific PUFAs on neuronal cell viability; although supplementation with minerals and vitB5 did not enhance this effect.


Rhinovirus infection preferentially increases lower airway responsiveness in allergic subjects.
Rhinovirus (RV) infections are important triggers of acute asthma symptoms in susceptible persons. To determine whether the presence of allergy is a risk factor for enhanced lower airway effects during RV infection, we experimentally infected (RV16) 18 volunteers with allergic rhinitis and 13 normal control subjects and measured the effects on the response of the lower airways to histamine. All subjects were successfully infected, as indicated by increased upper respiratory symptoms and RV16 cultured from nasal secretions. The change in histamine PD20(deltaPD20) caused by RV infection was significantly different in allergic subjects from that in nonallergic control subjects (deltaPD20 = -0.40 versus -0.03 log units, p = 0.04). This relationship was strengthened after adjusting for initial PD20 and FEV1 (mean deltaPD20 = -0.43 versus 0.01 log units, p < 0.01). The virus-induced deltaPD20 was also influenced by baseline lung function: there was a positive correlation between initial FEV1 and deltaPD20, and a weak but significant negative correlation between baseline PD20 and deltaPD20. These findings indicate that host factors such as allergy, baseline FEV1, and baseline PD20 influence the changes in lower airway physiology caused by RV infection and raise the possibility that these factors contribute to the increased lower airway effects of RV infection in subjects with asthma.


Loganin attenuates diabetic nephropathy in C57BL/6J mice with diabetes induced by streptozotocin and fed with diets containing high level of advanced glycation end products.
Diabetic nephropathy is the most common cause of end-stage renal disease in patients with diabetes. Advanced glycation end-products (AGEs) play a prominent role in the development of diabetic nephropathy. We herein evaluated the effects of loganin on diabetic nephropathy in vivo. We established a diabetic nephropathy model in C57BL/6J mice with diabetes induced by streptozotocin and fed with diets containing high level of AGEs. Diabetic symptoms, renal functions, and pathohistology of pancreas and kidney were evaluated. AGE-RAGE pathway and oxidative stress parameters were determined. The model mice exhibited characteristic symptoms of diabetes including weight loss, polydipsia, polyphagia, polyuria, elevated blood glucose levels and low serum insulin levels during the experiments. However, loganin at doses of 0.02 and 0.1g/kg effectively improved these diabetic symptoms. Loganin reduced kidney/body weight ratio, 24h urine protein levels, and serum levels of urea nitrogen and creatinine in diabetic mice to different degrees compared to positive controls. Moreover, loganin improved the histology of pancreas and kidney, and alleviated the structural alterations in endothelial cells, mesangial cells and podocytes in renal cortex. Finally, we found that loganin reduced AGE levels in serum and kidney and downregulated mRNA and protein expression of receptors for AGEs in kidney in diabetic mice. Loganin also reduced the levels of malondialdehyde and increased the levels of superoxide dismutase in serum and kidney. Loganin improved diabetic nephropathy in vivo associated with inhibition of AGE pathways, and could be a promising remedy for diabetic nephropathy.


Enhancement of endothelial function inhibits left atrial thrombi development in an animal model of spontaneous left atrial thrombosis.
Left atrial (LA) thrombosis is an important cause of systemic embolization. The SPORTS rat model of LA thrombi (Spontaneously-Running Tokushima-Shikoku), which have a unique characteristic of high voluntary wheel running, was previously established. The aim of the present study was to investigate how SPORTS rats develop LA thrombi. Nitric oxide (NO) produced from cardiovascular endothelial cells plays an important protective role in the local regulation of blood flow, vascular tone, and platelet aggregation. No evidence of atrial fibrillation or hypercoagulability in SPORTS rats regardless of age was found; however, SPORTS rats demonstrated endothelial dysfunction and a decrease of NO production from a young age. In addition, endothelial NO synthase activity was significantly decreased in the LA and thoracic aorta endothelia of SPORTS rats. While voluntary wheel running was able to intermittently increase NO levels, running did not statistically decrease the incidence of LA thrombi at autopsy. However, L-arginine treatment significantly increased NO production and provided protection from the development of LA thrombi in SPORTS rats. They present study results indicate that NO has an important role in the development of LA thrombus, and endothelia pathways could provide new targets of therapy to prevent LA thrombosis.


Migration of Entamoeba histolytica under agarose.
A procedure for visualizing and quantifying motility of Entamoeba histolytica by migration under agarose is described. Agarose suspended in tissue culture medium 199 supplemented with bovine albumin was poured into plastic dishes and allowed to harden. Six pairs of wells were cut out in a circular configuration. To the inner wells a suspension of E. histolytica in Eagle's Medium (24 X 10(6) cells/ml) was added, and to the outer wells a chemoattractant or the control medium. After overnight incubation at 37 degrees C, the amebae were fixed and stained. The chemotactic and spontaneous migrations were measured in an enlarging projector. Escherichia coli filtrates, suspensions of intact and lysed erythrocytes, and the complement factor C5a acted as good chemoattractants. Both the random and chemotactic motility were correlated to the time of the incubation. Cytochalasin B effected a dose-related inhibition of both chemotactic and random migration, while colchicine caused a decrease of the chemotaxis only. The reproducibility of the method, measured by 10 intra-assay tests, was good. Thus, the described method can be useful for comparative determinations of the motility of different ameba populations. Furthermore, different factors affecting the motility of amebae can be studied.


A Demonstration of Le Chatelier's Principle on the Nanoscale.
Photothermal desorption of molecules from plasmonic nanoparticles is an example of a light-triggered molecular release due to heating of the system. However, this phenomenon ought to work only if the molecule-nanoparticle interaction is exothermic in nature. In this study, we compare protein adsorption behavior onto gold nanoparticles for both endothermic and exothermic complexation reactions, and demonstrate that Le Chatelier's principle can be applied to predict protein adsorption or desorption on nanomaterial surfaces. Polyelectrolyte-wrapped gold nanorods were used as adsorption platforms for two different proteins, which we were able to adsorb/desorb from the nanorod surface depending on the thermodynamics of their interactions. Furthermore, we show that the behaviors hold up under more complex biological environments such as fetal bovine serum.


Augmenting responses evoked in area 17 of the cat by intracortical axon collaterals of cortico-geniculate cells.
Evoked potentials were recorded in the visual cortex of the cat after electrical stimulation of the lateral geniculate nucleus (l.g.n.). The primary response, mediated by geniculo-cortical fibres, was depressed at stimulation frequencies above 7 Hz and replaced by a late potential, the incremental response, which gradually increased in amplitude with successive stimuli. The incremental response was a negative-positive potential in the depth of the cortex with the negative component having maximal amplitude in layer 4. The response reversed polarity in layer 1 to become a positive-negative potential at the surface. The latency of the negative component of the incremental response was about 3.5-4 ms in layer 4, compared to about 1.5 and 2.5 ms for the mono- and disynaptic components of the primary response. The incremental response could only be evoked from the l.g.n. and the optic radiation, not from the optic tract, superior colliculus or other surrounding structures. Within the l.g.n., the effect was only evoked from stimulation sites in approximate retinotopic register with the recording site in the cortex. Low threshold points were found in the A laminae, completely overlapping with the low threshold points for the primary response. Thresholds increased steeply when the stimulation electrode was lowered into the C laminae. The incremental response could still be evoked ten days after the destruction of all cells in the l.g.n. complex by kainic acid. It is concluded that the described incremental response is identical to the augmenting response of Dempsey & Morison (1943) and is mediated by intracortical axon collaterals of antidromically activated cortico-geniculate neurones.


Cloning and characterization of Physarum polycephalum tectonins. Homologues of Limulus lectin L-6.
Previous investigators have reported the presence of two dominant proteins, tectonin I (25 kDa) and tectonin II (39 kDa), in nuclei and nuclear matrix from plasmodia of Physarum polycephalum. We demonstrate, by a modification of the nuclear isolation protocol and by protease sensitivity, that the tectonins are not nuclear proteins but rather are located on the exterior surface of the plasma membrane. We report the sequences of cDNAs of tectonins I and II, which encode 217 and 353 amino acids, respectively. Tectonin I is homologous to the C-terminal two-thirds of tectonin II. Both proteins contain six tandem repeats that are each 33-37 amino acids in length and define a new consensus sequence. Homologous repeats are found in L-6, a bacterial lipopolysaccharide-binding lectin from horseshoe crab hemocytes. The repetitive sequences of the tectonins and L-6 are reminiscent of the WD repeats of the beta-subunit of G proteins, suggesting that they form beta-propeller domains. Tectonin II has an additional N-terminal domain that includes a 47-residue sequence highly similar to the galactoside-binding sequence of the B-chain of ricin. The tectonins may be lectins that function as part of a transmembrane signaling complex during phagocytosis.


Toward a Model of Social Influence that Explains Minority Student Integration into the Scientific Community.
Students from several ethnic minority groups are underrepresented in the sciences, such that minority students more frequently drop out of the scientific career path than non-minority students. Viewed from a perspective of social influence, this pattern suggests that minority students do not integrate into the scientific community at the same rate as non-minority students. Kelman (1958, 2006) describes a tripartite integration model of social influence (TIMSI) by which a person orients to a social system. To test if this model predicts integration into the scientific community, we conducted analyses of data from a national panel of minority science students. A structural equation model framework showed that self-efficacy (operationalized consistent with Kelman's 'rule-orientation') predicted student intentions to pursue a scientific career. However, when identification as a scientist and internalization of values are added to the model, self-efficacy becomes a poorer predictor of intention. Additional mediation analyses support the conclusion that while having scientific self-efficacy is important, identifying with and endorsing the values of the social system reflect a deeper integration and more durable motivation to persist as a scientist.


Late blockade of T cell costimulation interrupts progression of experimental chronic allograft rejection.
Early blockade of T cell-costimulatory activation pathways prevents development of experimental chronic allograft rejection. Ongoing T cell recognition of alloantigen and activation may also play an important role in progression of chronic rejection, but definitive evidence is lacking. We used the fusion protein CTLA4Ig to block CD28-B7 T cell costimulation late after the onset of initial graft injury. Using the F334 into LEW rat model of chronic renal allograft rejection, transplant recipients were treated with a 10-d course of cyclosporine, and a subgroup received a single injection of CTLA4Ig at 8 wk after transplant. Functionally, CTLA4Ig administration prevented development of progressive proteinuria (14.3+/-4.1 mg/24 h versus 41.0+/-12.0 mg/24 h at 24 wk after transplant, P < 0.05). Histologically, graft mononuclear cell infiltration, glomerular hypertrophy, focal and segmental glomerulosclerosis, and intimal vascular hyperplasia were all attenuated in CTLA4Ig-treated animals. Lastly, reverse transcriptase-PCR and immunohistologic studies showed a significant reduction in the intragraft expression of key products of T cell and macrophage activation, and upregulation of what have recently been termed as "protective" genes, including the bcl family members, Bcl-2 and Bcl-xL, and hemoxygenase. Our data are the first to demonstrate that blocking T cell-costimulatory activation late after transplantation, after initial graft injury, prevents progression of chronic allograft rejection supporting the hypothesis that ongoing T cell recognition of alloantigen and activation are key mediators of ongoing chronic allograft rejection.


Ectromelia virus-induced changes in primary cultures of mouse hepatocytes.
Mouse hepatocytes were isolated by collagenase perfusion, maintained in non-proliferating monolayer culture and shown to retain liver cell function as judged by gluconeogenesis for 15 to 18 h. Such cells could be infected with and support the replication of a virulent strain of ectromelia virus. Virus antigen and characteristic cytoplasmic 'B'-type poxvirus inclusion bodies were demonstrated by immunofluorescence in virtually all cells. By electron microscopy it was shown that 'B'-type inclusions were the site of virus replication, and that the biogenesis of ectromelia virus and ultrastructural changes in hepatocytes were similar to those observed in infected mouse livers. Early cell rounding effects, a normal characteristic of poxvirus infections in tissue culture cells, were not seen in ectromelia-infected hepatocytes, although late degenerative changes did occur. Pulse-labelling of hepatocyte cultures with [35S]methionine showed that ectromelia virus inhibited the rise in protein synthesis seen in controls and imposed a gradual decline in host protein synthesis to an extent and at a rate significantly different from that in mouse L929 cells. Gluconeogenesis was inhibited by ectromelia virus infection of hepatocytes.


Henoch-Schölein purpura and polysaccharide meningococcal vaccine.
We describe here a case of Henoch-Schönlein purpura (HSP) that occurred 10 days after administration of the meningococcal polysaccharide vaccine and came to the attention of a Vaccine Safety Datalink (VSD) investigator (but did not occur in the VSD cohort). Periodic case reports have linked vaccines to HSP. To better understand the potential risk for HSP after immunization with the meningococcal polysaccharide vaccine. We studied the VSD cohort to estimate the 42-day postvaccination incidence rate of HSP in the VSD population 16 to 20 years of age. Electronic data from all 8 VSD sites were gathered. All subjects aged 16 to 20 years who received a meningococcal polysaccharide vaccine were followed for 42 days after that vaccination for evidence of HSP. Background rates were determined by examining all the nonexposed time of the same cohort. No cases of HSP were seen in the 42 days after 49,027 doses of meningococcal polysaccharide vaccine among the entire VSD adolescent and young adult population. The background incidence rate was 4.2 per 100,000 person-years. These data provide the strongest evidence so far that HSP is not associated with receipt of meningococcal polysaccharide vaccine in the 16- to 20-year age group.


Reducing and correcting for contamination of ecosystem water stable isotopes measured by isotope ratio infrared spectroscopy.
Concern exists about the suitability of laser spectroscopic instruments for the measurement of the (18)O/(16)O and (2)H/(1)H values of liquid samples other than pure water. It is possible to derive erroneous isotope values due to optical interference by certain organic compounds, including some commonly present in ecosystem-derived samples such as leaf or soil waters. Here we investigated the reliability of wavelength-scanned cavity ring-down spectroscopy (CRDS) (18)O/(16)O and (2)H/(1)H measurements from a range of ecosystem-derived waters, through comparison with isotope ratio mass spectrometry (IRMS). We tested the residual of the spectral fit S(r) calculated by the CRDS instrument as a means to quantify the difference between the CRDS and IRMS δ-values. There was very good overall agreement between the CRDS and IRMS values for both isotopes, but differences of up to 2.3‰ (δ(18)O values) and 23‰ (δ(2)H values) were observed in leaf water extracts from Citrus limon and Alnus cordata. The S(r) statistic successfully detected contaminated samples. Treatment of Citrus leaf water with activated charcoal reduced, but did not eliminate, δ(2)H(CRDS) - δ(2)H(IRMS) linearly for the tested range of 0-20% charcoal. The effect of distillation temperature on the degree of contamination was large, particularly for δ(2)H values but variable, resulting in positive, negative or no correlation with distillation temperature. S(r) and δ(CRDS) - δ(IRMS) were highly correlated, in particular for δ(2)H values, across the range of samples that we tested, indicating the potential to use this relationship to correct the δ-values of contaminated plant water extracts. We also examined the sensitivity of the CRDS system to changes in the temperature of its operating environment. We found that temperature changes ≥4 °C for δ(18)O values and ≥10 °C for δ(2)H values resulted in errors larger than the CRDS precision for the respective isotopes and advise the use of such instruments only in sufficiently temperature-stabilised environments.


Computer Use and Computer Anxiety in Older Korean Americans.
Responding to the limited literature on computer use in ethnic minority older populations, the present study examined predictors of computer use and computer anxiety in older Korean Americans. Separate regression models were estimated for computer use and computer anxiety with the common sets of predictors: (a) demographic variables (age, gender, marital status, and education), (b) physical health indicators (chronic conditions, functional disability, and self-rated health), and (c) sociocultural factors (acculturation and attitudes toward aging). Approximately 60% of the participants were computer-users, and they had significantly lower levels of computer anxiety than non-users. A higher likelihood of computer use and lower levels of computer anxiety were commonly observed among individuals with younger age, male gender, advanced education, more positive ratings of health, and higher levels of acculturation. In addition, positive attitudes toward aging were found to reduce computer anxiety. Findings provide implications for developing computer training and education programs for the target population.


Outcome of cardiac tamponades in interventional electrophysiology.
The aim of this study was to analyse tamponades following electrophysiological procedures regarding frequency and mortality in a high-volume centre and to identify independent predictors for severe tamponades. We performed a retrospective study on 34 982 consecutive patients undergoing diagnostic electrophysiological studies or catheter ablation of cardiac arrhythmias. The combined endpoint was defined as severe tamponade. Criteria for severe tamponade included surgical repair, repeat pericardiocentesis, cardiopulmonary resuscitation, intrahospital death or death during follow-up, and thrombo-embolic events or complications due to therapeutic management. Multivariate analysis was performed to identify independent predictors for severe tamponade. A total of 226 tamponades were identified. Overall frequency of tamponades was 0.6%. Procedures requiring epicardial approach had the highest rate of tamponades (9.4%). Twenty-nine patients with tamponade underwent surgery (12.8% of all tamponades and 21.4% of tamponades during epicardial procedures). Overall tamponade-related mortality was 0.03% (9 deaths). Fifty-six patients (24.8%) experienced severe tamponade. Independent risk factors for severe tamponades were endocardial ablation of ventricular tachycardia, epicardial approach, balloon device ablation, high aspiration volume during pericardiocentesis and structural heart disease. The frequency of tamponades is strongly dependent on the type of procedure performed. Overall tamponade-related mortality was low but significantly higher in patients undergoing epicardial procedures. Surgical backup should be considered for patients undergoing complex ventricular tachycardia ablation and left atrial ablation procedures.