Immunogenicity and safety of fractional doses of yellow fever vaccines: a randomised, double-blind, non-inferiority trial.
Stocks of yellow fever vaccine are insufficient to cover exceptional demands for outbreak response. Fractional dosing has shown efficacy, but evidence is limited to the 17DD substrain vaccine. We assessed the immunogenicity and safety of one-fifth fractional dose compared with standard dose of four WHO-prequalified yellow fever vaccines produced from three substrains. We did this randomised, double-blind, non-inferiority trial at research centres in Mbarara, Uganda, and Kilifi, Kenya. Eligible participants were aged 18-59 years, had no contraindications for vaccination, were not pregnant or lactating, had no history of yellow fever vaccination or infection, and did not require yellow fever vaccination for travel. Eligible participants were recruited from communities and randomly assigned to one of eight groups, corresponding to the four vaccines at standard or fractional dose. The vaccine was administered subcutaneously by nurses who were not masked to treatment, but participants and other study personnel were masked to vaccine allocation. The primary outcome was proportion of participants with seroconversion 28 days after vaccination. Seroconversion was defined as post-vaccination neutralising antibody titres at least 4 times pre-vaccination measurement measured by 50% plaque reduction neutralisation test (PRNT50). We defined non-inferiority as less than 10% decrease in seroconversion in fractional compared with standard dose groups 28 days after vaccination. The primary outcome was measured in the per-protocol population, and safety analyses included all vaccinated participants. This trial is registered with ClinicalTrials.gov, NCT02991495. Between Nov 6, 2017, and Feb 21, 2018, 1029 participants were assessed for inclusion. 69 people were ineligible, and 960 participants were enrolled and randomly assigned to vaccine manufacturer and dose (120 to Bio-Manguinhos-Fiocruz standard dose, 120 to Bio-Manguinhos-Fiocruz fractional dose, 120 to Chumakov Institute of Poliomyelitis and Viral Encephalitides standard dose, 120 to Chumakov Institute of Poliomyelitis and Viral Encephalitides fractional dose, 120 to Institut Pasteur Dakar standard dose, 120 to Institut Pasteur Dakar fractional dose, 120 to Sanofi Pasteur standard dose, and 120 to Sanofi Pasteur fractional dose). 49 participants had detectable PRNT50 at baseline and 11 had missing PRNT50 results at baseline or 28 days. 900 were included in the per-protocol analysis. 959 participants were included in the safety analysis. The absolute difference in seroconversion between fractional and standard doses by vaccine was 1·71% (95% CI -2·60 to 5·28) for Bio-Manguinhos-Fiocruz, -0·90% (-4·24 to 3·13) for Chumakov Institute of Poliomyelitis and Viral Encephalitides, 1·82% (-2·75 to 5·39) for Institut Pasteur Dakar, and 0·0% (-3·32 to 3·29) for Sanofi Pasteur. Fractional doses from all four vaccines met the non-inferiority criterion. The most common treatment-related adverse events were headache (22·2%), fatigue (13·7%), myalgia (13·3%) and self-reported fever (9·0%). There were no study-vaccine related serious adverse events. Fractional doses of all WHO-prequalified yellow fever vaccines were non-inferior to the standard dose in inducing seroconversion 28 days after vaccination, with no major safety concerns. These results support the use of fractional dosage in the general adult population for outbreak response in situations of vaccine shortage. The study was funded by Médecins Sans Frontières Foundation, Wellcome Trust (grant no. 092654), and the UK Department for International Development. Vaccines were donated in kind.


Synthesis and properties of the very-low-density-lipoprotein receptor and a comparison with the low-density-lipoprotein receptor.
The properties of the very-low-density lipoprotein (VLDL) receptor have been studied in Chinese hamster ovary (CHO) cells stably transfected with human VLDL-receptor cDNA and compared with those of the low-density lipoprotein (LDL) receptor expressed under the same conditions. Immunoblotting showed that the cells produced a mature VLDL receptor protein, of apparent Mr 123000 on non-reduced and 158000 on reduced gels, that was less extensively glycosylated than the LDL receptor. The VLDL receptor was more slowly processed than the LDL receptor, with only approx. 70% of the precursor being converted into the mature protein. Nevertheless, the majority of the receptor in the cells was in the mature form, and most of this was present on the cell surface. The human VLDL receptor bound rabbit very-low-density lipoprotein with beta electrophoretic mobility (betaVLDL), but not human LDL, and uptake through the receptor led to stimulation of oleate incorporation into cholesteryl esters. At 37 degrees C, the characteristics of VLDL-receptor-mediated uptake and degradation of betaVLDL were essentially the same as those mediated by the LDL receptor. However, the VLDL receptor apparently did not show the increase in affinity and decrease in binding of betaVLDL on cooling to 4 degrees C that was exhibited by the LDL receptor. Thus the overexpressed VLDL receptor in CHO cells appears to behave as a lipoprotein receptor with similar, but not identical, properties to the LDL receptor.


Adherence to Artemisinin Combination Therapy for the treatment of uncomplicated malaria in the Democratic Republic of the Congo.
Between 2011 and 2013 the number of recorded malaria cases had more than doubled, and between 2009 and 2013 had increased almost 4-fold in MSF-OCA (Médecins sans Frontières - Operational Centre Amsterdam) programmes in the Democratic Republic of the Congo (DRC). The reasons for this rise are unclear. Incorrect intake of Artemisinin Combination Therapy (ACT) could result in failure to treat the infection and potential recurrence. An adherence study was carried out to assess whether patients were completing the full course of ACT. One hundred and eight malaria patients in Shamwana, Katanga province, DRC were visited in their households the day after ACT was supposed to be completed. They were asked a series of questions about ACT administration and the blister pack was observed (if available). Sixty seven (62.0%) patients were considered probably adherent. This did not take into account the patients that vomited or spat their pills or took them at the incorrect time of day, in which case adherence dropped to 46 (42.6%). The most common reason that patients gave for incomplete/incorrect intake was that they were vomiting or felt unwell (10 patients (24.4%), although the reasons were not recorded for 22 (53.7%) patients). This indicates that there may be poor understanding of the importance of completing the treatment or that the side effects of ACT were significant enough to over-ride the pharmacy instructions. Adherence to ACT was poor in this setting. Health education messages emphasising the need to complete ACT even if patients vomit doses, feel unwell or their health conditions improve should be promoted.


Cholesterol feeding increases low density lipoprotein synthesis.
This study examines the effects of increased dietary cholesterol (6 eggs/d) on the metabolism of low density lipoproteins in a group of seven healthy volunteers. Egg supplementation raised high density and low density lipoprotein cholesterol levels by 18 and 40%, respectively. The composition of the low density lipoprotein was unaltered and therefore the number of circulating particles must have increased. Kinetic studies indicated that this was due primarily to a 23% rise in the rate of synthesis of the lipoprotein. Catabolism was also affected. The fractional removal rate of native low density lipoprotein fell by 10% (P less than 0.05). However, the clearance of the 1,2 cyclohexanedione-treated lipoprotein remained unchanged (control fractional clearance rate [FCR] = 0.188 pools/d; cholesterol feeding FCR = 0.183 pools/d). Therefore, the reduction in low density lipoprotein catabolism appeared to be due to a fall in receptor activity. Consequently, an increased sterol load (34.2 mumol/kg per d vs. 27.7 mumol/kg per d in the control phase, P less than 0.02) was channelled into the receptor-independent route during egg feeding.


Transplacental transmission of Plasmodium falciparum in rural Malawi.
Malaria during pregnancy may result in fetal exposure to malaria when parasites are transmitted across the placenta. To document the rate of transplacental passage of Plasmodium falciparum and to identify the risk factors for congenitally acquired malaria infection, we examined umbilical cord blood for malaria parasites from 2,080 newborn infants born to mothers enrolled in a study of malaria prophylaxis during pregnancy. Cord blood parasitemia was detected in 140 (6.7%) newborn infants with a geometric mean density of 187 parasites/microliter (range 12-99, 752 parasites/microliter). The likelihood of umbilical cord blood parasitemia was closely linked to the parasite density of placental malaria infection and the density of maternal peripheral blood parasitemia at the time of delivery; all babies born to women with both placental and peripheral blood parasitemia densities > or = 10,000/microliter had cord blood parasitemia. In a multivariate logistic regression model, male sex, premature delivery, and placental and maternal peripheral blood malaria parasitemia were independently associated with a baby being born with umbilical cord blood parasitemia. In this setting, highly endemic for malaria, transplacental transmission of malaria from infected placentae occurs frequently and is directly related to the density of maternal malaria infection.


How robust is the 'surprise question' in predicting short-term mortality risk in haemodialysis patients?
The 'surprise question' (SQ) may aid timely identification of patients with end-of-life care needs. We assessed its prognostic value and variability among clinicians caring for a cohort of haemodialysis (HD) patients. Clinicians (29 nurses and 6 nephrologists) in each of our 3 HD units were asked to pose the SQ concerning all patients dialysing in their unit. There were 344 patients, 116 in Unit 1, 132 in Unit 2 and 96 in Unit 3. An adverse SQ response: 'I would not be surprised if this patient were to die in the next 12 months' was reported by individual clinicians for between 6 and 43% of patients (mean 24 ± 9%). Nephrologists responded adversely for more patients than nurses did. Fifty-two patients died during the 12 months of follow-up. There were wide variations between clinicians in the predictive power of SQ responses. Mean odds ratios were significantly higher for nephrologists than for nurses. SQ responses of 49% of clinicians improved baseline models of 12-month mortality, more so for nephrologists (67%) than for senior nurses (50%) and nurses of lesser seniority (36%). Unit performance differed significantly. Agreements between clinicians on SQ responses improved the positive predictive value, i.e. the more clinicians agreed on an adverse response, the greater its predictive power. SQ provides a unique contribution to the prediction of short-term prognosis in HD patients, though predictive power varies with clinical discipline, seniority and clinical setting. Agreements between clinicians on adverse responses may have clinical utility.


Insight into the Recent Genome Duplication of the Halophilic Yeast Hortaea werneckii: Combining an Improved Genome with Gene Expression and Chromatin Structure.
Extremophilic organisms demonstrate the flexibility and adaptability of basic biological processes by highlighting how cell physiology adapts to environmental extremes. Few eukaryotic extremophiles have been well studied and only a small number are amenable to laboratory cultivation and manipulation. A detailed characterization of the genome architecture of such organisms is important to illuminate how they adapt to environmental stresses. One excellent example of a fungal extremophile is the halophile Hortaea werneckii (Pezizomycotina, Dothideomycetes, Capnodiales), a yeast-like fungus able to thrive at near-saturating concentrations of sodium chloride and which is also tolerant to both UV irradiation and desiccation. Given its unique lifestyle and its remarkably recent whole genome duplication, H. werneckii provides opportunities for testing the role of genome duplications and adaptability to extreme environments. We previously assembled the genome of H. werneckii using short-read sequencing technology and found a remarkable degree of gene duplication. Technology limitations, however, precluded high-confidence annotation of the entire genome. We therefore revisited the H. wernickii genome using long-read, single-molecule sequencing and provide an improved genome assembly which, combined with transcriptome and nucleosome analysis, provides a useful resource for fungal halophile genomics. Remarkably, the ∼50 Mb H. wernickii genome contains 15,974 genes of which 95% (7608) are duplicates formed by a recent whole genome duplication (WGD), with an average of 5% protein sequence divergence between them. We found that the WGD is extraordinarily recent, and compared to Saccharomyces cerevisiae, the majority of the genome's ohnologs have not diverged at the level of gene expression of chromatin structure.


Quality of care for preschool children with asthma: the role of social factors and practice setting.
To determine whether patient race or source of payment is associated with differences in the quality of inpatient and outpatient treatment for young children with asthma. Structured medical record review. Tertiary care pediatric hospital. We studied 354 patients aged 1 to 6 years discharged with asthma between October 1, 1989 and September 30, 1990. We developed indicators of the quality of asthma care provided before and during hospitalization and planned after discharge. Outpatient indicators were the use of inhaled beta-agonists and the use of preventive anti-inflammatory medications (inhaled steroids or cromolyn sodium) before admission. In-hospital indicators were the intensity of inhaled beta-agonist therapy in the emergency department and length of stay. Planning for post-hospital care was assessed by the prescription of a nebulizer for home use. We examined associations between these indicators and patient race and source of payment, and explored the influence of primary-care practice type on these associations. After adjustment for potential confounders, we found that Hispanic patients were less likely than white patients to have taken inhaled beta-agonists before admission. Both black and Hispanic patients were less likely than white patients to have taken anti-inflammatory medications. When we adjusted for the patients' primary-care practice type, the effect of patient race did not persist for these indicators of outpatient care. We found no differences by patient race in emergency department care or length of hospital stay. However, black and Hispanic patients were much less likely to be prescribed a nebulizer for home use upon discharge. After adjustment for confounders, there were no differences in the quality of asthma care by source of payment. We found that young children of racial minorities admitted for an asthma exacerbation were less likely to have received maximally effective preventive therapy. We also identified marked differences in the quality of care planned after hospital discharge for black and Hispanic patients, compared with white patients. Particularly in an era of health reform, attention should focus on barriers to high-quality care for underserved children, who are already at high risk for asthma-related morbidity.


Novae. Fermi establishes classical novae as a distinct class of gamma-ray sources.
A classical nova results from runaway thermonuclear explosions on the surface of a white dwarf that accretes matter from a low-mass main-sequence stellar companion. In 2012 and 2013, three novae were detected in γ rays and stood in contrast to the first γ-ray-detected nova V407 Cygni 2010, which belongs to a rare class of symbiotic binary systems. Despite likely differences in the compositions and masses of their white dwarf progenitors, the three classical novae are similarly characterized as soft-spectrum transient γ-ray sources detected over 2- to 3-week durations. The γ-ray detections point to unexpected high-energy particle acceleration processes linked to the mass ejection from thermonuclear explosions in an unanticipated class of Galactic γ-ray sources.


Effects of gemcitabine and gemcitabine in combination with carboplatin on five canine transitional cell carcinoma cell lines.
To evaluate in vitro effects of gemcitabine alone and in combination with carboplatin on canine transitional cell carcinoma (TCC) cell lines. In vitro cultures of 5 canine TCC cell lines. Cells were treated with gemcitabine, carboplatin, or a combination of both at various concentrations. Cell proliferation was assessed via a fluorescence-based microplate cell proliferation assay. Cell cycle was evaluated via propidium iodide staining, and apoptosis was assessed by measurement of caspase 3 and 7 enzymatic activity. Synergy between gemcitabine and carboplatin was quantified via combination index analyses. Treatment of 5 canine TCC cell lines with gemcitabine or carboplatin decreased cell proliferation, increased apoptosis, and induced cell cycle arrest. Cell cycle arrest and apoptosis were markedly increased when cell lines were treated with both gemcitabine and carboplatin simultaneously or sequentially. Order of administration during sequential treatment did not consistently affect cell proliferation results in TCC cell lines. When TCC cell lines were treated with gemcitabine and carboplatin in combination at therapeutically relevant concentrations (gemcitabine concentration, < 10μM; carboplatin concentration, < 250μM), a significant decrease in cell proliferation was observed, compared with cell proliferation following treatment with gemcitabine or carboplatin alone. In combination, the effects of gemcitabine and carboplatin were synergistic in 3 of 5 cell lines and additive in the other 2. Gemcitabine had antitumor effects on canine TCC cells in vitro, and the combination of gemcitabine and carboplatin had synergistic activity at biologically achievable concentrations.


Association of ideal cardiovascular health at age 50 with incidence of dementia: 25 year follow-up of Whitehall II cohort study.
To examine the association between the Life Simple 7 cardiovascular health score at age 50 and incidence of dementia. Prospective cohort study. Civil service departments in London (Whitehall II study; study inception 1985-88). 7899 participants with data on the cardiovascular health score at age 50. The cardiovascular health score included four behavioural (smoking, diet, physical activity, body mass index) and three biological (fasting glucose, blood cholesterol, blood pressure) metrics, coded on a three point scale (0, 1, 2). The cardiovascular health score was the sum of seven metrics (score range 0-14) and was categorised into poor (scores 0-6), intermediate (7-11), and optimal (12-14) cardiovascular health. Incident dementia, identified through linkage to hospital, mental health services, and mortality registers until 2017. 347 incident cases of dementia were recorded over a median follow-up of 24.7 years. Compared with an incidence rate of dementia of 3.2 (95% confidence interval 2.5 to 4.0) per 1000 person years among the group with poor cardiovascular health, the absolute rate differences per 1000 person years were -1.5 (95% confidence interval -2.3 to -0.7) for the group with intermediate cardiovascular health and -1.9 (-2.8 to -1.1) for the group with optimal cardiovascular health. Higher cardiovascular health score was associated with a lower risk of dementia (hazard ratio 0.89 (0.85 to 0.95) per 1 point increment in the cardiovascular health score). Similar associations with dementia were observed for the behavioural and biological subscales (hazard ratios per 1 point increment in the subscores 0.87 (0.81 to 0.93) and 0.91 (0.83 to 1.00), respectively). The association between cardiovascular health at age 50 and dementia was also seen in people who remained free of cardiovascular disease over the follow-up (hazard ratio 0.89 (0.84 to 0.95) per 1 point increment in the cardiovascular health score). Adherence to the Life Simple 7 ideal cardiovascular health recommendations in midlife was associated with a lower risk of dementia later in life.


The Ste5 scaffold allosterically modulates signaling output of the yeast mating pathway.
Scaffold proteins organize signaling proteins into pathways and are often viewed as passive assembly platforms. We found that the Ste5 scaffold has a more active role in the yeast mating pathway: A fragment of Ste5 allosterically activated autophosphorylation of the mitogen-activated protein kinase Fus3. The resulting form of Fus3 is partially active-it is phosphorylated on only one of two key residues in the activation loop. Unexpectedly, at a systems level, autoactivated Fus3 appears to have a negative regulatory role, promoting Ste5 phosphorylation and a decrease in pathway transcriptional output. Thus, scaffolds not only direct basic pathway connectivity but can precisely tune quantitative pathway input-output properties.


Molecular structure of the sarcomeric Z-disk: two types of titin interactions lead to an asymmetrical sorting of alpha-actinin.
The sarcomeric Z-disk, the anchoring plane of thin (actin) filaments, links titin (also called connectin) and actin filaments from opposing sarcomere halves in a lattice connected by alpha-actinin. We demonstrate by protein interaction analysis that two types of titin interactions are involved in the assembly of alpha-actinin into the Z-disk. Titin interacts via a single binding site with the two central spectrin-like repeats of the outermost pair of alpha-actinin molecules. In the central Z-disk, titin can interact with multiple alpha-actinin molecules via their C-terminal domains. These interactions allow the assembly of a ternary complex of titin, actin and alpha-actinin in vitro, and are expected to constrain the path of titin in the Z-disk. In thick skeletal muscle Z-disks, titin filaments cross over the Z-disk centre by approximately 30 nm, suggesting that their alpha-actinin-binding sites overlap in an antiparallel fashion. The combination of our biochemical and ultrastructural data now allows a molecular model of the sarcomeric Z-disk, where overlapping titin filaments and their interactions with the alpha-actinin rod and C-terminal domain can account for the essential ultrastructural features.


Urinary CD80 is elevated in minimal change disease but not in focal segmental glomerulosclerosis.
Controversy exists as to whether minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) represent different diseases or are manifestations within the same disease spectrum. Urinary excretion of CD80 (also known as B7.1) is elevated in patients with MCD and hence we tested whether urinary CD80 excretion might distinguish between patients with MCD from those with FSGS. Urinary CD80 was measured in 17 patients with biopsy-proven MCD and 22 with proven FSGS using a commercially available enzyme-linked immunosorbent assay and its molecular size determined by western blot analysis. A significant increase in urinary CD80, normalized to urinary creatinine, was found in patients with MCD in relapse compared to those in remission or those with FSGS. No significant differences were seen when CD80 urinary excretion from MCD patients in remission were compared to those with FSGS. In seven of eight MCD patients in relapse, CD80 was found in glomeruli by immunohistochemical analysis of their biopsy specimen. No CD80 was found in glomeruli of two patients with FSGS and another MCD patient in remission. Thus, our study supports the hypothesis that MCD and FSGS represent two different diseases rather than a continuum of one disease. Urinary CD80 excretion may be a useful marker to differentiate between MCD and FSGS.


Patients' goals related to health and function in the first 13 months after allogeneic stem cell transplantation.
Patient participation in goal setting and decision making is a core component of the rehabilitation process, but there is little information on what patients want to achieve after allogeneic stem cell transplantation (allo-SCT). The aim of this study was to describe adult patients' perceptions of goals related to health and function, as well as self-perceived limitations and facilitating strategies in the first 13 months after allo-SCT. Fifteen patients with a median age of 44 years (range, 22-65 years) were interviewed on one occasion during the first year after allo-SCT. Data were analysed using qualitative content analysis. Results showed that patients felt that time after allo-SCT largely concerned: "to be healthy" and "to participate in a normal life". Some patients felt it was easy to set goals while others found it difficult. Most described goals had a long-term character. Patients were faced with a wide variety of limitations of which a few did not link to a described goal. Several facilitating strategies were described that either had or could help patients to reach their goals. Our results indicate that assistance with setting achievable goals, including individualised strategies and support from health care professionals to realise the goals, may assist in the rehabilitation to restore health and function after allo-SCT.


Low-temperature-induced structural changes in the Apo regulatory domain of skeletal muscle troponin C.
Contractile activity of skeletal muscle is triggered by a Ca2+-induced "opening" of the regulatory N-domain of troponin C (apo-NTnC residues 1-90). This structural transition has become a paradigm for large-scale conformational changes that affect the interaction between proteins. The regulatory domain is comprised of two basic structural elements: one contributed by the N-, A-, and D-helices (NAD unit) and the other by the B- and C-helices (BC unit). The Ca2+-induced opening is characterized by a movement of the BC unit away from the NAD unit with a concomitant change in conformation at two hinges (Glu41 and Val65) of the BC unit. To examine the effect of low temperatures on this Ca2+-induced structural change and the implications for contractile regulation, we have examined nuclear magnetic resonance (NMR) spectral changes of apo-NTnC upon decreasing the temperature from 30 to 4 degrees C. In addition, we have determined the solution structure of apo-NTnC at 4 degrees C using multinuclear multidimensional NMR spectroscopy. Decreasing temperatures induce a decrease in the rates and amplitudes of pico to nanosecond time scale backbone dynamics and an increase in alpha-helical content for the terminal helices of apo-NTnC. In addition, chemical shift changes for the Halpha resonances of Val65 and Asp66, the hinge residues of the BC, unit were observed. Compared to the solution structure of apo-NTnC determined at 30 degrees C, the BC unit packs more tightly against the NAD unit in the solution structure determined at 4 degrees C. Concomitant with the tighter packing of the BC and NAD structural units, a decrease in the total exposed hydrophobic surface area is observed. The results have broad implications relative to structure determination of proteins in the presence of large domain movements, and help to elucidate the relevance of structures determined under different conditions of physical state and temperature, reflecting forces ranging from crystal packing to solution dynamics.


First Report of Crown Rot of Strawberry Caused by Macrophomina phaseolina in Chile.
In recent years, an increase of collapsed and dead strawberry plants has been observed in several fields in central Chile, specifically in San Pedro, Melipilla, an important area for strawberry cultivation in the country. To determine the causal agent of the disease and the extent of the problem, 25 sample sites of 1 ha each, distributed in different San Pedro zones, were surveyed at the end of the 2011 season (from December 2010 to February 2011). Cross sections of the crowns of symptomatic strawberry plants showed necrotic tissue and brown-red to dark brown areas on the vascular ring. Samples of the affected crowns were superficially disinfested and plated on potato dextrose agar with 200 μg/ml of streptomycin sulfate. Dark gray colonies were observed after 7 days of incubation at 24°C. Pure cultures of the pathogen showed aerial mycelium and abundant dark oblong sclerotia. Fifty sclerotia were measured, averaging 120 × 74 μm. Twenty-one isolates were identified molecularly utilizing the species specific primers MpKFI and MpKRI (2) that yielded a 350-bp fragment. The amplified DNA fragments were sequenced and BLAST analysis showed a 99% nucleotide sequence identity with Macrophomina phaseolina (GeneBank Accession No JX535007.1). Both morphological and molecular analyses confirmed that the isolated species corresponded to M. phaseolina, causal agent of crown and root rot in strawberry. Four representative isolates were selected to conduct pathogenicity tests. Inoculum was prepared by incubating the pathogen for 28 days at 20°C in sterilized oat seeds. Pots of 1.5 liters were filled with a mixed substrate of peat and perlite (2:1), amended with inoculated oats at 9 g per liter of substrate. 'Camarosa' strawberry plants were planted and grown in a glasshouse for 1 month. Six replicated plants per isolate and six plants growing on non-inoculated substrate were left as controls. Ninety-five percent of the inoculated plants showed wilt and collapse symptoms 22 days after transplant, whereas no symptoms were observed in the control plants. M. phaseolina was reisolated from the crowns of symptomatic plants, fulfilling Koch's postulates. The pathogen was isolated from symptomatic strawberry plants in 14 of the 25 sampled sites. Although M. phaseolina was described previously on other crops in Chile, to our knowledge, this is the first report of M. phaseolina causing crown rot of strawberry. The disease has been recently reported in Spain, the United States, and Argentina (1,3,4). References: (1) M. Avilés et al. Plant Pathol. 57:382, 2008. (2) B. Babu et al. Mycologia 99:797, 2007. (3) O. Baino et al. Plant Dis. 95:1477, 2011. (4) S. Koike. Plant Dis. 92:1253, 2008.


Even good bots fight: The case of Wikipedia.
In recent years, there has been a huge increase in the number of bots online, varying from Web crawlers for search engines, to chatbots for online customer service, spambots on social media, and content-editing bots in online collaboration communities. The online world has turned into an ecosystem of bots. However, our knowledge of how these automated agents are interacting with each other is rather poor. Bots are predictable automatons that do not have the capacity for emotions, meaning-making, creativity, and sociality and it is hence natural to expect interactions between bots to be relatively predictable and uneventful. In this article, we analyze the interactions between bots that edit articles on Wikipedia. We track the extent to which bots undid each other's edits over the period 2001-2010, model how pairs of bots interact over time, and identify different types of interaction trajectories. We find that, although Wikipedia bots are intended to support the encyclopedia, they often undo each other's edits and these sterile "fights" may sometimes continue for years. Unlike humans on Wikipedia, bots' interactions tend to occur over longer periods of time and to be more reciprocated. Yet, just like humans, bots in different cultural environments may behave differently. Our research suggests that even relatively "dumb" bots may give rise to complex interactions, and this carries important implications for Artificial Intelligence research. Understanding what affects bot-bot interactions is crucial for managing social media well, providing adequate cyber-security, and designing well functioning autonomous vehicles.


In vitro infection of human nervous cells by two strains of Toxoplasma gondii: a kinetic analysis of immune mediators and parasite multiplication.
The severity of toxoplasmic infection depends mainly on the immune status of the host, but also on the Toxoplasma gondii strains, which differ by their virulence profile. The relationship between the human host and T. gondii has not yet been elucidated because few studies have been conducted on human models. The immune mechanisms involved in the persistence of T. gondii in the brains of immunocompetent subjects and during the reactivation of latent infections are still unclear. In this study, we analyzed the kinetics of immune mediators in human nervous cells in vitro, infected with two strains of T. gondii. Human neuroblast cell line (SH SY5Y), microglial (CMH5) and endothelial cells (Hbmec) were infected separately by RH (type I) or PRU (type II) strains for 8 h, 14 h, 24 h and 48 h (ratio 1 cell: 2 tachyzoites). Pro-inflammatory protein expression was different between the two strains and among different human nervous cells. The cytokines IL-6, IL-8 and the chemokines MCP-1 and GROα, and SERPIN E1 were significantly increased in CMH5 and SH SY5Y at 24 h pi. At this point of infection, the parasite burden declined in microglial cells and neurons, but remained high in endothelial cells. This differential effect on the early parasite multiplication may be correlated with a higher production of immune mediators by neurons and microglial cells compared to endothelial cells. Regarding strain differences, PRU strain, but not RH strain, stimulates all cells to produce pro-inflammatory growth factors, G-CSF and GM-CSF. These proteins could increase the inflammatory effect of this type II strain. These results suggest that the different protein expression profiles depend on the parasitic strain and on the human nervous cell type, and that this could be at the origin of diverse brain lesions caused by T. gondii.


Iatrogenic contralateral foraminal stenosis following lumbar spine fusion surgery: illustrative cases.
Lumbar spine fusion is the mainstay treatment for degenerative spine disease. Multiple potential complications of spinal fusion have been found. Acute contralateral radiculopathy postoperatively has been reported in previous literature, with unclear underlying pathology. Few articles reported the incidence of contralateral iatrogenic foraminal stenosis after lumbar fusion surgery. The aim of current article is to explore the possible causes and prevention of this complication. The authors present 4 cases in which patients developed acute postoperative contralateral radiculopathy requiring revision surgery. In addition, we present a fourth case in which preventive measures have been applied. The aim of this article was to explore the possible causes and prevention to this complication. Iatrogenic foraminal stenosis of the lumbar spine is a common complication; preoperative evaluation and middle intervertebral cage positioning are needed to prevent this complication.


HIV-1 Tat protein vaccination in mice infected with Mycobacterium tuberculosis is safe, immunogenic and reduces bacterial lung pathology.
The therapeutic HIV-1 Tat protein vaccine is in advanced clinical development. Tuberculosis, the main AIDS co-infection, is highly endemic in areas where AIDS prevention through vaccination is needed. However, safety and immunogenicity of Tat vaccination in the course of Mycobacterium tuberculosis (Mtb) infection is still unknown and it prevents the possibility to administer the vaccine to Mtb-infected individuals. We addressed the interplay and effects of Tat vaccination on Mtb infection in immunocompetent mice. C57BL/6 mice were vaccinated or not with Bacillus Calmette-Guerin (BCG), the current tuberculosis vaccine, and after 5 weeks were infected with Mtb by intravenous route. The Tat protein was injected intradermally at 1, 2 and 4 weeks after Mtb challenge. Eight weeks after Mtb infection, all mice were sacrificed, and both the degree of pathology and immune responses to Mtb and Tat were evaluated. As additional control, some mice were either vaccinated or not with BCG, were not challenged with Mtb, but received the Tat protein. Statistical significances were evaluated by one-way or two-way ANOVA and Tukey's multiple comparisons post-test. In the lungs of Mtb-infected mice, Tat-vaccine did not favour Mtb replication and indeed reduced both area of cellular infiltration and protein levels of Interferon-γ, Chemokine (C-C motif) ligand-4 and Interleukin-1β, pathological events triggered by Mtb-infection. Moreover, the protection against Mtb infection conferred by BCG remained good after Tat protein treatment. In spleen cells of Mtb-infected mice, Tat vaccination enhanced Mtb-specific Interferon-γ and Interleukin-17 responses, which may have a protective role. Of note, Mtb infection reduced, but did not suppress, the development of anti-Tat antibodies, required for Tat vaccine efficacy and the titer of anti-Tat IgG was potentiated by BCG vaccination in Mtb-free mice. In general, Tat treatment was well tolerated in both Mtb-infected and Mtb-free mice. Tat protein vaccine, administered in Mtb-infected mice with a protocol resembling that used in the clinical trials, was safe, immunogenic, limited the lung Mtb-associated immunopathology and did not abrogate the protective efficacy of BCG. These data provide preliminary evidence for a safe use of Tat vaccine in people vaccinated with BCG and/or suffering from tuberculosis.


A fast adaptive memetic algorithm for online and offline control design of PMSM drives.
A fast adaptive memetic algorithm (FAMA) is proposed which is used to design the optimal control system for a permanent-magnet synchronous motor. The FAMA is a memetic algorithm with a dynamic parameter setting and two local searchers adaptively launched, either one by one or simultaneously, according to the necessities of the evolution. The FAMA has been tested for both offline and online optimization. The former is based on a simulation of the whole system--control system and plant--using a model obtained through identification tests. The online optimization is model free because each fitness evaluation consists of an experimental test on the real motor drive. The proposed algorithm has been compared with other optimization approaches, and a matching analysis has been carried out offline and online. Excellent results are obtained in terms of optimality, convergence, and algorithmic efficiency. Moreover, the FAMA has given very robust results in the presence of noise in the experimental system.


Testing the FMR1 promoter for mosaicism in DNA methylation among CpG sites, strands, and cells in FMR1-expressing males with fragile X syndrome.
Variability among individuals in the severity of fragile X syndrome (FXS) is influenced by epigenetic methylation mosaicism, which may also be common in other complex disorders. The epigenetic signal of dense promoter DNA methylation is usually associated with gene silencing, as was initially reported for FMR1 alleles in individuals with FXS. A paradox arose when significant levels of FMR1 mRNA were reported for some males with FXS who had been reported to have predominately methylated alleles. We have used hairpin-bisufite PCR, validated with molecular batch-stamps and barcodes, to collect and assess double-stranded DNA methylation patterns from these previously studied males. These patterns enable us to distinguish among three possible forms of methylation mosaicism, any one of which could explain FMR1 expression in these males. Our data indicate that cryptic inter-cell mosaicism in DNA methylation can account for the presence of FMR1 mRNA in some individuals with FXS.


The impact of anatomic tumor location on inter-fraction tumor motion during lung stereotactic body radiation therapy (SBRT).
Narrow PTV margins and steep dose gradients underscore the importance of evaluating breathing-associated tumor motion for lung SBRT. The specific aim of this study was to determine the impact of anatomic tumor location on inter-fraction tumor motion. Forty-one patients underwent standard free-breathing 4DCT simulation and daily image-guidance 4DCTs during lung SBRT. Absolute tumor motion amplitude in the mediolateral (ML), anterior-posterior (AP), and superior-inferior (SI) directions was analyzed from 159 total 4DCT scans (simulation and daily pre-treatment). Overall, the inter-fraction tumor motion amplitude in the ML, AP, and SI directions was small (mean ≤2.5 mm). Similarly, while both upper lobe (UL) and lower lobe (LL) tumors exhibited limited inter-fraction motion in both the ML and AP directions (mean ≤2.2 mm), tumors in the LL had increased inter-fraction motion in the SI direction compared to UL tumors (mean 4.3±4.0 mm vs. 1.7±1.7 mm, p=0.008). Moreover, 28.6% (n=4) of LL tumors exhibited mean inter-fraction motion along the SI direction >5 mm (all of which resided in the supra-diaphragmatic basal segments of the LL). Mean inter-fraction tumor motion amplitude along the SI direction exceeded our PTV margins (an isotropic 5 mm expansion of the ITV) in 28.6% of LL tumors (all of which resided in the basal segments). These results suggest that typical ITV-to-PTV margins may be insufficient for a subset of LL lesions and that increased PTV margins, daily breathing motion re-assessment and/or adaptive re-planning may benefit patients with supra-diaphragmatic tumors in the LL.


Beneficial effects of x-irradiation on recovery of lesioned mammalian central nervous tissue.
We examined the potential of x-irradiation, at clinical dose levels, to manipulate the cellular constituents and thereby change the consequences of transection injury to adult mammalian central nervous tissue (rat olfactory bulb). Irradiation resulted in reduction or elimination of reactive astrocytes at the site of incision provided that it was delivered within a defined time window postinjury. Under conditions optimal for the elimination of gliosis (15-18 days postinjury), irradiation of severed olfactory bulbs averted some of the degenerative consequences of lesion. We observed that irradiation was accompanied by prevention of tissue degeneration around the site of lesion, structural healing with maintenance of the typical cell lamination, and rescue of some axotomized mitral cells (principal bulb neurons). Thus radiation resulted in partial preservation of normal tissue morphology. It is postulated that intrusive cell populations are generated in response to injury and reactive astrocytes are one such group. Our results suggest that selective elimination of these cells by irradiation enabled some of the regenerative processes that are necessary for full recovery to maintain their courses. The cellular targets of these cells, their modes of intervention in recovery, and the potential role of irradiation as a therapeutic modality for injured central nervous system are discussed.


Status and ecological effects of the world's largest carnivores.
Large carnivores face serious threats and are experiencing massive declines in their populations and geographic ranges around the world. We highlight how these threats have affected the conservation status and ecological functioning of the 31 largest mammalian carnivores on Earth. Consistent with theory, empirical studies increasingly show that large carnivores have substantial effects on the structure and function of diverse ecosystems. Significant cascading trophic interactions, mediated by their prey or sympatric mesopredators, arise when some of these carnivores are extirpated from or repatriated to ecosystems. Unexpected effects of trophic cascades on various taxa and processes include changes to bird, mammal, invertebrate, and herpetofauna abundance or richness; subsidies to scavengers; altered disease dynamics; carbon sequestration; modified stream morphology; and crop damage. Promoting tolerance and coexistence with large carnivores is a crucial societal challenge that will ultimately determine the fate of Earth's largest carnivores and all that depends upon them, including humans.


Revealing and resolving patient safety defects: the impact of leadership WalkRounds on frontline caregiver assessments of patient safety.
To evaluate the impact of rigorous WalkRounds on frontline caregiver assessments of safety climate, and to clarify the steps and implementation of rigorous WalkRounds. Primary outcome variables were baseline and post WalkRounds safety climate scores from the Safety Attitudes Questionnaire (SAQ). Secondary outcomes were safety issues elicited through WalkRounds. Study period was August 2002 to April 2005; seven hospitals in Massachusetts agreed to participate; and the project was implemented in all patient care areas. Prospective study of the impact of rigorously applied WalkRounds on frontline caregivers assessments of safety climate in their patient care area. WalkRounds were conducted weekly and according to the seven-step WalkRounds Guide. The SAQ was administered at baseline and approximately 18 months post-WalkRounds implementation to all caregivers in patient care areas. Two of seven hospitals complied with the rigorous WalkRounds approach; hospital A was an academic teaching center and hospital B a community teaching hospital. Of 21 patient care areas, SAQ surveys were received from 62 percent of respondents at baseline and 60 percent post WalkRounds. At baseline, 10 of 21 care areas (48 percent) had safety climate scores below 60 percent, whereas post-WalkRounds three care areas (14 percent) had safety climate scores below 60 percent without improving by 10 points or more. Safety climate scale scores in hospital A were 62 percent at baseline and 77 percent post-WalkRounds (t=2.67, p=.03), and in hospital B were 46 percent at baseline and 56 percent post WalkRounds (t=2.06, p=.06). Main safety issues by category were equipment/facility (A [26 percent] and B [33 percent]) and communication (A [24 percent] and B [18 percent]). WalkRounds implementation requires significant organizational will; sustainability requires outstanding project management and leadership engagement. In the patient care areas that rigorously implemented WalkRounds, frontline caregiver assessments of patient safety increased. SAQ results such as safety climate scores facilitate the triage of quality improvement efforts, and provide consensus assessments of frontline caregivers that identify themes for improvement.


A comparison of prospective and retrospective responses on sudden infant death syndrome by case and control mothers.
Based on information from two studies of sudden infant death syndrome (SIDS) from 1988-1991 in Tasmania, Australia, prospective and retrospective maternal responses to an identical set of questions were compared for 27 cases and 25 controls. There was good agreement on demographic factors, maternal obstetric history, parental smoking, and infant feeding practices. Reported changes in sleep habits were slightly greater for cases, and further work is needed to determine if this reflects recall bias or real changes during early infant life. Case mother reports regarding family history of disease and infant bedding were more discrepant, suggesting recall bias and supporting prospective collection of this information.


Ultrastructural variation of cuticular layers in cephalobinae (nemata: rhabditida).
The ultrastructure of the body wall cuticle in Acrobeles complexus, Cervidellus alutus, and Zeldia punctata was studied as a step toward understanding biological diversity within Cephalobinae, and to discover new characters for phylogeny-based classification of the suborder. In each species the cuticle consists of cortical, median, and basal layers. The cortical layer includes an external trilaminate and internal granular zone; the basal layer is striated. In Z. punctata the median layer is electron-lucent, vacuolar, and penetrates the cortical layer; it also includes periodically dense columns that apparently correspond to punctuations visible with light microscopy. In contrast, the median layer of the body wall cuticle in A. complexus and C. alutus is bisected by a zone that undulates parallel to the nematode surface and with periodicity corresponding to annuli. Phylogenetic analysis, using derived cuticle patterns of Cephalobinae, requires an understanding of ecological pressures that could result in convergent evolution of cuticle characters.


Stenting of the arterial duct combined with banding of the pulmonary arteries and atrial septectomy or septostomy: a new approach to palliation for the hypoplastic left heart syndrome.
To assess the feasibility of pulmonary artery banding, atrial septectomy or septostomy, and percutaneous stenting of the arterial duct in babies with the hypoplastic left heart syndrome. Four infants with hypoplastic left heart syndrome. Two supraregional paediatric cardiac centres. Ductal patency was maintained initially with prostaglandin E. Banding of the proximal branch pulmonary arteries was performed through a median sternotomy and open atrial septectomy was performed if balloon septostomy was not. Stainless steel stents (Johnson & Johnson) mounted in a balloon catheter were implanted into the arterial duct under radiographic control and expanded to a diameter of approximately 8 mm, prostaglandin treatment was then stopped. All the patients survived the immediate postoperative period and maintenance of wide ductal patency was achieved in three of the four patients by stent implantation. Two weeks after the procedure two babies died of right ventricular failure and respiratory infection: some distal ductal constriction had occurred in one where the stent was not quite sufficiently distally placed. One child was discharged home 15 days after treatment and was well at follow up at age 16 weeks and one was stable but required diuretic therapy five weeks after the procedure. This new approach is technically feasible. At least in the short term it seems to offer hope of effective palliation for the hypoplastic left heart syndrome and it warrants further study.


Effect of combination of aripiprazole with carbamazepine and fluvoxamine on liver functions in experimental animals.
Aripiprazole, a new atypical antipsychotic drug extensively metabolized by enzyme CYP3A4, is found to produce asymptomatic elevation of serum transaminase levels on long-term treatment. The present study aims to evaluate the hepatotoxic effect of aripiprazole when coprescribed with carbamazepine and fluvoxamine. The rats were subjected to chronic treatment with two different doses, therapeutic dose (TD) and maximum therapeutic dose (MTD), of aripiprazole in combination with carbamazepine and fluvoxamine. The changes in hepatic function was assessed by various biochemical liver enzyme markers like serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), alkaline phosphatase (ALP), total bilirubin, histological studies, and physical parameters (liver weight, liver volume, and body weight). The combination of aripiprazole with fluvoxamine at both TD and MTD showed the hepatic damage and significant elevation in serum transaminase level which is supported by histological reports. The coadministration of aripiprazole with carbamazepine leads to significant decrease in blood concentration of aripiprazole possibly due to induction of enzyme CYP3A4 resulting in loss or reduction of clinical efficacy. There would be an accumulation of aripiprazole when coadministered with fluvoxamine, a known inhibitor of CYP3A4, leading to hepatic damage and reduction in aripiprazole when administered along with carbamazepine. Therefore, aripiprazole with fluvoxamine and carbamazepine should be coprescribed with caution. The patients should be monitored for signs of adverse effects like hepatic damage or decreased efficacy of these drugs.


Genetic variations in polyunsaturated fatty acid metabolism--implications for child health?
Sufficient nutritional supply with polyunsaturated fatty acids (PUFAs) has long been considered as beneficial for child health, especially in regard to neuronal development and allergic diseases. In recent years, genetic association studies showed that in addition to nutritional influences, the genetic background is highly important for PUFA composition in human tissues. Specifically, polymorphisms in the fatty acid desaturase genes or FADS determine the efficiency of how PUFAs are processed endogenously. Recent gene-nutrition interaction studies suggest that these polymorphisms modulate the effect of nutritional fatty acid intake on complex phenotypes such as cognitive outcomes and asthma risk in children. These early results may provide the basis for future well-specified dietary recommendations to achieve optimal health benefit for all children. This article presents results from recent gene-nutrition interaction studies, discusses its implications for child health, and gives an outlook how this association might translate into clinical practice in the future.


Cadmium exposure in association with history of stroke and heart failure.
It is unclear whether environmental cadmium exposure is associated with cardiovascular disease, although recent data suggest associations with myocardial infarction and peripheral arterial disease. The objective of this study was to evaluate the association of measured cadmium exposure with stroke and heart failure (HF) in the general population. We analyzed data from 12,049 participants, aged 30 years and older, in the 1999-2006 National Health and Nutrition Examination Survey (NHANES) for whom information was available on body mass index, smoking status, alcohol consumption, and socio-demographic characteristics. At their interviews, 492 persons reported a history of stroke, and 471 a history of HF. After adjusting for demographic and cardiovascular risk factors, a 50% increase in blood cadmium corresponded to a 35% increased odds of prevalent stroke [OR: 1.35; 95% confidence interval (CI): 1.12-1.65] and a 50% increase in urinary cadmium corresponded to a 9% increase in prevalent stroke [OR: 1.09; 95% CI: 1.00-1.19]. This association was higher among women [OR: 1.38; 95% CI: 1.11-1.72] than men [OR: 1.30; 95% CI: 0.93-1.79] (p-value for interaction=0.05). A 50% increase in blood cadmium corresponded to a 48% increased odds of prevalent HF [OR: 1.48; 95% CI: 1.17-1.87] and a 50% increase in urinary cadmium corresponded to a 12% increase in prevalent HF [OR: 1.12; 95% CI: 1.03-1.20], with no difference in sex-specific associations. Environmental exposure to cadmium was associated with significantly increased stroke and heart failure prevalence. Cadmium exposure may increase these important manifestations of cardiovascular disease.


Gender differences of aortic wave reflection and influence of menopause on central blood pressure in patients with arterial hypertension.
Evidences suggest that central hemodynamics indexes are independent predictors of future cardiovascular events and all-cause mortality. Multiple factors have been pointed to have potential influence on central aortic function: height, heart rate, left ventricular ejection duration and blood pressure level. Data related to the influence of gender and postmenopausal status on aortic waveform reflection is scarce. We aim to evaluate the impact of gender and menopause on central blood pressure of hypertensive patients. In a cross sectional study 122 hypertensive patients (52 men and 70 women) were studied. Hypertension was defined as blood pressure (BP) levels ≥140/90 mmHg or use of antihypertensive drugs. Central arterial pressure, augmentation index (AIx) and augmentation index normalized to 75 bpm (AIx75) were obtained using applanation tonometry. Menopause and postmenopause history were accessed by a direct series of questions. Postmenopause was defined as at least one year since last menstruation. Patients were paired by age, gender and menopausal status, and the data were compared considering gender and menopausal status. Height and weight were significantly lower in women than in men at the same age. Conversely, AIx (32.7 ± 9.8% vs. 20.1 ± 11.7%, p < 0.01), AIx75 (29.6 ± 6.7% vs. 18.3 ± 9.4%, p < 0.01) and central systolic blood pressure (136 ± 30 vs. 125 ± 23 mmHg, p = 0.03) were higher in women than men. The menopausal women (mean age of menopause = 48 years) had the worst indexes of aortic wave reflection, compared to men at the same age and younger women. Hypertensive women had both higher reflected aortic pressure waveform and central blood pressure indexes than hypertensive men, and these findings were worsened by the menopausal status.


Diagnostic impact of CSF biomarkers for Alzheimer's disease in a tertiary memory clinic.
We aimed to assess the impact of cerebrospinal fluid (CSF) biomarkers for Alzheimer's disease on decision making and patient management in a tertiary memory clinic. We included all patients, for 1 year, visiting the VUmc Alzheimer Center for cognitive screening. Neurologists completed questionnaires before and after CSF disclosure. We assessed the change of diagnosis, diagnostic confidence, and impact on patient management. A total of 438 patients (age 63 ± 8 years, 39% women) were included, of whom 351 (80%) underwent lumbar puncture. After the disclosure of CSF 23/351 diagnoses (7%) were changed. Diagnostic confidence increased from 84% to 89% (P < .001). There were consequences for management in 44/351 patients (13%) with CSF, and 13/87 patients (15%) because of unavailable CSF. There was no effect of age on these results. CSF biomarkers aid clinicians with decision making during diagnostic work-up of cognitive disorders. This study may be useful for developing guidelines for the implementation of CSF biomarkers in daily practice.


Prevalence of cardio-metabolic syndrome in Nigeria: a systematic review.
This is a systematic review of the distribution of cardiometabolic syndrome (CMS) in Nigeria, the clinical definitions widely used and how it affects the proposition of a national prevalence of CMS that will advise management interventions. Systematic review of literature. To present a comprehensive report of the distribution of CMS in Nigeria, extensive searches was carried out on PubMed, African Journals Online (AJOL), SCOPUS, EBSCOhost (CINAHL Plus), Google Scholar and Science Direct using terms: Nigeria, metabolic syndrome, cardio-metabolic syndrome, syndrome X, World Health Organization, International Diabetic Federation, National Cholesterol Education Program Adult Treatment Panel III, European Group for study on Insulin Resistance, American Association of Clinical Endocrinologist, American Heart Association/National Heart, Lung and Blood Institute. All published data between January 2002 and December 2013 were collated into a database. Information gathered and recorded for each source were the population sampled, age and number of population, locality, clinical definition used, longitude and latitude, and period of the study. Out of 32 studies, 9 (28.1%) adopted the WHO classification, 19 (59.4%) used the ATPIII definition, while the remaining 10 (31.3%) studies used the IDF definitions. Twenty (62.5%) were hospital-based studies on diabetic, hypertensive, HIV, asthmatic and thyroid disorder patients. The remaining 12 (37.5%) studies were population-based studies in urban, suburb and rural settings. The mean overall prevalence of CMS in Nigeria is 31.7%, 27.9% and 28.1% according to the WHO, ATPIII and IDF definitions, respectively. Most of the studies were from the Southern region. Age groups mostly studied were those from ≥35 years. The report of this review provides an essential overview on the current distribution of CMS in Nigeria. It provides an insight to direct future studies such as the need to (1) study rural communities where lifestyles are not westernized as in the urban areas, and (2) young adults, as well as (3) develop a consensus on the definition of CMS among the Sub-Saharan African populations.


Characterisation of methacrylate monoliths for bacteriophage purification.
Binding of three different bacteriophages (phages), namely T7, lambda and M13 on methacrylate monoliths was investigated. Phage M13 exhibited the highest dynamic binding capacity of 4.5×10(13) pfu/mL while T7 and lambda showed capacity of 1×10(13) pfu/mL, all corresponding to values of around 1mg/mL. Interestingly, capacity for lambda phage was increased 5-fold by increasing NaCl concentration in a loaded sample from 0 to 0.2M while there was a constant capacity decrease for T7 and M13 phages. Under optimal conditions, recovery for all three phages approached 100%. Measurement of a pressure drop increase during loading enabled estimation of adsorbed phage layer thickness. At a maximal capacity it was calculated to be around 50 nm for T7 phage and 60 nm for lambda phage matching closely capside size thus indicating monolayer adsorption while 80 nm layer thickness was estimated for M13 phage showing its orientation along the pore.


Using simulation technology for undergraduate nursing education.
As simulation technology is rapidly expanding, nursing programs are making large investments in this technology, which has great potential for undergraduate nursing programs. Unfortunately, this potential is underestimated and underused. With simulation technology, undergraduate students can gain and improve skills in a safe, non-threatening, experiential environment that also provides opportunities for decision making, critical thinking, and team building. This article describes how to use simulation technology to enhance undergraduate nursing education. The process for simulation technology instruction, leveling content from simple to complex, and faculty resources are discussed. An example of a simulation program is included.


FSH receptor (FSHR) expression in human extragonadal reproductive tissues and the developing placenta, and the impact of its deletion on pregnancy in mice.
Expression and function of the follicle-stimulating hormone receptor (FSHR) in females were long thought to be limited to the ovary. Here, however, we identify extragonadal FSHR in both the human female reproductive tract and the placenta, and test its physiological relevance in mice. We show that in nonpregnant women FSHR is present on: endothelial cells of blood vessels in the endometrium, myometrium, and cervix; endometrial glands of the proliferative and secretory endometrium; cervical glands and the cervical stroma; and (at low levels) stromal cells and muscle fibers of the myometrium. In pregnant women, placental FSHR was detected as early as 8-10 wk of gestation and continued through term. It was expressed on: endothelial cells in fetal portions of the placenta and the umbilical cord; epithelial cells of the amnion; decidualized cells surrounding the maternal arteries in the maternal decidua; and the stromal cells and muscle fibers of the myometrium, with particularly strong expression at term. These findings suggest that FSHR expression is upregulated during decidualization and upregulated in myometrium as a function of pregnancy. The presence of FSHR in the placental vasculature suggests a role in placental angiogenesis. Analysis of genetically modified mice in which Fshr is lacking in fetal portions of the placenta revealed adverse effects on fetoplacental development. Our data further demonstrate FSHB and CGA mRNAs in placenta and uterus, consistent with potential local sources of FSH. Collectively, our data suggest heretofore unappreciated roles of extragonadal FSHR in female reproductive physiology.


Visual neglect in pretrigeminal cats with lateral suprasylvian lesions.
Eleven cats with brain stem transected at the pretrigeminal level were used. The cortex of the middle suprasylvian sulcus was removed on the left side. The vertical following reflex was evoked by a slit of light (1 degree x 4 degrees) or a black bar (1 degree x 1 degree x 4 degrees) moving along the vertical meridian or parallel to it out to 40 degrees in the left or right hemifield. In all cats the following reflexes to the contralesional hemifield were low or absent. A corresponding suprasylvian lesion was made subsequently on the right side. In 6 cats the reflexes to both hemifields were absent or low. In contrast, surprisingly in 5 cats the reflexes were large, much higher than those evoked previously from the contralateral hemifield after the first lesion. This might be due to a process of disinhibition occurring in the superior colliculi.


Otorhinolaryngological manifestations in 61 patients with mucopolysaccharidosis.
The mucopolysaccharidoses (MPS) are inherited lysosomal storage disorders with multisystemic and highly variable clinical manifestation. ENT symptoms are common and early signs of MPS. The most common ENT diagnoses are chronic/recurrent rhinosinusitis, acute otitis media, otitis media with effusion, hearing loss and airway obstruction. A single-centre retrospective chart review of 61 patients (36 M/25F) with different MPS subtypes (MPS I (n = 15), MPS II (n = 10), MPS III (n = 17), MPS IV (n = 15) and MPS VI (n = 4)) was conducted. The age of ENT presentation and frequency of ENT symptoms, surgeries and their distribution among MPS subtypes was studied. The relationship between ENT presentation, first ENT surgery and the age of diagnosis was also evaluated. Median age at the first ENT manifestation was 2.8 years, median age at MPS diagnosis 4.1 years. The great majority of patients (90%) manifested at least one ENT diagnosis; often before the diagnosis of MPS (75%). Chronic/recurrent rhinosinusitis was the most prevalent ENT diagnosis (77%), followed by upper airway obstruction (65%) and hearing loss (53%). Chronic/recurrent rhinosinusitis was the first ENT symptom to appear (median age 2.2 years), followed by otitis media with effusion (3.7 years) and hearing loss (4.5 years). At least one ENT surgery was performed in 57% of patients; in 69% before MPS diagnosis was established. Median age of the first ENT surgery was 4.1 years. ENT symptoms and surgical procedures were earliest present in MPS II. Our study documents high and early occurrence of various otolaryngologic symptoms in MPS and thus highlights the role of ENT specialist in prompt diagnosis of these rare diseases and their long-term management.


Platinum-based combination chemotherapy for the treatment of advanced-stage squamous cell carcinoma of the vulva.
Chemoradiation is an alternative to radical vulvectomy with en bloc node dissection for advanced vulvar cancer. We report a case of complete clinical and pathologic response with chemotherapy alone in a patient with advanced vulvar cancer. A middle-aged woman known to have had human immunodeficiency virus (HIV) for 10 years was newly diagnosed with advanced-stage squamous carcinoma of the vulva. She was treated with a total of nine cycles of platinum-based combination chemotherapy, with complete clinical and pathologic response. She remains in complete clinical remission without evidence of recurrent disease by noninvasive testing in the absence of any further therapy 24 months after her last chemotherapy treatment. Platinum-based combination chemotherapy may be used successfully for patients with advanced-stage squamous carcinoma of the vulva.


Nephroblastoma in infants, 1969-75: variations in treatment and survival.
In a series of 79 infants aged under 1 year with nephroblastoma diagnosed during 1969-75 all the patients underwent nephrectomy, 33 (42%) received a course of radiotherapy, and 49 (62%) received chemotherapy. The overall three-year survival rate for patients who survived at least one week after diagnosis was 65%. The corresponding rate for infants with stage I tumours was 76%. The survival rate in children with early-stage tumours was significantly higher in those who were treated by nephrectomy and chemotherapy alone compared with those who also received radiotherapy. In a large proportion of cases nephrectomy and chemotherapy together constituted sufficient treatment for the cure of infants with nephroblastoma, and in some instances nephrectomy alone proved adequate. There was no general tendency for children under 1 year old to be unable to withstand chemotherapy.


Evaluation of glucocorticoid receptor function in COPD lung macrophages using beclomethasone-17-monopropionate.
Previous studies of glucocorticoid receptor (GR) function in COPD lung macrophages have used dexamethasone to evaluate inhibition of cytokine production. We have now used the clinically relevant corticosteroid beclomethasone-17-monopropionate (17-BMP) to assess GR function in COPD lung macrophages, and investigated the transactivation of glucocorticoid sensitive genes and GR phosphorylation in addition to cytokine production. Lung macrophages were purified from surgically acquired lung tissue, from patients with COPD, smokers, and non-smokers. The transactivation of glucocorticoid sensitive genes (FKBP51 and GILZ) by 17-BMP were analysed by polymerase chain reaction. 17-BMP suppression of LPS-induced TNFα, IL-6 and CXCL8 was measured by ELISA and GR phosphorylation was measured by immunohistochemistry and Western blot. 17-BMP reduced cytokine release in a concentration dependent manner, with >70% inhibition of all cytokines, and no difference between COPD patients and controls. Similarly, the transactivation of FKBP51 and GILZ, and GR phosphorylation was similar between COPD patients and controls. In this context, GR function in COPD lung macrophages is unaltered. 17-BMP effectively suppresses cytokine production in COPD lung macrophages.


Reduced lung-cancer mortality with low-dose computed tomographic screening.
The aggressive and heterogeneous nature of lung cancer has thwarted efforts to reduce mortality from this cancer through the use of screening. The advent of low-dose helical computed tomography (CT) altered the landscape of lung-cancer screening, with studies indicating that low-dose CT detects many tumors at early stages. The National Lung Screening Trial (NLST) was conducted to determine whether screening with low-dose CT could reduce mortality from lung cancer. From August 2002 through April 2004, we enrolled 53,454 persons at high risk for lung cancer at 33 U.S. medical centers. Participants were randomly assigned to undergo three annual screenings with either low-dose CT (26,722 participants) or single-view posteroanterior chest radiography (26,732). Data were collected on cases of lung cancer and deaths from lung cancer that occurred through December 31, 2009. The rate of adherence to screening was more than 90%. The rate of positive screening tests was 24.2% with low-dose CT and 6.9% with radiography over all three rounds. A total of 96.4% of the positive screening results in the low-dose CT group and 94.5% in the radiography group were false positive results. The incidence of lung cancer was 645 cases per 100,000 person-years (1060 cancers) in the low-dose CT group, as compared with 572 cases per 100,000 person-years (941 cancers) in the radiography group (rate ratio, 1.13; 95% confidence interval [CI], 1.03 to 1.23). There were 247 deaths from lung cancer per 100,000 person-years in the low-dose CT group and 309 deaths per 100,000 person-years in the radiography group, representing a relative reduction in mortality from lung cancer with low-dose CT screening of 20.0% (95% CI, 6.8 to 26.7; P=0.004). The rate of death from any cause was reduced in the low-dose CT group, as compared with the radiography group, by 6.7% (95% CI, 1.2 to 13.6; P=0.02). Screening with the use of low-dose CT reduces mortality from lung cancer. (Funded by the National Cancer Institute; National Lung Screening Trial ClinicalTrials.gov number, NCT00047385.).


A summary measure of health inequalities for a pay-for-population health performance system.
A system that rewards population health must be able to measure and track health inequalities. Health inequalities have most commonly been measured in a bivariate fashion, as a joint distribution of health and another attribute such as income, education, or race/ethnicity. I argue this practice gives insufficient information to reduce health inequalities and propose a summary measure of health inequalities, which gives information both on overall health inequality and bivariate health inequalities. I introduce 2 approaches to develop a summary measure of health inequalities. The bottom-up approach defines attributes of interest, measures bivariate health inequalities related to these attributes separately, and then combines these bivariate health inequalities into a summary index. The top-down approach measures overall health inequality and then breaks it down into health inequalities related to different attributes. After describing the 2 approaches in terms of building-block measurement properties, aggregation, value, data and sample size requirements, and communication, I recommend that, when data are available, a summary measure should use the top-down approach. In addition, a strong communication strategy is necessary to allow users of the summary measure to understand how it was calculated and what it means.


Metabolic stress during hypoglycaemia clamp assessed by microdialysis.
Microdialysis allows the biochemical analysis of interstitial fluids as a bedside procedure. This technique is of interest to evaluate the glucose dependent metabolism in hypoglycaemic patients. It was the aim to perform subcutaneous and blood microdialysis during hypoglycaemic clamp experiments in 12 healthy young men to reveal basis data for critical care microdialysis practice. The hyperinsulinaemic clamp was induced with a continuous infusion of 1.5 mU min(-1) kg(-1) insulin (H-insulin, Hoechst, Frankfurt, Germany). A 20% dextrose solution simultaneously was infused at a variable rate to control blood glucose levels. For hypoglycaemia blood glucose levels were reduced to 40 mg/dL for a 30 min period. Glucose, lactate, pyruvate and glycerol concentrations were semicontinuously measured. The absolute concentrations of glucose and glycerol in blood vs subcutaneous microdialysate were significant different during observation. Until the end of hypoglycaemia, glucose concentration in both compartments declined in parallel, followed by an increase thereafter. During the clamp the subcutaneous glycerol increased threefold, whereas blood glycerol rose with a delay of 15 min and increased only twofold. After the clamp in both compartments glycerol values normalized. The lactate-pyruvate-ratio persisted in normal range throughout the examination. In our experiment subcutaneous lipolysis increased faster and more profound than blood microdialysis. We propose the microdialysis technique as an additional monitoring tool in hypoglycaemia patients.


Potential risk factors and triggers for back pain in children and young adults. A scoping review, part II: unclear or mixed types of back pain.
Back pain is a global problem in terms of disability and financially, with a large burden both to the individual and to society. Back pain was previously believed to be uncommon in children. However, there is a growing body of evidence that this is not the case. Part I of this scoping review studied risk factors of incident and episodic back pain. In this part II we aimed to identify all risk factors and triggers with unclear or mixed type back pain in young people and to identify any gaps in the literature. A scoping review design was selected to summarise the evidence, as there are many studies on "risk factors" for back pain. The scoping review followed the PRISMSA-ScR guidelines. We considered all studies that tested potential risk factors and triggers for thoracic and/or lumbar spine pain, in children, adolescents, and young adults (≤ 24 years). PubMed and Cochrane databases were searched from inception to September 2018, to identify relevant English language articles. The results regarding potential risk factors were separated into temporal precursors and bidirectional risk factors and the studies were classified by study design. Our comprehensive search strategy identified 7356 articles, of which 83 articles were considered eligible for this review (part II). There were 53 cross-sectional studies and 30 cohort studies. Potential risk factors for back pain were: female sex, older age, later pubertal status, positive family history of back pain, increased growth, and a history of back pain, most of which are temporal precursor variables. There was limited research for the illness factors, spinal posture, and muscle endurance in the development of back pain. Many of the included studies approached risk factors in similar ways and found factors that were associated with back pain but were not obvious risk factors as causality was uncertain. Future research should be more rigorous and innovative in the way that risk factors are considered. This could be through statistical approaches including cumulative exposures, or longitudinal approaches including multi-trajectory methods. Additionally, data on proposed risk factors should be collected before the onset of back pain.


A lock-in-based method to examine the thermal signatures of magnetic nanoparticles in the liquid, solid and aggregated states.
We propose a new methodology based on lock-in thermography to study and quantify the heating power of magnetic nanoparticles. Superparamagnetic iron oxide nanoparticles exposed to a modulated alternating magnetic field were used as model materials to demonstrate the potency of the system. Both quantitative and qualitative information on their respective heating power was extracted at high thermal resolutions under increasingly complex conditions, including nanoparticles in the liquid, solid and aggregated states. Compared to conventional techniques, this approach offers a fast, sensitive and non-intrusive alternative to investigate multiple and dilute specimens simultaneously, which is essential for optimizing and accelerating screening procedures and comparative studies.


Physical activity for the prevention and treatment of major chronic disease: an overview of systematic reviews.
The evidence that higher levels of physical activity and/or lower levels of physical inactivity are associated with beneficial health-related outcomes stems mainly from observational studies. Findings from these studies often differ from randomised controlled trials and systematic reviews currently demonstrate mixed results, due partly to heterogeneity in physical activity interventions, methodologies used and populations studied. As a result, translation into clinical practice has been difficult. It is therefore essential that an overview is carried out to compare and contrast systematic reviews, and to identify those physical activity interventions that are the most effective in preventing and/or treating major chronic disease. This protocol has been registered on PROSPERO 2013: CRD42013003523. We will carry out an overview of Cochrane systematic reviews. We will search the Cochrane Database of Systematic Reviews for systematic reviews of randomised controlled trials that have a primary focus on disease-related outcomes. We will restrict reviews to those in selected major chronic diseases. Two authors will independently screen search outputs, select studies, extract data and assess the quality of included reviews using the assessment of multiple systematic reviews tool; all discrepancies will be resolved by discussing and reaching a consensus, or by arbitration with a third author. The data extraction form will summarise key information from each review, including details of the population(s) (for example, disease condition), the context (for example, prevention, treatment or management), the participants, the intervention(s), the comparison(s) and the outcomes. The primary outcomes of interest are the prevention of chronic disease and/or improved outcomes, in the treatment or management of chronic disease. These outcomes will be summarised and presented for individual chronic diseases (for example, any change in blood pressure in hypertension or glucose control in diabetes). Secondary outcomes of interest are to describe the structure and delivery of physical activity interventions across chronic disease conditions and adverse events associated with physical activity. We anticipate that our results could inform researchers, guideline groups and policymakers of the most efficacious physical activity interventions in preventing and/or managing major chronic disease.


Sweet potato leaf extract inhibits the simulated in vitro gastrointestinal digestion of native starch.
Several studies have reported the therapeutic use of caffeoylquinic acid (CQA) derivatives in the management of hyperglycemia. This study used a simulated in vitro gastrointestinal digestion model to assess the inhibitory effects of CQA derivatives-rich sweet potato leaf extract (SPLE) and a commercially produced green coffee bean extract (GCBE), each with total polyphenols contents of 452 mg g-1 and 278 mg g-1, respectively, against starch digestion. The changes in the amounts of total polyphenols and total CQA derivatives during in vitro gastrointestinal digestion were also examined. The results indicated that both extracts contained substantial levels of CQA derivatives (136 mg g-1 and 83.5 mg g-1 of extract for SPLE and GCBE, respectively). The amounts of total polyphenols and total CQA derivatives in 20 mg of SPLE and GCBE samples decreased from 9.04 mg to 0.58 mg and from 5.56 mg to 0.58 mg, and from 2.72 mg to 0.16 mg and from 1.67 mg to 0.10 mg, respectively, following in vitro gastrointestinal digestion and subsequent dialysis. When SPLE and GCBE were accompanied with starch for in vitro digestion test, they both exhibited inhibitory effect against starch digestion during simulated intestinal digestion, with estimated half maximal inhibitory concentration (IC50) values of 4.91 mg and 6.06 mg polyphenols, respectively. The amount of glucose permeated through dialysis membrane also decreased significantly in comparison with the extract-negative control. Thus, both SPLE and GCBE were capable of modulating the release of glucose from starch digestion in simulated intestinal tract. The observed inhibitory effects against glucose release were presumably due in part to the presence of CQA derivatives in the tested extracts. The SPLE had higher inhibitory effect against in vitro starch digestion than the commercially prepared reference GCBE. Therefore, the SPLE might be used to manage hyperglycemia over the long term.


Identifying antimicrobial resistance genes of human clinical relevance within Salmonella isolated from food animals in Great Britain.
To investigate the occurrence of antimicrobial resistance genes of human clinical relevance in Salmonella isolated from livestock in Great Britain. Two hundred and twenty-five Salmonella enterica isolates were characterized using an antimicrobial resistance gene chip and disc diffusion assays. Plasmid profiling, conjugation experiments and identification of Salmonella genomic island 1 (SGI1) were performed for selected isolates. Approximately 43% of Salmonella harboured single or multiple antimicrobial resistance genes with pig isolates showing the highest numbers where 96% of Salmonella Typhimurium harboured one or more resistance genes. Isolates harbouring multiple resistances divided into three groups. Group 1 isolates harboured ampicillin/streptomycin/sulphonamide/tetracycline resistance and similar phenotypes. This group contained isolates from pigs, cattle and poultry that were from several serovars including Typhimurium, 4,[5],12:i:-, Derby, Ohio and Indiana. All Group 2 isolates were from pigs and were Salmonella Typhimurium. They contained a non-sul-type class 1 integron and up to 13 transferrable resistances. All Group 3 isolates harboured a class 1 integron and were isolated from all animal species included in the study. Most isolates were Salmonella Typhimurium and harboured SGI1. Salmonella isolated from livestock was shown to harbour antimicrobial resistance genes although no or little resistance to third-generation cephalosporins or ciprofloxacin, respectively, was detected. The preponderance in pigs of multidrug-resistant Salmonella Typhimurium makes it important to introduce control measures such as improved biosecurity to ensure that they do not pass through the food chain and limit human therapeutic options.


Civic Service as an Intervention to Promote Psychosocial Health and Implications for Mental Health in Post-9/11/01 Era Women Veterans.
Background: Women veterans experience significant morbidity with poorer health and mental health outcomes relative to nonveteran counterparts. Little is known about how to best promote health and well-being among reintegrating female veterans. Civic service has been shown to improve mental health in civilians, but its impact on female veterans is unknown. This study characterizes the physical and mental health and psychosocial functioning of female veterans and evaluates changes in these domains following completion of an intensive civic service program. Materials and Methods: Data were obtained from an observational, pre-post cohort study of post-9/11/01 era veterans who completed a 6-month, 20-hour per week civic service program. Of the 346 participants, 107 were women. Participants completed online pre- and post-program surveys. Nine measures of health, mental health, and psychosocial functioning were analyzed. Results: Before starting the program, 47% of women screened positive for a probable diagnosis of post-traumatic stress disorder (PTSD), 24% for depression, and 51% reported seeking assistance for mental health problems. Pre-post change scores indicated significant improvements on nine measures of health, mental health, and psychosocial functioning (p < 0.05). Perceived self-efficacy change scores predicted PTSD change scores, F(1, 93) = 8.00, p < 0.05. Seeking professional assistance for mental health problems and social isolation and loneliness change scores predicted depression change scores, F(2, 95) = 15.618, p < 0.05, explaining 23% of the variance. Conclusions: Civic service has the potential to promote and support the maintenance of psychosocial well-being for returning post-9/11/01 era women veterans with symptoms of PTSD or depression.


Food for trans-Atlantic rowers: a menu planning model and case study.
Every 4 years, rowers from around the world compete in a 50- to 60-day trans-Atlantic rowing challenge. These ultra-distance rowers require a diet that provides adequate calories, protein, vitamins, minerals, and fluids so they can perform well day after day, minimize fatigue, and stay healthy. Yet, the rowers are confronted with menu planning challenges. The food needs to be lightweight, compact, sturdy, non-spoiling in tropical temperatures, calorie dense, easy to prepare, quick to cook, and good tasting. Financial concerns commonly add another menu planning challenge. The purpose of this case study is to summarize the rowers' food experiences and to provide guidance for sports nutrition professionals who work with ultra-endurance athletes embarking on a physical challenge with similar food requirements. The article provides food and nutrition recommendations as well as practical considerations for ultra-distance athletes. We describe an 8,000 calorie per day menu planning model that uses food exchanges based on familiar, tasty, and reasonably priced supermarket foods that provide the required nutrients and help contain financial costs.


Single-step processing of copper-doped titania nanomaterials in a flame aerosol reactor.
Synthesis and characterization of long wavelength visible-light absorption Cu-doped TiO2 nanomaterials with well-controlled properties such as size, composition, morphology, and crystal phase have been demonstrated in a single-step flame aerosol reactor. This has been feasible by a detailed understanding of the formation and growth of nanoparticles in the high-temperature flame region. The important process parameters controlled were: molar feed ratios of precursors, temperature, and residence time in the high-temperature flame region. The ability to vary the crystal phase of the doped nanomaterials while keeping the primary particle size constant has been demonstrated. Results indicate that increasing the copper dopant concentration promotes an anatase to rutile phase transformation, decreased crystalline nature and primary particle size, and better suspension stability. Annealing the Cu-doped TiO2 nanoparticles increased the crystalline nature and changed the morphology from spherical to hexagonal structure. Measurements indicate a band gap narrowing by 0.8 eV (2.51 eV) was achieved at 15-wt.% copper dopant concentration compared to pristine TiO2 (3.31 eV) synthesized under the same flame conditions. The change in the crystal phase, size, and band gap is attributed to replacement of titanium atoms by copper atoms in the TiO2 crystal.


Development and characterization of human ependymoma xenograft HxBr5.
We describe the successful heterotransplantation of a human ependymoma in CBA/CaJ mice immune deprived by infant thymectomy and whole-body irradiation. The xenograft, HxBr5, was established from a fourth ventricular ependymoma, locally recurrent in an 11-yr-old girl who had been treated with radiation therapy to the posterior fossa. HxBr5 retains histological and ultrastructural fidelity to the tumor from which it was derived as does the DNA content, as confirmed by flow cytometric analysis. The karyotype of the xenograft, which is pseudodiploid and exhibits trisomy 1q and deletion of 1p, is the first human ependymoma banded karyotype to be reported. Growth rates of the xenograft tumors are similar to the primary tumor as clinically observed with a doubling time of approximately 42 days. Cell kinetic parameters indicate that this slow-growing tumor has a relatively high growth fraction of 70.8% with a high cell loss of approximately 91%. We anticipate that HxBr5 may be useful as one component of a more complex model for studying the biology and differentiation of human ependymoma.


Transcriptional analysis of abdominal fat in genetically fat and lean chickens reveals adipokines, lipogenic genes and a link between hemostasis and leanness.
This descriptive study of the abdominal fat transcriptome takes advantage of two experimental lines of meat-type chickens (Gallus domesticus), which were selected over seven generations for a large difference in abdominal (visceral) fatness. At the age of selection (9 wk), the fat line (FL) and lean line (LL) chickens exhibit a 2.5-fold difference in abdominal fat weight, while their feed intake and body weight are similar. These unique avian models were originally created to unravel genetic and endocrine regulation of adiposity and lipogenesis in meat-type chickens. The Del-Mar 14K Chicken Integrated Systems microarray was used for a time-course analysis of gene expression in abdominal fat of FL and LL chickens during juvenile development (1-11 weeks of age). Microarray analysis of abdominal fat in FL and LL chickens revealed 131 differentially expressed (DE) genes (FDR≤0.05) as the main effect of genotype, 254 DE genes as an interaction of age and genotype and 3,195 DE genes (FDR≤0.01) as the main effect of age. The most notable discoveries in the abdominal fat transcriptome were higher expression of many genes involved in blood coagulation in the LL and up-regulation of numerous adipogenic and lipogenic genes in FL chickens. Many of these DE genes belong to pathways controlling the synthesis, metabolism and transport of lipids or endocrine signaling pathways activated by adipokines, retinoid and thyroid hormones. The present study provides a dynamic view of differential gene transcription in abdominal fat of chickens genetically selected for fatness (FL) or leanness (LL). Remarkably, the LL chickens over-express a large number of hemostatic genes that could be involved in proteolytic processing of adipokines and endocrine factors, which contribute to their higher lipolysis and export of stored lipids. Some of these changes are already present at 1 week of age before the divergence in fatness. In contrast, the FL chickens have enhanced expression of numerous lipogenic genes mainly after onset of divergence, presumably directed by multiple transcription factors. This transcriptional analysis shows that abdominal fat of the chicken serves a dual function as both an endocrine organ and an active metabolic tissue, which could play a more significant role in lipogenesis than previously thought.


Comparative effects of caffeine and albuterol on the bronchoconstrictor response to exercise in asthmatic athletes.
The main aim of this study was to evaluate the comparative and additive effects of caffeine and albuterol (short-acting beta (2)-agonist) on the severity of EIB. Ten asthmatic subjects with EIB (exercise-induced bronchoconstriction) participated in a randomized, double-blind, double-dummy crossover study. One hour before an exercise challenge, each subject was given 0, 3, 6, or 9 mg/kg of caffeine or placebo mixed in a flavored sugar drink. Fifteen minutes before the exercise bout, an inhaler containing either albuterol (180 microg) or placebo was administered to each subject. Pulmonary function tests were conducted pre- and post-exercise. Caffeine at a dose of 6 and 9 mg/kg significantly reduced (p<0.05) the mean maximum % fall in post-exercise FEV (1) to -9.0+/-9.2% and -6.8+/-6.5% respectively compared to the double-placebo (-14.3+/-11.1%) and baseline (-18.4+/-7.2%). There was no significant difference (p>0.05) in the post-exercise % fall in FEV (1) between albuterol ( PLUS CAFFEINE PLACEBO) (-4.0+/-5.2%) and the 9 mg/kg dose of caffeine (-6.8+/-6.5%). Interestingly, there was no significant difference (p>0.05) in the post-exercise % fall in FEV (1) between albuterol ( PLUS CAFFEINE PLACEBO) (-4.0+/-5.2%) and albuterol with 3, 6 or 9 mg/kg of caffeine (-4.4+/-3.8, -6.8+/-5.6, -4.4+/-6.0% respectively). Similar changes were observed for the post-exercise % fall in FVC, FEF (25-75%) and PEF. These data indicate that moderate (6 mg/kg) to high doses (9 mg/kg) of caffeine provide a significant protective effect against EIB. It is feasible that the negative effects of daily use of short-acting beta (2)-agonists by asthmatic athletes could be reduced simply by increasing caffeine consumption prior to exercise.


Behavioral health in the gulf coast region following the Deepwater Horizon oil spill: findings from two federal surveys.
This article summarizes findings from two large-scale, population-based surveys conducted by Substance Abuse and Mental Health Services Administration (SAMHSA) and Centers for Disease Control and Prevention (CDC) in the Gulf Coast region following the 2010 Deepwater Horizon oil spill, to measure the prevalence of mental and substance use disorders, chronic health conditions, and utilization of behavioral health services. Although many area residents undoubtedly experienced increased levels of anxiety and stress following the spill, findings suggest only modest or minimal changes in behavioral health at the aggregate level before and after the spill. The studies do not address potential long-term effects of the spill on physical and behavioral health nor did they target subpopulations that might have been most affected by the spill. Resources mobilized to reduce the economic and behavioral health impacts of the spill on coastal residents-including compensation for lost income from BP and increases in available mental health services-may have resulted in a reduction in potential mental health problems.


A density functional study on beryllium-doped carbon dianion clusters CnBe2- (n = 4-14).
Making use of the software of molecular graphics, we designed numerous models of C(n)()Be(2-) (n = 4-14). We carried out geometry optimization and calculation on vibration frequency by means of the B3LYP density functional method. After comparison of structure stability, we found that the ground-state isomers of C(n)()Be(2-) (n = 4-14) are linear with the beryllium atom located inside the C(n)() chain. When a side carbon chain is with an even number of carbon atoms, it is polyacetylene-like, whereas when a side chain is with an odd number of carbon atoms, it is cumulene-like. The C(n)Be(2-) (n = 4-14) clusters with an even number of carbon atoms are more stable than that with an odd number of carbon atoms, matching the peak pattern observed in accelerator mass spectrometry (AMS) and Coulomb Explosion Imaging (CEI) investigations of C(n)()Be(2-) (n = 4-14). The trend of such odd/even alternation is explained based on concepts of bonding characteristics, electronic configuration, electron detachment, and incremental binding energy.


Ultrafiltration modeling of non-ionic microgels.
Membrane ultrafiltration (UF) is a pressure driven process allowing for the separation and enrichment of protein solutions and dispersions of nanosized microgel particles. The permeate flux and the near-membrane concentration-polarization (CP) layer in this process is determined by advective-diffusive dispersion transport and the interplay of applied and osmotic transmembrane pressure contributions. The UF performance is thus strongly dependent on the membrane properties, the hydrodynamic structure of the Brownian particles, their direct and hydrodynamic interactions, and the boundary conditions. We present a macroscopic description of cross-flow UF of non-ionic microgels modeled as solvent-permeable spheres. Our filtration model involves recently derived semi-analytic expressions for the concentration-dependent collective diffusion coefficient and viscosity of permeable particle dispersions [Riest et al., Soft Matter, 2015, 11, 2821]. These expressions have been well tested against computer simulation and experimental results. We analyze the CP layer properties and the permeate flux at different operating conditions and discuss various filtration process efficiency and cost indicators. Our results show that the proper specification of the concentration-dependent transport coefficients is important for reliable filtration process predictions. We also show that the solvent permeability of microgels is an essential ingredient to the UF modeling. The particle permeability lowers the particle concentration at the membrane surface, thus increasing the permeate flux.