Radiosensitization and DNA repair inhibition by the combined use of novel inhibitors of DNA-dependent protein kinase and poly(ADP-ribose) polymerase-1.
The DNA repair enzymes, DNA-dependent protein kinase (DNA-PK) and poly(ADP-ribose) polymerase-1 (PARP-1), are key determinants of radio- and chemo-resistance. We have developed and evaluated novel specific inhibitors of DNA-PK (NU7026) and PARP-1 (AG14361) for use in anticancer therapy. PARP-1- and DNA-PK-deficient cell lines were 4-fold more sensitive to ionizing radiation (IR) alone, and showed reduced potentially lethal damage recovery (PLDR) in G(0) cells, compared with their proficient counterparts. NU7026 (10 micro M) potentiated IR cytotoxicity [potentiation factor at 90% cell kill (PF(90)) = 1.51 +/- 0.04] in exponentially growing DNA-PK proficient but not deficient cells. Similarly, AG14361 (0.4 micro M) potentiated IR in PARP-1(+/+) (PF(90) = 1.37 +/- 0.03) but not PARP-1(-/-) cells. When NU7026 and AG14361 were used in combination, their potentiating effects were additive (e.g., PF(90) = 2.81 +/- 0.19 in PARP-1(+/+) cells). Both inhibitors alone reduced PLDR approximately 3-fold in the proficient cell lines. Furthermore, the inhibitor combination completely abolished PLDR. IR-induced DNA double strand break (DNA DSB) repair was inhibited by both NU7026 and AG14361, and use of the inhibitor combination prevented 90% of DNA DSB rejoining, even 24-h postirradiation. Thus, there was a correlation between the ability of the inhibitors to prevent IR-induced DNA DSB repair and their ability to potentiate cytotoxicity. Thus, individually, or in combination, the DNA-PK and PARP-1 inhibitors act as potent radiosensitizers and show potential as tools for anticancer therapeutic intervention.


Clostridium difficile toxin synthesis is negatively regulated by TcdC.
Clostridium difficile toxin synthesis is growth phase-dependent and is regulated by various environmental signals. The toxin genes tcdA and tcdB are located in a pathogenicity locus, which also includes three accessory genes, tcdR, tcdC and tcdE. TcdR has been shown to act as an alternative sigma factor that mediates positive regulation of both the toxin genes and its own gene. The tcdA, tcdB and tcdR genes are transcribed during the stationary growth phase. The tcdC gene, however, is expressed during exponential phase. This expression pattern suggested that TcdC may act as a negative regulator of toxin gene expression. TcdC is a small acidic protein without any conserved DNA-binding motif. It is able to form dimers and its N-terminal region includes a putative transmembrane domain. Genetic and biochemical evidence showed that TcdC negatively regulates C. difficile toxin synthesis by interfering with the ability of TcdR-containing RNA polymerase to recognize the tcdA and tcdB promoters. In addition, the C. difficile NAP1/027 epidemic strains that produce higher levels of toxins have mutations in tcdC. Interestingly, a frameshift mutation at position 117 of the tcdC coding sequence seems to be, at least in part, responsible for the hypertoxigenicity phenotype of these epidemic strains.


Opinion survey regarding pediatric orthopaedic trauma call and emergency trauma management.
To determine the attitudes and practices of pediatric orthopaedic surgeons regarding on-call coverage and emergency fracture management. A 32-question online survey was sent to all 597 active members of the Pediatric Orthopaedic Society of North America. There were 296 completed surveys, for a response rate of 49.6%. Of the respondents, 85.1% were male. The respondents ranged in age from 30 to older than 70 years, with 54% between 36 and 50 years of age, corresponding to an average of 15 years in practice. Seventy-seven percent of the respondents felt that taking trauma call is an integral aspect of being a pediatric orthopaedist. Of the respondents, 64.9% take call 1 to 9 times per month, 15.8% take 10 to 19 calls, 2.7% take 20 or more, and 16.6% take no call. The number of orthopaedists taking call per practice was fairly evenly distributed between 3 and 10. Call was shared equally in 32% of practices, and mandatory in 72%. Twenty-eight percent of the respondents were additionally compensated for taking calls, in amounts ranging from $100 to $2000 per night, with 1000 dollars the most common rate. One third of operative cases are done that night; one third, the next day; and one third, later in the week. Twenty-four percent of the respondents have dedicated operative block time on the day after the call. Forty-seven percent have a dedicated fracture clinic, of which 51% receive institutional support. Providing emergency trauma care for children is an integral aspect of pediatric orthopaedics. This survey provides information on the attitudes and strategies of practicing pediatric orthopaedic surgeons in the face of decreasing manpower and increasing demand for such services.


Lactobacillus plantarum 2142 prevents intestinal oxidative stress in optimized in vitro systems.
Recently, there has been a growing interest to replace antibiotics' administration with the application of probiotics. The aim of our investigations was to reveal the influence of spent culture supernatant of Lactobacillus plantarum 2142 on the response of enterocytes to oxidative stress, and the spent culture supernatant's ability to protect them from oxidative injury. The experiments were performed on non-carcinogenic porcine epithelial cell line, IPEC-J2 isolated from a neonatal piglet and on human colon adenocarcinoma cell line, Caco-2. The cells cultured on membrane inserts were treated with millimolar hydrogen peroxide solution to provoke oxidative stress. The peroxide-triggered cell response profile was evaluated via determination of change in transepithelial electrical resistance, quantification of extent of cell death by 4',6-diamidino-2 phenylindole (DAPI) staining and via estimation of proinflammatory cytokine, IL-8 production using ELISA technique. Non-starter lactobacilli supernatant-mediated inhibition of peroxide-triggered upregulation of IL-8 production confirmed the antiinflammatory properties of active metabolites produced by Lactobacillus plantarum 2142 in acute oxidative stress.


Isolation and characterization of strains CVO and FWKO B, two novel nitrate-reducing, sulfide-oxidizing bacteria isolated from oil field brine.
Bacterial strains CVO and FWKO B were isolated from produced brine at the Coleville oil field in Saskatchewan, Canada. Both strains are obligate chemolithotrophs, with hydrogen, formate, and sulfide serving as the only known energy sources for FWKO B, whereas sulfide and elemental sulfur are the only known electron donors for CVO. Neither strain uses thiosulfate as an energy source. Both strains are microaerophiles (1% O(2)). In addition, CVO grows by denitrification of nitrate or nitrite whereas FWKO B reduces nitrate only to nitrite. Elemental sulfur is the sole product of sulfide oxidation by FWKO B, while CVO produces either elemental sulfur or sulfate, depending on the initial concentration of sulfide. Both strains are capable of growth under strictly autotrophic conditions, but CVO uses acetate as well as CO(2) as its sole carbon source. Neither strain reduces sulfate; however, FWKO B reduces sulfur and displays chemolithoautotrophic growth in the presence of elemental sulfur, hydrogen, and CO(2). Both strains grow at temperatures between 5 and 40 degrees C. CVO is capable of growth at NaCl concentrations as high as 7%. The present 16s rRNA analysis suggests that both strains are members of the epsilon subdivision of the division Proteobacteria, with CVO most closely related to Thiomicrospira denitrifcans and FWKO B most closely related to members of the genus Arcobacter. The isolation of these two novel chemolithotrophic sulfur bacteria from oil field brine suggests the presence of a subterranean sulfur cycle driven entirely by hydrogen, carbon dioxide, and nitrate.


The relationship between phoria and the ratio of convergence peak velocity to divergence peak velocity.
The purpose of this study was to investigate the relationship between phoria and the dynamics of vergence eye movements as described by the ratio of convergence average peak velocity to divergence average peak velocity, termed the vergence peak velocity ratio. Phoria and vergence step responses were recorded. Three measures of phoria were assessed: baseline phoria, which is the initial phoria measurement; adapted phoria, which is the phoria measured after a visual task; and change in phoria, which is defined as adapted phoria minus baseline phoria. Phoria was modified in two experiments: vergence steps located at different initial positions and different sustained convergent fixations. Four linear regression analyses were conducted to study the interactions among baseline phoria and vergence peak velocity ratio, adapted phoria and vergence peak velocity ratio, baseline and adapted phoria, and baseline phoria and change in phoria. Baseline and adapted phoria were significantly correlated to vergence peak velocity ratio. Adapted phoria and baseline phoria were also significantly correlated. The change in phoria induced by the vergence steps or a sustained fixation task was independent of the baseline phoria. These data support that phoria is a factor in the asymmetry between peak velocity of convergence and divergence and that baseline phoria level is not a factor in the amount of change observed in phoria level (adapted phoria minus baseline phoria). Future oculomotor models of vergence should incorporate phoria within the design.


Improving Cell Engraftment in Cardiac Stem Cell Therapy.
Myocardial infarction (MI) affects millions of people worldwide. MI causes massive cardiac cell death and heart function decrease. However, heart tissue cannot effectively regenerate by itself. While stem cell therapy has been considered an effective approach for regeneration, the efficacy of cardiac stem cell therapy remains low due to inferior cell engraftment in the infarcted region. This is mainly a result of low cell retention in the tissue and poor cell survival under ischemic, immune rejection and inflammatory conditions. Various approaches have been explored to improve cell engraftment: increase of cell retention using biomaterials as cell carriers; augmentation of cell survival under ischemic conditions by preconditioning cells, genetic modification of cells, and controlled release of growth factors and oxygen; and enhancement of cell survival by protecting cells from excessive inflammation and immune surveillance. In this paper, we review current progress, advantages, disadvantages, and potential solutions of these approaches.


Machine learning model for fast prediction of the natural frequencies of protein molecules.
Natural vibrations and resonances are intrinsic features of protein structures and enable differentiation of one structure from another. These nanoscale features are important to help to understand the dynamics of a protein molecule and identify the effects of small sequence or other geometric alterations that may not cause significant visible structural changes, such as point mutations associated with disease or drug design. Although normal mode analysis provides a powerful way to accurately extract the natural frequencies of a protein, it must meet several critical conditions, including availability of high-resolution structures, availability of good chemical force fields and memory-intensive large-scale computing resources. Here, we study the natural frequency of over 100 000 known protein molecular structures from the Protein Data Bank and use this dataset to carefully investigate the correlation between their structural features and these natural frequencies by using a machine learning model composed of a Feedforward Neural Network made of four hidden layers that predicts the natural frequencies in excellent agreement with full-atomistic normal mode calculations, but is significantly more computationally efficient. In addition to the computational advance, we demonstrate that this model can be used to directly obtain the natural frequencies by merely using five structural features of protein molecules as predictor variables, including the largest and smallest diameter, and the ratio of amino acid residues with alpha-helix, beta strand and 3-10 helix domains. These structural features can be either experimentally or computationally obtained, and do not require a full-atomistic model of a protein of interest. This method is helpful in predicting the absorption and resonance functions of an unknown protein molecule without solving its full atomic structure.


Determinants of Neonatal Vitamin D Levels as Measured on Neonatal Dried Blood Spot Samples.
Vitamin D deficiency is linked to adverse childhood health outcomes, yet data on the distribution and quantifiable determinants of neonatal 25-hydroxyvitamin D3 (25OHD) concentration, a vitamin D biomarker, are limited. Our aim was to identify determinants of neonatal 25OHD concentration, measured using neonatal dried blood spots (DBS). A total of 259 ethnically diverse children aged 0-16 years born in Victoria, Australia, were recruited. Data included maternal sun exposure, skin type, 25OHD concentration on stored neonatal DBS, and genotypes at the target genes. Associations were investigated using multiple linear regression models. The median 25OHD concentration was 29.2 nmol/l (IQR 18.0-47.4). Measured 25OHD was <50 nmol/l in almost half of the neonatal sample. Ambient ultraviolet radiation (UVR) 6 weeks before birth was the strongest predictor of neonatal 25OHD, accounting for 23% of its variation. A further 10% was explained by infant genetic variants at GC (rs2282679), the gene encoding the vitamin D binding protein, and DHCR7 (rs12785878), a gene required for synthesis of 7-dehydrocholesterol, a precursor to 25OHD. DBS age explained 7%, and patterns of maternal sun exposure and clothing choices accounted for 4%. A child's skin colour was strongly associated with GC gene variants and not independent of these variants in predicting 25OHD. The final model explained 43% of the total variance in neonatal 25OHD concentration. Maternal lifestyle factors and infant genetic variants predict neonatal 25OHD levels; the importance of maternal UVR exposure in late pregnancy is highlighted.


HIV, HTLV-1, and HBV infections in a cohort of Italian intravenous drug abusers: analysis of risk factors.
A seroepidemiological survey of a group of 291 intravenous drug abusers (IVDAs), 45 household contacts of IVDAs, and 39 laboratory workers has been carried out to determine the prevalence of HIV-1, HIV-2, HTLV-1, and HBV antibodies in the sera, as well as to evaluate the role of various risk factors. Among i.v. drug abusers, the prevalence was 32.3% for HIV-1 and 6.6% for HTLV-1. For both viruses, the total figures did not significantly change from 1985 through 1987, accounting for a slow viral circulation in this group. No seropositivity (HIV-1, HTLV-1) was found among laboratory workers, whereas one subject was found seropositive for HIV-1 among household contacts. From 1985 to 1986, 5 out of 58 subjects seronegative for HIV-1 and 5 out of 82 seronegative for HTLV-1 seroconverted (incidence rates of 8.6 and 6.1%, respectively). From 1986 to 1987, none out of 11 seronegatives for HIV and 1 out of 16 seronegatives for HTLV-1 seroconverted. The total figures for hepatitis B markers were 79.2% among IVDAs, 24.4% among household contacts, and 25.6% among laboratory workers. A significant correlation was found between presence of HBV markers and seropositivity for HIV and HTLV-1. A significant association with HIV-1 seropositivity was found for history of sexual intercourse with HIV-1 seropositive partners and for sexual promiscuity. These data emphasize the important role played by sexual behavior in addition to needle-sharing in the spreading of multiple infections among drug abusers.


Correlates of prone infant sleeping position by period of birth.
Intervention to avoid the prone sleeping position during infancy has occurred in various countries after evidence that it increases the risk of sudden infant death syndrome (SIDS). This study examined cohort data to determine if correlates of the prone position differed by period of birth, before intervention (1 May 1988 to 30 April 1991) compared with after intervention (1 May 1991 to 30 April 1992). The usual prone sleeping position was more closely associated with the following factors after intervention: teenage motherhood, low maternal education, paternal unemployment, unmarried motherhood, non-specialist antenatal care, not reading books to prepare for a baby, poor smoking hygiene, and bottle feeding. For example, the association of usual prone position with being unmarried shown by the odds ratio (95% confidence interval) was 0.54 (0.47 to 0.63) in the period before intervention and 1.92 (1.18 to 3.15) in the period after intervention. The alteration in correlates of the prone position reported here provide an example to support the theoretical concept that well known 'modifiable' risk factors for disease tend to be associated with each other in both populations and individuals. This phenomenon was not evident in the population before intervention, that is, before the prone sleeping position became a well known SIDS risk factor.


Severe psychiatric disorders in mid-life and risk of dementia in late- life (age 65-84 years): a population based case-control study.
To examine the association of mid-life exposure to several psychiatric disorders with the development of late-life dementia. A matched case-control study using Western Australian state-wide hospital inpatient, outpatient mental health and emergency records linked to death records. Incident dementia cases (2000-2009) aged 65 to 84 years were sex- and age-matched to an electoral roll control. Records as far back as 1970 were used to assess exposure to medical risk factors before age 65 years. Candidate psychiatric risk factors were required to be present at least 10 years before dementia onset to ensure direction of potential causality. Odds ratios were estimated using conditional logistic regression. 13, 568 dementia cases (median age 78.7 years, 43.4 % male) were matched to a control. Depression, bipolar disorder, schizophrenia, anxiety disorder and alcohol dependence were found to be significant and independent risk factors for late-life dementia after adjusting for diabetes, heart disease, cerebrovascular disease and smoking risk factors. The effect of a history of depression, schizophrenia and alcohol dependency on dementia risk varied with age, being strongest for earlier onset late-life dementia and waning at older ages. Severe depression, anxiety disorder, bipolar disorder, schizophrenia and alcoholic dependency disorder treated by specialists in psychiatric facilities in mid-life are important risk factors for late-life dementia. These psychiatric conditions need to be considered in future studies of the risk and prevention of late-life dementia.


Implications and refinements of the establishing operation concept.
In this paper I discuss (a) three steps in the development of establishing operation (EO) terminology, (b) my early neglect of its possible relevance to applied behavior analysis, (c) the importance of functional analysis methodology for increasing awareness of EO issues, and (d) three comprehensive reviews that clarify the role of EOs in applied work. I then review and further analyze seven topics that require further clarification or that have been raised since my 1982 and 1993 articles: the EO evocative effect, deprivation and satiation, problem behavior maintained by attention, decreasing behavior evoked by a transitive conditioned establishing operation, EOs in the context of escape and avoidance, academic demand, and decreasing behavior evoked by a reflexive conditioned establishing operation.


Underuse of Cardiovascular Medications in Individuals With Known Lower Extremity Peripheral Artery Disease: HCHS/SOL.
Background Underuse of cardiovascular medications for secondary prevention among individuals with peripheral artery disease (PAD) has been reported. Little is known about PAD treatment status in the Hispanic/Latino population in the United States, who may have limited access to health care and who have worse clinical outcomes than non-Hispanic individuals. Methods and Results We studied the use of cardiovascular therapies in 1244 Hispanic/Latino individuals recruited from 4 sites in the United States, including 826 individuals who reported diagnosis of PAD by physician and 418 individuals with coronary artery disease alone, in the Hispanic Community Health Study/Study of Latinos. We compared the prevalence of using antiplatelet therapy, lipid-lowering therapy and antihypertensive therapy by PAD and coronary artery disease status. Among those with PAD, we studied factors associated with taking cardiovascular medications, including demographic and socioeconomic factors, acculturation, access to health care and comorbidities, using multivariable regression models. The overall prevalence for individuals with PAD taking antiplatelet therapy, lipid-lowering therapy and, among hypertensive individuals, antihypertensive therapy was 31%, 26% and 57%, respectively. Individuals of Mexican background had the lowest use for all classes of cardiovascular medications. Older age, number of doctor visits and existing hypertension and diabetes mellitus were significantly associated with taking cardiovascular therapies in adjusted models. Compared with those with PAD alone, individuals with PAD and concurrent coronary artery disease were 1.52 (95% CI, 1.20-1.93) and 1.74 (1.30-2.32) times more likely to use antiplatelet agents and statins according to multivariable analysis. No significant difference of antihypertensive medication use was found among PAD patients with or without coronary artery disease. Conclusions Hispanic/Latino individuals with known PAD underuse cardiovascular medications recommended in clinical guidelines. More efforts should be directed to improve treatment in this important group.


Dual-gated MoS2/WSe2 van der Waals tunnel diodes and transistors.
Two-dimensional layered semiconductors present a promising material platform for band-to-band-tunneling devices given their homogeneous band edge steepness due to their atomically flat thickness. Here, we experimentally demonstrate interlayer band-to-band tunneling in vertical MoS2/WSe2 van der Waals (vdW) heterostructures using a dual-gate device architecture. The electric potential and carrier concentration of MoS2 and WSe2 layers are independently controlled by the two symmetric gates. The same device can be gate modulated to behave as either an Esaki diode with negative differential resistance, a backward diode with large reverse bias tunneling current, or a forward rectifying diode with low reverse bias current. Notably, a high gate coupling efficiency of ∼80% is obtained for tuning the interlayer band alignments, arising from weak electrostatic screening by the atomically thin layers. This work presents an advance in the fundamental understanding of the interlayer coupling and electron tunneling in semiconductor vdW heterostructures with important implications toward the design of atomically thin tunnel transistors.


Macular Features in Retinitis Pigmentosa: Correlations Among Ganglion Cell Complex Thickness, Capillary Density, and Macular Function.
To investigate correlations among macular ganglion cell complex (GCC) layer thickness, macular capillary density, and macular function in patients affected by retinitis pigmentosa (RP). Fourteen patients (28 eyes) with previous diagnosis of RP were enrolled. The diagnosis of these conditions was made based on both clinical features and electrophysiological examination. All patients underwent a complete ophthalmologic examination, including optical coherence tomography angiography (OCTA) and multifocal electroretinogram (mfERG). Main outcome measures were macular GCC layer thickness; superficial capillary plexus (SCP) vessel density; deep capillary plexus (DCP) vessel density; choriocapillaris plexus (CCP) vessel density; and amplitudes of mfERG N1 and P1 waves. Average GCC thickness was significantly thinner in RP patients (76.0 ± 25.1 and 109.2 ± 17.5 μm, P = 0.028). Superficial capillary plexus density was 42.2 ± 3.4% in the RP group and 51.4 ± 2.3% in the control group (P < 0.001). Deep capillary plexus density was reduced in RP patients (42.7 ± 6.2%) after the comparison with healthy subjects (56.6 ± 2.2%, P < 0.001). Choriocapillaris plexus density was significantly less in RP patients than in the control group (65.3 ± 2.7% and 67.2 ± 1.4%, P = 0.024). Superficial capillary plexus and DCP density were significantly correlated with both mfERG values and GCC thickness. We showed that both choroid and retinal vessels were modified in RP patients after comparison with healthy subjects. Moreover, we demonstrated that the SCP and DCP vessel densities are correlated with the macular function, as well as with the GCC thickness.


Rebuilding and guiding a care community: A grounded theory of end-of-life nursing care practice in long-term care settings.
To investigate the end-of-life (EOL) nursing care practice process in long-term care (LTC) settings for older adults in Japan. A qualitative study based on grounded theory developed by Corbin and Strauss. Sampling, interviewing, and analysis were performed cyclically, with results for each stage used as the basis for data collection and next-stage analysis decisions. Semi-structured interviews were conducted from March 2015-March 2019 with 22 nurses from eight LTC settings. Analysis was performed using coding, constant comparison, and emerging categories. The core category, "guiding the rebuilt care community to assist the dying resident" comprised five categories: "assessing the resident's stage," "harmonizing care with the dying process," "rebuilding a care community," "helping community members care for the resident," and "encouraging community members to give meaning." The participants were described as "traditional village elders" who were the integral members of the care community, as well as guides who helped and encouraged the community. Results revealed the holistic process of EOL nursing-care practice in Japan. Nurses aimed to allow LTC residents to die as social human beings, surrounded by people, and not just responding physical and psychological distress. Such practice requires nursing expertise, healthcare skills, and leadership qualities to build and serve care communities. Nurses must also consider residents' uncertainties and vulnerabilities as well as their cultural backgrounds. This study showed that the nurses hold unique roles in providing dying people with care from a community. These findings can potentially be applied for developing a universal model for LTC nurses in many aging populations, to modify their EOL care practice, educate new LTC nurses, and collaborate with other healthcare professionals.


Mouse model for Lowe syndrome/Dent Disease 2 renal tubulopathy.
The Lowe oculocerebrorenal syndrome is an X-linked disorder characterized by congenital cataracts, cognitive disability, and proximal tubular dysfunction. Both this syndrome and Dent Disease 2 result from loss-of-function mutations in the OCRL gene, which encodes a type II phosphatidylinositol bisphosphate 5-phosphatase. Ocrl-deficient mice are unaffected, however, which we believe reflects a difference in how humans and mice cope with the enzyme deficiency. Inpp5b and INPP5B, paralogous autosomal genes that encode another type II phosphoinositide 5-phosphatase in mice and humans, respectively, might explain the distinct phenotype in the two species because they are the closest paralogs to Ocrl and OCRL in their respective genomes yet differ between the two species with regard to expression and splicing. Here, we generated Ocrl(-/-) mice that express INPP5B but not Inpp5b. Similar to the human syndromes, all showed reduced postnatal growth, low molecular weight proteinuria, and aminoaciduria. Thus, we created an animal model for OCRL and Dent Disease 2 tubulopathy by humanizing a modifier paralog in mice already carrying the mutant disease gene.


Use of a DNA method, QF-PCR, in the prenatal diagnosis of fetal aneuploidies.
To provide Canadian health care providers with current information on the use of quantitative fluorescent polymerase chain reaction (QF-PCR) or equivalent technology in the prenatal diagnosis of fetal chromosomal abnormalities. Over the last few decades, prenatal diagnosis of fetal chromosomal abnormalities has relied on conventional cytogenetic analysis of cultured amniocytes, chorionic villi, or fetal blood. In the last few years, the clinical validity of a newer technique, QF-PCR, to detect the common aneuploidies has been reported by a number of investigators. This technique has the advantage of providing rapid results for the diagnosis or exclusion of aneuploidy in chromosomes 13, 18, 21, X or Y. It is now possible to choose standard chromosome analysis or QF-PCR for the prenatal diagnosis of chromosomal abnormalities, or to perform both tests, depending on the clinical indication for testing. This document reviews the clinical utility of QF-PCR and makes recommendations for its use in the care of Canadian patients. Medline and PubMed were searched for articles published in English between January 2000 and December 2010 that presented data on the use of QF-PCR versus standard cytogenetic analysis of prenatal samples. A second search was done to identify publications in English that provided results of cytogenetic analysis performed on prenatal samples for women at an increased risk of fetal aneuploidy because of maternal age, abnormal prenatal screening results, or fetal soft ultrasound markers suggestive of an increased risk of aneuploidy. Publications were included if they provided detailed information on the abnormalities detected, regardless of whether or not rapid aneuploidy screening was undertaken. Results were restricted to systematic reviews, randomized controlled trials, and relevant observational studies. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. The quality of evidence was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care (Table 1). This guideline promotes the use of a rapid aneuploidy DNA test for women at increased risk of having a pregnancy affected by a common aneuploidy. This will have the benefit of providing rapid and accurate results to women at increased risk of fetal Down syndrome, trisomy 13, trisomy 18, sex chromosome aneuploidy or triploidy. It will also promote better use of laboratory resources and reduce the cost of prenatal diagnosis. However, a small percentage of pregnancies with a potentially clinically significant chromosomal abnormality will remain undetected by QF-PCR but detectable by conventional cytogenetics. Recommendations 1. QF-PCR is a reliable method to detect trisomies and should replace conventional cytogenetic analysis whenever prenatal testing is performed solely because of an increased risk of aneuploidy in chromosomes 13, 18, 21, X or Y. As with all tests, pretest counselling should include a discussion of the benefits and limitations of the test. In the initial period of use, education for health care providers will be required. (II-2A) 2. Both conventional cytogenetics and QF-PCR should be performed in all cases of prenatal diagnosis referred for a fetal ultrasound abnormality (including an increased nuchal translucency measurement > 3.5 mm) or a familial chromosomal rearrangement. (II-2A) 3. Cytogenetic follow-up of QF-PCR findings of trisomy 13 and 21 is recommended to rule out inherited Robertsonian translocations. However, the decision to set up a back-up culture for all cases that would allow for traditional cytogenetic testing if indicated by additional clinical or laboratory information should be made by each centre offering the testing according to the local clinical and laboratory experience and resources. (III-A) 4. Other technologies for the rapid detection of aneuploidy may replace QF-PCR if they offer a similar or improved performance for the detection of trisomy 13, 18, 21, and sex chromosome aneuploidy. (III-A).


Maternal occupational exposure during pregnancy and the risk of spina bifida.
A case-control study was carried out to explore associations between spina bifida and occupational exposure of the mother. The cases were children with spina bifida aperta born between 1980 and 1992 from nine hospitals in the Netherlands. The controls were children born healthy in the same period as the cases, from hospitals and from the general population. Data collection was carried out in two steps. Firstly, postal questionnaires were sent to all the parents of cases and controls to gather information on occupations and potential confounders. In the second phase of the study, information on specific exposures was collected by means of job and task specific personal interviews. Interviews were performed with 55 case mothers and 66 control mothers who had occupations with a potential for chemical or physical exposure. Those exposures were assumed to be negligible for--for example, teachers and secretaries, so personal interviews were not indicated for these women. Information was collected on specific tasks in the period just after conception, and on the associated use of chemical or physical agents, frequency of exposure, and use of protective equipment. The analyses of occupation showed an increased risk for women working in agricultural occupations (OR = 3.4, CI:1.3-9.0), and, although less distinct, for cleaning women (OR = 1.7, CI:0.9-3.4). Only a few women seemed to be occupationally exposed to chemical or physical agents. No differences in occurrence of specific exposures could be detected between cases and controls. Besides, no differences were seen in pesticide or disinfectant exposure among case and control mothers in agricultural occupations. Occupational exposures of the mother during pregnancy were infrequent and did not seem to play an important part in the aetiology of spina bifida in this study. The association found between spina bifida and maternal agricultural occupations could not be explained by the use of pesticides by the mother or by any other occupational exposure.


Neural correlates of attentional capture in visual search.
Much behavioral research has shown that the presence of a unique singleton distractor during a task of visual search will typically capture attention and thus disrupt target search. Here we examined the neural correlates of such attentional capture using functional magnetic resonance imaging in human subjects during performance of a visual search task. The presence (vs. absence) of a salient yet irrelevant color singleton distractor was associated with activity in the superior parietal cortex and frontal cortex. These findings imply that the singleton distractor induced spatial shifts of attention despite its irrelevance, as predicted from an AC account. Moreover, behavioral interference by singleton distractors was strongly and negatively correlated with frontal activity. These findings provide direct evidence that the frontal cortex is involved in control of interference from irrelevant but attention-capturing distractors.


The development of a method for the preparation of rat intestinal epithelial cell primary cultures.
We describe a reproducible method for growing small intestinal epithelium (derived from the suckling rat intestine) in short-term (primary) cultures. Optimal culture conditions were determined by quantitative assays of proliferation (i.e. changes in cellularity and DNA synthesis). Isolation of the epithelia and, significantly, preservation of its three-dimensional integrity was achieved using a collagenase/dispase digestion technique. Purification of the epithelium was also facilitated by the use of a simple differential sedimentation method. The results presented below support the idea that proliferation of normal gut epithelium ex vivo is initially dependent upon the maintenance of the structural integrity of this tissue and upon factors produced by heterologous mesenchymal cells. Proliferation in vitro was also critically dependent upon the quality of the medium and constituents used. Cultures reached confluence within 10-14 days and consisted of epithelial colonies together with varying amounts of smooth-muscle-like cells. Cultures have been maintained for periods up to one month, but the longer-term potential for growth by sub-culturing has not been examined. Strategies for reducing the proliferation of these non-epithelial cells are also described.


The complete DNA sequence of yeast chromosome III.
The entire DNA sequence of chromosome III of the yeast Saccharomyces cerevisiae has been determined. This is the first complete sequence analysis of an entire chromosome from any organism. The 315-kilobase sequence reveals 182 open reading frames for proteins longer than 100 amino acids, of which 37 correspond to known genes and 29 more show some similarity to sequences in databases. Of 55 new open reading frames analysed by gene disruption, three are essential genes; of 42 non-essential genes that were tested, 14 show some discernible effect on phenotype and the remaining 28 have no overt function.


Optimising poly(lactic-co-glycolic acid) microparticle fabrication using a Taguchi orthogonal array design-of-experiment approach.
The objective of this study was to identify, understand and generate a Taguchi orthogonal array model for the formation of 10-50 μm microparticles with applications in topical/ocular controlled drug delivery. Poly(lactic-co-glycolic acid) (PLGA) microparticles were fabricated by the single emulsion oil-in-water method and the particle size was characterized using laser diffraction and scanning electronic microscopy (SEM). Sequential Taguchi L12 and L18 orthogonal array (OA) designs were employed to study the influence of ten and eight parameters, respectively, on microparticle size (response). The first optimization step using the L12 design showed that all parameters significantly influenced the particle size of the prepared PLGA microparticles with exception of the concentration of poly(vinyl alcohol) (PVA) in the hardening bath. The smallest mean particle size obtained from the L12 design was 54.39 μm. A subsequent L18 design showed that the molecular weight of PLGA does not significantly affect the particle size. An experimental run comprising of defined parameters including molecular weight of PLGA (89 kDa), concentration of PLGA (20% w/v), concentration of PVA in the emulsion (0.8% w/v), solvent type (ethyl acetate), organic/aqeuous phase ratio (1:1 v/v), vortexing speed (9), vortexing duration (60 seconds), concentration of PVA in hardening bath (0.8% w/v), stirring speed of hardening bath (1200 rpm) and solvent evaporation duration (24 hours) resulted in the lowest mean particle size of 23.51 μm which was predicted and confirmed by the L18 array. A comparable size was demonstrated during the fabrication of BSA-incorporated microparticles. Taguchi OA design proved to be a valuable tool in determining the combination of process parameters that can provide the optimal condition for microparticle formulation. Taguchi OA design can be used to correctly predict the size of microparticles fabricated by the single emulsion process and can therefore, ultimately, save time and costs during the manufacturing process of drug delivery formulations by minimising experimental runs.


VERP and brain imaging for identifying levels of visual dorsal and ventral stream function in typical and preterm infants.
Visual development is a key area for understanding and assessing early brain development. Different levels in the hierarchy of visual processing, from the initial response to flashes of light, through selective responses to contour orientation and motion in primary visual cortex (V1), to global processing in extrastriate of large-scale patterns of form and motion, can each be assessed using stimuli designed to isolate specific neural activity in visual event-related potentials (VERPs). This approach has been used to reveal the sequence of emergence of different visual cortical functions in the first 6 months of typical human development, and to provide early indicators of anomalies in brain development. Delayed or absent onset of orientation-reversal (OR-)VERPs, as a measure of cortical development, has been shown to be a sensitive indicator of perinatal brain damage in both term-born and prematurely born infants. Direction-reversal (DR-)VERPs appear a few weeks later than OR-VERPs in typical development, and are further delayed in even healthy children born preterm, reflecting possible early vulnerability of the motion (dorsal stream) system. High-density recordings of responses to global motion and global form patterns show that these extrastriate systems are typically functional by 5 months of age, but the topography of the activity distributions shows that the brain systems underlying these responses are radically reorganized between infancy and adulthood. In prematurely born infants whose structural brain MRI was evaluated at birth, the onset of the response is absent or delayed in those with severe brain injury, while in those with mild/moderate brain injury the response is present but its spatial organization is further from the adult pattern than those in controls. These findings are related to the development of distinct networks of brain areas in the dorsal and ventral cortical streams, and the apparent vulnerability of the dorsal-stream network in a wide range of both genetic and acquired developmental disorders.


1H nuclear magnetic resonance studies of seminal plasma from fertile and infertile men.
Glycerylphosphorylcholine (GPC), glycerylphosphorylethanolamine (GPE), citrate, and lactate content of human seminal plasma was analysed by measuring the peak area of 1H nuclear magnetic resonance (NMR) spectra in samples from four groups of patients: 21 spermatogenic failure subjects; 14 obstructive azoospermic subjects (vasectomized); seven patients presenting very severe oligoasthenozoospermia (OAT) and 18 normozoospermic subjects (control). The peak areas for GPC, citrate and lactate in seminal plasma were significantly smaller for patients with azoospermia than for the control group: 16.79, 8.18 and 2.28 versus 23.38, 10.58 and 4.30, respectively (P < 0.01). The peak area ratios for citrate:lactate and GPC:lactate were significantly different (P < 0.01) between the control group and the spermatogenic failure or obstructive azoospermia groups. A significant difference was also found in GPE:GPC peak intensity ratio between spermatogenic failure and obstructive azoospermia subjects (P < 0.001). These results provide some quantitative markers which may be used for examining infertility by using 1H NMR of seminal plasma samples.


Interobserver Agreement on Pathologic Features of Liver Biopsy Tissue in Patients with Nonalcoholic Fatty Liver Disease.
The histomorphologic criteria for the pathological features of liver tissue from patients with non-alcoholic fatty liver disease (NAFLD) remain subjective, causing confusion among pathologists and clinicians. In this report, we studied interobserver agreement of NAFLD pathologic features and analyzed causes of disagreement. Thirty-one cases of clinicopathologically diagnosed NAFLD from 10 hospitals were selected. One hematoxylin and eosin and one Masson's trichrome-stained virtual slide from each case were blindly reviewed with regard to 12 histological parameters by 13 pathologists in a gastrointestinal study group of the Korean Society of Pathologists. After the first review, we analyzed the causes of disagreement and defined detailed morphological criteria. The glass slides from each case were reviewed a second time after a consensus meeting. The degree of interobserver agreement was determined by multi-rater kappa statistics. Kappa values of the first review ranged from 0.0091-0.7618. Acidophilic bodies (k = 0.7618) and portal inflammation (k = 0.5914) showed high levels of agreement, whereas microgranuloma (k = 0.0984) and microvesicular fatty change (k = 0.0091) showed low levels of agreement. After the second review, the kappa values of the four major pathological features increased from 0.3830 to 0.5638 for steatosis grade, from 0.1398 to 0.2815 for lobular inflammation, from 0.1923 to 0.3362 for ballooning degeneration, and from 0.3303 to 0.4664 for fibrosis. More detailed histomorphological criteria must be defined for correct diagnosis and high interobserver agreement of NAFLD.


The gastrointestinal stimulus to insulin release. II. A dual action of secretin.
The insulin release after an oral glucose load is both earlier and greater than would be expected from the glycemic stimulus. This augmentation of insulin release has been attributed to humoral factors from the gut. It has been previously demonstrated that secretin is released very rapidly after oral glucose and postulated that it acts as an early trigger to insulin release. This effect would not explain the magnitude of the peak insulin response which occurs about 30 min after peak secretin levels. The present studies, however, demonstrate an additional action of secretin which may explain this. To further study the role of secretin in insulin release in normal subjects, two consecutive 20 min intravenous glucose infusions were administered 150 min apart with and without an intervening secretin infusion (10 U) given to approximate serum secretin levels seen after oral glucose ingestion. A highly significant (P<0.01) potentiation of the insulin response to the post-secretin glucose infusion was observed. This occurred both when secretin was given 7 min or 25 min before glucose. In the latter case, serum secretin was undetectable during the glucose infusion. These studies demonstrate that secretin potentiates the glycemic release of insulin. Despite the augmented insulin response, no consistent change in blood glucose variation was observed. This is consistent with the suggestion that the facilitated disposal of an alimentary glucose load is not dependent solely on enhanced insulin secretion. Secretin appears to have a dual role in insulin release, an early direct stimulation followed by a prolonged potentiation of the glycemic stimulus. The potentiating effect is of such magnitude to suggest that secretin is the dominant factor in the enteric component of insulin release after an oral glucose load.


Colorectal cancer screening of Californian adults of Mexican origin as a function of acculturation.
Californian Latinos have lower rates of colorectal cancer (CRC) screening compared to non-Latino whites, which may account in part for disparities in colorectal incidence trends. Participants, 603 Mexican-American men and 893 women aged 50 and older who had not been diagnosed with colon cancer, reported CRC screening behavior on the 2005 California Health Interview Survey. A 7-item acculturation index (English language use/proficiency, nativity, citizenship, and years living in the U.S.) was developed. A logistic regression model predicted CRC screening as a function of acculturation. Higher acculturated Mexican-Americans were 3-4 times more likely to have had both fecal occult blood test and endoscopic CRC screening. Lower acculturated Mexican men and women were twice as likely to not have any CRC screening. Colorectal screening is effective in preventing cancer; educational and outreach efforts and efforts to decrease language barriers among lower-acculturated Mexican-Americans should be intensified.


Specific adsorption of perchlorate anions on Pt{hkl} single crystal electrodes.
The voltammetry of Pt{111}, Pt{100}, Pt{110} and Pt{311} single crystal electrodes as a function of perchloric acid concentration (0.05-2.00 M) has been studied in order to test the assertion made in recent reports by Watanabe et al. that perchlorate anions specifically adsorb on polycrystalline platinum. Such an assertion would have significant ramifications for our understanding of electrocatalytic processes at platinum surfaces since perchlorate anions at low pH have classically been assumed not to specifically adsorb. For Pt{111}, it is found that OHad and electrochemical oxide states are both perturbed significantly as perchloric acid concentration is increased. We suggest that this is due to specific adsorption of perchlorate anions competing with OHad for adsorption sites. The hydrogen underpotential deposition (H UPD) region of Pt{111} however remains unchanged although evidence for perchlorate anion decomposition to chloride on Pt{111} is reported. In contrast, for Pt{100} no variation in the onset of electrochemical oxide formation is found nor any shift in the potential of the OHad state which normally results from the action of specifically adsorbing anions. This suggests that perchlorate anions are non-specifically adsorbed on this plane although strong changes in all H UPD states are observed as perchloric acid concentration is increased. This manifests itself as a redistribution of charge from the H UPD state situated at more positive potential to the one at more negative potential. For Pt{110} and Pt{311}, marginal changes in the onset of electrochemical oxide formation are recorded, associated with specific adsorption of perchlorate. Specific adsorption of perchlorate anions on Pt{111} is deleterious to electrocatalytic activity in relation to the oxygen reduction reaction (ORR) as measured using a rotating disc electrode (RDE) in a hanging meniscus configuration. This study supports previous work suggesting that a large component of the ORR activity on platinum is governed by simple site blocking by specifically adsorbed anions and/or electrosorbed oxide.


Identification of patients at risk for anaphylaxis due to streptokinase.
To identify patients at risk for immediate-type allergic reactions to streptokinase, we performed streptokinase skin tests on patients immediately before planned administration of intravenous streptokinase for treatment of acute myocardial infarction. Forty-five patients had negative skin tests and received streptokinase without allergic reaction. One patient had a positive skin test and was given urokinase instead, without incident. Positive skin tests were also present in a patient who had recently had an anaphylactic reaction to streptokinase, and in two physician volunteers who had been sensitized to streptokinase during initial determination of the optimal skin testing dose. Immunoassays for IgE to streptokinase were performed on serum samples from skin-tested patients and volunteers, and on 16 other patients who had not been skin tested but had previously received streptokinase without allergic reactions. The skin test was a sensitive and specific indicator of elevated levels of IgE to streptokinase. We propose that skin testing immediately before streptokinase administration is a practical approach for identifying patients at risk for immediate-type allergic reactions to streptokinase, and its use may possibly prevent anaphylaxis and death.


From consumerism to active dependence: Patterns of medicines use and treatment decisions among patients with atopic dermatitis.
In this article, findings from in-depth interviews with 12 people diagnosed with atopic dermatitis (AD) are described. The findings describe the range of strategies used to manage atopic dermatitis, including use of conventional medicines. A strong theme identified in informants' accounts centred on concerns about the risks of illness and long-term use of conventional medicines, which acted as a strong incentive for patients to seek alternatives to conventional treatments. However, despite their significant efforts to do so, patients were eventually forced to return to and rely on conventional medicines because of their efficacy in alleviating and treating symptoms. These findings are discussed in relation to the sociological literature on consumerism, risk and reflexivity in health. We argue that our findings exemplify how living with and managing a chronic illness may not be straightforward and the choices of treatment at hand may be limited. Consequently, this may limit the potential opportunities accruing from adopting a reflexive or consumerist approach to managing illness.


Rhomboid 3 orchestrates Slit-independent repulsion of tracheal branches at the CNS midline.
EGF-receptor ligands act as chemoattractants for migrating epithelial cells during organogenesis and wound healing. We present evidence that Rhomboid 3/EGF signalling, which originates from the midline of the Drosophila ventral nerve cord, repels tracheal ganglionic branches and prevents them from crossing it. rho3 acts independently from the main midline repellent Slit, and originates from a different sub-population of midline cells: the VUM neurons. Expression of dominant-negative Egfr or Ras induces midline crosses, whereas activation of the Egfr or Ras in the leading cell of the ganglionic branch can induce premature turns away from the midline. This suggests that the level of Egfr intracellular signalling, rather than the asymmetric activation of the receptor on the cell surface, is an important determinant in ganglionic branch repulsion. We propose that Egfr activation provides a necessary switch for the interpretation of a yet unknown repellent function of the midline.


UBR2 of the N-end rule pathway is required for chromosome stability via histone ubiquitylation in spermatocytes and somatic cells.
The N-end rule pathway is a proteolytic system in which its recognition components (N-recognins) recognize destabilizing N-terminal residues of short-lived proteins as an essential element of specific degrons, called N-degrons. The RING E3 ligases UBR2 and UBR1 are major N-recognins that share size (200 kDa), conserved domains and substrate specificities to N-degrons. Despite the known function of the N-end rule pathway in degradation of cytosolic proteins, the major phenotype of UBR2-deficient male mice is infertility caused by arrest of spermatocytes at meiotic prophase I. UBR2-deficient spermatocytes are impaired in transcriptional silencing of sex chromosome-linked genes and ubiquitylation of histone H2A. In this study we show that the recruitment of UBR2 to meiotic chromosomes spatiotemporally correlates to the induction of chromatin-associated ubiquitylation, which is significantly impaired in UBR2-deficient spermatocytes. UBR2 functions as a scaffold E3 that promotes HR6B/UbcH2-dependent ubiquitylation of H2A and H2B but not H3 and H4, through a mechanism distinct from typical polyubiquitylation. The E3 activity of UBR2 in histone ubiquitylation is allosterically activated by dipeptides bearing destabilizing N-terminal residues. Insufficient monoubiquitylation and polyubiquitylation on UBR2-deficient meiotic chromosomes correlate to defects in double strand break (DSB) repair and other meiotic processes, resulting in pachytene arrest at stage IV and apoptosis. Some of these functions of UBR2 are observed in somatic cells, in which UBR2 is a chromatin-binding protein involved in chromatin-associated ubiquitylation upon DNA damage. UBR2-deficient somatic cells show an array of chromosomal abnormalities, including hyperproliferation, chromosome instability, and hypersensitivity to DNA damage-inducing reagents. UBR2-deficient mice enriched in C57 background die upon birth with defects in lung expansion and neural development. Thus, UBR2, known as the recognition component of a major cellular proteolytic system, is associated with chromatin and controls chromatin dynamics and gene expression in both germ cells and somatic cells.


Impact of a 3-Day High-Altitude Trek on Xue Mountain (3886 m), Taiwan, on the Emotional States of Children: A Prospective Observational Study.
Changes in emotions associated with mountain treks have rarely been reported. This study examined emotional state changes in sixth-grade elementary school students before and after a 3-day high-altitude mountain trek from the trailhead (2140 m) to Xue Mountain (3886 m) in Taiwan. In June 2011, 201 students participated in the trek. The round-trip distance was 21.8 km. The age, gender, blood group, and family configuration of the participants were documented before the trek. A 36-item short-form survey instrument, including the Mood and Anxiety Symptom Questionnaire and the Positive and Negative Affect Scale for Children, was used to evaluate the participants' emotional states (happiness, anticipation, sadness, and anger). The participants answered the questionnaires 1 month before and 1 week after the trek. A Likert scale was used to evaluate individual items (range 1-4; from strongly disagree to strongly agree). We calculated scores for each index before and after the trek. The incidence and presentation of acute mountain sickness (AMS) among the participants was also studied and published previously. In total, 187 (112 boys and 75 girls) participants (mean age 11.9 ± 0.4 years) completed the trek and the survey. The sadness and anger scores (negative emotions) were significantly lower after than before the trek (39.5 vs. 36.6; p < 0.01). The happiness and anticipation scores (positive emotions) before and after the trek did not differ significantly (49.9 vs. 48.9; p = 0.11). No participant used AMS prophylaxis, while 78 participants met the AMS criteria. Negative emotions decreased more in those with AMS than without AMS (-4.6 vs. -1.8; p = 0.04), and the use of medications or acetazolamide did not alter the emotions. A 3-day high-altitude mountain trek can reduce children's negative emotions. Negative emotions decreased more in those with AMS, whereas medications or acetazolamide did not alter their emotions.


Output irradiance of tapered lightpipes.
A light cone efficiently transports, distributes, and concentrates the incoming radiation. I derive a formula for the spatial irradiance (or illuminance) distribution at the exit aperture of a tapered light pipe. The theory is demonstrated by Monte Carlo ray-tracing for lightpipes with light-emitting diodes at the input face. The analysis is based on the addition of the radiation patterns of the multiple virtual sources that, as in a three-dimensional kaleidoscope, are seen through a tapered light tube. Given its explicit dependence on the structural and optical parameters, this analysis may be a useful tool in the development and application of light cones.


Frequency of serum creatinine monitoring during allopurinol therapy in ambulatory patients.
Allopurinol dosage reduction is recommended in patients with renal dysfunction because drug toxicity risk is increased. Little information is available about serum creatinine (SCr) monitoring in ambulatory patients taking allopurinol. To evaluate SCr monitoring among patients prescribed allopurinol, identify associated factors, and evaluate administrative data in assessing monitoring. Information for this retrospective cohort study was drawn from a dataset of 2 020 037 individuals; approximately 200 000 members from each of 10 organizations. Study patients had received at least one year of ongoing allopurinol prescription dispensings. Patient variables analyzed included age, gender, chronic diseases, outpatient visits, hospitalizations, gout diagnosis, and SCr monitoring. A random sample of medical records was reviewed to assess the accuracy of the automated data. Statistical analysis included descriptive and logistic regression techniques. Overall, 1139 (26%) of 4357 patients did not have SCr monitoring. For individuals without recent hospitalization, factors protective against lack of monitoring were increasing age (OR 0.77 per 10 y; 95% CI 0.74 to 0.79), more chronic diseases (OR 0.81; 95% CI 0.78 to 0.83), more outpatient visits (OR 0.87 per 5 visits; 95% CI 0.83 to 0.91), and gout diagnosis (OR 0.74; 95% CI 0.65 to 0.85). The sensitivity and specificity of administrative data compared with medical records for SCr monitoring were 92% and 65%, respectively. More than one-fourth of patients dispensed allopurinol did not have SCr monitoring during one year of therapy. Lack of monitoring and lack of subsequent possible dosage adjustment put patients at increased risk of allopurinol toxicity.


Benzene inhalation by parts washers: new estimates based on measures of occupational exposure to solvent coaromatics.
Questions persist regarding assessment of workers' exposures to products containing low levels of benzene, such as mineral spirit solvent (MSS). This study summarizes previously unpublished data for parts-washing activities, and evaluates potential daily and lifetime cumulative benzene exposures incurred by workers who used historical and current formulations of a recycled mineral spirits solvent in manual parts washers. Measured benzene concentrations in historical samples from parts-washing operations were frequently below analytical detection limits. To better assess benzene exposure among these workers, air-to-solvent concentration ratios measured for toluene, ethylbenzene, and xylenes (TEX) were used to predict those for benzene based on a statistical model, conditional on physical-chemical theory supported by new thermodynamic calculations of TEX and benzene activity coefficients in a modeled MSS-type solvent. Using probabilistic methods, the distributions of benzene concentrations were then combined with distributions of other exposure parameters to estimate eight-hour time-weighted average (TWA) exposure concentration distributions and corresponding daily respiratory dose distributions for workers using these solvents in parts washers. The estimated 50th (95th) percentile of the daily respiratory dose and corresponding eight-hour TWA air concentration for workers performing parts washing are 0.079 (0.77) mg and 0.0030 (0.028) parts per million by volume (ppm) for historical solvent, and 0.020 (0.20) mg and 0.00078 (0.0075) ppm for current solvent, respectively. Both 95th percentile eight-hour TWA respiratory exposure estimates for solvent formulations are less than 10% of the current Occupational Safety and Health Administration permissible exposure limit of 1.0 ppm for benzene.


Prevalence and determinants of risky sexual practice in Ethiopia: Systematic review and Meta-analysis.
Risky sexual practice is a major public health problem in Ethiopia. There are various studies on the prevalence and determinants of risky sexual practice in different regions of the country but there is no study which shows the national estimate of risky sexual practices in Ethiopia. Therefore, this review was conducted to estimate the national pooled prevalence of risky sexual practice and its risk factors in Ethiopia. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline was followed to review published and unpublished studies in Ethiopia. The databases used were; PubMed, Google Scholar, CINAHL and African Journals Online. Search terms were; risky sexual behavior, risky sexual practice, unprotected sex, multiple sexual partner, early sexual initiation, and/or Ethiopia. Joanna Briggs Institute Meta-Analysis of Statistics Assessment and Review Instrument was used for critical appraisal. The meta-analysis was conducted using Review Manager software. Descriptive information of studies was presented in narrative form and quantitative results were presented in forest plots. The Cochran Q test and I 2 test statistics were used to test heterogeneity across studies. The pooled estimate prevalence and the odd ratios with 95% confidence intervals were computed by a random effect model. A total of 31 studies with 43,695 participants were included in the meta-analysis. The pooled prevalence of risky sexual practice was 42.80% (95% CI: 35.64%, 49.96%). Being male (OR: 1.69; 95% CI: 1.21, 2.37), substance use (OR: 3.42; 95% CI: 1.41, 8.31), peer pressure (OR: 3.41; 95% CI: 1.69, 6.87) and watching pornography (OR: 3.6; 95% CI: 2.21, 5.86) were factors associated with an increase in risky sexual practices. The prevalence of risky sexual practices is high in Ethiopia. Being male, substance use, peer pressure and viewing pornographic materials were found to be associated with risky sexual practices. Therefore, life skills training is recommended to reduce peer pressure among individuals. Interventions should be designed to reduce substance use and viewing pornography.


Functional magnetic resonance imaging of the retina.
This study explored the feasibility of mapping the retina's responses to visual stimuli noninvasively, by using functional magnetic resonance imaging (fMRI). fMRI was performed on a 9.4-Tesla scanner to map activity-evoked signal changes of the retina-choroid complex associated with visual stimulation in anesthetized cats (n = 6). Three to 12 1-mm slices were acquired in a single shot using inversion-recovery, echo-planar imaging with a nominal in-plane resolution of 468 x 468 microm(2). Visual stimuli were presented to the full visual field and to the upper and lower visual fields. The stimuli were drifting or stationary gratings, which were compared with the dark condition. Activation maps were computed using cross-correlation analysis and overlaid on anatomic images. Multislice activation maps were reconstructed and flattened onto a two-dimensional surface. fMRI activation maps showed robust increased activity in the retina-choroid complex after visual stimulation. The average stimulus-evoked fMRI signal increase associated with drifting-grating stimulus was 1.7% +/- 0.5% (P < 10(-4), n = 6) compared with dark. Multislice functional images of the retina flattened onto a two-dimensional surface showed relatively uniform activation. No statistically significant activation was observed in and around the optic nerve head. Hemifield stimulation studies demonstrated that stimuli presented to the upper half of the visual field activated the lower part of the retina, and stimuli presented to the lower half of the visual field activated the upper part of the retina, as expected. Signal changes evoked by the stationary gratings compared with the dark basal condition were positive but were approximately half that evoked by the drifting gratings (1.0% +/- 0.1% versus 2.1% +/- 0.3%, P < 10(-4)). To the best of our knowledge, this is the first fMRI study of the retina, demonstrating its feasibility in imaging retinal function dynamically in a noninvasive manner and at relatively high spatial resolution.


Multilayered pigment epithelial detachment in neovascular age-related macular degeneration.
To describe the spectral domain optical coherence tomography findings in eyes with chronic fibrovascular pigment epithelial detachment (PED) receiving intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy. Retrospective observational case series of patients with chronic fibrovascular PEDs receiving serial intravitreal anti-VEGF therapy. Corresponding spectral domain optical coherence tomography scans of chronic PEDs were studied in detail over multiple visits. The internal structure within the sub-PED compartment was analyzed, characteristic features were identified, and then correlated with visual outcome. Thirty-eight eyes of 34 patients with fibrovascular PEDs were included. Mean and median Snellen visual acuity was 20/50 (range, 20/20-20/400). Eyes received a mean of 28.2 intravitreal anti-VEGF injections (median, 23.0; range, 3-70) administered over a mean of 36.9 months (median, 37.5; range, 6-84). A fusiform, or spindle-shaped, complex of highly organized layered hyperreflective bands was noted within each PED. Nineteen eyes demonstrated heterogenous, dilated, irregular neovascular tissue adherent to the undersurface of the retinal pigment epithelium. Additionally, 25 eyes demonstrated a hyporeflective cavity separating the choroidal neovascularization complex from the underlying choroid. Chronic fibrovascular PEDs receiving serial anti-VEGF therapy demonstrate a characteristic fusiform complex of highly organized, layered, hyperreflective bands, termed a "multilayered PED," which is often seen in conjunction with neovascular tissue adherent to the undersurface of the retinal pigment epithelium monolayer. On the basis of previous histopathologic correlations, these bands may represent a fibrous tissue complex with contractile properties. An associated hyporeflective space, termed a "pre-choroidal cleft," separates the fusiform complex from the underlying choroid and may be due to contraction, the exudation of fluid, or both. Many of these eyes maintain good visual acuity, presumably because the neovascular and cicatricial process is suppressed within the sub-retinal pigment epithelium space by chronic anti-VEGF therapy, thus permitting the viability of the photoreceptor population through preservation of the retinal pigment epithelium.


Species effects on nitrogen cycling: a test with perennial grasses.
To test for differing effects of plant species on nitrogen dynamics, we planted monocultures of five perennial grasses (Agropyron repens, Agrostis scabra, Poa pratensis, Schizachyrium scoparium, and Andropogon gerardi) on a series of soils ranging from sand to black soil. In situ net N mineralization was measured in the monocultures for three years. By the third year, initially identical soils under different species had diverged up to 10-fold in annual net mineralization. This divergence corresponded to differences in the tissue N concentrations, belowground lignin concentrations, and belowground biomasses of the species. These results demonstrate the potential for strong feedbacks between the species composition of vegetation and N cycling. If individual plant species can affect N mineralization and N availability, then competition for N may lead to positive or negative feedbacks between the processes controlling species composition and ecosystem processes such as N and C cycling. These feedbacks create the potential for alternative stable states for the vegetation-soil system given the same initial abiotic conditions.


Three-dimensional structure of dendritic spines in the rat neostriatum.
Dendritic spines of rat neostriatal neurons were examined by light microscopy and high voltage stereo electron microscopy (HVEM) following selective staining by intracellular microinjection of horseradish peroxidase. Conventionally prepared material also was used for quantitative analysis of dendritic spines from serial thin sections of neostriatum. Stereo electron microscopy of semithin sections from rat neostriatum fixed using a protocol designed to preserve cytoskeletal integrity was employed to examine the organization of the dendritic spine cytoplasm. Light microscopic and HVEM examination of spiny dendrites and quantitative analysis of serial thin sections from normal material revealed no distinct spine types but rather continuous and independent variation of spine head diameter, stalk diameter, and stalk length. Likewise, there was no systematic relationship between any of these spine dimensions and dendritic diameter. Spine head membrane surface area was directly related to the area of the synaptic junctional membrane of the spine head. In semithin sections, the cytoplasm of the spine contained membranous saccules of spine apparatus and a delicate cytoskeletal network composed of microfilaments and a set of finer and more variable cytoskeletal filaments. It is proposed that this cytoskeletal network together with the spine apparatus is responsible for the maintenance and alteration of spine shape and in this way controls the effectiveness of axospinous synapses.


Heme oxygenase-1 aggravates heat stress-induced neuronal injury and decreases autophagy in cerebellar Purkinje cells of rats.
We previously reported that heat stroke induces autophagy as a protection mechanism against neurodegeneration in the brain. Heme oxygenase (HO)-1 is a stress protein and can be induced by heat stress (HS). Cerebellar Purkinje cells are selectively vulnerable to heat-induced injury. In this study, we first validated an animal model of HS (38°C for 4 h) in which sustained increase of Purkinje cell injury, HO-1 expression up to 24 h post HS (HS₂₄), and hyperthermia reaching a rectal temperature 41.52 ± 0.32 were observed. In subsequent experiments, we investigated the effects of HO-1 on HS-induced Purkinje cell injury. Rats were divided into four groups: one normothermic control group receiving saline vehicle (1 mL/kg, intraperitoneal [i.p.]) and exposed to 25 for 4 h; and three HS groups receiving saline, or HO-1 inducer haemin (30 mg/kg, i.p.) or HO-1 inhibitor tin protoporphyrin (SnPP, 30 mg/kg, i.p.), respectively, at 12 h prior to HS. HS-induced Purkinje cell injury was further enhanced by HO-1 inducer but attenuated by HO-1 inhibitor as evaluated by immunoreactivity of apoptosis marker (active caspase-3) as well as Fluoro-Jade B histochemistry (staining for degenerating neurons), suggesting a detrimental role of HO-1. Interestingly, the protective autophagy was reduced by HO-1 inducer but enhanced by HO-1 inhibitor as demonstrated by autophagy markers including Beclin-1 and microtubule-associated protein light chain 3 in Purkinje cells. Double immunofluorescent labelling of Beclin-1 or 8-hydroxydeoxyguanosine (an oxidative DNA damage marker) with HO-1 immunoreactivity not only demonstrated their co-localization, but also confirmed that HO-1 negatively regulated Beclin-1 but increased oxidative stress in the same Purkinje cell. Taken together, our results indicate that HO-1 aggravates HS injury in cerebellar Purkinje cells. Our findings shed new light on cell damage mechanisms by HS in central nervous system and may help to provide potential therapeutic foci.


Continuous immunotypes describe human immune variation and predict diverse responses.
The immune system consists of many specialized cell populations that communicate with each other to achieve systemic immune responses. Our analyses of various measured immune cell population frequencies in healthy humans and their responses to diverse stimuli show that human immune variation is continuous in nature, rather than characterized by discrete groups of similar individuals. We show that the same three key combinations of immune cell population frequencies can define an individual's immunotype and predict a diverse set of functional responses to cytokine stimulation. We find that, even though interindividual variations in specific cell population frequencies can be large, unrelated individuals of younger age have more homogeneous immunotypes than older individuals. Across age groups, cytomegalovirus seropositive individuals displayed immunotypes characteristic of older individuals. The conceptual framework for defining immunotypes suggested by our results could guide the development of better therapies that appropriately modulate collective immunotypes, rather than individual immune components.


Airborne concentrations of benzene for dock workers at the ExxonMobil refinery and chemical plant, Baton Rouge, Louisiana, USA (1977-2005).
Benzene is a natural constituent of crude oil and natural gas (0.1-3.0% by volume). Materials that are refined from crude oil and natural gas contain some residual benzene. Few datasets have appeared in the peer-reviewed literature characterizing exposures to benzene at specific refineries or during specific tasks. In this study, historical samples of airborne benzene collected from 1977-2005 at the ExxonMobil Baton Rouge, Louisiana, USA, docks were evaluated. Workers were categorized into 11 job titles, and both non-task (≤180 min sample duration) and task-related (<180 min) benzene concentrations were assessed. Approximately 800 personal air samples (406 non-task and 397 task-related) were analyzed. Non-task samples showed that concentrations varied significantly across job titles and generally resulted from exposures during short-duration tasks such as tank sampling. The contractor - tankerman job title had the highest average concentration [N=38, mean 1.4 parts per million (ppm), standard deviation (SD) 2.6]. Task-related samples indicated that the highest exposures were associated with the disconnection of cargo loading hoses (N=134, mean 11 ppm, SD 32). Non-task samples for specific job categories showed that concentrations have decreased over the past 30 years. Recognizing the potential for benzene exposure, this facility has required workers to use respiratory protective equipment during selected tasks and activities; thus, the concentrations measured were likely greater than those that the employee actually experienced. This study provides a job title- and task-focused analysis of occupational exposure to benzene during dock facility operations that is insightful for understanding the Baton Rouge facility and others similar to it over the past 30 years.


Acid rain: a serious regional environmental problem.
At present, acid rain or snow is falling on most of the northeastern United States. The annual acidity value averages about pH 4, but values between pH 2.1 and 5 have been recorded for individual storms. The acidity of precipitation in this region apparently increased about 20 years ago, and the increase may have been associated with the augmented use of natural gas and with the installation of particle-removal devices in tall smokestacks. Only some of the ecological and economic effects of this widespread introduction of strong acids into natural systems are known at present, but clearly they must be considered in proposals for new energy sources and in the development of air quality emission standards.


Links between socio-economic circumstances and changes in smoking behavior in the Mexican population: 2002-2010.
While deleterious consequences of smoking on health have been widely publicized, in many developing countries, smoking prevalence is high and increasing. Little is known about the dynamics underlying changes in smoking behavior. This paper examines socio-economic and demographic characteristics associated with smoking initiation and quitting in Mexico between 2002 and 2010. In addition to the influences of age, gender, education, household economic resources and location of residence, changes in marital status, living arrangements and health status are examined. Drawing data from the Mexican Family Life Survey, a rich population-based longitudinal study of individuals, smoking behavior of individuals in 2002 is compared with their behavior in 2010. Logistic models are used to examine socio-demographic and health factors that are associated with initiating and quitting smoking. There are three main findings. First, part of the relationship between education and smoking reflects the role of economic resources. Second, associations of smoking with education and economic resources differ for females and males. Third, there is considerable heterogeneity in the factors linked to smoking behavior in Mexico indicating that the smoking epidemic may be at different stages in different population subgroups. Mexico has recently implemented fiscal policies and public health campaigns aimed at reducing smoking prevalence and discouraging smoking initiation. These programs are likely to be more effective if they target particular socio-economic and demographic sub-groups.


Leptin and insulin stimulation of signalling pathways in arcuate nucleus neurones: PI3K dependent actin reorganization and KATP channel activation.
Leptin and insulin are long-term regulators of body weight. They act in hypothalamic centres to modulate the function of specific neuronal subtypes, by altering transcriptional control of releasable peptides and by modifying neuronal electrical activity. A key cellular signalling intermediate, implicated in control of food intake by these hormones, is the enzyme phosphoinositide 3-kinase. In this study we have explored further the linkage between this enzyme and other cellular mediators of leptin and insulin action on rat arcuate nucleus neurones and the mouse hypothalamic cell line, GT1-7. Leptin and insulin increased the levels of various phosphorylated signalling intermediates, associated with the JAK2-STAT3, MAPK and PI3K cascades in the arcuate nucleus. Inhibitors of PI3K were shown to reduce the hormone driven phosphorylation through the PI3K and MAPK pathways. Using isolated arcuate neurones, leptin and insulin were demonstrated to increase the activity of KATP channels in a PI3K dependent manner, and to increase levels of PtdIns(3,4,5)P3. KATP activation by these hormones in arcuate neurones was also sensitive to the presence of the actin filament stabilising toxin, jasplakinolide. Using confocal imaging of fluorescently labelled actin and direct analysis of G- and F-actin concentration in GT1-7 cells, leptin was demonstrated directly to induce a re-organization of cellular actin, by increasing levels of globular actin at the expense of filamentous actin in a PI3-kinase dependent manner. Leptin stimulated PI3-kinase activity in GT1-7 cells and an increase in PtdIns(3,4,5)P3 could be detected, which was prevented by PI3K inhibitors. Leptin and insulin mediated phosphorylation of cellular signalling intermediates and of KATP channel activation in arcuate neurones is sensitive to PI3K inhibition, thus strengthening further the likely importance of this enzyme in leptin and insulin mediated energy homeostasis control. The sensitivity of leptin and insulin stimulation of KATP channel opening in arcuate neurones to jasplakinolide indicates that cytoskeletal remodelling may be an important contributor to the cellular signalling mechanisms of these hormones in hypothalamic neurones. This hypothesis is reinforced by the finding that leptin induces actin filament depolymerization, in a PI3K dependent manner in a mouse hypothalamic cell line.


[Quantification of bladder-outlet obstruction in males: standard method vc VBN method].
To compare the merits of two methods, standard (Abrams-Griffiths number, Schafer's classification, etc.) and VBN, to study bladder-outlet obstruction in men with benign prostatic hyperplasia (BPH). The parameters deduced from both methods and from repeated pressure-flow studies were computed for a population of patients with BPH. Correlation coefficients between standard and VBN parameters were systematically evaluated. Test-retest reliability and inter-rater reliability of the VBN parameters were investigated. The VBN obstruction parameter was linearly corelated to the A-G number (R = 0.992) and thus is related to the provisional ICS obstruction nomogram. A simple modification to the standard index projected isometric pressure (PIP) yields an mPIP parameter strongly correlated with the VBN detrusor contraction-strength parameter (R = 0.962). VBN analysis reveals minor phenomena such as premature fading of the detrusor contraction to be responsible for much of the void-to-void variability of pressure-flow studies. Consequently, the primary VBN obstruction and contraction-strength parameters exhibit better test-retest and inter-rater reliability than the standard parameters and are less sensitive to changes in testing circumstances (bladder volume, urethral catheter size and psychological factors). With the standard approach to test bladder obstruction, two values: A-G and mPIP, derived from pressure-flow studies, best qualify the patient's voiding status. These parameters are simple to calculate but are sensitive to testing variations and minor phenomena. The VBN approach is more complicated, but its parameters for obstruction and detrusor contraction strength are less dependent on testing variations.


Lighting System for Visual Perception Enhancement in Volume Rendering.
We introduce a lighting system that enhances the visual cues in a rendered image for the perception of 3D volumetric objects. We divide the lighting effects into global and local effects, and deploy three types of directional lights: the key light and accessory lights (fill and detail lights). The key light provides both lighting effects and carries the visual cues for the perception of local and global shapes and depth. The cues for local shapes are conveyed by gradient; those for global shapes are carried by shadows; and those for depth are provided by shadows and translucent objects. Fill lights produce global effects to increase the perceptibility. Detail lights generate local effects to improve the cues for local shapes. Our method quantifies the perception and uses an exhaustive search to set the lights. It configures accessory lights with the consideration of preserving the global impression conveyed by the key light. It ensures the feeling of smooth light movements in animations. With simplification, it achieves interactive frame rates and produces results that are visually indistinguishable from results using the nonsimplified algorithm. The major contributions of this paper are our lighting system, perception measurement and lighting design algorithm with our indistinguishable simplification.


Morphological and Molecular Characterization of a New Root-Knot Nematode, Meloidogyne thailandica n. sp. (Nematoda: Meloidogynidae), Parasitizing Ginger (Zingiber sp.).
A root-knot nematode Meloidogyne thailandica n. sp. was discovered on roots of ginger (Zingiber spp.) intercepted from Thailand in October 2002 by the U.S. Department of Agriculture Animal and Plant Health Inspection Service at the port of San Francisco. Comparison by light microscopy (LM) and scanning electron microscopy (SEM) to five other morphologically related species (M. incognita, M. arenaria, M. microcephala, M. megatyla, and M. enterolobii) revealed that the new species differs from these by one or more of the following: body, tail and hyaline tail length, shape of head, tail and tail terminus of second-stage juveniles; stylet length and shape of spicules in males; perineal pattern, stylet length and shape of knobs in females. The distinctive perineal pattern is oval to rectangular, with smooth to moderately wavy and coarse striae, and with characteristic radial structures present underneath the pattern area; the dorsal arch is high, sometimes round to rectangular, and striae in and around the anal area form a thick network-like pattern interrupted by lateral lines and large phasmids. Second-stage juveniles have a long, slender tail and long, gradually tapering hyaline tail region ending in a rounded terminus. Male spicules commonly have an acutely angled shaft with a bidentate terminus. Molecular data from the ribosomal large subunit D3 expansion segment revealed four haplotypes, two of which were unique and distinguish M. thailandica n. sp. from M. arenaria, M. incognita, and M. javanica.


Demographic transition and the dynamics of measles in six provinces in China: A modeling study.
Industrialization and demographic transition generate nonstationary dynamics in human populations that can affect the transmission and persistence of infectious diseases. Decades of increasing vaccination and development have led to dramatic declines in the global burden of measles, but the virus remains persistent in much of the world. Here we show that a combination of demographic transition, as a result of declining birth rates, and reduced measles prevalence, due to improved vaccination, has shifted the age distribution of susceptibility to measles throughout China. We fit a novel time-varying catalytic model to three decades of age-specific measles case reporting in six provinces in China to quantify the change in the age-specific force of infection for measles virus over time. We further quantified the impact of supplemental vaccination campaigns on the reduction of susceptible individuals. The force of infection of measles has declined dramatically (90%-97% reduction in transmission rate) in three industrialized eastern provinces during the last decade, driving a concomitant increase in both the relative proportion and absolute number of adult cases, while three central and western provinces exhibited dynamics consistent with endemic persistence (24%-73% reduction in transmission rate). The reduction in susceptible individuals due to supplemental vaccination campaigns is frequently below the nominal campaign coverage, likely because campaigns necessarily vaccinate those who may already be immune. The impact of these campaigns has significantly improved over time: campaigns prior to 2005 were estimated to have achieved less than 50% reductions in the proportion susceptible in the target age classes, but campaigns from 2005 onwards reduced the susceptible proportion by 32%-87%. A limitation of this study is that it relies on case surveillance, and thus inference may be biased by age-specific variation in measles reporting. The age distribution of measles cases changes in response to both demographic and vaccination processes. Combining both processes in a novel catalytic model, we illustrate that age-specific incidence patterns reveal regional differences in the progress to measles elimination and the impact of vaccination controls in China. The shift in the age distribution of measles susceptibility in response to demographic and vaccination processes emphasizes the importance of progressive control strategies and measures to evaluate program success that anticipate and react to this transition in observed incidence.


Quercetin Protects Mice from ConA-Induced Hepatitis by Inhibiting HMGB1-TLR Expression and Down-Regulating the Nuclear Factor Kappa B Pathway.
The dietary flavonoid quercetin has hepatoprotective effects. We analyzed the effects of quercetin on concanavalin A (ConA)-induced hepatitis in mice and its underlying molecular mechanisms of action. Mice were administered quercetin (50 mg/kg body weight, i.p.) or vehicle 30 min before intravenous administration of ConA. Quercetin pretreatment significantly reduced the ConA-induced elevations in plasma aminotransferase concentrations and liver necrosis, as well as reducing serum concentrations of the pro-inflammatory cytokines tumor necrosis factor (TNF)-α, interferon-γ, and interleukin-4. Quercetin pretreatment also reduced expression of high-mobility group box 1 protein (HMGB1) and toll-like receptor (TLR)-2 and TLR-4 messenger RNA (mRNA) and protein in liver tissues. Quercetin pretreatment significantly inhibited degradation of inhibitory kappa B alpha and modulated ConA-induced nuclear translocation in the liver of nuclear factor kappa B (NF-κB) p65. These results demonstrate that quercetin protects against ConA-mediated hepatitis in mice by attenuating the HMGB1-TLRs-NF-κB signaling pathway.


Overweight and obesity in infants and pre-school children in the European Union: a review of existing data.
The objective of this study was to synthesize available information on prevalence and time trends of overweight and obesity in pre-school children in the European Union. Retrieval and analysis or re-analysis of existing data were carried out. Data sources include WHO databases, Medline and Google, contact with authors of published and unpublished documents. Data were analysed using the International Obesity Task Force reference and cut-offs, and the WHO standard. Data were available from 18/27 countries. Comparisons were problematic because of different definitions and methods of data collection and analysis. The reported prevalence of overweight plus obesity at 4 years ranges from 11.8% in Romania (2004) to 32.3% in Spain (1998-2000). Countries in the Mediterranean region and the British islands report higher rates than those in middle, northern and eastern Europe. Rates are generally higher in girls than in boys. With the possible exception of England, there was no obvious trend towards increasing prevalence in the past 20-30 years in the five countries with data. The use of the WHO standard with cut-offs at 1, 2 and 3 standard deviations yields lower rates and removes gender differences. Data on overweight and obesity in pre-school children are scarce; their interpretation is difficult. Standard methods of surveillance, and research and policies on prevention and treatment, are urgently needed.


Executive Function Performance for Children With Epilepsy Localized to the Frontal or Temporal Lobes.
Research with adults with epilepsy consistently indicates deficits in executive function (EF). There is less research specific to children with epilepsy and EF. The purpose of this study was to consider EF deficits in children with complex partial epilepsy and complex partial with secondary generalization epilepsy with onset localized to the frontal or temporal lobes. This was a retrospective study of 28 children followed in an outpatient pediatric epilepsy clinic who were consecutively referred for neuropsychological assessment, which included measures of EF. The sample was predominantly White and male, with a mean age of 12.88 years (SD = 1.64) and mean cognitive ability of 89.39 (SD = 13.41). Comparison of right-temporal, left-temporal, and frontal groups yielded significant differences (p = .01) between the left-temporal and frontal groups on the Wisconsin Card-Sorting Test (WCST) Categories with the frontal group demonstrating the greatest deficits. Although mean differences were not significant, the frequency of impaired performance by the frontal group on the Attention/Concentration Index was greater than in the temporal groups. Results indicate that for children with complex partial and complex partial with secondary generalized seizures localized to the frontal and temporal lobes, there is an increased likelihood for impaired EF evident on the WCST, but not on others. Implications of these findings for prevention and intervention are discussed.


Transcatheter closure of patent arterial ducts using controlled-release coils.
To determine the efficacy of transcatheter closure of patent arterial ducts using controlled-release coils. Transcatheter closure of patent arterial ducts was attempted in 52 patients using controlled-release coils. For the study, four tertiary paediatric cardiology units were used, two of which were in the U.K., one in Italy and one in Turkey. The 52 patients ranged in age between 3-5 months and 61 years (median 3-5 years), and weighted between 4.5 kg and 62 kg. The duct diameters were 1 mm to 6.5 mm. In four patients the ducts were too large for safe release of the coils. In the remaining 48, one coil was inserted in 33 patients, two coils in nine, three coils in four and four coils in two patients. Immediately at the end of the procedure, the duct was completely occluded in 26/47 (55%) patients. Haemolysis occurred in one patient, in whom the coil was removed by a snare catheter and a large umbrella device was implanted with resolution of the haemolysis. Coil embolization to the pulmonary artery occurred in five (10%) patients. All were easily retrieved and replaced by larger coils. At the latest follow-up by colour Doppler echocardiography, the duct was completely occluded in 44/47 (94%) patients. Transcatheter closure of patent arterial ducts by controlled-release coils is effective and safe. Even when more than one coil is inserted the technique is still less cumbersome and considerably cheaper than transcatheter umbrella closure.


Critical analysis of the accuracy of models predicting or extracting liquid structure information.
This work aims at a critical assessment of properties predicting or extracting information on the density and structure of liquids. State-of-the-art NVT and NpT molecular dynamics (MD) simulations have been performed on five liquids: methanol, chloroform, acetonitrile, tetrahydrofuran, and ethanol. These simulations allow the computation of properties based on first principles, including the equilibrium density and radial distribution functions (RDFs), characterizing the liquid structure. Refinements have been incorporated in the MD simulations by taking into account basis set superposition errors (BSSE). An extended BSSE model for an instantaneous evaluation of the BSSE corrections has been proposed, and their impact on the liquid properties has been assessed. If available, the theoretical RDFs have been compared with the experimentally derived RDFs. For some liquids, significant discrepancies have been observed, and a profound but critical investigation is presented to unravel the origin of these deficiencies. This discussion is focused on tetrahydrofuran where the experiment reveals some prominent peaks completely missing in any MD simulation. Experiments providing information on liquid structure consist mainly of neutron diffraction measurements offering total structure factors as the primary observables. The splitting of these factors in reciprocal space into intra- and intermolecular contributions is extensively discussed, together with their sensitivity in reproducing correct RDFs in coordinate space.


Cortical Brain Activity Reflecting Attentional Biasing Toward Reward-Predicting Cues Covaries with Economic Decision-Making Performance.
Adaptive choice behavior depends critically on identifying and learning from outcome-predicting cues. We hypothesized that attention may be preferentially directed toward certain outcome-predicting cues. We studied this possibility by analyzing event-related potential (ERP) responses in humans during a probabilistic decision-making task. Participants viewed pairs of outcome-predicting visual cues and then chose to wager either a small (i.e., loss-minimizing) or large (i.e., gain-maximizing) amount of money. The cues were bilaterally presented, which allowed us to extract the relative neural responses to each cue by using a contralateral-versus-ipsilateral ERP contrast. We found an early lateralized ERP response, whose features matched the attention-shift-related N2pc component and whose amplitude scaled with the learned reward-predicting value of the cues as predicted by an attention-for-reward model. Consistently, we found a double dissociation involving the N2pc. Across participants, gain-maximization positively correlated with the N2pc amplitude to the most reliable gain-predicting cue, suggesting an attentional bias toward such cues. Conversely, loss-minimization was negatively correlated with the N2pc amplitude to the most reliable loss-predicting cue, suggesting an attentional avoidance toward such stimuli. These results indicate that learned stimulus-reward associations can influence rapid attention allocation, and that differences in this process are associated with individual differences in economic decision-making performance.