947 resultados para 4-nitroquinoline 1-oxide
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Not having enough physical activity leads to poorer health. Regular physical activity can reduce the risk of chronic disease and improve one's health and well being. The lack of physical activity is a common and growing health problem. To address this, 25 studies have used improvement activities directed at communities using more than one approach in a single program. When we looked at the available research, we observed that there was a lack of good studies which could show whether this approach was or wasn't beneficial. For example, some research studies claimed that community wide programs improved physical activities and other studies did not. It was not possible to determine what might work. Future research is needed with improved designs, measures of outcomes and larger samples of participants.
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Background Canonical serine protease inhibitors commonly bind to their targets through a rigid loop stabilised by an internal hydrogen bond network and disulfide bond(s). The smallest of these is sunflower trypsin inhibitor (SFTI-1), a potent and broad-range protease inhibitor. Recently, we re-engineered the contact β-sheet of SFTI-1 to produce a selective inhibitor of kallikrein-related peptidase 4 (KLK4), a protease associated with prostate cancer progression. However, modifications in the binding loop to achieve specificity may compromise structural rigidity and prevent re-engineered inhibitors from reaching optimal binding affinity. Methodology/Principal Findings In this study, the effect of amino acid substitutions on the internal hydrogen bonding network of SFTI were investigated using an in silico screen of inhibitor variants in complex with KLK4 or trypsin. Substitutions favouring internal hydrogen bond formation directly correlated with increased potency of inhibition in vitro. This produced a second generation inhibitor (SFTI-FCQR Asn14) which displayed both a 125-fold increased capacity to inhibit KLK4 (Ki = 0.0386±0.0060 nM) and enhanced selectivity over off-target serine proteases. Further, SFTI-FCQR Asn14 was stable in cell culture and bioavailable in mice when administered by intraperitoneal perfusion. Conclusion/Significance These findings highlight the importance of conserving structural rigidity of the binding loop in addition to optimising protease/inhibitor contacts when re-engineering canonical serine protease inhibitors.
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Background Physical activity may reduce the risk of adverse maternal outcomes, yet there are very few studies that have examined the correlates of exercise amongst obese women during pregnancy. We examined which relevant sociodemographic, obstetric, and health behaviour variables and pregnancy symptoms were associated with exercise in a small sample of obese pregnant women. Methods This was a secondary analysis using data from an exercise intervention for the prevention of gestational diabetes in obese pregnant women. Using the Pregnancy Physical Activity Questionnaire (PPAQ), 50 obese pregnant women were classified as "Exercisers" if they achieved ≥900 kcal/wk of exercise and "Non-Exercisers" if they did not meet this criterion. Analyses examined which relevant variables were associated with exercise status at 12, 20, 28 and 36 weeks gestation. Results Obese pregnant women with a history of miscarriage; who had children living at home; who had a lower pre-pregnancy weight; reported no nausea and vomiting; and who had no lower back pain, were those women who were most likely to have exercised in early pregnancy. Exercise in late pregnancy was most common among tertiary educated women. Conclusions Offering greater support to women from disadvantaged backgrounds and closely monitoring women who report persistent nausea and vomiting or lower back pain in early pregnancy may be important. The findings may be particularly useful for other interventions aimed at reducing or controlling weight gain in obese pregnant women.
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Background With the increasing prevalence of childhood obesity, the metabolic syndrome has been studied among children in many countries but not in Malaysia. Hence, this study aimed to compare metabolic risk factors between overweight/obese and normal weight children and to determine the influence of gender and ethnicity on the metabolic syndrome among school children aged 9-12 years in Kuala Lumpur and its metropolitan suburbs. Methods A case control study was conducted among 402 children, comprising 193 normal-weight and 209 overweight/obese. Weight, height, waist circumference (WC) and body composition were measured, and WHO (2007) growth reference was used to categorise children into the two weight groups. Blood pressure (BP) was taken, and blood was drawn after an overnight fast to determine fasting blood glucose (FBG) and full lipid profile, including triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC). International Diabetes Federation (2007) criteria for children were used to identify metabolic syndrome. Results Participants comprised 60.9% (n = 245) Malay, 30.9% (n = 124) Chinese and 8.2% (n = 33) Indian. Overweight/obese children showed significantly poorer biochemical profile, higher body fat percentage and anthropometric characteristics compared to the normal-weight group. Among the metabolic risk factors, WC ≥90th percentile was found to have the highest odds (OR = 189.0; 95%CI 70.8, 504.8), followed by HDL-C≤1.03 mmol/L (OR = 5.0; 95%CI 2.4, 11.1) and high BP (OR = 4.2; 95%CI 1.3, 18.7). Metabolic syndrome was found in 5.3% of the overweight/obese children but none of the normal-weight children (p < 0.01). Overweight/obese children had higher odds (OR = 16.3; 95%CI 2.2, 461.1) of developing the metabolic syndrome compared to normal-weight children. Binary logistic regression showed no significant association between age, gender and family history of communicable diseases with the metabolic syndrome. However, for ethnicity, Indians were found to have higher odds (OR = 5.5; 95%CI 1.5, 20.5) compared to Malays, with Chinese children (OR = 0.3; 95%CI 0.0, 2.7) having the lowest odds. Conclusions We conclude that being overweight or obese poses a greater risk of developing the metabolic syndrome among children. Indian ethnicity is at higher risk compared to their counterparts of the same age. Hence, primary intervention strategies are required to prevent this problem from escalating.
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Flexible tubular structures fabricated from solution electrospun fibers are finding increasing use in tissue engineering applications. However it is difficult to control the deposition of fibers due to the chaotic nature of the solution electrospinning jet. By using non-conductive polymer melts instead of polymer solutions the path and collection of the fiber becomes predictable. In this work we demonstrate the melt electrospinning of polycaprolactone in a direct writing mode onto a rotating cylinder. This allows the design and fabrication of tubes using 20 μm diameter fibers with controllable micropatterns and mechanical properties. A key design parameter is the fiber winding angle, where it allows control over scaffold pore morphology (e.g. size, shape, number and porosity). Furthermore, the establishment of a finite element model as a predictive design tool is validated against mechanical testing results of melt electrospun tubes to show that a lesser winding angle provides improved mechanical response to uniaxial tension and compression. In addition, we show that melt electrospun tubes support the growth of three different cell types in vitro and are therefore promising scaffolds for tissue engineering applications.
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A biomass pretreatment process was developed using acidified ionic liquid (IL) solutions containing 10-30% water. Pretreatment of sugarcane bagasse at 130°C for 30min by aqueous 1-butyl-3-methylimidazolium chloride (BMIMCl) solution containing 1.2% HCl resulted in a glucan digestibility of 94-100% after 72h of enzymatic hydrolysis. HCl was found to be a more effective catalyst than H(2)SO(4) or FeCl(3). Increasing acid concentration (from 0.4% to 1.2%) and reaction temperature (from 90 to 130°C) increased glucan digestibility. The glucan digestibility of solid residue obtained with the acidified BMIMCl solution that was re-used for three times was >97%. The addition of water to ILs for pretreatment could significantly reduce IL solvent costs and allow for increased biomass loadings, making the pretreatment by ILs a more economic proposition.
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Objective: To investigate the mental and general health of infertile women who had not sought medical advice for their recognized infertility and were therefore not represented in clinical populations. Design: Longitudinal cohort study.Setting Population based.Patient(s) Participants in the Australian Longitudinal Study on Women's Health aged 28-33 years in 2006 who had ever tried to conceive or had been pregnant (n = 5,936).Intervention(s) None.Main Outcome Measure(s) Infertility, not seeking medical advice. Result(s): Compared with fertile women (n = 4,905), infertile women (n = 1,031) had higher odds of self-reported depression (odds ratio [OR] 1.20, 95% confidence interval [CI] 1.01-1.43), endometriosis (5.43, 4.01-7.36), polycystic ovary syndrome (9.52, 7.30-12.41), irregular periods (1.99, 1.68-2.36), type II diabetes (4.70, 1.79-12.37), or gestational diabetes (1.66, 1.12-2.46). Compared with infertile women who sought medical advice (n = 728), those who had not sought medical advice (n = 303) had higher odds of self-reported depression (1.67, 1.18-2.37), other mental health problems (3.14, 1.14-8.64), urinary tract infections (1.67, 1.12-2.49), heavy periods (1.63, 1.16-2.29), or a cancer diagnosis (11.33, 2.57-49.89). Infertile women who had or had not sought medical advice had similar odds of reporting an anxiety disorder or anxiety-related symptoms. Conclusion(s): Women with self-reported depression were unlikely to have sought medical advice for infertility. Depression and depressive symptoms may be barriers to seeking medical advice for infertility.
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The rapid growth in use of the Internet as a business tool provides a new perspective in the study of the organizational challenges of new technologies. The innovation literature has grown vastly since its establishment in the 1920s, covering a broad range of disciplines (Foxall 1984) and measures a wide variety of variables (Rogers 1995). At first glance, studies that look at the relationship between innovation and firm survival appear contradictory. However, the results appear compatible when additional factors, such as industry type, organizational age, company size or the duration of the study are taken into account.
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This article critically analyses the role that criminological theory and specific policy formulations of culture play in the New Zealand state’s response to the over-representation of Māori in the criminal justice system. Part one provides an overview of the changing criminological explanations of, and responses to, Māori offending in New Zealand from the 1980s onwards and how these understandings extended colonialist approaches to Māori and crime into the neo-colonial context. In particular, we chart the shift in policy development from theorising Māori offending as attributable to loss of cultural identity to a focus on socio-economic and institutional antecedents and, finally, through the risk factors, assessment, and criminogenic needs approaches that have gained prominence in the current policy context. In part two, the focus moves to the strategies employed by members of the academy to elevate their own epistemological constructions of Māori social reality within the policy development process. In particular, the critique scrutinises recent attempts to portray Indigenous responses to social harm as “unscientific” and, in part, responsible for the continuing over-representation of Māori in New Zealand’s criminal justice system. The purpose of this analysis is to focus the critical, criminological gaze firmly on the activities of policy makers and administrative criminologists, to examine how their policies and approaches impact on Māori as an Indigenous people.
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In this paper, we analyse the impact of a (small) heterogeneity of jump type on the most simple localized solutions of a 3-component FitzHugh–Nagumo-type system. We show that the heterogeneity can pin a 1-front solution, which travels with constant (non-zero) speed in the homogeneous setting, to a fixed, explicitly determined, distance from the heterogeneity. Moreover, we establish the stability of this heterogeneous pinned 1-front solution. In addition, we analyse the pinning of 1-pulse, or 2-front, solutions. The paper is concluded with simulations in which we consider the dynamics and interactions of N-front patterns in domains with M heterogeneities of jump type (N = 3, 4, M ≥ 1).
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Goethite and Al-substituted goethite were synthesized and were characterized using XRD and XRF. The kinetic study of goethite dehydrate was investigated by TG and DTG at different heating rates (2, 5, 10, 15, 20 ◦C/min) and the effect of Al substitution for Fe on dehydrate was studied. The results showed that two types of absorbed water with the same Ed values of 3.4, 6.2 kJ/mol were confirmed on goethite and Alsubstituted goethite. Three types of hydroxyl units were proved, one being on the surface and the other two being in the structure of goethite. The substitution of Al for Fe in the structure of goethite decreases the desorption rate of hydroxyl, increases the dehydroxylation temperature, broadens the desorption peaks in DTG curves, and improves the Ed values from 19.4, 20.4, 26.1 kJ/mol to 21.6, 30, 33.6 kJ/mol when Al substitution comes to 9.1%.
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Purpose: To determine whether neuroretinal function differs in healthy persons with and without common risk gene variants for age- related macular degeneration (AMD) and no ophthalmoscopic signs of AMD, and to compare those findings in persons with manifest early AMD. Methods and Participants: Neuroretinal function was assessed with the multifocal electroretinogram (mfERG) (VERIS, Redwood City, CA,) in 32 participants (22 healthy persons with no clinical signs of AMD and 10 early AMD patients). The 22 healthy participants with no AMD were risk genotypes for either the CFH (rs380390) and/or ARMS2 (rs10490920). We used a slow flash mfERG paradigm (3 inserted frames) and a 103 hexagon stimulus array. Recordings were made with DTL electrodes; fixation and eye movements were monitored online. Trough N1 to peak P1 (N1P1) response densities and P1-implicit times (IT) were analysed in 5 concentric rings. Results: N1P1 response densities (mean ± SD) for concentric rings 1-3 were on average significantly higher in at-risk genotypes (ring 1: 17.97 nV/deg2 ± 1.9, ring 2: 11.7 nV/deg2 ±1.3, ring 3: 8.7 nV/deg2 ± 0.7) compared to those without risk (ring 1: 13.7 nV/deg2 ± 1.9, ring 2: 9.2 nV/deg2 ±0.8, ring 3: 7.3 nV/deg2 ± 1.1) and compared to persons with early AMD (ring 1: 15.3 nV/deg2 ± 4.8, ring 2: 9.1 nV/deg2 ±2.3, ring 3 nV/deg2: 7.3± 1.3) (p<0.5). The group implicit times, P1-ITs for ring 1 were on average delayed in the early AMD patients (36.4 ms ± 1.0) compared to healthy participants with (35.1 ms ± 1.1) or without risk genotypes (34.8 ms ±1.3), although these differences were not significant. Conclusion: Neuroretinal function in persons with normal fundi can be differentiated into subgroups based on their genetics. Increased neuroretinal activity in persons who carry AMD risk genotypes may be due to genetically determined subclinical inflammatory and/or histological changes in the retina. Assessment of neuroretinal function in healthy persons genetically susceptible to AMD may be a useful early biomarker before there is clinical manifestation of AMD.
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Background: Xanthine oxidase (XO) is a complex molybdeno-flavoprotein occurring with high activity in the milk fat globule membrane (MFGM) in all mammalian milk and is involved in the final stage of degradation of purine nucleotides. It catalyzes the sequential oxidation of hypoxanthine to xanthine and uric acid, accompanied by production of hydrogen peroxide and superoxide anion. Human saliva has been extensively described for its composition of proteins, electrolytes, cortisol, melatonin and some metabolites such as amino acids, but little is known about nucleotide metabolites. Method: Saliva was collected with swabs from babies; at full-term 1-4 days, 6-weeks, 6-months and 12-months. Unstimulated fasting (morning) saliva samples were collected directly from 77 adults. Breast milk was collected from 24 new mothers. Saliva was extracted from swabs and ultra-filtered. Nucleotide metabolites were analyzed by RP-HPLC with UV-photodiode array and ESI-MS/MS. XO activity was measured as peroxide production from hypoxanthine. Bacterial inhibition over time was assessed using CFU/mL or OD. Results: Median concentrations (μmol/L) of salivary nucleobases and nucleosides for neonates/6-weeks/6-months/12-months/adult respectively were: uracil 5.3/0.8/1.4/0.7/0.8, hypoxanthine 27/7.0/1.1/0.8/2.0, xanthine 19/7.0/2.0/2.0/2.0, adenosine 12/7.0/0.9/0.8/0.1, inosine 11/5.0/0.3/0.4/0.2, guanosine 7.0/6.0/0.5/0.4/0.1, uridine 12/0.8/0.3/0.9/0.4. Deoxynucleosides and dihydropyrimidines concentrations were essentially negligible. XO activity (Vmax:mean ± SD) in breast milk was 8.9 ± 6.2 μmol/min/L and endogenous peroxide was 27 ± 12 μmol/L; mixing breast milk with neonate saliva generated ~40 μmol/L peroxide,which inhibited Staphylococcus aureus. Conclusions: Salivary metabolites, particularly xanthine/hypoxanthine, are high in neonates, transitioning to low adult levels between 6-weeks to 6-months (p < 0.001). Peroxide occurs in breast milk and is boosted during suckling as an antibacterial system.
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Penalties and sanctions to deter risky/illegal behaviours are important components of traffic law enforcement. Sanctions can be applied to the vehicle (e.g., impoundment), the person (e.g., remedial programs or jail), or the licence (e.g., disqualification). For licence sanctions, some offences attract automatic suspension while others attract demerit points which can indirectly lead to licence loss. In China, a licence is suspended when a driver accrues twelve demerit points within one year. When this occurs, the person must undertake a one-week retraining course at their own expense and successfully pass an examination to become relicensed. Little is known about the effectiveness of this program. A pilot study was conducted in Zhejiang Province to examine basic information about participants of a retraining course. The aim was to gather baseline data for future comparison. Participants were recruited at a driver retraining centre in a large city in Zhejiang Province. In total, 239 suspended drivers completed an anonymous questionnaire which included demographic information, driving history, and crash involvement. Overall, 87% were male with an overall mean age of 35.02 years (SD=8.77; range 21-60 years). A large proportion (83.3%) of participants owned a vehicle. Commuting to work was reported by 64% as their main reason for driving, while 16.3% reported driving for work. Only 6.4% reported holding a licence for 1 year or less (M=8.14 years, SD=6.5, range 1-31 years) and people reported driving an average of 18.06 hours/week (SD=14.4, range 1-86 hours). This represents a relatively experienced group, especially given the increase in new drivers in China. The number of infringements reportedly received in the previous year ranged from 2 to 18 (M=4.6, SD=3.18); one third of participants reported having received 5 or more infringements. Approximately one third also reported having received infringements in the previous year but not paid them. Various strategies for avoiding penalties were reported. The most commonly reported traffic violations were: drink driving (DUI; 0.02-0.08 mg/100ml) with 61.5% reporting 1 such violation; and speeding (47.7% reported 1-10 violations). Only 2.2% of participants reported the more serious drunk driving violation (DWI; above 0.08mg/100ml). Other violations included disobeying traffic rules, using inappropriate licence, and licence plate destroyed/not displayed. Two-thirds of participants reported no crash involvement in the previous year while 14.2% reported involvement in 2-5 crashes. The relationship between infringements and crashes was limited, however there was a small, positive significant correlation between crashes and speeding infringements (r=.2, p=.004). Overall, these results indicate the need for improved compliance with the law among this sample of traffic offenders. For example, lower level drink driving (DUI) and speeding were the most commonly reported violations with some drivers having committed a large number in the previous year. It is encouraging that the more serious offence of drunk driving (DWI) was rarely reported. The effectiveness of this driver retraining program and the demerit point penalty system in China is currently unclear. Future research including driver follow up via longitudinal study is recommended to determine program effectiveness to enhance road safety in China.