Miracle-dz/UniFAR-FTUs huggingface dataset:
[Association of Pro12Ala mutation in peroxisome proliferator-activated receptor gamma 2 with obesity and diabetes in Chinese population].

OBJECTIVE To investigate peroxisome proliferator-activated receptors gamma 2 (PPAR gamma 2) polymorphism and its association with obesity or diabetes in Chinese population. METHODS Normal weight group(91) and overweight and obese group(140) were included in this study, according to BMI. 103 subjects had normal glucose tolerance, 50 had impaired glucose tolerance, and 78 had diabetes mellitus, according to WHO Criteria for Diagnosis of Diabetes Mellitus. We evaluated these subjects for the Pro12Ala mutation in the PPAR gene using PCR-restriction fragment length polymorphism. RESULTS Allele frequencies of Pro12Ala mutation of PPAR gamma 2 in overweight and obese subjects (qA = 3.93%) were not significantly different from those in normal weight group (qA = 3.85%, P > 0.05). Both in overweight and obese group and normal weight group, the genotype of PA(AA) had lower plasma resistin as compared with the genotype of PP(P < 0.05). Allele frequencies of Pro12Ala were not different among Chinese subjects with normal glucose tolerance (qA = 3.88%), those with impaired glucose tolerance (qA = 4.00%), and those with diabetes mellitus (qA = 3.85%, P > 0.05). In these three groups, the genotype of PA(AA) had lower plasma resistin as compared with the genotype of PP, only in impaired glucose tolerance group the difference was not significant (P > 0.05). CONCLUSION The Pro12Ala mutation in PPAR gamma 2 was not associated with either diabetes or obesity. The PPAR gamma 2 Ala allele may be involved in the expression of resistin and insulin sensitivity.
The role of bacterial hydrophobicity in infection: bacterial adhesion and phagocytic ingestion.

The role that bacterial surface hydrophobicity (surface tension) plays in determining the extent of adhesion of polymer substrates and phagocytic ingestion is reviewed. The early attachment phase in bacterial adhesion is shown to depend critically on the relative surface tensions of the three interacting phases; i.e., bacteria, substrate, and suspending liquid surface tension. When suspended in a liquid with a high surface tension such as Hanks balanced salt solution, the most hydrophobic bacteria adhere to all surfaces to the greatest extent. When the liquid surface tension (gamma LV) is larger than the bacterial surface tension (gamma BV), then for any single bacterial species the extent of adhesion decreases with increasing substrate surface tension (gamma SV). When gamma LV less than gamma BV then adhesion increases with increasing gamma SV. Bacterial surface tension also determines in part the extent of phagocytic ingestion and the degree to which antibodies specifically adsorb onto the bacterium resulting in opsonization. The nonspecific adsorption of antibodies results in a considerable modification in the surface properties of the bacteria. Bacterial surface hydrophobicity can be altered significantly through exposure to subinhibitory concentrations of antibiotics, surfactants, lectins, etc. The effect of these changes on subsequent phagocytic ingestion is discussed.
Towards an understanding of equine pleuropneumonia: factors relevant for control.

OBJECTIVE To review relevant literature on factors associated with the development of equine pleuropneumonia. DESIGN A review of the literature using a range of databases including Current Contents, Medline, ChemAbstracts, Biological Abstracts and CAB and a comprehensive search strategy which involved use of keywords, author and subject category searches. Additional sources included review of articles cited by key accumulated references. RESULTS Since the early years of this century, many of the "gaps" in our knowledge of the pathogenesis of this disease have been filled. We now know that equine pleuropneumonia results from contamination of the lower respiratory tract with bacteria similar to the normal oropharyngeal microbiota of the horse and that transportation of any mode, especially over long distances (and consequently with no or short rest periods), is the single most important predisposing factor for this disease. This is associated with restraint of horses such that they are unable to lower their heads, which leads to increased opportunity for lower respiratory tract contamination and a reduced opportunity for clearance. Strenuous exercise also results in lower respiratory tract contamination and exercise subsequent to transportation exerts additive detrimental effects on the defenses of the lower respiratory tract. CLINICAL IMPLICATIONS While modern veterinary medicine and surgery have significantly reduced the death rate from pleuropneumonia, horses that develop the disease have a high probability of not returning to their prior use. This underscores the importance of developing the most effective strategies for its prevention.
An epidemiological study of blood pressure and metabolic phenotypes in relation to the Gβ3 C825T polymorphism

Background The 825T allele of the G-protein β3-subunit gene is associated with increased intracellular signalling and adipogenesis in experimental studies. We studied the C825T polymorphism in relation to blood pressure, obesity and intermediate phenotypes in a Caucasian population. Methods We genotyped 737 men and 775 women (participation rate, 64.3%) enrolled in a Belgian population study. Dichotomous phenotypes were tested for association with the C825T polymorphism by Fisher's exact test and multiple logistic regression. For continuous traits, we used analysis of covariance and generalized estimating equations. Results The T allele (39.7 versus 29.1%) and TT genotype (16.1 versus 7.7%) were more prevalent in obese men than in non-obese men (P ⩽ 0.01). TT homozygous men, compared with C allele carriers, had higher daytime ambulatory blood pressure (mean systolic/diastolic differences, 3.6/2.5 mmHg; P ⩽ 0.02), higher body weight (2.7 kg, P = 0.04), greater risk of obesity (risk ratio, 1.90; P = 0.005), increased triceps skinfold thickness (2.3 mm, P = 0.007), higher serum insulin concentration (4.1 mU/l, P = 0.006), more insulin resistance (P = 0.01), and increased erythrocyte count (0.11 × 1012 cells/l, P = 0.04) and haematocrit (0.9%, P = 0.02). In women, haematocrit and erythrocyte count were also higher (P ⩽ 0.03) in T allele carriers, but other phenotypes were not correlated with the C825T polymorphism. Conclusion Male and female carriers of the T allele at position 825 of the G-protein β3-subunit gene have a slightly higher haematocrit and erythrocyte count. Male TT homozygotes have a higher blood pressure and are more obese and insulin-resistant than C allele carriers. We speculate that the higher blood pressure in TT homozygous men might arise via a metabolic pathway characterized by obesity and insulin resistance as well as via increased peripheral resistance secondary to the higher haematocrit.
From street-level to screen-level bureaucracy: Front-line public servants’ recordkeeping behaviours in ICT-enabled agencies

Recordkeeping is a ubiquitous task within the public sector: public agencies rely on evidence of activities, in the form of public records, to coordinate activities, track resources, establish precedents, monitor performance as well as maintain consistency and continuity. Many public servants are responsible for recordkeeping; however, to date, little is known about the recordkeeping behaviours of these individuals, particularly about the recordkeeping behaviours of public servants who interact with members of the public on a daily basis. The purpose of this study is to explore the recordkeeping behaviours of New Zealand front-line public servants within ICT-enabled state sector agencies to understand these behaviours and their associated governance implications. This inductive study began with multiple case studies that sought to explore the recordkeeping behaviours of front-line public servants. The second data collection phase involved a series of qualitative focus group interviews that explored the wider implications of the case studies, with the specific focus on understanding the governance implications. The empirical data was reviewed, drawing on the three theoretical concepts that established the analytical lens for this study: recordkeeping informatics, personal information management strategies, and the influencing factors on front-line public servants’ decision-making behaviours. Findings from this study suggest that front-line public servants have varying degrees of discretion to perform recordkeeping behaviours. A key outcome of this research is the identification of factors that influence the recordkeeping behaviours of front-line public servants: personal characteristics, organisational characteristics and the broader community.
Subclinical anthracycline- and trastuzumab-induced cardiotoxicity in the long-term follow-up of asymptomatic breast cancer survivors: a speckle tracking echocardiographic study

Objective To examine the long-term effects of standard chemotherapy on myocardial function in asymptomatic breast cancer survivors using two-dimensional speckle tracking echocardiography. Methods Seventy women (chemotherapy group) aged 54±8 years who had received anthracycline treatment with (n=19) or without (n=51) adjuvant trastuzumab up to 6 years previously, and 50 female controls were studied. Left ventricular systolic (ejection fraction (EF%), peak systolic myocardial excursion, (Sm)) and diastolic (peak mitral E and A velocities, six-point average of mitral annular E′ velocities) function, 2D global and regional longitudinal and radial strain were determined using standard 2D Doppler and tissue Doppler echocardiographic methods and speckle tracking software. Results Despite normal EF% (62±4% vs 60±3%, p=0.051) the chemotherapy group had reduced E/A ratios (0.9±0.3 vs 1.1±0.3, p=0.003), global E′ (10.2±2 vs 11.2±2.3, p=0.036), global Sm (9.0±1.3 vs 9.6±1.3, p=0.029) and global longitudinal 2D strain (−18.1±2.2 vs −19.6±1.8, p=0.0001) in comparison with controls. In 18 (26%) of the chemotherapy group, global longitudinal strain was below the lower limit of the control group. Cigarette smoking was a negative predictor of longitudinal strain, but only in the chemotherapy group. Radial strain did not differ significantly between the two groups. There were no significant differences in EF%, global Sm and longitudinal strain between trastuzumab-treated individuals and controls. Conclusions Subclinical systolic and diastolic myocardial abnormalities were present in asymptomatic breast cancer survivors up to 6 years after standard chemotherapy. Cigarette smoking had a negative effect on longitudinal strain in these individuals. Adjuvant trastuzumab treatment did not appear to have an additive adverse impact on myocardial function in the medium–long term.
Development of Y‐axon innervation of cortical area 18 in the cat.

1. Geniculocortical Y‐axons (n = 38) in the optic radiations of 4‐5‐week‐old kittens (n = 20) and adult cats (n = 18) were studied both physiologically and morphologically. Axons were recorded from intracellularly and subsequently filled ionophoretically with horseradish peroxidase (HRP). The HRP filled the axons' terminal arborizations in visual cortex (particularly well for those innervating area 18). Fourteen axons appeared to be completely filled with HRP (n = 8 in kitten, n = 6 in adult) and served as the basis for the quantitative analysis of the terminal arborizations reported in this study. 2. The distribution and correspondence of the axonal boutons to presynaptic elements in cortical layer 4A was analysed at both the light and electron microscope level using computerized three‐dimensional analysis and serial section reconstruction, respectively. Compared to adult axons, the boutons of the kitten axons were smaller (means = 0.75 vs. 1.75 microns length, P less than 0.001) and more densely spaced both along individual axon branches (means = 6.60 vs. 11.20 microns interbouton interval, P less than 0.001) and between neighbouring branches of the same axon (means = 4.7 vs. 6.4 microns nearest‐neighbour distance, P less than 0.01). 3. Most kitten boutons made a single Gray's type 1 synapse on a cortical neurone, unlike adult boutons which usually contacted two or more postsynaptic targets. Both kitten and adult axons had dendritic spines as their major target. Occasionally, HRP reaction‐product was observed in cortical neurones postsynaptic to the labelled geniculocortical axon, which gave some estimate of the number of synaptic contacts between a single geniculocortical axon and target cell (about five). 4. The kitten Y‐axons innervated the visual cortex in a pattern similar to that of the adult, with the richest terminal branching and bouton density in layer 4A with some additional boutons distributed in layers 3, 4B and 6. The extent of the terminal arborizations primarily in layer 4A (as measured in surface views) of kitten Y‐axons in area 18 was significantly less than that of adult Y‐axons in area 18 (means = 0.9 mm2 vs. means = 1.2 mm2, P = 0.04). 5. We conclude that between 4 and 5 postnatal weeks and 1 year, geniculocortical Y‐axons projecting to cortical area 18 undergo four major changes. These include a reduction in synaptic bouton density (both in three‐dimensional space and along individual branches), a concomitant moderate expansion in the surface area of cortex innervated, an increase in bouton size and an increase in the number of synaptic contacts made by each bouton. A general proportional growth of the individual axons' terminal arborization together with fusion and/or separation of neighbouring boutons is sufficient to explain this development.
Elevated plasma concentrations of S100 calcium-binding protein B and tumor necrosis factor alpha in children with autism spectrum disorders

Objective: To investigate plasma concentrations of S100B (a calcium-binding protein derived primarily from the glia) and inflammatory cytokines in children with autism and the relationship between S100B and cytokine concentrations. Methods: Plasma levels of S100B, tumor necrosis factor alpha (TNF-α), interferon gamma, interleukin (IL)-1β, IL-4, IL-6, IL-10, and IL-17A were measured in 40 unmedicated children with autism and 35 normally developing healthy children. The severity of autism was assessed using the Childhood Autism Rating Scale (CARS). Results: Concentrations of both S100B and TNF-α were higher in children with autism before and after adjusting for a priori-selected confounders (age, sex, and body mass index). S100B concentrations were higher in children with severe autism compared to children with mild-moderate autism. However, this association remained as a trend after adjusting for confounders. S100B concentrations correlated positively with TNF-α concentrations. Conclusion: Our findings showing an increase in peripheral concentrations of S100B and TNF-α provide limited support to the hypothesis about the roles of altered immune function and S100B in autism spectrum disorder (ASD). Studies of larger numbers of well-characterized individuals with ASD are needed to clarify the potential role of the immune system in the pathophysiology of this disorder.
Simulation of platelet adhesion and aggregation regulated by fibrinogen and von Willebrand factor

Summary We propose a method to analyze platelet adhesion and aggregation computationally, taking into account the distinct properties of two plasma proteins, vonWillebrand factor (vWF) and fibrinogen (Fbg). In this method, the hydrodynamic interactions between platelet particles under simple shear flow were simulated using Stokesian dynamics based on the additivity of velocities. The binding force between particles mediated by vWF and Fbg was modeled using the Voigt model. Two Voigt models with different properties were introduced to consider the distinct behaviors of vWF and Fbg. Our results qualitatively agreed with the general observation of a previous in-vitro experiment, thus demonstrating that the significant development of thrombus formation in height requires not only vWF, but also Fbg. This agreement of simulation and experimental results qualitatively validates our model and suggests that consideration of the distinct roles of vWF and Fbg is essential to investigate the physiological and pathophysiological mechanisms of thrombus formation using a computational approach.
Persistent sleep disturbance is associated with treatment response in adolescents with depression

Background: Sleep disturbances are highly prevalent in adolescents with depressive disorders. To date there is limited evidence of the extent to which sleep disturbances are associated with treatment response in adolescents. This study aimed to examine the extent to which self-reported sleep disturbances are associated with treatment response in adolescents with depression. Method: Sleep data were gathered from a sample of 166 adolescents (aged 12–18 years) with a diagnosis of a DSM-IV depressive disorder who underwent 3 months of treatment (psychosocial and/or pharmacotherapy (sertraline)) in community-based research programs. The subjective report of sleep disturbance within depressive disorders was assessed using the Kiddie Schedule for Affective Disorders and Schizophrenia for School Age Children at three time points: pre-treatment, post-treatment and 6-month follow-up. Results: Sixty-nine percent of participants had a sleep disturbance pre-treatment and approximately 75% of these participants had threshold symptoms. Threshold sleep disturbances that persisted from pre- to post-treatment assessments were positively associated with depression at the 6-month follow-up. An ordered logistic regression model controlling for gender, treatment group and comorbid anxiety estimated a 70% risk of depression or partial remission for those with persistent sleep disturbance. Treatment group, anxiety and gender generally had no significant effect on the relationship between sleep and depression. Conclusion: Sleep disturbances were highly related to depressive state and were associated with poorer treatment response in adolescents with depression. These results provide a rationale for further exploration of sleep-related treatments for adolescents with depression. Knowledge of patient-reported persistent sleep disturbances can help clinicians to predict treatment outcomes and may direct them to augment treatment or focus on sleep-related treatment strategies.
Factors influencing the progression of fibrosis in patients with recurrent hepatitis C after liver transplantation under antiviral therapy: A retrospective analysis of 939 liver biopsies in a single center

Recurrent hepatitis C after liver transplantation (LT) is a major problem, since up to 30% of patients develop cirrhosis only 5 years after LT in the absence of antiviral therapy. The aim of this study was to examine the rate of progression of fibrosis and its associated risk factors in patients submitted to an early antiviral treatment post‐LT. Included in the study were 105 patients submitted to LT between September 1990 and December 2004, 70 of whom were treated with interferon and/or ribavirin. A total of 939 liver biopsies were studied. The median fibrosis stage was 0.8 after 1 year post‐LT, 1.1 after 3 years, 1.3 after 5 years, and 1.5 after 10 years. LT recipients with fibrosis >2 (13% at 10 years) had a significantly reduced survival rate (63% vs. 87% at 10 years, P = 0.03). Univariate analysis disclosed that recipient male gender, antiviral therapy before LT, LT after 1998, induction immunosuppressive regimen including tacrolimus, induction immunosuppressive regimen including mycophenolate (or without azathioprine), and short duration of prednisolone (<12 months) were significantly associated with progression of fibrosis. In a multivariate analysis, recipient male gender (P = 0.04), antiviral treatment before LT (P = 0.001), and initial immunosuppressive regimen without azathioprine (P = 0.03) were associated with progression of fibrosis. In conclusion, our study has documented that fibrosis progression is not linear over time and that occurrence of severe fibrosis is related to previously described factors related to immunosuppressive regimen or donor age and also to a past history of pre‐LT antiviral therapy. Liver Transpl 13:294–301, 2007. © 2007 AASLD.
Effects of Nickel Chloride on Human Platelets: Enhancement of Lipid Peroxidation, Inhibition of Aggregation and Interaction with Ascorbic Acid

This study was undertaken to examine the effects of nickel (Ni) on human platelet function. In a (concentration-dependent manner, Ni significantly inhibited the function of platelet aggregation induced by collagen. The phenomenon of lipid peroxidation was involved as Ni significantly increased malondialdehyde (MDA) levels with reduction in platelet reduced glutathione (GSH) and alpha-tocopherol content. Further, platelet thromboxane B2, formation was markedly inhibited and the levels of cyclic AMP were significantly elevated by Ni. Treatment with ascorbic acid (Vit C) significantly lowered the levels of MDA and increased the content of alpha-tocopherol and reduced GSH. Vit C also significantly increased platelet aggregation and thromboxane B2 when coincubated with Ni. Data show that Ni is toxic as evidenced by lipid peroxidative damage and inhibition of human platelet aggregation, but that ascorbic acid provides protection, at least partially, against this metal.
Fibroblast Growth Factor Receptor Inhibition Synergizes With Paclitaxel and Doxorubicin in Endometrial Cancer Cells

Objective The fibroblast growth factor (FGF) family of signaling molecules has been associated with chemoresistance and poor prognosis in a number of cancer types, including lung, breast, ovarian, prostate, and head and neck carcinomas. Given the identification of activating mutations in the FGF receptor 2 (FGFR2) receptor tyrosine kinase in a subset of endometrial tumors, agents with activity against FGFRs are currently being tested in clinical trials for recurrent and progressive endometrial cancer. Here, we evaluated the effect of FGFR inhibition on the in vitro efficacy of chemotherapy in endometrial cancer cell lines. Methods Human endometrial cancer cell lines with wild-type or activating FGFR2 mutations were used to determine any synergism with concurrent use of the pan-FGFR inhibitor, PD173074, and the chemotherapeutics, doxorubicin and paclitaxel, on cell proliferation and apoptosis. Results FGFR2 mutation status did not alter sensitivity to either chemotherapeutic agent alone. The combination of PD173074 with paclitaxel or doxorubicin showed synergistic activity in the 3 FGFR2 mutant cell lines evaluated. In addition, although nonmutant cell lines were resistant to FGFR inhibition alone, the addition of PD173074 potentiated the cytostatic effect of paclitaxel and doxorubicin in a subset of FGFR2 wild-type endometrial cancer cell lines. Conclusions Together these data suggest a potential therapeutic benefit to combining an FGFR inhibitor with standard chemotherapeutic agents in endometrial cancer therapy particularly in patients with FGFR2 mutation positive tumors.