Miracle-dz/UniFAR-FTUs huggingface dataset:
Associations between CYP1A1 rs1048943 A > G and rs4646903 T > C genetic variations and colorectal cancer risk: Proof from 26 case-control studies

Cytochrome P450 1A1 (CYP1A1) enzyme is one of the most important metabolizing enzymes responsible for the metabolism of numerous xenobiotics. Numerous individual case-control studies have investigated the associations between the CYP1A1 rs1048943 A > G and rs4646903 T > C genetic variations and colorectal cancer (CRC) risk, but the conclusions were controversial. To obtain a scientific conclusion, we performed a meta-analysis based on a total of 26 publications, including 20 studies with 8665 cases and 9953 controls on rs1048943 A > G and 19 studies with 6416 cases and 7551 controls on rs4646903 T > C, respectively. The pooled analysis indicated that rs1048943 A > G was associated with an increased risk of CRC (G vs. A: OR = 1.28, 95% CI = 1.08−1.52; GG vs. AA: OR = 1.54, 95% CI = 1.25−1.91; GA vs. AA: OR = 1.26, 95% CI = 1.00−1.60; GG/GA vs. AA: OR = 1.31, 95% CI = 1.05−1.64; GG vs. GA/AA: OR = 1.56, 95% CI = 1.26−1.91). Stratification analysis showed the association between rs1048943 A > G and CRC risk was more obvious in studies with the population-based (PB) design or high quality score. The association between rs4646903 T > C and CRC risk did not reach statistical significance in the pooled analysis as well as stratification analysis. This meta-analysis demonstrated CYP1A1 rs1048943 A > G may increase the susceptibility to CRC instead of rs4646903 T > C. This conclusion suggested CYP1A1 may contribute to the pathogenesis of CRC.
Cooperative Assembly of Androgen Receptor into a Nucleoprotein Complex That Regulates the Prostate-specific Antigen Enhancer*

Prostate cancer is characterized by elevated serum levels of prostate-specific antigen (PSA). PSA gene expression is controlled by an androgen-responsive transcriptional enhancer. Our study suggests that formation of a nucleoprotein complex, encompassing 170 base pairs of enhancer DNA, mediates androgen-responsive PSA enhancer activity. The complex is assembled by cooperative binding of androgen receptor to at least four tandem, nonconsensus androgen response elements (AREs). Systematic mutagenesis of the AREs demonstrated that they act synergistically to stimulate androgen receptor-responsive gene expression. We discuss a mechanism whereby a combination of high androgen receptor levels in the prostate and low affinity AREs contribute to the cell type specificity and activity of the enhancer.
Dopamine deficits in the brain: the neurochemical basis of parkinsonian symptoms in AIDS

We sought to determine whether the motor dysfunctions and neuroleptic sensitivity that can occur in patients with AIDS relates to a deficit of striatal dopamine innervation similar to that of Parkinson's disease. For this purpose we measured concentrations of dopamine and its major metabolite homovanillic acid (HVA) in caudate nucleus tissue taken post-mortem from patients with AIDS and from appropriate age-matched control subjects. Dopamine and HVA concentrations were both significantly reduced in the AIDS group, with 20 of 34 patients exhibiting dopamine concentrations below the control range. This finding is consistent with a loss of nigrostriatal dopaminergic neurones, and may underlie the motor dysfunction and neuroleptic sensitivity that can occur in AIDS patients, indicating the potential value of antiparkinsonian therapy in such patients.
Ultrastructural studies on the intracellular fate of 125I‐nerve growth factor in cultured rat sympathetic neurons

Primary cell cultures of sympathetic neurons from rat were exposed to 125I‐nerve growth factor (NGF) and the fate of the NGF in the cell was followed using electron microscopic autoradiography. The intracellular localization of NGF was determined in the cell bodies and in the proximal neurites of neurons that had been grown in three‐chamber dishes, following 5 or 24 hr of retrograde transport of NGF from the distal portions of the neurites. Label in the proximal neurites was predominantly associated with lysosomes and multivesicular bodies (MVBs), and at 5 hr elongated tubular elements were especially heavily labeled. Most of the label in the cell bodies was concentrated in lysosomes and MVBs. Lysosomes accounted for the largest fraction (45–60%) of the grains in the cell body, with a labeling density (LD = % grains/% area) of 3–5, while MVBs accounted for 5–10% of the grains with an LD of 5–20. We observed no evidence of nuclear labeling after 5 or 24 hr of retrograde transport. Mass cultures of neurons were incubated for 22 hr with NGF in the presence of the lysosomal inhibitors chloroquine (CQ, 0.05 mM) or methylamine (MA, 10 mM). In both agents the lysosomes were swollen with membranous material but still sequestered NGF, especially in CQ where the lysosomes were associated with almost 65% of the grains and had an LD of 6. CQ and MA had different effects on the morphology of the MVBs: in CQ they were few in number and compact while in MA they were numerous and appeared swollen and vacuolated. We observed no evidence for the nuclear accumulation of NGF even in the presence of the lysosomotropic agents.
Efficacy of adjunctive aripiprazole to either valproate or lithium in bipolar mania patients partially nonresponsive to valproate/lithium monotherapy: a placebo-controlled study.

OBJECTIVE The authors evaluated the efficacy and safety of adjunctive aripiprazole in bipolar I patients with mania partially nonresponsive to lithium/valproate monotherapy. METHOD This multicenter, randomized, placebo-controlled study included outpatients experiencing a manic or mixed episode (with or without psychotic features). Patients with partial nonresponse to lithium/valproate monotherapy (defined as a Young Mania Rating Scale total score >/=16 at the end of phases 1 and 2, with a decrease of </=25% between phases) with target serum concentrations of lithium (0.6-1.0 mmol/liter) or valproate (50-125 mug/ml) were randomly assigned in a 2:1 ratio to adjunctive aripiprazole (N=253; 15 or 30 mg/day) or placebo (N=131) for 6 weeks. RESULTS Mean improvement from baseline in Young Mania Rating Scale total score at week 6 (primary endpoint) was significantly greater with aripiprazole (-13.3) than with placebo (-10.7). Significant improvements in Young Mania Rating Scale total score with aripiprazole versus placebo occurred from week 1 onward. In addition, the mean improvement in Clinical Global Impression Bipolar Version (CGI-BP) severity of illness (mania) score from baseline to week 6 was significantly greater with aripiprazole (-1.9) than with placebo (-1.6). Discontinuation rates due to adverse events were higher with aripiprazole than with placebo (9% versus 5%, respectively). Akathisia was the most frequently reported extrapyramidal symptom-related adverse event and occurred significantly more frequently among those receiving aripiprazole (18.6%) than among those receiving placebo (5.4%). There were no significant differences between treatments in weight change from baseline to week 6 (+0.55 kg and +0.23 kg for aripiprazole and placebo, respectively; last observation carried forward). CONCLUSIONS Adjunctive aripiprazole therapy showed significant improvements in mania symptoms as early as week 1 and demonstrated a tolerability profile similar to that of monotherapy studies.
The role of autonomic and myocardial factors in cardiac control.

The classical Starling hypothesis, based on studies of isolated heart preparations, assigns the dominant role in cardiac control to the functional relation between end-diastolic fiber length and stroke work; it acknowledges the influence of autonomic factors, but considers them less fundamental than the intrinsic myocardial factor (1, 2). At the other extreme is the view that cardiac response to stress in the intact human being is largely a matter of change in rate, the autonomic factor almost completely overshadowing any intrinsic mechanism (3). Graded treadmill studies in normal human subjects, however, suggest that both an increase in stroke volume and in pulse rate are employed in adapting to exercise (4). The increase in stroke volume is not linear with the increase in severity of exercise, as has been pointed out by Rushmer (5). Even in experimental animals, the role of increase of stroke voltume and, by inference. of intrinsic myocardial factors, is difficult to assess because such factors, if present, are obscured by powerful autonomic effects. The need for quantitative studies in which autonomic influences can be eliminated in otherwise intact animals, and in which change in ventricular volume can be measured directly, has often been noted and was partly met by earlier work from this laboratory (6). In addition, Ashkar and Hamilton recently reported that cardiac denervation in dogs caused restriction of "the normal increase in oxygen consumption and cardiac output with exercise' (7). Donald and Shepherd obtained similar results, also in dogs, and noted that after cardiac denervation. adaptation to exercise depended solely on increase in stroke volume (8). The following project seas undertaken primarily
Specialization in the default mode: Task‐induced brain deactivations dissociate between visual working memory and attention

The idea of an organized mode of brain function that is present as default state and suspended during goal‐directed behaviors has recently gained much interest in the study of human brain function. The default mode hypothesis is based on the repeated observation that certain brain areas show task‐induced deactivations across a wide range of cognitive tasks. In this event‐related functional resonance imaging study we tested the default mode hypothesis by comparing common and selective patterns of BOLD deactivation in response to the demands on visual attention and working memory (WM) that were independently modulated within one task. The results revealed task‐induced deactivations within regions of the default mode network (DMN) with a segregation of areas that were additively deactivated by an increase in the demands on both attention and WM, and areas that were selectively deactivated by either high attentional demand or WM load. Attention‐selective deactivations appeared in the left ventrolateral and medial prefrontal cortex and the left lateral temporal cortex. Conversely, WM‐selective deactivations were found predominantly in the right hemisphere including the medial‐parietal, the lateral temporo‐parietal, and the medial prefrontal cortex. Moreover, during WM encoding deactivated regions showed task‐specific functional connectivity. These findings demonstrate that task‐induced deactivations within parts of the DMN depend on the specific characteristics of the attention and WM components of the task. The DMN can thus be subdivided into a set of brain regions that deactivate indiscriminately in response to cognitive demand (“the core DMN”) and a part whose deactivation depends on the specific task. Hum Brain Mapp, 2010. © 2009 Wiley‐Liss, Inc.
Neuropeptide Y Modulation of Interleukin-1β (IL-1β)-induced Nitric Oxide Production in Microglia*

Given the modulatory role of neuropeptide Y (NPY) in the immune system, we investigated the effect of NPY on the production of NO and IL-1β in microglia. Upon LPS stimulation, NPY treatment inhibited NO production as well as the expression of inducible nitric-oxide synthase (iNOS). Pharmacological studies with a selective Y1 receptor agonist and selective antagonists for Y1, Y2, and Y5 receptors demonstrated that inhibition of NO production and iNOS expression was mediated exclusively through Y1 receptor activation. Microglial cells stimulated with LPS and ATP responded with a massive release of IL-1β, as measured by ELISA. NPY inhibited this effect, suggesting that it can strongly impair the release of IL-1β. Furthermore, we observed that IL-1β stimulation induced NO production and that the use of a selective IL-1 receptor antagonist prevented NO production upon LPS stimulation. Moreover, NPY acting through Y1 receptor inhibited LPS-stimulated release of IL-1β, inhibiting NO synthesis. IL-1β activation of NF-κB was inhibited by NPY treatment, as observed by confocal microscopy and Western blotting analysis of nuclear translocation of NF-κB p65 subunit, leading to the decrease of NO synthesis. Our results showed that upon LPS challenge, microglial cells release IL-1β, promoting the production of NO through a NF-κB-dependent pathway. Also, NPY was able to strongly inhibit NO synthesis through Y1 receptor activation, which prevents IL-1β release and thus inhibits nuclear translocation of NF-κB. The role of NPY in key inflammatory events may contribute to unravel novel gateways to modulate inflammation associated with brain pathology.
Analgesic Effect of Breast Milk Versus Sucrose for Analgesia During Heel Lance in Late Preterm Infants

OBJECTIVE: The purpose of this trial was to investigate whether breast milk (either breastfed or bottle-fed) has a better analgesic effect than sucrose in newborns born at a postmenstrual age between 32 and 37 weeks. METHODS: We conducted a randomized controlled trial at a secondary care neonatal unit in the Netherlands on 71 preterm neonates (postmenstrual age at birth 32–37 weeks), undergoing heel lance with an automated piercing device. Newborns were randomly assigned to breast milk (either breastfed or bottle-fed) administered during heel lance or oral sucrose administered before heel lance. We assessed the Premature Infant Pain Profile (PIPP) score (range, 0–21) to investigate whether there was a difference in pain score between neonates receiving breast milk and those receiving sucrose solution. RESULTS: There was no significant difference in mean PIPP score between neonates receiving breast milk (6.1) and those receiving sucrose (5.5), with a mean difference of 0.6 (95% confidence interval −1.6 to 2.8; P = .58). CONCLUSIONS: From this study, it cannot be concluded that breast milk has a better analgesic effect than sucrose in late preterm infants. From the results, it follows with 95% confidence that the analgesic effect of breast milk is not >1.6 points better and not > 2.8 points worse on the PIPP scale (SD 3.7) than the analgesic effect of sucrose in late preterm infants.
GROWTH OF VIRULENT AND ATTENUATED ECTROMELIA VIRUS IN CULTURED MACROPHAGES FROM NORMAL AND ECTROMELIAIMMUNE MICE.

Growth of ectromelia virus in cultured mouse peritoneal macrophages is described. Macrophages in vitro are more susceptible to infection by a virulent than by an attenuated strain of ectromelia virus. Macrophages from susceptible and resistant strains of mouse are equally susceptible to infection in vitro with virulent ectromelia virus. Macrophages from immune mice are more readily infected than are normal macrophages. This effect is attributed to the greater phagocytic activity of the macrophages from immune mice. Even in the presence of immune serum, macrophages from immune mice are more readily infected than are macrophages from normal mice.
A Stochastic Framework for Short-Term Operation of a Distribution Company

This paper presents a stochastic framework for short-term operation of a distribution company (disco). The proposed framework optimizes disco's operational decisions in two hierarchical stages. The first stage, called day-ahead operation stage (DAOS), deals with the operational decisions on purchases from the day-ahead market and commitment of distributed generation (DG) units. The objective of this stage is to minimize the expected operating cost while the financial risk exposed by uncertain real-time prices and loads is restricted to a given level. The model associated with this stage is based on the mixed-integer programming (MIP) format. The second stage, named real-time operation stage (RTOS), deals with disco's activities in real-time. In RTOS, decisions are made on real-time market transactions, dispatch of online DGs, and invocation of load curtailments (LCs) such that the expected operating cost is minimized. This stage is formulated as a nonlinear programming (NLP) problem. To investigate the effectiveness of the developed framework, it is applied to a typical Finnish 20-kV urban distribution network.
Data on the HL‐A linkage group

Lod scores from a study in 229 families of the linkage relations of HL-A-PGM3 to 19 marker loci and cystic fibrosis are reported. The data exclude that ADA belongs to this linkage group while they give weak support for the inclusion of P. There is weak evidence for linkage of cystic fibrosis to PGM3, but none for linkage to HL-A. No new suggestive linkages appeared.
The P Wave and P‐R Interval: Effects of the Site of Origin of Atrial Depolarization

The atria of 37 patients were paced from selected sites during cardiac surgery. When the atria were paced from endocardial sites low in the right atrium, the P waves in ECG leads II, III, and aVF were shown to be either negative, biphasic, or positive, depending on the site paced. When the endocardial sites were paced, the P-R intervals were, almost without exception, less than 0.12 sec. When those endocardial sites closest to the A-V junction were paced, the P-R intervals were always less than 0.12 sec. When the atria were paced, from the epicardial sites, the P-R intervals were always greater than 0.12 sec. Negative P waves in ECG leads II, III, and aVF were recorded when the atria were paced from the postero-inferior left atrium and the caudal right atrium. The P-R interval did not always reflect the initial period of atrial activation because an isoelectric interval, generally of 0.01 to 0.025 sec, was frequently present between the onset of atrial stimulation and the first clear evidence of the P wave in the ECG. The implications of these results are discussed.
The Natural Autoantibody Repertoire of Nonobese Diabetic Mice Is Highly Active1

Analysis of spontaneous hybridomas generated from nonobese diabetic (NOD) mice indicates that the natural autoantibody repertoire of NOD mice is highly active compared with C57BL/6 and BALB/c mice. This property of increased B cell activity is present early in life (4 wk) and persists in older mice of both sexes. Even when selected for binding to a prototypic β cell Ag, such as insulin, NOD mAb have characteristics of natural autoantibodies that include low avidity and broad specificity for multiple Ags. Analyses of the variable region of Ig H chain (VH) and variable region κ L chain genes expressed by six insulin binding mAb show that V gene segments are often germline encoded and are identical with those used by autoantibodies, especially anti-dsDNA, from systemic autoimmune disease in MRL, NZB/W, and motheaten mice. VH genes used by four mAb are derived from the large J558 family and two mAb use VH7183 and VHQ52 genes. The third complementarity-determining region of Ig H chain of these mAb have limited N segment diversity, and some mAb contain DNA segments indicative of gene replacement. Genetic abnormalities in the regulation of self-reactive B cells may be a feature that is shared between NOD and conventional systemic autoimmune disorders. In NOD, the large pool of self-reactive B cells may fuel autoimmune β cell destruction by facilitating T-B cell interactions, as evidenced by the identification of one mAb that has undergone Ag-driven somatic hypermutation.
Osseointegration and Bioscience of Implant Surfaces - Current Concepts at Bone-Implant Interface

The high success rates for the dental rehabilitation of patients with endosseous implants have resulted from many research approaches with the aim of enhancing and accelerating bone anchorage to the implant, thereby providing optimal support for the intraoral prosthetic devices. This revolutionary breakthrough has first evolved from the research efforts of the Branemark group in the late 1960s by pioneering the insertion of machined screw-type commercially pure titanium (cpTi) implants with minimum surgical trauma and a consolidation period for the healing of the bone (Albrektsson et al., 1981; Branemark et al., 1969). This first endosseous titanium implant was produced with an industrial turning process, which led to surfaces with minimally rough topographies at the micron level. The bone bonding ability, termed as “osseointegration” by Branemark et al. (1977), of this machined implant was mainly the result of the proper surgical technique providing macrostability to the implant and the biocompatible nature of the bulk titanium. In the past three decades, much has been learned about the concept of osseointegration and significant improvements on the design and surface of implants were done to eliminate the important challenges of the implant dentistry. Osseointegration was first defined as a direct contact between living bone and the surface of a load-carrying implant at the histological level (Branemark, 1983) and, in clinical terms, as a biomechanical phenomenon whereby clinically asymptomatic rigid fixation of the implant is achieved and maintained in bone during functional loading (Albrektsson & Johansson, 2001). Typically, an implant is considered to be osseointegrated when there is an absence of movement between the implant and bone under normal conditions of loading following a defined healing period. This clinical state is the result of direct bone apposition to an implant surface without formation of a poorly vascularised collagenous capsule, termed as fibrous encapsulation. Although the concept of “osseointegration” was first put forth to define the connection between bone and titanium, it has been shown that bone anchorage can also be achieved with the use of other materials without an adverse tissue reaction (Wenz et al., 2008). Thus, osseointegration is currently accepted as a general term for boneimplant surface contact. However, the quality of the host bone/foreign implant interface is
The prevalence of mental disorders in Spanish prisons.

BACKGROUND The prevalence of mental disorders among prisoners has been researched in a few countries worldwide but never previously in Spain. AIM Our aim was to estimate the lifetime and last month prevalence of mental disorders in a Spanish prison population. METHODS This is a descriptive, cross-sectional, epidemiological study of 707 male prisoners. Sociodemographic, clinical and offending data were collected by interviewers. Offending data were confirmed using penitentiary records. Mental disorders were assessed with the clinical version of the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition Axis I Disorders, and personality disorders were assessed through the Spanish version of the International Personality Disorders Examination. RESULTS The lifetime prevalence of mental disorder was 84.4%. Substance use disorder (abuse and dependence) was the most frequent disorder (76.2%) followed by anxiety disorder (45.3%), mood disorder (41%) and psychotic disorder (10.7%). The period (last month) prevalence of any mental disorder was 41.2%. Anxiety disorder was the most prevalent (23.3%) followed by substance use disorder (abuse and dependence; 17.5%), mood disorder (14.9%) and psychotic disorder (4.2%). CONCLUSION Although period prevalence figures, which are those generally provided in research into rates of mental disorder among prisoners, are useful for planning improvements to services within prisons, the fact that almost all of these men had a lifetime prevalence of at least one mental disorder suggests a much wider need for improving services, including community services, for this group.