Miracle-dz/UniFAR-FTUs huggingface dataset:
Carotid Artery Intima-Media Thickness in Young Adults with Family History of Coronary Artery Disease.

BACKGROUND It is well established that accelerated athero-sclerosis occurs in middle-aged and elderly adults with family history of coronary artery disease (CAD). However similar data on younger population with genetic predisposition is lacking. As identifying and treating this target group at an early stage will help in postponing the disease progression and delay the onset of clinical events later in life. AIM We undertook the present study to investigate whether structural vascular changes related to atherosclerosis are detectable in healthy young adults with family history of CAD by non-invasive high resolution scan of the carotid artery intima media thickness (CIMT). MATERIALS AND METHODS Fifty healthy young adults of both sexes, aged 18-25 years with family history of CAD were taken as cases and fifty age, sex, body mass index (BMI) and blood pressure matched subjects without family history of CAD served as control. All participants completed a standardized cardiovascular disease risk assessment questionnaire and resting blood pressure, pulse rate and BMI were recorded. None of the subjects were smoker or alcoholic. Both cases and controls were subjected to high resolution B-mode ultrasonographic evaluation of CIMT. Fasting blood samples were drawn for baseline investigations and lipid profile estimation. RESULTS Compared to control subjects, cases had increased CIMT (mean of combined sites 0.57 ± 0.08 mm vs 0.46 ± 0.05 mm in controls, p<0.001). Offspring with family history of CAD exhibited an unfavourable lipid profile. We observed a direct association between carotid intima media thickness and triglyceride concentration (Correlation coefficient=0.32). Multiple logistic regression analysis showed family history of CAD to be independent risk factor for CIMT (Odds ratio=5.36, confidence interval 1.84 - 10.53, p=0.003). CONCLUSION Arterial wall abnormalities are present at an early age in offspring with family history of CAD. Identifying such high risk individuals is feasible with an easy, non-invasive and reproducible technique like CIMT measurement and hence is recommended.
Trafficking patterns of beta-arrestin and G protein-coupled receptors determined by the kinetics of beta-arrestin deubiquitination.

Agonist-dependent internalization of G protein-coupled receptors via clathrin-coated pits is dependent on the adaptor protein beta-arrestin, which interacts with elements of the endocytic machinery such as AP2 and clathrin. For the beta(2)-adrenergic receptor (beta(2)AR) this requires ubiquitination of beta-arrestin by E3 ubiquitin ligase, Mdm2. Based on trafficking patterns and affinity of beta-arrestin, G protein-coupled receptors are categorized into two classes. For class A receptors (e.g. beta(2)AR), which recycle rapidly, beta-arrestin directs the receptors to clathrin-coated pits but does not internalize with them. For class B receptors (e.g. V2 vasopressin receptors), which recycle slowly, beta-arrestin internalizes with the receptor into endosomes. In COS-7 and human embryonic kidney (HEK)-293 cells, stimulation of the beta(2)AR or V2 vasopressin receptor leads, respectively, to transient or stable beta-arrestin ubiquitination. The time course of ubiquitination and deubiquitination of beta-arrestin correlates with its association with and dissociation from each type of receptor. Chimeric receptors, constructed by switching the cytoplasmic tails of the two classes of receptors (beta(2)AR and V2 vasopressin receptors), demonstrate reversal of the patterns of both beta-arrestin trafficking and beta-arrestin ubiquitination. To explore the functional consequences of beta-arrestin ubiquitination we constructed a yellow fluorescent protein-tagged beta-arrestin2-ubiquitin chimera that cannot be deubiquitinated by cellular deubiquitinases. This "permanently ubiquitinated" beta-arrestin did not dissociate from the beta(2)AR but rather internalized with it into endosomes, thus transforming this class A receptor into a class B receptor with respect to its trafficking pattern. Overexpression of this beta-arrestin ubiquitin chimera in HEK-293 cells also results in enhancement of beta(2)AR internalization and degradation. In the presence of N-ethylmaleimide (an inhibitor of deubiquitinating enzymes), coimmunoprecipitation of the receptor and beta-arrestin was increased dramatically, suggesting that deubiquitination of beta-arrestin triggers its dissociation from the receptor. Thus the ubiquitination status of beta-arrestin determines the stability of the receptor-beta-arrestin complex as well as the trafficking pattern of beta-arrestin.
Patient-Based Outcomes Analysis of Patients With Single Torsion Thoracolumbar—Lumbar Scoliosis Treated With Anterior or Posterior Instrumentation: An Average 5- to 9-Year Follow-up Study

Introduction. Since the advent of single, stiff rod anterior instrumentation, and now dual rod anterior instrumentation, most thoracolumbar–lumbar scoliosis is treated with an anterior approach. We have previously reported a retrospective comparison of patients with single torsion thoracolumbar–lumbar scoliosis treated with either anterior or posterior instrumented fusion. The purpose of this study is to examine the patient-based outcomes in this cohort of patients at an average of 5 years (anterior instrumentation) and 9 years (posterior instrumentation). Materials and Methods. Inclusion criteria were as follows: 1) single torsion thoracolumbar or lumbar curve of ≤70°; 2) thoracic curve bends to ≤20° on nonstressed supine bends; and 3) thoracic kyphosis of ≤60°. Fourteen patients were treated with posterior transpedicular instrumented fusion from 1989 to 1993 (none treated with anterior discectomy). Fourteen patients were treated with anterior, single, solid rod instrumented fusion from 1993 to 1996. SRS 22 was performed after surgery in 12 of 14 patients from the posterior group (average 9.2 years) and in 14 of 14 patients from the anterior group (average 5.1 years). Results. Posterior: The average age was 14.8 years (range 12–17.8 years). Curve correction at average 6.5 years (range 4.0–10.9 years) was 75%. The average lower instrumented vertebra was L3.1. There were no complications. Twelve of 14 patients completed SRS 22 at an average of 9.2 years (range 6.2–10.9 years). Domain scores for Pain, Self-Image, Function, Mental Health, Satisfaction, and Total were 3.8, 4.1, 4.0, 3.8, 4.5, and 4.1, respectively. Anterior: The mean age was 14.5 years (range 12.5–16.5 years). Curve correction at average 4.8 years (range 2.3–7.6 years) was 63% (instrumented segment 89%). The average lower instrumented vertebra was L2.6. Complications included one intercostal neuritis that resolved with suture removal, one broken inferior screw that healed with some loss of correction, and one pseudarthrosis treated successfully with posterior fusion. Fourteen of 14 patients completed SRS 22 at an average of 5.3 years (range 2.0–7.6 years). Domain scores for Pain, Self-Image, Function, Mental Health, Satisfaction, and Total were 4.1, 4.3, 4.4, 4.0, 4.5, and 4.3, respectively. There were no statistically significant differences in any of the domains or the Total score, although there was a trend toward improved function in the patients treated anteriorly. The follow-up was statistically longer in the posterior group. Conclusion. At an average of 9 years of follow-up, patients treated with posterior transpedicular instrumentation have equivalent patient-based outcomes to patients treated with anterior single solid rod instrumentation at an average of 5 years of follow-up.
Severe COPD is correlated with mild radiation pneumonitis following stereotactic body radiotherapy.

BACKGROUND The primary cause of COPD and lung cancer is smoking. Thus, patients with COPD frequently have lung cancer that often is inoperable. Stereotactic body radiation therapy (SBRT) is anticipated to be the standard of care for inoperable early stage non-small cell lung cancer. The most critical toxicity following SBRT is radiation pneumonitis (RP). We analyzed predictive factors for RP following SBRT and investigated the degree and occurrence of RP in patients with severe COPD. METHODS We retrospectively evaluated 265 lung tumors treated with SBRT between 2005 and 2010 with a minimum follow-up of 6 months. Predictive factors for RP, including GOLD (Global Initiative for Chronic Obstructive Lung Disease) stage and pack-years smoked, were evaluated by univariate and multivariate analyses. RP was graded according to the Common Terminology Criteria for Adverse Events version 3.0 scale. RESULTS Median follow-up was 19.2 months (range, 6.0-72.0 months). RP grades of 0, 1, 2, 3, 4, and 5 occurred in 101, 102, 49, 12, 0, and one of these patients, respectively. Multivariate analysis revealed that high normal lung volume receiving ≥ 20 Gy, fewer pack-years smoked, and high total dose were significant predictive factors for RP ≥ grade 1, and high normal lung volume receiving 20 Gy, fewer pack-years smoked, and a history of lung resection were predictive for RP ≥ grade 2. RP in patients with more severe COPD was relatively milder than in patients with normal lung function and with mild COPD. Pack-year scales were significantly correlated with GOLD stage. CONCLUSIONS RP following SBRT in patients with severe COPD was relatively mild. Heavy smoking was the strongest negative predictor for severe RP and was correlated with severe COPD. Further follow-up and quantitative analysis of lung function might be needed to ascertain longer tolerability to SBRT.
Adaptive Response and the Bystander Effect Induced by Radiation in C3H 10T½ Cells in Culture

Abstract Sawant, S. G. , Randers-Pehrson, G. , Metting, N. and Hall, E. J. Adaptive Response and the Bystander Effect Induced by Radiation in C3H 10T½ Cells in Culture. Radiat. Res. 156, 177–180 (2001). This paper discusses two phenomena of importance at low doses that have an impact on the shape of the dose–response relationship. First, there is the bystander effect, the term used to describe the biological effects observed in cells that are not themselves traversed by a charged particle, but are neighbors of cells that are; this exaggerates the effect of small doses of radiation. Second, there is the adaptive response, whereby exposure to a low level of DNA stress renders cells resistant to a subsequent exposure; this reduces the effect of low doses of radiation. The present work was undertaken to assess the relative importance of the adaptive response and the bystander effect induced by radiation in C3H 10T½ cells in culture. When the single-cell microbeam delivered from 1 to 12 α particles through the nuclei of 10% of C3H 10T½ cells, more cells were inactivated than were actually traversed by α particles. The magnitude of this bystander effect increased with the number of particles per cell. An adaptive dose of 2 cGy of γ rays, delivered 6 h beforehand, canceled out about half of the bystander effect produced by the α particles.
Distinct In Vivo Roles of Colony-Stimulating Factor-1 Isoforms in Renal Inflammation1

CSF-1, the major regulator of macrophage (Mφ) development, has three biologically active isoforms: a membrane-spanning, cell surface glycoprotein, a secreted glycoprotein, and a secreted proteoglycan. We hypothesized that there are shared and unique roles of individual CSF-1 isoforms during renal inflammation. To test this, we evaluated transgenic mice only expressing the cell surface or precursors of the secreted CSF-1 isoforms for Mφ accumulation, activation, and Mφ-mediated tubular epithelial cell (TEC) apoptosis during unilateral ureteral obstruction. The only difference between secreted proteoglycan and secreted glycoprotein CSF-1 isoforms is the presence (proteoglycan) or absence (glycoprotein) of an 18-kDa chondroitin sulfate glycosaminoglycan. We report that 1) cell surface CSF-1 isoform is sufficient to restore Mφ accumulation, activation, and TEC apoptosis to wild-type levels and is substantially more effective than the secreted CSF-1 isoforms; 2) the chondroitin sulfate glycosaminoglycan facilitates Mφ accumulation, activation, and TEC apoptosis; 3) increasing the level of secreted proteoglycan CSF-1 in serum amplifies renal inflammation; and 4) cell-cell contact is required for Mφ to up-regulate CSF-1-dependent expression of IFN-γ. Taken together, we have identified central roles for the cell surface CSF-1 and the chondroitin sulfate chain on secreted proteoglycan CSF-1 during renal inflammation.
Asticcacaulis endophyticus sp. nov., a prosthecate bacterium isolated from the root of Geum aleppicum.

A strictly aerobic, light-yellow-coloured, stalked bacterium, designated strain ZFGT-14(T), was isolated from the root of Geum aleppicum Jacq. collected from Taibai Mountain in Shaanxi province, north-west China, and was subjected to a taxonomic study using a polyphasic approach. This novel isolate grew at 7-33 °C (optimum 25-28 °C) and pH 6.0-10.0 (optimum pH 7.0-8.0). Flexirubin-type pigments were not produced. Cells were Gram-stain-negative, rod-shaped and motile with a single polar flagellum. The predominant respiratory quinone was Q-10. The major cellular fatty acids were summed feature 8 (comprising C18 : 1ω7c/C18 : 1ω6c), C16 : 0, C19 : 0 cyclo ω8c and summed feature 3 (comprising C16 : 1ω7c and/or C16 : 1ω6c) and the major polar lipids were phosphatidylglycerol and glycolipids. The DNA G+C content was 57.8 mol%. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain ZFGT-14(T) was most closely related to the genus Asticcacaulis and had low sequence similarity (95.0-95.9 %) with all species with validly published names within the genus Asticcacaulis. Based on the phenotypic, phylogenetic and genotypic data, strain ZFGT-14(T) is considered to represent a novel species of the genus Asticcacaulis, for which the name Asticcacaulis endophyticus sp. nov. is proposed. The type strain is ZFGT-14(T) ( = CCTCC AB 2013012(T) = KCTC 32296(T) = LMG 27605(T)).
Human Immunodeficiency Virus Type 1 Induction Mediated by Genistein Is Linked to Cell Cycle Arrest in G2

ABSTRACT Protein tyrosine kinase (PTK) phosphorylation is involved in cellular proliferation and differentiation processes that are key factors for human immunodeficiency virus type 1 (HIV-1) regulation in infected monocytic cells. Short-term exposure of the chronically infected promyelocytic OM10 cell line with the PTK inhibitor genistein induced a dose-dependent increase in p24 antigen production in culture supernatants. This induction persisted in the presence of the reverse transcriptase inhibitor, zidovudine, and was associated with an increased transcription of HIV-1 multiply spliced and unspliced RNAs, suggesting a transcriptional mechanism targeting the integrated provirus. Genistein induced cell differentiation, apoptosis, and a G2 arrest in the OM10 cells. Cell differentiation and apoptosis were not directly involved in the observed increase in HIV-1 replication that was closely linked to genistein-induced G2 arrest. Alleviation of the G2 arrest by pentoxyfylline resulted in a concomitant reduction of HIV-1 to baseline replication. Additionally, by flow cytometry, a significant increase in the number of p24 antigen-expressing cells was observed in cells arrested in G2 compared to those located in G1 or S. Tyrosine kinase inhibition was found not to be essential for enhanced viral replication, which seemed to be related to two other properties of genistein, inhibition of topoisomerase II activity and inhibition of phosphotidylinositol turnover. These findings are consistent with the recent observation that HIV-1 Vpr induces viral replication through preventing proliferation of cells by arresting them in G2 of the cell cycle and strongly suggest that manipulation of the cell cycle plays an important role in HIV-1 pathogenesis.
Effect of five nights of normobaric hypoxia on cardiovascular responses to acute isocapnic hypoxia in humans: relationship to ventilatory chemosensitivity

The aim of this study was to elucidate (1) the cardiovascular responses to acute isocapnic hypoxia stimuli following five nights of normobaric poikilocapnic hypoxia, and (2) whether the changes in the cardiovascular responses to hypoxia are correlated to the change in acute hypoxic ventilatory (AHVR) chemosensitivity. Twelve male subjects [26.6 ± 4.1 (SD) years] slept 8–9 h day−1 overnight for five consecutive days at a simulated altitude of 4300 m (FiO2 = ∼13.8%). Using the technique of dynamic end-tidal forcing, the AHVR was assessed twice, prior to and immediately after the hypoxic exposure. During each AHVR test, mean arterial blood pressure (MAP) and heart rate (HR) were measured continuously using finger photoplethysmography and an ECG monitor, respectively. Immediately following the exposure, AHVR and MAP sensitivities were increased by 1.80 ± 1.30 l min−1 %−1 (p < 0.01) and 0.69 ± 0.40 mmHg %−1 (p < 0.05), respectively, and there were significant correlations between the increases in the AHVR and MAP sensitivities (r = 0.67; p < 0.05). In summary, following five nights of normobaric hypoxia, there is an enhanced MAP response to hypoxic stimuli. The relationship between the enhanced AHVR and MAP sensitivity raises the possibility of a common pathway in the regulation of peripheral chemosensitivity and MAP responses during periods of isocapnic hypoxia.
De novo mutations in ATP1A2 and CACNA1A are frequent in early-onset sporadic hemiplegic migraine

Objective: Hemiplegic migraine (HM) is a rare subtype of migraine with aura that may occur as a familial (FHM) or sporadic condition (SHM). Screening of FHM genes in previous series of patients with SHM detected a very low proportion of mutated patients. In this study, we investigated the FHM genes in patients with an early onset sporadic form of HM (onset before 16 years). Methods: Twenty-five patients were included. Each one and his or her 2 parents were blood sampled. Mean age at diagnosis was 14.7 ± 8.2 years and mean age at clinical onset was 7.7 ± 3.4 years. Sequencing of ATP1A2 and CACNA1A was conducted in each proband and all identified variants were looked for in both parents. SCN1A was screened in all patients without CACNA1A or ATP1A2 de novo mutation. Results: Twenty-three different amino acid variants were identified in 23 of the 25 patients. The variants occurred de novo in 19 patients (76%), strongly in favor of their causal role. SCN1A analysis did not show any mutation. Among the 19 patients with a de novo mutation, 5 had a pure HM and 14 had associated neurologic signs such as ataxia, epilepsy, or intellectual disabilities. Conclusions: FHM genes are involved in early-onset SHM, in particular when associated with neurologic signs. Molecular analysis can be helpful in those cases. Our study identified 14 novel de novo mutations that will help to interpret genetic tests in molecular diagnosis practice.
Determination of choline, betaine, and dimethylglycine in plasma by a high-throughput method based on normal-phase chromatography-tandem mass spectrometry.

BACKGROUND The quaternary ammonium compounds, choline and betaine, and dimethylglycine (DMG) reside along a metabolic pathway linked to the synthesis of neurotransmitters and membrane phospholipids and to homocysteine remethylation and, therefore, folate status. Lack of a convenient, high-throughput method for the determination of these compounds has prevented population-based studies of their possible associations with lifestyle, nutrition, and chronic diseases. METHODS Serum or plasma samples were deproteinized by mixing with three volumes of acetonitrile that contained d(9)-choline and d(9)-betaine as internal standards. We used a normal-phase silica column for the separation of choline (retention time, 2.8 min), betaine (1.3 min), DMG (1.15 min), and internal standards, which were detected as positive ions by tandem mass spectroscopy in the multiple-reaction monitoring mode, using the molecular transitions m/z 104-->60 (choline), m/z 113-->69 (d(9)-choline), m/z 118-->59 (betaine), m/z 127-->68 (d(9)-betaine), and m/z 104-->58 (DMG). RESULTS For all three metabolites, the assay was linear in the range 0.4-400 micromol/L, and the lower limit of the detection (signal-to-noise ratio = 5) was < or =0.3 micromol/L. The within- and between-day imprecision (CVs) was 2.1-7.2% and 3.5-8.8%, respectively. The analytical recovery was 87-105%. The fasting plasma concentrations (median, 25th-75th percentiles) were 8.0 (7.0-9.3) micromol/L for choline, 31.7 (27.0-41.1) micromol/L for betaine, and 1.66 (1.30-2.02) micromol/L for DMG in 60 healthy blood donors. In individuals who had eaten a light breakfast, plasma concentrations of all three metabolites were significantly (25-30%) higher than in fasting individuals. CONCLUSION This is the first method for the combined measurement of choline, betaine, and DMG in human plasma or serum. The assay is characterized by simple sample preparation, no derivatization, high throughput, imprecision (CV) <10%, detection limits below the values seen in volunteers, and the high specificity provided by tandem mass spectroscopy.
Self-preventive oral behavior in an Italian university student population.

BACKGROUND/AIM The aim of this study was to assess the oral hygiene attitude and the professional preventive examination compliance in Italian university students. METHOD A sample of 202 students attending the University of Bologna was randomly selected and interviewed about their preventive oral health attitude and compliance. All students reported using toothpaste and most of them (92.1%) brushed their teeth at least 2x a day using artificial, medium stiffness bristles. The toothbrush was generally (81.6%) replaced within 3 months. Few subjects (14.9%) said they used dental floss daily or utilized other devices. A majority of subjects (59.9%) had a dental examination within the year previous to the interview. Cluster analysis was performed. RESULTS 4 groups were identified with homogeneous oral hygiene behavior and compliance toward professional preventive examination. Only one cluster, representing 33.6% of the sample, showed consistent frequency and modalities of oral hygiene habits. The other clusters seemed to be defective with interproximal cleaning procedures and compliance toward professional preventive care. Since the sample was characterized by a young, urbanized, homogeneous group with a high educational level and frequently from an upper middle class social status, the analysis probably gives a supra-estimation of the positive behavior. CONCLUSION It is rational to suppose that strategies to promote dental service utilization, patients' compliance and a professional style oriented toward prevention may be useful to improve the oral health condition in the young adult Italian population.