tbuckley/cabot-search huggingface dataset:
Rapid R2 Retrotransposition Leads to the Loss of Previously Inserted Copies via Large Deletions of the rDNA Locus
Authors: X. Zhang, J. Zhou, T. H. Eickbush
Journal: Molecular Biology and Evolution (2007)

R2 non–long terminal repeat retrotransposable elements insert specifically into the 28S rRNA genes of a wide range of animals. These elements maintain long-term stable relationships with the host genome. By scoring the variation present at the 5′ ends of individual R2 copies, lines of Drosophila simulans have been identified with high rates of R2 retrotransposition. Comparing the R2 elements present in the parents with that of their progeny after 1 or 30 generations in this report revealed that retrotransposition rates were higher through the female germ line compared with the male germ line. In addition, most events in females occur late in germ line development. Surprisingly, the gain of new R2 insertions by retrotranspositions was counterbalanced by deletions of preexisting R2 insertions. These deletions occurred by the loss of large segments of the rDNA units that contained on average an estimated 15 R2 elements. When monitored over single generations, the rate of loss of preexisting elements was higher than the rate of new insertions. However, the chromosomes with the largest deletions appear to be eliminated from the population because the rates of R2 insertions and deletions after 30 generations were approximately equal. These findings suggest that high rates of R2 retrotransposition do not necessarily lead to dramatic increases in the level of R2 insertions in the rDNA locus but can lead to a more rapid turnover of rDNA units.
Bortezomib, Bendamustine, and Rituximab in Patients With Relapsed or Refractory Follicular Lymphoma: The Phase II VERTICAL Study
Authors: Nathan Fowler, Brad S. Kahl, Peter Lee, Jeffrey V. Matous, Amanda F. Cashen, Samuel A. Jacobs, Jeffrey Letzer, Bipinkumar Amin, Michael E. Williams, Sonali Smith, Alfred Saleh, Peter Rosen, Hongliang Shi, Sudha Parasuraman, Bruce D. Cheson
Journal: Journal of Clinical Oncology (2011)

The aims of this multicenter study were to evaluate the response rate, progression-free survival, and toxicity of the combination of bortezomib, bendamustine, and rituximab in patients with follicular lymphoma whose disease was relapsed or refractory to prior treatment.Patients received five 35-day cycles of bortezomib, bendamustine, and rituximab: bortezomib administered intravenously (IV) at a dose of 1.6 mg/m(2) on days 1, 8, 15, and 22, cycles one to five; bendamustine 50, 70, or 90 mg/m(2) IV over a 60-minute infusion on days 1 and 2, cycles one to five; and rituximab 375 mg/m(2) on days 1, 8, 15, and 22 of cycle one and day 1 of subsequent cycles. Patients were assessed using the International Workshop Response Criteria, with the primary end point of 60% complete response rate.Seventy-three patients were enrolled. During the dose-escalation phase, the maximum-tolerated dose for bendamustine was not reached; the 90 mg/m(2) dose level was expanded for the efficacy assessment, and a total of 63 patients received bendamustine 90 mg/m(2). In these 63 patients, the overall response rate was 88% (including 53% complete response). Median duration of response was 11.7 months (95% CI, 9.2 to 13.3). Median progression-free survival was 14.9 months (95% CI, 11.1 to 23.7). Toxicities were manageable; myelosuppression was the main toxicity (25% and 14% of patients experienced grade 3 to 4 neutropenia and grade 3 to 4 thrombocytopenia, respectively). Transient grade 3 to 4 neuropathy occurred in 11% of patients.The combination of bortezomib, bendamustine, and rituximab is highly active in patients with follicular lymphoma who have received previous treatment.
External Validation of Mathematical Models to Distinguish Between Benign and Malignant Adnexal Tumors: A Multicenter Study by the International Ovarian Tumor Analysis Group
Authors: Caroline Van Holsbeke, Ben Van Calster, Lil Valentin, Antonia C. Testa, Enrico Ferrazzi, Ioannis Dimou, Chuan Lu, Philippe Moerman, Sabine Van Huffel, Ignace Vergote, Dirk Timmerman
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Several scoring systems have been developed to distinguish between benign and malignant adnexal tumors. However, few of them have been externally validated in new populations. Our aim was to compare their performance on a prospectively collected large multicenter data set. Experimental Design: In phase I of the International Ovarian Tumor Analysis multicenter study, patients with a persistent adnexal mass were examined with transvaginal ultrasound and color Doppler imaging. More than 50 end point variables were prospectively recorded for analysis. The outcome measure was the histologic classification of excised tissue as malignant or benign. We used the International Ovarian Tumor Analysis data to test the accuracy of previously published scoring systems. Receiver operating characteristic curves were constructed to compare the performance of the models. Results: Data from 1,066 patients were included; 800 patients (75%) had benign tumors and 266 patients (25%) had malignant tumors. The morphologic scoring system used by Lerner gave an area under the receiver operating characteristic curve (AUC) of 0.68, whereas the multimodal risk of malignancy index used by Jacobs gave an AUC of 0.88. The corresponding values for logistic regression and artificial neural network models varied between 0.76 and 0.91 and between 0.87 and 0.90, respectively. Advanced kernel-based classifiers gave an AUC of up to 0.92. Conclusion: The performance of the risk of malignancy index was similar to that of most logistic regression and artificial neural network models. The best result was obtained with a relevance vector machine with radial basis function kernel. Because the models were tested on a large multicenter data set, results are likely to be generally applicable.
Urinary CTX-II levels are associated with radiographic subtypes of osteoarthritis in hip, knee, hand, and facet joints in subject with familial osteoarthritis at multiple sites: the GARP study
Authors: I Meulenbelt
Journal: Annals of the Rheumatic Diseases (2005)

To assess the relation between the urinary concentrations of type II collagen C-telopeptide (UCTX-II) and radiographic signs of osteoarthritis (ROA) in the GARP (Genetics, Arthrosis and Progression) study.UCTX-II levels were measured in GARP study participants, who are sibling pairs predominantly with symptomatic osteoarthritis at multiple sites. Kellgren and Lawrence scores were used to assess ROA in the knees, hips, hands, and vertebral facet joints, and spinal disc degeneration. A proportionate score was made for each joint location, based on the number of joints with ROA. The sum total ROA score represents a measure of cartilage abnormalities within each patient. By using linear mixed models the total ROA score and the joint site specific ROA scores were correlated with the UCTX-II level.In 302 subjects the mean (SD) and median (range) for UCTX-II were 265 (168) and 219 (1346) ng/mmol creatine, respectively. There was a significant association between the total ROA score and UCTX-II levels. Subsequent multivariate analysis showed that the joint site specific ROA score at all joint sites, except for spinal disc degeneration, contributed independently to this association.The total ROA score of GARP patients, representing cartilage abnormalities at the most prevalent ROA joint locations, showed an excellent correlation with UCTX-II levels. The specific ROA scores at the hip, hand, facet, and knee joints additively and independently explained this association. Even in patients with osteoarthritis at multiple sites, UCTX-II may be a sensitive quantitative marker of ROA.
Effects of acute unilateral renal denervation in the rat.
Authors: E Bello-Reuss, R E Colindres, E Pastoriza-Muñoz, R A Mueller, C W Gottschalk
Journal: Journal of Clinical Investigation (1975)

Studies were undertaken to characterize the renal responses to acute unilateral renal denervation and the mechanisms involved in these responses. Denervation was produced in anesthetized nondiuretic rats by application of phenol to the left renal artery. Studies were also performed in sham-denervated nondiuretic rats. Whole kidney and individual nephron studies were performed before and after denervation or sham denervation. Denervation increased urine volume from the left kidney to about twice its control value (P less than 0.001) and increased urinary sodium excretion from 332 neq min minus -1 to 1,887 neq min minus -1 (P less than 0.001). Glomerular filtration rate (GFR) and renal plasma flow (RPF) remained unchanged in both kidneys after the procedure. The innervated right kidney showed no changes in urine volume or in sodium excretion. After denervation, late proximal ratio of tubular fluid inulin concentration to that of plasma [(F/P)In] decreased from 2.23 to 1.50 (P less than 0.001) while single nephron GFR remained unchanged. Absolute reabsorption decreased from 16.5 to 9.9 n. min minus -1 (P less than 0.001). (F/P)In ratios were also decreased in early distal (from 6.21 to 3.18, P less 0.001) and late distal convolutions (from 16.41 to 8.33, P less than 0.001) during the experimental period. (F/P)Na ratios remained unchanged in the early distal convolutions, but increased from 0.18 to 0.38 (P less than 0.01) in late distal convolutions after denervation. Absolute Na reabsorption after denervation increased in the loop of Henle, distal convolution, and collecting ducts. Any changes in intrarenal hydrostatic pressures after denervation were always small. There were no changes in GFR, RPF, urine volume, urinary sodium excretion, or late proximal (F/P)In after sham denervation. We conclude that the diuresis and natriuresis seen after acute renal denervation were caused by a marked depression of sodium and water reabsorption in the proximal tubule with partial compensation in more distal nephron segments. These responses appeared to be unrelated to systemic or intrarenal hemodynamic changes. The results demonstrate an effect of the renal nerves on proximal tubular function.
Changes in performance, skinfold thicknesses, and fat patterning after three years of intense athletic conditioning in high level runners
Authors: A Legaz, R Eston
Journal: British Journal of Sports Medicine (2005)

To determine if the changes in specific skinfold sites induced by intense athletic conditioning over a three year period were associated with changes in running performance in high level athletes.Thirty seven top class runners (eight male and five female sprint trained, 16 male and eight female endurance trained) volunteered to participate in the study. The athletes were divided into class A (n = 18) and class B (n = 17), with class A having the best performance. Biceps, triceps, subscapular, pectoral, iliac crest, abdominal, front thigh, and medial calf skinfold thickness and the best running performance were recorded at the beginning and after one, two, and three years of training. A one way analysis of variance and a linear regression analysis were conducted to determine changes and association between performance and skinfold thicknesses. Analyses were controlled for sex, sprint event or endurance event, and class.Training resulted in a significant increase in performance and decreases in sum of six skinfolds, abdominal, front thigh, and medial calf skinfolds, and the ratio of extremity to trunk skinfolds (E/T, Sigmatriceps, front thigh, medial calf/Sigmasubscapular, iliac crest, abdominal). There were no significant differences in body weight. Except for the abdominal skinfold, there was no significant difference in trunk skinfolds. Significant differences in these changes were observed by sex for E/T, which decreased and increased in male and female runners respectively, and by class. Class B runners significantly improved performance, with decreased skinfold thicknesses in the lower limb. There were no significant changes in performance or skinfold thicknesses in class A runners. Improvements in performance were consistently associated with a decrease in the lower limb skinfolds.On the basis of these findings, anthropometric assessment of top class athletes should include an evaluation of all skinfolds. The loss of body fat appears to be specific to the muscular groups used during training. The lower limb skinfolds may be particularly useful predictors of running performance.
Exosomes
Authors: Derek M. Yellon, Sean M. Davidson
Journal: Circulation Research (2014)

Exosomes are nanosized lipid vesicles released from cells. They are capable of transferring proteins, mRNA, and miRNA between cells and, therefore, represent a potential means of intercellular communication. Exosomes can be proangiogenic and may have cardioprotective properties. In contrast, their larger cousins, microvesicles, seem to have generally detrimental effects that are prothrombotic and proinflammatory. Exosomes are released from multivesicular bodies via an exocytic pathway and have the potential for cell-specific targeting. This normal process is hijacked during various pathological conditions, such as cancer, viral infection, and amyloidopathies. We assess the evidence for a role of exosomes and microvesicles in normal cardiovascular physiology, as well as during cardiovascular disease. In addition to offering a potential source of cardiovascular biomarkers, exosomes may offer a nonimmunogenic means of manipulating the heart.
Tetralogy of Fallot with pulmonary atresia. Rehabilitation of diminutive pulmonary arteries.
Authors: J J Rome, J E Mayer, A R Castaneda, J E Lock
Journal: Circulation (1993)

BACKGROUND Patients with tetralogy of Fallot, pulmonary atresia, and diminutive pulmonary arteries are a high-risk group for whom there is no consensus on the correct approach to medical management. The purpose of this report is to review a 14-year experience in the treatment of these patients comparing management schemes. METHODS AND RESULTS Between January 1978 and August 1988, 91 patients with tetralogy of Fallot and pulmonary atresia had an adequate evaluation of their pulmonary artery anatomy before any surgical management. Forty-eight of these patients had diminutive pulmonary arteries (38 to 104 mm2/m2) supplied by aortopulmonary collaterals and were managed in four different fashions. Of the 9 patients repaired primarily, 7 died early and the two survivors had poor hemodynamic outcome. Of the 9 patients conservatively managed with no intervention before 5 years of age, 4 died and only 1 had a satisfactory hemodynamic result after repair. Of 10 shunted patients, 3 died and 3 had satisfactory repairs. Since 1984, we have rehabilitated pulmonary arteries with (1) right ventricle to pulmonary artery surgical graft, (2) balloon dilation of residual pulmonary artery stenoses and embolization of collaterals, and (3) surgical closure of ventricular septal defect and repair of remaining obstructions. Of 20 patients so managed, 7 died after various stages, but 10 of 20 had complete repairs. All repaired patients with subsystemic right ventricular pressures had at least one successful pulmonary artery dilation. CONCLUSIONS A combined catheter-surgery approach begun at an early age in patients with tetralogy of Fallot and pulmonary atresia with diminutive pulmonary arteries appears to enhance the chances of satisfactory complete repair.
Lung sound intensity in patients with emphysema and in normal subjects at standardised airflows.
Authors: H J Schreur, P J Sterk, J Vanderschoot, H C van Klink, E van Vollenhoven, J H Dijkman
Journal: Thorax (1992)

BACKGROUND: A common auscultatory finding in pulmonary emphysema is a reduction of lung sounds. This might be due to a reduction in the generation of sounds due to the accompanying airflow limitation or to poor transmission of sounds due to destruction of parenchyma. Lung sound intensity was investigated in normal and emphysematous subjects in relation to airflow. METHODS: Eight normal men (45-63 years, FEV1 79-126% predicted) and nine men with severe emphysema (50-70 years, FEV1 14-63% predicted) participated in the study. Emphysema was diagnosed according to pulmonary history, results of lung function tests, and radiographic criteria. All subjects underwent phonopneumography during standardised breathing manoeuvres between 0.5 and 2 1 below total lung capacity with inspiratory and expiratory target airflows of 2 and 1 l/s respectively during 50 seconds. The synchronous measurements included airflow at the mouth and lung volume changes, and lung sounds at four locations on the right chest wall. For each microphone airflow dependent power spectra were computed by using fast Fourier transformation. Lung sound intensity was expressed as log power (in dB) at 200 Hz at inspiratory flow rates of 1 and 2 l/s and at an expiratory flow rate of 1 l/s. RESULTS: Lung sound intensity was well repeatable on two separate days, the intraclass correlation coefficient ranging from 0.77 to 0.94 between the four microphones. The intensity was strongly influenced by microphone location and airflow. There was, however, no significant difference in lung sound intensity at any flow rate between the normal and the emphysema group. CONCLUSION: Airflow standardised lung sound intensity does not differ between normal and emphysematous subjects. This suggests that the auscultatory finding of diminished breath sounds during the regular physical examination in patients with emphysema is due predominantly to airflow limitation.
Psychological Outcomes of Patients With Screen-Detected Type 2 Diabetes
Authors: Bart J. Thoolen, Denise T. de Ridder, Jozien M. Bensing, Kees J. Gorter, Guy E. Rutten
Journal: Diabetes Care (2006)

The objective of this study was to investigate how time since diagnosis and treatment intensity influence psychological outcomes in patients with screen-detected type 2 diabetes.A 2 x 2 factorial cross-sectional design was used to examine psychological outcomes in 196 patients with screen-detected diabetes diagnosed 3-33 months previously who were receiving usual care or intensive multifactorial pharmacological treatment. Outcomes included anxiety, depression, diabetes-related distress, perceived seriousness and vulnerability, self-efficacy, and self-care. Multivariate analysis was used to examine variations in outcomes based on time since diagnosis (<1 vs. 2-3 years) and treatment intensity.Most patients reported little distress, low perceived seriousness and vulnerability, high self-efficacy, and low self-care, but outcomes varied considerably across conditions. Time effects were found for perceived vulnerability, which increases significantly with time since diagnosis. Time x treatment interactions were found for anxiety, diabetes-related distress, and self-efficacy; notably, intensively treated patients showed more distress and less self-efficacy in the 1st year, and usual-care patients reported more distress and less self-efficacy 2-3 years after diagnosis.Screen-detected patients generally do not experience much difficulty with their condition in the first few years, but early and intensive treatment can influence patients' psychological outcomes, leading to relatively more anxiety and less self-efficacy in the 1st year after diagnosis but not necessarily improving self-care. This suggests that intensive treatments confront patients with their diabetes earlier on whereas milder treatments may delay confrontation. This finding should be taken into account in the development and timing of psychological interventions for patients with newly diagnosed diabetes.
SIGNAL TRANSDUCTION IN THE <i>CAENORHABDITIS ELEGANS</i> NERVOUS SYSTEM
Authors: Cornelia I. Bargmann, Joshua M. Kaplan
Journal: Annual Review of Neuroscience (1998)

▪ Abstract Caenorhabditis elegans interacts with its environment by sensing chemicals, touch, and temperature; genetic analysis of each of these responses has led to the identification of candidate signaling molecules within sensory neurons. A molecular model for touch sensation has emerged from studies of the mechanosensory response; the receptors and signal transduction mechanisms in olfactory neurons are being elucidated; and an unusual neuroendocrine role for a TGF-β-related peptide in chemosensory neurons has been discovered. Presynaptic and postsynaptic components of neuronal synapses have been identified in behavioral and pharmacological mutant screens. Mutations have been found in multiple classes of nicotinic acetylcholine receptor genes, excitatory and inhibitory glutamate receptor genes, and candidate gap junction genes, allowing their function to be studied in vivo. Different G-protein signaling pathways have characteristic effects on behavior, neuronal degeneration, and embryonic development.
"A generation of cancer patients is being sacrificed" because of drug shortages in Europe, expert says
Authors: A. Garcia Rada
Journal: BMJ (2012)

Italy’s health minister, Renato Balduzzi, has asked the European Commission to tackle the shortage of anticancer drugs affecting Greece and other European Union countries as a result of austerity measures.1 

The request was made during a press conference of the Open Forum of the European Partnership for Action Against Cancer (EPAAC), held in Rome on 19-20 June.

Asked by the BMJ whether European institutions shouldn’t demand joint action, John Dalli, the European commissioner for health and consumers, said that healthcare was the responsibility of member states, which would not countenance …
Comparison of effects of a home exercise programme and a supervised exercise programme for the management of lateral elbow tendinopathy
Authors: D Stasinopoulos, I Stasinopoulos, M Pantelis, K Stasinopoulou
Journal: British Journal of Sports Medicine (2009)

Background Home and supervised exercise programmes consisting of stretching and eccentric exercises have been recommended for the management of lateral elbow tendinopathy (LET). No studies have examined their comparative efficacy effectiveness. Objective In this study, whether a home exercise programme is more successful than a supervised exercise programme in treating patients with LET was investigated. Methods Patients with unilateral LET for at least 4 weeks were included in this trial. They were sequentially allocated to receive either a home exercise programme or a supervised exercise programme five times a week for 12 weeks. The exercise programme consisted of slow progressive eccentric exercises of wrist extensors and static stretching of the extensor carpi radialis brevis tendon. Outcome measures were pain, using a visual analogue scale, and function, using a visual analogue scale and the pain-free grip strength. Patients were evaluated at baseline, at the end of treatment (week 12), and 3 months (week 24) after the end of treatment. Results 70 patients met the inclusion criteria. At the end of treatment, there was a decline in pain and a rise in function in both groups compared with baseline (p&lt;0.0005, paired t test). There were significant differences in the reduction of pain and the improvement of function between the groups at the end of treatment and at the 3-month follow up; the supervised exercise programme produced the largest effect (p&lt;0.0005, independent t test). Conclusions Supervised exercise programme is superior to home exercise programme to reduce pain and improve function in patients with LET at the end of the treatment and at the follow-up. Further research is needed to confirm our results.