428 research outputs found
Regional Transfer Multipliers
A series of discontinuities in the allocation mechanism of federal transfers, to municipal governments in Brazil allow us to identify the causal effect of public spending on local labor markets, using a ‘fuzzy’ Regression Discontinuity Design (RDD). Our estimates imply a cost per job of about 8,000 US dollars per year and a local income multiplier around two. The effect comes mostly from employment in services and is more pronounced among less financially developed municipalities
DynNav: Toward Open and Interoperable Dynamic Navigation Services
So far, navigation devices, including navigation apps for smartphones, have been proprietary and closed. A new scenario is emerging with the Open Mobile Alliance Dynamic Navigation Enabler, which lets developers create novel navigation services characterized by openness and interoperability across different information providers
FFAs and QT intervals in obese women with visceral adiposity: Effects of sustained weight loss over 1 year
We evaluated 66 obese patients grouped by waist-to-hip ratio (WHR) into group A (WHR > 0.85, n = 30) and group B (WHR ≤ 0.85, n = 36), before and after 1 yr of diet-induced weight loss compared with 25 nonobese women. Before diet, the longest values of QT intervals and the highest levels of FFA and catecholamines were in group A (P < 0.01). In obese women (both groups), the corrected QT (QTc); interval correlated with plasma FFA (P < 0.01) and catecholamine (P < 0.02) concentrations. After 1 yr of diet, at the same levels of body weight reduction, the decrement of the QTc interval (P < 0.02), FFA (P < 0.01) and catecholamine (P < 0.02) levels were significantly greater in-group A than group B. In multivariate analysis, the decline of the QTc interval after weight loss was associated with changes in plasma FFA independently of changes in WHR and plasma catecholamines. Our data suggest that the QTc interval is tightly correlated with plasma FFA levels; shortening of cardiac repolarization times in the course of long-lasting weight reduction may reduce the risk of ventricular electrical instability, especially in women with abdominal adiposity
Relationship Between Jump Capacity and Performance in BMX Cycling
The objective of this study is to assess the relationship between the results obtained on different vertical jump tests and the top score recorded during a BMX (Bicycle Moto-Cross) test and the rider''s performance. To do so, 10 BMX pilots participated in this study; 5 regarded as the elite group (EG) (age: 18.8 +/- 3.7, weight: 68.4 +/- 8.5 kg, height: 174 +/- 9 cm and previous BMX experience: 8 +/- 3.8 years) and 5 regarded as the recreational group (RG) (age: 19.8 +/- 4.8, weight: 69.2 +/- 11.7 kg, height: 170 +/- 9 cm, previous BMX experience: 4.2 +/- 1.3 years). Vertical jump capacity was obtained using the Bosco protocol, i.e. vertical squat jump (SJ), vertical countermovement jump (CMJ), drop jump (DJ) and repetitive jump (RJ), and time in race in a BMX circuit was determined. The results indicate a direct relationship between the time used to complete the circuit and the height of the jump reached in SJ (r: -.801; p:.017), CMJ (r : -.798; p :.018) and DJ (r : -.782; p:.022). This all suggests that assessing jump capacity using the Bosco test may be a useful tool for assessing BMX performance
Knowledge and Health Care resource allocation: CME/CPD course guidelines-based efficacy
Background: Most Health Care Systems consider Continuing Medical Education a potential tool to improve quality of care and reduce disease management costs. Its efficacy in general practitioners needs to be further explored. Objective: This study assesses the effectiveness of a one-year continuing medical education/continuing professional development course for general practitioners, regarding the improvement in knowledge of ARIA and GINA guidelines and compliance with them in asthma management. Methods: Sixty general practitioners, covering 68,146 inhabitants, were randomly allocated to continuing medical education/continuing professional development (five residential events + four short distance-learning refresher courses over one year) or no training. Participants completed a questionnaire after each continuing medical education event; key questions were repeated at least twice. The Local Health Unit prescription database was used to verify prescription habits (diagnostic investigations and pharmacological therapy) and hospitalizations over one year before and after training. Results: Fourteen general practitioners (46.7%) reached the cut-off of 50% attendance of the training courses. Knowledge improved significantly after training (p<0.001, correct answers to key questions +13%). Training resulted in pharmaceutical cost containment (trained general practitioners +0.5% vs controls +18.8%) and greater attention to diagnosis and monitoring (increase in spirometry +63.4%, p<0.01). Conclusion: This study revealed an encouraging impact of educational events on improvement in general practitioner knowledge of guidelines and daily practice behavioral changes. Long-term studies of large populations are required to assess the effectiveness of education on the behavior of physicians in asthma management, and to establish the best format for educational events
Binding site plasticity in viral PPxY Late domain recognition by the third WW domain of human NEDD4
The recognition of PPxY viral Late domains by the third WW domain of the HECT-E3 ubiquitin ligase
NEDD4 (hNEDD4-WW3) is essential for the completion of the budding process of numerous enveloped
viruses, including Ebola, Marburg, HTLV1 or Rabies. hNEDD4-WW3 has been validated as a promising
target for the development of novel host-oriented broad spectrum antivirals. Nonetheless, finding
inhibitors with good properties as therapeutic agents remains a challenge since the key determinants
of binding affinity and specificity are still poorly understood. We present here a detailed structural
and thermodynamic study of the interactions of hNEDD4-WW3 with viral Late domains combining
isothermal titration calorimetry, NMR structural determination and molecular dynamics simulations.
Structural and energetic differences in Late domain recognition reveal a highly plastic hNEDD4-WW3
binding site that can accommodate PPxY-containing ligands with varying orientations. These
orientations are mostly determined by specific conformations adopted by residues I859 and T866.
Our results suggest a conformational selection mechanism, extensive to other WW domains, and
highlight the functional relevance of hNEDD4-WW3 domain conformational flexibility at the binding
interface, which emerges as a key element to consider in the search for potent and selective inhibitors of
therapeutic interest.This research has been financed by grants BIO2009-13261-C02, BIO2012-39922-CO2 and
BIO2016-78746-C2-1-R from the Spanish Ministry of Education and Science (I.L.) including AEI/FEDER
EU funds, by CTQ2017-83810-R grant (F.J.B) and by BFU2014-53787-P, the IRB Barcelona and the BBVA
Foundation (M.J.M)
Prescriptive adherence to GINA guidelines and asthma control: An Italian cross sectional study in general practice
Background: Although general practitioners (GPs) are frequently the first healthcare professionals whom asthma patients refer to for their symptoms, few studies have explored the extent of adherence to guidelines for asthma management based on data provided directly by GPs. Aims of the present study were to assess drug prescriptions for asthma by GPs and to evaluate prescriptive adherence to GINA guidelines (GL) and its relationship with disease control in real life. Methods: 995 asthmatic patients (45% males, mean age 43.3 ± 17.7 yrs) were enrolled by 107 Italian GPs distributed throughout the country. Data on diagnosis, disease severity, prescribed anti-asthmatic drugs and control were collected through questionnaires filled out by GPs taking into consideration the 2009 GINA Guidelines. Data on drug use and chronic sinusitis, nasal polyposis, chronic bronchitis, emphysema were reported by patients through a self-administered questionnaire. Results: The large majority of patients were classified by GPs as having intermittent (48.4%) or mild persistent asthma (25.3%); 61% had co-morbid allergic rhinitis (AR). The prevalent therapeutic regimen used by patients was a combination of inhaled corticosteroids (ICS) plus long-acting β2-agonists (LABA) (54.1%), even in the intermittent/mild persistent group. ICS as mono-therapy or in combination with other drugs but LABA, was the second most frequently adopted treatment (14.4%). In general, the GPs adherence to GL treatment indications was 28.8%, with a significant association with a good asthma control (OR 1.85, 95% CI 1.18–2.92). On the other hand, comorbidity (OR 0.52, 95% CI 0.32–0.84), moderate (0.44, 0.28–0.69) and severe (0.06, 0.02–0.20) persistent asthma showed significant negative effects on asthma control. Conclusions: Our results show that over-treatment of intermittent/mild persistent asthma is frequent in the GPs setting while therapeutic regimens are more appropriately applied for moderate/severe asthma. In general, we found low adherence to GINA GL treatment recommendations even if its relevance in asthma control was confirmed
SIRT1 activity in peripheral blood mononuclear cells correlates with altered lung function in patients with chronic obstructive pulmonary disease
Background. Oxidative stress is a recognized pathogenic mechanism in chronic obstructive pulmonary disease (COPD). Expression of the NAD+-dependent deacetylase Sirtuin 1 (SIRT1), an antiaging molecule with a key role in oxidative stress response, has been described as decreased in the lung of COPD patients. No studies so far investigated whether systemic SIRT1 activity was associated to decreased lung function in this disease. Methods. We measured SIRT1 protein expression and activity in peripheral blood mononuclear cells (PBMCs) and total oxidative status (TOS), total antioxidant capacity (TEAC), and oxidative stress index (TOS/TEAC) in the plasma of 25 COPD patients, 20 healthy nonsmokers (HnS), and 20 healthy smokers (HS). Results. The activity of SIRT1 was significantly lower in COPD patients compared to both control groups while protein expression decreased progressively (HnS > HS > COPD). TOS levels were significantly lower in HnS than in smoke-associated subjects (COPD and HS), while TEAC levels were progressively lower according (HnS > HS > COPD). In COPD patients, SIRT1 activity, but not protein levels, correlated significantly with both lung function parameters (FEV1/FVC and FEV1) and TEAC. Conclusions. These findings suggest loss of SIRT1-driven antioxidant activity as relevant in COPD pathogenesis and identify SIRT1 activity as a potential convenient biomarker for identification of mild/moderate, stable COPD
RUNX/AML and C/EBP factors regulate CD11a integrin expression in myeloid cells through overlapping regulatory elements
The CD11a/CD18 (leukocyte functionassociated
antigen 1 [LFA-1]) integrin mediates
critical leukocyte adhesive interactions
during immune and inflammatory
responses. The CD11a promoter directs
CD11a/CD18 integrin expression, and its
activity in lymphoid cells depends on a
functional RUNX1/AML-1–binding site
(AML-110) within the MS7 sequence. We
now report that MS7 contains a C/EBPbinding
site (C/EBP-100), which overlaps
with AML-110 and is bound by C/EBP
factors in myeloid cells. C/EBP and RUNX/
AML factors compete for binding to their
respective cognate elements and bind to
the CD11a promoter MS7 sequence in a
cell lineage- and differentiation-dependent
manner. In myeloid cells MS7 is
primarily recognized by C/EBP factors in
proliferating cells whereas RUNX/AMLfactors
(especially RUNX3/AML-2) bind to
MS7 in differentiated cells. RUNX3/AML-2
binding to the CD11a promoter correlates
with increased RUNX3/AML-2 protein levels
and enhanced CD11a/CD18 cell surface
expression. The relevance of the
AML-110 element is underscored by the
ability of AML-1/ETO to inhibit CD11a promoter
activity, thus explaining the low
CD11a/CD18 expression in t(8;21)–containing
myeloid leukemia cells. Therefore,
the expression of the CD11a/CD18
integrin in myeloid cells is determined
through the differential occupancy of the
CD11a proximal promoter by transcription
factors implicated in the pathogenesis
of myeloid leukemia
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