PdI2 as a simple and efficient catalyst for the hydroamination of arylacetylenes with anilines

The hydroamination reaction is a convenient alternative strategy for the formation of C– N bonds. Herein, we report a new versatile and convenient protocol for the hydroamination of arylacetylenes with anilines using palladium iodide in the absence of any added ligand as catalyst. Mild conditions, excellent regio-and stereoselectivity, and high functional group tolerance are the main features of this methodology. A subsequent reduction step gives access to a wide variety of secondary aromatic amines

Contemporary data on treatment practices for low-density lipoprotein cholesterol in 3867 patients who had suffered an acute coronary syndrome across the world

DYSIS II ACS was a longitudinal, observational study in 3867 patients from 18 countries. They were being hospitalized after suffering an acute coronary syndrome. Evaluations were performed at the time of admission and again 120±15 days following the date of admission (the follow-up time point). 2521 patients were on active lipid lowering treatment (LLT) at admission. Mean atorvastatin dose was 22 mg per day and 2.7% received ezetimibe in combination with a statin. At discharge from hospital, 3767 patients received LLT expressed as a mean atorvastatin dose of 36 mg per day with 4.8% receiving ezetimibe on top of a statin. After 120 days, intensity in lipid lowering treatment was reduced to 32 mg per day with 4.9% of the patients receiving ezetimibe and a statin. Of note, during this 4-month follow up period, only 32% of all patients received laboratory lipid testing. 37% attained the low density lipoprotein cholesterol (LDL-C) target value of <70 mg/dl after 120 days. There are differences in the therapy administered as well as in the switch strategies when comparing the data from the respective countries studied. Conclusions: Only one in three patients achieved the LDL-C target value following only marginal improvements in atorvastatin dose or combination therapy after an ACS event. Keywords: Low-density lipoprotein cholesterol, Treatment target, Global, Region, Statin

Dynamics of macrophage polarization reveal new mechanism to inhibit IL-1β release through pyrophosphates

In acute inflammation, extracellular ATP activates P2X7 ion channel receptors (P2X7R) on M1 polarized macrophages to release pro-inflammatory IL-1β through activation of the caspase-1/nucleotide-binding domain and leucine-rich repeat receptor containing pyrin domain 3 (NLRP3) inflammasome. In contrast, M2 polarized macrophages are critical to the resolution of inflammation but neither actions of P2X7R on these macrophages nor mechanisms by which macrophages switch from pro-inflammatory to anti-inflammatory phenotypes are known. Here, we investigated extracellular ATP signalling over a dynamic macrophage polarity gradient from M1 through M2 phenotypes. In macrophages polarized towards, but not at, M2 phenotype, in which intracellular IL-1β remains high and the inflammasome is intact, P2X7R activation selectively uncouples to the NLRP3-inflammasome activation but not to upstream ion channel activation. In these intermediate M1/M2 polarized macrophages, extracellular ATP now acts through its pyrophosphate chains, independently of other purine receptors, to inhibit IL-1β release by other stimuli through two independent mechanisms: inhibition of ROS production and trapping of the inflammasome complex through intracellular clustering of actin filaments

Anthropometry, dietary intake, physical activity and sitting time patterns in adolescents aged 15-17 years: an international comparison in eight Latin American countries

BACKGROUND: Although there is high prevalence of obesity and other cardiovascular risk factors among Latin American adolescents, there is limited evidence on dietary intake and physical activity (PA) patterns in this population. Therefore, we characterized anthropometry, dietary intake, PA and sitting time (ST) in adolescents aged 15-17 years from eight Latin American countries. METHODS: Six hundred seventy-one adolescents (41.4% girls) from the Latin American Study of Nutrition and Health (ELANS) were included. Nutritional status was classified by four BMI (kg/m2) categories. Waist circumference (WC) was categorized as above or below thresholds. Dietary intake was assessed through two non-consecutive 24-h dietary recalls. PA and ST were measured using the International Physical Activity Questionnaire (IPAQ). We calculated overall and country-specific estimates by sex and tested for differences between boys and girls. RESULTS: Differences in the prevalence of overweightness (15.1 and 21.6%) and obesity (8.5 and 6.5%) between boys and girls, respectively, were statistically insignificant (p = 0.059). Average energy intake was 2289.7 kcal/day (95% CI: 2231-2350) for boys and 1904.2 kcal/day (95% CI: 1840-1963) for girls (p  0.05 for all outcomes). There was no statistically significant difference in the prevalence of total energy (TE) saturated fat and added sugar (>10% of TE) between girls and boys (49.6% versus 44.8 and 81.7% versus 76.1%, respectively). Prevalence of physical inactivity was 19% in boys and 43.7% in girls (p  0.05). CONCLUSIONS: These findings highlight the high prevalence of poor dietary intake and physical inactivity in adolescents from Latin American countries. Therefore, effective and sustainable strategies and programmes are needed that promote healthier diets, regular PA and reduce ST among Latin American adolescents. TRIAL REGISTRATION: Clinical Trials NCT02226627. Retrospectively registered on August 27, 2014

A pragmatic cluster randomised trial evaluating three implementation interventions

Background Implementation research is concerned with bridging the gap between evidence and practice through the study of methods to promote the uptake of research into routine practice. Good quality evidence has been summarised into guideline recommendations to show that peri-operative fasting times could be considerably shorter than patients currently experience. The objective of this trial was to evaluate the effectiveness of three strategies for the implementation of recommendations about peri-operative fasting. Methods A pragmatic cluster randomised trial underpinned by the PARIHS framework was conducted during 2006 to 2009 with a national sample of UK hospitals using time series with mixed methods process evaluation and cost analysis. Hospitals were randomised to one of three interventions: standard dissemination (SD) of a guideline package, SD plus a web-based resource championed by an opinion leader, and SD plus plan-do-study-act (PDSA). The primary outcome was duration of fluid fast prior to induction of anaesthesia. Secondary outcomes included duration of food fast, patients' experiences, and stakeholders' experiences of implementation, including influences. ANOVA was used to test differences over time and interventions. Results Nineteen acute NHS hospitals participated. Across timepoints, 3,505 duration of fasting observations were recorded. No significant effect of the interventions was observed for either fluid or food fasting times. The effect size was 0.33 for the web-based intervention compared to SD alone for the change in fluid fasting and was 0.12 for PDSA compared to SD alone. The process evaluation showed different types of impact, including changes to practices, policies, and attitudes. A rich picture of the implementation challenges emerged, including inter-professional tensions and a lack of clarity for decision-making authority and responsibility. Conclusions This was a large, complex study and one of the first national randomised controlled trials conducted within acute care in implementation research. The evidence base for fasting practice was accepted by those participating in this study and the messages from it simple; however, implementation and practical challenges influenced the interventions' impact. A set of conditions for implementation emerges from the findings of this study, which are presented as theoretically transferable propositions that have international relevance. Trial registration ISRCTN18046709 - Peri-operative Implementation Study Evaluation (POISE

Protocol for the Foot in Juvenile Idiopathic Arthritis trial (FiJIA): a randomised controlled trial of an integrated foot care programme for foot problems in JIA

&lt;b&gt;Background&lt;/b&gt;: Foot and ankle problems are a common but relatively neglected manifestation of juvenile idiopathic arthritis. Studies of medical and non-medical interventions have shown that clinical outcome measures can be improved. However existing data has been drawn from small non-randomised clinical studies of single interventions that appear to under-represent the adult population suffering from juvenile idiopathic arthritis. To date, no evidence of combined therapies or integrated care for juvenile idiopathic arthritis patients with foot and ankle problems exists. &lt;b&gt;Methods/design&lt;/b&gt;: An exploratory phase II non-pharmacological randomised controlled trial where patients including young children, adolescents and adults with juvenile idiopathic arthritis and associated foot/ankle problems will be randomised to receive integrated podiatric care via a new foot care programme, or to receive standard podiatry care. Sixty patients (30 in each arm) including children, adolescents and adults diagnosed with juvenile idiopathic arthritis who satisfy the inclusion and exclusion criteria will be recruited from 2 outpatient centres of paediatric and adult rheumatology respectively. Participants will be randomised by process of minimisation using the Minim software package. The primary outcome measure is the foot related impairment measured by the Juvenile Arthritis Disability Index questionnaire's impairment domain at 6 and 12 months, with secondary outcomes including disease activity score, foot deformity score, active/limited foot joint counts, spatio-temporal and plantar-pressure gait parameters, health related quality of life and semi-quantitative ultrasonography score for inflammatory foot lesions. The new foot care programme will comprise rapid assessment and investigation, targeted treatment, with detailed outcome assessment and follow-up at minimum intervals of 3 months. Data will be collected at baseline, 6 months and 12 months from baseline. Intention to treat data analysis will be conducted. A full health economic evaluation will be conducted alongside the trial and will evaluate the cost effectiveness of the intervention. This will consider the cost per improvement in Juvenile Arthritis Disability Index, and cost per quality adjusted life year gained. In addition, a discrete choice experiment will elicit willingness to pay values and a cost benefit analysis will also be undertaken

Stable optical trapping and sensitive characterization of nanostructures using standing- wave Raman tweezers

Optical manipulation and label-free characterization of nanoscale structures open up new possibilities for assembly and control of nanodevices and biomolecules. Optical tweezers integrated with Raman spectroscopy allows analyzing a single trapped particle, but is generally less effective for individual nanoparticles. The main challenge is the weak gradient force on nanoparticles that is insufficient to overcome the destabilizing effect of scattering force and Brownian motion. Here, we present standing-wave Raman tweezers for stable trapping and sensitive characterization of single isolated nanostructures with a low laser power by combining a standing-wave optical trap with confocal Raman spectroscopy. This scheme has stronger intensity gradients and balanced scattering forces, and thus can be used to analyze many nanoparticles that cannot be measured with single-beam Raman tweezers, including individual single-walled carbon nanotubes (SWCNT), graphene flakes, biological particles, SERS-active metal nanoparticles, and high-refractive semiconductor nanoparticles. This would enable sorting and characterization of specific SWCNTs and other nanoparticles based on their increased Raman fingerprints

Socio-demographic patterning of objectively measured physical activity and sedentary behaviours in eight Latin American countries: findings from the ELANS study

Physical activity (PA) and sedentary behaviours (SB) are two independent risk factors for non-communicable diseases. However, there is a lack of objectively measured information on PA and SB in low- and middle-income countries. The aim of this study was to use objective data to characterise socio-demographic patterns of PA and SB in eight Latin American countries. 2,732 participants (aged 15-65 years) from the Latin American Study of Nutrition and Health (ELANS) were included. PA and SB data were collected using accelerometers. Overall and country-specific average levels of time spent in PA and SB were compared by sex, age, socioeconomic and education level. Overall, the mean time spent in SB was 571.6 min/day, ranging from 553.8 min/day in Chile to 596.7 min/day in Peru. Average levels of light, moderate-to-vigorous physical activity (MVPA) and total PA were 311.1 min/day (95% CI: 307.7; 314.5), 34.9 min/day (95% CI: 34.0; 35.9) and 7531.2 MET-min/week (95% CI: 7450.4; 7611.9), respectively. MVPA and total PA were higher in men than women. The prevalence of physical inactivity was 40.6%, ranging from 26.9% (Chile) to 47% (Costa Rica and Venezuela). Women were more physically inactive than men (47.7% versus 33.0%). SB levels were highest among those with higher education; PA graded positively with socioeconomic level. Our findings can inform the planning of health policies and programmes designed to reduce levels of physical inactivity, as well as inform the local and cultural adaptation of these policies and programmes for implementation in Latin America

Serum amyloid A primes microglia for ATP-dependent interleukin-1\u3b2 release

Acute-phase response is a systemic reaction to environmental/inflammatory insults and involves production of acute-phase proteins, including serum amyloid A (SAA). Interleukin-1\u3b2 (IL-1\u3b2), a master regulator of neuroinflammation produced by activated inflammatory cells of the myeloid lineage, in particular microglia, plays a key role in the pathogenesis of acute and chronic diseases of the peripheral nervous system and CNS. IL-1\u3b2 release is promoted by ATP acting at the purinergic P2X7 receptor (P2X7R) in cells primed with toll-like receptor (TLR) ligands

Rizatriptan versus rizatriptan plus rofecoxib versus rizatriptan plus tolfenamic acid in the acute treatment of migraine

BACKGROUND: Rizatriptan is an effective and fast acting drug for the acute treatment of migraine. Some nonsteroidal anti-inflammatory drugs (NSAID) have also demonstrated efficacy in treating migraine attacks. There is evidence that the combination of a triptan and a NSAID decreases migraine recurrence in clinical practice. The primary aim of this randomized open label study was to assess the recurrence rates in migraine sufferers acutely treated with rizatriptan (RI) alone vs. rizatriptan plus a COX-2 enzyme inhibitor (rofecoxib, RO) vs. rizatriptan plus a traditional NSAID (tolfenamic acid, TO). We were also interested in comparing the efficacy rates within these three groups. METHODS: We assessed 45 patients from a headache clinic in Rio de Janeiro (35 women and 10 men, ages 18 to 65 years, mean 37 years). Patients with IHS migraine were randomized to one out of 3 groups, where they had to treat 6 consecutive moderate or severe attacks in counterbalanced order. In group 1, patients treated the first two attacks with 10 mg RI, the third and fourth attacks with RI + 50 mg RO and the last attacks with RI + 200 mg of TA. In group 2, we began with RI + TA, followed by RI, and RI + RO. Group 3 treated in the following order: RI + RO, RI + TA, RI alone. The presence of headache, nausea and photophobia at 1, 2 and 4 hours, as well as recurrence and side effects were compared. RESULTS: A total of 33 patients finished the study, treating 184 attacks. The pain-free rates at 1 hour were: RI: 15.5%; RI + RO: 22.6%; RI + TA: 20.3%(NS). Pain-free rates at 2 h were: RI: 37.9%; RI + RO: 62.9%, and RI + TA: 40.6% (p = 0.008 for RI vs. RI + RO; p = 0.007 for RI + RO vs. RI + TA, NS for RI vs RI + TA). At 4 h, pain-free rates were: RI: 69%; RI + RO: 82.3%; RI + TA: 78.1% (NS for all comparisons). The combination of RI + RO was superior to RI and to RI + TA in regard of the absense of nausea and photophobia at 4 hours. Recurrence (after being pain-free at 2 h) was observed in 50% of patients treated with RI, in 15,4% of those treated with RI + RO, and in 7,7% of those treated with RI + TA. CONCLUSIONS: Despite the methodological limitations of this study, the combination of RI and RO revealed a higher response rate at 2 hours. Recurrence was also clearly decreased with both combinations in relation to the use of RI alone. Controlled studies are necessary to provide additional evidence