Perinatal asphyxia: CNS development and deficits with delayed onset

Perinatal asphyxia constitutes a prototype of obstetric complications occurring when pulmonary oxygenation is delayed or interrupted. The primary insult relates to the duration of the period lacking oxygenation, leading to death if not re-established. Re-oxygenation leads to a secondary insult, related to a cascade of biochemical events required for restoring proper function. Perinatal asphyxia interferes with neonatal development, resulting in long-term deficits associated to mental and neurological diseases with delayed clinical onset, by mechanisms not yet clarified. In the experimental scenario, the effects observed long after perinatal asphyxia have been explained by over expression of sentinel proteins, such as poly(ADP-ribose) polymerase-1 (PARP-1), competing for NAD+ during re-oxygenation, leading to the idea that sentinel protein inhibition constitutes a suitable therapeutic strategy. Asphyxia induces transcriptional activation of proinflammatory factors, in tandem with PARP-1 overactivation, and pharmacologically induced PARP-1 inhibition also down-regulates the expression of proinflammatory cytokines. Nicotinamide has been proposed as a suitable PARP-1 inhibitor. Its effect has been studied in an experimental model of global hypoxia in rats. In that model, the insult is induced by immersing rat foetuses into a water bath for various periods of time. Following asphyxia, the pups are delivered, treated, and nursed by surrogate dams, pending further experiments. Nicotinamide rapidly distributes into the brain following systemic administration, reaching steady state concentrations sufficient to inhibit PARP-1 activity for several hours, preventing several of the long-term consequences of perinatal asphyxia, supporting the idea that it constitutes a lead for exploring compounds with similar or better pharmacological profiles

The Science Performance of JWST as Characterized in Commissioning

This paper characterizes the actual science performance of the James Webb Space Telescope (JWST), as determined from the six month commissioning period. We summarize the performance of the spacecraft, telescope, science instruments, and ground system, with an emphasis on differences from pre-launch expectations. Commissioning has made clear that JWST is fully capable of achieving the discoveries for which it was built. Moreover, almost across the board, the science performance of JWST is better than expected; in most cases, JWST will go deeper faster than expected. The telescope and instrument suite have demonstrated the sensitivity, stability, image quality, and spectral range that are necessary to transform our understanding of the cosmos through observations spanning from near-earth asteroids to the most distant galaxies

Metabolic constituents of grapevine and grape-derived products

The numerous uses of the grapevine fruit, especially for wine and beverages, have made it one of the most important plants worldwide. The phytochemistry of grapevine is rich in a wide range of compounds. Many of them are renowned for their numerous medicinal uses. The production of grapevine metabolites is highly conditioned by many factors like environment or pathogen attack. Some grapevine phytoalexins have gained a great deal of attention due to their antimicrobial activities, being also involved in the induction of resistance in grapevine against those pathogens. Meanwhile grapevine biotechnology is still evolving, thanks to the technological advance of modern science, and biotechnologists are making huge efforts to produce grapevine cultivars of desired characteristics. In this paper, important metabolites from grapevine and grape derived products like wine will be reviewed with their health promoting effects and their role against certain stress factors in grapevine physiology

Odanacatib for the treatment of postmenopausal osteoporosis. results of the LOFT multicentre, randomised, double-blind, placebo-controlled trial and LOFT extension study

Background: Odanacatib, a cathepsin K inhibitor, reduces bone resorption while maintaining bone formation. Previous work has shown that odanacatib increases bone mineral density in postmenopausal women with low bone mass. We aimed to investigate the efficacy and safety of odanacatib to reduce fracture risk in postmenopausal women with osteoporosis. Methods: The Long-term Odanacatib Fracture Trial (LOFT) was a multicentre, randomised, double-blind, placebo-controlled, event-driven study at 388 outpatient clinics in 40 countries. Eligible participants were women aged at least 65 years who were postmenopausal for 5 years or more, with a femoral neck or total hip bone mineral density T-score between −2·5 and −4·0 if no previous radiographic vertebral fracture, or between −1·5 and −4·0 with a previous vertebral fracture. Women with a previous hip fracture, more than one vertebral fracture, or a T-score of less than −4·0 at the total hip or femoral neck were not eligible unless they were unable or unwilling to use approved osteoporosis treatment. Participants were randomly assigned (1:1) to either oral odanacatib (50 mg once per week) or matching placebo. Randomisation was done using an interactive voice recognition system after stratification for previous radiographic vertebral fracture, and treatment was masked to study participants, investigators and their staff, and sponsor personnel. If the study completed before 5 years of double-blind treatment, consenting participants could enrol in a double-blind extension study (LOFT Extension), continuing their original treatment assignment for up to 5 years from randomisation. Primary endpoints were incidence of vertebral fractures as assessed using radiographs collected at baseline, 6 and 12 months, yearly, and at final study visit in participants for whom evaluable radiograph images were available at baseline and at least one other timepoint, and hip and non-vertebral fractures adjudicated as being a result of osteoporosis as assessed by clinical history and radiograph. Safety was assessed in participants who received at least one dose of study drug. The adjudicated cardiovascular safety endpoints were a composite of cardiovascular death, myocardial infarction, or stroke, and new-onset atrial fibrillation or flutter. Individual cardiovascular endpoints and death were also assessed. LOFT and LOFT Extension are registered with ClinicalTrials.gov (number NCT00529373) and the European Clinical Trials Database (EudraCT number 2007-002693-66). Findings: Between Sept 14, 2007, and Nov 17, 2009, we randomly assigned 16 071 evaluable patients to treatment: 8043 to odanacatib and 8028 to placebo. After a median follow-up of 36·5 months (IQR 34·43–40·15) 4297 women assigned to odanacatib and 3960 assigned to placebo enrolled in LOFT Extension (total median follow-up 47·6 months, IQR 35·45–60·06). In LOFT, cumulative incidence of primary outcomes for odanacatib versus placebo were: radiographic vertebral fractures 3·7% (251/6770) versus 7·8% (542/6910), hazard ratio (HR) 0·46, 95% CI 0·40–0·53; hip fractures 0·8% (65/8043) versus 1·6% (125/8028), 0·53, 0·39–0·71; non-vertebral fractures 5·1% (412/8043) versus 6·7% (541/8028), 0·77, 0·68–0·87; all p<0·0001. Combined results from LOFT plus LOFT Extension for cumulative incidence of primary outcomes for odanacatib versus placebo were: radiographic vertebral fractures 4·9% (341/6909) versus 9·6% (675/7011), HR 0·48, 95% CI 0·42–0·55; hip fractures 1·1% (86/8043) versus 2·0% (162/8028), 0·52, 0·40–0·67; non-vertebral fractures 6·4% (512/8043) versus 8·4% (675/8028), 0·74, 0·66–0·83; all p<0·0001. In LOFT, the composite cardiovascular endpoint of cardiovascular death, myocardial infarction, or stroke occurred in 273 (3·4%) of 8043 patients in the odanacatib group versus 245 (3·1%) of 8028 in the placebo group (HR 1·12, 95% CI 0·95–1·34; p=0·18). New-onset atrial fibrillation or flutter occurred in 112 (1·4%) of 8043 patients in the odanacatib group versus 96 (1·2%) of 8028 in the placebo group (HR 1·18, 0·90–1·55; p=0·24). Odanacatib was associated with an increased risk of stroke (1·7% [136/8043] vs 1·3% [104/8028], HR 1·32, 1·02–1·70; p=0·034), but not myocardial infarction (0·7% [60/8043] vs 0·9% [74/8028], HR 0·82, 0·58–1·15; p=0·26). The HR for all-cause mortality was 1·13 (5·0% [401/8043] vs 4·4% [356/8028], 0·98–1·30; p=0·10). When data from LOFT Extension were included, the composite of cardiovascular death, myocardial infarction, or stroke occurred in significantly more patients in the odanacatib group than in the placebo group (401 [5·0%] of 8043 vs 343 [4·3%] of 8028, HR 1·17, 1·02–1·36; p=0·029, as did stroke (2·3% [187/8043] vs 1·7% [137/8028], HR 1·37, 1·10–1·71; p=0·0051). Interpretation: Odanacatib reduced the risk of fracture, but was associated with an increased risk of cardiovascular events, specifically stroke, in postmenopausal women with osteoporosis. Based on the overall balance between benefit and risk, the study's sponsor decided that they would no longer pursue development of odanacatib for treatment of osteoporosis. Funding: Merck Sharp & Dohme Corp, a subsidiary of Merck & Co, Inc, Kenilworth, NJ, USA

CIGR E-Journal Volume 6

(1.) P. Kumar and K. Dewangan. Deflection and Contact Characteristics of a Power Tiller Tyre. (January 2004). ...(2.) S. Li and Y. Lin. Modeling a Single-stage Hydrocyclone for Potato Starch Separation.(February 2004). ...(3.) Y. Cui, Y. Li, Z. Mao, J. Lance and A. Musy. Strategies for Improving the Water Supply System in HCID, Upper Reaches of the Yellow River Basin, China . (March 2004). ...(4.) S. Mutaf, S. Alkan and N. Seber. The Effects of Natural Ventilation Air Exchange on Psychrometric Results in Poultry Houses in Hot Environment - Design Characteristics. (March 2004). ...(5.) N. Abu-Khalaf, B. Bennedsen and G. Bjorn. Distinguishing Carrot???s Characteristics by Near Infrared (NIR) Reflectance and Multivariate Data Analysis. (March 2004). ...(6.) S. Sakhamuri, J. Bober, J. Irudayaraj and A. Demirci. Simultaneous Determination of Multiple Components in Nisin Fermentation Using FTIR Spectroscopy. (March 2004). ...(7.) A. van Wagenberg, B. Bjerg and G. Bot. Measurement and Simulation of Climatic Conditions in the Animal Occupied Zone in a Door Ventilated Room for Piglets. (April 2004). ...(8.) P. Picuno and C. Sica. Mechanical and Spectroradiometrical Characteristics of Agricultural Plastic Films. (April 2004). ...(9.) R. Medjo Eko. Use of Isotropic Stress State Framework to Evaluate the Effect of Suction on Some Mechanical Parameters of Sainte-Rosalie Clay Submitted to Confined Compression. (April 2004). ...(10.) J. Khazaei and D. Mann. Effects of Temperature and Loading Characteristics on Mechanical and Stress-Relaxation Properties of Sea Buckthorn Berries. Part 1. Compression Tests. (April 2004). ...(11.) J. Khazaei and D. Mann. Effects of Temperature and Loading Characteristics on Mechanical and Stress-Relaxation Properties of Sea Buckthorn Berries. Part 2. Puncture Tests. (April 2004). ...(12.) K. Rosentrater. Laboratory Analysis of an Electrostatic Dust Collection System. (April 2004). ...(13.) A. Yuwono and P. Schulze Lammers. Performance Test of a Sensor Array-Based Odor Detection Instrument. (May 2004). ...(14.) M. Massoud, M. El-Fadel, M. Scrimshaw, and J. Lester. Land Use Impact on the Spatial and Seasonal Variation of the Contaminant Loads to Abou Ali River and Its Coastal Zone in North Lebanon. (May 2004). ...(15.) J. Bober and A. Demirci. Nisin Fermentation by Lactoccocus lactis subsp. lactis Using Plastic Composite Supports in Biofilm Reactors.(June 2004). ...(16.) A. Vejasit and V. Salokhe. Studies on Machine-Crop Parameters of an Axial Flow Thresher for Threshing Soybean. (July 2004). ...(17.) G. van Straten and Th. Gieling. Ion Control in Closed Growing Systems with Inert Media: Controller Settings and Modes of Operation. (July 2004). ...(18.) A. Kalbasi-Ashtari. Effects of Post-harvest Pre-cooling Processes and Cyclical Heat Treatment on the Physico-chemical Properties of ???Red Haven Peaches??? and ???Shahmiveh Pears??? During Cold Storage. (July 2004). ...(19.) B. Blackmore, S. Fountas, L. Tang, and H. Have. Systems Requirements for a Small Autonomous Tractor. (July 2004). ...(20.) J. Cancela, X. Neira, T. Cuesta, C. Alvarez, and R. Crecente. Socio-Economic Evaluation of the Terra Cha Irrigators Community by using a Geographic Information System - Spain. (July 2004). ...(21.) A. Atiku, N. Aviara, and M. Haque. Performance Evaluation of a Bambara Ground Nut Sheller. (July 2004). ...(22.) I. Audu, A. Oloso, and B. Umar. Development of a Concentric Cylinder Locust Bean Dehuller. (August 2004). ...(23.) B. Bjerg, P. Kai, S. Morsing, and H. Takai. CFD Analysis to Predict Close Range Spreading of Ventilation Air from Livestock Buildings. (August 2004). ...(24.) G. Munoz-Hernandez, M. Gonzalez-Valadez, and J. Dominguez-Dominguez. An Easy Way to Determine the Working Parameters of the Mechanical Densification Process. (August 2004). ...(25.) J. Montero, P. Galletero, C. Neumeister, and J. Diaz. Comparative Study Between Rigid Frames and Truss Steel Structures. (August 2004). ...(26.) B. Hermiyanto, M. Zoebisch, G. Singh, S. Ranamukhaarachchi, R. Clemente and F. Agus. Comparing Runoff, Soil and Nutrient Losses from Three Small Watersheds in Indonesia. (September 2004). ...(27.) G. Tomaselli, G. Pappalardo, M. Di Marco, and P. Russo. Building Design Solutions for Sheep and Goat Breeding in the Protected Areas of Sicily. (September 2004). ...(28.) Y. Yuan, A. Hansen, and Q. Zhang. The Specific Gravity of Biodiesel Fuels and their Blends with Diesel Fuel. (September 2004). ...(29.) A. De Montis and S. De Montis. Mandatory and Spontaneous Processes of Impact Assessment: A Comparative Study Referred to Sardinia, Italy. (October 2004). ...(30.) S. Dasylva, C. Cosandey, D. Orange, and S. Sambou. Rainwater Infiltration Rate and Groundwater Sustainable Management in the Dakar Region. (October 2004). ...(31.) C. Bravo, D. Moshou, R. Oberti, J. West, A. McCartney, L. Bodria and H. Ramon. Foliar Disease Detection in the Field Using Optical Sensor Fusion. (December 2004). ...(32.) S. Korfali and B. Davies. The Relationships of Metals in River Sediments (Nahr-Ibrahim, Lebanon) and Adjacent Floodplain Soils. (Dec 2004). ...(33.) H. Sun, H. Keener, W. Deng and F. Michel, Jr. Development and Validation of 3-D CFD Models to Simulate Airflow and Ammonia Distribution in a High-Rise Hog Building during Summer and Winter Conditions. (December 2004). ...(34.) P. Kai and A. Schafer. Identification of Key Odour Components in Pig House Air using Hyphenated Gas Chromatography Olfactometry. (December 2004). ...(35.) L. Jacobsen and O. Frosig Nielsen. Modelling Airflow Rate through Perforated Benches in Greenhouses. (December 2004). ...(36.) J. Khazaei and D. Mann. Effects of Temperature and Loading Characteristics on Mechanical and Stress-Relaxation Behavior of Sea Buckthorn Berries. Part 3. Relaxation Behavior. (December 2004). (37.) M.Sangha, P. Gupta, V. Thapar, and S. Verma. Storage Studies on Plant Oils and Their Methyl Esters. (December 2004). ...(38.) M. Islam, B. Marks, and F. Bakker-Arkema. Optimization of Commercial Ear-Corn Dryers. (December 2004). ...(39.) B. Pathak, F. Kazama, and I. Toshiaki. Monitoring of Nitrogen Leaching from a Tropical Paddy in Thailand. (December 2004). ...(40.) C. Noeme and R. Fragoso. Evaluation of Alternative Policies of Irrigation Water Price. Application to Large Farms in Alentejo Region. (December 2004). ...(41.) P. Sousa and S. Pedersen. Ammonia Emission from Fattening Pig Houses in Relation to Animal Activity and Carbon Dioxide Production. (December 2004). ...(42.) M. Fadel. Performance Assessment of VRT-based Granular Fertilizer Broadcasting Systems. (December 2004). ...(43.) S. Saptomo, B. Setiawan, and Y. Nakano. Water Regulation in Tidal Peatland Agriculture using Wetland Water level Control Simulator. (December 2004). ...(44.) J. Perez, M. Santamarina, J. Valles, A. Pena, D. Valera, and A. Carreno. Optimal Layout for Milk Goats Livestock Farms Using Genetic Algorithms. (December 2004). ---Invited Articles----(1.) H. Harms. Possibilities to Reduce Manufacturing and Management Costs of Tractors and Agricultural Equipment. (April 2004). ...(2.) A. Yuwono and P. Schulze Lammers. Odor Pollution in the Environment and the Detection Instrumentation. (July 2004). ...(3.) D. Ampratwum, A. Dorvlo, and L. Opara. Usage of Tractors and Field Machinery in Oman. (July 2004). ...(4.) L. Opara. Emerging Technological Innovation Triad for Smart Agriculture in the 21st Century. Part I. Prospects and Impacts of Nanotechnology in Agriculture.(July 2004). ...(5.) L. Kipkurui, I. Kithyo, P. Okemwa, and J. Korir. Modernisation in Automotive Technology and performance of Informal Sector Mechanics in Kenya. (August 2004). ...(6.) S. Pedersen, G. Monteny, H. Xin, and H. Takai. Progress in Research into Ammonia and Greenhouse Gas Emissions from Animal Production Facilities. (August 2004)