Key Grazing Behaviours of Beef Cattle Identify Specific Genotypes of the Glutamate Metabotropic Receptor 5 Gene (GRM5).

Genotype-phenotype associations between the bovine genome and grazing behaviours measured over time and across contexts have been reported in the past decade, with these suggesting the potential for genetic control over grazing personalities in beef cattle. From the large array of metrics used to describe grazing personality behaviours (GP-behaviours), it is still unclear which ones are linked to specific genes. Our prior observational study has reported associations and trends towards associations between genotypes of the glutamate metabotropic receptor 5 gene (GRM5) and four GP-behaviours, yet the unbalanced representation of GRM5 genotypes occurring in observational studies may have limited the ability to detect associations. Here, we applied a subsampling technique to create a genotypically-balanced dataset in a quasi-manipulative experiment with free ranging cows grazing in steep and rugged terrain of New Zealand's South Island. Using quadratic discriminant analysis, two combinations of eleven GP-behaviours (and a total of fifteen behaviours) were selected to build an exploration model and an elevation model, respectively. Both models achieved ∼ 86% accuracy in correctly discriminating cows' GRM5 genotypes with the training dataset, and the exploration model achieved 85% correct genotype prediction of cows from a testing dataset. Our study suggests a potential pleiotropic effect, with GRM5 controlling multiple grazing behaviours, and with implications for the grazing of steep and rugged grasslands. The study highlights the importance of grazing behavioural genetics in cattle and the potential use of GRM5 markers to select individuals with desired grazing personalities and built herds that collectively utilize steep and rugged rangelands sustainably.

The glutamate metabotropic receptor 5 (GRM5) gene is associated with beef cattle home range and movement tortuosity.

BACKGROUND: The grazing behaviour of herbivores and their grazing personalities might in part be determined genetically, but there are few studies in beef cattle illustrating this. In this study, we investigated for first time the genetic variation within a candidate 'grazing gene', the glutamate metabotropic receptor 5 gene (GRM5), and tested associations between variation in that gene and variation in grazing personality behaviours (GP-behaviours) displayed by free-ranging cows during winter grazing in the steep and rugged rangelands of New Zealand. Mature beef cows (n = 303, from 3 to 10 years of age) were tracked with global positioning system (GPS) and, with 5-minutes (min) relocation frequency, various GP-behaviours were calculated. These included horizontal and vertical distances travelled, mean elevation, elevation range, elevation gain, slope, home range and movement tortuosity, variously calculated using daily relocation trajectories with repeated measurements (i.e., 7 to 24 days (d)) and satellite-derived digital elevation models (DEM). The different GP-behaviours were fitted into mixed models to ascertain their associations with variant sequences and genotypes of GRM5. RESULTS: We discovered three GRM5 variants (A, B and C) and identified the six possible genotypes in the cattle studied. The mixed models revealed that A was significantly associated with elevation range, home range and movement tortuosity. Similarly, GRM5 genotypes were associated (P < 0.05) to home range and movement tortuosity, while trends suggesting association (P <  0.1) were also revealed for elevation range and horizontal distance travelled. Most GP-behaviour models were improved by correcting for cow age-class as a fixed factor. The analysis of GP-behaviours averaged per cow age-class suggests that grazing personality is fully established as beef cows reached 4 years of age. Home range and movement tortuosity were not only associated with GRM5 variation, but also negatively correlated with each other (r = - 0.27, P < 0.001). CONCLUSIONS: There seems to be a genetically determined trade-off between home range and movement tortuosity that may be useful in beef cattle breeding programmes aiming to improve the grazing distribution and utilisation of steep and rugged rangelands.

Grasses procure key soil nutrients for clovers.

Rhizobial nitrogen fixation in legumes provides spillover benefits to neighbouring plants such as pasture grasses. Generally, it is understood to be unidirectional between plant functional groups, providing a benefit from legumes to grasses. We question whether bidirectional complementarity also exists in terms of exploiting the wider soil nutrient pool. We test this hypothesis using soil cores with their component vegetation assemblages sampled from a hill country pasture in South Island, New Zealand. The soil was deficient in key essential elements: P, S, B, Mo and Ni. Facilitation from grasses to clovers was evident; legume-grass mixtures procured more nutrients from the soil than when either species was growing alone. When grasses and clover grow together in unfertilized grassland, more nitrogen is procured by the plant community, and other limiting plant nutrients in the soil are better exploited. Coexistence with grasses is favourable to clovers in terms of soil biogeochemistry.

A landscape review of controlled release urea products: Patent objective, formulation and technology.

Fertiliser has been a vital part of agriculture due to it boosting crop productivity and preventing starvation throughout the world. Despite this huge contribution, the application of nitrogen (N) fertilisers results in N leaching and the formation of greenhouse gases, which threaten the environment and human health. To minimise the impacts, slow/controlled release fertilisers (S/CRFs) have been being developed since the beginning of the 20th century. Despite the efforts made over a century, the basic terminological and classification information of these fertilisers remains vague. The scientific knowledge published in S/CRF patents has also been overlooked since the beginning. This review focused on the information gaps, clarified the definitions, differentiation and classification methods that have been randomly used in previous literature. The objectives, formulations and technologies of 109 controlled release urea patents involving sulphur coated urea, polymer coated urea and urea matrix fertilisers published in the years since these products emerged were also reviewed to 1) highlight the overlooked scientific knowledge in the patents; 2) understand the evolutionary processes and current research states of the products; 3) clarify research preferences and challenges to date; 4) identify remaining gaps for the future direction. It is expected that the organised basic information and the patent knowledge highlighted in this paper can be new resources and foster the development of S/CRFs in the future.

Plant Species Complementarity in Low-Fertility Degraded Soil.

The aim of this study was to investigate the compatibility of plants with contrasting root systems, in terms of procurement of limiting soil nutrients. Paired combinations of species of proteas and grasses were grown in a pot experiment using soil from a site with impoverished vegetation and degraded soil. The soil contained sufficient N but was low to deficient in P, Mn, S, Fe, and B. The uptake of chemical elements into the foliage differed significantly according to whether the plants were growing as single or mixed species. When two species of Grevillea and grasses with evolutionary origins in low fertility soils were growing together, there was an enhanced uptake of P and Mn, in one or both species, in addition to other elements that were in low concentrations in the experimental soil. In contrast to this, Protea neriifolia that probably originated from a more fertile soil procured lesser amounts of the six elements from the soil when growing together with grasses. Two grasses tolerant of less fertile soils (Dactylis glomerata and Poa cita) obtained more nutrients when they grew together with proteas; this was a much stronger neighbour effect than was measured in Lolium perenne which is better adapted to high fertility soils. The findings illustrate both the functional compatibility and competition for plant nutrients in mixed-species rhizospheres. Species combinations substantially increased the acquisition of key elements from the soil nutrient pool.

Varied diets: implications for lamb performance, rumen characteristics, total antioxidant status, and welfare.

Intensive pastoral systems have moved away from diverse and varied diets towards overly simple monotonous diets. Feed choice through time is an obsolete way of providing forage to animals, as intensive management schemes generally allocate a single herbage or a dyad mixed sward. Monotonous feeding regimes impose nutritional repetition, which may impair animal performance and welfare. The objective of this experiment was to determine the impact of a diverse diet [DIV; free choice from perennial ryegrass (Lolium perenne L.), plantain (Plantago lanceolata L.), alfalfa (Medicago sativa L.), and chicory (Cichorium intybus L.) at all times], a varied diet [VAR; choice from ryegrass and plantain in the AM (0700-1600 h), and chicory and alfalfa in PM (1600-0700 h)], and a single forage diet of alfalfa [SFA; alfalfa at all times], on DMI, performance, and welfare of lambs. Six-month-old Coopworth ram lambs (n = 21) were offered their respective fresh-forage treatment (n = 7) diet indoors for 20 d. The DIV lambs consumed 1.64 ± 0.03 kg DM/d (mean ± SEm), which was 6% more (P < 0.05; 1.54 ± 0.03 kg DM/d) than the SFA and were not different (P > 0.05; 1.59 ± 0.03 kg DM/d) to the VAR lambs. Average daily gain (ADG) of DIV (296 g/d) and VAR (378 g/d) was 30% and 67% greater (P < 0.05) than that in the SFA lambs (227 g/d), respectively. The VAR lambs had 28% greater (P < 0.05) ADG than the DIV lambs. Differences among treatments were detected (P < 0.05) for the proportion of the day spent conducting the following behaviors: eating, ruminating, idling, lying, and standing. In addition, the number of bouts of stereotypic behaviors recorded from the SFA lambs (13.2 ± 2.2) was 150% greater (P < 0.05) than the DIV (5.1 ± 1.0) and VAR (5.5 ± 1.0) lambs. Our results suggest that the varied diet offered can improve animal performance and welfare compared to a monotonous SFA diet. Feeding management to provide a varied diet can improve performance relative to giving lambs free choice from taxonomically diverse forage options. Moreover, performance is affected by more than the primary chemical composition of the diet consumed, but how the diet is presented through time and the herbage species and quantities of each that are consumed to reach that chemical composition.

Negative effects of energy supplementation at peak lactation of sheep can be offset by the addition of Lactobacillus-fermented plant extracts.

Energy supplementation may reduce oxidative stress by correcting a negative energy balance, but in some contexts, it has been shown to increase oxidative stress, especially at peak lactation. The current experiment examined if a pelleted energy supplement with or without the addition of Lactobacillus-fermented seaweed or seaweed plus terrestrial plants extracts affected oxidative stress of ewes from late gestation through to weaning and ewe and lamb production from lambing to weaning. Treatments were either no supplement (CON-), a pelleted supplement only (CON+, 100 g/ewe per d), CON+ with seaweed extract only (SWO, 10 mL/ewe per day), or CON+ with seaweed plus an arrangement of terrestrial plant extract (SWP, 10 mL/ewe per d). Ewes (n = 160; mean initial BW = 72.3 ± 9.5 kg [mean ± SD]) were randomized to pastures (n = 4 pastures per treatment with 10 ewes each). After lambing, ewes with twins were reallocated to pastures (n = 3 pastures per treatment with 10 ewes each) according to lambing date. At 4 wk in milk, supplementation tended to reduce total antioxidant status (TAS; P = 0.10) and increased glutathione peroxidase (GPx) activity compared with nonsupplemented ewes (P = 0.04). The addition of seaweed and terrestrial plants extracts to the concentrate, that is, SWO and SWP, increased TAS and reduced GPx activity compared with CON+ (P < 0.01). Supplementation increased milk yield at weeks 4, 6, and 8 of lactation, and protein, lactose, and total milk solids yield at peak lactation (week 4; P < 0.05). The CON- ewes had greater somatic cell count than the supplemented ewes at weeks 4, 8, and 10 of lactation (P = 0.03). Our results suggest that energy supplementation, alone, increases oxidative stress of lactating ewes, which may relate to increased oxidative phosphorylation. Most importantly, these results indicate that in situations where energy supplementation is needed to increase animal performance, negative effects of energy supplementation around peak lactation can be offset by the addition of Lactobacillus-fermented plant extracts (SWO and SWP) to improve antioxidant status.

Toward a Monte Carlo approach to selecting climate variables in MaxEnt.

MaxEnt is an important aid in understanding the influence of climate change on species distributions. There is growing interest in using IPCC-class global climate model outputs as environmental predictors in this work. These models provide realistic, global representations of the climate system, projections for hundreds of variables (including Essential Climate Variables), and combine observations from an array of satellite, airborne, and in-situ sensors. Unfortunately, direct use of this important class of data in MaxEnt modeling has been limited by the large size of climate model output collections and the fact that MaxEnt can only operate on a relatively small set of predictors stored in a computer's main memory. In this study, we demonstrate the feasibility of a Monte Carlo method that overcomes this limitation by finding a useful subset of predictors in a larger, externally-stored collection of environmental variables in a reasonable amount of time. Our proposed solution takes an ensemble approach wherein many MaxEnt runs, each drawing on a small random subset of variables, converges on a global estimate of the top contributing subset of variables in the larger collection. In preliminary tests, the Monte Carlo approach selected a consistent set of top six variables within 540 runs, with the four most contributory variables of the top six accounting for approximately 93% of overall permutation importance in a final model. These results suggest that a Monte Carlo approach could offer a viable means of screening environmental predictors prior to final model construction that is amenable to parallelization and scalable to very large data sets. This points to the possibility of near-real-time multiprocessor implementations that could enable broader and more exploratory use of global climate model outputs in environmental niche modeling and aid in the discovery of viable predictors.

Functional diversity vs. monotony: the effect of a multiforage diet as opposed to a single forage diet on animal intake, performance, welfare, and urinary nitrogen excretion.

The objective of this study was to determine the effect of offering animals a multiforage choice (MF) of fresh herbages on dry matter intake (DMI), live weight gain, and animal welfare, in comparison with a monotonous diet of ryegrass (Lolium perenne L.). Twenty ram lambs (30.5 ± 0.9 kg initial live weight; mean ± SEM), were randomly allocated to either a diet consisting of diverse MF choice or a single forage ryegrass (SF) diet (n = 10 per treatment) for 35 d. Both diets were fed ad libitum; however, the MF diet was composed of set dry matter ratios of 24% chicory (Cichorium intybus L.), 30% lucerne (Medicago sativa L.), 25% plantain (Plantago lanceolata L.), and 21% ryegrass. The DMI of the MF lambs was 48% greater (P < 0.01) and the within animal day-to-day coefficient of variation (CV) of intake was 26% lower (P < 0.01) than the SF lambs. The average daily gain (ADG) of lambs offered the MF diet was 92% greater (P < 0.01) than the lambs offered the SF diet. The within-animal day-to-day CV of intake was negatively related to ADG (r = -0.59; P < 0.01). The MF lamb's urinary N concentration was 30% lower (P < 0.01) than that of the SF lambs. The SF lambs spent more time (P < 0.05) exhibiting stereotypic behaviors in the afternoon and spent more time observing other animals than the MF. Overall, allocating an MF choice of fresh herbages as opposed to a single forage diet of ryegrass increases DMI and thereby animal performance, while potentially reducing urinary N excretion.

Functional Traits, Morphology, and Herbage Production of Vernalised and Non-Vernalised Chicory cv. Choice (Cichorium intybus L.) in Response to Defoliation Frequency and Height.

Chicory (Cichorium intybus L.) used in pastoral systems has the attributes required of a forage species to reduce animal urinary nitrogen loading to soil, increase milk production, and enhance milk fatty acid profile to improve pastoral farm systems for matching increasing global demand for dairy products and environmental standards of livestock systems. Greater adoption of chicory requires confidence in management decisions that can control risks to farm production, namely bolting after vernalisation or a decline in persistence of chicory swards, which have slowed its adoption in pastoral systems. We, therefore, measured functional traits, morphology and herbage production of chicory under irrigated field conditions before and after vernalisation in Canterbury, New Zealand. The experimental site was laid out in a complete randomized block design with four replications where two regrowth intervals and two defoliation heights were applied. Regrowth interval had a stronger influence over functional traits and herbage production than defoliation height, with more pronounced effects after vernalisation. Plants managed under shorter regrowth intervals had narrower roots with lower concentration of sugars than plants under longer intervals, which might compromise their longevity. In addition, plants managed under shorter intervals remained mostly vegetative with heavier and longer leaves, though with reduced photosynthetic capacity than those managed under longer intervals. The thermal time to initiate stem elongation in plants managed under longer intervals was ~274 growing degree-days, with a mean stem elongation rate increasing linearly at 1.4 ± 0.08 mm/growing degree-days. The key outcomes of this research quantify the growing degree-days to initiate stem elongation post vernalisation, which provides management directive for timing of defoliation of chicory in order to maintain feed quality for grazing livestock. Alternating frequent and infrequent defoliation regimes might be used to optimise vegetative growth, root reserves, and pasture persistence.

A single-center, retrospective study of COVID-19 features in children: a descriptive investigation.

BACKGROUND: Compared to adults, there are relatively few studies on COVID-19 infection in children, and even less focusing on the unique features of COVID-19 in children in terms of laboratory findings, locations of computerized tomography (CT) lesions, and the role of CT in evaluating clinical recovery. The objective of this study is to report the results from patients at Wuhan Children's Hospital, located within the initial center of the outbreak. METHODS: Clinical, imaging, and laboratory data of 76 children were collected retrospectively and analyzed with the Fisher exact test and Cox regression statistical methods. RESULTS: Among 50 children with a positive COVID-19 real-time reverse-transcriptase polymerase chain reaction (PCR), five had negative PCR results initially but showed positive results in subsequent tests. Eight (16%) patients had lymphopenia, seven (14%) with thrombocytopenia, four (8%) with lymphocytosis, two (4%) with thrombocytosis, ten (20%) with elevated C-reactive protein, four (8%) with hemoglobin above, and six (12%) with below standard reference values. Seven (14%) of the 50 had no radiologic evidence of disease on chest CT. For the 43 patients who had abnormal CT findings, in addition to previously reported patterns of ground-glass opacity (67%), local patchy shadowing (37%), local bilateral patchy shadowing (21%), and lesion location of lower lobes (65%), other CT features include that an overwhelming number of pediatric patients had lesions in the subpleural area (95%) and 22 of the 28 lower lobe lesions were in the posterior segment (78%). Lesions in most of the 15 patients (67%) who received chest CT at discharge were not completely absorbed, and 26% of these pediatric patients had CT lesions that were either unchanged or worse. CONCLUSIONS: There were a few differences between COVID-19 children and COVID-19 adults in terms of laboratory findings and CT characteristics. CT is a powerful tool to detect and characterize COVID-19 pneumonia but has little utility in evaluating clinical recovery for children. These results oppose current COVID-19 hospital discharge criteria in China, as one requirement is that pulmonary imaging must show significant lesion absorption prior to discharge. These differences between pediatric and adult cases of COVID-19 may necessitate pediatric-specific discharge criteria.

On the Search for Grazing Personalities: From Individual to Collective Behaviors.

While grazing lands can offer a diverse range of forages, individuals within herds prefer to graze some habitats and not others. They can have consistent differences in grazing patterns and occupy specific spatial domains, whilst developing tactics and strategies for foraging that are specific to their grazing personalities. In this review, we explore the development of our understanding of grazing personalities, as we move away from the search for an "optimal animal" toward designing behavior-customized herds with an arrangement of individual grazing personalities that enhance ecosystem services and productivity. We present a "grazing personality model" that accounts for the personality of individual animals and for collective behaviors of herds. We argue that grazing personalities of grazing ruminants and other large herbivores are in part genetically determined, and that they can act at the individual and collective level. The social and biophysical environments as well as the emotional state of animals regulate the expression of "grazing genes" that are observed phenotypically as distinct grazing personalities. The reproductive and sexual successes of individuals and herds filter for allele variants of grazing genes and in turn determines their relative frequency. While the selection of one grazing personality may be adequate for homogeneous pastoral systems, the design of herds with a range of grazing personalities that are matched to the habitat diversity may be a better approach to improving the distribution of grazing animals, enhancing ecosystem services, and maximizing productivity.

Strategic grazing management and nitrous oxide fluxes from pasture soils in tropical dairy systems.

Greenhouse gases emissions are considered one of the most important environmental issues of dairy farming systems. Nitrous oxide (N2O) has particular importance owing to its global warming potential and stratospheric ozone depletion. The objective of this study was to investigate the influence of two rotational grazing strategies characterized by two pre-grazing targets (95% and maximum canopy light interception; LI95% and LIMax, respectively) on milk production efficiency and N2O fluxes from soil in a tropical dairy farming system based on elephant grass (Pennisetum purpureum Schum. cv. Cameroon). Results indicated that LI95% pre-grazing target provided more frequent defoliations than LIMax. Water-filled pore space, soil and chamber temperatures were affected by sampling periods (P1 and P2). There was a significant pre-grazing target treatment × sampling period interaction effect on soil NH4+ concentration, which was most likely associated with urinary-N discharge. During P1, there was a greater urinary-N discharge for LI95% than LIMax (26.3 vs. 20.9 kg of urinary-N/paddock) caused by higher stocking rate, which resulted in greater N2O fluxes for LI95%. Inversely, during P2, the soil NH4+ and N2O fluxes were greater for LIMax than LI95%. During this period, the greater urinary-N discharge (46.8 vs. 44.8 kg of urinary-N/paddock) was likely associated with longer stocking period for LIMax relative to LI95%, since both treatments had similar stocking rate. Converting hourly N2O fluxes to daily basis and relating to milk production efficiency, LI95% was 40% more efficient than LIMax (0.34 vs. 0.57 g N-N2O/kg milk·ha). In addition, LI95% pre-grazing target decreased urea-N loading per milk production by 34%. Strategic grazing management represented by the LI95% pre-grazing target allows for intensification of tropical pasture-based dairy systems, enhanced milk production efficiency and decreased N-N2O emission intensity.

Effect of Two-Dimensional Crystal Orbitals on Fermi Surfaces and Electron Transport in Three-Dimensional Perovskite Oxides.

Perovskite oxides are candidate materials in catalysis, fuel cells, thermoelectrics, and electronics, where electronic transport is vital to their use. While the fundamental transport properties of these materials have been heavily studied, there are still key features that are not well understood, including the temperature-squared behavior of their resistivities. Standard transport models fail to account for this atypical property because Fermi surfaces of many perovskite oxides are low-dimensional and distinct from traditional semiconductors. In this work, the low-dimensional Fermi surfaces of perovskite oxides are chemically interpreted in terms of two-dimensional crystal orbitals that form the conduction bands. Using SrTiO3 as a case study, the d/p-hybridization that creates these low-dimensional electronic structures is reviewed and connected to its fundamentally different electronic properties. A low-dimensional band model explains several experimental transport properties, including the temperature and carrier-density dependence of the effective mass, the carrier-density dependence of scattering, and the temperature dependence of resistivity. This work highlights how chemical bonding influences semiconductor transport.

Strategic grazing management towards sustainable intensification at tropical pasture-based dairy systems.

Agricultural systems are responsible for environmental impacts that can be mitigated through the adoption of more sustainable principles. Our objective was to investigate the influence of two pre-grazing targets (95% and maximum canopy light interception during pasture regrowth; LI95% and LIMax, respectively) on sward structure and herbage nutritive value of elephant grass cv. Cameroon, and dry matter intake (DMI), milk yield, stocking rate, enteric methane (CH4) emissions by Holstein × Jersey dairy cows. We hypothesized that grazing strategies modifying the sward structure of elephant grass (Pennisetum purpureum Schum.) improves nutritive value of herbage, increasing DMI and reducing intensity of enteric CH4 emissions, providing environmental and productivity benefits to tropical pasture-based dairy systems. Results indicated that pre-sward surface height was greater for LIMax (≈135 cm) than LI95% (≈100 cm) and can be used as a reliable field guide for monitoring sward structure. Grazing management based on LI95% criteria improved herbage nutritive value and grazing efficiency, allowing greater DMI, milk yield and stocking rate by dairy cows. Daily enteric CH4 emission was not affected; however, cows grazing elephant grass at LI95% were more efficient and emitted 21% less CH4/kg of milk yield and 18% less CH4/kg of DMI. The 51% increase in milk yield per hectare overcame the 29% increase in enteric CH4 emissions per hectare in LI95% grazing management. Thereby the same resource allocation resulted in a 16% mitigation of the main greenhouse gas from pasture-based dairy systems. Overall, strategic grazing management is an environmental friendly practice that improves use efficiency of allocated resources through optimization of processes evolving plant, ruminant and their interface, and enhances milk production efficiency of tropical pasture-based systems.

Chondroprotective supplementation promotes the mechanical properties of injectable scaffold for human nucleus pulposus tissue engineering.

A result of intervertebral disc (IVD) degeneration, the nucleus pulposus (NP) is no longer able to withstand applied load leading to pain and disability. The objective of this study is to fabricate a tissue-engineered injectable scaffold with chondroprotective supplementation in vitro to improve the mechanical properties of a degenerative NP. Tissue-engineered scaffolds were fabricated using different concentrations of alginate and calcium chloride and mechanically evaluated. Fabrication conditions were based on structural and mechanical resemblance to the native NP. Chondroprotective supplementation, glucosamine (GCSN) and chondroitin sulfate (CS), were added to scaffolds at concentrations of 0:0µg/mL (0:0-S), 125:100µg/mL (125:100-S), 250:200µg/mL (250:200-S), and 500:400µg/mL (500:400-S), GCSN and CS, respectively. Scaffolds were used to fabricate tissue-engineered constructs through encapsulation of human nucleus pulposus cells (HNPCs). The tissue-engineered constructs were collected at days 1, 14, and 28 for biochemical and biomechanical evaluations. Confocal microscopy showed HNPC viability and rounded morphology over the 28 day period. MTT analysis resulted in significant increases in cell proliferation for each group. Collagen type II ELISA quantification and compressive aggregate moduli (HA) showed increasing trends for both 250:200-S and the 500:400-S groups on Day 28 with significantly greater HA compared to 0:0-S group. Glycosaminoglycan and water content decreased for all groups. Results indicate the increased mechanical properties of the 250:200-S and the 500:400-S was due to production of a functional matrix. This study demonstrated potential for a chondroprotective supplemented injectable scaffold to restore biomechanical function of a degenerative disc through the production of a mechanically functional matrix.

A 13-week, multicenter, randomized, double-blind study of lumiracoxib in hip osteoarthritis.

The aim of this 13-week, multicenter, randomized, double-blind, double-dummy, placebo- and positive-internal (celecoxib)-controlled, parallel-group study was to demonstrate the efficacy, safety, and tolerability of lumiracoxib in primary hip osteoarthritis (OA) patients. Eligible patients (n = 1,262; ACR criteria) were randomized (1:1:1) to receive lumiracoxib 100 mg once daily (o.d.) (n = 427), celecoxib 200 mg o.d. (n = 419), or matching placebo o.d. (n = 416) administered orally. The primary objective was to compare lumiracoxib 100 mg o.d. and placebo with respect to three co-primary efficacy variables: the pain subscale of the Western Ontario and McMaster Universities Osteoarthritis Index Likert version 3.1 (WOMAC™ LK 3.1) questionnaire, the function subscale of the WOMAC™ LK 3.1 questionnaire, and patient's global assessment of disease activity (100-mm visual analog scale (VAS)) after 13 weeks of treatment. Of the 1,262 randomized patients, 951 completed the study. All randomized patients were included in the intention-to-treat and safety populations. Lumiracoxib was superior to the placebo (p < 0.001) after 13 weeks for all three co-primary endpoints. By week 13, the patient's global assessment of disease activity (100-mm VAS) improved by 23.3 mm (±SD, 27.83 mm) with lumiracoxib and 13.3 mm (±26.71 mm) with placebo. The WOMAC™ function score decreased by 10.4 (±13.56) with lumiracoxib and 6.8 (±12.55) with placebo. The WOMAC™ pain scores decreased by 3.4 (±4.16) with lumiracoxib and 2.2 (±3.94) with placebo at week 13. Similar results were observed for secondary endpoints: OA pain intensity and WOMAC™ total score. Lumiracoxib was similar to celecoxib for all three co-primary endpoints. All treatments were well tolerated. In conclusion, lumiracoxib is effective in reducing pain and improving function in hip OA patients.

Comparison of the blood pressure-lowering effects and tolerability of Losartan- and Amlodipine-based regimens in patients with isolated systolic hypertension.

BACKGROUND: Elevated systolic blood pressure is a more important risk factor for cardiovascular and renal disease than elevated diastolic blood pressure. Isolated systolic hypertension (ISH) is the predominant form of hypertension in the elderly. Effects of angiotensin II on the vascular wall and endothelium may contribute to development of ISH. OBJECTIVE: The primary objective of this study was to compare the effects on trough sitting systolic blood pressure (SiSBP) of a regimen of losartan, a selective angiotensin II-receptor antagonist, and an amlodipine-based regimen in patients with ISH. METHODS: This multicenter, prospective, randomized, double-blind, parallel-group study consisted of a 4-week placebo phase and an 18-week active-treatment phase. The losartan-based regimen consisted of losartan 50 mg, increased as needed to losartan 50 mg/hydrochlorothiazide (HCTZ) 12.5 mg at week 6 and to losartan 100 mg/HCTZ 25 mg at week 12 to achieve a target SiSBP <140 mm Hg. the amlodipine-based regimen consisted of amlodipine 5 mg, increased as needed to amlodipine 10 mg at week 6 and to amlodipine 10 mg/HCTZ 25 mg at week 12. The primary efficacy measure was change in trough SiSBP from baseline to week 18. Information on the tolerability of study treatments was collected at each visit, including the investigator's and patient's observations of clinical adverse experiences (CAEs), laboratory adverse experiences, and responses to a symptom questionnaire. RESULTS: Eight hundred fifty-seven patients (65.6% female) were randomized to treatment, 432 in the losartan group and 425 in the amlodipine group. Their mean age was 67.6 years, and they had a mean duration of hypertension of 6.7 years at baseline. The losartan and amlodipine groups (intent-to-treat population) had baseline mean SiSBP values of 171.2 and 171.9 mm Hg, respectively. At week 18 (the primary end point), the mean change from baseline in SiSBP was -27.4 mm Hg for 426 patients who received losartan and -28.1 mm Hg for 419 patients who received amlodipine (estimated least-square mean difference, 0.3 mm Hg; 95% CI, -1.4 to 2.0), indicating that losartan's effect on systolic blood pressure was noninferior to that of amlodipine. The proportion of patients who responded (SiSBP <140 mm Hg or a > or =20-mm Hg decrease in SiSBP from baseline) was comparable between groups (73.9% losartan, 75.4% amlodipine). The incidence of CAEs and drug-related CAEs was significantly greater in the amlodipine group (amlodipine, 79.8% and 43.8%, respectively; losartan, 67.8% and 25.5%; P < or = 0.001). In addition, more patients in the amlodipine group discontinued therapy due to a drug-related CAE compared with patients in the losartan group (12.9% vs 4.4%, respectively; P < or = 0.001). Lower-extremity edema was the most common drug-related CAE in the amlodipine group (24.0% amlodipine, 2.5% losartan; P < or = 0.001); dizziness was the most common drug-related CAE in the losartan group (6.0% losartan, 4.0% amlodipine). CONCLUSIONS: In these patients with ISH, losartan and amlodipine produced comparable clinically relevant reductions in SiSBP; however, losartan was better tolerated, as evidenced by fewer CAEs and discontinuations compared with amlodipine. Losartan may be considered for the initial treatment of ISH.