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Aim: To assess the effect of tirzepatide on long‐term risk of atherosclerotic cardiovascular disease (ASCVD) among people with obesity or overweight without diabetes from SURMOUNT‐1. Materials and Methods: SURMOUNT‐1, a phase 3 trial, evaluated the efficacy and safety of tirzepatide in adults with body mass index ≥30 or ≥27 kg/m2 and at least one weight‐related complication, excluding diabetes. Participants were randomly assigned to tirzepatide (5/10/15 mg) or placebo. Changes from baseline in cardiometabolic variables were assessed. The predicted 10‐year ASCVD risk scores were calculated (American College of Cardiology/American Heart Association risk engine) at baseline, week 24, and week 72 in SURMOUNT‐1 participants without a history of ASCVD. Percent change in risk scores from baseline to weeks 24 and 72 was compared between tirzepatide and placebo using mixed model for repeated measures analysis. Analyses were also conducted in participants with intermediate to high risk at baseline. Results: Tirzepatide‐treated groups demonstrated reductions in cardiometabolic variables over 72 weeks. In participants without a history of ASCVD (N = 2461), the baseline median risk score was low and did not differ across groups (1.5%–1.6%). Relative change in risk from baseline to week 72 was greater for tirzepatide (−23.5% to −16.4%) than placebo (12.7%; P < 0.001). Relative change among participants with intermediate‐to‐high baseline risk was significantly greater for tirzepatide (P < 0.05). Intermediate‐to‐high‐risk participants demonstrated similar relative change but greater absolute risk reduction compared to the overall population. Conclusion: Tirzepatide treatment significantly reduced the 10‐year predicted risk of ASCVD versus placebo in patients with obesity or overweight without diabetes. [ABSTRACT FROM AUTHOR]

Aim: To compare the efficacy of tirzepatide 10 and 15 mg with semaglutide 2.4 mg using an indirect treatment comparison. Materials and Methods: Using SURMOUNT‐1 and STEP 1 trial data, mean percentage change in body weight from baseline and odds ratio (OR) of achieving 5% or greater weight loss were compared between tirzepatide 10 and 15 mg at week 72 and semaglutide 2.4 mg at week 68 using matching‐adjusted indirect comparison of the efficacy estimand. Sensitivity analyses were completed using different methods, including the Bucher method, also using different estimands and/or time points. Results: Greater reductions in percentage change in body weight were observed with tirzepatide 10 and 15 mg versus semaglutide 2.4 mg (tirzepatide 10 mg mean difference: −4.67% [95% CI −5.91%, −3.43%]; tirzepatide 15 mg mean difference: −5.92% [95% CI −7.16%, −4.68%]; both P <.001). Similarly, more participants achieved 5% or greater weight loss with tirzepatide 10 mg (OR 2.61 [95% CI 1.48, 4.57]; P <.001) and 15 mg (OR 2.75 [95% CI 1.57, 4.81]; P <.001) compared with semaglutide 2.4 mg. All sensitivity analyses were consistent, except for an OR of achieving 5% or greater weight loss with tirzepatide 10 mg using the Bucher method to analyse the treatment regimen estimand (P =.074). Conclusions: Currently there are no direct comparisons of tirzepatide and semaglutide for weight management. Using the matching‐adjusted indirect treatment comparison method to compare the efficacy of tirzepatide and semaglutide for chronic weight management, this analysis showed greater weight loss with tirzepatide 10 and 15 mg versus semaglutide 2.4 mg. [ABSTRACT FROM AUTHOR]

Context: Opportunity exists to expand serradella (Ornithopus spp.) use onto heavier, duplex soil types in permanent pasture environments of south-eastern Australia. This requires cultivars with appropriate flowering times and flowering-date stability (i.e. flowering at the same date in spring regardless of timing of the autumn break). Aim: This work examined evidence of variation in flowering date and flowering-date stability in the NSW southern tablelands for a widely-used French serradella (O. sativus) cv. Margurita. Methods: Seed (sourced from a commercial supplier) was sown 21 March 2019 (Canberra, ACT) and 231 individual plants were monitored for time to first flower. A subset of plants exhibiting 'early' or 'late' flowering were identified and their seeds collected. In 2020, seed from ~15 plants from each selection was sown in Canberra in late March and early May to represent an 'early' and a 'later' break of season (n = 3). Key results: In the early-sown treatment, 'early-flowering' selections typically reached the median date of first flower (50%-flowering) from mid- to late August, while 'late-flowering' selections reached 50%-flowering early- to mid-September. When sown later, the 'early-flowering' selections began flowering from mid- to late September, while the 'late-flowering' selections flowered mid-September to early October. The 'early' selections exhibited greater flowering-date instability than 'late' selections and flowered particularly early when sown early. This indicated diversity within cv. Margurita for flowering-time control (e.g. vernalisation and/or photoperiod requirements). Implications: Evaluating cultivars of serradellas for flowering date and flowering date stability in their target environment(s) is essential to ensure cultivars are suitably adapted to these environments. Serradellas (Ornithopus spp.) are a novel legume option for the permanent pasture environments of south-eastern Australia. This paper investigated evidence of variation in flowering time characteristics within a widely used cultivar of French serradella. We recommend that new cultivars of serradellas be evaluated for flowering time characteristics in their target environment(s) to assess whether the cultivars are suitably adapted to these environments. This is essential to maximise production, feeding value and facilitate effective grazing management. [ABSTRACT FROM AUTHOR]

Context: There is interest in using serradella (Ornithopus spp.) in permanent pastures of the high rainfall zone of south-eastern Australia. However, there is little information concerning levels of hardseededness or patterns of seed softening in these environments. Aim: This study quantified seed softening of serradella species in comparison with subterranean clover (Trifolium subterraneum L.) in the Southern Tablelands and Central Slopes districts of eastern Australia. Methods: Mature seeds were placed in mesh pouches on the soil surface and were retrieved periodically to assess residual hard seed proportions throughout the growing season(s) in four experiments conducted over 2018 and 2019. Key results: Patterns of seed softening among adapted cultivars of subterranean clover were consistent: initially high proportions of hard seed, followed by rapid softening from mid-summer to the end of autumn with the remnant portion of seeds remaining hard. In contrast, diverse patterns of seed softening were observed among serradella cultivars, ranging from highly soft-seeded through to high initial hard seed portions that either softened rapidly or softened over a lengthy period. Rates of seed softening were faster in the warmer/drier environment of Cowra compared to the wetter/cooler environment of Canberra. Conclusions: The study revealed seed softening patterns among serradellas to be diverse and different to subterranean clover. This will affect management and suitability of serradella cultivars for permanent pastures. Implications: In permanent pastures, serradellas that soften slowly over several years are likely to have limited regeneration in the year after pasture establishment with a high potential for weed invasion. Serradella has many advantages as a pasture legume, however persistence and productivity in permanent pastures can be inadequate. This study quantified seed softening of serradella species in comparison with subterranean clover in the Southern Tablelands and Central Slopes districts of eastern Australia. Diverse patterns of seed softening were observed among serradella cultivars, in contrast to subterranean clover. Implications for pasture establishment of serradella in high rainfall zone permanent pastures is discussed. [ABSTRACT FROM AUTHOR]

Differences in root morphology and acclimation to low‐phosphorus (P) soil were examined among eight legume species from the Trifolium Section Tricocephalum to understand how these root attributes determine P acquisition. Ornithopus sativus was included as a highly P‐efficient benchmark species. Plants were grown as microswards in pots with five rates of P supplied in a topsoil layer to mimic uneven P distribution within a field soil profile. Topsoil and subsoil roots were harvested separately to enable measurement of the nutrient‐foraging responses. Critical P requirement (lowest P supply for maximum yield) varied over a threefold range, reflecting differences in root morphology and acclimation of nutrient‐foraging roots to P stress. Among the species, there was a 3.2‐fold range in root length density, a 1.7‐fold range in specific root length, and a 2.1‐fold range in root hair length. O. sativus had the lowest critical P requirement, displayed a high root length density, the highest specific root length, and the longest root hairs. Acquisition of P from P‐deficient soil was facilitated by development of a large root hair cylinder (i.e. a large root–soil interface). This, in turn, was determined by the intrinsic root morphology attributes of each genotype, and the plasticity of its root morphology response to internal P stress. Root acclimation in low‐P soil by all species was mostly associated with preferential allocation of mass to nutrient‐foraging roots. Only O. sativus and four of the Trifolium species adjusted specific root length beneficially, and only O. sativus increased its root hair length in low‐P soil. [ABSTRACT FROM AUTHOR]

The role of epidermal growth factors (EGFs) and transforming growth factor-beta (TGF-beta) in the expression of neutral endopeptidase (NEP) was analyzed in rabbit renal vascular smooth muscle cells (VSMCs). The presence of EGF in serum cultures containing rabbit renal VSMCs downregulated the expression of NEP. The downregulation of NEP was also induced by the presence of TGF-beta which enhanced the EGF-dependent cell proliferation.

The presence of neutral endopeptidase (NEP) in cultured vascular smooth muscle cells (VSMC) and its possible involvement in the degradation of atrial natriuretic factors (ANF) were investigated. Synthetic substrate hydrolysis, anti-NEP antibodies and Northern blot analysis revealed the presence of NEP in VSMC. Incubation of labeled ANF with VSMC and the NEP inhibitor thiorpan showed that NEP is involved in the catabolism of ANF by VSMC.

Background and aims: The growth and root morphology responses to soil phosphorus (P) fertility by five cultivars of Trifolium subterraneum (a temperate annual pasture legume) were examined to assess whether differences in root morphology and/or root acclimation to P stress influenced P-acquisition by the clover varieties, or their critical P requirements (i.e. the rate of P supply needed for maximum shoot yield).Methods: The clovers were grown as microswards in soil with P stratified in a topsoil layer to mimic growth conditions and soil P availability in a pasture. Yield and P content of shoots, and roots from the topsoil and subsoil layers was determined after 5 weeks growth in a controlled-environment cabinet. The lengths, diameters, and root hair lengths of nutrient foraging roots from the topsoil layer were quantified.Results: The shoot yield of the cultivars was similar when grown with high soil P fertility. However, the cultivars varied up to 1.5-fold in their ability to yield at low levels of soil P supply, and by 1.6-fold in their critical P requirements. All cultivars acclimated to low P soil by increasing root length density in the topsoil but those that yielded relatively well did so by maintaining a large root hair cylinder volume (i.e. they explored more soil) under low soil P conditions. This was associated with maintenance of dry matter allocations to topsoil roots and higher specific root lengths. Both factors assisted development of high root length density for nutrient foraging. Root acclimation responses to P were compared among the cultivars at equivalent relative shoot yields to assess the influence of plant P stress as a trigger for nutrient foraging. The least P-efficient cultivars slowed their allocation of dry matter to foraging roots at lower levels of P stress.Conclusions: The results suggest variation within T. subterraneum for root proliferation and specific root length could be targeted in breeding for improved P-acquisition efficiency. [ABSTRACT FROM AUTHOR]

Examines the role of epidermal growth factor (EGF) and transforming growth factor-beta1 (TGF-) in the downregulated and the consequences of the changes in neutral endopeptidase (NEP) activity. Relation between NEP and the common acute leukemia antigen; Involvement of NEP in the metabolism of peptides.

Examines the role of epidermal growth factor (EGF) and transforming growth factor-beta1 in the downregulation and the consequences of the changes in neutral endopeptidase (NEP) activity on their mitogenic effects. Effects of NEP inhibition on EGF-induced cell proliferation.