Review of \u3ci\u3eUrochloa\u3c/i\u3e Breeder’s Toolbox with the Theory of Change and Stage Gate System Approach

Livestock production in the global south is at crossroads as there is a demand to increase Animal Source Foods to address hunger and pressure to lighten the environmental footprint often associated with livestock production. To satisfy both needs, the use of technologies that improve animal performance, while reducing land use and net Greenhouse Gas emissions produced by animals is essential. One of such technologies are Urochloa forage grasses. Urochloa forage grasses are well known for their rusticity and their ability to grow in soils of low fertility and high aluminum content. These characteristics allow Urochloa to grow in areas temporally or spatially less suitable for crop production, but also have made ruminants production profitable in areas that would not be otherwise. However, productivity and sustainability of ruminant production in these areas is likely to fall within the next decade due to climate change unless action is taken. Despite these known benefits of Urochloa forage species, breeding programs have long delayed initiation due to apomixes and differences in ploidy. In the mid-1980s, the development of suitable sexual germplasm allowed crossings, and therefore favoured the emergence of breeding programs. In recent decades, several advances in biology, molecular biology, phenotyping, population genetics, genomics and transcriptomics have generated a plethora of information that ought to be integrated for its use in a single breeding toolbox. We use the Theory of Change and Stage-Gate systems approach to review these advances in research and the utility of the current and future available tools. Further, we address the remaining lack of information, thus bridging the knowledge gap and enabling us to maximize the genetic gain in the different Urochloa breeding programs. In this way, we identify breeding bottlenecks and help to pinpoint priorities for Urochloa research and development

Book reviews

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45119/1/10943_2005_Article_BF01533201.pd

Impact of pulmonary disease on the prognosis in heart failure with preserved ejection fraction: the TOPCAT trial

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154618/1/ejhf1593_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154618/2/ejhf1593.pd

Spironolactone for heart failure with preserved ejection fraction

BACKGROUND: Mineralocorticoid-receptor antagonists improve the prognosis for patients with heart failure and a reduced left ventricular ejection fraction. We evaluated the effects of spironolactone in patients with heart failure and a preserved left ventricular ejection fraction. METHODS: In this randomized, double-blind trial, we assigned 3445 patients with symptomatic heart failure and a left ventricular ejection fraction of 45% or more to receive either spironolactone (15 to 45 mg daily) or placebo. The primary outcome was a composite of death from cardiovascular causes, aborted cardiac arrest, or hospitalization for the management of heart failure. RESULTS: With a mean follow-up of 3.3 years, the primary outcome occurred in 320 of 1722 patients in the spironolactone group (18.6%) and 351 of 1723 patients in the placebo group (20.4%) (hazard ratio, 0.89; 95% confidence interval [CI], 0.77 to 1.04; P = 0.14). Of the components of the primary outcome, only hospitalization for heart failure had a significantly lower incidence in the spironolactone group than in the placebo group (206 patients [12.0%] vs. 245 patients [14.2%]; hazard ratio, 0.83; 95% CI, 0.69 to 0.99, P = 0.04). Neither total deaths nor hospitalizations for any reason were significantly reduced by spironolactone. Treatment with spironolactone was associated with increased serum creatinine levels and a doubling of the rate of hyperkalemia (18.7%, vs. 9.1% in the placebo group) but reduced hypokalemia. With frequent monitoring, there were no significant differences in the incidence of serious adverse events, a serum creatinine level of 3.0 mg per deciliter (265 μmol per liter) or higher, or dialysis. CONCLUSIONS: In patients with heart failure and a preserved ejection fraction, treatment with spironolactone did not significantly reduce the incidence of the primary composite outcome of death from cardiovascular causes, aborted cardiac arrest, or hospitalization for the management of heart failure

'Gain with no pain’: anabolic-androgenic steroids trafficking in the UK

Anabolic-androgenic steroids are performance and image enhancing drugs (PIED) that can improve endurance and athletic performance, reduce body fat and stimulate muscle growth. The use of steroids has been studied extensively in the medical and psychological literature, as well as in the sociology of sport, health and masculinity. From the late 2000s, the worldwide trade in steroids increased significantly. However, trafficking in steroids remains a largely under-researched criminological phenomenon with a few notable exceptions. Currently in the UK there are only small and fragmented pieces of information available relating to steroids trafficking in autobiographical accounts of professional criminals. Drawing on original empirical data, the purpose of this article is to provide an account of the social organization of the steroids trafficking business in the UK. The trade in steroids is decentralized, highly flexible with no hierarchies, and open to anyone willing to either order the merchandise online or travel to producing countries and obtain steroids in bulk from legitimate manufacturers. The patterns of trafficking of this specific type of substance are patently conditioned by its embeddedness in the gym/bodybuilding scene and this greatly affects relations between actors in the business. In the steroids market, one typically encounters a multitude of individuals likely to drift between legality and illegality, online and offline, use and supply

Effects of Sacubitril-Valsartan, versus Valsartan, in Women Compared to Men with Heart Failure and Preserved Ejection Fraction: Insights from PARAGON-HF

Unlike heart failure with reduced ejection fraction, there is no approved treatment for heart failure with preserved ejection fraction (HFpEF), the predominant phenotype in women. Therefore, there is a greater heart failure therapeutic deficit in women, compared with men. In a pre-specified subgroup analysis, we examined outcomes according to sex in the PARAGON-HF trial which compared sacubitril-valsartan and valsartan in patients with HFpEF. The primary outcome was a composite of first and recurrent hospitalizations for heart failure and death from cardiovascular causes. We also report secondary efficacy and safety outcomes. Overall, 2479 women (51.7%) and 2317 men (48.3%) were randomized. Women were older, had more obesity, less coronary disease, and lower estimated glomerular filtration rate and NT-proBNP levels than men. For the primary outcome, the rate ratio for sacubitril-valsartan versus valsartan was 0.73 (95% CI 0.59-0.90) in women and 1.03 (0.84-1.25) in men; P interaction=0.017. The benefit from sacubitril-valsartan was due to reduction in heart failure hospitalization. The improvement in NYHA class and renal function with sacubitril-valsartan was similar in women and men, whereas the improvement in KCCQ-CSS was less in women than in men. The difference in adverse events, between sacubitril-valsartan and valsartan, was similar in women and men. As compared with valsartan, sacubitril-valsartan seemed to reduce the risk of heart failure hospitalization more in women than in men. While the possible sex-related modification of the effect of treatment has several potential explanations, the present study does not provide a definite mechanistic basis for this finding. URL: https://clinicaltrials.gov Unique Identifier: NCT01920711

Modification of neuropathic pain sensation through microglial ATP receptors

Neuropathic pain that typically develops when peripheral nerves are damaged through surgery, bone compression in cancer, diabetes, or infection is a major factor causing impaired quality of life in millions of people worldwide. Recently, there has been a rapidly growing body of evidence indicating that spinal glia play a critical role in the pathogenesis of neuropathic pain. Accumulating findings also indicate that nucleotides play an important role in neuron-glia communication through P2 purinoceptors. Damaged neurons release or leak nucleotides including ATP and UTP to stimulate microglia through P2 purinoceptors expressing on microglia. It was shown in an animal model of neuropathic pain that microglial P2X4 and P2X7 receptors are crucial in pain signaling after peripheral nerve lesion. In this review, we describe the modification of neuropathic pain sensation through microglial P2X4 and P2X7, with the possibility of P2Y6 and P2Y12 involvement

Evidence for a Common Mechanism of SIRT1 Regulation by Allosteric Activators

A molecule that treats multiple age-related diseases would have a major impact on global health and economics. The SIRT1 deacetylase has drawn attention in this regard as a target for drug design. Yet controversy exists around the mechanism of sirtuin-activating compounds (STACs). We found that specific hydrophobic motifs found in SIRT1 substrates such as PGC-1α and FOXO3a facilitate SIRT1 activation by STACs. A single amino acid in SIRT1, Glu[superscript 230], located in a structured N-terminal domain, was critical for activation by all previously reported STAC scaffolds and a new class of chemically distinct activators. In primary cells reconstituted with activation-defective SIRT1, the metabolic effects of STACs were blocked. Thus, SIRT1 can be directly activated through an allosteric mechanism common to chemically diverse STACs.Glenn Foundation for Medical ResearchEllison Medical FoundationJuvenile Diabetes Research Foundation InternationalUnited Mitochondrial Disease FoundationNational Institutes of Health (U.S.)National Institute of Allergy and Infectious Diseases (U.S.